Review ArticleSurface Modification Chemistries of Materials Used inDiagnostic Platforms with Biomolecules

Mukesh Digambar Sonawane and Satish Balasaheb Nimse

Institute for Applied Chemistry and Department of Chemistry Hallym University Chuncheon 200-702 Republic of Korea

Correspondence should be addressed to Satish Balasaheb Nimse satish nimsehallymackr

Received 10 February 2016 Revised 8 April 2016 Accepted 10 April 2016

Academic Editor Dimosthenis L Giokas

Copyright copy 2016 M D Sonawane and S B Nimse This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

Biomolecules including DNA protein and enzymes are of prime importance in biomedical field There are several reports on thetechnologies for the detection of these biomolecules on various diagnostic platforms It is important to note that the performanceof the biosensor is highly dependent on the substrate material used and its meticulous modification for particular applicationsTherefore it is critical to understand the principles of a biosensor to identify the correct substrate material and its surfacemodification chemistry The imperative surface modification for the attachment of biomolecules without losing their bioactivity isa key to sensitive detection Therefore finding of a modification method which gives minimum damage to the surface as well asbiomolecule is highly inevitable Different surface modification technologies are invented according to the type of a substrate usedSurface modification techniques of the materials used as platforms in the fabrication of biosensors are reviewed in this paper

1 Introduction

In recent years biosensors became one of the indispensabletools as point-of-care (PoC) diagnostics [1] A biosensor isan analytical device which combines a biological componentwith a physicochemical detector used for the detection of ananalyte [2] The general aim of the design of any biosensor isto allow the rapid accurate and convenient testing in the PoCsettings where the patient is receiving care [3]

Advances in biosensor technologies have enabled devel-oping the diagnostic biosensors which have high accuracyhigh speed and an ability of parallel screening of multipleanalytes [4] So far numerous types of biosensors have beendeveloped [5]Classificationof thebiosensors can be rationali-zed by looking at the principle biomolecular interactions usedin that particular biosensor In generalmost of the biosensorsare majorly based on the antibodyantigen interactions [6]enzymatic interactions [7] DNA-DNA interactions [1 8]cellular structurescells [9] or biomimetic materials [10 11]

Irrespective of a type of biosensor and a final detectionstep of an analyte either at the solid-liquid interface or in

the solution phase involving nanoparticle (NP) the surfaceattachment of antibody enzyme DNA or cell is inevitable Itis well known that the conformation of biomolecules such asantibodies and enzymes plays a crucial role in determiningboth efficiency and selectivity of these molecules for analytes[12] Therefore the performance of the biosensors greatlydepends on the surface chemistry of the materials used andalso the chemistries used in the conjugation of the compo-nents of biosensors such as antibodies and enzymes on thesurfaceThe attachment chemistries used for the immobiliza-tion processes can alter the natural molecular environment ofproteins thus resulting in the loss of their activity indicatedby a significant drop in the sensitivity and selectivity Varioussurfaces used for the immobilization of biomolecules includesilicon glass (silicon dioxide) nitrocellulose gold silverpolystyrene and graphene In this critical review we havehighlighted the materials and respective chemistries usedfor the immobilization of biomolecules Merits and demeritsof some of the materials and their surface modificationchemistries for the application in the selective and sensitivedetection of analytes are discussed

Hindawi Publishing CorporationJournal of ChemistryVolume 2016 Article ID 9241378 19 pageshttpdxdoiorg10115520169241378

2 Journal of Chemistry

Figure 1 The macroporous surface of modified silicon (adapted from [13])

2 Material and Techniques forSurface Modification

Modification of a surface is crucial to producing biomoleculedetection platforms In general the functional groups presentin biomolecules are allowed to react with the functionalgroups on the modified surfaces for their immobilizationMost common biomolecules immobilized on the surface forthe fabrication of the diagnostic devices are DNA proteinsand carbohydrates DNA oligomers can be synthesized tohave terminal amine and aldehyde groups Proteins naturallycontain amine sulfhydryl and carboxylic acid functionalgroups Carbohydrates in general have hydroxyl functionalgroups and amine functional groups in case of glucosamineDepending on these groups surfaces of the substrate aremodified for biomolecule attachment The efficiency of thedetection platform is strongly affected by the proper immo-bilization of biomolecules Therefore the materials and theirsurface modification chemistries are discussed in detail Thecommon surfaces used in the diagnostic devices are siliconglass slide glass membranes carbon nitrocellulose polysty-rene silver gold and so forth

21 Silicon Silicon is the element of periodic table that rarelyoccurs in pure form It occurs in a stable oxidized formThe typical application of silicon in electronic devices is as asemiconductor Electrochemical detection of protein is wellknown because it is label-free and allows real-time detec-tion Physical adsorption is one of the choices for antibodyimmobilization as it does not need temperature and humiditycontrols [13]The shorter time of immobilizationmakes assayfaster compare to other methods [14] Porous form of siliconsurface makes it more efficient for the immobilization due toformation of pseudo-three-dimensional surface [15 16] Theporous silicon (P-Si) surface shows high spot homogeneitylow internal fluorescence little wetting ability and lessnonspecificity [17] Depending on the pore size the P-Si hasthree categories microporous (less than 10 nm) mesoporous(10ndash50 nm) and macroporous (larger than 50 nm) It hasbeen reported that the macroporous silicon surface is highly

suitable for antibody immobilization [13] There are severalreports on the techniques used for the fabrication of siliconsurface

211 Electrochemical Modification The physisorption ofbiomolecules on the P-Si depends heavily on its micro- andnanomorphology controlled by the surface etching condi-tions and selection of silicon type A great deal of work isreported on the fabrication of micro- and nanoporous siliconfor antibody adsorption [18 19] Lee et al selected a boron sil-icon wafer with a specific resistivity (sim6ndash8Ωcm) and placedit in the electrochemical cell

As depicted in Figure 1 a self-supporting layer of P-Si is fabricated by growing an anodic oxide followed byits dissolution using an electropolishing current in a 15hydrofluoric acid solution leading to the formation of poresThe macroporous P-Si is then cut into pieces and fitted inmicrotitre plate for deposition of capture antibodies (cAb)for sandwich immunoassay [20]There are several reports onthe applications of the P-Si surfaces for the electrochemicaldetection of various chemicals and bacteria [21 22]

212 Covalent Modification P-Si microparticles have highand unique reflectance properties The antibodies which cantarget and capture specific antigens or cells can be cova-lently immobilized on the P-Si microparticles The hydride-terminated surface of the P-Si microparticles can be pas-sivated by hydrosilylation with dialkyne species Guan andcoworker used Cu(I)-catalyzed alkyne-azide cycloaddition(CuAAC) followed by succinimidyl activation reaction forcoupling of the antibodies to P-Si As shown in Figure 2 anti-body modified P-Si microparticles were employed for theselective capture and detection of HeLa cells [23] SimilarCuAAC based surface modification for adhesion of cell sur-face has also been reported [24]

Other applications of P-Si surface include fabricationof protein microarray for PSA detection with the limit ofdetection (LOD) of 800 fgmL A successful covalent modi-fication of P-Si has been reported by Rossi et al for detectionof MS2 virus with the LOD of 2 times 107 plaque-forming

Journal of Chemistry 3

Visible light Reflectance lightSelective target of antibody modified

particles to fluorescent cells

Porous silicon microparticle

mCherry antibodyTfR-mCherry

Cell membrane

Figure 2 Covalent bonding of antibodies to P-Si microparticles for detection of cells (adapted from [23])

DNA

Amine-modifiedglass surface

SiO

SiO

SiO

SiO

SiO

SiO

SiO

SiO

SiO

SiO O O O O O O O O O

H3N+ H3N+ H3N+ H3N+ H3N+ H3N+H3N+ H3N+ H3N+ H3N+

Figure 3 Physisorption of DNA on the amine-modified glass surface

units per mL (pfumL) [25] As explained earlier the strictfabrication protocol is needed for accurate size of poresChange in the concentrations of reagents and change incurrent and time affect the reproducibility of the result Othercovalent ethylene glycol modified silicon surfaces for specificadsorption of protein through photochemical reaction [26]and silicon covalent surface modification for agarose cross-linking in form of catheter have been reported for infectioninhibition and omental wrapping [27]

22 Glass (SiO2) A glass is made up of a silicon dioxide

(SiO2)Theoxide layer protects the silicon fromchemical deg-

radation and reactions Silicon dioxide is abundant in natureand thermally stable due to a large number of silicon andoxygen bonds Glass substrates are easily available and simpleto handle and have high mechanical stability Glass surfacesare widely used for the immobilization of DNA proteins andother low molecular weight biomolecules [28] In diagnosticfield glass surface plays a crucial role as microarray platformfor detection of various pathogenic DNA as well as biomarkerprotein [29 30]

221 Physisorption Based Modification Physical adsorptionor physisorption is one of the simplest techniques used for thebiomolecule immobilization on glass surfaces As shown inFigure 3 the negatively charged phosphate backbone onDNAforms an ionic interaction with the positively charged surface

of amine-modified glass surface through charge interactions[38]

Lemeshko et al reported that the aminosilanization ofthe glass surface by treatment with 3-(aminopropyl) trime-thoxysilane (APTMS) affords the positively charged surfaceUnfortunately the immobilization of DNAswith thismethoddoes not result in the reproducible DNA detection platformBecause the multiple interaction of negatively charged DNAbackbone with the cationic surface orients it parallel to theglass surface thus its availability for hybridization with thecomplimentary DNA (cDNA) is significantly low

The random orientation of the immobilized DNAs isalso related to the nonspecific hybridization and low repro-ducibility The change in pH of solution and temperaturesignificantly affects the performance of the platform based onthe method of physisorption

222 Covalent Modification Due to various disadvantagesof physisorption methods the covalent surface modificationstrategy has been widely used Covalent bond is stronger andmore stable than electrostatic interaction at solution-surfaceinterfaces [40 41] The glass surfaces and be modified withthe different functional groups suitable for making covalentbonds with the biomolecules to be immobilized In generalthe biomolecules have amine carboxylic acid and sulfhydrylfunctional groups These functional groups can be used forthe immobilization of biomolecules on the surface There are

4 Journal of Chemistry

OO

GlutaraldehydeN O NNH2 N-DNA-Cy3

-DNA-Cy3H2N

Scheme 1 Aldehyde modification of glass slide

Si

Si

O

O

O

O

O

O

Si

Si

O

O

O

OH

OH

OP

O-d(NNN)

O-d(NNN)

O

O

OO O

P

O

O

O

Ominus

Ominus

d(NNN)=OP32minus

MW 10min35∘C 4hr

Scheme 2 Covalent attachment of phosphorylated DNA

various reports on the glass surfacemodification for the cova-lent attachment of biomolecules

(1) Aldehyde Modification For the aldehyde modification ofthe glass surface the silanol groups on the surface are con-verted to an amine by different methods using amine mod-ification reagents such as (3-Aminopropyl)triethoxysilane(APTES) [42] Fixe et al reported the aldehyde modificationusing glutaraldehyde As shown in Scheme 1 the amine-modified surface is then treated with glutaraldehyde (25vv) in 01M PBS for 2 h at room temperature The slide isthen washed with water and dried The solution containingamine-modified DNAs is spotted on the slide and incubatedin humidified chamber for up to 24 h to afford the DNAmicroarray However it is important to note that the unre-acted aldehyde functional groups on the glass surface shouldbe blocked by reacting them with the sodium borohydride(NaBH

4) [43]

Similar to the DNA immobilization the cAb can alsobe immobilized on the aldehyde-modified glass surfaces toafford protein microarrays However the cAbs on the proteinmicroarrays obtained by using aldehyde chemistry have alower binding affinity as well as reduced specificity for the tar-get antigens [44] Another method of aldehyde modificationof ester functionalized slide can be done by reduction to alco-hol followed by controlled oxidation of alcohol to aldehydeusing pyridinium chlorochromate (PCC) [45] Apart fromthe glass chips surface the glass bead surface is also modifiedto produce a surface with aldehyde functions using APTESand glutaraldehyde reagents [46]

(2) Epoxy Modification Apart from silanization epoxylationis a commonly used approach for glass surface modificationThe epoxy functional group on the epoxy-modified glasssurfaces are allowed to react with the amine-containingbiomolecules for their immobilization [47]Thus the amine-modified DNAs and proteins with their native amine groups

can be immobilized by this method on the glass surfaces forthe generation of DNA microarray and protein microarrayrespectively As shown in Scheme 2 the epoxy functionalizedsurfaces can be used for the covalent attachment of phospho-rylated DNAs

The advantage of this method is that the 31015840 phosphategroup can make a covalent bond with epoxy groups Thisallows immobilization of larger fragments of DNA or PCRproducts on the surface As explained by Mahajan et al theepoxylation of glass surface is carried out by keeping the glassin a 2 solution glycidoxypropyltrimethoxysilane (GOPTS)in toluene for 4-5 h at 50∘C followed by washing and dryingAfter epoxylation of glass surface the probe immobilizationis done by spotting the 31015840 phosphate DNA on the surface andmicrowave treatment for 10min in a buffer of pH 10 Afterthe DNA immobilization excess epoxy groups are maskedby using capping buffer of pH 9 containing 01M Tris with50mM ethanolamine for 15min at 50∘C [48]

One of the disadvantages of this approach is the need forhigh pH at which glass surface starts to degrade leading tothe inconsistent results [49] Furthermore the high pH alsodamaged the native three-dimensional structure of proteinsresulting in decreased sensitivity and increased nonspecificinteractions

(3) Carboxylate Modification The amine-modified DNAs arecommonly used because of the simple chemistry involved intheir conjugation with fluorescence molecules with carbonylfunctional groups Same chemistry can be attributed toimmobilizing the amine-modified DNAs on the carboxylicacid modified glass surfaceThe coupling between carboxylicacid and amine is direct without any linker in betweenthem The 1-ethyl-3-(3-dimethylaminopropyl) carbodiimidehydrochloride (EDC) is a commonly used reagent for amidecoupling reactions Other common coupling reagents are N-hydroxysuccinimide (NHS) hydroxybenzotriazole (HOBt)and NNN1015840N1015840-Tetramethyl-O-(benzotriazol-1-yl)uronium

Journal of Chemistry 5

(1) GA(2) DCCNHS

O O O

Si Si SiO O O

HNHN

O O

OO OONO O NO O

H2N

O O O

Si Si SiO O O

H2N H2NH2N

Scheme 3 Surface modification with activated carboxylic acid

tetrafluoroborate (TBTU) The free amino functional groupsin lysine containing proteins are targeted for the immobiliza-tion of proteins on the glass surface through amide couplingreactions The polyamidoamine (PAMAM) dendrimer isused as a linker for immobilization of the DNAs on the glasssurfaces [50 51] PAMAM was initially invented in the 1980sto increase the amino groups on the outer surface of sphere[52] Its application is now extended for DNA immobiliza-tion Firstly the silylation is performed using 95 3 2 vvsolution of ethanol water and APTES by treating the glassslides for 2 h

As depicted in Scheme 3 Benters et al treated the silylatedsurface overnight with the solution of glutaric anhydride(GA) in DMF Slides are then washed with DMF multipletimes to remove the unreacted reagents Carboxyl groups areactivated by using activating reagent such as 1mM solutionof NHS or dicyclohexylcarbodiimide (DCC) in DMF for 1 hfollowed by washing with DMF For the covalent attachmentof dendrimer 100120583L of 10 PAMAM in methanol is allowedto react with the activated carboxyl functional groups on thesurface for 12 h at room temperature followed by washingwith methanol to remove the excess dendrimer Before theimmobilization of DNAs on the surface these dendrimers areactivated by using GANHS as described above [53]

(4) Diazotization Diazo one of the stable bonds in organicchemistry makes its use imperative in the surface modifica-tion process For diazotization the amine-modified surfaceis needed Commonly a cleaned glass using piranha solutionfor 30min followed by deionized (DI) water is used [54]The cleaned glass surface is then allowed to react with the(4-aminophenyl) trimethoxysilane in ethanol solution for30min After silanization the amine-modified surface istreated with the sodium nitrite (NaNO

2) to generate dia-

zobenzyl surface as depicted in Scheme 4 The diazotizationreaction is done at 4∘C using solution of 40mL water 80mLHCl (400mM) and 32mL NaNO

2(200mM) as reported by

Alwine et al [55] After the reaction surface is washed withice-cold sodium acetate buffer deionized water and ethanolThen the solution containing the probe DNAs is spottedon the ice-cold diazotized surface and air dried for 1-2 hDolan et almentioned that the unreacted diazo groups on the

surface are blocked by reaction with the glycine or UV-cross-linked followed by baking for two hours at 80∘C [56] Theimmobilized DNAs can be allowed to hybridize with the PCRproducts for the detection and discrimination of pathogens

(5) Surface Modification with Supramolecules In the lastdecade tremendous work is done on the various applicationsof supramolecules in particular calixarenes [31 57 58] Thecalix[4]crown-5 derivatives are well known for their abilityto capture the cationic substrates including metal cations andammonium ions [59] The cavities of calixarenes are wellknown to capture the amino groups of proteins and formstable complexes with them According to the report Leeet al exploited the ability of calixarenes to form complexeswith proteins to fabricate the protein microarrays on glasssurfaces as depicted in Figure 4 [60 61] For the fabricationof the protein microarrays the calix[4]crown-5 derivativescontaining aldehyde functional groups are reacted with theamine functional groups on the amine-modified glass chip togenerate a monolayer

Then the protein in PBS solution with 30 glycerol isspotted on calix[4]crown-5 derivative modified glass surfaceand incubated at 37∘C for 3 h Then the chip is washed withthe 10mMPBS solution containing 05 Tween 20 for 10minat room temperature and dried under a stream of N

2gasThe

unreacted calix[4]crown-5 derivatives the free amine groupson the glass surface are blocked by immersing the chip intothe 3 BSA in PBS solution for 1 h at room temperature

Similar to protein microarrays [62] Nimse et al reportedthe DNA microarrays based on the 9G technology whichuses the interactions of the monolayer of calix[4]arenederivatives on the glass surface and the DNAs appended tothe nine consecutive guanines (9G) are also reported [32]The aminocalix[4]arene (AMCA) derivative with aldehydefunctional groups is allowed to reactwith the amine-modifiedglass surface to generate the AMCA slides As depicted inFigure 5 the determination of contact angle of water onthe AMCA modified glass surface indicates that the AMCAmolecules make the glass surface hydrophobic

Once the AMCA immobilization is done the solutioncontaining DNA probes appended to 9G is spotted on the

6 Journal of Chemistry

OH O OH

N

N

N

OH OHO

Si

Si

N

N

lowast

lowast

SiO2

SiO2

OH O OH

Si

SiO2

OH OH OH

SiO2

OH OHO

Si

SiO2

Si(OCH3)2

Single strandedunlabeled target DNA

+NClminus

NaNO2 + HCl

Diazonium ion

Cy3Cy5-dCTPDNA

For 14ndash16hr

lowast

lowast

NH2

NH2

Hybridized at 42∘Cat 4∘C

at 30min4∘C

Scheme 4 Covalent immobilization of probe DNA on a glass surface by diazotization and subsequent hybridization

O O O

O O

O

O

X X X X

+N

H4

+N

H4

H3C CH3O O O

O O

O

O

X X X X

H3C CH3

1 cm

1 cm

Figure 4 Interaction of calix[4]crown-5 derivative with proteins for the fabrication of protein microarray (adapted from [31])

Journal of Chemistry 7

(a) (b)

Figure 5 Contact angle comparison (a) bare glass and (b) AMCA modified glass slide (adapted from [32])

surface by using microarray After incubation at room tem-perature for 4 h the slides are washed to remove excess DNAsand driedThe free AMCAmolecules on the surface are thenblocked with the 4x SSC solution containing BSA and 01SDS Finally the slides are dried to obtain 9G DNAChips[63 64]

23 Carbon In recent years a nanoparticle-based structurelike nanotubes and nanowires has got tremendous attentionin biomedical and diagnostic fields [65 66] Before 1991 sp3hybridized form of carbon (diamond) sp2 hybridized formslike graphite and C60 fullerene were the only known formsof carbon with potential applications [67] In 1991 allotropeslike carbon nanotubes (CNT)were first reported and success-fully synthesized by Iijima with multiwall faces (MWCNT)[68]

Due to thermal electrical and magnetically uniqueproperties CNT became an important material in the devel-opment of biosensor platforms Commonly reportedmethodfor preparation of CNT includes chemical vapour deposition[69 70] arc discharge [71] and laser ablation [72]

Apart from CNT other carbon-based nanostructuresincluding carbondots carbon fibers andPDMSalso attractedresearchers due to their diverse properties for biomoleculeconjugation [73 74]Themajor advantage of carbon nanoma-terial is their large surface area which allows maximum spacefor biomolecule attachment

Immobilization of protein carbohydrate and nucleic acidon the CNT surfaces allows various biological applications[75 76]Themost important part in biomolecule conjugationis the surface functionalization of carbon-basedmaterialThegeneral techniques for carbon surface modification are (phy-sisorption) noncovalent and covalent modifications Thereare several reports on the different techniques of surfacemodification of carbon-based surfaces Due to the vastnessof the research on carbon-based material only few methodsare described in this paper

231 Physisorption Thehydrophobic character of CNT side-walls and the strong 120587-120587 interactions between the individualtubes causes them to aggregate and reduce their solubility in

common solvents which is considered as a problem for theirbiological applicationsHowever the samehydrophobic char-acter of theCNT surface is exploited for fabrication of biosen-sors by immobilizing biomolecules onto the CNT surfacesthrough hydrophobic-hydrophobic interactions [77ndash79]

The advantage of noncovalent interaction is a limiteddistortion of the three-dimensional structure of a protein orenzyme to be immobilized The hydrophobic amino acidsin proteins and enzymes develop the 120587-120587 interactions withthe hydrophobic part of CNT which make them adsorbedon the surface of CNT [80ndash83] As mentioned earlier theplatforms modified by noncovalent interactions suffer fromthe typical drawbacks of nonspecific interactions resulting inthe decreased specificity and sensitivity of a biosensor

To eliminate the problem of nonspecific interactions oftarget proteins with the sensor surface the novel approachof polyethylene oxide (PEO) polymer coating is adopted bymany researchers The PEO is well known for its proteinrepelling ability [84] Bomboi et al reported the use of Tween20 which is composed of three PEO branches and P103another molecule with hydrophobic polypropylene oxideunits to modify the surface of CNT before adsorption ofproteins on it The surface of Tween 20 and P103 modifiedCNT becomes slightly hydrophilic compared with bare CNTwhich results in the decrease in its interaction with thehydrophobic amino acid chains of biomarker proteins [85]

As depicted in Figure 6 for the selective immobilizationof streptavidin on the CNT surface Chen et al used mixednoncovalent and covalent approach which allows the highlyspecific immobilization of streptavidin and blocks the non-specific binding of other proteins like BSA [33]

Conjugation of a fluorescent molecule on the CNT sur-face is an immerging technology for highly sensitive detec-tion of biomolecules Nakayama-Ratchford et al reported theimmobilization of the fluorescent molecules like fluoresceinon the surface of CNT through 120587-120587 interactions [86] Thereare several reports on the applications of CNT surfaces mod-ified with the fluorescent molecules through noncovalentinteractions [87ndash90]

232 Chemical Modification To prevent the nonspecificbinding and to avoid the leaching of biomolecules from the

8 Journal of Chemistry

OH

OH

OH

O

HO

HO

HO

O

OO

OO

NH

O

NH

O

NH

OO

NH O

NH

O

NH

65 HON3

Boiling t = 8h

C2H4(NH2)2

NH2

H2N (CH2)2

(CH2)2

NH2(CH2)2

NH2(CH2)2

H2N (CH2)2

H2N (CH2)2

Scheme 5 Amine modification of CNT

BB

B

B B

B

SA SA

Figure 6 Streptavidin recognition by a nanotube coated with biot-inylated Tween (adapted from [33])

CNT surface a covalent modification technique is reportedThere are two types of covalent modifications namely (i)indirect method for example carboxylation of CNT surfaceand (ii) direct method for example fluorination of CNT sur-face where surface carbons change from sp2 to sp3 hybridiza-tion Esterification or amidation and sidewall covalent attach-ment are other approaches for covalent attachment [91 92]

(1) Carboxyl Modification The modification of the sensorsurfaces with the carboxyl groups is a general and highly usedsurface modification method Once the surface is modifiedwith the carboxyl groups it can be converted to a vari-ety of functional groups through reaction with appropriatereagents Furthermore the carboxylated surfaces can bedirectly conjugated with proteins or DNA through theiramine functional groups using coupling reagents A mixtureof sulphuric acid and nitric acid is a commonly used reagentfor the carboxylation of CNT surface

Marshall et al reported the method for carboxyl modifi-cation of CNT [93] According to this method a 2mg sampleof SWCNT is added to the 75 mixture of concentratedsulphuric acid and nitric acid (1mL) The mixture is allowedto sonicate in sonicator at 20∘CThe reaction mixture is thendiluted to 250mL by using deionized waterThe carboxylatedCNTs are then filtered through polytetrafluoroethylene filter(PTFE) of 045 120583m size Finally the collected nanotubes arewashedwith water at acidic pH followed by ethanol and driedin a vacuum desiccator

O OOH

O OOO

n

Figure 7 Structure of Epon resin 828

(2) Amine Modification Amide coupling is the most com-monly used conjugation technique in biomolecule attach-ment Either the amine or acid part of DNA or protein canbe used for conjugation using amide coupling reaction Forthe conjugation ofDNA toCNT through its phosphate groupamine modification is needed

Tam et al reported the DNA sensor based on the aminemodification of MWCNT as depicted in Scheme 5 [94] TheMWCNT were boiled in the 15M nitric acid for 12 h to gen-erate the carboxylated MWCNT The purified carboxylatedMWCNT were reacted with ethylenediamine to obtain theamine-modified MWCNT The amine-modified MWCNTwere conjugated to DNA by using EDC coupling reaction

Other reports for aminemodification of CNT include theuse of nitric acid and sulphuric acidmixture for carboxylationof the surface followed by ethylenediamine reaction [95]There are several reports on the covalent conjugation offluorescent molecules to the CNT surfaces [96ndash98]

(3) Epoxy Modification Epoxide group is a highly reactivefunctional group used in many substitution reactions as anelectrophile Eitan et al reported the covalent attachmentof epoxide-terminated molecules to carbon nanotubes byreaction between epoxide rings and carboxylic acid groupsthat are initially formed on the nanotube surface [99] Forepoxidation of CNT the surface is first carboxylated bydispersing the CNT in 75 solution of sulphuric acid in nitricacid for 3 h The purified carboxylated CNT were kept in theacetone with sonication for 1 hThen the solution containingthe carboxylated CNT is mixed with the solution of Eponresin 828 (Figure 7) in acetone to allow the reaction betweenEpon resin 828 and carboxyl groups on the CNT surface asdepicted in Scheme 6

Journal of Chemistry 9

O

O

O

O

R

OOCatalyst

O

O

O

O

O

O

CHHO

R

O

HC OH

R

O

H2C

O

HC OH

R

O

H2C

CH2

O

CHHO

R

O

CH2

HOHO

OHOH

+

Scheme 6 Epoxy modification of CNT

The mixture of solutions is sonicated for 1 h followedby stirring and heating at 70∘C The reaction was quenchedby addition of appropriate amount of potassium hydroxideThen the epoxilated CNT were purified and a number ofepoxy groups on the CNT surface were determined by usingthermogravimetric analysis

24 Nitrocellulose A PoC diagnosis system is always expe-cted to deliver final results in few minutes Though themicroarrays based on the glass and gold surfaces are usefulfor detection of multiple analytes at a time they need longertime for final data interpretation Microfluidic systems basedon paper or nitrocellulose membranes are emerging surfacesfor detection of bacteria viruses and proteins A paper isadvantageous due to its hydrophilic nature which allowsthe aqueous solutions to penetrate without the need of anyexternal force [100] The essential constituent of paper iscelluloseThe cellulose has hydroxyl functional groups whichcan be modified and changed according to surface propertiesneeded for a particular detection device [101] Due to lowcost and high availability paper is preferred for large scaleproduction Moreover the devices required for the tests areportable and disposable [102ndash105] The very first example ofpaper based detection is glucose detection in urine [106] andpregnancy test kit [107]There are different types of paper likeWhatman filter paper glossy paper [108] membrane and soforth Whatman filter is used because of its high penetrationand flow rate [109ndash112] but in some cases it does not havethe necessary characteristic for surface modification Mem-branes on the other hand are planner sheets and providelarger surface area for immobilization of biomolecules such

as DNA and protein The nitrocellulose (NC) membrane isbroadly used for immobilization of DNA [113] protein [114]and enzymes [115] due to its hydrophobic surface

241 Physical Adsorption Single-stranded DNAs are irre-versibly bound to the surface of the NCmembrane with non-covalent interactionsTheprimary interactions are hydropho-bic and electrostatic between the positively charged surfaceof the membrane and negatively charged DNAs The nitro-cellulose offers very high binding capacity for DNAs andproteins Fabrication of NC membranes can be done bydifferent methods including the photolithography The waxpatterningmethod is fast cheap and easy to process and doesnot need organic solvents The NCmembranes with the poresize of 045 120583mdo not need pretreatment for penetrationThefabrication process includesmainly printing and baking stepswhich can be finished in 10min As shown in Figure 8 firstlythe wax is printed on the surface of NCmembrane and bakedat 125∘C for 5min in the oven The melting of the wax onmembrane makes it more hydrophobic and affords surfacesuitable for the immunoassay For immunoassays Lu et alcoated the cAbs on the surface and the free area is blockedwith the 1 BSA

During baking melted wax passes through the mem-brane The 121∘ contact angle of backside membrane assuresthe melting of wax thoroughly The efficiency of wax treatedmembrane is compared with the untreated membrane byimmobilizing fluorescence labeled goat antihuman IgG Theimmobilization on wax printed surface is more uniform thanthe untreated membrane Apart from this a large volumeof liquid can be used because ring effect of protein on the

10 Journal of Chemistry

HO

OSH AuNP

AuNP-mAb

mAbEDCNHS

001M PBS

(CH2)15(CH2)11

NaBH4HAuCl4 + SH + HO

pH sim 74

Scheme 7 Immobilization on antibodies on AuNP

NC membrane

Cross section view

PrintingStep 1

Step 2 Baking

Wax patternedNC membrane

Wax is printed onto thesurface of NC membrane

Wax melts and penetratesthrough NC membrane

Nitrocellulose

Wax

Figure 8Wax printing on nitrocellulosemembranes (adapted from[34])

untreated membrane is avoided Wax printing method gen-erates 100 120583mmicrochannel which removes the micrometersize contaminants and makes the wax printed membranessuitable for the applications in microfluidic assays Apartfrom immobilization wax printing has application in dotimmunoassay and sample purifications [34]

Due to advantages of NC membrane for high bindingcapacity and good flow of solution it is also used on the chipsurfaces The glass slide can be coated with the 12 120583m layer ofNC to afford a platform with the intrinsic properties of NCThe solution of cAbs in PBS buffer containing 10 glycerolis then spotted on the modified surface After spotting theslides are incubated for one hour After incubation slides arewashed with 01 Tween 20 in PBS buffer and dried to gen-erate the platform for detection of biomarker proteins [116]

Apart from routine microarray applications NC mem-brane is also used for the detection of circulating tumor cells(CTC) as reported by Zhang et al The binding of CTCs bythe cAbs immobilized on the NC membrane is detected bySurface Enhanced Raman Scattering (SERS) as depicted inFigure 9

Usually the antibodies specific for cancer cells are usedas a capture substrate and immobilized on the surface TheNC membrane is cut into 1 cm times 1 cm pieces Then thesepieces are immersed in the ethanol and then tiled on thePMMA wafer After washing the membrane is activated byusing PBS buffer containing antibodies at 37∘C for 30minDuring this process the cAbs are avidly immobilized on theNC membrane The 1 BSA solution is loaded to block thefree surface area to avoid any background signals due tononspecific interactions Finally the membranes are washedwith PBS buffer and stored at 4∘CThe gold nanoparticle andRaman probes are used to detect the CTCs by SERS [35]

25 Gold Application of nanoparticles is amost focused areain the field of inorganic chemistry and it has also attractedimaginations of many biologists too Inorganic nanoparti-cles including gold silver and ferrous oxides have foundmany important applications in cell signaling drug deliveryand colorimetric and fluorescence-based detections Goldnanoparticles (AuNP) functionalized with proteins DNAsor Raman probes are well known in the field of biosensorsand nanobiotechnology for their applications in the molec-ular diagnostics [117ndash119] protein detection [120ndash122] generegulation [123] and cell imaging [124]

251 Covalent Modification

(1) Thiol Based Modification AuNPs are commonly usedin the electrochemical and optical detection systems Theconjugation with biomolecule does not change the opticalproperties ofAuNP [125]Di Pasqua et al reported thiolmod-ification for the detection of E coli O157H7 E coli specificantibodies were conjugated with the AuNPs [126] As shownin Scheme 7 the 10 nmAuNPs are carboxylated and then cou-pled to E coli specific monoclonal antibody (mAb) throughamide coupling

For the generation of AuNPs to the solution containing410mg of HAuCl

4sdot3H2O in 6mL of water ethanoic solutions

of 11-mercapto-1-undecanol and 16-mercaptohexadecanoicacid are added Upon addition of NaBH

4to this mixture at

0∘C the solution turns brown The product AuNP cappedwith alkanethiol pendant alcohol and carboxylic acid func-tional groups precipitate upon three hours of stirring Theprecipitated particles are then thoroughly washed with etha-nol and an ethanolic solution containing a small amountof 1M HCl The AuNPs are then dried under vacuum forten hours For the conjugation of mABs with the AuNPsthe carboxylic acid functional groups on the AuNPs are

Journal of Chemistry 11

SERSimaging

AuNPs

Raman labelNC membrane

AntibodyCancer cell

Figure 9 Detection of circulating tumor cells on NC membranes containing immobilized cAbs (adapted from [35])

activated by reacting the AuNPs with 1-ethyl-3-3(3-dimeth-ylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in the PBS buffer The mABs arethen added to this solution and the suspension is stirred atroom temperature for 30min The mAB-conjugated AuNPsare then collected by centrifugation and washing with PBSand ethanol The mAB-conjugated AuNPs successfully bindto E coli when incubated in PBS at pH 74 In other reportsthe AuNPs were found very effective in the detection ofcancerous pancreatic cells

The AuNPs are known to suffer from the problem ofaggregation upon long-term storage Therefore to solve thisissue the AuNPs are conjugated with the polyethylene glycol(PEG) to prevent their aggregation [127 128]The conjugationof PEGwith the AuNPsmakes the later hydrophilic thus pre-venting agglomeration induced by hydrophobic interactionsA PEGwith the heterobifunctional groups (dithiol at one endand a carboxyl at another end) is coated on the AuNP Thedithiol group allows stable anchoring heterobifunctional PEGligands on the surface of AuNP and the terminal carboxylgroup is used for coupling with antibodies The carboxy-terminated bifunctional PEG linker is synthesized by follow-ing a method reported by Eck et al which is depicted inScheme 8 The anionic polymerization of compound 1 withan excess of ethylene oxide allows synthesizing compound 2The treatment of compound 2 with chloroacetic acid at 60∘Callows generating compound 3 The reaction of an excess ofthe elemental bromine in dichloromethane at 0∘C for fourhours in the dark with compound 3 produces dibromidecompound 4 Compound 5 is obtained by reaction withcompound 4 in water with the excess of sodium hydrosulfidehydrate

The synthesized bifunctional PEG linker is then conju-gated with the citrate-stabilized gold nanoparticles by simpleligand exchangeThe citrate-stabilized gold nanoparticles areknown to aggregate in the buffer containing salts Thereforethe ligand exchange from citrate to PEG should be done inpure water The PEGylated AuNPs are conjugated to mono-clonal F19 antibodies for the detection of human pancreaticcarcinoma through EDCNHS coupling reaction [129]

OHO

(2) HCl

1

2

3

4

5

Br Br

HS SH

(CH2)9

(CH2)9

(CH2)9

(CH2)9

+

NaHDMF60∘C

(OCH2CH2)n

(OCH2CH2)n

(OCH2CH2)n

OCH2COOH

OCH2COOH

(CH2)9 (OCH2CH2)n OCH2COOH

OminusNa+

Br2

(2) Acetic acid (1) NaSHH2O

60∘C(1) ClCH2-COONa

Scheme 8 Synthesis of bifunctional PEG linker using conjugationwith AuNP

(2) Hydrazide Modification According to the report by Zhiet al the hydrazide-derivatized self-assembledmonolayer ona gold surface is used for the efficient and selective anchor-ing of oligosaccharide [39] The generated oligosaccharidemicroarrays allow the fluorescence-based detection of targetproteins The use of gold as a substrate for the fluorescence-based detection suffers from the drawbacks including flu-orescence quenching and nonspecific surface adsorption ofproteins However the use of120596-thiolated fatty acid (C

16) self-

assembledmonolayer between the gold surface andhydrazide

12 Journal of Chemistry

AuC C

C

C

OHOHO O

O

O

O

O

O

O

O

O

CHR

NN

H

N

N

N

H

NH

NH

NH

H

NH

C

O

O

O NNH

NH

HNH

H

S

S

S

S

HS Au

Au

Au

Au

Au

C16 SAM

Adipic dihydrazideEDC

(Sugar)R-CHO

Binding to protein

Sugarprobe

Protein Alexafluoro 532

SAM andblocking layer

Ab 2nd Ab

NH2

NH2H2N

CH2R

Scheme 9 Application of hydrazide-derivatized SAM on a goldsurface for the fabrication of oligosaccharide microarray (adaptedfrom [39])

groups minimizes the quenching effect Moreover the effec-tive blocking of the surface with the poly(ethylene glycol)aldehyde and BSA reduces the nonspecific adsorption ofprotein on the surface

For the fabrication of the reported oligosaccharidemicroarrays the gold substrate is prepared by following amethod depicted in Scheme 9 The self-assembled mono-layer (SAM) of 16-mercaptohexadecanoic acid (MHDA) isobtained by soaking the gold coated slides in the isobutylalcohol for 2 days The slides are then washed in ethanolto remove excess reagents and are dried under the nitrogenstream The carboxyl functional groups on the SAM areconverted to the hydrazide groups by incubation of the SAMcovered slides in the dimethyl sulfoxide solution containing1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and adipicdihydrazide The ethanol-washed and dried slides are thenused for the oligosaccharide printing to obtain oligosaccha-ride microarrays

The generated oligosaccharide microarray platformallows interrogation of carbohydrate-protein interactions ina high-throughput manner

26 Silver Similar to AuNPs silver nanoparticles (AgNP) arealso used for the immobilization of proteins and enzymesThe surface of AgNP allows adsorption of proteins Henceit can be utilized as a host matrix for various biomoleculesSilver is a suitable substrate for the immobilization of wholecell or the isolated enzymes [130 131]

Texp lt Tm

Ag

AgAg

Ag

AgAg

Texp gt Tm

Figure 10 AgNPs-oligonucleotide conjugates (adapted from [36])

261 Electrostatic Modification The electrostatic interac-tions allow the physical adsorption of biomolecules on thesurface of AgNPs Shen et al reported that the AgNPs aresynthesized by reduction of silver nitrate in the presence ofsodium citrate During the reduction process the solutionis sonicated for 15min to obtain the yellow silver colloidwhich is then kept at 4∘C for several days away from lightThen isolated nanoparticles can be used for physisorption ofproteins at a pH higher than their isoelectric point [132]

262 Covalent Modification As depicted in Scheme 10the AgNPs prepared by the citrate reduction method andstabilized with citrate [133] can be functionalized with car-boxyl groups upon treatment with 3-mercaptopropanoic acid(MPA) As reported by the Petkova et al for the immobi-lization of alcohol dehydrogenase from Thermoanaerobiumbrockii (TbADH) the carboxyl-modified AgNPs were treatedwith the solution containing TbADH under continuousstirring for 7 h at 26∘C a research by [134] The AgNPsmodified with the TbADH were successfully used for thebiotransformation studies

The application of a bifunctional linker for the modifica-tion of AgNPs is reported [135 136] The bifunctional linker11-mercaptoundecanoic acid was used with 1-octanethiol in1 1 ratio to generate the mixed SAM on the surface of AgNPThe IgG antibodies are then conjugated with the mixed SAMmodified AgNPs It is reported that upon covalent conjuga-tion of biomolecules with AgNPs their stability and activityis maintained [137]

According to another report on the covalent modifi-cation AgNPs-oligonucleotide conjugates are prepared byusing DNA and triple cyclic disulfide moieties [36] Asdepicted in Figure 10 the two types ofAgNPs-oligonucleotideconjugates with complementary DNA sequences undergoDNA hybridization driven coagulation resulting in the colorchange

As depicted in Figure 11 the AgNP-DNA conjugates wereprepared by treatment of AgNPs with the cyclic disulfidemodified oligonucleotide The AgNP and oligonucleotideswere allowed to react with each other with 1 4 ratio inthe presence of 1 sodium dodecyl sulfate and NaCl Theovernight incubation of solution results in the AgNP-DNAconjugates which are collected by centrifugation and washedto remove the excess DNAs

Journal of Chemistry 13

Ag AgMPAOH

OO OH

O

HOCitrate

Citrate

Ag

COOH

COOH

TbADHAg

CONH

COOH

TbADHOminusNa+

H2N

Scheme 10 Covalent conjugation of enzymes on the surface of carboxyl-modified AgNPs

OHO

EDC HOSu Bis-amino

polyethylene glycol

NH

OO

44GMBS N

H

OO N

H44

ON

O

O3

CoA

NH

OO N

H44

ON

O

O3

SHN

O

OH

OP O

OPO

O O

OHO

NNN

N

PO

OminusOminus

OminusOminus

NH2

NH2

Scheme 11 Covalent conjugation of coenzyme A to polystyrene nanoparticles

O OOO P

OHSS

5998400 (DSP)3-A10-ATT-ATC-ACT 3998400

DSP cyclic disulfide-containingphosphate derivative =

Figure 11 Conjugation of AgNPs with oligonucleotides by usingDSP as a linker molecule (adapted from [36])

27 Polystyrene Polystyrene is an aromatic polymerobtained by polymerization of styrene monomers [138] Thepolystyrene-based NPs are widely used in the moleculardiagnostics for the detection of biomarker proteins andgenomic DNAs Polystyrene can be employed as a coating ona variety of nanoparticles as its functional groups can be easilymodified or conjugated with other molecules The otherapplication of polystyrene is in the fabrication of fluorescencebeads (FBs) The fluorescence molecules are loaded into thepolystyrene shell to produce FBs which are then used invarious sensing applications The polystyrene is also used tocoat the magnetic NPs so they can be conjugated with otherbiomolecules such as DNA and Proteins The applications ofpolystyrene include but are not limited to the detection ofE coli [139] the detection of cardiac Troponin T (cTnT) thedetection of Herpes simplex virus and many more

271 Covalent Modification Covalent modification throughcarboxyl group iswell known formodification of biomolecule

Most of the polystyrene-based nanoparticles bear large num-bers of pendant carboxyl which increases the loading amountof biomolecule

Enzyme catalyzed covalent immobilization of the pro-teins bearing a small 12-mer ldquoybbRrdquo tag onto the polystyrenenanoparticles (PSNP) is recently reported by Wong et al[140] As depicted in Scheme 11 the carboxyl-PSNPs werereacted with the bis-amino-polyethylene glycol in the pres-ence of HOSu and EDC to generate the amino-pegylatedPSNPs These PSNPs are then reacted with the g-maleimi-dobutyric acid succinimidyl (GMBS) to obtain maleimide-functionalized PSNPs The maleimide-functionalized PSNPsupon chemoligation with coenzyme A (CoA) produce theCoA-derivatized PSNPs

As depicted in Scheme 12 the protein of interest bearingybbR-tag is immobilized on the CoA-derivatized PSNPsThephosphopantetheinyl transferase (Sfp) catalyzed the reactionbetween the serine residue of the ybbR-tag and the phos-phopantetheine moiety of CoA with the simultaneous lossof 3101584051015840-adenine diphosphate results in the attachment ofproteins onto the surface of PSNPs It is reported that theenzymes immobilized by this method retain their activity

There are several reports on the use of fluoromicrobeadsfor the detection of biomarkers Primarily the fluoromi-crobeads are made up of carboxylated polystyrene as a coat-ingmaterial entrapping the fluorescentmolecules Accordingto the recent report by Song et al [37] the fluoromicrobeadswere used for the detection of the cTnT on the proteinmicroarray as depicted in Figure 12

The carboxylate modified fluoromicrobeads were conju-gated with the anti cTnI mAb through EDCNHS-mediated

14 Journal of Chemistry

HN

O

OH

OP

O

O

PO

O

OHO

N

NN

P

O

S

HN

O

Coenzyme A

Phosphopantetheine

PO

O

O

OHO

N Sfp

NN

N

P

O

ybbr-protein

HN

O

OH

OP

O

O

S

HN

O

NH2

NH2

Ominus

Ominus

Ominus

minusO

minusO

Mg2+

HO∙∙

Ominus

OminusOminus

minusO

N

O

Polystyrenenanoparticle

Scheme 12 Protein conjugation to polystyrene NP

System 1 antibody-conjugated fluoromicrobeads

System 2 avidin-conjugated fluoromicrobeads

DTSP SAM

Anti-cTnI cAb

cTnI

Figure 12 Application of the polystyrene-coated fluoromicrobeadsfor the detection of cTnI on the protein microarray (adapted from[37])

coupling reaction The use of fluoromicrobeads alloweddetecting the cTnI in plasma samples with a range of 01ndash100 ngmL

272 Affinity-Based Modification The affinity interactionsare used for the attachment of oligonucleotides with thefluoromicrobeads or polystyrene-coated magnetic beads Togenerate the oligonucleotide conjugated fluoromicrobeads ormagnetic beads respective polystyrene-coated beads are firstconjugated with the streptavidin using the EDCNHS cou-pling reaction as reported by Zhang et al [141] As depicted

B

B

MB MB

MB

BB

Magnetic bead

Streptavidin

DNA labeled biotin

Figure 13 DNA attachment to the magnetic beads

in Figure 13 the streptavidinmodified beads are then allowedto incubate with the biotinylated oligonucleotides Due to theaffinity of biotin for streptavidin the biotinylated oligonu-cleotides can be readily immobilized on the streptavidincoated beads

The binding affinity of streptavidin and biotin in solutionis up to 25 times 1013 (molL)minus1 [142] This interaction is about amillion times stronger than the antigen and antibody inter-action The antibodies directly immobilized onto the sur-face lose 90 of their biological activity [143] Howeverthe biotinylated antibodies immobilized on the streptavidincoated surface can retain their bioactivity [144]

Journal of Chemistry 15

3 Conclusions

Surface modification techniques of the materials used asplatforms in the fabrication of biosensors are reviewed inthis paper There are several reports on materials and vari-ous methods for altering their physicochemical propertiesHence one of these methods can be chosen according tothe targeted use and needed physiochemical properties Itis important to note that the performance of the biosensoris highly dependent on the substrate material used and itsmeticulous modification for particular applications There-fore it is critical to understand the principles of a biosensor toidentify the correct substrate material and its surface modifi-cation chemistry Furthermore it is important to look at thelatest advances in the materials and techniques used for thefabrication of a biosensor before the processing

Competing Interests

All authors declare that there is no conflict of interests

Acknowledgments

This research was supported by the Hallym UniversityResearch Fund (HRF-201601-010) This work was also sup-ported by the fund obtained through Industry-Academic col-laboration between Biometrix Technology Inc (ChuncheonSouth Korea) and Hallym University

References

[1] A Sassolas B D Leca-Bouvier and L J Blum ldquoDNA biosen-sors andmicroarraysrdquoChemical Reviews vol 108 no 1 pp 109ndash139 2008

[2] A Cavalcanti B Shirinzadeh M Zhang and L C KretlyldquoNanorobot hardware architecture for medical defenserdquo Sen-sors vol 8 no 5 pp 2932ndash2958 2008

[3] R-Q Zhang S-L Liu W Zhao et al ldquoA simple point-of-caremicrofluidic immunomagnetic fluorescence assay for path-ogensrdquo Analytical Chemistry vol 85 no 5 pp 2645ndash2651 2013

[4] S B Nimse K S Song M D Sonawane D R Sayyed and TS Kim ldquoImmobilization techniques for microarray challengesand applicationsrdquo Sensors vol 14 no 12 pp 22208ndash22229 2014

[5] A P F Turner ldquoBiosensors sense and sensibilityrdquo ChemicalSociety Reviews vol 42 no 8 pp 3184ndash3196 2013

[6] L Wu and X Qu ldquoCancer biomarker detection recent achieve-ments and challengesrdquoChemical Society Reviews vol 44 no 10pp 2963ndash2997 2015

[7] K Ariga Q Ji T Mori et al ldquoEnzyme nanoarchitectonicsorganization and device applicationrdquo Chemical Society Reviewsvol 42 no 15 pp 6322ndash6345 2013

[8] W-W Zhao J-J Xu and H-Y Chen ldquoPhotoelectrochemicalDNA biosensorsrdquo Chemical Reviews vol 114 no 15 pp 7421ndash7441 2014

[9] Q Liu C Wu H Cai N Hu J Zhou and P Wang ldquoCell-basedbiosensors and their application in biomedicinerdquo ChemicalReviews vol 114 no 12 pp 6423ndash6461 2014

[10] X Zhao S Nampalli A J Serino and S Kumar ldquoImmobi-lization of oligodeoxyribonucleotides with multiple anchors to

microchipsrdquo Nucleic Acids Research vol 29 no 4 pp 955ndash9592001

[11] P Kumar S K Agrawal A Misra and K C Gupta ldquoA newheterobifunctional reagent for immobilization of biomoleculeson glass surfacerdquo Bioorganic 120572Medicinal Chemistry Letters vol14 no 5 pp 1097ndash1099 2004

[12] F Secundo ldquoConformational changes of enzymes upon immo-bilisationrdquo Chemical Society Reviews vol 42 no 15 pp 6250ndash6261 2013

[13] S Lee S Kim J Malm O C Jeong H Lilja and T LaurellldquoImproved porous silicon microarray based prostate specificantigen immunoassay by optimized surface density of thecapture antibodyrdquoAnalytica Chimica Acta vol 796 pp 108ndash1142013

[14] K Jaras A A Tajudin A Ressine et al ldquoENSAM europiumnanoparticles for signal enhancement of antibody microarrayson nanoporous siliconrdquo Journal of Proteome Research vol 7 no3 pp 1308ndash1314 2008

[15] C Steinhauer A Ressine G Marko-Varga T Laurell C AK Borrebaeck and C Wingren ldquoBiocompatibility of surfacesfor antibody microarrays design of macroporous silicon sub-stratesrdquo Analytical Biochemistry vol 341 no 2 pp 204ndash2132005

[16] K Jaras B Adler A Tojo et al ldquoPorous silicon antibodymicroarrays for quantitative analysis measurement of free andtotal PSA in clinical plasma samplesrdquo Clinica Chimica Acta vol414 pp 76ndash84 2012

[17] S W Lee K Hosokawa S Kim et al ldquoA highly sensitive poroussilicon (P-Si)-based human Kallikrein 2 (hK2) immunoassayplatform toward accurate diagnosis of prostate cancerrdquo Sensorsvol 15 no 5 pp 11972ndash11987 2015

[18] C Roychaudhuri ldquoA review on porous silicon based electro-chemical biosensors beyond surface area enhancement factorrdquoSensors and Actuators B Chemical vol 210 pp 310ndash323 2015

[19] ARessine S EkstromGMarko-Varga andT Laurell ldquoMacro-nanoporous silicon as a support for high-performance proteinmicroarraysrdquo Analytical Chemistry vol 75 no 24 pp 6968ndash6974 2003

[20] S Lee E Silajdzic H Yang et al ldquoA porous silicon immunoas-say platform for fluorometric determination of 120572-synuclein inhuman cerebrospinal fluidrdquo Microchimica Acta vol 181 no 9-10 pp 1143ndash1149 2014

[21] S Belhousse N Belhaneche-Bensemra K Lasmi et alldquoModified porous silicon for electrochemical sensor of para-nitrophenolrdquo Materials Science and Engineering B vol 189 pp76ndash81 2014

[22] N Reta A Michelmore C Saint B Prieto-Simon and NH Voelcker ldquoPorous silicon membrane-modified electrodesfor label-free voltammetric detection of MS2 bacteriophagerdquoBiosensors and Bioelectronics vol 80 pp 47ndash53 2016

[23] B Guan A Magenau S Ciampi K Gaus P J Reece and J JGooding ldquoAntibody modified porous silicon microparticles forthe selective capture of cellsrdquo Bioconjugate Chemistry vol 25no 7 pp 1282ndash1289 2014

[24] S Vutti N Buch-Manson S Schoffelen N Bovet K LMartinez and M Meldal ldquoCovalent and stable CuAAC mod-ification of silicon surfaces for control of cell adhesionrdquo Chem-BioChem vol 16 no 5 pp 782ndash791 2015

[25] A M Rossi L Wang V Reipa and T E Murphy ldquoPoroussilicon biosensor for detection of virusesrdquo Biosensors andBioelectronics vol 23 no 5 pp 741ndash745 2007

16 Journal of Chemistry

[26] T L Lasseter B H Clare N L Abbott and R J HamersldquoCovalently modified silicon and diamond surfaces resistanceto nonspecific protein adsorption and optimization for biosens-ingrdquo Journal of the American Chemical Society vol 126 no 33pp 10220ndash10221 2004

[27] M Li K-G Neoh E-T Kang T Lau and E E ChiongldquoSurface modification of silicone with covalently immobilizedand crosslinked agarose for potential application in the inhibi-tion of infection and omental wrappingrdquo Advanced FunctionalMaterials vol 24 no 11 pp 1631ndash1643 2014

[28] G MacBeath and S L Schreiber ldquoPrinting proteins as microar-rays for high-throughput function determinationrdquo Science vol289 no 5485 pp 1760ndash1763 2000

[29] S B Nimse M D Sonawane K S Song and T Kim ldquoBio-marker detection technologies and future directionsrdquoThe Ana-lyst vol 141 no 3 pp 740ndash755 2016

[30] M D Sonawane S B Nimse K Song and T Kim ldquoDetectionquantification and profiling of PSA current microarray tech-nologies and future directionsrdquo RSC Advances vol 6 no 9 pp7599ndash7609 2016

[31] S B Nimse and T Kim ldquoBiological applications of function-alized calixarenesrdquo Chemical Society Reviews vol 42 no 1 pp366ndash386 2013

[32] K-S Song S B Nimse J Kim et al ldquo9GDNAChip microarraybased on the multiple interactions of 9 consecutive guaninesrdquoChemical Communications vol 47 no 25 pp 7101ndash7103 2011

[33] R J Chen S Bangsaruntip K A Drouvalakis et al ldquoNonco-valent functionalization of carbon nanotubes for highly specificelectronic biosensorsrdquo Proceedings of the National Academy ofSciences of the United States of America vol 100 no 9 pp 4984ndash4989 2003

[34] Y Lu W Shi J Qin and B Lin ldquoFabrication and characteri-zation of paper-based microfluidics prepared in nitrocellulosemembrane by wax printingrdquo Analytical Chemistry vol 82 no1 pp 329ndash335 2010

[35] P Zhang R Zhang M Gao and X Zhang ldquoNovel nitrocel-lulose membrane substrate for efficient analysis of circulatingtumor cells coupled with surface-enhanced raman scatteringimagingrdquo ACS Applied Materials and Interfaces vol 6 no 1 pp370ndash376 2014

[36] J-S Lee A K R Lytton-Jean S J Hurst and C AMirkin ldquoSil-ver nanoparticlemdasholigonucleotide conjugates based on DNAwith triple cyclic disulfide moietiesrdquo Nano Letters vol 7 no 7pp 2112ndash2115 2007

[37] S Y Song Y D Han K Kim S S Yang and H C YoonldquoA fluoro-microbead guiding chip for simple and quantifiableimmunoassay of cardiac troponin I (cTnI)rdquo Biosensors andBioelectronics vol 26 no 9 pp 3818ndash3824 2011

[38] S V Lemeshko T Powdrill Y Y Belosludtsev and M HoganldquoOligonucleotides form a duplex with non-helical properties ona positively charged surfacerdquoNucleic Acids Research vol 29 no14 pp 3051ndash3058 2001

[39] Z-L Zhi A K Powell and J E Turnbull ldquoFabrication ofcarbohydrate microarrays on gold surfaces direct attachmentof nonderivatized oligosaccharides to hydrazide-modified self-assembledmonolayersrdquoAnalytical Chemistry vol 78 no 14 pp4786ndash4793 2006

[40] S L Pan and L Rothberg ldquoChemical control of electrodefunctionalization for detection of DNA hybridization by elec-trochemical impedance spectroscopyrdquo Langmuir vol 21 no 3pp 1022ndash1027 2005

[41] Z Lu C M Li Q Zhou Q-L Bao and X Cui ldquoCovalentlylinked DNAprotein multilayered film for controlled DNAreleaserdquo Journal of Colloid and Interface Science vol 314 no 1pp 80ndash88 2007

[42] L-S Jang and H-J Liu ldquoFabrication of protein chips basedon 3-aminopropyltriethoxysilane as a monolayerrdquo BiomedicalMicrodevices vol 11 no 2 pp 331ndash338 2009

[43] F Fixe M Dufva P Telleman and C B Christensen ldquoFunc-tionalization of poly(methyl methacrylate) (PMMA) as a sub-strate for DNAmicroarraysrdquoNucleic Acids Research vol 32 no1 article e9 2004

[44] A Lueking M Horn H Eickhoff K Bussow H Lehrachand G Walter ldquoProtein microarrays for gene expression andantibody screeningrdquo Analytical Biochemistry vol 270 no 1 pp103ndash111 1999

[45] N Zammatteo L Jeanmart S Hamels et al ldquoComparisonbetween different strategies of covalent attachment of DNA toglass surfaces to build DNA microarraysrdquo Analytical Biochem-istry vol 280 no 1 pp 143ndash150 2000

[46] M Ozmen K Can I Akin et al ldquoSurface modification of glassbeads with glutaraldehyde characterization and their adsorp-tion property for metal ionsrdquo Journal of Hazardous Materialsvol 171 no 1ndash3 pp 594ndash600 2009

[47] C Funk PM Dietrich T Gross HMinW E S Unger andWWeigel ldquoEpoxy-functionalized surfaces for microarray appli-cations surface chemical analysis and fluorescence labeling ofsurface speciesrdquo Surface and Interface Analysis vol 44 no 8pp 890ndash894 2012

[48] S Mahajan P Kumar and K C Gupta ldquoOligonucleotide mic-roarrays immobilization of phosphorylated oligonucleotideson epoxylated surfacerdquo Bioconjugate Chemistry vol 17 no 5pp 1184ndash1189 2006

[49] M C Pirrung J D Davis and A L Odenbaugh ldquoNovelreagents and procedures for immobilization of DNA on glassmicrochips for primer extensionrdquo Langmuir vol 16 no 5 pp2185ndash2191 2000

[50] E Southern K Mir and M Shchepinov ldquoMolecular interac-tions on microarraysrdquo Nature Genetics vol 21 no 1 pp 5ndash91999

[51] M S Shchepinov S C Case-Green and E M SouthernldquoSteric factors influencing hybridisation of nucleic acids tooligonucleotide arraysrdquo Nucleic Acids Research vol 25 no 6pp 1155ndash1161 1997

[52] D A Tomalia A M Naylor and W A Goddard III ldquoStarbustdendrimers molecular-level control of size shape surfacechemistry topology and flexibility from atoms to macroscopicmatterrdquo Angewandte ChemiemdashInternational Edition in Englishvol 29 no 2 pp 138ndash175 1990

[53] R Benters C M Niemeyer D Drutschmann D Blohm andD Wohrle ldquoDNA microarrays with PAMAM dendritic linkersystemsrdquo Nucleic Acids Research vol 30 no 2 p e10 2002

[54] J H Moon J W Shin S Y Kim and J W Park ldquoFormationof uniform aminosilane thin layers an imine formation tomeasure relative surface density of the amine grouprdquo Langmuirvol 12 no 20 pp 4621ndash4624 1996

[55] J C Alwine D J Kemp and G R Stark ldquoMethod fordetection of specific RNAs in agarose gels by transfer to diazo-benzyloxymethyl-paper and hybridization with DNA probesrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 74 no 12 pp 5350ndash5354 1977

[56] P L Dolan Y Wu L K Ista R L Metzenberg M A Nelsonand G P Lopez ldquoRobust and efficient synthetic method for

Journal of Chemistry 17

forming DNA microarraysrdquo Nucleic Acids Research vol 29 no21 article e107 2001

[57] S B Nimse J Kim K-S Song et al ldquoSelective recognitionof the ditopic trimethylammonium cations by water-solubleaminocalix[4]arenerdquo Tetrahedron Letters vol 52 no 29 pp3751ndash3755 2011

[58] V-T Ta S B Nimse K-S Song et al ldquoCharacterization ofthe mixed self-assembled monolayer at the molecular scalerdquoChemical Communications vol 47 no 40 pp 11261ndash11263 2011

[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

[60] Y Lee E K Lee YW Cho et al ldquoProteoChip a highly sensitiveprotein microarray prepared by a novel method of proteinimmobilization for application of protein-protein interactionstudiesrdquo Proteomics vol 3 no 12 pp 2289ndash2304 2003

[61] S W Oh J D Moon H J Lim et al ldquoCalixarene derivative asa tool for highly sensitive detection and oriented immobiliza-tion of proteins in a microarray format through noncovalentmolecular interactionrdquo The FASEB Journal vol 19 no 10 pp1335ndash1337 2005

[62] S B Nimse K-S Song J Kim D R Sayyed and T Kimldquo9G DNAChip technology self-assembled monolayer (SAM)of ssDNA for ultra-sensitive detection of biomarkersrdquo Interna-tional Journal ofMolecular Sciences vol 14 no 3 pp 5723ndash57332013

[63] V-T Nguyen S B Nimse K-S Song et al ldquoHPAI 9GDNAChip discrimination of highly pathogenic influenza virusgenesrdquo Chemical Communications vol 48 no 38 pp 4582ndash4584 2012

[64] K-S Song S B Nimse J Kim D R Sayyed and T Kim ldquoAnew platform for a convenient genotyping systemrdquo ChemicalCommunications vol 49 no 26 pp 2661ndash2663 2013

[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

[67] F Hennrich C Chan VMoore M Rolandi andM OrsquoConnellCarbonNanotubes Properties and Applications Taylor amp FrancisGroup Abingdon UK 2006

[68] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

[69] C Singh M Shaffer I Kinloch and A Windle ldquoProductionof aligned carbon nanotubes by the CVD injection methodrdquoPhysica B Condensed Matter vol 323 no 1ndash4 pp 339ndash3402002

[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

[71] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

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Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

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Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

2 Journal of Chemistry

Figure 1 The macroporous surface of modified silicon (adapted from [13])

2 Material and Techniques forSurface Modification

Modification of a surface is crucial to producing biomoleculedetection platforms In general the functional groups presentin biomolecules are allowed to react with the functionalgroups on the modified surfaces for their immobilizationMost common biomolecules immobilized on the surface forthe fabrication of the diagnostic devices are DNA proteinsand carbohydrates DNA oligomers can be synthesized tohave terminal amine and aldehyde groups Proteins naturallycontain amine sulfhydryl and carboxylic acid functionalgroups Carbohydrates in general have hydroxyl functionalgroups and amine functional groups in case of glucosamineDepending on these groups surfaces of the substrate aremodified for biomolecule attachment The efficiency of thedetection platform is strongly affected by the proper immo-bilization of biomolecules Therefore the materials and theirsurface modification chemistries are discussed in detail Thecommon surfaces used in the diagnostic devices are siliconglass slide glass membranes carbon nitrocellulose polysty-rene silver gold and so forth

21 Silicon Silicon is the element of periodic table that rarelyoccurs in pure form It occurs in a stable oxidized formThe typical application of silicon in electronic devices is as asemiconductor Electrochemical detection of protein is wellknown because it is label-free and allows real-time detec-tion Physical adsorption is one of the choices for antibodyimmobilization as it does not need temperature and humiditycontrols [13]The shorter time of immobilizationmakes assayfaster compare to other methods [14] Porous form of siliconsurface makes it more efficient for the immobilization due toformation of pseudo-three-dimensional surface [15 16] Theporous silicon (P-Si) surface shows high spot homogeneitylow internal fluorescence little wetting ability and lessnonspecificity [17] Depending on the pore size the P-Si hasthree categories microporous (less than 10 nm) mesoporous(10ndash50 nm) and macroporous (larger than 50 nm) It hasbeen reported that the macroporous silicon surface is highly

suitable for antibody immobilization [13] There are severalreports on the techniques used for the fabrication of siliconsurface

211 Electrochemical Modification The physisorption ofbiomolecules on the P-Si depends heavily on its micro- andnanomorphology controlled by the surface etching condi-tions and selection of silicon type A great deal of work isreported on the fabrication of micro- and nanoporous siliconfor antibody adsorption [18 19] Lee et al selected a boron sil-icon wafer with a specific resistivity (sim6ndash8Ωcm) and placedit in the electrochemical cell

As depicted in Figure 1 a self-supporting layer of P-Si is fabricated by growing an anodic oxide followed byits dissolution using an electropolishing current in a 15hydrofluoric acid solution leading to the formation of poresThe macroporous P-Si is then cut into pieces and fitted inmicrotitre plate for deposition of capture antibodies (cAb)for sandwich immunoassay [20]There are several reports onthe applications of the P-Si surfaces for the electrochemicaldetection of various chemicals and bacteria [21 22]

212 Covalent Modification P-Si microparticles have highand unique reflectance properties The antibodies which cantarget and capture specific antigens or cells can be cova-lently immobilized on the P-Si microparticles The hydride-terminated surface of the P-Si microparticles can be pas-sivated by hydrosilylation with dialkyne species Guan andcoworker used Cu(I)-catalyzed alkyne-azide cycloaddition(CuAAC) followed by succinimidyl activation reaction forcoupling of the antibodies to P-Si As shown in Figure 2 anti-body modified P-Si microparticles were employed for theselective capture and detection of HeLa cells [23] SimilarCuAAC based surface modification for adhesion of cell sur-face has also been reported [24]

Other applications of P-Si surface include fabricationof protein microarray for PSA detection with the limit ofdetection (LOD) of 800 fgmL A successful covalent modi-fication of P-Si has been reported by Rossi et al for detectionof MS2 virus with the LOD of 2 times 107 plaque-forming

Journal of Chemistry 3

Visible light Reflectance lightSelective target of antibody modified

particles to fluorescent cells

Porous silicon microparticle

mCherry antibodyTfR-mCherry

Cell membrane

Figure 2 Covalent bonding of antibodies to P-Si microparticles for detection of cells (adapted from [23])

DNA

Amine-modifiedglass surface

SiO

SiO

SiO

SiO

SiO

SiO

SiO

SiO

SiO

SiO O O O O O O O O O

H3N+ H3N+ H3N+ H3N+ H3N+ H3N+H3N+ H3N+ H3N+ H3N+

Figure 3 Physisorption of DNA on the amine-modified glass surface

units per mL (pfumL) [25] As explained earlier the strictfabrication protocol is needed for accurate size of poresChange in the concentrations of reagents and change incurrent and time affect the reproducibility of the result Othercovalent ethylene glycol modified silicon surfaces for specificadsorption of protein through photochemical reaction [26]and silicon covalent surface modification for agarose cross-linking in form of catheter have been reported for infectioninhibition and omental wrapping [27]

22 Glass (SiO2) A glass is made up of a silicon dioxide

(SiO2)Theoxide layer protects the silicon fromchemical deg-

radation and reactions Silicon dioxide is abundant in natureand thermally stable due to a large number of silicon andoxygen bonds Glass substrates are easily available and simpleto handle and have high mechanical stability Glass surfacesare widely used for the immobilization of DNA proteins andother low molecular weight biomolecules [28] In diagnosticfield glass surface plays a crucial role as microarray platformfor detection of various pathogenic DNA as well as biomarkerprotein [29 30]

221 Physisorption Based Modification Physical adsorptionor physisorption is one of the simplest techniques used for thebiomolecule immobilization on glass surfaces As shown inFigure 3 the negatively charged phosphate backbone onDNAforms an ionic interaction with the positively charged surface

of amine-modified glass surface through charge interactions[38]

Lemeshko et al reported that the aminosilanization ofthe glass surface by treatment with 3-(aminopropyl) trime-thoxysilane (APTMS) affords the positively charged surfaceUnfortunately the immobilization of DNAswith thismethoddoes not result in the reproducible DNA detection platformBecause the multiple interaction of negatively charged DNAbackbone with the cationic surface orients it parallel to theglass surface thus its availability for hybridization with thecomplimentary DNA (cDNA) is significantly low

The random orientation of the immobilized DNAs isalso related to the nonspecific hybridization and low repro-ducibility The change in pH of solution and temperaturesignificantly affects the performance of the platform based onthe method of physisorption

222 Covalent Modification Due to various disadvantagesof physisorption methods the covalent surface modificationstrategy has been widely used Covalent bond is stronger andmore stable than electrostatic interaction at solution-surfaceinterfaces [40 41] The glass surfaces and be modified withthe different functional groups suitable for making covalentbonds with the biomolecules to be immobilized In generalthe biomolecules have amine carboxylic acid and sulfhydrylfunctional groups These functional groups can be used forthe immobilization of biomolecules on the surface There are

4 Journal of Chemistry

OO

GlutaraldehydeN O NNH2 N-DNA-Cy3

-DNA-Cy3H2N

Scheme 1 Aldehyde modification of glass slide

Si

Si

O

O

O

O

O

O

Si

Si

O

O

O

OH

OH

OP

O-d(NNN)

O-d(NNN)

O

O

OO O

P

O

O

O

Ominus

Ominus

d(NNN)=OP32minus

MW 10min35∘C 4hr

Scheme 2 Covalent attachment of phosphorylated DNA

various reports on the glass surfacemodification for the cova-lent attachment of biomolecules

(1) Aldehyde Modification For the aldehyde modification ofthe glass surface the silanol groups on the surface are con-verted to an amine by different methods using amine mod-ification reagents such as (3-Aminopropyl)triethoxysilane(APTES) [42] Fixe et al reported the aldehyde modificationusing glutaraldehyde As shown in Scheme 1 the amine-modified surface is then treated with glutaraldehyde (25vv) in 01M PBS for 2 h at room temperature The slide isthen washed with water and dried The solution containingamine-modified DNAs is spotted on the slide and incubatedin humidified chamber for up to 24 h to afford the DNAmicroarray However it is important to note that the unre-acted aldehyde functional groups on the glass surface shouldbe blocked by reacting them with the sodium borohydride(NaBH

4) [43]

Similar to the DNA immobilization the cAb can alsobe immobilized on the aldehyde-modified glass surfaces toafford protein microarrays However the cAbs on the proteinmicroarrays obtained by using aldehyde chemistry have alower binding affinity as well as reduced specificity for the tar-get antigens [44] Another method of aldehyde modificationof ester functionalized slide can be done by reduction to alco-hol followed by controlled oxidation of alcohol to aldehydeusing pyridinium chlorochromate (PCC) [45] Apart fromthe glass chips surface the glass bead surface is also modifiedto produce a surface with aldehyde functions using APTESand glutaraldehyde reagents [46]

(2) Epoxy Modification Apart from silanization epoxylationis a commonly used approach for glass surface modificationThe epoxy functional group on the epoxy-modified glasssurfaces are allowed to react with the amine-containingbiomolecules for their immobilization [47]Thus the amine-modified DNAs and proteins with their native amine groups

can be immobilized by this method on the glass surfaces forthe generation of DNA microarray and protein microarrayrespectively As shown in Scheme 2 the epoxy functionalizedsurfaces can be used for the covalent attachment of phospho-rylated DNAs

The advantage of this method is that the 31015840 phosphategroup can make a covalent bond with epoxy groups Thisallows immobilization of larger fragments of DNA or PCRproducts on the surface As explained by Mahajan et al theepoxylation of glass surface is carried out by keeping the glassin a 2 solution glycidoxypropyltrimethoxysilane (GOPTS)in toluene for 4-5 h at 50∘C followed by washing and dryingAfter epoxylation of glass surface the probe immobilizationis done by spotting the 31015840 phosphate DNA on the surface andmicrowave treatment for 10min in a buffer of pH 10 Afterthe DNA immobilization excess epoxy groups are maskedby using capping buffer of pH 9 containing 01M Tris with50mM ethanolamine for 15min at 50∘C [48]

One of the disadvantages of this approach is the need forhigh pH at which glass surface starts to degrade leading tothe inconsistent results [49] Furthermore the high pH alsodamaged the native three-dimensional structure of proteinsresulting in decreased sensitivity and increased nonspecificinteractions

(3) Carboxylate Modification The amine-modified DNAs arecommonly used because of the simple chemistry involved intheir conjugation with fluorescence molecules with carbonylfunctional groups Same chemistry can be attributed toimmobilizing the amine-modified DNAs on the carboxylicacid modified glass surfaceThe coupling between carboxylicacid and amine is direct without any linker in betweenthem The 1-ethyl-3-(3-dimethylaminopropyl) carbodiimidehydrochloride (EDC) is a commonly used reagent for amidecoupling reactions Other common coupling reagents are N-hydroxysuccinimide (NHS) hydroxybenzotriazole (HOBt)and NNN1015840N1015840-Tetramethyl-O-(benzotriazol-1-yl)uronium

Journal of Chemistry 5

(1) GA(2) DCCNHS

O O O

Si Si SiO O O

HNHN

O O

OO OONO O NO O

H2N

O O O

Si Si SiO O O

H2N H2NH2N

Scheme 3 Surface modification with activated carboxylic acid

tetrafluoroborate (TBTU) The free amino functional groupsin lysine containing proteins are targeted for the immobiliza-tion of proteins on the glass surface through amide couplingreactions The polyamidoamine (PAMAM) dendrimer isused as a linker for immobilization of the DNAs on the glasssurfaces [50 51] PAMAM was initially invented in the 1980sto increase the amino groups on the outer surface of sphere[52] Its application is now extended for DNA immobiliza-tion Firstly the silylation is performed using 95 3 2 vvsolution of ethanol water and APTES by treating the glassslides for 2 h

As depicted in Scheme 3 Benters et al treated the silylatedsurface overnight with the solution of glutaric anhydride(GA) in DMF Slides are then washed with DMF multipletimes to remove the unreacted reagents Carboxyl groups areactivated by using activating reagent such as 1mM solutionof NHS or dicyclohexylcarbodiimide (DCC) in DMF for 1 hfollowed by washing with DMF For the covalent attachmentof dendrimer 100120583L of 10 PAMAM in methanol is allowedto react with the activated carboxyl functional groups on thesurface for 12 h at room temperature followed by washingwith methanol to remove the excess dendrimer Before theimmobilization of DNAs on the surface these dendrimers areactivated by using GANHS as described above [53]

(4) Diazotization Diazo one of the stable bonds in organicchemistry makes its use imperative in the surface modifica-tion process For diazotization the amine-modified surfaceis needed Commonly a cleaned glass using piranha solutionfor 30min followed by deionized (DI) water is used [54]The cleaned glass surface is then allowed to react with the(4-aminophenyl) trimethoxysilane in ethanol solution for30min After silanization the amine-modified surface istreated with the sodium nitrite (NaNO

2) to generate dia-

zobenzyl surface as depicted in Scheme 4 The diazotizationreaction is done at 4∘C using solution of 40mL water 80mLHCl (400mM) and 32mL NaNO

2(200mM) as reported by

Alwine et al [55] After the reaction surface is washed withice-cold sodium acetate buffer deionized water and ethanolThen the solution containing the probe DNAs is spottedon the ice-cold diazotized surface and air dried for 1-2 hDolan et almentioned that the unreacted diazo groups on the

surface are blocked by reaction with the glycine or UV-cross-linked followed by baking for two hours at 80∘C [56] Theimmobilized DNAs can be allowed to hybridize with the PCRproducts for the detection and discrimination of pathogens

(5) Surface Modification with Supramolecules In the lastdecade tremendous work is done on the various applicationsof supramolecules in particular calixarenes [31 57 58] Thecalix[4]crown-5 derivatives are well known for their abilityto capture the cationic substrates including metal cations andammonium ions [59] The cavities of calixarenes are wellknown to capture the amino groups of proteins and formstable complexes with them According to the report Leeet al exploited the ability of calixarenes to form complexeswith proteins to fabricate the protein microarrays on glasssurfaces as depicted in Figure 4 [60 61] For the fabricationof the protein microarrays the calix[4]crown-5 derivativescontaining aldehyde functional groups are reacted with theamine functional groups on the amine-modified glass chip togenerate a monolayer

Then the protein in PBS solution with 30 glycerol isspotted on calix[4]crown-5 derivative modified glass surfaceand incubated at 37∘C for 3 h Then the chip is washed withthe 10mMPBS solution containing 05 Tween 20 for 10minat room temperature and dried under a stream of N

2gasThe

unreacted calix[4]crown-5 derivatives the free amine groupson the glass surface are blocked by immersing the chip intothe 3 BSA in PBS solution for 1 h at room temperature

Similar to protein microarrays [62] Nimse et al reportedthe DNA microarrays based on the 9G technology whichuses the interactions of the monolayer of calix[4]arenederivatives on the glass surface and the DNAs appended tothe nine consecutive guanines (9G) are also reported [32]The aminocalix[4]arene (AMCA) derivative with aldehydefunctional groups is allowed to reactwith the amine-modifiedglass surface to generate the AMCA slides As depicted inFigure 5 the determination of contact angle of water onthe AMCA modified glass surface indicates that the AMCAmolecules make the glass surface hydrophobic

Once the AMCA immobilization is done the solutioncontaining DNA probes appended to 9G is spotted on the

6 Journal of Chemistry

OH O OH

N

N

N

OH OHO

Si

Si

N

N

lowast

lowast

SiO2

SiO2

OH O OH

Si

SiO2

OH OH OH

SiO2

OH OHO

Si

SiO2

Si(OCH3)2

Single strandedunlabeled target DNA

+NClminus

NaNO2 + HCl

Diazonium ion

Cy3Cy5-dCTPDNA

For 14ndash16hr

lowast

lowast

NH2

NH2

Hybridized at 42∘Cat 4∘C

at 30min4∘C

Scheme 4 Covalent immobilization of probe DNA on a glass surface by diazotization and subsequent hybridization

O O O

O O

O

O

X X X X

+N

H4

+N

H4

H3C CH3O O O

O O

O

O

X X X X

H3C CH3

1 cm

1 cm

Figure 4 Interaction of calix[4]crown-5 derivative with proteins for the fabrication of protein microarray (adapted from [31])

Journal of Chemistry 7

(a) (b)

Figure 5 Contact angle comparison (a) bare glass and (b) AMCA modified glass slide (adapted from [32])

surface by using microarray After incubation at room tem-perature for 4 h the slides are washed to remove excess DNAsand driedThe free AMCAmolecules on the surface are thenblocked with the 4x SSC solution containing BSA and 01SDS Finally the slides are dried to obtain 9G DNAChips[63 64]

23 Carbon In recent years a nanoparticle-based structurelike nanotubes and nanowires has got tremendous attentionin biomedical and diagnostic fields [65 66] Before 1991 sp3hybridized form of carbon (diamond) sp2 hybridized formslike graphite and C60 fullerene were the only known formsof carbon with potential applications [67] In 1991 allotropeslike carbon nanotubes (CNT)were first reported and success-fully synthesized by Iijima with multiwall faces (MWCNT)[68]

Due to thermal electrical and magnetically uniqueproperties CNT became an important material in the devel-opment of biosensor platforms Commonly reportedmethodfor preparation of CNT includes chemical vapour deposition[69 70] arc discharge [71] and laser ablation [72]

Apart from CNT other carbon-based nanostructuresincluding carbondots carbon fibers andPDMSalso attractedresearchers due to their diverse properties for biomoleculeconjugation [73 74]Themajor advantage of carbon nanoma-terial is their large surface area which allows maximum spacefor biomolecule attachment

Immobilization of protein carbohydrate and nucleic acidon the CNT surfaces allows various biological applications[75 76]Themost important part in biomolecule conjugationis the surface functionalization of carbon-basedmaterialThegeneral techniques for carbon surface modification are (phy-sisorption) noncovalent and covalent modifications Thereare several reports on the different techniques of surfacemodification of carbon-based surfaces Due to the vastnessof the research on carbon-based material only few methodsare described in this paper

231 Physisorption Thehydrophobic character of CNT side-walls and the strong 120587-120587 interactions between the individualtubes causes them to aggregate and reduce their solubility in

common solvents which is considered as a problem for theirbiological applicationsHowever the samehydrophobic char-acter of theCNT surface is exploited for fabrication of biosen-sors by immobilizing biomolecules onto the CNT surfacesthrough hydrophobic-hydrophobic interactions [77ndash79]

The advantage of noncovalent interaction is a limiteddistortion of the three-dimensional structure of a protein orenzyme to be immobilized The hydrophobic amino acidsin proteins and enzymes develop the 120587-120587 interactions withthe hydrophobic part of CNT which make them adsorbedon the surface of CNT [80ndash83] As mentioned earlier theplatforms modified by noncovalent interactions suffer fromthe typical drawbacks of nonspecific interactions resulting inthe decreased specificity and sensitivity of a biosensor

To eliminate the problem of nonspecific interactions oftarget proteins with the sensor surface the novel approachof polyethylene oxide (PEO) polymer coating is adopted bymany researchers The PEO is well known for its proteinrepelling ability [84] Bomboi et al reported the use of Tween20 which is composed of three PEO branches and P103another molecule with hydrophobic polypropylene oxideunits to modify the surface of CNT before adsorption ofproteins on it The surface of Tween 20 and P103 modifiedCNT becomes slightly hydrophilic compared with bare CNTwhich results in the decrease in its interaction with thehydrophobic amino acid chains of biomarker proteins [85]

As depicted in Figure 6 for the selective immobilizationof streptavidin on the CNT surface Chen et al used mixednoncovalent and covalent approach which allows the highlyspecific immobilization of streptavidin and blocks the non-specific binding of other proteins like BSA [33]

Conjugation of a fluorescent molecule on the CNT sur-face is an immerging technology for highly sensitive detec-tion of biomolecules Nakayama-Ratchford et al reported theimmobilization of the fluorescent molecules like fluoresceinon the surface of CNT through 120587-120587 interactions [86] Thereare several reports on the applications of CNT surfaces mod-ified with the fluorescent molecules through noncovalentinteractions [87ndash90]

232 Chemical Modification To prevent the nonspecificbinding and to avoid the leaching of biomolecules from the

8 Journal of Chemistry

OH

OH

OH

O

HO

HO

HO

O

OO

OO

NH

O

NH

O

NH

OO

NH O

NH

O

NH

65 HON3

Boiling t = 8h

C2H4(NH2)2

NH2

H2N (CH2)2

(CH2)2

NH2(CH2)2

NH2(CH2)2

H2N (CH2)2

H2N (CH2)2

Scheme 5 Amine modification of CNT

BB

B

B B

B

SA SA

Figure 6 Streptavidin recognition by a nanotube coated with biot-inylated Tween (adapted from [33])

CNT surface a covalent modification technique is reportedThere are two types of covalent modifications namely (i)indirect method for example carboxylation of CNT surfaceand (ii) direct method for example fluorination of CNT sur-face where surface carbons change from sp2 to sp3 hybridiza-tion Esterification or amidation and sidewall covalent attach-ment are other approaches for covalent attachment [91 92]

(1) Carboxyl Modification The modification of the sensorsurfaces with the carboxyl groups is a general and highly usedsurface modification method Once the surface is modifiedwith the carboxyl groups it can be converted to a vari-ety of functional groups through reaction with appropriatereagents Furthermore the carboxylated surfaces can bedirectly conjugated with proteins or DNA through theiramine functional groups using coupling reagents A mixtureof sulphuric acid and nitric acid is a commonly used reagentfor the carboxylation of CNT surface

Marshall et al reported the method for carboxyl modifi-cation of CNT [93] According to this method a 2mg sampleof SWCNT is added to the 75 mixture of concentratedsulphuric acid and nitric acid (1mL) The mixture is allowedto sonicate in sonicator at 20∘CThe reaction mixture is thendiluted to 250mL by using deionized waterThe carboxylatedCNTs are then filtered through polytetrafluoroethylene filter(PTFE) of 045 120583m size Finally the collected nanotubes arewashedwith water at acidic pH followed by ethanol and driedin a vacuum desiccator

O OOH

O OOO

n

Figure 7 Structure of Epon resin 828

(2) Amine Modification Amide coupling is the most com-monly used conjugation technique in biomolecule attach-ment Either the amine or acid part of DNA or protein canbe used for conjugation using amide coupling reaction Forthe conjugation ofDNA toCNT through its phosphate groupamine modification is needed

Tam et al reported the DNA sensor based on the aminemodification of MWCNT as depicted in Scheme 5 [94] TheMWCNT were boiled in the 15M nitric acid for 12 h to gen-erate the carboxylated MWCNT The purified carboxylatedMWCNT were reacted with ethylenediamine to obtain theamine-modified MWCNT The amine-modified MWCNTwere conjugated to DNA by using EDC coupling reaction

Other reports for aminemodification of CNT include theuse of nitric acid and sulphuric acidmixture for carboxylationof the surface followed by ethylenediamine reaction [95]There are several reports on the covalent conjugation offluorescent molecules to the CNT surfaces [96ndash98]

(3) Epoxy Modification Epoxide group is a highly reactivefunctional group used in many substitution reactions as anelectrophile Eitan et al reported the covalent attachmentof epoxide-terminated molecules to carbon nanotubes byreaction between epoxide rings and carboxylic acid groupsthat are initially formed on the nanotube surface [99] Forepoxidation of CNT the surface is first carboxylated bydispersing the CNT in 75 solution of sulphuric acid in nitricacid for 3 h The purified carboxylated CNT were kept in theacetone with sonication for 1 hThen the solution containingthe carboxylated CNT is mixed with the solution of Eponresin 828 (Figure 7) in acetone to allow the reaction betweenEpon resin 828 and carboxyl groups on the CNT surface asdepicted in Scheme 6

Journal of Chemistry 9

O

O

O

O

R

OOCatalyst

O

O

O

O

O

O

CHHO

R

O

HC OH

R

O

H2C

O

HC OH

R

O

H2C

CH2

O

CHHO

R

O

CH2

HOHO

OHOH

+

Scheme 6 Epoxy modification of CNT

The mixture of solutions is sonicated for 1 h followedby stirring and heating at 70∘C The reaction was quenchedby addition of appropriate amount of potassium hydroxideThen the epoxilated CNT were purified and a number ofepoxy groups on the CNT surface were determined by usingthermogravimetric analysis

24 Nitrocellulose A PoC diagnosis system is always expe-cted to deliver final results in few minutes Though themicroarrays based on the glass and gold surfaces are usefulfor detection of multiple analytes at a time they need longertime for final data interpretation Microfluidic systems basedon paper or nitrocellulose membranes are emerging surfacesfor detection of bacteria viruses and proteins A paper isadvantageous due to its hydrophilic nature which allowsthe aqueous solutions to penetrate without the need of anyexternal force [100] The essential constituent of paper iscelluloseThe cellulose has hydroxyl functional groups whichcan be modified and changed according to surface propertiesneeded for a particular detection device [101] Due to lowcost and high availability paper is preferred for large scaleproduction Moreover the devices required for the tests areportable and disposable [102ndash105] The very first example ofpaper based detection is glucose detection in urine [106] andpregnancy test kit [107]There are different types of paper likeWhatman filter paper glossy paper [108] membrane and soforth Whatman filter is used because of its high penetrationand flow rate [109ndash112] but in some cases it does not havethe necessary characteristic for surface modification Mem-branes on the other hand are planner sheets and providelarger surface area for immobilization of biomolecules such

as DNA and protein The nitrocellulose (NC) membrane isbroadly used for immobilization of DNA [113] protein [114]and enzymes [115] due to its hydrophobic surface

241 Physical Adsorption Single-stranded DNAs are irre-versibly bound to the surface of the NCmembrane with non-covalent interactionsTheprimary interactions are hydropho-bic and electrostatic between the positively charged surfaceof the membrane and negatively charged DNAs The nitro-cellulose offers very high binding capacity for DNAs andproteins Fabrication of NC membranes can be done bydifferent methods including the photolithography The waxpatterningmethod is fast cheap and easy to process and doesnot need organic solvents The NCmembranes with the poresize of 045 120583mdo not need pretreatment for penetrationThefabrication process includesmainly printing and baking stepswhich can be finished in 10min As shown in Figure 8 firstlythe wax is printed on the surface of NCmembrane and bakedat 125∘C for 5min in the oven The melting of the wax onmembrane makes it more hydrophobic and affords surfacesuitable for the immunoassay For immunoassays Lu et alcoated the cAbs on the surface and the free area is blockedwith the 1 BSA

During baking melted wax passes through the mem-brane The 121∘ contact angle of backside membrane assuresthe melting of wax thoroughly The efficiency of wax treatedmembrane is compared with the untreated membrane byimmobilizing fluorescence labeled goat antihuman IgG Theimmobilization on wax printed surface is more uniform thanthe untreated membrane Apart from this a large volumeof liquid can be used because ring effect of protein on the

10 Journal of Chemistry

HO

OSH AuNP

AuNP-mAb

mAbEDCNHS

001M PBS

(CH2)15(CH2)11

NaBH4HAuCl4 + SH + HO

pH sim 74

Scheme 7 Immobilization on antibodies on AuNP

NC membrane

Cross section view

PrintingStep 1

Step 2 Baking

Wax patternedNC membrane

Wax is printed onto thesurface of NC membrane

Wax melts and penetratesthrough NC membrane

Nitrocellulose

Wax

Figure 8Wax printing on nitrocellulosemembranes (adapted from[34])

untreated membrane is avoided Wax printing method gen-erates 100 120583mmicrochannel which removes the micrometersize contaminants and makes the wax printed membranessuitable for the applications in microfluidic assays Apartfrom immobilization wax printing has application in dotimmunoassay and sample purifications [34]

Due to advantages of NC membrane for high bindingcapacity and good flow of solution it is also used on the chipsurfaces The glass slide can be coated with the 12 120583m layer ofNC to afford a platform with the intrinsic properties of NCThe solution of cAbs in PBS buffer containing 10 glycerolis then spotted on the modified surface After spotting theslides are incubated for one hour After incubation slides arewashed with 01 Tween 20 in PBS buffer and dried to gen-erate the platform for detection of biomarker proteins [116]

Apart from routine microarray applications NC mem-brane is also used for the detection of circulating tumor cells(CTC) as reported by Zhang et al The binding of CTCs bythe cAbs immobilized on the NC membrane is detected bySurface Enhanced Raman Scattering (SERS) as depicted inFigure 9

Usually the antibodies specific for cancer cells are usedas a capture substrate and immobilized on the surface TheNC membrane is cut into 1 cm times 1 cm pieces Then thesepieces are immersed in the ethanol and then tiled on thePMMA wafer After washing the membrane is activated byusing PBS buffer containing antibodies at 37∘C for 30minDuring this process the cAbs are avidly immobilized on theNC membrane The 1 BSA solution is loaded to block thefree surface area to avoid any background signals due tononspecific interactions Finally the membranes are washedwith PBS buffer and stored at 4∘CThe gold nanoparticle andRaman probes are used to detect the CTCs by SERS [35]

25 Gold Application of nanoparticles is amost focused areain the field of inorganic chemistry and it has also attractedimaginations of many biologists too Inorganic nanoparti-cles including gold silver and ferrous oxides have foundmany important applications in cell signaling drug deliveryand colorimetric and fluorescence-based detections Goldnanoparticles (AuNP) functionalized with proteins DNAsor Raman probes are well known in the field of biosensorsand nanobiotechnology for their applications in the molec-ular diagnostics [117ndash119] protein detection [120ndash122] generegulation [123] and cell imaging [124]

251 Covalent Modification

(1) Thiol Based Modification AuNPs are commonly usedin the electrochemical and optical detection systems Theconjugation with biomolecule does not change the opticalproperties ofAuNP [125]Di Pasqua et al reported thiolmod-ification for the detection of E coli O157H7 E coli specificantibodies were conjugated with the AuNPs [126] As shownin Scheme 7 the 10 nmAuNPs are carboxylated and then cou-pled to E coli specific monoclonal antibody (mAb) throughamide coupling

For the generation of AuNPs to the solution containing410mg of HAuCl

4sdot3H2O in 6mL of water ethanoic solutions

of 11-mercapto-1-undecanol and 16-mercaptohexadecanoicacid are added Upon addition of NaBH

4to this mixture at

0∘C the solution turns brown The product AuNP cappedwith alkanethiol pendant alcohol and carboxylic acid func-tional groups precipitate upon three hours of stirring Theprecipitated particles are then thoroughly washed with etha-nol and an ethanolic solution containing a small amountof 1M HCl The AuNPs are then dried under vacuum forten hours For the conjugation of mABs with the AuNPsthe carboxylic acid functional groups on the AuNPs are

Journal of Chemistry 11

SERSimaging

AuNPs

Raman labelNC membrane

AntibodyCancer cell

Figure 9 Detection of circulating tumor cells on NC membranes containing immobilized cAbs (adapted from [35])

activated by reacting the AuNPs with 1-ethyl-3-3(3-dimeth-ylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in the PBS buffer The mABs arethen added to this solution and the suspension is stirred atroom temperature for 30min The mAB-conjugated AuNPsare then collected by centrifugation and washing with PBSand ethanol The mAB-conjugated AuNPs successfully bindto E coli when incubated in PBS at pH 74 In other reportsthe AuNPs were found very effective in the detection ofcancerous pancreatic cells

The AuNPs are known to suffer from the problem ofaggregation upon long-term storage Therefore to solve thisissue the AuNPs are conjugated with the polyethylene glycol(PEG) to prevent their aggregation [127 128]The conjugationof PEGwith the AuNPsmakes the later hydrophilic thus pre-venting agglomeration induced by hydrophobic interactionsA PEGwith the heterobifunctional groups (dithiol at one endand a carboxyl at another end) is coated on the AuNP Thedithiol group allows stable anchoring heterobifunctional PEGligands on the surface of AuNP and the terminal carboxylgroup is used for coupling with antibodies The carboxy-terminated bifunctional PEG linker is synthesized by follow-ing a method reported by Eck et al which is depicted inScheme 8 The anionic polymerization of compound 1 withan excess of ethylene oxide allows synthesizing compound 2The treatment of compound 2 with chloroacetic acid at 60∘Callows generating compound 3 The reaction of an excess ofthe elemental bromine in dichloromethane at 0∘C for fourhours in the dark with compound 3 produces dibromidecompound 4 Compound 5 is obtained by reaction withcompound 4 in water with the excess of sodium hydrosulfidehydrate

The synthesized bifunctional PEG linker is then conju-gated with the citrate-stabilized gold nanoparticles by simpleligand exchangeThe citrate-stabilized gold nanoparticles areknown to aggregate in the buffer containing salts Thereforethe ligand exchange from citrate to PEG should be done inpure water The PEGylated AuNPs are conjugated to mono-clonal F19 antibodies for the detection of human pancreaticcarcinoma through EDCNHS coupling reaction [129]

OHO

(2) HCl

1

2

3

4

5

Br Br

HS SH

(CH2)9

(CH2)9

(CH2)9

(CH2)9

+

NaHDMF60∘C

(OCH2CH2)n

(OCH2CH2)n

(OCH2CH2)n

OCH2COOH

OCH2COOH

(CH2)9 (OCH2CH2)n OCH2COOH

OminusNa+

Br2

(2) Acetic acid (1) NaSHH2O

60∘C(1) ClCH2-COONa

Scheme 8 Synthesis of bifunctional PEG linker using conjugationwith AuNP

(2) Hydrazide Modification According to the report by Zhiet al the hydrazide-derivatized self-assembledmonolayer ona gold surface is used for the efficient and selective anchor-ing of oligosaccharide [39] The generated oligosaccharidemicroarrays allow the fluorescence-based detection of targetproteins The use of gold as a substrate for the fluorescence-based detection suffers from the drawbacks including flu-orescence quenching and nonspecific surface adsorption ofproteins However the use of120596-thiolated fatty acid (C

16) self-

assembledmonolayer between the gold surface andhydrazide

12 Journal of Chemistry

AuC C

C

C

OHOHO O

O

O

O

O

O

O

O

O

CHR

NN

H

N

N

N

H

NH

NH

NH

H

NH

C

O

O

O NNH

NH

HNH

H

S

S

S

S

HS Au

Au

Au

Au

Au

C16 SAM

Adipic dihydrazideEDC

(Sugar)R-CHO

Binding to protein

Sugarprobe

Protein Alexafluoro 532

SAM andblocking layer

Ab 2nd Ab

NH2

NH2H2N

CH2R

Scheme 9 Application of hydrazide-derivatized SAM on a goldsurface for the fabrication of oligosaccharide microarray (adaptedfrom [39])

groups minimizes the quenching effect Moreover the effec-tive blocking of the surface with the poly(ethylene glycol)aldehyde and BSA reduces the nonspecific adsorption ofprotein on the surface

For the fabrication of the reported oligosaccharidemicroarrays the gold substrate is prepared by following amethod depicted in Scheme 9 The self-assembled mono-layer (SAM) of 16-mercaptohexadecanoic acid (MHDA) isobtained by soaking the gold coated slides in the isobutylalcohol for 2 days The slides are then washed in ethanolto remove excess reagents and are dried under the nitrogenstream The carboxyl functional groups on the SAM areconverted to the hydrazide groups by incubation of the SAMcovered slides in the dimethyl sulfoxide solution containing1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and adipicdihydrazide The ethanol-washed and dried slides are thenused for the oligosaccharide printing to obtain oligosaccha-ride microarrays

The generated oligosaccharide microarray platformallows interrogation of carbohydrate-protein interactions ina high-throughput manner

26 Silver Similar to AuNPs silver nanoparticles (AgNP) arealso used for the immobilization of proteins and enzymesThe surface of AgNP allows adsorption of proteins Henceit can be utilized as a host matrix for various biomoleculesSilver is a suitable substrate for the immobilization of wholecell or the isolated enzymes [130 131]

Texp lt Tm

Ag

AgAg

Ag

AgAg

Texp gt Tm

Figure 10 AgNPs-oligonucleotide conjugates (adapted from [36])

261 Electrostatic Modification The electrostatic interac-tions allow the physical adsorption of biomolecules on thesurface of AgNPs Shen et al reported that the AgNPs aresynthesized by reduction of silver nitrate in the presence ofsodium citrate During the reduction process the solutionis sonicated for 15min to obtain the yellow silver colloidwhich is then kept at 4∘C for several days away from lightThen isolated nanoparticles can be used for physisorption ofproteins at a pH higher than their isoelectric point [132]

262 Covalent Modification As depicted in Scheme 10the AgNPs prepared by the citrate reduction method andstabilized with citrate [133] can be functionalized with car-boxyl groups upon treatment with 3-mercaptopropanoic acid(MPA) As reported by the Petkova et al for the immobi-lization of alcohol dehydrogenase from Thermoanaerobiumbrockii (TbADH) the carboxyl-modified AgNPs were treatedwith the solution containing TbADH under continuousstirring for 7 h at 26∘C a research by [134] The AgNPsmodified with the TbADH were successfully used for thebiotransformation studies

The application of a bifunctional linker for the modifica-tion of AgNPs is reported [135 136] The bifunctional linker11-mercaptoundecanoic acid was used with 1-octanethiol in1 1 ratio to generate the mixed SAM on the surface of AgNPThe IgG antibodies are then conjugated with the mixed SAMmodified AgNPs It is reported that upon covalent conjuga-tion of biomolecules with AgNPs their stability and activityis maintained [137]

According to another report on the covalent modifi-cation AgNPs-oligonucleotide conjugates are prepared byusing DNA and triple cyclic disulfide moieties [36] Asdepicted in Figure 10 the two types ofAgNPs-oligonucleotideconjugates with complementary DNA sequences undergoDNA hybridization driven coagulation resulting in the colorchange

As depicted in Figure 11 the AgNP-DNA conjugates wereprepared by treatment of AgNPs with the cyclic disulfidemodified oligonucleotide The AgNP and oligonucleotideswere allowed to react with each other with 1 4 ratio inthe presence of 1 sodium dodecyl sulfate and NaCl Theovernight incubation of solution results in the AgNP-DNAconjugates which are collected by centrifugation and washedto remove the excess DNAs

Journal of Chemistry 13

Ag AgMPAOH

OO OH

O

HOCitrate

Citrate

Ag

COOH

COOH

TbADHAg

CONH

COOH

TbADHOminusNa+

H2N

Scheme 10 Covalent conjugation of enzymes on the surface of carboxyl-modified AgNPs

OHO

EDC HOSu Bis-amino

polyethylene glycol

NH

OO

44GMBS N

H

OO N

H44

ON

O

O3

CoA

NH

OO N

H44

ON

O

O3

SHN

O

OH

OP O

OPO

O O

OHO

NNN

N

PO

OminusOminus

OminusOminus

NH2

NH2

Scheme 11 Covalent conjugation of coenzyme A to polystyrene nanoparticles

O OOO P

OHSS

5998400 (DSP)3-A10-ATT-ATC-ACT 3998400

DSP cyclic disulfide-containingphosphate derivative =

Figure 11 Conjugation of AgNPs with oligonucleotides by usingDSP as a linker molecule (adapted from [36])

27 Polystyrene Polystyrene is an aromatic polymerobtained by polymerization of styrene monomers [138] Thepolystyrene-based NPs are widely used in the moleculardiagnostics for the detection of biomarker proteins andgenomic DNAs Polystyrene can be employed as a coating ona variety of nanoparticles as its functional groups can be easilymodified or conjugated with other molecules The otherapplication of polystyrene is in the fabrication of fluorescencebeads (FBs) The fluorescence molecules are loaded into thepolystyrene shell to produce FBs which are then used invarious sensing applications The polystyrene is also used tocoat the magnetic NPs so they can be conjugated with otherbiomolecules such as DNA and Proteins The applications ofpolystyrene include but are not limited to the detection ofE coli [139] the detection of cardiac Troponin T (cTnT) thedetection of Herpes simplex virus and many more

271 Covalent Modification Covalent modification throughcarboxyl group iswell known formodification of biomolecule

Most of the polystyrene-based nanoparticles bear large num-bers of pendant carboxyl which increases the loading amountof biomolecule

Enzyme catalyzed covalent immobilization of the pro-teins bearing a small 12-mer ldquoybbRrdquo tag onto the polystyrenenanoparticles (PSNP) is recently reported by Wong et al[140] As depicted in Scheme 11 the carboxyl-PSNPs werereacted with the bis-amino-polyethylene glycol in the pres-ence of HOSu and EDC to generate the amino-pegylatedPSNPs These PSNPs are then reacted with the g-maleimi-dobutyric acid succinimidyl (GMBS) to obtain maleimide-functionalized PSNPs The maleimide-functionalized PSNPsupon chemoligation with coenzyme A (CoA) produce theCoA-derivatized PSNPs

As depicted in Scheme 12 the protein of interest bearingybbR-tag is immobilized on the CoA-derivatized PSNPsThephosphopantetheinyl transferase (Sfp) catalyzed the reactionbetween the serine residue of the ybbR-tag and the phos-phopantetheine moiety of CoA with the simultaneous lossof 3101584051015840-adenine diphosphate results in the attachment ofproteins onto the surface of PSNPs It is reported that theenzymes immobilized by this method retain their activity

There are several reports on the use of fluoromicrobeadsfor the detection of biomarkers Primarily the fluoromi-crobeads are made up of carboxylated polystyrene as a coat-ingmaterial entrapping the fluorescentmolecules Accordingto the recent report by Song et al [37] the fluoromicrobeadswere used for the detection of the cTnT on the proteinmicroarray as depicted in Figure 12

The carboxylate modified fluoromicrobeads were conju-gated with the anti cTnI mAb through EDCNHS-mediated

14 Journal of Chemistry

HN

O

OH

OP

O

O

PO

O

OHO

N

NN

P

O

S

HN

O

Coenzyme A

Phosphopantetheine

PO

O

O

OHO

N Sfp

NN

N

P

O

ybbr-protein

HN

O

OH

OP

O

O

S

HN

O

NH2

NH2

Ominus

Ominus

Ominus

minusO

minusO

Mg2+

HO∙∙

Ominus

OminusOminus

minusO

N

O

Polystyrenenanoparticle

Scheme 12 Protein conjugation to polystyrene NP

System 1 antibody-conjugated fluoromicrobeads

System 2 avidin-conjugated fluoromicrobeads

DTSP SAM

Anti-cTnI cAb

cTnI

Figure 12 Application of the polystyrene-coated fluoromicrobeadsfor the detection of cTnI on the protein microarray (adapted from[37])

coupling reaction The use of fluoromicrobeads alloweddetecting the cTnI in plasma samples with a range of 01ndash100 ngmL

272 Affinity-Based Modification The affinity interactionsare used for the attachment of oligonucleotides with thefluoromicrobeads or polystyrene-coated magnetic beads Togenerate the oligonucleotide conjugated fluoromicrobeads ormagnetic beads respective polystyrene-coated beads are firstconjugated with the streptavidin using the EDCNHS cou-pling reaction as reported by Zhang et al [141] As depicted

B

B

MB MB

MB

BB

Magnetic bead

Streptavidin

DNA labeled biotin

Figure 13 DNA attachment to the magnetic beads

in Figure 13 the streptavidinmodified beads are then allowedto incubate with the biotinylated oligonucleotides Due to theaffinity of biotin for streptavidin the biotinylated oligonu-cleotides can be readily immobilized on the streptavidincoated beads

The binding affinity of streptavidin and biotin in solutionis up to 25 times 1013 (molL)minus1 [142] This interaction is about amillion times stronger than the antigen and antibody inter-action The antibodies directly immobilized onto the sur-face lose 90 of their biological activity [143] Howeverthe biotinylated antibodies immobilized on the streptavidincoated surface can retain their bioactivity [144]

Journal of Chemistry 15

3 Conclusions

Surface modification techniques of the materials used asplatforms in the fabrication of biosensors are reviewed inthis paper There are several reports on materials and vari-ous methods for altering their physicochemical propertiesHence one of these methods can be chosen according tothe targeted use and needed physiochemical properties Itis important to note that the performance of the biosensoris highly dependent on the substrate material used and itsmeticulous modification for particular applications There-fore it is critical to understand the principles of a biosensor toidentify the correct substrate material and its surface modifi-cation chemistry Furthermore it is important to look at thelatest advances in the materials and techniques used for thefabrication of a biosensor before the processing

Competing Interests

All authors declare that there is no conflict of interests

Acknowledgments

This research was supported by the Hallym UniversityResearch Fund (HRF-201601-010) This work was also sup-ported by the fund obtained through Industry-Academic col-laboration between Biometrix Technology Inc (ChuncheonSouth Korea) and Hallym University

References

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[2] A Cavalcanti B Shirinzadeh M Zhang and L C KretlyldquoNanorobot hardware architecture for medical defenserdquo Sen-sors vol 8 no 5 pp 2932ndash2958 2008

[3] R-Q Zhang S-L Liu W Zhao et al ldquoA simple point-of-caremicrofluidic immunomagnetic fluorescence assay for path-ogensrdquo Analytical Chemistry vol 85 no 5 pp 2645ndash2651 2013

[4] S B Nimse K S Song M D Sonawane D R Sayyed and TS Kim ldquoImmobilization techniques for microarray challengesand applicationsrdquo Sensors vol 14 no 12 pp 22208ndash22229 2014

[5] A P F Turner ldquoBiosensors sense and sensibilityrdquo ChemicalSociety Reviews vol 42 no 8 pp 3184ndash3196 2013

[6] L Wu and X Qu ldquoCancer biomarker detection recent achieve-ments and challengesrdquoChemical Society Reviews vol 44 no 10pp 2963ndash2997 2015

[7] K Ariga Q Ji T Mori et al ldquoEnzyme nanoarchitectonicsorganization and device applicationrdquo Chemical Society Reviewsvol 42 no 15 pp 6322ndash6345 2013

[8] W-W Zhao J-J Xu and H-Y Chen ldquoPhotoelectrochemicalDNA biosensorsrdquo Chemical Reviews vol 114 no 15 pp 7421ndash7441 2014

[9] Q Liu C Wu H Cai N Hu J Zhou and P Wang ldquoCell-basedbiosensors and their application in biomedicinerdquo ChemicalReviews vol 114 no 12 pp 6423ndash6461 2014

[10] X Zhao S Nampalli A J Serino and S Kumar ldquoImmobi-lization of oligodeoxyribonucleotides with multiple anchors to

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[11] P Kumar S K Agrawal A Misra and K C Gupta ldquoA newheterobifunctional reagent for immobilization of biomoleculeson glass surfacerdquo Bioorganic 120572Medicinal Chemistry Letters vol14 no 5 pp 1097ndash1099 2004

[12] F Secundo ldquoConformational changes of enzymes upon immo-bilisationrdquo Chemical Society Reviews vol 42 no 15 pp 6250ndash6261 2013

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[14] K Jaras A A Tajudin A Ressine et al ldquoENSAM europiumnanoparticles for signal enhancement of antibody microarrayson nanoporous siliconrdquo Journal of Proteome Research vol 7 no3 pp 1308ndash1314 2008

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[16] K Jaras B Adler A Tojo et al ldquoPorous silicon antibodymicroarrays for quantitative analysis measurement of free andtotal PSA in clinical plasma samplesrdquo Clinica Chimica Acta vol414 pp 76ndash84 2012

[17] S W Lee K Hosokawa S Kim et al ldquoA highly sensitive poroussilicon (P-Si)-based human Kallikrein 2 (hK2) immunoassayplatform toward accurate diagnosis of prostate cancerrdquo Sensorsvol 15 no 5 pp 11972ndash11987 2015

[18] C Roychaudhuri ldquoA review on porous silicon based electro-chemical biosensors beyond surface area enhancement factorrdquoSensors and Actuators B Chemical vol 210 pp 310ndash323 2015

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[24] S Vutti N Buch-Manson S Schoffelen N Bovet K LMartinez and M Meldal ldquoCovalent and stable CuAAC mod-ification of silicon surfaces for control of cell adhesionrdquo Chem-BioChem vol 16 no 5 pp 782ndash791 2015

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16 Journal of Chemistry

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[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

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[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

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[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

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[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

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[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

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[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

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[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

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Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

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[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

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[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

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[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

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International Journal ofPhotoenergy

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Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Medicinal ChemistryInternational Journal of

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CatalystsJournal of

Journal of Chemistry 3

Visible light Reflectance lightSelective target of antibody modified

particles to fluorescent cells

Porous silicon microparticle

mCherry antibodyTfR-mCherry

Cell membrane

Figure 2 Covalent bonding of antibodies to P-Si microparticles for detection of cells (adapted from [23])

DNA

Amine-modifiedglass surface

SiO

SiO

SiO

SiO

SiO

SiO

SiO

SiO

SiO

SiO O O O O O O O O O

H3N+ H3N+ H3N+ H3N+ H3N+ H3N+H3N+ H3N+ H3N+ H3N+

Figure 3 Physisorption of DNA on the amine-modified glass surface

units per mL (pfumL) [25] As explained earlier the strictfabrication protocol is needed for accurate size of poresChange in the concentrations of reagents and change incurrent and time affect the reproducibility of the result Othercovalent ethylene glycol modified silicon surfaces for specificadsorption of protein through photochemical reaction [26]and silicon covalent surface modification for agarose cross-linking in form of catheter have been reported for infectioninhibition and omental wrapping [27]

22 Glass (SiO2) A glass is made up of a silicon dioxide

(SiO2)Theoxide layer protects the silicon fromchemical deg-

radation and reactions Silicon dioxide is abundant in natureand thermally stable due to a large number of silicon andoxygen bonds Glass substrates are easily available and simpleto handle and have high mechanical stability Glass surfacesare widely used for the immobilization of DNA proteins andother low molecular weight biomolecules [28] In diagnosticfield glass surface plays a crucial role as microarray platformfor detection of various pathogenic DNA as well as biomarkerprotein [29 30]

221 Physisorption Based Modification Physical adsorptionor physisorption is one of the simplest techniques used for thebiomolecule immobilization on glass surfaces As shown inFigure 3 the negatively charged phosphate backbone onDNAforms an ionic interaction with the positively charged surface

of amine-modified glass surface through charge interactions[38]

Lemeshko et al reported that the aminosilanization ofthe glass surface by treatment with 3-(aminopropyl) trime-thoxysilane (APTMS) affords the positively charged surfaceUnfortunately the immobilization of DNAswith thismethoddoes not result in the reproducible DNA detection platformBecause the multiple interaction of negatively charged DNAbackbone with the cationic surface orients it parallel to theglass surface thus its availability for hybridization with thecomplimentary DNA (cDNA) is significantly low

The random orientation of the immobilized DNAs isalso related to the nonspecific hybridization and low repro-ducibility The change in pH of solution and temperaturesignificantly affects the performance of the platform based onthe method of physisorption

222 Covalent Modification Due to various disadvantagesof physisorption methods the covalent surface modificationstrategy has been widely used Covalent bond is stronger andmore stable than electrostatic interaction at solution-surfaceinterfaces [40 41] The glass surfaces and be modified withthe different functional groups suitable for making covalentbonds with the biomolecules to be immobilized In generalthe biomolecules have amine carboxylic acid and sulfhydrylfunctional groups These functional groups can be used forthe immobilization of biomolecules on the surface There are

4 Journal of Chemistry

OO

GlutaraldehydeN O NNH2 N-DNA-Cy3

-DNA-Cy3H2N

Scheme 1 Aldehyde modification of glass slide

Si

Si

O

O

O

O

O

O

Si

Si

O

O

O

OH

OH

OP

O-d(NNN)

O-d(NNN)

O

O

OO O

P

O

O

O

Ominus

Ominus

d(NNN)=OP32minus

MW 10min35∘C 4hr

Scheme 2 Covalent attachment of phosphorylated DNA

various reports on the glass surfacemodification for the cova-lent attachment of biomolecules

(1) Aldehyde Modification For the aldehyde modification ofthe glass surface the silanol groups on the surface are con-verted to an amine by different methods using amine mod-ification reagents such as (3-Aminopropyl)triethoxysilane(APTES) [42] Fixe et al reported the aldehyde modificationusing glutaraldehyde As shown in Scheme 1 the amine-modified surface is then treated with glutaraldehyde (25vv) in 01M PBS for 2 h at room temperature The slide isthen washed with water and dried The solution containingamine-modified DNAs is spotted on the slide and incubatedin humidified chamber for up to 24 h to afford the DNAmicroarray However it is important to note that the unre-acted aldehyde functional groups on the glass surface shouldbe blocked by reacting them with the sodium borohydride(NaBH

4) [43]

Similar to the DNA immobilization the cAb can alsobe immobilized on the aldehyde-modified glass surfaces toafford protein microarrays However the cAbs on the proteinmicroarrays obtained by using aldehyde chemistry have alower binding affinity as well as reduced specificity for the tar-get antigens [44] Another method of aldehyde modificationof ester functionalized slide can be done by reduction to alco-hol followed by controlled oxidation of alcohol to aldehydeusing pyridinium chlorochromate (PCC) [45] Apart fromthe glass chips surface the glass bead surface is also modifiedto produce a surface with aldehyde functions using APTESand glutaraldehyde reagents [46]

(2) Epoxy Modification Apart from silanization epoxylationis a commonly used approach for glass surface modificationThe epoxy functional group on the epoxy-modified glasssurfaces are allowed to react with the amine-containingbiomolecules for their immobilization [47]Thus the amine-modified DNAs and proteins with their native amine groups

can be immobilized by this method on the glass surfaces forthe generation of DNA microarray and protein microarrayrespectively As shown in Scheme 2 the epoxy functionalizedsurfaces can be used for the covalent attachment of phospho-rylated DNAs

The advantage of this method is that the 31015840 phosphategroup can make a covalent bond with epoxy groups Thisallows immobilization of larger fragments of DNA or PCRproducts on the surface As explained by Mahajan et al theepoxylation of glass surface is carried out by keeping the glassin a 2 solution glycidoxypropyltrimethoxysilane (GOPTS)in toluene for 4-5 h at 50∘C followed by washing and dryingAfter epoxylation of glass surface the probe immobilizationis done by spotting the 31015840 phosphate DNA on the surface andmicrowave treatment for 10min in a buffer of pH 10 Afterthe DNA immobilization excess epoxy groups are maskedby using capping buffer of pH 9 containing 01M Tris with50mM ethanolamine for 15min at 50∘C [48]

One of the disadvantages of this approach is the need forhigh pH at which glass surface starts to degrade leading tothe inconsistent results [49] Furthermore the high pH alsodamaged the native three-dimensional structure of proteinsresulting in decreased sensitivity and increased nonspecificinteractions

(3) Carboxylate Modification The amine-modified DNAs arecommonly used because of the simple chemistry involved intheir conjugation with fluorescence molecules with carbonylfunctional groups Same chemistry can be attributed toimmobilizing the amine-modified DNAs on the carboxylicacid modified glass surfaceThe coupling between carboxylicacid and amine is direct without any linker in betweenthem The 1-ethyl-3-(3-dimethylaminopropyl) carbodiimidehydrochloride (EDC) is a commonly used reagent for amidecoupling reactions Other common coupling reagents are N-hydroxysuccinimide (NHS) hydroxybenzotriazole (HOBt)and NNN1015840N1015840-Tetramethyl-O-(benzotriazol-1-yl)uronium

Journal of Chemistry 5

(1) GA(2) DCCNHS

O O O

Si Si SiO O O

HNHN

O O

OO OONO O NO O

H2N

O O O

Si Si SiO O O

H2N H2NH2N

Scheme 3 Surface modification with activated carboxylic acid

tetrafluoroborate (TBTU) The free amino functional groupsin lysine containing proteins are targeted for the immobiliza-tion of proteins on the glass surface through amide couplingreactions The polyamidoamine (PAMAM) dendrimer isused as a linker for immobilization of the DNAs on the glasssurfaces [50 51] PAMAM was initially invented in the 1980sto increase the amino groups on the outer surface of sphere[52] Its application is now extended for DNA immobiliza-tion Firstly the silylation is performed using 95 3 2 vvsolution of ethanol water and APTES by treating the glassslides for 2 h

As depicted in Scheme 3 Benters et al treated the silylatedsurface overnight with the solution of glutaric anhydride(GA) in DMF Slides are then washed with DMF multipletimes to remove the unreacted reagents Carboxyl groups areactivated by using activating reagent such as 1mM solutionof NHS or dicyclohexylcarbodiimide (DCC) in DMF for 1 hfollowed by washing with DMF For the covalent attachmentof dendrimer 100120583L of 10 PAMAM in methanol is allowedto react with the activated carboxyl functional groups on thesurface for 12 h at room temperature followed by washingwith methanol to remove the excess dendrimer Before theimmobilization of DNAs on the surface these dendrimers areactivated by using GANHS as described above [53]

(4) Diazotization Diazo one of the stable bonds in organicchemistry makes its use imperative in the surface modifica-tion process For diazotization the amine-modified surfaceis needed Commonly a cleaned glass using piranha solutionfor 30min followed by deionized (DI) water is used [54]The cleaned glass surface is then allowed to react with the(4-aminophenyl) trimethoxysilane in ethanol solution for30min After silanization the amine-modified surface istreated with the sodium nitrite (NaNO

2) to generate dia-

zobenzyl surface as depicted in Scheme 4 The diazotizationreaction is done at 4∘C using solution of 40mL water 80mLHCl (400mM) and 32mL NaNO

2(200mM) as reported by

Alwine et al [55] After the reaction surface is washed withice-cold sodium acetate buffer deionized water and ethanolThen the solution containing the probe DNAs is spottedon the ice-cold diazotized surface and air dried for 1-2 hDolan et almentioned that the unreacted diazo groups on the

surface are blocked by reaction with the glycine or UV-cross-linked followed by baking for two hours at 80∘C [56] Theimmobilized DNAs can be allowed to hybridize with the PCRproducts for the detection and discrimination of pathogens

(5) Surface Modification with Supramolecules In the lastdecade tremendous work is done on the various applicationsof supramolecules in particular calixarenes [31 57 58] Thecalix[4]crown-5 derivatives are well known for their abilityto capture the cationic substrates including metal cations andammonium ions [59] The cavities of calixarenes are wellknown to capture the amino groups of proteins and formstable complexes with them According to the report Leeet al exploited the ability of calixarenes to form complexeswith proteins to fabricate the protein microarrays on glasssurfaces as depicted in Figure 4 [60 61] For the fabricationof the protein microarrays the calix[4]crown-5 derivativescontaining aldehyde functional groups are reacted with theamine functional groups on the amine-modified glass chip togenerate a monolayer

Then the protein in PBS solution with 30 glycerol isspotted on calix[4]crown-5 derivative modified glass surfaceand incubated at 37∘C for 3 h Then the chip is washed withthe 10mMPBS solution containing 05 Tween 20 for 10minat room temperature and dried under a stream of N

2gasThe

unreacted calix[4]crown-5 derivatives the free amine groupson the glass surface are blocked by immersing the chip intothe 3 BSA in PBS solution for 1 h at room temperature

Similar to protein microarrays [62] Nimse et al reportedthe DNA microarrays based on the 9G technology whichuses the interactions of the monolayer of calix[4]arenederivatives on the glass surface and the DNAs appended tothe nine consecutive guanines (9G) are also reported [32]The aminocalix[4]arene (AMCA) derivative with aldehydefunctional groups is allowed to reactwith the amine-modifiedglass surface to generate the AMCA slides As depicted inFigure 5 the determination of contact angle of water onthe AMCA modified glass surface indicates that the AMCAmolecules make the glass surface hydrophobic

Once the AMCA immobilization is done the solutioncontaining DNA probes appended to 9G is spotted on the

6 Journal of Chemistry

OH O OH

N

N

N

OH OHO

Si

Si

N

N

lowast

lowast

SiO2

SiO2

OH O OH

Si

SiO2

OH OH OH

SiO2

OH OHO

Si

SiO2

Si(OCH3)2

Single strandedunlabeled target DNA

+NClminus

NaNO2 + HCl

Diazonium ion

Cy3Cy5-dCTPDNA

For 14ndash16hr

lowast

lowast

NH2

NH2

Hybridized at 42∘Cat 4∘C

at 30min4∘C

Scheme 4 Covalent immobilization of probe DNA on a glass surface by diazotization and subsequent hybridization

O O O

O O

O

O

X X X X

+N

H4

+N

H4

H3C CH3O O O

O O

O

O

X X X X

H3C CH3

1 cm

1 cm

Figure 4 Interaction of calix[4]crown-5 derivative with proteins for the fabrication of protein microarray (adapted from [31])

Journal of Chemistry 7

(a) (b)

Figure 5 Contact angle comparison (a) bare glass and (b) AMCA modified glass slide (adapted from [32])

surface by using microarray After incubation at room tem-perature for 4 h the slides are washed to remove excess DNAsand driedThe free AMCAmolecules on the surface are thenblocked with the 4x SSC solution containing BSA and 01SDS Finally the slides are dried to obtain 9G DNAChips[63 64]

23 Carbon In recent years a nanoparticle-based structurelike nanotubes and nanowires has got tremendous attentionin biomedical and diagnostic fields [65 66] Before 1991 sp3hybridized form of carbon (diamond) sp2 hybridized formslike graphite and C60 fullerene were the only known formsof carbon with potential applications [67] In 1991 allotropeslike carbon nanotubes (CNT)were first reported and success-fully synthesized by Iijima with multiwall faces (MWCNT)[68]

Due to thermal electrical and magnetically uniqueproperties CNT became an important material in the devel-opment of biosensor platforms Commonly reportedmethodfor preparation of CNT includes chemical vapour deposition[69 70] arc discharge [71] and laser ablation [72]

Apart from CNT other carbon-based nanostructuresincluding carbondots carbon fibers andPDMSalso attractedresearchers due to their diverse properties for biomoleculeconjugation [73 74]Themajor advantage of carbon nanoma-terial is their large surface area which allows maximum spacefor biomolecule attachment

Immobilization of protein carbohydrate and nucleic acidon the CNT surfaces allows various biological applications[75 76]Themost important part in biomolecule conjugationis the surface functionalization of carbon-basedmaterialThegeneral techniques for carbon surface modification are (phy-sisorption) noncovalent and covalent modifications Thereare several reports on the different techniques of surfacemodification of carbon-based surfaces Due to the vastnessof the research on carbon-based material only few methodsare described in this paper

231 Physisorption Thehydrophobic character of CNT side-walls and the strong 120587-120587 interactions between the individualtubes causes them to aggregate and reduce their solubility in

common solvents which is considered as a problem for theirbiological applicationsHowever the samehydrophobic char-acter of theCNT surface is exploited for fabrication of biosen-sors by immobilizing biomolecules onto the CNT surfacesthrough hydrophobic-hydrophobic interactions [77ndash79]

The advantage of noncovalent interaction is a limiteddistortion of the three-dimensional structure of a protein orenzyme to be immobilized The hydrophobic amino acidsin proteins and enzymes develop the 120587-120587 interactions withthe hydrophobic part of CNT which make them adsorbedon the surface of CNT [80ndash83] As mentioned earlier theplatforms modified by noncovalent interactions suffer fromthe typical drawbacks of nonspecific interactions resulting inthe decreased specificity and sensitivity of a biosensor

To eliminate the problem of nonspecific interactions oftarget proteins with the sensor surface the novel approachof polyethylene oxide (PEO) polymer coating is adopted bymany researchers The PEO is well known for its proteinrepelling ability [84] Bomboi et al reported the use of Tween20 which is composed of three PEO branches and P103another molecule with hydrophobic polypropylene oxideunits to modify the surface of CNT before adsorption ofproteins on it The surface of Tween 20 and P103 modifiedCNT becomes slightly hydrophilic compared with bare CNTwhich results in the decrease in its interaction with thehydrophobic amino acid chains of biomarker proteins [85]

As depicted in Figure 6 for the selective immobilizationof streptavidin on the CNT surface Chen et al used mixednoncovalent and covalent approach which allows the highlyspecific immobilization of streptavidin and blocks the non-specific binding of other proteins like BSA [33]

Conjugation of a fluorescent molecule on the CNT sur-face is an immerging technology for highly sensitive detec-tion of biomolecules Nakayama-Ratchford et al reported theimmobilization of the fluorescent molecules like fluoresceinon the surface of CNT through 120587-120587 interactions [86] Thereare several reports on the applications of CNT surfaces mod-ified with the fluorescent molecules through noncovalentinteractions [87ndash90]

232 Chemical Modification To prevent the nonspecificbinding and to avoid the leaching of biomolecules from the

8 Journal of Chemistry

OH

OH

OH

O

HO

HO

HO

O

OO

OO

NH

O

NH

O

NH

OO

NH O

NH

O

NH

65 HON3

Boiling t = 8h

C2H4(NH2)2

NH2

H2N (CH2)2

(CH2)2

NH2(CH2)2

NH2(CH2)2

H2N (CH2)2

H2N (CH2)2

Scheme 5 Amine modification of CNT

BB

B

B B

B

SA SA

Figure 6 Streptavidin recognition by a nanotube coated with biot-inylated Tween (adapted from [33])

CNT surface a covalent modification technique is reportedThere are two types of covalent modifications namely (i)indirect method for example carboxylation of CNT surfaceand (ii) direct method for example fluorination of CNT sur-face where surface carbons change from sp2 to sp3 hybridiza-tion Esterification or amidation and sidewall covalent attach-ment are other approaches for covalent attachment [91 92]

(1) Carboxyl Modification The modification of the sensorsurfaces with the carboxyl groups is a general and highly usedsurface modification method Once the surface is modifiedwith the carboxyl groups it can be converted to a vari-ety of functional groups through reaction with appropriatereagents Furthermore the carboxylated surfaces can bedirectly conjugated with proteins or DNA through theiramine functional groups using coupling reagents A mixtureof sulphuric acid and nitric acid is a commonly used reagentfor the carboxylation of CNT surface

Marshall et al reported the method for carboxyl modifi-cation of CNT [93] According to this method a 2mg sampleof SWCNT is added to the 75 mixture of concentratedsulphuric acid and nitric acid (1mL) The mixture is allowedto sonicate in sonicator at 20∘CThe reaction mixture is thendiluted to 250mL by using deionized waterThe carboxylatedCNTs are then filtered through polytetrafluoroethylene filter(PTFE) of 045 120583m size Finally the collected nanotubes arewashedwith water at acidic pH followed by ethanol and driedin a vacuum desiccator

O OOH

O OOO

n

Figure 7 Structure of Epon resin 828

(2) Amine Modification Amide coupling is the most com-monly used conjugation technique in biomolecule attach-ment Either the amine or acid part of DNA or protein canbe used for conjugation using amide coupling reaction Forthe conjugation ofDNA toCNT through its phosphate groupamine modification is needed

Tam et al reported the DNA sensor based on the aminemodification of MWCNT as depicted in Scheme 5 [94] TheMWCNT were boiled in the 15M nitric acid for 12 h to gen-erate the carboxylated MWCNT The purified carboxylatedMWCNT were reacted with ethylenediamine to obtain theamine-modified MWCNT The amine-modified MWCNTwere conjugated to DNA by using EDC coupling reaction

Other reports for aminemodification of CNT include theuse of nitric acid and sulphuric acidmixture for carboxylationof the surface followed by ethylenediamine reaction [95]There are several reports on the covalent conjugation offluorescent molecules to the CNT surfaces [96ndash98]

(3) Epoxy Modification Epoxide group is a highly reactivefunctional group used in many substitution reactions as anelectrophile Eitan et al reported the covalent attachmentof epoxide-terminated molecules to carbon nanotubes byreaction between epoxide rings and carboxylic acid groupsthat are initially formed on the nanotube surface [99] Forepoxidation of CNT the surface is first carboxylated bydispersing the CNT in 75 solution of sulphuric acid in nitricacid for 3 h The purified carboxylated CNT were kept in theacetone with sonication for 1 hThen the solution containingthe carboxylated CNT is mixed with the solution of Eponresin 828 (Figure 7) in acetone to allow the reaction betweenEpon resin 828 and carboxyl groups on the CNT surface asdepicted in Scheme 6

Journal of Chemistry 9

O

O

O

O

R

OOCatalyst

O

O

O

O

O

O

CHHO

R

O

HC OH

R

O

H2C

O

HC OH

R

O

H2C

CH2

O

CHHO

R

O

CH2

HOHO

OHOH

+

Scheme 6 Epoxy modification of CNT

The mixture of solutions is sonicated for 1 h followedby stirring and heating at 70∘C The reaction was quenchedby addition of appropriate amount of potassium hydroxideThen the epoxilated CNT were purified and a number ofepoxy groups on the CNT surface were determined by usingthermogravimetric analysis

24 Nitrocellulose A PoC diagnosis system is always expe-cted to deliver final results in few minutes Though themicroarrays based on the glass and gold surfaces are usefulfor detection of multiple analytes at a time they need longertime for final data interpretation Microfluidic systems basedon paper or nitrocellulose membranes are emerging surfacesfor detection of bacteria viruses and proteins A paper isadvantageous due to its hydrophilic nature which allowsthe aqueous solutions to penetrate without the need of anyexternal force [100] The essential constituent of paper iscelluloseThe cellulose has hydroxyl functional groups whichcan be modified and changed according to surface propertiesneeded for a particular detection device [101] Due to lowcost and high availability paper is preferred for large scaleproduction Moreover the devices required for the tests areportable and disposable [102ndash105] The very first example ofpaper based detection is glucose detection in urine [106] andpregnancy test kit [107]There are different types of paper likeWhatman filter paper glossy paper [108] membrane and soforth Whatman filter is used because of its high penetrationand flow rate [109ndash112] but in some cases it does not havethe necessary characteristic for surface modification Mem-branes on the other hand are planner sheets and providelarger surface area for immobilization of biomolecules such

as DNA and protein The nitrocellulose (NC) membrane isbroadly used for immobilization of DNA [113] protein [114]and enzymes [115] due to its hydrophobic surface

241 Physical Adsorption Single-stranded DNAs are irre-versibly bound to the surface of the NCmembrane with non-covalent interactionsTheprimary interactions are hydropho-bic and electrostatic between the positively charged surfaceof the membrane and negatively charged DNAs The nitro-cellulose offers very high binding capacity for DNAs andproteins Fabrication of NC membranes can be done bydifferent methods including the photolithography The waxpatterningmethod is fast cheap and easy to process and doesnot need organic solvents The NCmembranes with the poresize of 045 120583mdo not need pretreatment for penetrationThefabrication process includesmainly printing and baking stepswhich can be finished in 10min As shown in Figure 8 firstlythe wax is printed on the surface of NCmembrane and bakedat 125∘C for 5min in the oven The melting of the wax onmembrane makes it more hydrophobic and affords surfacesuitable for the immunoassay For immunoassays Lu et alcoated the cAbs on the surface and the free area is blockedwith the 1 BSA

During baking melted wax passes through the mem-brane The 121∘ contact angle of backside membrane assuresthe melting of wax thoroughly The efficiency of wax treatedmembrane is compared with the untreated membrane byimmobilizing fluorescence labeled goat antihuman IgG Theimmobilization on wax printed surface is more uniform thanthe untreated membrane Apart from this a large volumeof liquid can be used because ring effect of protein on the

10 Journal of Chemistry

HO

OSH AuNP

AuNP-mAb

mAbEDCNHS

001M PBS

(CH2)15(CH2)11

NaBH4HAuCl4 + SH + HO

pH sim 74

Scheme 7 Immobilization on antibodies on AuNP

NC membrane

Cross section view

PrintingStep 1

Step 2 Baking

Wax patternedNC membrane

Wax is printed onto thesurface of NC membrane

Wax melts and penetratesthrough NC membrane

Nitrocellulose

Wax

Figure 8Wax printing on nitrocellulosemembranes (adapted from[34])

untreated membrane is avoided Wax printing method gen-erates 100 120583mmicrochannel which removes the micrometersize contaminants and makes the wax printed membranessuitable for the applications in microfluidic assays Apartfrom immobilization wax printing has application in dotimmunoassay and sample purifications [34]

Due to advantages of NC membrane for high bindingcapacity and good flow of solution it is also used on the chipsurfaces The glass slide can be coated with the 12 120583m layer ofNC to afford a platform with the intrinsic properties of NCThe solution of cAbs in PBS buffer containing 10 glycerolis then spotted on the modified surface After spotting theslides are incubated for one hour After incubation slides arewashed with 01 Tween 20 in PBS buffer and dried to gen-erate the platform for detection of biomarker proteins [116]

Apart from routine microarray applications NC mem-brane is also used for the detection of circulating tumor cells(CTC) as reported by Zhang et al The binding of CTCs bythe cAbs immobilized on the NC membrane is detected bySurface Enhanced Raman Scattering (SERS) as depicted inFigure 9

Usually the antibodies specific for cancer cells are usedas a capture substrate and immobilized on the surface TheNC membrane is cut into 1 cm times 1 cm pieces Then thesepieces are immersed in the ethanol and then tiled on thePMMA wafer After washing the membrane is activated byusing PBS buffer containing antibodies at 37∘C for 30minDuring this process the cAbs are avidly immobilized on theNC membrane The 1 BSA solution is loaded to block thefree surface area to avoid any background signals due tononspecific interactions Finally the membranes are washedwith PBS buffer and stored at 4∘CThe gold nanoparticle andRaman probes are used to detect the CTCs by SERS [35]

25 Gold Application of nanoparticles is amost focused areain the field of inorganic chemistry and it has also attractedimaginations of many biologists too Inorganic nanoparti-cles including gold silver and ferrous oxides have foundmany important applications in cell signaling drug deliveryand colorimetric and fluorescence-based detections Goldnanoparticles (AuNP) functionalized with proteins DNAsor Raman probes are well known in the field of biosensorsand nanobiotechnology for their applications in the molec-ular diagnostics [117ndash119] protein detection [120ndash122] generegulation [123] and cell imaging [124]

251 Covalent Modification

(1) Thiol Based Modification AuNPs are commonly usedin the electrochemical and optical detection systems Theconjugation with biomolecule does not change the opticalproperties ofAuNP [125]Di Pasqua et al reported thiolmod-ification for the detection of E coli O157H7 E coli specificantibodies were conjugated with the AuNPs [126] As shownin Scheme 7 the 10 nmAuNPs are carboxylated and then cou-pled to E coli specific monoclonal antibody (mAb) throughamide coupling

For the generation of AuNPs to the solution containing410mg of HAuCl

4sdot3H2O in 6mL of water ethanoic solutions

of 11-mercapto-1-undecanol and 16-mercaptohexadecanoicacid are added Upon addition of NaBH

4to this mixture at

0∘C the solution turns brown The product AuNP cappedwith alkanethiol pendant alcohol and carboxylic acid func-tional groups precipitate upon three hours of stirring Theprecipitated particles are then thoroughly washed with etha-nol and an ethanolic solution containing a small amountof 1M HCl The AuNPs are then dried under vacuum forten hours For the conjugation of mABs with the AuNPsthe carboxylic acid functional groups on the AuNPs are

Journal of Chemistry 11

SERSimaging

AuNPs

Raman labelNC membrane

AntibodyCancer cell

Figure 9 Detection of circulating tumor cells on NC membranes containing immobilized cAbs (adapted from [35])

activated by reacting the AuNPs with 1-ethyl-3-3(3-dimeth-ylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in the PBS buffer The mABs arethen added to this solution and the suspension is stirred atroom temperature for 30min The mAB-conjugated AuNPsare then collected by centrifugation and washing with PBSand ethanol The mAB-conjugated AuNPs successfully bindto E coli when incubated in PBS at pH 74 In other reportsthe AuNPs were found very effective in the detection ofcancerous pancreatic cells

The AuNPs are known to suffer from the problem ofaggregation upon long-term storage Therefore to solve thisissue the AuNPs are conjugated with the polyethylene glycol(PEG) to prevent their aggregation [127 128]The conjugationof PEGwith the AuNPsmakes the later hydrophilic thus pre-venting agglomeration induced by hydrophobic interactionsA PEGwith the heterobifunctional groups (dithiol at one endand a carboxyl at another end) is coated on the AuNP Thedithiol group allows stable anchoring heterobifunctional PEGligands on the surface of AuNP and the terminal carboxylgroup is used for coupling with antibodies The carboxy-terminated bifunctional PEG linker is synthesized by follow-ing a method reported by Eck et al which is depicted inScheme 8 The anionic polymerization of compound 1 withan excess of ethylene oxide allows synthesizing compound 2The treatment of compound 2 with chloroacetic acid at 60∘Callows generating compound 3 The reaction of an excess ofthe elemental bromine in dichloromethane at 0∘C for fourhours in the dark with compound 3 produces dibromidecompound 4 Compound 5 is obtained by reaction withcompound 4 in water with the excess of sodium hydrosulfidehydrate

The synthesized bifunctional PEG linker is then conju-gated with the citrate-stabilized gold nanoparticles by simpleligand exchangeThe citrate-stabilized gold nanoparticles areknown to aggregate in the buffer containing salts Thereforethe ligand exchange from citrate to PEG should be done inpure water The PEGylated AuNPs are conjugated to mono-clonal F19 antibodies for the detection of human pancreaticcarcinoma through EDCNHS coupling reaction [129]

OHO

(2) HCl

1

2

3

4

5

Br Br

HS SH

(CH2)9

(CH2)9

(CH2)9

(CH2)9

+

NaHDMF60∘C

(OCH2CH2)n

(OCH2CH2)n

(OCH2CH2)n

OCH2COOH

OCH2COOH

(CH2)9 (OCH2CH2)n OCH2COOH

OminusNa+

Br2

(2) Acetic acid (1) NaSHH2O

60∘C(1) ClCH2-COONa

Scheme 8 Synthesis of bifunctional PEG linker using conjugationwith AuNP

(2) Hydrazide Modification According to the report by Zhiet al the hydrazide-derivatized self-assembledmonolayer ona gold surface is used for the efficient and selective anchor-ing of oligosaccharide [39] The generated oligosaccharidemicroarrays allow the fluorescence-based detection of targetproteins The use of gold as a substrate for the fluorescence-based detection suffers from the drawbacks including flu-orescence quenching and nonspecific surface adsorption ofproteins However the use of120596-thiolated fatty acid (C

16) self-

assembledmonolayer between the gold surface andhydrazide

12 Journal of Chemistry

AuC C

C

C

OHOHO O

O

O

O

O

O

O

O

O

CHR

NN

H

N

N

N

H

NH

NH

NH

H

NH

C

O

O

O NNH

NH

HNH

H

S

S

S

S

HS Au

Au

Au

Au

Au

C16 SAM

Adipic dihydrazideEDC

(Sugar)R-CHO

Binding to protein

Sugarprobe

Protein Alexafluoro 532

SAM andblocking layer

Ab 2nd Ab

NH2

NH2H2N

CH2R

Scheme 9 Application of hydrazide-derivatized SAM on a goldsurface for the fabrication of oligosaccharide microarray (adaptedfrom [39])

groups minimizes the quenching effect Moreover the effec-tive blocking of the surface with the poly(ethylene glycol)aldehyde and BSA reduces the nonspecific adsorption ofprotein on the surface

For the fabrication of the reported oligosaccharidemicroarrays the gold substrate is prepared by following amethod depicted in Scheme 9 The self-assembled mono-layer (SAM) of 16-mercaptohexadecanoic acid (MHDA) isobtained by soaking the gold coated slides in the isobutylalcohol for 2 days The slides are then washed in ethanolto remove excess reagents and are dried under the nitrogenstream The carboxyl functional groups on the SAM areconverted to the hydrazide groups by incubation of the SAMcovered slides in the dimethyl sulfoxide solution containing1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and adipicdihydrazide The ethanol-washed and dried slides are thenused for the oligosaccharide printing to obtain oligosaccha-ride microarrays

The generated oligosaccharide microarray platformallows interrogation of carbohydrate-protein interactions ina high-throughput manner

26 Silver Similar to AuNPs silver nanoparticles (AgNP) arealso used for the immobilization of proteins and enzymesThe surface of AgNP allows adsorption of proteins Henceit can be utilized as a host matrix for various biomoleculesSilver is a suitable substrate for the immobilization of wholecell or the isolated enzymes [130 131]

Texp lt Tm

Ag

AgAg

Ag

AgAg

Texp gt Tm

Figure 10 AgNPs-oligonucleotide conjugates (adapted from [36])

261 Electrostatic Modification The electrostatic interac-tions allow the physical adsorption of biomolecules on thesurface of AgNPs Shen et al reported that the AgNPs aresynthesized by reduction of silver nitrate in the presence ofsodium citrate During the reduction process the solutionis sonicated for 15min to obtain the yellow silver colloidwhich is then kept at 4∘C for several days away from lightThen isolated nanoparticles can be used for physisorption ofproteins at a pH higher than their isoelectric point [132]

262 Covalent Modification As depicted in Scheme 10the AgNPs prepared by the citrate reduction method andstabilized with citrate [133] can be functionalized with car-boxyl groups upon treatment with 3-mercaptopropanoic acid(MPA) As reported by the Petkova et al for the immobi-lization of alcohol dehydrogenase from Thermoanaerobiumbrockii (TbADH) the carboxyl-modified AgNPs were treatedwith the solution containing TbADH under continuousstirring for 7 h at 26∘C a research by [134] The AgNPsmodified with the TbADH were successfully used for thebiotransformation studies

The application of a bifunctional linker for the modifica-tion of AgNPs is reported [135 136] The bifunctional linker11-mercaptoundecanoic acid was used with 1-octanethiol in1 1 ratio to generate the mixed SAM on the surface of AgNPThe IgG antibodies are then conjugated with the mixed SAMmodified AgNPs It is reported that upon covalent conjuga-tion of biomolecules with AgNPs their stability and activityis maintained [137]

According to another report on the covalent modifi-cation AgNPs-oligonucleotide conjugates are prepared byusing DNA and triple cyclic disulfide moieties [36] Asdepicted in Figure 10 the two types ofAgNPs-oligonucleotideconjugates with complementary DNA sequences undergoDNA hybridization driven coagulation resulting in the colorchange

As depicted in Figure 11 the AgNP-DNA conjugates wereprepared by treatment of AgNPs with the cyclic disulfidemodified oligonucleotide The AgNP and oligonucleotideswere allowed to react with each other with 1 4 ratio inthe presence of 1 sodium dodecyl sulfate and NaCl Theovernight incubation of solution results in the AgNP-DNAconjugates which are collected by centrifugation and washedto remove the excess DNAs

Journal of Chemistry 13

Ag AgMPAOH

OO OH

O

HOCitrate

Citrate

Ag

COOH

COOH

TbADHAg

CONH

COOH

TbADHOminusNa+

H2N

Scheme 10 Covalent conjugation of enzymes on the surface of carboxyl-modified AgNPs

OHO

EDC HOSu Bis-amino

polyethylene glycol

NH

OO

44GMBS N

H

OO N

H44

ON

O

O3

CoA

NH

OO N

H44

ON

O

O3

SHN

O

OH

OP O

OPO

O O

OHO

NNN

N

PO

OminusOminus

OminusOminus

NH2

NH2

Scheme 11 Covalent conjugation of coenzyme A to polystyrene nanoparticles

O OOO P

OHSS

5998400 (DSP)3-A10-ATT-ATC-ACT 3998400

DSP cyclic disulfide-containingphosphate derivative =

Figure 11 Conjugation of AgNPs with oligonucleotides by usingDSP as a linker molecule (adapted from [36])

27 Polystyrene Polystyrene is an aromatic polymerobtained by polymerization of styrene monomers [138] Thepolystyrene-based NPs are widely used in the moleculardiagnostics for the detection of biomarker proteins andgenomic DNAs Polystyrene can be employed as a coating ona variety of nanoparticles as its functional groups can be easilymodified or conjugated with other molecules The otherapplication of polystyrene is in the fabrication of fluorescencebeads (FBs) The fluorescence molecules are loaded into thepolystyrene shell to produce FBs which are then used invarious sensing applications The polystyrene is also used tocoat the magnetic NPs so they can be conjugated with otherbiomolecules such as DNA and Proteins The applications ofpolystyrene include but are not limited to the detection ofE coli [139] the detection of cardiac Troponin T (cTnT) thedetection of Herpes simplex virus and many more

271 Covalent Modification Covalent modification throughcarboxyl group iswell known formodification of biomolecule

Most of the polystyrene-based nanoparticles bear large num-bers of pendant carboxyl which increases the loading amountof biomolecule

Enzyme catalyzed covalent immobilization of the pro-teins bearing a small 12-mer ldquoybbRrdquo tag onto the polystyrenenanoparticles (PSNP) is recently reported by Wong et al[140] As depicted in Scheme 11 the carboxyl-PSNPs werereacted with the bis-amino-polyethylene glycol in the pres-ence of HOSu and EDC to generate the amino-pegylatedPSNPs These PSNPs are then reacted with the g-maleimi-dobutyric acid succinimidyl (GMBS) to obtain maleimide-functionalized PSNPs The maleimide-functionalized PSNPsupon chemoligation with coenzyme A (CoA) produce theCoA-derivatized PSNPs

As depicted in Scheme 12 the protein of interest bearingybbR-tag is immobilized on the CoA-derivatized PSNPsThephosphopantetheinyl transferase (Sfp) catalyzed the reactionbetween the serine residue of the ybbR-tag and the phos-phopantetheine moiety of CoA with the simultaneous lossof 3101584051015840-adenine diphosphate results in the attachment ofproteins onto the surface of PSNPs It is reported that theenzymes immobilized by this method retain their activity

There are several reports on the use of fluoromicrobeadsfor the detection of biomarkers Primarily the fluoromi-crobeads are made up of carboxylated polystyrene as a coat-ingmaterial entrapping the fluorescentmolecules Accordingto the recent report by Song et al [37] the fluoromicrobeadswere used for the detection of the cTnT on the proteinmicroarray as depicted in Figure 12

The carboxylate modified fluoromicrobeads were conju-gated with the anti cTnI mAb through EDCNHS-mediated

14 Journal of Chemistry

HN

O

OH

OP

O

O

PO

O

OHO

N

NN

P

O

S

HN

O

Coenzyme A

Phosphopantetheine

PO

O

O

OHO

N Sfp

NN

N

P

O

ybbr-protein

HN

O

OH

OP

O

O

S

HN

O

NH2

NH2

Ominus

Ominus

Ominus

minusO

minusO

Mg2+

HO∙∙

Ominus

OminusOminus

minusO

N

O

Polystyrenenanoparticle

Scheme 12 Protein conjugation to polystyrene NP

System 1 antibody-conjugated fluoromicrobeads

System 2 avidin-conjugated fluoromicrobeads

DTSP SAM

Anti-cTnI cAb

cTnI

Figure 12 Application of the polystyrene-coated fluoromicrobeadsfor the detection of cTnI on the protein microarray (adapted from[37])

coupling reaction The use of fluoromicrobeads alloweddetecting the cTnI in plasma samples with a range of 01ndash100 ngmL

272 Affinity-Based Modification The affinity interactionsare used for the attachment of oligonucleotides with thefluoromicrobeads or polystyrene-coated magnetic beads Togenerate the oligonucleotide conjugated fluoromicrobeads ormagnetic beads respective polystyrene-coated beads are firstconjugated with the streptavidin using the EDCNHS cou-pling reaction as reported by Zhang et al [141] As depicted

B

B

MB MB

MB

BB

Magnetic bead

Streptavidin

DNA labeled biotin

Figure 13 DNA attachment to the magnetic beads

in Figure 13 the streptavidinmodified beads are then allowedto incubate with the biotinylated oligonucleotides Due to theaffinity of biotin for streptavidin the biotinylated oligonu-cleotides can be readily immobilized on the streptavidincoated beads

The binding affinity of streptavidin and biotin in solutionis up to 25 times 1013 (molL)minus1 [142] This interaction is about amillion times stronger than the antigen and antibody inter-action The antibodies directly immobilized onto the sur-face lose 90 of their biological activity [143] Howeverthe biotinylated antibodies immobilized on the streptavidincoated surface can retain their bioactivity [144]

Journal of Chemistry 15

3 Conclusions

Surface modification techniques of the materials used asplatforms in the fabrication of biosensors are reviewed inthis paper There are several reports on materials and vari-ous methods for altering their physicochemical propertiesHence one of these methods can be chosen according tothe targeted use and needed physiochemical properties Itis important to note that the performance of the biosensoris highly dependent on the substrate material used and itsmeticulous modification for particular applications There-fore it is critical to understand the principles of a biosensor toidentify the correct substrate material and its surface modifi-cation chemistry Furthermore it is important to look at thelatest advances in the materials and techniques used for thefabrication of a biosensor before the processing

Competing Interests

All authors declare that there is no conflict of interests

Acknowledgments

This research was supported by the Hallym UniversityResearch Fund (HRF-201601-010) This work was also sup-ported by the fund obtained through Industry-Academic col-laboration between Biometrix Technology Inc (ChuncheonSouth Korea) and Hallym University

References

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[2] A Cavalcanti B Shirinzadeh M Zhang and L C KretlyldquoNanorobot hardware architecture for medical defenserdquo Sen-sors vol 8 no 5 pp 2932ndash2958 2008

[3] R-Q Zhang S-L Liu W Zhao et al ldquoA simple point-of-caremicrofluidic immunomagnetic fluorescence assay for path-ogensrdquo Analytical Chemistry vol 85 no 5 pp 2645ndash2651 2013

[4] S B Nimse K S Song M D Sonawane D R Sayyed and TS Kim ldquoImmobilization techniques for microarray challengesand applicationsrdquo Sensors vol 14 no 12 pp 22208ndash22229 2014

[5] A P F Turner ldquoBiosensors sense and sensibilityrdquo ChemicalSociety Reviews vol 42 no 8 pp 3184ndash3196 2013

[6] L Wu and X Qu ldquoCancer biomarker detection recent achieve-ments and challengesrdquoChemical Society Reviews vol 44 no 10pp 2963ndash2997 2015

[7] K Ariga Q Ji T Mori et al ldquoEnzyme nanoarchitectonicsorganization and device applicationrdquo Chemical Society Reviewsvol 42 no 15 pp 6322ndash6345 2013

[8] W-W Zhao J-J Xu and H-Y Chen ldquoPhotoelectrochemicalDNA biosensorsrdquo Chemical Reviews vol 114 no 15 pp 7421ndash7441 2014

[9] Q Liu C Wu H Cai N Hu J Zhou and P Wang ldquoCell-basedbiosensors and their application in biomedicinerdquo ChemicalReviews vol 114 no 12 pp 6423ndash6461 2014

[10] X Zhao S Nampalli A J Serino and S Kumar ldquoImmobi-lization of oligodeoxyribonucleotides with multiple anchors to

microchipsrdquo Nucleic Acids Research vol 29 no 4 pp 955ndash9592001

[11] P Kumar S K Agrawal A Misra and K C Gupta ldquoA newheterobifunctional reagent for immobilization of biomoleculeson glass surfacerdquo Bioorganic 120572Medicinal Chemistry Letters vol14 no 5 pp 1097ndash1099 2004

[12] F Secundo ldquoConformational changes of enzymes upon immo-bilisationrdquo Chemical Society Reviews vol 42 no 15 pp 6250ndash6261 2013

[13] S Lee S Kim J Malm O C Jeong H Lilja and T LaurellldquoImproved porous silicon microarray based prostate specificantigen immunoassay by optimized surface density of thecapture antibodyrdquoAnalytica Chimica Acta vol 796 pp 108ndash1142013

[14] K Jaras A A Tajudin A Ressine et al ldquoENSAM europiumnanoparticles for signal enhancement of antibody microarrayson nanoporous siliconrdquo Journal of Proteome Research vol 7 no3 pp 1308ndash1314 2008

[15] C Steinhauer A Ressine G Marko-Varga T Laurell C AK Borrebaeck and C Wingren ldquoBiocompatibility of surfacesfor antibody microarrays design of macroporous silicon sub-stratesrdquo Analytical Biochemistry vol 341 no 2 pp 204ndash2132005

[16] K Jaras B Adler A Tojo et al ldquoPorous silicon antibodymicroarrays for quantitative analysis measurement of free andtotal PSA in clinical plasma samplesrdquo Clinica Chimica Acta vol414 pp 76ndash84 2012

[17] S W Lee K Hosokawa S Kim et al ldquoA highly sensitive poroussilicon (P-Si)-based human Kallikrein 2 (hK2) immunoassayplatform toward accurate diagnosis of prostate cancerrdquo Sensorsvol 15 no 5 pp 11972ndash11987 2015

[18] C Roychaudhuri ldquoA review on porous silicon based electro-chemical biosensors beyond surface area enhancement factorrdquoSensors and Actuators B Chemical vol 210 pp 310ndash323 2015

[19] ARessine S EkstromGMarko-Varga andT Laurell ldquoMacro-nanoporous silicon as a support for high-performance proteinmicroarraysrdquo Analytical Chemistry vol 75 no 24 pp 6968ndash6974 2003

[20] S Lee E Silajdzic H Yang et al ldquoA porous silicon immunoas-say platform for fluorometric determination of 120572-synuclein inhuman cerebrospinal fluidrdquo Microchimica Acta vol 181 no 9-10 pp 1143ndash1149 2014

[21] S Belhousse N Belhaneche-Bensemra K Lasmi et alldquoModified porous silicon for electrochemical sensor of para-nitrophenolrdquo Materials Science and Engineering B vol 189 pp76ndash81 2014

[22] N Reta A Michelmore C Saint B Prieto-Simon and NH Voelcker ldquoPorous silicon membrane-modified electrodesfor label-free voltammetric detection of MS2 bacteriophagerdquoBiosensors and Bioelectronics vol 80 pp 47ndash53 2016

[23] B Guan A Magenau S Ciampi K Gaus P J Reece and J JGooding ldquoAntibody modified porous silicon microparticles forthe selective capture of cellsrdquo Bioconjugate Chemistry vol 25no 7 pp 1282ndash1289 2014

[24] S Vutti N Buch-Manson S Schoffelen N Bovet K LMartinez and M Meldal ldquoCovalent and stable CuAAC mod-ification of silicon surfaces for control of cell adhesionrdquo Chem-BioChem vol 16 no 5 pp 782ndash791 2015

[25] A M Rossi L Wang V Reipa and T E Murphy ldquoPoroussilicon biosensor for detection of virusesrdquo Biosensors andBioelectronics vol 23 no 5 pp 741ndash745 2007

16 Journal of Chemistry

[26] T L Lasseter B H Clare N L Abbott and R J HamersldquoCovalently modified silicon and diamond surfaces resistanceto nonspecific protein adsorption and optimization for biosens-ingrdquo Journal of the American Chemical Society vol 126 no 33pp 10220ndash10221 2004

[27] M Li K-G Neoh E-T Kang T Lau and E E ChiongldquoSurface modification of silicone with covalently immobilizedand crosslinked agarose for potential application in the inhibi-tion of infection and omental wrappingrdquo Advanced FunctionalMaterials vol 24 no 11 pp 1631ndash1643 2014

[28] G MacBeath and S L Schreiber ldquoPrinting proteins as microar-rays for high-throughput function determinationrdquo Science vol289 no 5485 pp 1760ndash1763 2000

[29] S B Nimse M D Sonawane K S Song and T Kim ldquoBio-marker detection technologies and future directionsrdquoThe Ana-lyst vol 141 no 3 pp 740ndash755 2016

[30] M D Sonawane S B Nimse K Song and T Kim ldquoDetectionquantification and profiling of PSA current microarray tech-nologies and future directionsrdquo RSC Advances vol 6 no 9 pp7599ndash7609 2016

[31] S B Nimse and T Kim ldquoBiological applications of function-alized calixarenesrdquo Chemical Society Reviews vol 42 no 1 pp366ndash386 2013

[32] K-S Song S B Nimse J Kim et al ldquo9GDNAChip microarraybased on the multiple interactions of 9 consecutive guaninesrdquoChemical Communications vol 47 no 25 pp 7101ndash7103 2011

[33] R J Chen S Bangsaruntip K A Drouvalakis et al ldquoNonco-valent functionalization of carbon nanotubes for highly specificelectronic biosensorsrdquo Proceedings of the National Academy ofSciences of the United States of America vol 100 no 9 pp 4984ndash4989 2003

[34] Y Lu W Shi J Qin and B Lin ldquoFabrication and characteri-zation of paper-based microfluidics prepared in nitrocellulosemembrane by wax printingrdquo Analytical Chemistry vol 82 no1 pp 329ndash335 2010

[35] P Zhang R Zhang M Gao and X Zhang ldquoNovel nitrocel-lulose membrane substrate for efficient analysis of circulatingtumor cells coupled with surface-enhanced raman scatteringimagingrdquo ACS Applied Materials and Interfaces vol 6 no 1 pp370ndash376 2014

[36] J-S Lee A K R Lytton-Jean S J Hurst and C AMirkin ldquoSil-ver nanoparticlemdasholigonucleotide conjugates based on DNAwith triple cyclic disulfide moietiesrdquo Nano Letters vol 7 no 7pp 2112ndash2115 2007

[37] S Y Song Y D Han K Kim S S Yang and H C YoonldquoA fluoro-microbead guiding chip for simple and quantifiableimmunoassay of cardiac troponin I (cTnI)rdquo Biosensors andBioelectronics vol 26 no 9 pp 3818ndash3824 2011

[38] S V Lemeshko T Powdrill Y Y Belosludtsev and M HoganldquoOligonucleotides form a duplex with non-helical properties ona positively charged surfacerdquoNucleic Acids Research vol 29 no14 pp 3051ndash3058 2001

[39] Z-L Zhi A K Powell and J E Turnbull ldquoFabrication ofcarbohydrate microarrays on gold surfaces direct attachmentof nonderivatized oligosaccharides to hydrazide-modified self-assembledmonolayersrdquoAnalytical Chemistry vol 78 no 14 pp4786ndash4793 2006

[40] S L Pan and L Rothberg ldquoChemical control of electrodefunctionalization for detection of DNA hybridization by elec-trochemical impedance spectroscopyrdquo Langmuir vol 21 no 3pp 1022ndash1027 2005

[41] Z Lu C M Li Q Zhou Q-L Bao and X Cui ldquoCovalentlylinked DNAprotein multilayered film for controlled DNAreleaserdquo Journal of Colloid and Interface Science vol 314 no 1pp 80ndash88 2007

[42] L-S Jang and H-J Liu ldquoFabrication of protein chips basedon 3-aminopropyltriethoxysilane as a monolayerrdquo BiomedicalMicrodevices vol 11 no 2 pp 331ndash338 2009

[43] F Fixe M Dufva P Telleman and C B Christensen ldquoFunc-tionalization of poly(methyl methacrylate) (PMMA) as a sub-strate for DNAmicroarraysrdquoNucleic Acids Research vol 32 no1 article e9 2004

[44] A Lueking M Horn H Eickhoff K Bussow H Lehrachand G Walter ldquoProtein microarrays for gene expression andantibody screeningrdquo Analytical Biochemistry vol 270 no 1 pp103ndash111 1999

[45] N Zammatteo L Jeanmart S Hamels et al ldquoComparisonbetween different strategies of covalent attachment of DNA toglass surfaces to build DNA microarraysrdquo Analytical Biochem-istry vol 280 no 1 pp 143ndash150 2000

[46] M Ozmen K Can I Akin et al ldquoSurface modification of glassbeads with glutaraldehyde characterization and their adsorp-tion property for metal ionsrdquo Journal of Hazardous Materialsvol 171 no 1ndash3 pp 594ndash600 2009

[47] C Funk PM Dietrich T Gross HMinW E S Unger andWWeigel ldquoEpoxy-functionalized surfaces for microarray appli-cations surface chemical analysis and fluorescence labeling ofsurface speciesrdquo Surface and Interface Analysis vol 44 no 8pp 890ndash894 2012

[48] S Mahajan P Kumar and K C Gupta ldquoOligonucleotide mic-roarrays immobilization of phosphorylated oligonucleotideson epoxylated surfacerdquo Bioconjugate Chemistry vol 17 no 5pp 1184ndash1189 2006

[49] M C Pirrung J D Davis and A L Odenbaugh ldquoNovelreagents and procedures for immobilization of DNA on glassmicrochips for primer extensionrdquo Langmuir vol 16 no 5 pp2185ndash2191 2000

[50] E Southern K Mir and M Shchepinov ldquoMolecular interac-tions on microarraysrdquo Nature Genetics vol 21 no 1 pp 5ndash91999

[51] M S Shchepinov S C Case-Green and E M SouthernldquoSteric factors influencing hybridisation of nucleic acids tooligonucleotide arraysrdquo Nucleic Acids Research vol 25 no 6pp 1155ndash1161 1997

[52] D A Tomalia A M Naylor and W A Goddard III ldquoStarbustdendrimers molecular-level control of size shape surfacechemistry topology and flexibility from atoms to macroscopicmatterrdquo Angewandte ChemiemdashInternational Edition in Englishvol 29 no 2 pp 138ndash175 1990

[53] R Benters C M Niemeyer D Drutschmann D Blohm andD Wohrle ldquoDNA microarrays with PAMAM dendritic linkersystemsrdquo Nucleic Acids Research vol 30 no 2 p e10 2002

[54] J H Moon J W Shin S Y Kim and J W Park ldquoFormationof uniform aminosilane thin layers an imine formation tomeasure relative surface density of the amine grouprdquo Langmuirvol 12 no 20 pp 4621ndash4624 1996

[55] J C Alwine D J Kemp and G R Stark ldquoMethod fordetection of specific RNAs in agarose gels by transfer to diazo-benzyloxymethyl-paper and hybridization with DNA probesrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 74 no 12 pp 5350ndash5354 1977

[56] P L Dolan Y Wu L K Ista R L Metzenberg M A Nelsonand G P Lopez ldquoRobust and efficient synthetic method for

Journal of Chemistry 17

forming DNA microarraysrdquo Nucleic Acids Research vol 29 no21 article e107 2001

[57] S B Nimse J Kim K-S Song et al ldquoSelective recognitionof the ditopic trimethylammonium cations by water-solubleaminocalix[4]arenerdquo Tetrahedron Letters vol 52 no 29 pp3751ndash3755 2011

[58] V-T Ta S B Nimse K-S Song et al ldquoCharacterization ofthe mixed self-assembled monolayer at the molecular scalerdquoChemical Communications vol 47 no 40 pp 11261ndash11263 2011

[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

[60] Y Lee E K Lee YW Cho et al ldquoProteoChip a highly sensitiveprotein microarray prepared by a novel method of proteinimmobilization for application of protein-protein interactionstudiesrdquo Proteomics vol 3 no 12 pp 2289ndash2304 2003

[61] S W Oh J D Moon H J Lim et al ldquoCalixarene derivative asa tool for highly sensitive detection and oriented immobiliza-tion of proteins in a microarray format through noncovalentmolecular interactionrdquo The FASEB Journal vol 19 no 10 pp1335ndash1337 2005

[62] S B Nimse K-S Song J Kim D R Sayyed and T Kimldquo9G DNAChip technology self-assembled monolayer (SAM)of ssDNA for ultra-sensitive detection of biomarkersrdquo Interna-tional Journal ofMolecular Sciences vol 14 no 3 pp 5723ndash57332013

[63] V-T Nguyen S B Nimse K-S Song et al ldquoHPAI 9GDNAChip discrimination of highly pathogenic influenza virusgenesrdquo Chemical Communications vol 48 no 38 pp 4582ndash4584 2012

[64] K-S Song S B Nimse J Kim D R Sayyed and T Kim ldquoAnew platform for a convenient genotyping systemrdquo ChemicalCommunications vol 49 no 26 pp 2661ndash2663 2013

[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

[67] F Hennrich C Chan VMoore M Rolandi andM OrsquoConnellCarbonNanotubes Properties and Applications Taylor amp FrancisGroup Abingdon UK 2006

[68] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

[69] C Singh M Shaffer I Kinloch and A Windle ldquoProductionof aligned carbon nanotubes by the CVD injection methodrdquoPhysica B Condensed Matter vol 323 no 1ndash4 pp 339ndash3402002

[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

[71] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

4 Journal of Chemistry

OO

GlutaraldehydeN O NNH2 N-DNA-Cy3

-DNA-Cy3H2N

Scheme 1 Aldehyde modification of glass slide

Si

Si

O

O

O

O

O

O

Si

Si

O

O

O

OH

OH

OP

O-d(NNN)

O-d(NNN)

O

O

OO O

P

O

O

O

Ominus

Ominus

d(NNN)=OP32minus

MW 10min35∘C 4hr

Scheme 2 Covalent attachment of phosphorylated DNA

various reports on the glass surfacemodification for the cova-lent attachment of biomolecules

(1) Aldehyde Modification For the aldehyde modification ofthe glass surface the silanol groups on the surface are con-verted to an amine by different methods using amine mod-ification reagents such as (3-Aminopropyl)triethoxysilane(APTES) [42] Fixe et al reported the aldehyde modificationusing glutaraldehyde As shown in Scheme 1 the amine-modified surface is then treated with glutaraldehyde (25vv) in 01M PBS for 2 h at room temperature The slide isthen washed with water and dried The solution containingamine-modified DNAs is spotted on the slide and incubatedin humidified chamber for up to 24 h to afford the DNAmicroarray However it is important to note that the unre-acted aldehyde functional groups on the glass surface shouldbe blocked by reacting them with the sodium borohydride(NaBH

4) [43]

Similar to the DNA immobilization the cAb can alsobe immobilized on the aldehyde-modified glass surfaces toafford protein microarrays However the cAbs on the proteinmicroarrays obtained by using aldehyde chemistry have alower binding affinity as well as reduced specificity for the tar-get antigens [44] Another method of aldehyde modificationof ester functionalized slide can be done by reduction to alco-hol followed by controlled oxidation of alcohol to aldehydeusing pyridinium chlorochromate (PCC) [45] Apart fromthe glass chips surface the glass bead surface is also modifiedto produce a surface with aldehyde functions using APTESand glutaraldehyde reagents [46]

(2) Epoxy Modification Apart from silanization epoxylationis a commonly used approach for glass surface modificationThe epoxy functional group on the epoxy-modified glasssurfaces are allowed to react with the amine-containingbiomolecules for their immobilization [47]Thus the amine-modified DNAs and proteins with their native amine groups

can be immobilized by this method on the glass surfaces forthe generation of DNA microarray and protein microarrayrespectively As shown in Scheme 2 the epoxy functionalizedsurfaces can be used for the covalent attachment of phospho-rylated DNAs

The advantage of this method is that the 31015840 phosphategroup can make a covalent bond with epoxy groups Thisallows immobilization of larger fragments of DNA or PCRproducts on the surface As explained by Mahajan et al theepoxylation of glass surface is carried out by keeping the glassin a 2 solution glycidoxypropyltrimethoxysilane (GOPTS)in toluene for 4-5 h at 50∘C followed by washing and dryingAfter epoxylation of glass surface the probe immobilizationis done by spotting the 31015840 phosphate DNA on the surface andmicrowave treatment for 10min in a buffer of pH 10 Afterthe DNA immobilization excess epoxy groups are maskedby using capping buffer of pH 9 containing 01M Tris with50mM ethanolamine for 15min at 50∘C [48]

One of the disadvantages of this approach is the need forhigh pH at which glass surface starts to degrade leading tothe inconsistent results [49] Furthermore the high pH alsodamaged the native three-dimensional structure of proteinsresulting in decreased sensitivity and increased nonspecificinteractions

(3) Carboxylate Modification The amine-modified DNAs arecommonly used because of the simple chemistry involved intheir conjugation with fluorescence molecules with carbonylfunctional groups Same chemistry can be attributed toimmobilizing the amine-modified DNAs on the carboxylicacid modified glass surfaceThe coupling between carboxylicacid and amine is direct without any linker in betweenthem The 1-ethyl-3-(3-dimethylaminopropyl) carbodiimidehydrochloride (EDC) is a commonly used reagent for amidecoupling reactions Other common coupling reagents are N-hydroxysuccinimide (NHS) hydroxybenzotriazole (HOBt)and NNN1015840N1015840-Tetramethyl-O-(benzotriazol-1-yl)uronium

Journal of Chemistry 5

(1) GA(2) DCCNHS

O O O

Si Si SiO O O

HNHN

O O

OO OONO O NO O

H2N

O O O

Si Si SiO O O

H2N H2NH2N

Scheme 3 Surface modification with activated carboxylic acid

tetrafluoroborate (TBTU) The free amino functional groupsin lysine containing proteins are targeted for the immobiliza-tion of proteins on the glass surface through amide couplingreactions The polyamidoamine (PAMAM) dendrimer isused as a linker for immobilization of the DNAs on the glasssurfaces [50 51] PAMAM was initially invented in the 1980sto increase the amino groups on the outer surface of sphere[52] Its application is now extended for DNA immobiliza-tion Firstly the silylation is performed using 95 3 2 vvsolution of ethanol water and APTES by treating the glassslides for 2 h

As depicted in Scheme 3 Benters et al treated the silylatedsurface overnight with the solution of glutaric anhydride(GA) in DMF Slides are then washed with DMF multipletimes to remove the unreacted reagents Carboxyl groups areactivated by using activating reagent such as 1mM solutionof NHS or dicyclohexylcarbodiimide (DCC) in DMF for 1 hfollowed by washing with DMF For the covalent attachmentof dendrimer 100120583L of 10 PAMAM in methanol is allowedto react with the activated carboxyl functional groups on thesurface for 12 h at room temperature followed by washingwith methanol to remove the excess dendrimer Before theimmobilization of DNAs on the surface these dendrimers areactivated by using GANHS as described above [53]

(4) Diazotization Diazo one of the stable bonds in organicchemistry makes its use imperative in the surface modifica-tion process For diazotization the amine-modified surfaceis needed Commonly a cleaned glass using piranha solutionfor 30min followed by deionized (DI) water is used [54]The cleaned glass surface is then allowed to react with the(4-aminophenyl) trimethoxysilane in ethanol solution for30min After silanization the amine-modified surface istreated with the sodium nitrite (NaNO

2) to generate dia-

zobenzyl surface as depicted in Scheme 4 The diazotizationreaction is done at 4∘C using solution of 40mL water 80mLHCl (400mM) and 32mL NaNO

2(200mM) as reported by

Alwine et al [55] After the reaction surface is washed withice-cold sodium acetate buffer deionized water and ethanolThen the solution containing the probe DNAs is spottedon the ice-cold diazotized surface and air dried for 1-2 hDolan et almentioned that the unreacted diazo groups on the

surface are blocked by reaction with the glycine or UV-cross-linked followed by baking for two hours at 80∘C [56] Theimmobilized DNAs can be allowed to hybridize with the PCRproducts for the detection and discrimination of pathogens

(5) Surface Modification with Supramolecules In the lastdecade tremendous work is done on the various applicationsof supramolecules in particular calixarenes [31 57 58] Thecalix[4]crown-5 derivatives are well known for their abilityto capture the cationic substrates including metal cations andammonium ions [59] The cavities of calixarenes are wellknown to capture the amino groups of proteins and formstable complexes with them According to the report Leeet al exploited the ability of calixarenes to form complexeswith proteins to fabricate the protein microarrays on glasssurfaces as depicted in Figure 4 [60 61] For the fabricationof the protein microarrays the calix[4]crown-5 derivativescontaining aldehyde functional groups are reacted with theamine functional groups on the amine-modified glass chip togenerate a monolayer

Then the protein in PBS solution with 30 glycerol isspotted on calix[4]crown-5 derivative modified glass surfaceand incubated at 37∘C for 3 h Then the chip is washed withthe 10mMPBS solution containing 05 Tween 20 for 10minat room temperature and dried under a stream of N

2gasThe

unreacted calix[4]crown-5 derivatives the free amine groupson the glass surface are blocked by immersing the chip intothe 3 BSA in PBS solution for 1 h at room temperature

Similar to protein microarrays [62] Nimse et al reportedthe DNA microarrays based on the 9G technology whichuses the interactions of the monolayer of calix[4]arenederivatives on the glass surface and the DNAs appended tothe nine consecutive guanines (9G) are also reported [32]The aminocalix[4]arene (AMCA) derivative with aldehydefunctional groups is allowed to reactwith the amine-modifiedglass surface to generate the AMCA slides As depicted inFigure 5 the determination of contact angle of water onthe AMCA modified glass surface indicates that the AMCAmolecules make the glass surface hydrophobic

Once the AMCA immobilization is done the solutioncontaining DNA probes appended to 9G is spotted on the

6 Journal of Chemistry

OH O OH

N

N

N

OH OHO

Si

Si

N

N

lowast

lowast

SiO2

SiO2

OH O OH

Si

SiO2

OH OH OH

SiO2

OH OHO

Si

SiO2

Si(OCH3)2

Single strandedunlabeled target DNA

+NClminus

NaNO2 + HCl

Diazonium ion

Cy3Cy5-dCTPDNA

For 14ndash16hr

lowast

lowast

NH2

NH2

Hybridized at 42∘Cat 4∘C

at 30min4∘C

Scheme 4 Covalent immobilization of probe DNA on a glass surface by diazotization and subsequent hybridization

O O O

O O

O

O

X X X X

+N

H4

+N

H4

H3C CH3O O O

O O

O

O

X X X X

H3C CH3

1 cm

1 cm

Figure 4 Interaction of calix[4]crown-5 derivative with proteins for the fabrication of protein microarray (adapted from [31])

Journal of Chemistry 7

(a) (b)

Figure 5 Contact angle comparison (a) bare glass and (b) AMCA modified glass slide (adapted from [32])

surface by using microarray After incubation at room tem-perature for 4 h the slides are washed to remove excess DNAsand driedThe free AMCAmolecules on the surface are thenblocked with the 4x SSC solution containing BSA and 01SDS Finally the slides are dried to obtain 9G DNAChips[63 64]

23 Carbon In recent years a nanoparticle-based structurelike nanotubes and nanowires has got tremendous attentionin biomedical and diagnostic fields [65 66] Before 1991 sp3hybridized form of carbon (diamond) sp2 hybridized formslike graphite and C60 fullerene were the only known formsof carbon with potential applications [67] In 1991 allotropeslike carbon nanotubes (CNT)were first reported and success-fully synthesized by Iijima with multiwall faces (MWCNT)[68]

Due to thermal electrical and magnetically uniqueproperties CNT became an important material in the devel-opment of biosensor platforms Commonly reportedmethodfor preparation of CNT includes chemical vapour deposition[69 70] arc discharge [71] and laser ablation [72]

Apart from CNT other carbon-based nanostructuresincluding carbondots carbon fibers andPDMSalso attractedresearchers due to their diverse properties for biomoleculeconjugation [73 74]Themajor advantage of carbon nanoma-terial is their large surface area which allows maximum spacefor biomolecule attachment

Immobilization of protein carbohydrate and nucleic acidon the CNT surfaces allows various biological applications[75 76]Themost important part in biomolecule conjugationis the surface functionalization of carbon-basedmaterialThegeneral techniques for carbon surface modification are (phy-sisorption) noncovalent and covalent modifications Thereare several reports on the different techniques of surfacemodification of carbon-based surfaces Due to the vastnessof the research on carbon-based material only few methodsare described in this paper

231 Physisorption Thehydrophobic character of CNT side-walls and the strong 120587-120587 interactions between the individualtubes causes them to aggregate and reduce their solubility in

common solvents which is considered as a problem for theirbiological applicationsHowever the samehydrophobic char-acter of theCNT surface is exploited for fabrication of biosen-sors by immobilizing biomolecules onto the CNT surfacesthrough hydrophobic-hydrophobic interactions [77ndash79]

The advantage of noncovalent interaction is a limiteddistortion of the three-dimensional structure of a protein orenzyme to be immobilized The hydrophobic amino acidsin proteins and enzymes develop the 120587-120587 interactions withthe hydrophobic part of CNT which make them adsorbedon the surface of CNT [80ndash83] As mentioned earlier theplatforms modified by noncovalent interactions suffer fromthe typical drawbacks of nonspecific interactions resulting inthe decreased specificity and sensitivity of a biosensor

To eliminate the problem of nonspecific interactions oftarget proteins with the sensor surface the novel approachof polyethylene oxide (PEO) polymer coating is adopted bymany researchers The PEO is well known for its proteinrepelling ability [84] Bomboi et al reported the use of Tween20 which is composed of three PEO branches and P103another molecule with hydrophobic polypropylene oxideunits to modify the surface of CNT before adsorption ofproteins on it The surface of Tween 20 and P103 modifiedCNT becomes slightly hydrophilic compared with bare CNTwhich results in the decrease in its interaction with thehydrophobic amino acid chains of biomarker proteins [85]

As depicted in Figure 6 for the selective immobilizationof streptavidin on the CNT surface Chen et al used mixednoncovalent and covalent approach which allows the highlyspecific immobilization of streptavidin and blocks the non-specific binding of other proteins like BSA [33]

Conjugation of a fluorescent molecule on the CNT sur-face is an immerging technology for highly sensitive detec-tion of biomolecules Nakayama-Ratchford et al reported theimmobilization of the fluorescent molecules like fluoresceinon the surface of CNT through 120587-120587 interactions [86] Thereare several reports on the applications of CNT surfaces mod-ified with the fluorescent molecules through noncovalentinteractions [87ndash90]

232 Chemical Modification To prevent the nonspecificbinding and to avoid the leaching of biomolecules from the

8 Journal of Chemistry

OH

OH

OH

O

HO

HO

HO

O

OO

OO

NH

O

NH

O

NH

OO

NH O

NH

O

NH

65 HON3

Boiling t = 8h

C2H4(NH2)2

NH2

H2N (CH2)2

(CH2)2

NH2(CH2)2

NH2(CH2)2

H2N (CH2)2

H2N (CH2)2

Scheme 5 Amine modification of CNT

BB

B

B B

B

SA SA

Figure 6 Streptavidin recognition by a nanotube coated with biot-inylated Tween (adapted from [33])

CNT surface a covalent modification technique is reportedThere are two types of covalent modifications namely (i)indirect method for example carboxylation of CNT surfaceand (ii) direct method for example fluorination of CNT sur-face where surface carbons change from sp2 to sp3 hybridiza-tion Esterification or amidation and sidewall covalent attach-ment are other approaches for covalent attachment [91 92]

(1) Carboxyl Modification The modification of the sensorsurfaces with the carboxyl groups is a general and highly usedsurface modification method Once the surface is modifiedwith the carboxyl groups it can be converted to a vari-ety of functional groups through reaction with appropriatereagents Furthermore the carboxylated surfaces can bedirectly conjugated with proteins or DNA through theiramine functional groups using coupling reagents A mixtureof sulphuric acid and nitric acid is a commonly used reagentfor the carboxylation of CNT surface

Marshall et al reported the method for carboxyl modifi-cation of CNT [93] According to this method a 2mg sampleof SWCNT is added to the 75 mixture of concentratedsulphuric acid and nitric acid (1mL) The mixture is allowedto sonicate in sonicator at 20∘CThe reaction mixture is thendiluted to 250mL by using deionized waterThe carboxylatedCNTs are then filtered through polytetrafluoroethylene filter(PTFE) of 045 120583m size Finally the collected nanotubes arewashedwith water at acidic pH followed by ethanol and driedin a vacuum desiccator

O OOH

O OOO

n

Figure 7 Structure of Epon resin 828

(2) Amine Modification Amide coupling is the most com-monly used conjugation technique in biomolecule attach-ment Either the amine or acid part of DNA or protein canbe used for conjugation using amide coupling reaction Forthe conjugation ofDNA toCNT through its phosphate groupamine modification is needed

Tam et al reported the DNA sensor based on the aminemodification of MWCNT as depicted in Scheme 5 [94] TheMWCNT were boiled in the 15M nitric acid for 12 h to gen-erate the carboxylated MWCNT The purified carboxylatedMWCNT were reacted with ethylenediamine to obtain theamine-modified MWCNT The amine-modified MWCNTwere conjugated to DNA by using EDC coupling reaction

Other reports for aminemodification of CNT include theuse of nitric acid and sulphuric acidmixture for carboxylationof the surface followed by ethylenediamine reaction [95]There are several reports on the covalent conjugation offluorescent molecules to the CNT surfaces [96ndash98]

(3) Epoxy Modification Epoxide group is a highly reactivefunctional group used in many substitution reactions as anelectrophile Eitan et al reported the covalent attachmentof epoxide-terminated molecules to carbon nanotubes byreaction between epoxide rings and carboxylic acid groupsthat are initially formed on the nanotube surface [99] Forepoxidation of CNT the surface is first carboxylated bydispersing the CNT in 75 solution of sulphuric acid in nitricacid for 3 h The purified carboxylated CNT were kept in theacetone with sonication for 1 hThen the solution containingthe carboxylated CNT is mixed with the solution of Eponresin 828 (Figure 7) in acetone to allow the reaction betweenEpon resin 828 and carboxyl groups on the CNT surface asdepicted in Scheme 6

Journal of Chemistry 9

O

O

O

O

R

OOCatalyst

O

O

O

O

O

O

CHHO

R

O

HC OH

R

O

H2C

O

HC OH

R

O

H2C

CH2

O

CHHO

R

O

CH2

HOHO

OHOH

+

Scheme 6 Epoxy modification of CNT

The mixture of solutions is sonicated for 1 h followedby stirring and heating at 70∘C The reaction was quenchedby addition of appropriate amount of potassium hydroxideThen the epoxilated CNT were purified and a number ofepoxy groups on the CNT surface were determined by usingthermogravimetric analysis

24 Nitrocellulose A PoC diagnosis system is always expe-cted to deliver final results in few minutes Though themicroarrays based on the glass and gold surfaces are usefulfor detection of multiple analytes at a time they need longertime for final data interpretation Microfluidic systems basedon paper or nitrocellulose membranes are emerging surfacesfor detection of bacteria viruses and proteins A paper isadvantageous due to its hydrophilic nature which allowsthe aqueous solutions to penetrate without the need of anyexternal force [100] The essential constituent of paper iscelluloseThe cellulose has hydroxyl functional groups whichcan be modified and changed according to surface propertiesneeded for a particular detection device [101] Due to lowcost and high availability paper is preferred for large scaleproduction Moreover the devices required for the tests areportable and disposable [102ndash105] The very first example ofpaper based detection is glucose detection in urine [106] andpregnancy test kit [107]There are different types of paper likeWhatman filter paper glossy paper [108] membrane and soforth Whatman filter is used because of its high penetrationand flow rate [109ndash112] but in some cases it does not havethe necessary characteristic for surface modification Mem-branes on the other hand are planner sheets and providelarger surface area for immobilization of biomolecules such

as DNA and protein The nitrocellulose (NC) membrane isbroadly used for immobilization of DNA [113] protein [114]and enzymes [115] due to its hydrophobic surface

241 Physical Adsorption Single-stranded DNAs are irre-versibly bound to the surface of the NCmembrane with non-covalent interactionsTheprimary interactions are hydropho-bic and electrostatic between the positively charged surfaceof the membrane and negatively charged DNAs The nitro-cellulose offers very high binding capacity for DNAs andproteins Fabrication of NC membranes can be done bydifferent methods including the photolithography The waxpatterningmethod is fast cheap and easy to process and doesnot need organic solvents The NCmembranes with the poresize of 045 120583mdo not need pretreatment for penetrationThefabrication process includesmainly printing and baking stepswhich can be finished in 10min As shown in Figure 8 firstlythe wax is printed on the surface of NCmembrane and bakedat 125∘C for 5min in the oven The melting of the wax onmembrane makes it more hydrophobic and affords surfacesuitable for the immunoassay For immunoassays Lu et alcoated the cAbs on the surface and the free area is blockedwith the 1 BSA

During baking melted wax passes through the mem-brane The 121∘ contact angle of backside membrane assuresthe melting of wax thoroughly The efficiency of wax treatedmembrane is compared with the untreated membrane byimmobilizing fluorescence labeled goat antihuman IgG Theimmobilization on wax printed surface is more uniform thanthe untreated membrane Apart from this a large volumeof liquid can be used because ring effect of protein on the

10 Journal of Chemistry

HO

OSH AuNP

AuNP-mAb

mAbEDCNHS

001M PBS

(CH2)15(CH2)11

NaBH4HAuCl4 + SH + HO

pH sim 74

Scheme 7 Immobilization on antibodies on AuNP

NC membrane

Cross section view

PrintingStep 1

Step 2 Baking

Wax patternedNC membrane

Wax is printed onto thesurface of NC membrane

Wax melts and penetratesthrough NC membrane

Nitrocellulose

Wax

Figure 8Wax printing on nitrocellulosemembranes (adapted from[34])

untreated membrane is avoided Wax printing method gen-erates 100 120583mmicrochannel which removes the micrometersize contaminants and makes the wax printed membranessuitable for the applications in microfluidic assays Apartfrom immobilization wax printing has application in dotimmunoassay and sample purifications [34]

Due to advantages of NC membrane for high bindingcapacity and good flow of solution it is also used on the chipsurfaces The glass slide can be coated with the 12 120583m layer ofNC to afford a platform with the intrinsic properties of NCThe solution of cAbs in PBS buffer containing 10 glycerolis then spotted on the modified surface After spotting theslides are incubated for one hour After incubation slides arewashed with 01 Tween 20 in PBS buffer and dried to gen-erate the platform for detection of biomarker proteins [116]

Apart from routine microarray applications NC mem-brane is also used for the detection of circulating tumor cells(CTC) as reported by Zhang et al The binding of CTCs bythe cAbs immobilized on the NC membrane is detected bySurface Enhanced Raman Scattering (SERS) as depicted inFigure 9

Usually the antibodies specific for cancer cells are usedas a capture substrate and immobilized on the surface TheNC membrane is cut into 1 cm times 1 cm pieces Then thesepieces are immersed in the ethanol and then tiled on thePMMA wafer After washing the membrane is activated byusing PBS buffer containing antibodies at 37∘C for 30minDuring this process the cAbs are avidly immobilized on theNC membrane The 1 BSA solution is loaded to block thefree surface area to avoid any background signals due tononspecific interactions Finally the membranes are washedwith PBS buffer and stored at 4∘CThe gold nanoparticle andRaman probes are used to detect the CTCs by SERS [35]

25 Gold Application of nanoparticles is amost focused areain the field of inorganic chemistry and it has also attractedimaginations of many biologists too Inorganic nanoparti-cles including gold silver and ferrous oxides have foundmany important applications in cell signaling drug deliveryand colorimetric and fluorescence-based detections Goldnanoparticles (AuNP) functionalized with proteins DNAsor Raman probes are well known in the field of biosensorsand nanobiotechnology for their applications in the molec-ular diagnostics [117ndash119] protein detection [120ndash122] generegulation [123] and cell imaging [124]

251 Covalent Modification

(1) Thiol Based Modification AuNPs are commonly usedin the electrochemical and optical detection systems Theconjugation with biomolecule does not change the opticalproperties ofAuNP [125]Di Pasqua et al reported thiolmod-ification for the detection of E coli O157H7 E coli specificantibodies were conjugated with the AuNPs [126] As shownin Scheme 7 the 10 nmAuNPs are carboxylated and then cou-pled to E coli specific monoclonal antibody (mAb) throughamide coupling

For the generation of AuNPs to the solution containing410mg of HAuCl

4sdot3H2O in 6mL of water ethanoic solutions

of 11-mercapto-1-undecanol and 16-mercaptohexadecanoicacid are added Upon addition of NaBH

4to this mixture at

0∘C the solution turns brown The product AuNP cappedwith alkanethiol pendant alcohol and carboxylic acid func-tional groups precipitate upon three hours of stirring Theprecipitated particles are then thoroughly washed with etha-nol and an ethanolic solution containing a small amountof 1M HCl The AuNPs are then dried under vacuum forten hours For the conjugation of mABs with the AuNPsthe carboxylic acid functional groups on the AuNPs are

Journal of Chemistry 11

SERSimaging

AuNPs

Raman labelNC membrane

AntibodyCancer cell

Figure 9 Detection of circulating tumor cells on NC membranes containing immobilized cAbs (adapted from [35])

activated by reacting the AuNPs with 1-ethyl-3-3(3-dimeth-ylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in the PBS buffer The mABs arethen added to this solution and the suspension is stirred atroom temperature for 30min The mAB-conjugated AuNPsare then collected by centrifugation and washing with PBSand ethanol The mAB-conjugated AuNPs successfully bindto E coli when incubated in PBS at pH 74 In other reportsthe AuNPs were found very effective in the detection ofcancerous pancreatic cells

The AuNPs are known to suffer from the problem ofaggregation upon long-term storage Therefore to solve thisissue the AuNPs are conjugated with the polyethylene glycol(PEG) to prevent their aggregation [127 128]The conjugationof PEGwith the AuNPsmakes the later hydrophilic thus pre-venting agglomeration induced by hydrophobic interactionsA PEGwith the heterobifunctional groups (dithiol at one endand a carboxyl at another end) is coated on the AuNP Thedithiol group allows stable anchoring heterobifunctional PEGligands on the surface of AuNP and the terminal carboxylgroup is used for coupling with antibodies The carboxy-terminated bifunctional PEG linker is synthesized by follow-ing a method reported by Eck et al which is depicted inScheme 8 The anionic polymerization of compound 1 withan excess of ethylene oxide allows synthesizing compound 2The treatment of compound 2 with chloroacetic acid at 60∘Callows generating compound 3 The reaction of an excess ofthe elemental bromine in dichloromethane at 0∘C for fourhours in the dark with compound 3 produces dibromidecompound 4 Compound 5 is obtained by reaction withcompound 4 in water with the excess of sodium hydrosulfidehydrate

The synthesized bifunctional PEG linker is then conju-gated with the citrate-stabilized gold nanoparticles by simpleligand exchangeThe citrate-stabilized gold nanoparticles areknown to aggregate in the buffer containing salts Thereforethe ligand exchange from citrate to PEG should be done inpure water The PEGylated AuNPs are conjugated to mono-clonal F19 antibodies for the detection of human pancreaticcarcinoma through EDCNHS coupling reaction [129]

OHO

(2) HCl

1

2

3

4

5

Br Br

HS SH

(CH2)9

(CH2)9

(CH2)9

(CH2)9

+

NaHDMF60∘C

(OCH2CH2)n

(OCH2CH2)n

(OCH2CH2)n

OCH2COOH

OCH2COOH

(CH2)9 (OCH2CH2)n OCH2COOH

OminusNa+

Br2

(2) Acetic acid (1) NaSHH2O

60∘C(1) ClCH2-COONa

Scheme 8 Synthesis of bifunctional PEG linker using conjugationwith AuNP

(2) Hydrazide Modification According to the report by Zhiet al the hydrazide-derivatized self-assembledmonolayer ona gold surface is used for the efficient and selective anchor-ing of oligosaccharide [39] The generated oligosaccharidemicroarrays allow the fluorescence-based detection of targetproteins The use of gold as a substrate for the fluorescence-based detection suffers from the drawbacks including flu-orescence quenching and nonspecific surface adsorption ofproteins However the use of120596-thiolated fatty acid (C

16) self-

assembledmonolayer between the gold surface andhydrazide

12 Journal of Chemistry

AuC C

C

C

OHOHO O

O

O

O

O

O

O

O

O

CHR

NN

H

N

N

N

H

NH

NH

NH

H

NH

C

O

O

O NNH

NH

HNH

H

S

S

S

S

HS Au

Au

Au

Au

Au

C16 SAM

Adipic dihydrazideEDC

(Sugar)R-CHO

Binding to protein

Sugarprobe

Protein Alexafluoro 532

SAM andblocking layer

Ab 2nd Ab

NH2

NH2H2N

CH2R

Scheme 9 Application of hydrazide-derivatized SAM on a goldsurface for the fabrication of oligosaccharide microarray (adaptedfrom [39])

groups minimizes the quenching effect Moreover the effec-tive blocking of the surface with the poly(ethylene glycol)aldehyde and BSA reduces the nonspecific adsorption ofprotein on the surface

For the fabrication of the reported oligosaccharidemicroarrays the gold substrate is prepared by following amethod depicted in Scheme 9 The self-assembled mono-layer (SAM) of 16-mercaptohexadecanoic acid (MHDA) isobtained by soaking the gold coated slides in the isobutylalcohol for 2 days The slides are then washed in ethanolto remove excess reagents and are dried under the nitrogenstream The carboxyl functional groups on the SAM areconverted to the hydrazide groups by incubation of the SAMcovered slides in the dimethyl sulfoxide solution containing1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and adipicdihydrazide The ethanol-washed and dried slides are thenused for the oligosaccharide printing to obtain oligosaccha-ride microarrays

The generated oligosaccharide microarray platformallows interrogation of carbohydrate-protein interactions ina high-throughput manner

26 Silver Similar to AuNPs silver nanoparticles (AgNP) arealso used for the immobilization of proteins and enzymesThe surface of AgNP allows adsorption of proteins Henceit can be utilized as a host matrix for various biomoleculesSilver is a suitable substrate for the immobilization of wholecell or the isolated enzymes [130 131]

Texp lt Tm

Ag

AgAg

Ag

AgAg

Texp gt Tm

Figure 10 AgNPs-oligonucleotide conjugates (adapted from [36])

261 Electrostatic Modification The electrostatic interac-tions allow the physical adsorption of biomolecules on thesurface of AgNPs Shen et al reported that the AgNPs aresynthesized by reduction of silver nitrate in the presence ofsodium citrate During the reduction process the solutionis sonicated for 15min to obtain the yellow silver colloidwhich is then kept at 4∘C for several days away from lightThen isolated nanoparticles can be used for physisorption ofproteins at a pH higher than their isoelectric point [132]

262 Covalent Modification As depicted in Scheme 10the AgNPs prepared by the citrate reduction method andstabilized with citrate [133] can be functionalized with car-boxyl groups upon treatment with 3-mercaptopropanoic acid(MPA) As reported by the Petkova et al for the immobi-lization of alcohol dehydrogenase from Thermoanaerobiumbrockii (TbADH) the carboxyl-modified AgNPs were treatedwith the solution containing TbADH under continuousstirring for 7 h at 26∘C a research by [134] The AgNPsmodified with the TbADH were successfully used for thebiotransformation studies

The application of a bifunctional linker for the modifica-tion of AgNPs is reported [135 136] The bifunctional linker11-mercaptoundecanoic acid was used with 1-octanethiol in1 1 ratio to generate the mixed SAM on the surface of AgNPThe IgG antibodies are then conjugated with the mixed SAMmodified AgNPs It is reported that upon covalent conjuga-tion of biomolecules with AgNPs their stability and activityis maintained [137]

According to another report on the covalent modifi-cation AgNPs-oligonucleotide conjugates are prepared byusing DNA and triple cyclic disulfide moieties [36] Asdepicted in Figure 10 the two types ofAgNPs-oligonucleotideconjugates with complementary DNA sequences undergoDNA hybridization driven coagulation resulting in the colorchange

As depicted in Figure 11 the AgNP-DNA conjugates wereprepared by treatment of AgNPs with the cyclic disulfidemodified oligonucleotide The AgNP and oligonucleotideswere allowed to react with each other with 1 4 ratio inthe presence of 1 sodium dodecyl sulfate and NaCl Theovernight incubation of solution results in the AgNP-DNAconjugates which are collected by centrifugation and washedto remove the excess DNAs

Journal of Chemistry 13

Ag AgMPAOH

OO OH

O

HOCitrate

Citrate

Ag

COOH

COOH

TbADHAg

CONH

COOH

TbADHOminusNa+

H2N

Scheme 10 Covalent conjugation of enzymes on the surface of carboxyl-modified AgNPs

OHO

EDC HOSu Bis-amino

polyethylene glycol

NH

OO

44GMBS N

H

OO N

H44

ON

O

O3

CoA

NH

OO N

H44

ON

O

O3

SHN

O

OH

OP O

OPO

O O

OHO

NNN

N

PO

OminusOminus

OminusOminus

NH2

NH2

Scheme 11 Covalent conjugation of coenzyme A to polystyrene nanoparticles

O OOO P

OHSS

5998400 (DSP)3-A10-ATT-ATC-ACT 3998400

DSP cyclic disulfide-containingphosphate derivative =

Figure 11 Conjugation of AgNPs with oligonucleotides by usingDSP as a linker molecule (adapted from [36])

27 Polystyrene Polystyrene is an aromatic polymerobtained by polymerization of styrene monomers [138] Thepolystyrene-based NPs are widely used in the moleculardiagnostics for the detection of biomarker proteins andgenomic DNAs Polystyrene can be employed as a coating ona variety of nanoparticles as its functional groups can be easilymodified or conjugated with other molecules The otherapplication of polystyrene is in the fabrication of fluorescencebeads (FBs) The fluorescence molecules are loaded into thepolystyrene shell to produce FBs which are then used invarious sensing applications The polystyrene is also used tocoat the magnetic NPs so they can be conjugated with otherbiomolecules such as DNA and Proteins The applications ofpolystyrene include but are not limited to the detection ofE coli [139] the detection of cardiac Troponin T (cTnT) thedetection of Herpes simplex virus and many more

271 Covalent Modification Covalent modification throughcarboxyl group iswell known formodification of biomolecule

Most of the polystyrene-based nanoparticles bear large num-bers of pendant carboxyl which increases the loading amountof biomolecule

Enzyme catalyzed covalent immobilization of the pro-teins bearing a small 12-mer ldquoybbRrdquo tag onto the polystyrenenanoparticles (PSNP) is recently reported by Wong et al[140] As depicted in Scheme 11 the carboxyl-PSNPs werereacted with the bis-amino-polyethylene glycol in the pres-ence of HOSu and EDC to generate the amino-pegylatedPSNPs These PSNPs are then reacted with the g-maleimi-dobutyric acid succinimidyl (GMBS) to obtain maleimide-functionalized PSNPs The maleimide-functionalized PSNPsupon chemoligation with coenzyme A (CoA) produce theCoA-derivatized PSNPs

As depicted in Scheme 12 the protein of interest bearingybbR-tag is immobilized on the CoA-derivatized PSNPsThephosphopantetheinyl transferase (Sfp) catalyzed the reactionbetween the serine residue of the ybbR-tag and the phos-phopantetheine moiety of CoA with the simultaneous lossof 3101584051015840-adenine diphosphate results in the attachment ofproteins onto the surface of PSNPs It is reported that theenzymes immobilized by this method retain their activity

There are several reports on the use of fluoromicrobeadsfor the detection of biomarkers Primarily the fluoromi-crobeads are made up of carboxylated polystyrene as a coat-ingmaterial entrapping the fluorescentmolecules Accordingto the recent report by Song et al [37] the fluoromicrobeadswere used for the detection of the cTnT on the proteinmicroarray as depicted in Figure 12

The carboxylate modified fluoromicrobeads were conju-gated with the anti cTnI mAb through EDCNHS-mediated

14 Journal of Chemistry

HN

O

OH

OP

O

O

PO

O

OHO

N

NN

P

O

S

HN

O

Coenzyme A

Phosphopantetheine

PO

O

O

OHO

N Sfp

NN

N

P

O

ybbr-protein

HN

O

OH

OP

O

O

S

HN

O

NH2

NH2

Ominus

Ominus

Ominus

minusO

minusO

Mg2+

HO∙∙

Ominus

OminusOminus

minusO

N

O

Polystyrenenanoparticle

Scheme 12 Protein conjugation to polystyrene NP

System 1 antibody-conjugated fluoromicrobeads

System 2 avidin-conjugated fluoromicrobeads

DTSP SAM

Anti-cTnI cAb

cTnI

Figure 12 Application of the polystyrene-coated fluoromicrobeadsfor the detection of cTnI on the protein microarray (adapted from[37])

coupling reaction The use of fluoromicrobeads alloweddetecting the cTnI in plasma samples with a range of 01ndash100 ngmL

272 Affinity-Based Modification The affinity interactionsare used for the attachment of oligonucleotides with thefluoromicrobeads or polystyrene-coated magnetic beads Togenerate the oligonucleotide conjugated fluoromicrobeads ormagnetic beads respective polystyrene-coated beads are firstconjugated with the streptavidin using the EDCNHS cou-pling reaction as reported by Zhang et al [141] As depicted

B

B

MB MB

MB

BB

Magnetic bead

Streptavidin

DNA labeled biotin

Figure 13 DNA attachment to the magnetic beads

in Figure 13 the streptavidinmodified beads are then allowedto incubate with the biotinylated oligonucleotides Due to theaffinity of biotin for streptavidin the biotinylated oligonu-cleotides can be readily immobilized on the streptavidincoated beads

The binding affinity of streptavidin and biotin in solutionis up to 25 times 1013 (molL)minus1 [142] This interaction is about amillion times stronger than the antigen and antibody inter-action The antibodies directly immobilized onto the sur-face lose 90 of their biological activity [143] Howeverthe biotinylated antibodies immobilized on the streptavidincoated surface can retain their bioactivity [144]

Journal of Chemistry 15

3 Conclusions

Surface modification techniques of the materials used asplatforms in the fabrication of biosensors are reviewed inthis paper There are several reports on materials and vari-ous methods for altering their physicochemical propertiesHence one of these methods can be chosen according tothe targeted use and needed physiochemical properties Itis important to note that the performance of the biosensoris highly dependent on the substrate material used and itsmeticulous modification for particular applications There-fore it is critical to understand the principles of a biosensor toidentify the correct substrate material and its surface modifi-cation chemistry Furthermore it is important to look at thelatest advances in the materials and techniques used for thefabrication of a biosensor before the processing

Competing Interests

All authors declare that there is no conflict of interests

Acknowledgments

This research was supported by the Hallym UniversityResearch Fund (HRF-201601-010) This work was also sup-ported by the fund obtained through Industry-Academic col-laboration between Biometrix Technology Inc (ChuncheonSouth Korea) and Hallym University

References

[1] A Sassolas B D Leca-Bouvier and L J Blum ldquoDNA biosen-sors andmicroarraysrdquoChemical Reviews vol 108 no 1 pp 109ndash139 2008

[2] A Cavalcanti B Shirinzadeh M Zhang and L C KretlyldquoNanorobot hardware architecture for medical defenserdquo Sen-sors vol 8 no 5 pp 2932ndash2958 2008

[3] R-Q Zhang S-L Liu W Zhao et al ldquoA simple point-of-caremicrofluidic immunomagnetic fluorescence assay for path-ogensrdquo Analytical Chemistry vol 85 no 5 pp 2645ndash2651 2013

[4] S B Nimse K S Song M D Sonawane D R Sayyed and TS Kim ldquoImmobilization techniques for microarray challengesand applicationsrdquo Sensors vol 14 no 12 pp 22208ndash22229 2014

[5] A P F Turner ldquoBiosensors sense and sensibilityrdquo ChemicalSociety Reviews vol 42 no 8 pp 3184ndash3196 2013

[6] L Wu and X Qu ldquoCancer biomarker detection recent achieve-ments and challengesrdquoChemical Society Reviews vol 44 no 10pp 2963ndash2997 2015

[7] K Ariga Q Ji T Mori et al ldquoEnzyme nanoarchitectonicsorganization and device applicationrdquo Chemical Society Reviewsvol 42 no 15 pp 6322ndash6345 2013

[8] W-W Zhao J-J Xu and H-Y Chen ldquoPhotoelectrochemicalDNA biosensorsrdquo Chemical Reviews vol 114 no 15 pp 7421ndash7441 2014

[9] Q Liu C Wu H Cai N Hu J Zhou and P Wang ldquoCell-basedbiosensors and their application in biomedicinerdquo ChemicalReviews vol 114 no 12 pp 6423ndash6461 2014

[10] X Zhao S Nampalli A J Serino and S Kumar ldquoImmobi-lization of oligodeoxyribonucleotides with multiple anchors to

microchipsrdquo Nucleic Acids Research vol 29 no 4 pp 955ndash9592001

[11] P Kumar S K Agrawal A Misra and K C Gupta ldquoA newheterobifunctional reagent for immobilization of biomoleculeson glass surfacerdquo Bioorganic 120572Medicinal Chemistry Letters vol14 no 5 pp 1097ndash1099 2004

[12] F Secundo ldquoConformational changes of enzymes upon immo-bilisationrdquo Chemical Society Reviews vol 42 no 15 pp 6250ndash6261 2013

[13] S Lee S Kim J Malm O C Jeong H Lilja and T LaurellldquoImproved porous silicon microarray based prostate specificantigen immunoassay by optimized surface density of thecapture antibodyrdquoAnalytica Chimica Acta vol 796 pp 108ndash1142013

[14] K Jaras A A Tajudin A Ressine et al ldquoENSAM europiumnanoparticles for signal enhancement of antibody microarrayson nanoporous siliconrdquo Journal of Proteome Research vol 7 no3 pp 1308ndash1314 2008

[15] C Steinhauer A Ressine G Marko-Varga T Laurell C AK Borrebaeck and C Wingren ldquoBiocompatibility of surfacesfor antibody microarrays design of macroporous silicon sub-stratesrdquo Analytical Biochemistry vol 341 no 2 pp 204ndash2132005

[16] K Jaras B Adler A Tojo et al ldquoPorous silicon antibodymicroarrays for quantitative analysis measurement of free andtotal PSA in clinical plasma samplesrdquo Clinica Chimica Acta vol414 pp 76ndash84 2012

[17] S W Lee K Hosokawa S Kim et al ldquoA highly sensitive poroussilicon (P-Si)-based human Kallikrein 2 (hK2) immunoassayplatform toward accurate diagnosis of prostate cancerrdquo Sensorsvol 15 no 5 pp 11972ndash11987 2015

[18] C Roychaudhuri ldquoA review on porous silicon based electro-chemical biosensors beyond surface area enhancement factorrdquoSensors and Actuators B Chemical vol 210 pp 310ndash323 2015

[19] ARessine S EkstromGMarko-Varga andT Laurell ldquoMacro-nanoporous silicon as a support for high-performance proteinmicroarraysrdquo Analytical Chemistry vol 75 no 24 pp 6968ndash6974 2003

[20] S Lee E Silajdzic H Yang et al ldquoA porous silicon immunoas-say platform for fluorometric determination of 120572-synuclein inhuman cerebrospinal fluidrdquo Microchimica Acta vol 181 no 9-10 pp 1143ndash1149 2014

[21] S Belhousse N Belhaneche-Bensemra K Lasmi et alldquoModified porous silicon for electrochemical sensor of para-nitrophenolrdquo Materials Science and Engineering B vol 189 pp76ndash81 2014

[22] N Reta A Michelmore C Saint B Prieto-Simon and NH Voelcker ldquoPorous silicon membrane-modified electrodesfor label-free voltammetric detection of MS2 bacteriophagerdquoBiosensors and Bioelectronics vol 80 pp 47ndash53 2016

[23] B Guan A Magenau S Ciampi K Gaus P J Reece and J JGooding ldquoAntibody modified porous silicon microparticles forthe selective capture of cellsrdquo Bioconjugate Chemistry vol 25no 7 pp 1282ndash1289 2014

[24] S Vutti N Buch-Manson S Schoffelen N Bovet K LMartinez and M Meldal ldquoCovalent and stable CuAAC mod-ification of silicon surfaces for control of cell adhesionrdquo Chem-BioChem vol 16 no 5 pp 782ndash791 2015

[25] A M Rossi L Wang V Reipa and T E Murphy ldquoPoroussilicon biosensor for detection of virusesrdquo Biosensors andBioelectronics vol 23 no 5 pp 741ndash745 2007

16 Journal of Chemistry

[26] T L Lasseter B H Clare N L Abbott and R J HamersldquoCovalently modified silicon and diamond surfaces resistanceto nonspecific protein adsorption and optimization for biosens-ingrdquo Journal of the American Chemical Society vol 126 no 33pp 10220ndash10221 2004

[27] M Li K-G Neoh E-T Kang T Lau and E E ChiongldquoSurface modification of silicone with covalently immobilizedand crosslinked agarose for potential application in the inhibi-tion of infection and omental wrappingrdquo Advanced FunctionalMaterials vol 24 no 11 pp 1631ndash1643 2014

[28] G MacBeath and S L Schreiber ldquoPrinting proteins as microar-rays for high-throughput function determinationrdquo Science vol289 no 5485 pp 1760ndash1763 2000

[29] S B Nimse M D Sonawane K S Song and T Kim ldquoBio-marker detection technologies and future directionsrdquoThe Ana-lyst vol 141 no 3 pp 740ndash755 2016

[30] M D Sonawane S B Nimse K Song and T Kim ldquoDetectionquantification and profiling of PSA current microarray tech-nologies and future directionsrdquo RSC Advances vol 6 no 9 pp7599ndash7609 2016

[31] S B Nimse and T Kim ldquoBiological applications of function-alized calixarenesrdquo Chemical Society Reviews vol 42 no 1 pp366ndash386 2013

[32] K-S Song S B Nimse J Kim et al ldquo9GDNAChip microarraybased on the multiple interactions of 9 consecutive guaninesrdquoChemical Communications vol 47 no 25 pp 7101ndash7103 2011

[33] R J Chen S Bangsaruntip K A Drouvalakis et al ldquoNonco-valent functionalization of carbon nanotubes for highly specificelectronic biosensorsrdquo Proceedings of the National Academy ofSciences of the United States of America vol 100 no 9 pp 4984ndash4989 2003

[34] Y Lu W Shi J Qin and B Lin ldquoFabrication and characteri-zation of paper-based microfluidics prepared in nitrocellulosemembrane by wax printingrdquo Analytical Chemistry vol 82 no1 pp 329ndash335 2010

[35] P Zhang R Zhang M Gao and X Zhang ldquoNovel nitrocel-lulose membrane substrate for efficient analysis of circulatingtumor cells coupled with surface-enhanced raman scatteringimagingrdquo ACS Applied Materials and Interfaces vol 6 no 1 pp370ndash376 2014

[36] J-S Lee A K R Lytton-Jean S J Hurst and C AMirkin ldquoSil-ver nanoparticlemdasholigonucleotide conjugates based on DNAwith triple cyclic disulfide moietiesrdquo Nano Letters vol 7 no 7pp 2112ndash2115 2007

[37] S Y Song Y D Han K Kim S S Yang and H C YoonldquoA fluoro-microbead guiding chip for simple and quantifiableimmunoassay of cardiac troponin I (cTnI)rdquo Biosensors andBioelectronics vol 26 no 9 pp 3818ndash3824 2011

[38] S V Lemeshko T Powdrill Y Y Belosludtsev and M HoganldquoOligonucleotides form a duplex with non-helical properties ona positively charged surfacerdquoNucleic Acids Research vol 29 no14 pp 3051ndash3058 2001

[39] Z-L Zhi A K Powell and J E Turnbull ldquoFabrication ofcarbohydrate microarrays on gold surfaces direct attachmentof nonderivatized oligosaccharides to hydrazide-modified self-assembledmonolayersrdquoAnalytical Chemistry vol 78 no 14 pp4786ndash4793 2006

[40] S L Pan and L Rothberg ldquoChemical control of electrodefunctionalization for detection of DNA hybridization by elec-trochemical impedance spectroscopyrdquo Langmuir vol 21 no 3pp 1022ndash1027 2005

[41] Z Lu C M Li Q Zhou Q-L Bao and X Cui ldquoCovalentlylinked DNAprotein multilayered film for controlled DNAreleaserdquo Journal of Colloid and Interface Science vol 314 no 1pp 80ndash88 2007

[42] L-S Jang and H-J Liu ldquoFabrication of protein chips basedon 3-aminopropyltriethoxysilane as a monolayerrdquo BiomedicalMicrodevices vol 11 no 2 pp 331ndash338 2009

[43] F Fixe M Dufva P Telleman and C B Christensen ldquoFunc-tionalization of poly(methyl methacrylate) (PMMA) as a sub-strate for DNAmicroarraysrdquoNucleic Acids Research vol 32 no1 article e9 2004

[44] A Lueking M Horn H Eickhoff K Bussow H Lehrachand G Walter ldquoProtein microarrays for gene expression andantibody screeningrdquo Analytical Biochemistry vol 270 no 1 pp103ndash111 1999

[45] N Zammatteo L Jeanmart S Hamels et al ldquoComparisonbetween different strategies of covalent attachment of DNA toglass surfaces to build DNA microarraysrdquo Analytical Biochem-istry vol 280 no 1 pp 143ndash150 2000

[46] M Ozmen K Can I Akin et al ldquoSurface modification of glassbeads with glutaraldehyde characterization and their adsorp-tion property for metal ionsrdquo Journal of Hazardous Materialsvol 171 no 1ndash3 pp 594ndash600 2009

[47] C Funk PM Dietrich T Gross HMinW E S Unger andWWeigel ldquoEpoxy-functionalized surfaces for microarray appli-cations surface chemical analysis and fluorescence labeling ofsurface speciesrdquo Surface and Interface Analysis vol 44 no 8pp 890ndash894 2012

[48] S Mahajan P Kumar and K C Gupta ldquoOligonucleotide mic-roarrays immobilization of phosphorylated oligonucleotideson epoxylated surfacerdquo Bioconjugate Chemistry vol 17 no 5pp 1184ndash1189 2006

[49] M C Pirrung J D Davis and A L Odenbaugh ldquoNovelreagents and procedures for immobilization of DNA on glassmicrochips for primer extensionrdquo Langmuir vol 16 no 5 pp2185ndash2191 2000

[50] E Southern K Mir and M Shchepinov ldquoMolecular interac-tions on microarraysrdquo Nature Genetics vol 21 no 1 pp 5ndash91999

[51] M S Shchepinov S C Case-Green and E M SouthernldquoSteric factors influencing hybridisation of nucleic acids tooligonucleotide arraysrdquo Nucleic Acids Research vol 25 no 6pp 1155ndash1161 1997

[52] D A Tomalia A M Naylor and W A Goddard III ldquoStarbustdendrimers molecular-level control of size shape surfacechemistry topology and flexibility from atoms to macroscopicmatterrdquo Angewandte ChemiemdashInternational Edition in Englishvol 29 no 2 pp 138ndash175 1990

[53] R Benters C M Niemeyer D Drutschmann D Blohm andD Wohrle ldquoDNA microarrays with PAMAM dendritic linkersystemsrdquo Nucleic Acids Research vol 30 no 2 p e10 2002

[54] J H Moon J W Shin S Y Kim and J W Park ldquoFormationof uniform aminosilane thin layers an imine formation tomeasure relative surface density of the amine grouprdquo Langmuirvol 12 no 20 pp 4621ndash4624 1996

[55] J C Alwine D J Kemp and G R Stark ldquoMethod fordetection of specific RNAs in agarose gels by transfer to diazo-benzyloxymethyl-paper and hybridization with DNA probesrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 74 no 12 pp 5350ndash5354 1977

[56] P L Dolan Y Wu L K Ista R L Metzenberg M A Nelsonand G P Lopez ldquoRobust and efficient synthetic method for

Journal of Chemistry 17

forming DNA microarraysrdquo Nucleic Acids Research vol 29 no21 article e107 2001

[57] S B Nimse J Kim K-S Song et al ldquoSelective recognitionof the ditopic trimethylammonium cations by water-solubleaminocalix[4]arenerdquo Tetrahedron Letters vol 52 no 29 pp3751ndash3755 2011

[58] V-T Ta S B Nimse K-S Song et al ldquoCharacterization ofthe mixed self-assembled monolayer at the molecular scalerdquoChemical Communications vol 47 no 40 pp 11261ndash11263 2011

[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

[60] Y Lee E K Lee YW Cho et al ldquoProteoChip a highly sensitiveprotein microarray prepared by a novel method of proteinimmobilization for application of protein-protein interactionstudiesrdquo Proteomics vol 3 no 12 pp 2289ndash2304 2003

[61] S W Oh J D Moon H J Lim et al ldquoCalixarene derivative asa tool for highly sensitive detection and oriented immobiliza-tion of proteins in a microarray format through noncovalentmolecular interactionrdquo The FASEB Journal vol 19 no 10 pp1335ndash1337 2005

[62] S B Nimse K-S Song J Kim D R Sayyed and T Kimldquo9G DNAChip technology self-assembled monolayer (SAM)of ssDNA for ultra-sensitive detection of biomarkersrdquo Interna-tional Journal ofMolecular Sciences vol 14 no 3 pp 5723ndash57332013

[63] V-T Nguyen S B Nimse K-S Song et al ldquoHPAI 9GDNAChip discrimination of highly pathogenic influenza virusgenesrdquo Chemical Communications vol 48 no 38 pp 4582ndash4584 2012

[64] K-S Song S B Nimse J Kim D R Sayyed and T Kim ldquoAnew platform for a convenient genotyping systemrdquo ChemicalCommunications vol 49 no 26 pp 2661ndash2663 2013

[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

[67] F Hennrich C Chan VMoore M Rolandi andM OrsquoConnellCarbonNanotubes Properties and Applications Taylor amp FrancisGroup Abingdon UK 2006

[68] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

[69] C Singh M Shaffer I Kinloch and A Windle ldquoProductionof aligned carbon nanotubes by the CVD injection methodrdquoPhysica B Condensed Matter vol 323 no 1ndash4 pp 339ndash3402002

[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

[71] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Journal of Chemistry 5

(1) GA(2) DCCNHS

O O O

Si Si SiO O O

HNHN

O O

OO OONO O NO O

H2N

O O O

Si Si SiO O O

H2N H2NH2N

Scheme 3 Surface modification with activated carboxylic acid

tetrafluoroborate (TBTU) The free amino functional groupsin lysine containing proteins are targeted for the immobiliza-tion of proteins on the glass surface through amide couplingreactions The polyamidoamine (PAMAM) dendrimer isused as a linker for immobilization of the DNAs on the glasssurfaces [50 51] PAMAM was initially invented in the 1980sto increase the amino groups on the outer surface of sphere[52] Its application is now extended for DNA immobiliza-tion Firstly the silylation is performed using 95 3 2 vvsolution of ethanol water and APTES by treating the glassslides for 2 h

As depicted in Scheme 3 Benters et al treated the silylatedsurface overnight with the solution of glutaric anhydride(GA) in DMF Slides are then washed with DMF multipletimes to remove the unreacted reagents Carboxyl groups areactivated by using activating reagent such as 1mM solutionof NHS or dicyclohexylcarbodiimide (DCC) in DMF for 1 hfollowed by washing with DMF For the covalent attachmentof dendrimer 100120583L of 10 PAMAM in methanol is allowedto react with the activated carboxyl functional groups on thesurface for 12 h at room temperature followed by washingwith methanol to remove the excess dendrimer Before theimmobilization of DNAs on the surface these dendrimers areactivated by using GANHS as described above [53]

(4) Diazotization Diazo one of the stable bonds in organicchemistry makes its use imperative in the surface modifica-tion process For diazotization the amine-modified surfaceis needed Commonly a cleaned glass using piranha solutionfor 30min followed by deionized (DI) water is used [54]The cleaned glass surface is then allowed to react with the(4-aminophenyl) trimethoxysilane in ethanol solution for30min After silanization the amine-modified surface istreated with the sodium nitrite (NaNO

2) to generate dia-

zobenzyl surface as depicted in Scheme 4 The diazotizationreaction is done at 4∘C using solution of 40mL water 80mLHCl (400mM) and 32mL NaNO

2(200mM) as reported by

Alwine et al [55] After the reaction surface is washed withice-cold sodium acetate buffer deionized water and ethanolThen the solution containing the probe DNAs is spottedon the ice-cold diazotized surface and air dried for 1-2 hDolan et almentioned that the unreacted diazo groups on the

surface are blocked by reaction with the glycine or UV-cross-linked followed by baking for two hours at 80∘C [56] Theimmobilized DNAs can be allowed to hybridize with the PCRproducts for the detection and discrimination of pathogens

(5) Surface Modification with Supramolecules In the lastdecade tremendous work is done on the various applicationsof supramolecules in particular calixarenes [31 57 58] Thecalix[4]crown-5 derivatives are well known for their abilityto capture the cationic substrates including metal cations andammonium ions [59] The cavities of calixarenes are wellknown to capture the amino groups of proteins and formstable complexes with them According to the report Leeet al exploited the ability of calixarenes to form complexeswith proteins to fabricate the protein microarrays on glasssurfaces as depicted in Figure 4 [60 61] For the fabricationof the protein microarrays the calix[4]crown-5 derivativescontaining aldehyde functional groups are reacted with theamine functional groups on the amine-modified glass chip togenerate a monolayer

Then the protein in PBS solution with 30 glycerol isspotted on calix[4]crown-5 derivative modified glass surfaceand incubated at 37∘C for 3 h Then the chip is washed withthe 10mMPBS solution containing 05 Tween 20 for 10minat room temperature and dried under a stream of N

2gasThe

unreacted calix[4]crown-5 derivatives the free amine groupson the glass surface are blocked by immersing the chip intothe 3 BSA in PBS solution for 1 h at room temperature

Similar to protein microarrays [62] Nimse et al reportedthe DNA microarrays based on the 9G technology whichuses the interactions of the monolayer of calix[4]arenederivatives on the glass surface and the DNAs appended tothe nine consecutive guanines (9G) are also reported [32]The aminocalix[4]arene (AMCA) derivative with aldehydefunctional groups is allowed to reactwith the amine-modifiedglass surface to generate the AMCA slides As depicted inFigure 5 the determination of contact angle of water onthe AMCA modified glass surface indicates that the AMCAmolecules make the glass surface hydrophobic

Once the AMCA immobilization is done the solutioncontaining DNA probes appended to 9G is spotted on the

6 Journal of Chemistry

OH O OH

N

N

N

OH OHO

Si

Si

N

N

lowast

lowast

SiO2

SiO2

OH O OH

Si

SiO2

OH OH OH

SiO2

OH OHO

Si

SiO2

Si(OCH3)2

Single strandedunlabeled target DNA

+NClminus

NaNO2 + HCl

Diazonium ion

Cy3Cy5-dCTPDNA

For 14ndash16hr

lowast

lowast

NH2

NH2

Hybridized at 42∘Cat 4∘C

at 30min4∘C

Scheme 4 Covalent immobilization of probe DNA on a glass surface by diazotization and subsequent hybridization

O O O

O O

O

O

X X X X

+N

H4

+N

H4

H3C CH3O O O

O O

O

O

X X X X

H3C CH3

1 cm

1 cm

Figure 4 Interaction of calix[4]crown-5 derivative with proteins for the fabrication of protein microarray (adapted from [31])

Journal of Chemistry 7

(a) (b)

Figure 5 Contact angle comparison (a) bare glass and (b) AMCA modified glass slide (adapted from [32])

surface by using microarray After incubation at room tem-perature for 4 h the slides are washed to remove excess DNAsand driedThe free AMCAmolecules on the surface are thenblocked with the 4x SSC solution containing BSA and 01SDS Finally the slides are dried to obtain 9G DNAChips[63 64]

23 Carbon In recent years a nanoparticle-based structurelike nanotubes and nanowires has got tremendous attentionin biomedical and diagnostic fields [65 66] Before 1991 sp3hybridized form of carbon (diamond) sp2 hybridized formslike graphite and C60 fullerene were the only known formsof carbon with potential applications [67] In 1991 allotropeslike carbon nanotubes (CNT)were first reported and success-fully synthesized by Iijima with multiwall faces (MWCNT)[68]

Due to thermal electrical and magnetically uniqueproperties CNT became an important material in the devel-opment of biosensor platforms Commonly reportedmethodfor preparation of CNT includes chemical vapour deposition[69 70] arc discharge [71] and laser ablation [72]

Apart from CNT other carbon-based nanostructuresincluding carbondots carbon fibers andPDMSalso attractedresearchers due to their diverse properties for biomoleculeconjugation [73 74]Themajor advantage of carbon nanoma-terial is their large surface area which allows maximum spacefor biomolecule attachment

Immobilization of protein carbohydrate and nucleic acidon the CNT surfaces allows various biological applications[75 76]Themost important part in biomolecule conjugationis the surface functionalization of carbon-basedmaterialThegeneral techniques for carbon surface modification are (phy-sisorption) noncovalent and covalent modifications Thereare several reports on the different techniques of surfacemodification of carbon-based surfaces Due to the vastnessof the research on carbon-based material only few methodsare described in this paper

231 Physisorption Thehydrophobic character of CNT side-walls and the strong 120587-120587 interactions between the individualtubes causes them to aggregate and reduce their solubility in

common solvents which is considered as a problem for theirbiological applicationsHowever the samehydrophobic char-acter of theCNT surface is exploited for fabrication of biosen-sors by immobilizing biomolecules onto the CNT surfacesthrough hydrophobic-hydrophobic interactions [77ndash79]

The advantage of noncovalent interaction is a limiteddistortion of the three-dimensional structure of a protein orenzyme to be immobilized The hydrophobic amino acidsin proteins and enzymes develop the 120587-120587 interactions withthe hydrophobic part of CNT which make them adsorbedon the surface of CNT [80ndash83] As mentioned earlier theplatforms modified by noncovalent interactions suffer fromthe typical drawbacks of nonspecific interactions resulting inthe decreased specificity and sensitivity of a biosensor

To eliminate the problem of nonspecific interactions oftarget proteins with the sensor surface the novel approachof polyethylene oxide (PEO) polymer coating is adopted bymany researchers The PEO is well known for its proteinrepelling ability [84] Bomboi et al reported the use of Tween20 which is composed of three PEO branches and P103another molecule with hydrophobic polypropylene oxideunits to modify the surface of CNT before adsorption ofproteins on it The surface of Tween 20 and P103 modifiedCNT becomes slightly hydrophilic compared with bare CNTwhich results in the decrease in its interaction with thehydrophobic amino acid chains of biomarker proteins [85]

As depicted in Figure 6 for the selective immobilizationof streptavidin on the CNT surface Chen et al used mixednoncovalent and covalent approach which allows the highlyspecific immobilization of streptavidin and blocks the non-specific binding of other proteins like BSA [33]

Conjugation of a fluorescent molecule on the CNT sur-face is an immerging technology for highly sensitive detec-tion of biomolecules Nakayama-Ratchford et al reported theimmobilization of the fluorescent molecules like fluoresceinon the surface of CNT through 120587-120587 interactions [86] Thereare several reports on the applications of CNT surfaces mod-ified with the fluorescent molecules through noncovalentinteractions [87ndash90]

232 Chemical Modification To prevent the nonspecificbinding and to avoid the leaching of biomolecules from the

8 Journal of Chemistry

OH

OH

OH

O

HO

HO

HO

O

OO

OO

NH

O

NH

O

NH

OO

NH O

NH

O

NH

65 HON3

Boiling t = 8h

C2H4(NH2)2

NH2

H2N (CH2)2

(CH2)2

NH2(CH2)2

NH2(CH2)2

H2N (CH2)2

H2N (CH2)2

Scheme 5 Amine modification of CNT

BB

B

B B

B

SA SA

Figure 6 Streptavidin recognition by a nanotube coated with biot-inylated Tween (adapted from [33])

CNT surface a covalent modification technique is reportedThere are two types of covalent modifications namely (i)indirect method for example carboxylation of CNT surfaceand (ii) direct method for example fluorination of CNT sur-face where surface carbons change from sp2 to sp3 hybridiza-tion Esterification or amidation and sidewall covalent attach-ment are other approaches for covalent attachment [91 92]

(1) Carboxyl Modification The modification of the sensorsurfaces with the carboxyl groups is a general and highly usedsurface modification method Once the surface is modifiedwith the carboxyl groups it can be converted to a vari-ety of functional groups through reaction with appropriatereagents Furthermore the carboxylated surfaces can bedirectly conjugated with proteins or DNA through theiramine functional groups using coupling reagents A mixtureof sulphuric acid and nitric acid is a commonly used reagentfor the carboxylation of CNT surface

Marshall et al reported the method for carboxyl modifi-cation of CNT [93] According to this method a 2mg sampleof SWCNT is added to the 75 mixture of concentratedsulphuric acid and nitric acid (1mL) The mixture is allowedto sonicate in sonicator at 20∘CThe reaction mixture is thendiluted to 250mL by using deionized waterThe carboxylatedCNTs are then filtered through polytetrafluoroethylene filter(PTFE) of 045 120583m size Finally the collected nanotubes arewashedwith water at acidic pH followed by ethanol and driedin a vacuum desiccator

O OOH

O OOO

n

Figure 7 Structure of Epon resin 828

(2) Amine Modification Amide coupling is the most com-monly used conjugation technique in biomolecule attach-ment Either the amine or acid part of DNA or protein canbe used for conjugation using amide coupling reaction Forthe conjugation ofDNA toCNT through its phosphate groupamine modification is needed

Tam et al reported the DNA sensor based on the aminemodification of MWCNT as depicted in Scheme 5 [94] TheMWCNT were boiled in the 15M nitric acid for 12 h to gen-erate the carboxylated MWCNT The purified carboxylatedMWCNT were reacted with ethylenediamine to obtain theamine-modified MWCNT The amine-modified MWCNTwere conjugated to DNA by using EDC coupling reaction

Other reports for aminemodification of CNT include theuse of nitric acid and sulphuric acidmixture for carboxylationof the surface followed by ethylenediamine reaction [95]There are several reports on the covalent conjugation offluorescent molecules to the CNT surfaces [96ndash98]

(3) Epoxy Modification Epoxide group is a highly reactivefunctional group used in many substitution reactions as anelectrophile Eitan et al reported the covalent attachmentof epoxide-terminated molecules to carbon nanotubes byreaction between epoxide rings and carboxylic acid groupsthat are initially formed on the nanotube surface [99] Forepoxidation of CNT the surface is first carboxylated bydispersing the CNT in 75 solution of sulphuric acid in nitricacid for 3 h The purified carboxylated CNT were kept in theacetone with sonication for 1 hThen the solution containingthe carboxylated CNT is mixed with the solution of Eponresin 828 (Figure 7) in acetone to allow the reaction betweenEpon resin 828 and carboxyl groups on the CNT surface asdepicted in Scheme 6

Journal of Chemistry 9

O

O

O

O

R

OOCatalyst

O

O

O

O

O

O

CHHO

R

O

HC OH

R

O

H2C

O

HC OH

R

O

H2C

CH2

O

CHHO

R

O

CH2

HOHO

OHOH

+

Scheme 6 Epoxy modification of CNT

The mixture of solutions is sonicated for 1 h followedby stirring and heating at 70∘C The reaction was quenchedby addition of appropriate amount of potassium hydroxideThen the epoxilated CNT were purified and a number ofepoxy groups on the CNT surface were determined by usingthermogravimetric analysis

24 Nitrocellulose A PoC diagnosis system is always expe-cted to deliver final results in few minutes Though themicroarrays based on the glass and gold surfaces are usefulfor detection of multiple analytes at a time they need longertime for final data interpretation Microfluidic systems basedon paper or nitrocellulose membranes are emerging surfacesfor detection of bacteria viruses and proteins A paper isadvantageous due to its hydrophilic nature which allowsthe aqueous solutions to penetrate without the need of anyexternal force [100] The essential constituent of paper iscelluloseThe cellulose has hydroxyl functional groups whichcan be modified and changed according to surface propertiesneeded for a particular detection device [101] Due to lowcost and high availability paper is preferred for large scaleproduction Moreover the devices required for the tests areportable and disposable [102ndash105] The very first example ofpaper based detection is glucose detection in urine [106] andpregnancy test kit [107]There are different types of paper likeWhatman filter paper glossy paper [108] membrane and soforth Whatman filter is used because of its high penetrationand flow rate [109ndash112] but in some cases it does not havethe necessary characteristic for surface modification Mem-branes on the other hand are planner sheets and providelarger surface area for immobilization of biomolecules such

as DNA and protein The nitrocellulose (NC) membrane isbroadly used for immobilization of DNA [113] protein [114]and enzymes [115] due to its hydrophobic surface

241 Physical Adsorption Single-stranded DNAs are irre-versibly bound to the surface of the NCmembrane with non-covalent interactionsTheprimary interactions are hydropho-bic and electrostatic between the positively charged surfaceof the membrane and negatively charged DNAs The nitro-cellulose offers very high binding capacity for DNAs andproteins Fabrication of NC membranes can be done bydifferent methods including the photolithography The waxpatterningmethod is fast cheap and easy to process and doesnot need organic solvents The NCmembranes with the poresize of 045 120583mdo not need pretreatment for penetrationThefabrication process includesmainly printing and baking stepswhich can be finished in 10min As shown in Figure 8 firstlythe wax is printed on the surface of NCmembrane and bakedat 125∘C for 5min in the oven The melting of the wax onmembrane makes it more hydrophobic and affords surfacesuitable for the immunoassay For immunoassays Lu et alcoated the cAbs on the surface and the free area is blockedwith the 1 BSA

During baking melted wax passes through the mem-brane The 121∘ contact angle of backside membrane assuresthe melting of wax thoroughly The efficiency of wax treatedmembrane is compared with the untreated membrane byimmobilizing fluorescence labeled goat antihuman IgG Theimmobilization on wax printed surface is more uniform thanthe untreated membrane Apart from this a large volumeof liquid can be used because ring effect of protein on the

10 Journal of Chemistry

HO

OSH AuNP

AuNP-mAb

mAbEDCNHS

001M PBS

(CH2)15(CH2)11

NaBH4HAuCl4 + SH + HO

pH sim 74

Scheme 7 Immobilization on antibodies on AuNP

NC membrane

Cross section view

PrintingStep 1

Step 2 Baking

Wax patternedNC membrane

Wax is printed onto thesurface of NC membrane

Wax melts and penetratesthrough NC membrane

Nitrocellulose

Wax

Figure 8Wax printing on nitrocellulosemembranes (adapted from[34])

untreated membrane is avoided Wax printing method gen-erates 100 120583mmicrochannel which removes the micrometersize contaminants and makes the wax printed membranessuitable for the applications in microfluidic assays Apartfrom immobilization wax printing has application in dotimmunoassay and sample purifications [34]

Due to advantages of NC membrane for high bindingcapacity and good flow of solution it is also used on the chipsurfaces The glass slide can be coated with the 12 120583m layer ofNC to afford a platform with the intrinsic properties of NCThe solution of cAbs in PBS buffer containing 10 glycerolis then spotted on the modified surface After spotting theslides are incubated for one hour After incubation slides arewashed with 01 Tween 20 in PBS buffer and dried to gen-erate the platform for detection of biomarker proteins [116]

Apart from routine microarray applications NC mem-brane is also used for the detection of circulating tumor cells(CTC) as reported by Zhang et al The binding of CTCs bythe cAbs immobilized on the NC membrane is detected bySurface Enhanced Raman Scattering (SERS) as depicted inFigure 9

Usually the antibodies specific for cancer cells are usedas a capture substrate and immobilized on the surface TheNC membrane is cut into 1 cm times 1 cm pieces Then thesepieces are immersed in the ethanol and then tiled on thePMMA wafer After washing the membrane is activated byusing PBS buffer containing antibodies at 37∘C for 30minDuring this process the cAbs are avidly immobilized on theNC membrane The 1 BSA solution is loaded to block thefree surface area to avoid any background signals due tononspecific interactions Finally the membranes are washedwith PBS buffer and stored at 4∘CThe gold nanoparticle andRaman probes are used to detect the CTCs by SERS [35]

25 Gold Application of nanoparticles is amost focused areain the field of inorganic chemistry and it has also attractedimaginations of many biologists too Inorganic nanoparti-cles including gold silver and ferrous oxides have foundmany important applications in cell signaling drug deliveryand colorimetric and fluorescence-based detections Goldnanoparticles (AuNP) functionalized with proteins DNAsor Raman probes are well known in the field of biosensorsand nanobiotechnology for their applications in the molec-ular diagnostics [117ndash119] protein detection [120ndash122] generegulation [123] and cell imaging [124]

251 Covalent Modification

(1) Thiol Based Modification AuNPs are commonly usedin the electrochemical and optical detection systems Theconjugation with biomolecule does not change the opticalproperties ofAuNP [125]Di Pasqua et al reported thiolmod-ification for the detection of E coli O157H7 E coli specificantibodies were conjugated with the AuNPs [126] As shownin Scheme 7 the 10 nmAuNPs are carboxylated and then cou-pled to E coli specific monoclonal antibody (mAb) throughamide coupling

For the generation of AuNPs to the solution containing410mg of HAuCl

4sdot3H2O in 6mL of water ethanoic solutions

of 11-mercapto-1-undecanol and 16-mercaptohexadecanoicacid are added Upon addition of NaBH

4to this mixture at

0∘C the solution turns brown The product AuNP cappedwith alkanethiol pendant alcohol and carboxylic acid func-tional groups precipitate upon three hours of stirring Theprecipitated particles are then thoroughly washed with etha-nol and an ethanolic solution containing a small amountof 1M HCl The AuNPs are then dried under vacuum forten hours For the conjugation of mABs with the AuNPsthe carboxylic acid functional groups on the AuNPs are

Journal of Chemistry 11

SERSimaging

AuNPs

Raman labelNC membrane

AntibodyCancer cell

Figure 9 Detection of circulating tumor cells on NC membranes containing immobilized cAbs (adapted from [35])

activated by reacting the AuNPs with 1-ethyl-3-3(3-dimeth-ylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in the PBS buffer The mABs arethen added to this solution and the suspension is stirred atroom temperature for 30min The mAB-conjugated AuNPsare then collected by centrifugation and washing with PBSand ethanol The mAB-conjugated AuNPs successfully bindto E coli when incubated in PBS at pH 74 In other reportsthe AuNPs were found very effective in the detection ofcancerous pancreatic cells

The AuNPs are known to suffer from the problem ofaggregation upon long-term storage Therefore to solve thisissue the AuNPs are conjugated with the polyethylene glycol(PEG) to prevent their aggregation [127 128]The conjugationof PEGwith the AuNPsmakes the later hydrophilic thus pre-venting agglomeration induced by hydrophobic interactionsA PEGwith the heterobifunctional groups (dithiol at one endand a carboxyl at another end) is coated on the AuNP Thedithiol group allows stable anchoring heterobifunctional PEGligands on the surface of AuNP and the terminal carboxylgroup is used for coupling with antibodies The carboxy-terminated bifunctional PEG linker is synthesized by follow-ing a method reported by Eck et al which is depicted inScheme 8 The anionic polymerization of compound 1 withan excess of ethylene oxide allows synthesizing compound 2The treatment of compound 2 with chloroacetic acid at 60∘Callows generating compound 3 The reaction of an excess ofthe elemental bromine in dichloromethane at 0∘C for fourhours in the dark with compound 3 produces dibromidecompound 4 Compound 5 is obtained by reaction withcompound 4 in water with the excess of sodium hydrosulfidehydrate

The synthesized bifunctional PEG linker is then conju-gated with the citrate-stabilized gold nanoparticles by simpleligand exchangeThe citrate-stabilized gold nanoparticles areknown to aggregate in the buffer containing salts Thereforethe ligand exchange from citrate to PEG should be done inpure water The PEGylated AuNPs are conjugated to mono-clonal F19 antibodies for the detection of human pancreaticcarcinoma through EDCNHS coupling reaction [129]

OHO

(2) HCl

1

2

3

4

5

Br Br

HS SH

(CH2)9

(CH2)9

(CH2)9

(CH2)9

+

NaHDMF60∘C

(OCH2CH2)n

(OCH2CH2)n

(OCH2CH2)n

OCH2COOH

OCH2COOH

(CH2)9 (OCH2CH2)n OCH2COOH

OminusNa+

Br2

(2) Acetic acid (1) NaSHH2O

60∘C(1) ClCH2-COONa

Scheme 8 Synthesis of bifunctional PEG linker using conjugationwith AuNP

(2) Hydrazide Modification According to the report by Zhiet al the hydrazide-derivatized self-assembledmonolayer ona gold surface is used for the efficient and selective anchor-ing of oligosaccharide [39] The generated oligosaccharidemicroarrays allow the fluorescence-based detection of targetproteins The use of gold as a substrate for the fluorescence-based detection suffers from the drawbacks including flu-orescence quenching and nonspecific surface adsorption ofproteins However the use of120596-thiolated fatty acid (C

16) self-

assembledmonolayer between the gold surface andhydrazide

12 Journal of Chemistry

AuC C

C

C

OHOHO O

O

O

O

O

O

O

O

O

CHR

NN

H

N

N

N

H

NH

NH

NH

H

NH

C

O

O

O NNH

NH

HNH

H

S

S

S

S

HS Au

Au

Au

Au

Au

C16 SAM

Adipic dihydrazideEDC

(Sugar)R-CHO

Binding to protein

Sugarprobe

Protein Alexafluoro 532

SAM andblocking layer

Ab 2nd Ab

NH2

NH2H2N

CH2R

Scheme 9 Application of hydrazide-derivatized SAM on a goldsurface for the fabrication of oligosaccharide microarray (adaptedfrom [39])

groups minimizes the quenching effect Moreover the effec-tive blocking of the surface with the poly(ethylene glycol)aldehyde and BSA reduces the nonspecific adsorption ofprotein on the surface

For the fabrication of the reported oligosaccharidemicroarrays the gold substrate is prepared by following amethod depicted in Scheme 9 The self-assembled mono-layer (SAM) of 16-mercaptohexadecanoic acid (MHDA) isobtained by soaking the gold coated slides in the isobutylalcohol for 2 days The slides are then washed in ethanolto remove excess reagents and are dried under the nitrogenstream The carboxyl functional groups on the SAM areconverted to the hydrazide groups by incubation of the SAMcovered slides in the dimethyl sulfoxide solution containing1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and adipicdihydrazide The ethanol-washed and dried slides are thenused for the oligosaccharide printing to obtain oligosaccha-ride microarrays

The generated oligosaccharide microarray platformallows interrogation of carbohydrate-protein interactions ina high-throughput manner

26 Silver Similar to AuNPs silver nanoparticles (AgNP) arealso used for the immobilization of proteins and enzymesThe surface of AgNP allows adsorption of proteins Henceit can be utilized as a host matrix for various biomoleculesSilver is a suitable substrate for the immobilization of wholecell or the isolated enzymes [130 131]

Texp lt Tm

Ag

AgAg

Ag

AgAg

Texp gt Tm

Figure 10 AgNPs-oligonucleotide conjugates (adapted from [36])

261 Electrostatic Modification The electrostatic interac-tions allow the physical adsorption of biomolecules on thesurface of AgNPs Shen et al reported that the AgNPs aresynthesized by reduction of silver nitrate in the presence ofsodium citrate During the reduction process the solutionis sonicated for 15min to obtain the yellow silver colloidwhich is then kept at 4∘C for several days away from lightThen isolated nanoparticles can be used for physisorption ofproteins at a pH higher than their isoelectric point [132]

262 Covalent Modification As depicted in Scheme 10the AgNPs prepared by the citrate reduction method andstabilized with citrate [133] can be functionalized with car-boxyl groups upon treatment with 3-mercaptopropanoic acid(MPA) As reported by the Petkova et al for the immobi-lization of alcohol dehydrogenase from Thermoanaerobiumbrockii (TbADH) the carboxyl-modified AgNPs were treatedwith the solution containing TbADH under continuousstirring for 7 h at 26∘C a research by [134] The AgNPsmodified with the TbADH were successfully used for thebiotransformation studies

The application of a bifunctional linker for the modifica-tion of AgNPs is reported [135 136] The bifunctional linker11-mercaptoundecanoic acid was used with 1-octanethiol in1 1 ratio to generate the mixed SAM on the surface of AgNPThe IgG antibodies are then conjugated with the mixed SAMmodified AgNPs It is reported that upon covalent conjuga-tion of biomolecules with AgNPs their stability and activityis maintained [137]

According to another report on the covalent modifi-cation AgNPs-oligonucleotide conjugates are prepared byusing DNA and triple cyclic disulfide moieties [36] Asdepicted in Figure 10 the two types ofAgNPs-oligonucleotideconjugates with complementary DNA sequences undergoDNA hybridization driven coagulation resulting in the colorchange

As depicted in Figure 11 the AgNP-DNA conjugates wereprepared by treatment of AgNPs with the cyclic disulfidemodified oligonucleotide The AgNP and oligonucleotideswere allowed to react with each other with 1 4 ratio inthe presence of 1 sodium dodecyl sulfate and NaCl Theovernight incubation of solution results in the AgNP-DNAconjugates which are collected by centrifugation and washedto remove the excess DNAs

Journal of Chemistry 13

Ag AgMPAOH

OO OH

O

HOCitrate

Citrate

Ag

COOH

COOH

TbADHAg

CONH

COOH

TbADHOminusNa+

H2N

Scheme 10 Covalent conjugation of enzymes on the surface of carboxyl-modified AgNPs

OHO

EDC HOSu Bis-amino

polyethylene glycol

NH

OO

44GMBS N

H

OO N

H44

ON

O

O3

CoA

NH

OO N

H44

ON

O

O3

SHN

O

OH

OP O

OPO

O O

OHO

NNN

N

PO

OminusOminus

OminusOminus

NH2

NH2

Scheme 11 Covalent conjugation of coenzyme A to polystyrene nanoparticles

O OOO P

OHSS

5998400 (DSP)3-A10-ATT-ATC-ACT 3998400

DSP cyclic disulfide-containingphosphate derivative =

Figure 11 Conjugation of AgNPs with oligonucleotides by usingDSP as a linker molecule (adapted from [36])

27 Polystyrene Polystyrene is an aromatic polymerobtained by polymerization of styrene monomers [138] Thepolystyrene-based NPs are widely used in the moleculardiagnostics for the detection of biomarker proteins andgenomic DNAs Polystyrene can be employed as a coating ona variety of nanoparticles as its functional groups can be easilymodified or conjugated with other molecules The otherapplication of polystyrene is in the fabrication of fluorescencebeads (FBs) The fluorescence molecules are loaded into thepolystyrene shell to produce FBs which are then used invarious sensing applications The polystyrene is also used tocoat the magnetic NPs so they can be conjugated with otherbiomolecules such as DNA and Proteins The applications ofpolystyrene include but are not limited to the detection ofE coli [139] the detection of cardiac Troponin T (cTnT) thedetection of Herpes simplex virus and many more

271 Covalent Modification Covalent modification throughcarboxyl group iswell known formodification of biomolecule

Most of the polystyrene-based nanoparticles bear large num-bers of pendant carboxyl which increases the loading amountof biomolecule

Enzyme catalyzed covalent immobilization of the pro-teins bearing a small 12-mer ldquoybbRrdquo tag onto the polystyrenenanoparticles (PSNP) is recently reported by Wong et al[140] As depicted in Scheme 11 the carboxyl-PSNPs werereacted with the bis-amino-polyethylene glycol in the pres-ence of HOSu and EDC to generate the amino-pegylatedPSNPs These PSNPs are then reacted with the g-maleimi-dobutyric acid succinimidyl (GMBS) to obtain maleimide-functionalized PSNPs The maleimide-functionalized PSNPsupon chemoligation with coenzyme A (CoA) produce theCoA-derivatized PSNPs

As depicted in Scheme 12 the protein of interest bearingybbR-tag is immobilized on the CoA-derivatized PSNPsThephosphopantetheinyl transferase (Sfp) catalyzed the reactionbetween the serine residue of the ybbR-tag and the phos-phopantetheine moiety of CoA with the simultaneous lossof 3101584051015840-adenine diphosphate results in the attachment ofproteins onto the surface of PSNPs It is reported that theenzymes immobilized by this method retain their activity

There are several reports on the use of fluoromicrobeadsfor the detection of biomarkers Primarily the fluoromi-crobeads are made up of carboxylated polystyrene as a coat-ingmaterial entrapping the fluorescentmolecules Accordingto the recent report by Song et al [37] the fluoromicrobeadswere used for the detection of the cTnT on the proteinmicroarray as depicted in Figure 12

The carboxylate modified fluoromicrobeads were conju-gated with the anti cTnI mAb through EDCNHS-mediated

14 Journal of Chemistry

HN

O

OH

OP

O

O

PO

O

OHO

N

NN

P

O

S

HN

O

Coenzyme A

Phosphopantetheine

PO

O

O

OHO

N Sfp

NN

N

P

O

ybbr-protein

HN

O

OH

OP

O

O

S

HN

O

NH2

NH2

Ominus

Ominus

Ominus

minusO

minusO

Mg2+

HO∙∙

Ominus

OminusOminus

minusO

N

O

Polystyrenenanoparticle

Scheme 12 Protein conjugation to polystyrene NP

System 1 antibody-conjugated fluoromicrobeads

System 2 avidin-conjugated fluoromicrobeads

DTSP SAM

Anti-cTnI cAb

cTnI

Figure 12 Application of the polystyrene-coated fluoromicrobeadsfor the detection of cTnI on the protein microarray (adapted from[37])

coupling reaction The use of fluoromicrobeads alloweddetecting the cTnI in plasma samples with a range of 01ndash100 ngmL

272 Affinity-Based Modification The affinity interactionsare used for the attachment of oligonucleotides with thefluoromicrobeads or polystyrene-coated magnetic beads Togenerate the oligonucleotide conjugated fluoromicrobeads ormagnetic beads respective polystyrene-coated beads are firstconjugated with the streptavidin using the EDCNHS cou-pling reaction as reported by Zhang et al [141] As depicted

B

B

MB MB

MB

BB

Magnetic bead

Streptavidin

DNA labeled biotin

Figure 13 DNA attachment to the magnetic beads

in Figure 13 the streptavidinmodified beads are then allowedto incubate with the biotinylated oligonucleotides Due to theaffinity of biotin for streptavidin the biotinylated oligonu-cleotides can be readily immobilized on the streptavidincoated beads

The binding affinity of streptavidin and biotin in solutionis up to 25 times 1013 (molL)minus1 [142] This interaction is about amillion times stronger than the antigen and antibody inter-action The antibodies directly immobilized onto the sur-face lose 90 of their biological activity [143] Howeverthe biotinylated antibodies immobilized on the streptavidincoated surface can retain their bioactivity [144]

Journal of Chemistry 15

3 Conclusions

Surface modification techniques of the materials used asplatforms in the fabrication of biosensors are reviewed inthis paper There are several reports on materials and vari-ous methods for altering their physicochemical propertiesHence one of these methods can be chosen according tothe targeted use and needed physiochemical properties Itis important to note that the performance of the biosensoris highly dependent on the substrate material used and itsmeticulous modification for particular applications There-fore it is critical to understand the principles of a biosensor toidentify the correct substrate material and its surface modifi-cation chemistry Furthermore it is important to look at thelatest advances in the materials and techniques used for thefabrication of a biosensor before the processing

Competing Interests

All authors declare that there is no conflict of interests

Acknowledgments

This research was supported by the Hallym UniversityResearch Fund (HRF-201601-010) This work was also sup-ported by the fund obtained through Industry-Academic col-laboration between Biometrix Technology Inc (ChuncheonSouth Korea) and Hallym University

References

[1] A Sassolas B D Leca-Bouvier and L J Blum ldquoDNA biosen-sors andmicroarraysrdquoChemical Reviews vol 108 no 1 pp 109ndash139 2008

[2] A Cavalcanti B Shirinzadeh M Zhang and L C KretlyldquoNanorobot hardware architecture for medical defenserdquo Sen-sors vol 8 no 5 pp 2932ndash2958 2008

[3] R-Q Zhang S-L Liu W Zhao et al ldquoA simple point-of-caremicrofluidic immunomagnetic fluorescence assay for path-ogensrdquo Analytical Chemistry vol 85 no 5 pp 2645ndash2651 2013

[4] S B Nimse K S Song M D Sonawane D R Sayyed and TS Kim ldquoImmobilization techniques for microarray challengesand applicationsrdquo Sensors vol 14 no 12 pp 22208ndash22229 2014

[5] A P F Turner ldquoBiosensors sense and sensibilityrdquo ChemicalSociety Reviews vol 42 no 8 pp 3184ndash3196 2013

[6] L Wu and X Qu ldquoCancer biomarker detection recent achieve-ments and challengesrdquoChemical Society Reviews vol 44 no 10pp 2963ndash2997 2015

[7] K Ariga Q Ji T Mori et al ldquoEnzyme nanoarchitectonicsorganization and device applicationrdquo Chemical Society Reviewsvol 42 no 15 pp 6322ndash6345 2013

[8] W-W Zhao J-J Xu and H-Y Chen ldquoPhotoelectrochemicalDNA biosensorsrdquo Chemical Reviews vol 114 no 15 pp 7421ndash7441 2014

[9] Q Liu C Wu H Cai N Hu J Zhou and P Wang ldquoCell-basedbiosensors and their application in biomedicinerdquo ChemicalReviews vol 114 no 12 pp 6423ndash6461 2014

[10] X Zhao S Nampalli A J Serino and S Kumar ldquoImmobi-lization of oligodeoxyribonucleotides with multiple anchors to

microchipsrdquo Nucleic Acids Research vol 29 no 4 pp 955ndash9592001

[11] P Kumar S K Agrawal A Misra and K C Gupta ldquoA newheterobifunctional reagent for immobilization of biomoleculeson glass surfacerdquo Bioorganic 120572Medicinal Chemistry Letters vol14 no 5 pp 1097ndash1099 2004

[12] F Secundo ldquoConformational changes of enzymes upon immo-bilisationrdquo Chemical Society Reviews vol 42 no 15 pp 6250ndash6261 2013

[13] S Lee S Kim J Malm O C Jeong H Lilja and T LaurellldquoImproved porous silicon microarray based prostate specificantigen immunoassay by optimized surface density of thecapture antibodyrdquoAnalytica Chimica Acta vol 796 pp 108ndash1142013

[14] K Jaras A A Tajudin A Ressine et al ldquoENSAM europiumnanoparticles for signal enhancement of antibody microarrayson nanoporous siliconrdquo Journal of Proteome Research vol 7 no3 pp 1308ndash1314 2008

[15] C Steinhauer A Ressine G Marko-Varga T Laurell C AK Borrebaeck and C Wingren ldquoBiocompatibility of surfacesfor antibody microarrays design of macroporous silicon sub-stratesrdquo Analytical Biochemistry vol 341 no 2 pp 204ndash2132005

[16] K Jaras B Adler A Tojo et al ldquoPorous silicon antibodymicroarrays for quantitative analysis measurement of free andtotal PSA in clinical plasma samplesrdquo Clinica Chimica Acta vol414 pp 76ndash84 2012

[17] S W Lee K Hosokawa S Kim et al ldquoA highly sensitive poroussilicon (P-Si)-based human Kallikrein 2 (hK2) immunoassayplatform toward accurate diagnosis of prostate cancerrdquo Sensorsvol 15 no 5 pp 11972ndash11987 2015

[18] C Roychaudhuri ldquoA review on porous silicon based electro-chemical biosensors beyond surface area enhancement factorrdquoSensors and Actuators B Chemical vol 210 pp 310ndash323 2015

[19] ARessine S EkstromGMarko-Varga andT Laurell ldquoMacro-nanoporous silicon as a support for high-performance proteinmicroarraysrdquo Analytical Chemistry vol 75 no 24 pp 6968ndash6974 2003

[20] S Lee E Silajdzic H Yang et al ldquoA porous silicon immunoas-say platform for fluorometric determination of 120572-synuclein inhuman cerebrospinal fluidrdquo Microchimica Acta vol 181 no 9-10 pp 1143ndash1149 2014

[21] S Belhousse N Belhaneche-Bensemra K Lasmi et alldquoModified porous silicon for electrochemical sensor of para-nitrophenolrdquo Materials Science and Engineering B vol 189 pp76ndash81 2014

[22] N Reta A Michelmore C Saint B Prieto-Simon and NH Voelcker ldquoPorous silicon membrane-modified electrodesfor label-free voltammetric detection of MS2 bacteriophagerdquoBiosensors and Bioelectronics vol 80 pp 47ndash53 2016

[23] B Guan A Magenau S Ciampi K Gaus P J Reece and J JGooding ldquoAntibody modified porous silicon microparticles forthe selective capture of cellsrdquo Bioconjugate Chemistry vol 25no 7 pp 1282ndash1289 2014

[24] S Vutti N Buch-Manson S Schoffelen N Bovet K LMartinez and M Meldal ldquoCovalent and stable CuAAC mod-ification of silicon surfaces for control of cell adhesionrdquo Chem-BioChem vol 16 no 5 pp 782ndash791 2015

[25] A M Rossi L Wang V Reipa and T E Murphy ldquoPoroussilicon biosensor for detection of virusesrdquo Biosensors andBioelectronics vol 23 no 5 pp 741ndash745 2007

16 Journal of Chemistry

[26] T L Lasseter B H Clare N L Abbott and R J HamersldquoCovalently modified silicon and diamond surfaces resistanceto nonspecific protein adsorption and optimization for biosens-ingrdquo Journal of the American Chemical Society vol 126 no 33pp 10220ndash10221 2004

[27] M Li K-G Neoh E-T Kang T Lau and E E ChiongldquoSurface modification of silicone with covalently immobilizedand crosslinked agarose for potential application in the inhibi-tion of infection and omental wrappingrdquo Advanced FunctionalMaterials vol 24 no 11 pp 1631ndash1643 2014

[28] G MacBeath and S L Schreiber ldquoPrinting proteins as microar-rays for high-throughput function determinationrdquo Science vol289 no 5485 pp 1760ndash1763 2000

[29] S B Nimse M D Sonawane K S Song and T Kim ldquoBio-marker detection technologies and future directionsrdquoThe Ana-lyst vol 141 no 3 pp 740ndash755 2016

[30] M D Sonawane S B Nimse K Song and T Kim ldquoDetectionquantification and profiling of PSA current microarray tech-nologies and future directionsrdquo RSC Advances vol 6 no 9 pp7599ndash7609 2016

[31] S B Nimse and T Kim ldquoBiological applications of function-alized calixarenesrdquo Chemical Society Reviews vol 42 no 1 pp366ndash386 2013

[32] K-S Song S B Nimse J Kim et al ldquo9GDNAChip microarraybased on the multiple interactions of 9 consecutive guaninesrdquoChemical Communications vol 47 no 25 pp 7101ndash7103 2011

[33] R J Chen S Bangsaruntip K A Drouvalakis et al ldquoNonco-valent functionalization of carbon nanotubes for highly specificelectronic biosensorsrdquo Proceedings of the National Academy ofSciences of the United States of America vol 100 no 9 pp 4984ndash4989 2003

[34] Y Lu W Shi J Qin and B Lin ldquoFabrication and characteri-zation of paper-based microfluidics prepared in nitrocellulosemembrane by wax printingrdquo Analytical Chemistry vol 82 no1 pp 329ndash335 2010

[35] P Zhang R Zhang M Gao and X Zhang ldquoNovel nitrocel-lulose membrane substrate for efficient analysis of circulatingtumor cells coupled with surface-enhanced raman scatteringimagingrdquo ACS Applied Materials and Interfaces vol 6 no 1 pp370ndash376 2014

[36] J-S Lee A K R Lytton-Jean S J Hurst and C AMirkin ldquoSil-ver nanoparticlemdasholigonucleotide conjugates based on DNAwith triple cyclic disulfide moietiesrdquo Nano Letters vol 7 no 7pp 2112ndash2115 2007

[37] S Y Song Y D Han K Kim S S Yang and H C YoonldquoA fluoro-microbead guiding chip for simple and quantifiableimmunoassay of cardiac troponin I (cTnI)rdquo Biosensors andBioelectronics vol 26 no 9 pp 3818ndash3824 2011

[38] S V Lemeshko T Powdrill Y Y Belosludtsev and M HoganldquoOligonucleotides form a duplex with non-helical properties ona positively charged surfacerdquoNucleic Acids Research vol 29 no14 pp 3051ndash3058 2001

[39] Z-L Zhi A K Powell and J E Turnbull ldquoFabrication ofcarbohydrate microarrays on gold surfaces direct attachmentof nonderivatized oligosaccharides to hydrazide-modified self-assembledmonolayersrdquoAnalytical Chemistry vol 78 no 14 pp4786ndash4793 2006

[40] S L Pan and L Rothberg ldquoChemical control of electrodefunctionalization for detection of DNA hybridization by elec-trochemical impedance spectroscopyrdquo Langmuir vol 21 no 3pp 1022ndash1027 2005

[41] Z Lu C M Li Q Zhou Q-L Bao and X Cui ldquoCovalentlylinked DNAprotein multilayered film for controlled DNAreleaserdquo Journal of Colloid and Interface Science vol 314 no 1pp 80ndash88 2007

[42] L-S Jang and H-J Liu ldquoFabrication of protein chips basedon 3-aminopropyltriethoxysilane as a monolayerrdquo BiomedicalMicrodevices vol 11 no 2 pp 331ndash338 2009

[43] F Fixe M Dufva P Telleman and C B Christensen ldquoFunc-tionalization of poly(methyl methacrylate) (PMMA) as a sub-strate for DNAmicroarraysrdquoNucleic Acids Research vol 32 no1 article e9 2004

[44] A Lueking M Horn H Eickhoff K Bussow H Lehrachand G Walter ldquoProtein microarrays for gene expression andantibody screeningrdquo Analytical Biochemistry vol 270 no 1 pp103ndash111 1999

[45] N Zammatteo L Jeanmart S Hamels et al ldquoComparisonbetween different strategies of covalent attachment of DNA toglass surfaces to build DNA microarraysrdquo Analytical Biochem-istry vol 280 no 1 pp 143ndash150 2000

[46] M Ozmen K Can I Akin et al ldquoSurface modification of glassbeads with glutaraldehyde characterization and their adsorp-tion property for metal ionsrdquo Journal of Hazardous Materialsvol 171 no 1ndash3 pp 594ndash600 2009

[47] C Funk PM Dietrich T Gross HMinW E S Unger andWWeigel ldquoEpoxy-functionalized surfaces for microarray appli-cations surface chemical analysis and fluorescence labeling ofsurface speciesrdquo Surface and Interface Analysis vol 44 no 8pp 890ndash894 2012

[48] S Mahajan P Kumar and K C Gupta ldquoOligonucleotide mic-roarrays immobilization of phosphorylated oligonucleotideson epoxylated surfacerdquo Bioconjugate Chemistry vol 17 no 5pp 1184ndash1189 2006

[49] M C Pirrung J D Davis and A L Odenbaugh ldquoNovelreagents and procedures for immobilization of DNA on glassmicrochips for primer extensionrdquo Langmuir vol 16 no 5 pp2185ndash2191 2000

[50] E Southern K Mir and M Shchepinov ldquoMolecular interac-tions on microarraysrdquo Nature Genetics vol 21 no 1 pp 5ndash91999

[51] M S Shchepinov S C Case-Green and E M SouthernldquoSteric factors influencing hybridisation of nucleic acids tooligonucleotide arraysrdquo Nucleic Acids Research vol 25 no 6pp 1155ndash1161 1997

[52] D A Tomalia A M Naylor and W A Goddard III ldquoStarbustdendrimers molecular-level control of size shape surfacechemistry topology and flexibility from atoms to macroscopicmatterrdquo Angewandte ChemiemdashInternational Edition in Englishvol 29 no 2 pp 138ndash175 1990

[53] R Benters C M Niemeyer D Drutschmann D Blohm andD Wohrle ldquoDNA microarrays with PAMAM dendritic linkersystemsrdquo Nucleic Acids Research vol 30 no 2 p e10 2002

[54] J H Moon J W Shin S Y Kim and J W Park ldquoFormationof uniform aminosilane thin layers an imine formation tomeasure relative surface density of the amine grouprdquo Langmuirvol 12 no 20 pp 4621ndash4624 1996

[55] J C Alwine D J Kemp and G R Stark ldquoMethod fordetection of specific RNAs in agarose gels by transfer to diazo-benzyloxymethyl-paper and hybridization with DNA probesrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 74 no 12 pp 5350ndash5354 1977

[56] P L Dolan Y Wu L K Ista R L Metzenberg M A Nelsonand G P Lopez ldquoRobust and efficient synthetic method for

Journal of Chemistry 17

forming DNA microarraysrdquo Nucleic Acids Research vol 29 no21 article e107 2001

[57] S B Nimse J Kim K-S Song et al ldquoSelective recognitionof the ditopic trimethylammonium cations by water-solubleaminocalix[4]arenerdquo Tetrahedron Letters vol 52 no 29 pp3751ndash3755 2011

[58] V-T Ta S B Nimse K-S Song et al ldquoCharacterization ofthe mixed self-assembled monolayer at the molecular scalerdquoChemical Communications vol 47 no 40 pp 11261ndash11263 2011

[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

[60] Y Lee E K Lee YW Cho et al ldquoProteoChip a highly sensitiveprotein microarray prepared by a novel method of proteinimmobilization for application of protein-protein interactionstudiesrdquo Proteomics vol 3 no 12 pp 2289ndash2304 2003

[61] S W Oh J D Moon H J Lim et al ldquoCalixarene derivative asa tool for highly sensitive detection and oriented immobiliza-tion of proteins in a microarray format through noncovalentmolecular interactionrdquo The FASEB Journal vol 19 no 10 pp1335ndash1337 2005

[62] S B Nimse K-S Song J Kim D R Sayyed and T Kimldquo9G DNAChip technology self-assembled monolayer (SAM)of ssDNA for ultra-sensitive detection of biomarkersrdquo Interna-tional Journal ofMolecular Sciences vol 14 no 3 pp 5723ndash57332013

[63] V-T Nguyen S B Nimse K-S Song et al ldquoHPAI 9GDNAChip discrimination of highly pathogenic influenza virusgenesrdquo Chemical Communications vol 48 no 38 pp 4582ndash4584 2012

[64] K-S Song S B Nimse J Kim D R Sayyed and T Kim ldquoAnew platform for a convenient genotyping systemrdquo ChemicalCommunications vol 49 no 26 pp 2661ndash2663 2013

[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

[67] F Hennrich C Chan VMoore M Rolandi andM OrsquoConnellCarbonNanotubes Properties and Applications Taylor amp FrancisGroup Abingdon UK 2006

[68] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

[69] C Singh M Shaffer I Kinloch and A Windle ldquoProductionof aligned carbon nanotubes by the CVD injection methodrdquoPhysica B Condensed Matter vol 323 no 1ndash4 pp 339ndash3402002

[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

[71] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

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Analytical Methods in Chemistry

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Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

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Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

6 Journal of Chemistry

OH O OH

N

N

N

OH OHO

Si

Si

N

N

lowast

lowast

SiO2

SiO2

OH O OH

Si

SiO2

OH OH OH

SiO2

OH OHO

Si

SiO2

Si(OCH3)2

Single strandedunlabeled target DNA

+NClminus

NaNO2 + HCl

Diazonium ion

Cy3Cy5-dCTPDNA

For 14ndash16hr

lowast

lowast

NH2

NH2

Hybridized at 42∘Cat 4∘C

at 30min4∘C

Scheme 4 Covalent immobilization of probe DNA on a glass surface by diazotization and subsequent hybridization

O O O

O O

O

O

X X X X

+N

H4

+N

H4

H3C CH3O O O

O O

O

O

X X X X

H3C CH3

1 cm

1 cm

Figure 4 Interaction of calix[4]crown-5 derivative with proteins for the fabrication of protein microarray (adapted from [31])

Journal of Chemistry 7

(a) (b)

Figure 5 Contact angle comparison (a) bare glass and (b) AMCA modified glass slide (adapted from [32])

surface by using microarray After incubation at room tem-perature for 4 h the slides are washed to remove excess DNAsand driedThe free AMCAmolecules on the surface are thenblocked with the 4x SSC solution containing BSA and 01SDS Finally the slides are dried to obtain 9G DNAChips[63 64]

23 Carbon In recent years a nanoparticle-based structurelike nanotubes and nanowires has got tremendous attentionin biomedical and diagnostic fields [65 66] Before 1991 sp3hybridized form of carbon (diamond) sp2 hybridized formslike graphite and C60 fullerene were the only known formsof carbon with potential applications [67] In 1991 allotropeslike carbon nanotubes (CNT)were first reported and success-fully synthesized by Iijima with multiwall faces (MWCNT)[68]

Due to thermal electrical and magnetically uniqueproperties CNT became an important material in the devel-opment of biosensor platforms Commonly reportedmethodfor preparation of CNT includes chemical vapour deposition[69 70] arc discharge [71] and laser ablation [72]

Apart from CNT other carbon-based nanostructuresincluding carbondots carbon fibers andPDMSalso attractedresearchers due to their diverse properties for biomoleculeconjugation [73 74]Themajor advantage of carbon nanoma-terial is their large surface area which allows maximum spacefor biomolecule attachment

Immobilization of protein carbohydrate and nucleic acidon the CNT surfaces allows various biological applications[75 76]Themost important part in biomolecule conjugationis the surface functionalization of carbon-basedmaterialThegeneral techniques for carbon surface modification are (phy-sisorption) noncovalent and covalent modifications Thereare several reports on the different techniques of surfacemodification of carbon-based surfaces Due to the vastnessof the research on carbon-based material only few methodsare described in this paper

231 Physisorption Thehydrophobic character of CNT side-walls and the strong 120587-120587 interactions between the individualtubes causes them to aggregate and reduce their solubility in

common solvents which is considered as a problem for theirbiological applicationsHowever the samehydrophobic char-acter of theCNT surface is exploited for fabrication of biosen-sors by immobilizing biomolecules onto the CNT surfacesthrough hydrophobic-hydrophobic interactions [77ndash79]

The advantage of noncovalent interaction is a limiteddistortion of the three-dimensional structure of a protein orenzyme to be immobilized The hydrophobic amino acidsin proteins and enzymes develop the 120587-120587 interactions withthe hydrophobic part of CNT which make them adsorbedon the surface of CNT [80ndash83] As mentioned earlier theplatforms modified by noncovalent interactions suffer fromthe typical drawbacks of nonspecific interactions resulting inthe decreased specificity and sensitivity of a biosensor

To eliminate the problem of nonspecific interactions oftarget proteins with the sensor surface the novel approachof polyethylene oxide (PEO) polymer coating is adopted bymany researchers The PEO is well known for its proteinrepelling ability [84] Bomboi et al reported the use of Tween20 which is composed of three PEO branches and P103another molecule with hydrophobic polypropylene oxideunits to modify the surface of CNT before adsorption ofproteins on it The surface of Tween 20 and P103 modifiedCNT becomes slightly hydrophilic compared with bare CNTwhich results in the decrease in its interaction with thehydrophobic amino acid chains of biomarker proteins [85]

As depicted in Figure 6 for the selective immobilizationof streptavidin on the CNT surface Chen et al used mixednoncovalent and covalent approach which allows the highlyspecific immobilization of streptavidin and blocks the non-specific binding of other proteins like BSA [33]

Conjugation of a fluorescent molecule on the CNT sur-face is an immerging technology for highly sensitive detec-tion of biomolecules Nakayama-Ratchford et al reported theimmobilization of the fluorescent molecules like fluoresceinon the surface of CNT through 120587-120587 interactions [86] Thereare several reports on the applications of CNT surfaces mod-ified with the fluorescent molecules through noncovalentinteractions [87ndash90]

232 Chemical Modification To prevent the nonspecificbinding and to avoid the leaching of biomolecules from the

8 Journal of Chemistry

OH

OH

OH

O

HO

HO

HO

O

OO

OO

NH

O

NH

O

NH

OO

NH O

NH

O

NH

65 HON3

Boiling t = 8h

C2H4(NH2)2

NH2

H2N (CH2)2

(CH2)2

NH2(CH2)2

NH2(CH2)2

H2N (CH2)2

H2N (CH2)2

Scheme 5 Amine modification of CNT

BB

B

B B

B

SA SA

Figure 6 Streptavidin recognition by a nanotube coated with biot-inylated Tween (adapted from [33])

CNT surface a covalent modification technique is reportedThere are two types of covalent modifications namely (i)indirect method for example carboxylation of CNT surfaceand (ii) direct method for example fluorination of CNT sur-face where surface carbons change from sp2 to sp3 hybridiza-tion Esterification or amidation and sidewall covalent attach-ment are other approaches for covalent attachment [91 92]

(1) Carboxyl Modification The modification of the sensorsurfaces with the carboxyl groups is a general and highly usedsurface modification method Once the surface is modifiedwith the carboxyl groups it can be converted to a vari-ety of functional groups through reaction with appropriatereagents Furthermore the carboxylated surfaces can bedirectly conjugated with proteins or DNA through theiramine functional groups using coupling reagents A mixtureof sulphuric acid and nitric acid is a commonly used reagentfor the carboxylation of CNT surface

Marshall et al reported the method for carboxyl modifi-cation of CNT [93] According to this method a 2mg sampleof SWCNT is added to the 75 mixture of concentratedsulphuric acid and nitric acid (1mL) The mixture is allowedto sonicate in sonicator at 20∘CThe reaction mixture is thendiluted to 250mL by using deionized waterThe carboxylatedCNTs are then filtered through polytetrafluoroethylene filter(PTFE) of 045 120583m size Finally the collected nanotubes arewashedwith water at acidic pH followed by ethanol and driedin a vacuum desiccator

O OOH

O OOO

n

Figure 7 Structure of Epon resin 828

(2) Amine Modification Amide coupling is the most com-monly used conjugation technique in biomolecule attach-ment Either the amine or acid part of DNA or protein canbe used for conjugation using amide coupling reaction Forthe conjugation ofDNA toCNT through its phosphate groupamine modification is needed

Tam et al reported the DNA sensor based on the aminemodification of MWCNT as depicted in Scheme 5 [94] TheMWCNT were boiled in the 15M nitric acid for 12 h to gen-erate the carboxylated MWCNT The purified carboxylatedMWCNT were reacted with ethylenediamine to obtain theamine-modified MWCNT The amine-modified MWCNTwere conjugated to DNA by using EDC coupling reaction

Other reports for aminemodification of CNT include theuse of nitric acid and sulphuric acidmixture for carboxylationof the surface followed by ethylenediamine reaction [95]There are several reports on the covalent conjugation offluorescent molecules to the CNT surfaces [96ndash98]

(3) Epoxy Modification Epoxide group is a highly reactivefunctional group used in many substitution reactions as anelectrophile Eitan et al reported the covalent attachmentof epoxide-terminated molecules to carbon nanotubes byreaction between epoxide rings and carboxylic acid groupsthat are initially formed on the nanotube surface [99] Forepoxidation of CNT the surface is first carboxylated bydispersing the CNT in 75 solution of sulphuric acid in nitricacid for 3 h The purified carboxylated CNT were kept in theacetone with sonication for 1 hThen the solution containingthe carboxylated CNT is mixed with the solution of Eponresin 828 (Figure 7) in acetone to allow the reaction betweenEpon resin 828 and carboxyl groups on the CNT surface asdepicted in Scheme 6

Journal of Chemistry 9

O

O

O

O

R

OOCatalyst

O

O

O

O

O

O

CHHO

R

O

HC OH

R

O

H2C

O

HC OH

R

O

H2C

CH2

O

CHHO

R

O

CH2

HOHO

OHOH

+

Scheme 6 Epoxy modification of CNT

The mixture of solutions is sonicated for 1 h followedby stirring and heating at 70∘C The reaction was quenchedby addition of appropriate amount of potassium hydroxideThen the epoxilated CNT were purified and a number ofepoxy groups on the CNT surface were determined by usingthermogravimetric analysis

24 Nitrocellulose A PoC diagnosis system is always expe-cted to deliver final results in few minutes Though themicroarrays based on the glass and gold surfaces are usefulfor detection of multiple analytes at a time they need longertime for final data interpretation Microfluidic systems basedon paper or nitrocellulose membranes are emerging surfacesfor detection of bacteria viruses and proteins A paper isadvantageous due to its hydrophilic nature which allowsthe aqueous solutions to penetrate without the need of anyexternal force [100] The essential constituent of paper iscelluloseThe cellulose has hydroxyl functional groups whichcan be modified and changed according to surface propertiesneeded for a particular detection device [101] Due to lowcost and high availability paper is preferred for large scaleproduction Moreover the devices required for the tests areportable and disposable [102ndash105] The very first example ofpaper based detection is glucose detection in urine [106] andpregnancy test kit [107]There are different types of paper likeWhatman filter paper glossy paper [108] membrane and soforth Whatman filter is used because of its high penetrationand flow rate [109ndash112] but in some cases it does not havethe necessary characteristic for surface modification Mem-branes on the other hand are planner sheets and providelarger surface area for immobilization of biomolecules such

as DNA and protein The nitrocellulose (NC) membrane isbroadly used for immobilization of DNA [113] protein [114]and enzymes [115] due to its hydrophobic surface

241 Physical Adsorption Single-stranded DNAs are irre-versibly bound to the surface of the NCmembrane with non-covalent interactionsTheprimary interactions are hydropho-bic and electrostatic between the positively charged surfaceof the membrane and negatively charged DNAs The nitro-cellulose offers very high binding capacity for DNAs andproteins Fabrication of NC membranes can be done bydifferent methods including the photolithography The waxpatterningmethod is fast cheap and easy to process and doesnot need organic solvents The NCmembranes with the poresize of 045 120583mdo not need pretreatment for penetrationThefabrication process includesmainly printing and baking stepswhich can be finished in 10min As shown in Figure 8 firstlythe wax is printed on the surface of NCmembrane and bakedat 125∘C for 5min in the oven The melting of the wax onmembrane makes it more hydrophobic and affords surfacesuitable for the immunoassay For immunoassays Lu et alcoated the cAbs on the surface and the free area is blockedwith the 1 BSA

During baking melted wax passes through the mem-brane The 121∘ contact angle of backside membrane assuresthe melting of wax thoroughly The efficiency of wax treatedmembrane is compared with the untreated membrane byimmobilizing fluorescence labeled goat antihuman IgG Theimmobilization on wax printed surface is more uniform thanthe untreated membrane Apart from this a large volumeof liquid can be used because ring effect of protein on the

10 Journal of Chemistry

HO

OSH AuNP

AuNP-mAb

mAbEDCNHS

001M PBS

(CH2)15(CH2)11

NaBH4HAuCl4 + SH + HO

pH sim 74

Scheme 7 Immobilization on antibodies on AuNP

NC membrane

Cross section view

PrintingStep 1

Step 2 Baking

Wax patternedNC membrane

Wax is printed onto thesurface of NC membrane

Wax melts and penetratesthrough NC membrane

Nitrocellulose

Wax

Figure 8Wax printing on nitrocellulosemembranes (adapted from[34])

untreated membrane is avoided Wax printing method gen-erates 100 120583mmicrochannel which removes the micrometersize contaminants and makes the wax printed membranessuitable for the applications in microfluidic assays Apartfrom immobilization wax printing has application in dotimmunoassay and sample purifications [34]

Due to advantages of NC membrane for high bindingcapacity and good flow of solution it is also used on the chipsurfaces The glass slide can be coated with the 12 120583m layer ofNC to afford a platform with the intrinsic properties of NCThe solution of cAbs in PBS buffer containing 10 glycerolis then spotted on the modified surface After spotting theslides are incubated for one hour After incubation slides arewashed with 01 Tween 20 in PBS buffer and dried to gen-erate the platform for detection of biomarker proteins [116]

Apart from routine microarray applications NC mem-brane is also used for the detection of circulating tumor cells(CTC) as reported by Zhang et al The binding of CTCs bythe cAbs immobilized on the NC membrane is detected bySurface Enhanced Raman Scattering (SERS) as depicted inFigure 9

Usually the antibodies specific for cancer cells are usedas a capture substrate and immobilized on the surface TheNC membrane is cut into 1 cm times 1 cm pieces Then thesepieces are immersed in the ethanol and then tiled on thePMMA wafer After washing the membrane is activated byusing PBS buffer containing antibodies at 37∘C for 30minDuring this process the cAbs are avidly immobilized on theNC membrane The 1 BSA solution is loaded to block thefree surface area to avoid any background signals due tononspecific interactions Finally the membranes are washedwith PBS buffer and stored at 4∘CThe gold nanoparticle andRaman probes are used to detect the CTCs by SERS [35]

25 Gold Application of nanoparticles is amost focused areain the field of inorganic chemistry and it has also attractedimaginations of many biologists too Inorganic nanoparti-cles including gold silver and ferrous oxides have foundmany important applications in cell signaling drug deliveryand colorimetric and fluorescence-based detections Goldnanoparticles (AuNP) functionalized with proteins DNAsor Raman probes are well known in the field of biosensorsand nanobiotechnology for their applications in the molec-ular diagnostics [117ndash119] protein detection [120ndash122] generegulation [123] and cell imaging [124]

251 Covalent Modification

(1) Thiol Based Modification AuNPs are commonly usedin the electrochemical and optical detection systems Theconjugation with biomolecule does not change the opticalproperties ofAuNP [125]Di Pasqua et al reported thiolmod-ification for the detection of E coli O157H7 E coli specificantibodies were conjugated with the AuNPs [126] As shownin Scheme 7 the 10 nmAuNPs are carboxylated and then cou-pled to E coli specific monoclonal antibody (mAb) throughamide coupling

For the generation of AuNPs to the solution containing410mg of HAuCl

4sdot3H2O in 6mL of water ethanoic solutions

of 11-mercapto-1-undecanol and 16-mercaptohexadecanoicacid are added Upon addition of NaBH

4to this mixture at

0∘C the solution turns brown The product AuNP cappedwith alkanethiol pendant alcohol and carboxylic acid func-tional groups precipitate upon three hours of stirring Theprecipitated particles are then thoroughly washed with etha-nol and an ethanolic solution containing a small amountof 1M HCl The AuNPs are then dried under vacuum forten hours For the conjugation of mABs with the AuNPsthe carboxylic acid functional groups on the AuNPs are

Journal of Chemistry 11

SERSimaging

AuNPs

Raman labelNC membrane

AntibodyCancer cell

Figure 9 Detection of circulating tumor cells on NC membranes containing immobilized cAbs (adapted from [35])

activated by reacting the AuNPs with 1-ethyl-3-3(3-dimeth-ylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in the PBS buffer The mABs arethen added to this solution and the suspension is stirred atroom temperature for 30min The mAB-conjugated AuNPsare then collected by centrifugation and washing with PBSand ethanol The mAB-conjugated AuNPs successfully bindto E coli when incubated in PBS at pH 74 In other reportsthe AuNPs were found very effective in the detection ofcancerous pancreatic cells

The AuNPs are known to suffer from the problem ofaggregation upon long-term storage Therefore to solve thisissue the AuNPs are conjugated with the polyethylene glycol(PEG) to prevent their aggregation [127 128]The conjugationof PEGwith the AuNPsmakes the later hydrophilic thus pre-venting agglomeration induced by hydrophobic interactionsA PEGwith the heterobifunctional groups (dithiol at one endand a carboxyl at another end) is coated on the AuNP Thedithiol group allows stable anchoring heterobifunctional PEGligands on the surface of AuNP and the terminal carboxylgroup is used for coupling with antibodies The carboxy-terminated bifunctional PEG linker is synthesized by follow-ing a method reported by Eck et al which is depicted inScheme 8 The anionic polymerization of compound 1 withan excess of ethylene oxide allows synthesizing compound 2The treatment of compound 2 with chloroacetic acid at 60∘Callows generating compound 3 The reaction of an excess ofthe elemental bromine in dichloromethane at 0∘C for fourhours in the dark with compound 3 produces dibromidecompound 4 Compound 5 is obtained by reaction withcompound 4 in water with the excess of sodium hydrosulfidehydrate

The synthesized bifunctional PEG linker is then conju-gated with the citrate-stabilized gold nanoparticles by simpleligand exchangeThe citrate-stabilized gold nanoparticles areknown to aggregate in the buffer containing salts Thereforethe ligand exchange from citrate to PEG should be done inpure water The PEGylated AuNPs are conjugated to mono-clonal F19 antibodies for the detection of human pancreaticcarcinoma through EDCNHS coupling reaction [129]

OHO

(2) HCl

1

2

3

4

5

Br Br

HS SH

(CH2)9

(CH2)9

(CH2)9

(CH2)9

+

NaHDMF60∘C

(OCH2CH2)n

(OCH2CH2)n

(OCH2CH2)n

OCH2COOH

OCH2COOH

(CH2)9 (OCH2CH2)n OCH2COOH

OminusNa+

Br2

(2) Acetic acid (1) NaSHH2O

60∘C(1) ClCH2-COONa

Scheme 8 Synthesis of bifunctional PEG linker using conjugationwith AuNP

(2) Hydrazide Modification According to the report by Zhiet al the hydrazide-derivatized self-assembledmonolayer ona gold surface is used for the efficient and selective anchor-ing of oligosaccharide [39] The generated oligosaccharidemicroarrays allow the fluorescence-based detection of targetproteins The use of gold as a substrate for the fluorescence-based detection suffers from the drawbacks including flu-orescence quenching and nonspecific surface adsorption ofproteins However the use of120596-thiolated fatty acid (C

16) self-

assembledmonolayer between the gold surface andhydrazide

12 Journal of Chemistry

AuC C

C

C

OHOHO O

O

O

O

O

O

O

O

O

CHR

NN

H

N

N

N

H

NH

NH

NH

H

NH

C

O

O

O NNH

NH

HNH

H

S

S

S

S

HS Au

Au

Au

Au

Au

C16 SAM

Adipic dihydrazideEDC

(Sugar)R-CHO

Binding to protein

Sugarprobe

Protein Alexafluoro 532

SAM andblocking layer

Ab 2nd Ab

NH2

NH2H2N

CH2R

Scheme 9 Application of hydrazide-derivatized SAM on a goldsurface for the fabrication of oligosaccharide microarray (adaptedfrom [39])

groups minimizes the quenching effect Moreover the effec-tive blocking of the surface with the poly(ethylene glycol)aldehyde and BSA reduces the nonspecific adsorption ofprotein on the surface

For the fabrication of the reported oligosaccharidemicroarrays the gold substrate is prepared by following amethod depicted in Scheme 9 The self-assembled mono-layer (SAM) of 16-mercaptohexadecanoic acid (MHDA) isobtained by soaking the gold coated slides in the isobutylalcohol for 2 days The slides are then washed in ethanolto remove excess reagents and are dried under the nitrogenstream The carboxyl functional groups on the SAM areconverted to the hydrazide groups by incubation of the SAMcovered slides in the dimethyl sulfoxide solution containing1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and adipicdihydrazide The ethanol-washed and dried slides are thenused for the oligosaccharide printing to obtain oligosaccha-ride microarrays

The generated oligosaccharide microarray platformallows interrogation of carbohydrate-protein interactions ina high-throughput manner

26 Silver Similar to AuNPs silver nanoparticles (AgNP) arealso used for the immobilization of proteins and enzymesThe surface of AgNP allows adsorption of proteins Henceit can be utilized as a host matrix for various biomoleculesSilver is a suitable substrate for the immobilization of wholecell or the isolated enzymes [130 131]

Texp lt Tm

Ag

AgAg

Ag

AgAg

Texp gt Tm

Figure 10 AgNPs-oligonucleotide conjugates (adapted from [36])

261 Electrostatic Modification The electrostatic interac-tions allow the physical adsorption of biomolecules on thesurface of AgNPs Shen et al reported that the AgNPs aresynthesized by reduction of silver nitrate in the presence ofsodium citrate During the reduction process the solutionis sonicated for 15min to obtain the yellow silver colloidwhich is then kept at 4∘C for several days away from lightThen isolated nanoparticles can be used for physisorption ofproteins at a pH higher than their isoelectric point [132]

262 Covalent Modification As depicted in Scheme 10the AgNPs prepared by the citrate reduction method andstabilized with citrate [133] can be functionalized with car-boxyl groups upon treatment with 3-mercaptopropanoic acid(MPA) As reported by the Petkova et al for the immobi-lization of alcohol dehydrogenase from Thermoanaerobiumbrockii (TbADH) the carboxyl-modified AgNPs were treatedwith the solution containing TbADH under continuousstirring for 7 h at 26∘C a research by [134] The AgNPsmodified with the TbADH were successfully used for thebiotransformation studies

The application of a bifunctional linker for the modifica-tion of AgNPs is reported [135 136] The bifunctional linker11-mercaptoundecanoic acid was used with 1-octanethiol in1 1 ratio to generate the mixed SAM on the surface of AgNPThe IgG antibodies are then conjugated with the mixed SAMmodified AgNPs It is reported that upon covalent conjuga-tion of biomolecules with AgNPs their stability and activityis maintained [137]

According to another report on the covalent modifi-cation AgNPs-oligonucleotide conjugates are prepared byusing DNA and triple cyclic disulfide moieties [36] Asdepicted in Figure 10 the two types ofAgNPs-oligonucleotideconjugates with complementary DNA sequences undergoDNA hybridization driven coagulation resulting in the colorchange

As depicted in Figure 11 the AgNP-DNA conjugates wereprepared by treatment of AgNPs with the cyclic disulfidemodified oligonucleotide The AgNP and oligonucleotideswere allowed to react with each other with 1 4 ratio inthe presence of 1 sodium dodecyl sulfate and NaCl Theovernight incubation of solution results in the AgNP-DNAconjugates which are collected by centrifugation and washedto remove the excess DNAs

Journal of Chemistry 13

Ag AgMPAOH

OO OH

O

HOCitrate

Citrate

Ag

COOH

COOH

TbADHAg

CONH

COOH

TbADHOminusNa+

H2N

Scheme 10 Covalent conjugation of enzymes on the surface of carboxyl-modified AgNPs

OHO

EDC HOSu Bis-amino

polyethylene glycol

NH

OO

44GMBS N

H

OO N

H44

ON

O

O3

CoA

NH

OO N

H44

ON

O

O3

SHN

O

OH

OP O

OPO

O O

OHO

NNN

N

PO

OminusOminus

OminusOminus

NH2

NH2

Scheme 11 Covalent conjugation of coenzyme A to polystyrene nanoparticles

O OOO P

OHSS

5998400 (DSP)3-A10-ATT-ATC-ACT 3998400

DSP cyclic disulfide-containingphosphate derivative =

Figure 11 Conjugation of AgNPs with oligonucleotides by usingDSP as a linker molecule (adapted from [36])

27 Polystyrene Polystyrene is an aromatic polymerobtained by polymerization of styrene monomers [138] Thepolystyrene-based NPs are widely used in the moleculardiagnostics for the detection of biomarker proteins andgenomic DNAs Polystyrene can be employed as a coating ona variety of nanoparticles as its functional groups can be easilymodified or conjugated with other molecules The otherapplication of polystyrene is in the fabrication of fluorescencebeads (FBs) The fluorescence molecules are loaded into thepolystyrene shell to produce FBs which are then used invarious sensing applications The polystyrene is also used tocoat the magnetic NPs so they can be conjugated with otherbiomolecules such as DNA and Proteins The applications ofpolystyrene include but are not limited to the detection ofE coli [139] the detection of cardiac Troponin T (cTnT) thedetection of Herpes simplex virus and many more

271 Covalent Modification Covalent modification throughcarboxyl group iswell known formodification of biomolecule

Most of the polystyrene-based nanoparticles bear large num-bers of pendant carboxyl which increases the loading amountof biomolecule

Enzyme catalyzed covalent immobilization of the pro-teins bearing a small 12-mer ldquoybbRrdquo tag onto the polystyrenenanoparticles (PSNP) is recently reported by Wong et al[140] As depicted in Scheme 11 the carboxyl-PSNPs werereacted with the bis-amino-polyethylene glycol in the pres-ence of HOSu and EDC to generate the amino-pegylatedPSNPs These PSNPs are then reacted with the g-maleimi-dobutyric acid succinimidyl (GMBS) to obtain maleimide-functionalized PSNPs The maleimide-functionalized PSNPsupon chemoligation with coenzyme A (CoA) produce theCoA-derivatized PSNPs

As depicted in Scheme 12 the protein of interest bearingybbR-tag is immobilized on the CoA-derivatized PSNPsThephosphopantetheinyl transferase (Sfp) catalyzed the reactionbetween the serine residue of the ybbR-tag and the phos-phopantetheine moiety of CoA with the simultaneous lossof 3101584051015840-adenine diphosphate results in the attachment ofproteins onto the surface of PSNPs It is reported that theenzymes immobilized by this method retain their activity

There are several reports on the use of fluoromicrobeadsfor the detection of biomarkers Primarily the fluoromi-crobeads are made up of carboxylated polystyrene as a coat-ingmaterial entrapping the fluorescentmolecules Accordingto the recent report by Song et al [37] the fluoromicrobeadswere used for the detection of the cTnT on the proteinmicroarray as depicted in Figure 12

The carboxylate modified fluoromicrobeads were conju-gated with the anti cTnI mAb through EDCNHS-mediated

14 Journal of Chemistry

HN

O

OH

OP

O

O

PO

O

OHO

N

NN

P

O

S

HN

O

Coenzyme A

Phosphopantetheine

PO

O

O

OHO

N Sfp

NN

N

P

O

ybbr-protein

HN

O

OH

OP

O

O

S

HN

O

NH2

NH2

Ominus

Ominus

Ominus

minusO

minusO

Mg2+

HO∙∙

Ominus

OminusOminus

minusO

N

O

Polystyrenenanoparticle

Scheme 12 Protein conjugation to polystyrene NP

System 1 antibody-conjugated fluoromicrobeads

System 2 avidin-conjugated fluoromicrobeads

DTSP SAM

Anti-cTnI cAb

cTnI

Figure 12 Application of the polystyrene-coated fluoromicrobeadsfor the detection of cTnI on the protein microarray (adapted from[37])

coupling reaction The use of fluoromicrobeads alloweddetecting the cTnI in plasma samples with a range of 01ndash100 ngmL

272 Affinity-Based Modification The affinity interactionsare used for the attachment of oligonucleotides with thefluoromicrobeads or polystyrene-coated magnetic beads Togenerate the oligonucleotide conjugated fluoromicrobeads ormagnetic beads respective polystyrene-coated beads are firstconjugated with the streptavidin using the EDCNHS cou-pling reaction as reported by Zhang et al [141] As depicted

B

B

MB MB

MB

BB

Magnetic bead

Streptavidin

DNA labeled biotin

Figure 13 DNA attachment to the magnetic beads

in Figure 13 the streptavidinmodified beads are then allowedto incubate with the biotinylated oligonucleotides Due to theaffinity of biotin for streptavidin the biotinylated oligonu-cleotides can be readily immobilized on the streptavidincoated beads

The binding affinity of streptavidin and biotin in solutionis up to 25 times 1013 (molL)minus1 [142] This interaction is about amillion times stronger than the antigen and antibody inter-action The antibodies directly immobilized onto the sur-face lose 90 of their biological activity [143] Howeverthe biotinylated antibodies immobilized on the streptavidincoated surface can retain their bioactivity [144]

Journal of Chemistry 15

3 Conclusions

Surface modification techniques of the materials used asplatforms in the fabrication of biosensors are reviewed inthis paper There are several reports on materials and vari-ous methods for altering their physicochemical propertiesHence one of these methods can be chosen according tothe targeted use and needed physiochemical properties Itis important to note that the performance of the biosensoris highly dependent on the substrate material used and itsmeticulous modification for particular applications There-fore it is critical to understand the principles of a biosensor toidentify the correct substrate material and its surface modifi-cation chemistry Furthermore it is important to look at thelatest advances in the materials and techniques used for thefabrication of a biosensor before the processing

Competing Interests

All authors declare that there is no conflict of interests

Acknowledgments

This research was supported by the Hallym UniversityResearch Fund (HRF-201601-010) This work was also sup-ported by the fund obtained through Industry-Academic col-laboration between Biometrix Technology Inc (ChuncheonSouth Korea) and Hallym University

References

[1] A Sassolas B D Leca-Bouvier and L J Blum ldquoDNA biosen-sors andmicroarraysrdquoChemical Reviews vol 108 no 1 pp 109ndash139 2008

[2] A Cavalcanti B Shirinzadeh M Zhang and L C KretlyldquoNanorobot hardware architecture for medical defenserdquo Sen-sors vol 8 no 5 pp 2932ndash2958 2008

[3] R-Q Zhang S-L Liu W Zhao et al ldquoA simple point-of-caremicrofluidic immunomagnetic fluorescence assay for path-ogensrdquo Analytical Chemistry vol 85 no 5 pp 2645ndash2651 2013

[4] S B Nimse K S Song M D Sonawane D R Sayyed and TS Kim ldquoImmobilization techniques for microarray challengesand applicationsrdquo Sensors vol 14 no 12 pp 22208ndash22229 2014

[5] A P F Turner ldquoBiosensors sense and sensibilityrdquo ChemicalSociety Reviews vol 42 no 8 pp 3184ndash3196 2013

[6] L Wu and X Qu ldquoCancer biomarker detection recent achieve-ments and challengesrdquoChemical Society Reviews vol 44 no 10pp 2963ndash2997 2015

[7] K Ariga Q Ji T Mori et al ldquoEnzyme nanoarchitectonicsorganization and device applicationrdquo Chemical Society Reviewsvol 42 no 15 pp 6322ndash6345 2013

[8] W-W Zhao J-J Xu and H-Y Chen ldquoPhotoelectrochemicalDNA biosensorsrdquo Chemical Reviews vol 114 no 15 pp 7421ndash7441 2014

[9] Q Liu C Wu H Cai N Hu J Zhou and P Wang ldquoCell-basedbiosensors and their application in biomedicinerdquo ChemicalReviews vol 114 no 12 pp 6423ndash6461 2014

[10] X Zhao S Nampalli A J Serino and S Kumar ldquoImmobi-lization of oligodeoxyribonucleotides with multiple anchors to

microchipsrdquo Nucleic Acids Research vol 29 no 4 pp 955ndash9592001

[11] P Kumar S K Agrawal A Misra and K C Gupta ldquoA newheterobifunctional reagent for immobilization of biomoleculeson glass surfacerdquo Bioorganic 120572Medicinal Chemistry Letters vol14 no 5 pp 1097ndash1099 2004

[12] F Secundo ldquoConformational changes of enzymes upon immo-bilisationrdquo Chemical Society Reviews vol 42 no 15 pp 6250ndash6261 2013

[13] S Lee S Kim J Malm O C Jeong H Lilja and T LaurellldquoImproved porous silicon microarray based prostate specificantigen immunoassay by optimized surface density of thecapture antibodyrdquoAnalytica Chimica Acta vol 796 pp 108ndash1142013

[14] K Jaras A A Tajudin A Ressine et al ldquoENSAM europiumnanoparticles for signal enhancement of antibody microarrayson nanoporous siliconrdquo Journal of Proteome Research vol 7 no3 pp 1308ndash1314 2008

[15] C Steinhauer A Ressine G Marko-Varga T Laurell C AK Borrebaeck and C Wingren ldquoBiocompatibility of surfacesfor antibody microarrays design of macroporous silicon sub-stratesrdquo Analytical Biochemistry vol 341 no 2 pp 204ndash2132005

[16] K Jaras B Adler A Tojo et al ldquoPorous silicon antibodymicroarrays for quantitative analysis measurement of free andtotal PSA in clinical plasma samplesrdquo Clinica Chimica Acta vol414 pp 76ndash84 2012

[17] S W Lee K Hosokawa S Kim et al ldquoA highly sensitive poroussilicon (P-Si)-based human Kallikrein 2 (hK2) immunoassayplatform toward accurate diagnosis of prostate cancerrdquo Sensorsvol 15 no 5 pp 11972ndash11987 2015

[18] C Roychaudhuri ldquoA review on porous silicon based electro-chemical biosensors beyond surface area enhancement factorrdquoSensors and Actuators B Chemical vol 210 pp 310ndash323 2015

[19] ARessine S EkstromGMarko-Varga andT Laurell ldquoMacro-nanoporous silicon as a support for high-performance proteinmicroarraysrdquo Analytical Chemistry vol 75 no 24 pp 6968ndash6974 2003

[20] S Lee E Silajdzic H Yang et al ldquoA porous silicon immunoas-say platform for fluorometric determination of 120572-synuclein inhuman cerebrospinal fluidrdquo Microchimica Acta vol 181 no 9-10 pp 1143ndash1149 2014

[21] S Belhousse N Belhaneche-Bensemra K Lasmi et alldquoModified porous silicon for electrochemical sensor of para-nitrophenolrdquo Materials Science and Engineering B vol 189 pp76ndash81 2014

[22] N Reta A Michelmore C Saint B Prieto-Simon and NH Voelcker ldquoPorous silicon membrane-modified electrodesfor label-free voltammetric detection of MS2 bacteriophagerdquoBiosensors and Bioelectronics vol 80 pp 47ndash53 2016

[23] B Guan A Magenau S Ciampi K Gaus P J Reece and J JGooding ldquoAntibody modified porous silicon microparticles forthe selective capture of cellsrdquo Bioconjugate Chemistry vol 25no 7 pp 1282ndash1289 2014

[24] S Vutti N Buch-Manson S Schoffelen N Bovet K LMartinez and M Meldal ldquoCovalent and stable CuAAC mod-ification of silicon surfaces for control of cell adhesionrdquo Chem-BioChem vol 16 no 5 pp 782ndash791 2015

[25] A M Rossi L Wang V Reipa and T E Murphy ldquoPoroussilicon biosensor for detection of virusesrdquo Biosensors andBioelectronics vol 23 no 5 pp 741ndash745 2007

16 Journal of Chemistry

[26] T L Lasseter B H Clare N L Abbott and R J HamersldquoCovalently modified silicon and diamond surfaces resistanceto nonspecific protein adsorption and optimization for biosens-ingrdquo Journal of the American Chemical Society vol 126 no 33pp 10220ndash10221 2004

[27] M Li K-G Neoh E-T Kang T Lau and E E ChiongldquoSurface modification of silicone with covalently immobilizedand crosslinked agarose for potential application in the inhibi-tion of infection and omental wrappingrdquo Advanced FunctionalMaterials vol 24 no 11 pp 1631ndash1643 2014

[28] G MacBeath and S L Schreiber ldquoPrinting proteins as microar-rays for high-throughput function determinationrdquo Science vol289 no 5485 pp 1760ndash1763 2000

[29] S B Nimse M D Sonawane K S Song and T Kim ldquoBio-marker detection technologies and future directionsrdquoThe Ana-lyst vol 141 no 3 pp 740ndash755 2016

[30] M D Sonawane S B Nimse K Song and T Kim ldquoDetectionquantification and profiling of PSA current microarray tech-nologies and future directionsrdquo RSC Advances vol 6 no 9 pp7599ndash7609 2016

[31] S B Nimse and T Kim ldquoBiological applications of function-alized calixarenesrdquo Chemical Society Reviews vol 42 no 1 pp366ndash386 2013

[32] K-S Song S B Nimse J Kim et al ldquo9GDNAChip microarraybased on the multiple interactions of 9 consecutive guaninesrdquoChemical Communications vol 47 no 25 pp 7101ndash7103 2011

[33] R J Chen S Bangsaruntip K A Drouvalakis et al ldquoNonco-valent functionalization of carbon nanotubes for highly specificelectronic biosensorsrdquo Proceedings of the National Academy ofSciences of the United States of America vol 100 no 9 pp 4984ndash4989 2003

[34] Y Lu W Shi J Qin and B Lin ldquoFabrication and characteri-zation of paper-based microfluidics prepared in nitrocellulosemembrane by wax printingrdquo Analytical Chemistry vol 82 no1 pp 329ndash335 2010

[35] P Zhang R Zhang M Gao and X Zhang ldquoNovel nitrocel-lulose membrane substrate for efficient analysis of circulatingtumor cells coupled with surface-enhanced raman scatteringimagingrdquo ACS Applied Materials and Interfaces vol 6 no 1 pp370ndash376 2014

[36] J-S Lee A K R Lytton-Jean S J Hurst and C AMirkin ldquoSil-ver nanoparticlemdasholigonucleotide conjugates based on DNAwith triple cyclic disulfide moietiesrdquo Nano Letters vol 7 no 7pp 2112ndash2115 2007

[37] S Y Song Y D Han K Kim S S Yang and H C YoonldquoA fluoro-microbead guiding chip for simple and quantifiableimmunoassay of cardiac troponin I (cTnI)rdquo Biosensors andBioelectronics vol 26 no 9 pp 3818ndash3824 2011

[38] S V Lemeshko T Powdrill Y Y Belosludtsev and M HoganldquoOligonucleotides form a duplex with non-helical properties ona positively charged surfacerdquoNucleic Acids Research vol 29 no14 pp 3051ndash3058 2001

[39] Z-L Zhi A K Powell and J E Turnbull ldquoFabrication ofcarbohydrate microarrays on gold surfaces direct attachmentof nonderivatized oligosaccharides to hydrazide-modified self-assembledmonolayersrdquoAnalytical Chemistry vol 78 no 14 pp4786ndash4793 2006

[40] S L Pan and L Rothberg ldquoChemical control of electrodefunctionalization for detection of DNA hybridization by elec-trochemical impedance spectroscopyrdquo Langmuir vol 21 no 3pp 1022ndash1027 2005

[41] Z Lu C M Li Q Zhou Q-L Bao and X Cui ldquoCovalentlylinked DNAprotein multilayered film for controlled DNAreleaserdquo Journal of Colloid and Interface Science vol 314 no 1pp 80ndash88 2007

[42] L-S Jang and H-J Liu ldquoFabrication of protein chips basedon 3-aminopropyltriethoxysilane as a monolayerrdquo BiomedicalMicrodevices vol 11 no 2 pp 331ndash338 2009

[43] F Fixe M Dufva P Telleman and C B Christensen ldquoFunc-tionalization of poly(methyl methacrylate) (PMMA) as a sub-strate for DNAmicroarraysrdquoNucleic Acids Research vol 32 no1 article e9 2004

[44] A Lueking M Horn H Eickhoff K Bussow H Lehrachand G Walter ldquoProtein microarrays for gene expression andantibody screeningrdquo Analytical Biochemistry vol 270 no 1 pp103ndash111 1999

[45] N Zammatteo L Jeanmart S Hamels et al ldquoComparisonbetween different strategies of covalent attachment of DNA toglass surfaces to build DNA microarraysrdquo Analytical Biochem-istry vol 280 no 1 pp 143ndash150 2000

[46] M Ozmen K Can I Akin et al ldquoSurface modification of glassbeads with glutaraldehyde characterization and their adsorp-tion property for metal ionsrdquo Journal of Hazardous Materialsvol 171 no 1ndash3 pp 594ndash600 2009

[47] C Funk PM Dietrich T Gross HMinW E S Unger andWWeigel ldquoEpoxy-functionalized surfaces for microarray appli-cations surface chemical analysis and fluorescence labeling ofsurface speciesrdquo Surface and Interface Analysis vol 44 no 8pp 890ndash894 2012

[48] S Mahajan P Kumar and K C Gupta ldquoOligonucleotide mic-roarrays immobilization of phosphorylated oligonucleotideson epoxylated surfacerdquo Bioconjugate Chemistry vol 17 no 5pp 1184ndash1189 2006

[49] M C Pirrung J D Davis and A L Odenbaugh ldquoNovelreagents and procedures for immobilization of DNA on glassmicrochips for primer extensionrdquo Langmuir vol 16 no 5 pp2185ndash2191 2000

[50] E Southern K Mir and M Shchepinov ldquoMolecular interac-tions on microarraysrdquo Nature Genetics vol 21 no 1 pp 5ndash91999

[51] M S Shchepinov S C Case-Green and E M SouthernldquoSteric factors influencing hybridisation of nucleic acids tooligonucleotide arraysrdquo Nucleic Acids Research vol 25 no 6pp 1155ndash1161 1997

[52] D A Tomalia A M Naylor and W A Goddard III ldquoStarbustdendrimers molecular-level control of size shape surfacechemistry topology and flexibility from atoms to macroscopicmatterrdquo Angewandte ChemiemdashInternational Edition in Englishvol 29 no 2 pp 138ndash175 1990

[53] R Benters C M Niemeyer D Drutschmann D Blohm andD Wohrle ldquoDNA microarrays with PAMAM dendritic linkersystemsrdquo Nucleic Acids Research vol 30 no 2 p e10 2002

[54] J H Moon J W Shin S Y Kim and J W Park ldquoFormationof uniform aminosilane thin layers an imine formation tomeasure relative surface density of the amine grouprdquo Langmuirvol 12 no 20 pp 4621ndash4624 1996

[55] J C Alwine D J Kemp and G R Stark ldquoMethod fordetection of specific RNAs in agarose gels by transfer to diazo-benzyloxymethyl-paper and hybridization with DNA probesrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 74 no 12 pp 5350ndash5354 1977

[56] P L Dolan Y Wu L K Ista R L Metzenberg M A Nelsonand G P Lopez ldquoRobust and efficient synthetic method for

Journal of Chemistry 17

forming DNA microarraysrdquo Nucleic Acids Research vol 29 no21 article e107 2001

[57] S B Nimse J Kim K-S Song et al ldquoSelective recognitionof the ditopic trimethylammonium cations by water-solubleaminocalix[4]arenerdquo Tetrahedron Letters vol 52 no 29 pp3751ndash3755 2011

[58] V-T Ta S B Nimse K-S Song et al ldquoCharacterization ofthe mixed self-assembled monolayer at the molecular scalerdquoChemical Communications vol 47 no 40 pp 11261ndash11263 2011

[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

[60] Y Lee E K Lee YW Cho et al ldquoProteoChip a highly sensitiveprotein microarray prepared by a novel method of proteinimmobilization for application of protein-protein interactionstudiesrdquo Proteomics vol 3 no 12 pp 2289ndash2304 2003

[61] S W Oh J D Moon H J Lim et al ldquoCalixarene derivative asa tool for highly sensitive detection and oriented immobiliza-tion of proteins in a microarray format through noncovalentmolecular interactionrdquo The FASEB Journal vol 19 no 10 pp1335ndash1337 2005

[62] S B Nimse K-S Song J Kim D R Sayyed and T Kimldquo9G DNAChip technology self-assembled monolayer (SAM)of ssDNA for ultra-sensitive detection of biomarkersrdquo Interna-tional Journal ofMolecular Sciences vol 14 no 3 pp 5723ndash57332013

[63] V-T Nguyen S B Nimse K-S Song et al ldquoHPAI 9GDNAChip discrimination of highly pathogenic influenza virusgenesrdquo Chemical Communications vol 48 no 38 pp 4582ndash4584 2012

[64] K-S Song S B Nimse J Kim D R Sayyed and T Kim ldquoAnew platform for a convenient genotyping systemrdquo ChemicalCommunications vol 49 no 26 pp 2661ndash2663 2013

[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

[67] F Hennrich C Chan VMoore M Rolandi andM OrsquoConnellCarbonNanotubes Properties and Applications Taylor amp FrancisGroup Abingdon UK 2006

[68] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

[69] C Singh M Shaffer I Kinloch and A Windle ldquoProductionof aligned carbon nanotubes by the CVD injection methodrdquoPhysica B Condensed Matter vol 323 no 1ndash4 pp 339ndash3402002

[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

[71] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

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Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

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Quantum Chemistry

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Organic Chemistry International

ElectrochemistryInternational Journal of

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CatalystsJournal of

Journal of Chemistry 7

(a) (b)

Figure 5 Contact angle comparison (a) bare glass and (b) AMCA modified glass slide (adapted from [32])

surface by using microarray After incubation at room tem-perature for 4 h the slides are washed to remove excess DNAsand driedThe free AMCAmolecules on the surface are thenblocked with the 4x SSC solution containing BSA and 01SDS Finally the slides are dried to obtain 9G DNAChips[63 64]

23 Carbon In recent years a nanoparticle-based structurelike nanotubes and nanowires has got tremendous attentionin biomedical and diagnostic fields [65 66] Before 1991 sp3hybridized form of carbon (diamond) sp2 hybridized formslike graphite and C60 fullerene were the only known formsof carbon with potential applications [67] In 1991 allotropeslike carbon nanotubes (CNT)were first reported and success-fully synthesized by Iijima with multiwall faces (MWCNT)[68]

Due to thermal electrical and magnetically uniqueproperties CNT became an important material in the devel-opment of biosensor platforms Commonly reportedmethodfor preparation of CNT includes chemical vapour deposition[69 70] arc discharge [71] and laser ablation [72]

Apart from CNT other carbon-based nanostructuresincluding carbondots carbon fibers andPDMSalso attractedresearchers due to their diverse properties for biomoleculeconjugation [73 74]Themajor advantage of carbon nanoma-terial is their large surface area which allows maximum spacefor biomolecule attachment

Immobilization of protein carbohydrate and nucleic acidon the CNT surfaces allows various biological applications[75 76]Themost important part in biomolecule conjugationis the surface functionalization of carbon-basedmaterialThegeneral techniques for carbon surface modification are (phy-sisorption) noncovalent and covalent modifications Thereare several reports on the different techniques of surfacemodification of carbon-based surfaces Due to the vastnessof the research on carbon-based material only few methodsare described in this paper

231 Physisorption Thehydrophobic character of CNT side-walls and the strong 120587-120587 interactions between the individualtubes causes them to aggregate and reduce their solubility in

common solvents which is considered as a problem for theirbiological applicationsHowever the samehydrophobic char-acter of theCNT surface is exploited for fabrication of biosen-sors by immobilizing biomolecules onto the CNT surfacesthrough hydrophobic-hydrophobic interactions [77ndash79]

The advantage of noncovalent interaction is a limiteddistortion of the three-dimensional structure of a protein orenzyme to be immobilized The hydrophobic amino acidsin proteins and enzymes develop the 120587-120587 interactions withthe hydrophobic part of CNT which make them adsorbedon the surface of CNT [80ndash83] As mentioned earlier theplatforms modified by noncovalent interactions suffer fromthe typical drawbacks of nonspecific interactions resulting inthe decreased specificity and sensitivity of a biosensor

To eliminate the problem of nonspecific interactions oftarget proteins with the sensor surface the novel approachof polyethylene oxide (PEO) polymer coating is adopted bymany researchers The PEO is well known for its proteinrepelling ability [84] Bomboi et al reported the use of Tween20 which is composed of three PEO branches and P103another molecule with hydrophobic polypropylene oxideunits to modify the surface of CNT before adsorption ofproteins on it The surface of Tween 20 and P103 modifiedCNT becomes slightly hydrophilic compared with bare CNTwhich results in the decrease in its interaction with thehydrophobic amino acid chains of biomarker proteins [85]

As depicted in Figure 6 for the selective immobilizationof streptavidin on the CNT surface Chen et al used mixednoncovalent and covalent approach which allows the highlyspecific immobilization of streptavidin and blocks the non-specific binding of other proteins like BSA [33]

Conjugation of a fluorescent molecule on the CNT sur-face is an immerging technology for highly sensitive detec-tion of biomolecules Nakayama-Ratchford et al reported theimmobilization of the fluorescent molecules like fluoresceinon the surface of CNT through 120587-120587 interactions [86] Thereare several reports on the applications of CNT surfaces mod-ified with the fluorescent molecules through noncovalentinteractions [87ndash90]

232 Chemical Modification To prevent the nonspecificbinding and to avoid the leaching of biomolecules from the

8 Journal of Chemistry

OH

OH

OH

O

HO

HO

HO

O

OO

OO

NH

O

NH

O

NH

OO

NH O

NH

O

NH

65 HON3

Boiling t = 8h

C2H4(NH2)2

NH2

H2N (CH2)2

(CH2)2

NH2(CH2)2

NH2(CH2)2

H2N (CH2)2

H2N (CH2)2

Scheme 5 Amine modification of CNT

BB

B

B B

B

SA SA

Figure 6 Streptavidin recognition by a nanotube coated with biot-inylated Tween (adapted from [33])

CNT surface a covalent modification technique is reportedThere are two types of covalent modifications namely (i)indirect method for example carboxylation of CNT surfaceand (ii) direct method for example fluorination of CNT sur-face where surface carbons change from sp2 to sp3 hybridiza-tion Esterification or amidation and sidewall covalent attach-ment are other approaches for covalent attachment [91 92]

(1) Carboxyl Modification The modification of the sensorsurfaces with the carboxyl groups is a general and highly usedsurface modification method Once the surface is modifiedwith the carboxyl groups it can be converted to a vari-ety of functional groups through reaction with appropriatereagents Furthermore the carboxylated surfaces can bedirectly conjugated with proteins or DNA through theiramine functional groups using coupling reagents A mixtureof sulphuric acid and nitric acid is a commonly used reagentfor the carboxylation of CNT surface

Marshall et al reported the method for carboxyl modifi-cation of CNT [93] According to this method a 2mg sampleof SWCNT is added to the 75 mixture of concentratedsulphuric acid and nitric acid (1mL) The mixture is allowedto sonicate in sonicator at 20∘CThe reaction mixture is thendiluted to 250mL by using deionized waterThe carboxylatedCNTs are then filtered through polytetrafluoroethylene filter(PTFE) of 045 120583m size Finally the collected nanotubes arewashedwith water at acidic pH followed by ethanol and driedin a vacuum desiccator

O OOH

O OOO

n

Figure 7 Structure of Epon resin 828

(2) Amine Modification Amide coupling is the most com-monly used conjugation technique in biomolecule attach-ment Either the amine or acid part of DNA or protein canbe used for conjugation using amide coupling reaction Forthe conjugation ofDNA toCNT through its phosphate groupamine modification is needed

Tam et al reported the DNA sensor based on the aminemodification of MWCNT as depicted in Scheme 5 [94] TheMWCNT were boiled in the 15M nitric acid for 12 h to gen-erate the carboxylated MWCNT The purified carboxylatedMWCNT were reacted with ethylenediamine to obtain theamine-modified MWCNT The amine-modified MWCNTwere conjugated to DNA by using EDC coupling reaction

Other reports for aminemodification of CNT include theuse of nitric acid and sulphuric acidmixture for carboxylationof the surface followed by ethylenediamine reaction [95]There are several reports on the covalent conjugation offluorescent molecules to the CNT surfaces [96ndash98]

(3) Epoxy Modification Epoxide group is a highly reactivefunctional group used in many substitution reactions as anelectrophile Eitan et al reported the covalent attachmentof epoxide-terminated molecules to carbon nanotubes byreaction between epoxide rings and carboxylic acid groupsthat are initially formed on the nanotube surface [99] Forepoxidation of CNT the surface is first carboxylated bydispersing the CNT in 75 solution of sulphuric acid in nitricacid for 3 h The purified carboxylated CNT were kept in theacetone with sonication for 1 hThen the solution containingthe carboxylated CNT is mixed with the solution of Eponresin 828 (Figure 7) in acetone to allow the reaction betweenEpon resin 828 and carboxyl groups on the CNT surface asdepicted in Scheme 6

Journal of Chemistry 9

O

O

O

O

R

OOCatalyst

O

O

O

O

O

O

CHHO

R

O

HC OH

R

O

H2C

O

HC OH

R

O

H2C

CH2

O

CHHO

R

O

CH2

HOHO

OHOH

+

Scheme 6 Epoxy modification of CNT

The mixture of solutions is sonicated for 1 h followedby stirring and heating at 70∘C The reaction was quenchedby addition of appropriate amount of potassium hydroxideThen the epoxilated CNT were purified and a number ofepoxy groups on the CNT surface were determined by usingthermogravimetric analysis

24 Nitrocellulose A PoC diagnosis system is always expe-cted to deliver final results in few minutes Though themicroarrays based on the glass and gold surfaces are usefulfor detection of multiple analytes at a time they need longertime for final data interpretation Microfluidic systems basedon paper or nitrocellulose membranes are emerging surfacesfor detection of bacteria viruses and proteins A paper isadvantageous due to its hydrophilic nature which allowsthe aqueous solutions to penetrate without the need of anyexternal force [100] The essential constituent of paper iscelluloseThe cellulose has hydroxyl functional groups whichcan be modified and changed according to surface propertiesneeded for a particular detection device [101] Due to lowcost and high availability paper is preferred for large scaleproduction Moreover the devices required for the tests areportable and disposable [102ndash105] The very first example ofpaper based detection is glucose detection in urine [106] andpregnancy test kit [107]There are different types of paper likeWhatman filter paper glossy paper [108] membrane and soforth Whatman filter is used because of its high penetrationand flow rate [109ndash112] but in some cases it does not havethe necessary characteristic for surface modification Mem-branes on the other hand are planner sheets and providelarger surface area for immobilization of biomolecules such

as DNA and protein The nitrocellulose (NC) membrane isbroadly used for immobilization of DNA [113] protein [114]and enzymes [115] due to its hydrophobic surface

241 Physical Adsorption Single-stranded DNAs are irre-versibly bound to the surface of the NCmembrane with non-covalent interactionsTheprimary interactions are hydropho-bic and electrostatic between the positively charged surfaceof the membrane and negatively charged DNAs The nitro-cellulose offers very high binding capacity for DNAs andproteins Fabrication of NC membranes can be done bydifferent methods including the photolithography The waxpatterningmethod is fast cheap and easy to process and doesnot need organic solvents The NCmembranes with the poresize of 045 120583mdo not need pretreatment for penetrationThefabrication process includesmainly printing and baking stepswhich can be finished in 10min As shown in Figure 8 firstlythe wax is printed on the surface of NCmembrane and bakedat 125∘C for 5min in the oven The melting of the wax onmembrane makes it more hydrophobic and affords surfacesuitable for the immunoassay For immunoassays Lu et alcoated the cAbs on the surface and the free area is blockedwith the 1 BSA

During baking melted wax passes through the mem-brane The 121∘ contact angle of backside membrane assuresthe melting of wax thoroughly The efficiency of wax treatedmembrane is compared with the untreated membrane byimmobilizing fluorescence labeled goat antihuman IgG Theimmobilization on wax printed surface is more uniform thanthe untreated membrane Apart from this a large volumeof liquid can be used because ring effect of protein on the

10 Journal of Chemistry

HO

OSH AuNP

AuNP-mAb

mAbEDCNHS

001M PBS

(CH2)15(CH2)11

NaBH4HAuCl4 + SH + HO

pH sim 74

Scheme 7 Immobilization on antibodies on AuNP

NC membrane

Cross section view

PrintingStep 1

Step 2 Baking

Wax patternedNC membrane

Wax is printed onto thesurface of NC membrane

Wax melts and penetratesthrough NC membrane

Nitrocellulose

Wax

Figure 8Wax printing on nitrocellulosemembranes (adapted from[34])

untreated membrane is avoided Wax printing method gen-erates 100 120583mmicrochannel which removes the micrometersize contaminants and makes the wax printed membranessuitable for the applications in microfluidic assays Apartfrom immobilization wax printing has application in dotimmunoassay and sample purifications [34]

Due to advantages of NC membrane for high bindingcapacity and good flow of solution it is also used on the chipsurfaces The glass slide can be coated with the 12 120583m layer ofNC to afford a platform with the intrinsic properties of NCThe solution of cAbs in PBS buffer containing 10 glycerolis then spotted on the modified surface After spotting theslides are incubated for one hour After incubation slides arewashed with 01 Tween 20 in PBS buffer and dried to gen-erate the platform for detection of biomarker proteins [116]

Apart from routine microarray applications NC mem-brane is also used for the detection of circulating tumor cells(CTC) as reported by Zhang et al The binding of CTCs bythe cAbs immobilized on the NC membrane is detected bySurface Enhanced Raman Scattering (SERS) as depicted inFigure 9

Usually the antibodies specific for cancer cells are usedas a capture substrate and immobilized on the surface TheNC membrane is cut into 1 cm times 1 cm pieces Then thesepieces are immersed in the ethanol and then tiled on thePMMA wafer After washing the membrane is activated byusing PBS buffer containing antibodies at 37∘C for 30minDuring this process the cAbs are avidly immobilized on theNC membrane The 1 BSA solution is loaded to block thefree surface area to avoid any background signals due tononspecific interactions Finally the membranes are washedwith PBS buffer and stored at 4∘CThe gold nanoparticle andRaman probes are used to detect the CTCs by SERS [35]

25 Gold Application of nanoparticles is amost focused areain the field of inorganic chemistry and it has also attractedimaginations of many biologists too Inorganic nanoparti-cles including gold silver and ferrous oxides have foundmany important applications in cell signaling drug deliveryand colorimetric and fluorescence-based detections Goldnanoparticles (AuNP) functionalized with proteins DNAsor Raman probes are well known in the field of biosensorsand nanobiotechnology for their applications in the molec-ular diagnostics [117ndash119] protein detection [120ndash122] generegulation [123] and cell imaging [124]

251 Covalent Modification

(1) Thiol Based Modification AuNPs are commonly usedin the electrochemical and optical detection systems Theconjugation with biomolecule does not change the opticalproperties ofAuNP [125]Di Pasqua et al reported thiolmod-ification for the detection of E coli O157H7 E coli specificantibodies were conjugated with the AuNPs [126] As shownin Scheme 7 the 10 nmAuNPs are carboxylated and then cou-pled to E coli specific monoclonal antibody (mAb) throughamide coupling

For the generation of AuNPs to the solution containing410mg of HAuCl

4sdot3H2O in 6mL of water ethanoic solutions

of 11-mercapto-1-undecanol and 16-mercaptohexadecanoicacid are added Upon addition of NaBH

4to this mixture at

0∘C the solution turns brown The product AuNP cappedwith alkanethiol pendant alcohol and carboxylic acid func-tional groups precipitate upon three hours of stirring Theprecipitated particles are then thoroughly washed with etha-nol and an ethanolic solution containing a small amountof 1M HCl The AuNPs are then dried under vacuum forten hours For the conjugation of mABs with the AuNPsthe carboxylic acid functional groups on the AuNPs are

Journal of Chemistry 11

SERSimaging

AuNPs

Raman labelNC membrane

AntibodyCancer cell

Figure 9 Detection of circulating tumor cells on NC membranes containing immobilized cAbs (adapted from [35])

activated by reacting the AuNPs with 1-ethyl-3-3(3-dimeth-ylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in the PBS buffer The mABs arethen added to this solution and the suspension is stirred atroom temperature for 30min The mAB-conjugated AuNPsare then collected by centrifugation and washing with PBSand ethanol The mAB-conjugated AuNPs successfully bindto E coli when incubated in PBS at pH 74 In other reportsthe AuNPs were found very effective in the detection ofcancerous pancreatic cells

The AuNPs are known to suffer from the problem ofaggregation upon long-term storage Therefore to solve thisissue the AuNPs are conjugated with the polyethylene glycol(PEG) to prevent their aggregation [127 128]The conjugationof PEGwith the AuNPsmakes the later hydrophilic thus pre-venting agglomeration induced by hydrophobic interactionsA PEGwith the heterobifunctional groups (dithiol at one endand a carboxyl at another end) is coated on the AuNP Thedithiol group allows stable anchoring heterobifunctional PEGligands on the surface of AuNP and the terminal carboxylgroup is used for coupling with antibodies The carboxy-terminated bifunctional PEG linker is synthesized by follow-ing a method reported by Eck et al which is depicted inScheme 8 The anionic polymerization of compound 1 withan excess of ethylene oxide allows synthesizing compound 2The treatment of compound 2 with chloroacetic acid at 60∘Callows generating compound 3 The reaction of an excess ofthe elemental bromine in dichloromethane at 0∘C for fourhours in the dark with compound 3 produces dibromidecompound 4 Compound 5 is obtained by reaction withcompound 4 in water with the excess of sodium hydrosulfidehydrate

The synthesized bifunctional PEG linker is then conju-gated with the citrate-stabilized gold nanoparticles by simpleligand exchangeThe citrate-stabilized gold nanoparticles areknown to aggregate in the buffer containing salts Thereforethe ligand exchange from citrate to PEG should be done inpure water The PEGylated AuNPs are conjugated to mono-clonal F19 antibodies for the detection of human pancreaticcarcinoma through EDCNHS coupling reaction [129]

OHO

(2) HCl

1

2

3

4

5

Br Br

HS SH

(CH2)9

(CH2)9

(CH2)9

(CH2)9

+

NaHDMF60∘C

(OCH2CH2)n

(OCH2CH2)n

(OCH2CH2)n

OCH2COOH

OCH2COOH

(CH2)9 (OCH2CH2)n OCH2COOH

OminusNa+

Br2

(2) Acetic acid (1) NaSHH2O

60∘C(1) ClCH2-COONa

Scheme 8 Synthesis of bifunctional PEG linker using conjugationwith AuNP

(2) Hydrazide Modification According to the report by Zhiet al the hydrazide-derivatized self-assembledmonolayer ona gold surface is used for the efficient and selective anchor-ing of oligosaccharide [39] The generated oligosaccharidemicroarrays allow the fluorescence-based detection of targetproteins The use of gold as a substrate for the fluorescence-based detection suffers from the drawbacks including flu-orescence quenching and nonspecific surface adsorption ofproteins However the use of120596-thiolated fatty acid (C

16) self-

assembledmonolayer between the gold surface andhydrazide

12 Journal of Chemistry

AuC C

C

C

OHOHO O

O

O

O

O

O

O

O

O

CHR

NN

H

N

N

N

H

NH

NH

NH

H

NH

C

O

O

O NNH

NH

HNH

H

S

S

S

S

HS Au

Au

Au

Au

Au

C16 SAM

Adipic dihydrazideEDC

(Sugar)R-CHO

Binding to protein

Sugarprobe

Protein Alexafluoro 532

SAM andblocking layer

Ab 2nd Ab

NH2

NH2H2N

CH2R

Scheme 9 Application of hydrazide-derivatized SAM on a goldsurface for the fabrication of oligosaccharide microarray (adaptedfrom [39])

groups minimizes the quenching effect Moreover the effec-tive blocking of the surface with the poly(ethylene glycol)aldehyde and BSA reduces the nonspecific adsorption ofprotein on the surface

For the fabrication of the reported oligosaccharidemicroarrays the gold substrate is prepared by following amethod depicted in Scheme 9 The self-assembled mono-layer (SAM) of 16-mercaptohexadecanoic acid (MHDA) isobtained by soaking the gold coated slides in the isobutylalcohol for 2 days The slides are then washed in ethanolto remove excess reagents and are dried under the nitrogenstream The carboxyl functional groups on the SAM areconverted to the hydrazide groups by incubation of the SAMcovered slides in the dimethyl sulfoxide solution containing1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and adipicdihydrazide The ethanol-washed and dried slides are thenused for the oligosaccharide printing to obtain oligosaccha-ride microarrays

The generated oligosaccharide microarray platformallows interrogation of carbohydrate-protein interactions ina high-throughput manner

26 Silver Similar to AuNPs silver nanoparticles (AgNP) arealso used for the immobilization of proteins and enzymesThe surface of AgNP allows adsorption of proteins Henceit can be utilized as a host matrix for various biomoleculesSilver is a suitable substrate for the immobilization of wholecell or the isolated enzymes [130 131]

Texp lt Tm

Ag

AgAg

Ag

AgAg

Texp gt Tm

Figure 10 AgNPs-oligonucleotide conjugates (adapted from [36])

261 Electrostatic Modification The electrostatic interac-tions allow the physical adsorption of biomolecules on thesurface of AgNPs Shen et al reported that the AgNPs aresynthesized by reduction of silver nitrate in the presence ofsodium citrate During the reduction process the solutionis sonicated for 15min to obtain the yellow silver colloidwhich is then kept at 4∘C for several days away from lightThen isolated nanoparticles can be used for physisorption ofproteins at a pH higher than their isoelectric point [132]

262 Covalent Modification As depicted in Scheme 10the AgNPs prepared by the citrate reduction method andstabilized with citrate [133] can be functionalized with car-boxyl groups upon treatment with 3-mercaptopropanoic acid(MPA) As reported by the Petkova et al for the immobi-lization of alcohol dehydrogenase from Thermoanaerobiumbrockii (TbADH) the carboxyl-modified AgNPs were treatedwith the solution containing TbADH under continuousstirring for 7 h at 26∘C a research by [134] The AgNPsmodified with the TbADH were successfully used for thebiotransformation studies

The application of a bifunctional linker for the modifica-tion of AgNPs is reported [135 136] The bifunctional linker11-mercaptoundecanoic acid was used with 1-octanethiol in1 1 ratio to generate the mixed SAM on the surface of AgNPThe IgG antibodies are then conjugated with the mixed SAMmodified AgNPs It is reported that upon covalent conjuga-tion of biomolecules with AgNPs their stability and activityis maintained [137]

According to another report on the covalent modifi-cation AgNPs-oligonucleotide conjugates are prepared byusing DNA and triple cyclic disulfide moieties [36] Asdepicted in Figure 10 the two types ofAgNPs-oligonucleotideconjugates with complementary DNA sequences undergoDNA hybridization driven coagulation resulting in the colorchange

As depicted in Figure 11 the AgNP-DNA conjugates wereprepared by treatment of AgNPs with the cyclic disulfidemodified oligonucleotide The AgNP and oligonucleotideswere allowed to react with each other with 1 4 ratio inthe presence of 1 sodium dodecyl sulfate and NaCl Theovernight incubation of solution results in the AgNP-DNAconjugates which are collected by centrifugation and washedto remove the excess DNAs

Journal of Chemistry 13

Ag AgMPAOH

OO OH

O

HOCitrate

Citrate

Ag

COOH

COOH

TbADHAg

CONH

COOH

TbADHOminusNa+

H2N

Scheme 10 Covalent conjugation of enzymes on the surface of carboxyl-modified AgNPs

OHO

EDC HOSu Bis-amino

polyethylene glycol

NH

OO

44GMBS N

H

OO N

H44

ON

O

O3

CoA

NH

OO N

H44

ON

O

O3

SHN

O

OH

OP O

OPO

O O

OHO

NNN

N

PO

OminusOminus

OminusOminus

NH2

NH2

Scheme 11 Covalent conjugation of coenzyme A to polystyrene nanoparticles

O OOO P

OHSS

5998400 (DSP)3-A10-ATT-ATC-ACT 3998400

DSP cyclic disulfide-containingphosphate derivative =

Figure 11 Conjugation of AgNPs with oligonucleotides by usingDSP as a linker molecule (adapted from [36])

27 Polystyrene Polystyrene is an aromatic polymerobtained by polymerization of styrene monomers [138] Thepolystyrene-based NPs are widely used in the moleculardiagnostics for the detection of biomarker proteins andgenomic DNAs Polystyrene can be employed as a coating ona variety of nanoparticles as its functional groups can be easilymodified or conjugated with other molecules The otherapplication of polystyrene is in the fabrication of fluorescencebeads (FBs) The fluorescence molecules are loaded into thepolystyrene shell to produce FBs which are then used invarious sensing applications The polystyrene is also used tocoat the magnetic NPs so they can be conjugated with otherbiomolecules such as DNA and Proteins The applications ofpolystyrene include but are not limited to the detection ofE coli [139] the detection of cardiac Troponin T (cTnT) thedetection of Herpes simplex virus and many more

271 Covalent Modification Covalent modification throughcarboxyl group iswell known formodification of biomolecule

Most of the polystyrene-based nanoparticles bear large num-bers of pendant carboxyl which increases the loading amountof biomolecule

Enzyme catalyzed covalent immobilization of the pro-teins bearing a small 12-mer ldquoybbRrdquo tag onto the polystyrenenanoparticles (PSNP) is recently reported by Wong et al[140] As depicted in Scheme 11 the carboxyl-PSNPs werereacted with the bis-amino-polyethylene glycol in the pres-ence of HOSu and EDC to generate the amino-pegylatedPSNPs These PSNPs are then reacted with the g-maleimi-dobutyric acid succinimidyl (GMBS) to obtain maleimide-functionalized PSNPs The maleimide-functionalized PSNPsupon chemoligation with coenzyme A (CoA) produce theCoA-derivatized PSNPs

As depicted in Scheme 12 the protein of interest bearingybbR-tag is immobilized on the CoA-derivatized PSNPsThephosphopantetheinyl transferase (Sfp) catalyzed the reactionbetween the serine residue of the ybbR-tag and the phos-phopantetheine moiety of CoA with the simultaneous lossof 3101584051015840-adenine diphosphate results in the attachment ofproteins onto the surface of PSNPs It is reported that theenzymes immobilized by this method retain their activity

There are several reports on the use of fluoromicrobeadsfor the detection of biomarkers Primarily the fluoromi-crobeads are made up of carboxylated polystyrene as a coat-ingmaterial entrapping the fluorescentmolecules Accordingto the recent report by Song et al [37] the fluoromicrobeadswere used for the detection of the cTnT on the proteinmicroarray as depicted in Figure 12

The carboxylate modified fluoromicrobeads were conju-gated with the anti cTnI mAb through EDCNHS-mediated

14 Journal of Chemistry

HN

O

OH

OP

O

O

PO

O

OHO

N

NN

P

O

S

HN

O

Coenzyme A

Phosphopantetheine

PO

O

O

OHO

N Sfp

NN

N

P

O

ybbr-protein

HN

O

OH

OP

O

O

S

HN

O

NH2

NH2

Ominus

Ominus

Ominus

minusO

minusO

Mg2+

HO∙∙

Ominus

OminusOminus

minusO

N

O

Polystyrenenanoparticle

Scheme 12 Protein conjugation to polystyrene NP

System 1 antibody-conjugated fluoromicrobeads

System 2 avidin-conjugated fluoromicrobeads

DTSP SAM

Anti-cTnI cAb

cTnI

Figure 12 Application of the polystyrene-coated fluoromicrobeadsfor the detection of cTnI on the protein microarray (adapted from[37])

coupling reaction The use of fluoromicrobeads alloweddetecting the cTnI in plasma samples with a range of 01ndash100 ngmL

272 Affinity-Based Modification The affinity interactionsare used for the attachment of oligonucleotides with thefluoromicrobeads or polystyrene-coated magnetic beads Togenerate the oligonucleotide conjugated fluoromicrobeads ormagnetic beads respective polystyrene-coated beads are firstconjugated with the streptavidin using the EDCNHS cou-pling reaction as reported by Zhang et al [141] As depicted

B

B

MB MB

MB

BB

Magnetic bead

Streptavidin

DNA labeled biotin

Figure 13 DNA attachment to the magnetic beads

in Figure 13 the streptavidinmodified beads are then allowedto incubate with the biotinylated oligonucleotides Due to theaffinity of biotin for streptavidin the biotinylated oligonu-cleotides can be readily immobilized on the streptavidincoated beads

The binding affinity of streptavidin and biotin in solutionis up to 25 times 1013 (molL)minus1 [142] This interaction is about amillion times stronger than the antigen and antibody inter-action The antibodies directly immobilized onto the sur-face lose 90 of their biological activity [143] Howeverthe biotinylated antibodies immobilized on the streptavidincoated surface can retain their bioactivity [144]

Journal of Chemistry 15

3 Conclusions

Surface modification techniques of the materials used asplatforms in the fabrication of biosensors are reviewed inthis paper There are several reports on materials and vari-ous methods for altering their physicochemical propertiesHence one of these methods can be chosen according tothe targeted use and needed physiochemical properties Itis important to note that the performance of the biosensoris highly dependent on the substrate material used and itsmeticulous modification for particular applications There-fore it is critical to understand the principles of a biosensor toidentify the correct substrate material and its surface modifi-cation chemistry Furthermore it is important to look at thelatest advances in the materials and techniques used for thefabrication of a biosensor before the processing

Competing Interests

All authors declare that there is no conflict of interests

Acknowledgments

This research was supported by the Hallym UniversityResearch Fund (HRF-201601-010) This work was also sup-ported by the fund obtained through Industry-Academic col-laboration between Biometrix Technology Inc (ChuncheonSouth Korea) and Hallym University

References

[1] A Sassolas B D Leca-Bouvier and L J Blum ldquoDNA biosen-sors andmicroarraysrdquoChemical Reviews vol 108 no 1 pp 109ndash139 2008

[2] A Cavalcanti B Shirinzadeh M Zhang and L C KretlyldquoNanorobot hardware architecture for medical defenserdquo Sen-sors vol 8 no 5 pp 2932ndash2958 2008

[3] R-Q Zhang S-L Liu W Zhao et al ldquoA simple point-of-caremicrofluidic immunomagnetic fluorescence assay for path-ogensrdquo Analytical Chemistry vol 85 no 5 pp 2645ndash2651 2013

[4] S B Nimse K S Song M D Sonawane D R Sayyed and TS Kim ldquoImmobilization techniques for microarray challengesand applicationsrdquo Sensors vol 14 no 12 pp 22208ndash22229 2014

[5] A P F Turner ldquoBiosensors sense and sensibilityrdquo ChemicalSociety Reviews vol 42 no 8 pp 3184ndash3196 2013

[6] L Wu and X Qu ldquoCancer biomarker detection recent achieve-ments and challengesrdquoChemical Society Reviews vol 44 no 10pp 2963ndash2997 2015

[7] K Ariga Q Ji T Mori et al ldquoEnzyme nanoarchitectonicsorganization and device applicationrdquo Chemical Society Reviewsvol 42 no 15 pp 6322ndash6345 2013

[8] W-W Zhao J-J Xu and H-Y Chen ldquoPhotoelectrochemicalDNA biosensorsrdquo Chemical Reviews vol 114 no 15 pp 7421ndash7441 2014

[9] Q Liu C Wu H Cai N Hu J Zhou and P Wang ldquoCell-basedbiosensors and their application in biomedicinerdquo ChemicalReviews vol 114 no 12 pp 6423ndash6461 2014

[10] X Zhao S Nampalli A J Serino and S Kumar ldquoImmobi-lization of oligodeoxyribonucleotides with multiple anchors to

microchipsrdquo Nucleic Acids Research vol 29 no 4 pp 955ndash9592001

[11] P Kumar S K Agrawal A Misra and K C Gupta ldquoA newheterobifunctional reagent for immobilization of biomoleculeson glass surfacerdquo Bioorganic 120572Medicinal Chemistry Letters vol14 no 5 pp 1097ndash1099 2004

[12] F Secundo ldquoConformational changes of enzymes upon immo-bilisationrdquo Chemical Society Reviews vol 42 no 15 pp 6250ndash6261 2013

[13] S Lee S Kim J Malm O C Jeong H Lilja and T LaurellldquoImproved porous silicon microarray based prostate specificantigen immunoassay by optimized surface density of thecapture antibodyrdquoAnalytica Chimica Acta vol 796 pp 108ndash1142013

[14] K Jaras A A Tajudin A Ressine et al ldquoENSAM europiumnanoparticles for signal enhancement of antibody microarrayson nanoporous siliconrdquo Journal of Proteome Research vol 7 no3 pp 1308ndash1314 2008

[15] C Steinhauer A Ressine G Marko-Varga T Laurell C AK Borrebaeck and C Wingren ldquoBiocompatibility of surfacesfor antibody microarrays design of macroporous silicon sub-stratesrdquo Analytical Biochemistry vol 341 no 2 pp 204ndash2132005

[16] K Jaras B Adler A Tojo et al ldquoPorous silicon antibodymicroarrays for quantitative analysis measurement of free andtotal PSA in clinical plasma samplesrdquo Clinica Chimica Acta vol414 pp 76ndash84 2012

[17] S W Lee K Hosokawa S Kim et al ldquoA highly sensitive poroussilicon (P-Si)-based human Kallikrein 2 (hK2) immunoassayplatform toward accurate diagnosis of prostate cancerrdquo Sensorsvol 15 no 5 pp 11972ndash11987 2015

[18] C Roychaudhuri ldquoA review on porous silicon based electro-chemical biosensors beyond surface area enhancement factorrdquoSensors and Actuators B Chemical vol 210 pp 310ndash323 2015

[19] ARessine S EkstromGMarko-Varga andT Laurell ldquoMacro-nanoporous silicon as a support for high-performance proteinmicroarraysrdquo Analytical Chemistry vol 75 no 24 pp 6968ndash6974 2003

[20] S Lee E Silajdzic H Yang et al ldquoA porous silicon immunoas-say platform for fluorometric determination of 120572-synuclein inhuman cerebrospinal fluidrdquo Microchimica Acta vol 181 no 9-10 pp 1143ndash1149 2014

[21] S Belhousse N Belhaneche-Bensemra K Lasmi et alldquoModified porous silicon for electrochemical sensor of para-nitrophenolrdquo Materials Science and Engineering B vol 189 pp76ndash81 2014

[22] N Reta A Michelmore C Saint B Prieto-Simon and NH Voelcker ldquoPorous silicon membrane-modified electrodesfor label-free voltammetric detection of MS2 bacteriophagerdquoBiosensors and Bioelectronics vol 80 pp 47ndash53 2016

[23] B Guan A Magenau S Ciampi K Gaus P J Reece and J JGooding ldquoAntibody modified porous silicon microparticles forthe selective capture of cellsrdquo Bioconjugate Chemistry vol 25no 7 pp 1282ndash1289 2014

[24] S Vutti N Buch-Manson S Schoffelen N Bovet K LMartinez and M Meldal ldquoCovalent and stable CuAAC mod-ification of silicon surfaces for control of cell adhesionrdquo Chem-BioChem vol 16 no 5 pp 782ndash791 2015

[25] A M Rossi L Wang V Reipa and T E Murphy ldquoPoroussilicon biosensor for detection of virusesrdquo Biosensors andBioelectronics vol 23 no 5 pp 741ndash745 2007

16 Journal of Chemistry

[26] T L Lasseter B H Clare N L Abbott and R J HamersldquoCovalently modified silicon and diamond surfaces resistanceto nonspecific protein adsorption and optimization for biosens-ingrdquo Journal of the American Chemical Society vol 126 no 33pp 10220ndash10221 2004

[27] M Li K-G Neoh E-T Kang T Lau and E E ChiongldquoSurface modification of silicone with covalently immobilizedand crosslinked agarose for potential application in the inhibi-tion of infection and omental wrappingrdquo Advanced FunctionalMaterials vol 24 no 11 pp 1631ndash1643 2014

[28] G MacBeath and S L Schreiber ldquoPrinting proteins as microar-rays for high-throughput function determinationrdquo Science vol289 no 5485 pp 1760ndash1763 2000

[29] S B Nimse M D Sonawane K S Song and T Kim ldquoBio-marker detection technologies and future directionsrdquoThe Ana-lyst vol 141 no 3 pp 740ndash755 2016

[30] M D Sonawane S B Nimse K Song and T Kim ldquoDetectionquantification and profiling of PSA current microarray tech-nologies and future directionsrdquo RSC Advances vol 6 no 9 pp7599ndash7609 2016

[31] S B Nimse and T Kim ldquoBiological applications of function-alized calixarenesrdquo Chemical Society Reviews vol 42 no 1 pp366ndash386 2013

[32] K-S Song S B Nimse J Kim et al ldquo9GDNAChip microarraybased on the multiple interactions of 9 consecutive guaninesrdquoChemical Communications vol 47 no 25 pp 7101ndash7103 2011

[33] R J Chen S Bangsaruntip K A Drouvalakis et al ldquoNonco-valent functionalization of carbon nanotubes for highly specificelectronic biosensorsrdquo Proceedings of the National Academy ofSciences of the United States of America vol 100 no 9 pp 4984ndash4989 2003

[34] Y Lu W Shi J Qin and B Lin ldquoFabrication and characteri-zation of paper-based microfluidics prepared in nitrocellulosemembrane by wax printingrdquo Analytical Chemistry vol 82 no1 pp 329ndash335 2010

[35] P Zhang R Zhang M Gao and X Zhang ldquoNovel nitrocel-lulose membrane substrate for efficient analysis of circulatingtumor cells coupled with surface-enhanced raman scatteringimagingrdquo ACS Applied Materials and Interfaces vol 6 no 1 pp370ndash376 2014

[36] J-S Lee A K R Lytton-Jean S J Hurst and C AMirkin ldquoSil-ver nanoparticlemdasholigonucleotide conjugates based on DNAwith triple cyclic disulfide moietiesrdquo Nano Letters vol 7 no 7pp 2112ndash2115 2007

[37] S Y Song Y D Han K Kim S S Yang and H C YoonldquoA fluoro-microbead guiding chip for simple and quantifiableimmunoassay of cardiac troponin I (cTnI)rdquo Biosensors andBioelectronics vol 26 no 9 pp 3818ndash3824 2011

[38] S V Lemeshko T Powdrill Y Y Belosludtsev and M HoganldquoOligonucleotides form a duplex with non-helical properties ona positively charged surfacerdquoNucleic Acids Research vol 29 no14 pp 3051ndash3058 2001

[39] Z-L Zhi A K Powell and J E Turnbull ldquoFabrication ofcarbohydrate microarrays on gold surfaces direct attachmentof nonderivatized oligosaccharides to hydrazide-modified self-assembledmonolayersrdquoAnalytical Chemistry vol 78 no 14 pp4786ndash4793 2006

[40] S L Pan and L Rothberg ldquoChemical control of electrodefunctionalization for detection of DNA hybridization by elec-trochemical impedance spectroscopyrdquo Langmuir vol 21 no 3pp 1022ndash1027 2005

[41] Z Lu C M Li Q Zhou Q-L Bao and X Cui ldquoCovalentlylinked DNAprotein multilayered film for controlled DNAreleaserdquo Journal of Colloid and Interface Science vol 314 no 1pp 80ndash88 2007

[42] L-S Jang and H-J Liu ldquoFabrication of protein chips basedon 3-aminopropyltriethoxysilane as a monolayerrdquo BiomedicalMicrodevices vol 11 no 2 pp 331ndash338 2009

[43] F Fixe M Dufva P Telleman and C B Christensen ldquoFunc-tionalization of poly(methyl methacrylate) (PMMA) as a sub-strate for DNAmicroarraysrdquoNucleic Acids Research vol 32 no1 article e9 2004

[44] A Lueking M Horn H Eickhoff K Bussow H Lehrachand G Walter ldquoProtein microarrays for gene expression andantibody screeningrdquo Analytical Biochemistry vol 270 no 1 pp103ndash111 1999

[45] N Zammatteo L Jeanmart S Hamels et al ldquoComparisonbetween different strategies of covalent attachment of DNA toglass surfaces to build DNA microarraysrdquo Analytical Biochem-istry vol 280 no 1 pp 143ndash150 2000

[46] M Ozmen K Can I Akin et al ldquoSurface modification of glassbeads with glutaraldehyde characterization and their adsorp-tion property for metal ionsrdquo Journal of Hazardous Materialsvol 171 no 1ndash3 pp 594ndash600 2009

[47] C Funk PM Dietrich T Gross HMinW E S Unger andWWeigel ldquoEpoxy-functionalized surfaces for microarray appli-cations surface chemical analysis and fluorescence labeling ofsurface speciesrdquo Surface and Interface Analysis vol 44 no 8pp 890ndash894 2012

[48] S Mahajan P Kumar and K C Gupta ldquoOligonucleotide mic-roarrays immobilization of phosphorylated oligonucleotideson epoxylated surfacerdquo Bioconjugate Chemistry vol 17 no 5pp 1184ndash1189 2006

[49] M C Pirrung J D Davis and A L Odenbaugh ldquoNovelreagents and procedures for immobilization of DNA on glassmicrochips for primer extensionrdquo Langmuir vol 16 no 5 pp2185ndash2191 2000

[50] E Southern K Mir and M Shchepinov ldquoMolecular interac-tions on microarraysrdquo Nature Genetics vol 21 no 1 pp 5ndash91999

[51] M S Shchepinov S C Case-Green and E M SouthernldquoSteric factors influencing hybridisation of nucleic acids tooligonucleotide arraysrdquo Nucleic Acids Research vol 25 no 6pp 1155ndash1161 1997

[52] D A Tomalia A M Naylor and W A Goddard III ldquoStarbustdendrimers molecular-level control of size shape surfacechemistry topology and flexibility from atoms to macroscopicmatterrdquo Angewandte ChemiemdashInternational Edition in Englishvol 29 no 2 pp 138ndash175 1990

[53] R Benters C M Niemeyer D Drutschmann D Blohm andD Wohrle ldquoDNA microarrays with PAMAM dendritic linkersystemsrdquo Nucleic Acids Research vol 30 no 2 p e10 2002

[54] J H Moon J W Shin S Y Kim and J W Park ldquoFormationof uniform aminosilane thin layers an imine formation tomeasure relative surface density of the amine grouprdquo Langmuirvol 12 no 20 pp 4621ndash4624 1996

[55] J C Alwine D J Kemp and G R Stark ldquoMethod fordetection of specific RNAs in agarose gels by transfer to diazo-benzyloxymethyl-paper and hybridization with DNA probesrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 74 no 12 pp 5350ndash5354 1977

[56] P L Dolan Y Wu L K Ista R L Metzenberg M A Nelsonand G P Lopez ldquoRobust and efficient synthetic method for

Journal of Chemistry 17

forming DNA microarraysrdquo Nucleic Acids Research vol 29 no21 article e107 2001

[57] S B Nimse J Kim K-S Song et al ldquoSelective recognitionof the ditopic trimethylammonium cations by water-solubleaminocalix[4]arenerdquo Tetrahedron Letters vol 52 no 29 pp3751ndash3755 2011

[58] V-T Ta S B Nimse K-S Song et al ldquoCharacterization ofthe mixed self-assembled monolayer at the molecular scalerdquoChemical Communications vol 47 no 40 pp 11261ndash11263 2011

[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

[60] Y Lee E K Lee YW Cho et al ldquoProteoChip a highly sensitiveprotein microarray prepared by a novel method of proteinimmobilization for application of protein-protein interactionstudiesrdquo Proteomics vol 3 no 12 pp 2289ndash2304 2003

[61] S W Oh J D Moon H J Lim et al ldquoCalixarene derivative asa tool for highly sensitive detection and oriented immobiliza-tion of proteins in a microarray format through noncovalentmolecular interactionrdquo The FASEB Journal vol 19 no 10 pp1335ndash1337 2005

[62] S B Nimse K-S Song J Kim D R Sayyed and T Kimldquo9G DNAChip technology self-assembled monolayer (SAM)of ssDNA for ultra-sensitive detection of biomarkersrdquo Interna-tional Journal ofMolecular Sciences vol 14 no 3 pp 5723ndash57332013

[63] V-T Nguyen S B Nimse K-S Song et al ldquoHPAI 9GDNAChip discrimination of highly pathogenic influenza virusgenesrdquo Chemical Communications vol 48 no 38 pp 4582ndash4584 2012

[64] K-S Song S B Nimse J Kim D R Sayyed and T Kim ldquoAnew platform for a convenient genotyping systemrdquo ChemicalCommunications vol 49 no 26 pp 2661ndash2663 2013

[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

[67] F Hennrich C Chan VMoore M Rolandi andM OrsquoConnellCarbonNanotubes Properties and Applications Taylor amp FrancisGroup Abingdon UK 2006

[68] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

[69] C Singh M Shaffer I Kinloch and A Windle ldquoProductionof aligned carbon nanotubes by the CVD injection methodrdquoPhysica B Condensed Matter vol 323 no 1ndash4 pp 339ndash3402002

[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

[71] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

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Analytical Methods in Chemistry

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Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

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Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

8 Journal of Chemistry

OH

OH

OH

O

HO

HO

HO

O

OO

OO

NH

O

NH

O

NH

OO

NH O

NH

O

NH

65 HON3

Boiling t = 8h

C2H4(NH2)2

NH2

H2N (CH2)2

(CH2)2

NH2(CH2)2

NH2(CH2)2

H2N (CH2)2

H2N (CH2)2

Scheme 5 Amine modification of CNT

BB

B

B B

B

SA SA

Figure 6 Streptavidin recognition by a nanotube coated with biot-inylated Tween (adapted from [33])

CNT surface a covalent modification technique is reportedThere are two types of covalent modifications namely (i)indirect method for example carboxylation of CNT surfaceand (ii) direct method for example fluorination of CNT sur-face where surface carbons change from sp2 to sp3 hybridiza-tion Esterification or amidation and sidewall covalent attach-ment are other approaches for covalent attachment [91 92]

(1) Carboxyl Modification The modification of the sensorsurfaces with the carboxyl groups is a general and highly usedsurface modification method Once the surface is modifiedwith the carboxyl groups it can be converted to a vari-ety of functional groups through reaction with appropriatereagents Furthermore the carboxylated surfaces can bedirectly conjugated with proteins or DNA through theiramine functional groups using coupling reagents A mixtureof sulphuric acid and nitric acid is a commonly used reagentfor the carboxylation of CNT surface

Marshall et al reported the method for carboxyl modifi-cation of CNT [93] According to this method a 2mg sampleof SWCNT is added to the 75 mixture of concentratedsulphuric acid and nitric acid (1mL) The mixture is allowedto sonicate in sonicator at 20∘CThe reaction mixture is thendiluted to 250mL by using deionized waterThe carboxylatedCNTs are then filtered through polytetrafluoroethylene filter(PTFE) of 045 120583m size Finally the collected nanotubes arewashedwith water at acidic pH followed by ethanol and driedin a vacuum desiccator

O OOH

O OOO

n

Figure 7 Structure of Epon resin 828

(2) Amine Modification Amide coupling is the most com-monly used conjugation technique in biomolecule attach-ment Either the amine or acid part of DNA or protein canbe used for conjugation using amide coupling reaction Forthe conjugation ofDNA toCNT through its phosphate groupamine modification is needed

Tam et al reported the DNA sensor based on the aminemodification of MWCNT as depicted in Scheme 5 [94] TheMWCNT were boiled in the 15M nitric acid for 12 h to gen-erate the carboxylated MWCNT The purified carboxylatedMWCNT were reacted with ethylenediamine to obtain theamine-modified MWCNT The amine-modified MWCNTwere conjugated to DNA by using EDC coupling reaction

Other reports for aminemodification of CNT include theuse of nitric acid and sulphuric acidmixture for carboxylationof the surface followed by ethylenediamine reaction [95]There are several reports on the covalent conjugation offluorescent molecules to the CNT surfaces [96ndash98]

(3) Epoxy Modification Epoxide group is a highly reactivefunctional group used in many substitution reactions as anelectrophile Eitan et al reported the covalent attachmentof epoxide-terminated molecules to carbon nanotubes byreaction between epoxide rings and carboxylic acid groupsthat are initially formed on the nanotube surface [99] Forepoxidation of CNT the surface is first carboxylated bydispersing the CNT in 75 solution of sulphuric acid in nitricacid for 3 h The purified carboxylated CNT were kept in theacetone with sonication for 1 hThen the solution containingthe carboxylated CNT is mixed with the solution of Eponresin 828 (Figure 7) in acetone to allow the reaction betweenEpon resin 828 and carboxyl groups on the CNT surface asdepicted in Scheme 6

Journal of Chemistry 9

O

O

O

O

R

OOCatalyst

O

O

O

O

O

O

CHHO

R

O

HC OH

R

O

H2C

O

HC OH

R

O

H2C

CH2

O

CHHO

R

O

CH2

HOHO

OHOH

+

Scheme 6 Epoxy modification of CNT

The mixture of solutions is sonicated for 1 h followedby stirring and heating at 70∘C The reaction was quenchedby addition of appropriate amount of potassium hydroxideThen the epoxilated CNT were purified and a number ofepoxy groups on the CNT surface were determined by usingthermogravimetric analysis

24 Nitrocellulose A PoC diagnosis system is always expe-cted to deliver final results in few minutes Though themicroarrays based on the glass and gold surfaces are usefulfor detection of multiple analytes at a time they need longertime for final data interpretation Microfluidic systems basedon paper or nitrocellulose membranes are emerging surfacesfor detection of bacteria viruses and proteins A paper isadvantageous due to its hydrophilic nature which allowsthe aqueous solutions to penetrate without the need of anyexternal force [100] The essential constituent of paper iscelluloseThe cellulose has hydroxyl functional groups whichcan be modified and changed according to surface propertiesneeded for a particular detection device [101] Due to lowcost and high availability paper is preferred for large scaleproduction Moreover the devices required for the tests areportable and disposable [102ndash105] The very first example ofpaper based detection is glucose detection in urine [106] andpregnancy test kit [107]There are different types of paper likeWhatman filter paper glossy paper [108] membrane and soforth Whatman filter is used because of its high penetrationand flow rate [109ndash112] but in some cases it does not havethe necessary characteristic for surface modification Mem-branes on the other hand are planner sheets and providelarger surface area for immobilization of biomolecules such

as DNA and protein The nitrocellulose (NC) membrane isbroadly used for immobilization of DNA [113] protein [114]and enzymes [115] due to its hydrophobic surface

241 Physical Adsorption Single-stranded DNAs are irre-versibly bound to the surface of the NCmembrane with non-covalent interactionsTheprimary interactions are hydropho-bic and electrostatic between the positively charged surfaceof the membrane and negatively charged DNAs The nitro-cellulose offers very high binding capacity for DNAs andproteins Fabrication of NC membranes can be done bydifferent methods including the photolithography The waxpatterningmethod is fast cheap and easy to process and doesnot need organic solvents The NCmembranes with the poresize of 045 120583mdo not need pretreatment for penetrationThefabrication process includesmainly printing and baking stepswhich can be finished in 10min As shown in Figure 8 firstlythe wax is printed on the surface of NCmembrane and bakedat 125∘C for 5min in the oven The melting of the wax onmembrane makes it more hydrophobic and affords surfacesuitable for the immunoassay For immunoassays Lu et alcoated the cAbs on the surface and the free area is blockedwith the 1 BSA

During baking melted wax passes through the mem-brane The 121∘ contact angle of backside membrane assuresthe melting of wax thoroughly The efficiency of wax treatedmembrane is compared with the untreated membrane byimmobilizing fluorescence labeled goat antihuman IgG Theimmobilization on wax printed surface is more uniform thanthe untreated membrane Apart from this a large volumeof liquid can be used because ring effect of protein on the

10 Journal of Chemistry

HO

OSH AuNP

AuNP-mAb

mAbEDCNHS

001M PBS

(CH2)15(CH2)11

NaBH4HAuCl4 + SH + HO

pH sim 74

Scheme 7 Immobilization on antibodies on AuNP

NC membrane

Cross section view

PrintingStep 1

Step 2 Baking

Wax patternedNC membrane

Wax is printed onto thesurface of NC membrane

Wax melts and penetratesthrough NC membrane

Nitrocellulose

Wax

Figure 8Wax printing on nitrocellulosemembranes (adapted from[34])

untreated membrane is avoided Wax printing method gen-erates 100 120583mmicrochannel which removes the micrometersize contaminants and makes the wax printed membranessuitable for the applications in microfluidic assays Apartfrom immobilization wax printing has application in dotimmunoassay and sample purifications [34]

Due to advantages of NC membrane for high bindingcapacity and good flow of solution it is also used on the chipsurfaces The glass slide can be coated with the 12 120583m layer ofNC to afford a platform with the intrinsic properties of NCThe solution of cAbs in PBS buffer containing 10 glycerolis then spotted on the modified surface After spotting theslides are incubated for one hour After incubation slides arewashed with 01 Tween 20 in PBS buffer and dried to gen-erate the platform for detection of biomarker proteins [116]

Apart from routine microarray applications NC mem-brane is also used for the detection of circulating tumor cells(CTC) as reported by Zhang et al The binding of CTCs bythe cAbs immobilized on the NC membrane is detected bySurface Enhanced Raman Scattering (SERS) as depicted inFigure 9

Usually the antibodies specific for cancer cells are usedas a capture substrate and immobilized on the surface TheNC membrane is cut into 1 cm times 1 cm pieces Then thesepieces are immersed in the ethanol and then tiled on thePMMA wafer After washing the membrane is activated byusing PBS buffer containing antibodies at 37∘C for 30minDuring this process the cAbs are avidly immobilized on theNC membrane The 1 BSA solution is loaded to block thefree surface area to avoid any background signals due tononspecific interactions Finally the membranes are washedwith PBS buffer and stored at 4∘CThe gold nanoparticle andRaman probes are used to detect the CTCs by SERS [35]

25 Gold Application of nanoparticles is amost focused areain the field of inorganic chemistry and it has also attractedimaginations of many biologists too Inorganic nanoparti-cles including gold silver and ferrous oxides have foundmany important applications in cell signaling drug deliveryand colorimetric and fluorescence-based detections Goldnanoparticles (AuNP) functionalized with proteins DNAsor Raman probes are well known in the field of biosensorsand nanobiotechnology for their applications in the molec-ular diagnostics [117ndash119] protein detection [120ndash122] generegulation [123] and cell imaging [124]

251 Covalent Modification

(1) Thiol Based Modification AuNPs are commonly usedin the electrochemical and optical detection systems Theconjugation with biomolecule does not change the opticalproperties ofAuNP [125]Di Pasqua et al reported thiolmod-ification for the detection of E coli O157H7 E coli specificantibodies were conjugated with the AuNPs [126] As shownin Scheme 7 the 10 nmAuNPs are carboxylated and then cou-pled to E coli specific monoclonal antibody (mAb) throughamide coupling

For the generation of AuNPs to the solution containing410mg of HAuCl

4sdot3H2O in 6mL of water ethanoic solutions

of 11-mercapto-1-undecanol and 16-mercaptohexadecanoicacid are added Upon addition of NaBH

4to this mixture at

0∘C the solution turns brown The product AuNP cappedwith alkanethiol pendant alcohol and carboxylic acid func-tional groups precipitate upon three hours of stirring Theprecipitated particles are then thoroughly washed with etha-nol and an ethanolic solution containing a small amountof 1M HCl The AuNPs are then dried under vacuum forten hours For the conjugation of mABs with the AuNPsthe carboxylic acid functional groups on the AuNPs are

Journal of Chemistry 11

SERSimaging

AuNPs

Raman labelNC membrane

AntibodyCancer cell

Figure 9 Detection of circulating tumor cells on NC membranes containing immobilized cAbs (adapted from [35])

activated by reacting the AuNPs with 1-ethyl-3-3(3-dimeth-ylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in the PBS buffer The mABs arethen added to this solution and the suspension is stirred atroom temperature for 30min The mAB-conjugated AuNPsare then collected by centrifugation and washing with PBSand ethanol The mAB-conjugated AuNPs successfully bindto E coli when incubated in PBS at pH 74 In other reportsthe AuNPs were found very effective in the detection ofcancerous pancreatic cells

The AuNPs are known to suffer from the problem ofaggregation upon long-term storage Therefore to solve thisissue the AuNPs are conjugated with the polyethylene glycol(PEG) to prevent their aggregation [127 128]The conjugationof PEGwith the AuNPsmakes the later hydrophilic thus pre-venting agglomeration induced by hydrophobic interactionsA PEGwith the heterobifunctional groups (dithiol at one endand a carboxyl at another end) is coated on the AuNP Thedithiol group allows stable anchoring heterobifunctional PEGligands on the surface of AuNP and the terminal carboxylgroup is used for coupling with antibodies The carboxy-terminated bifunctional PEG linker is synthesized by follow-ing a method reported by Eck et al which is depicted inScheme 8 The anionic polymerization of compound 1 withan excess of ethylene oxide allows synthesizing compound 2The treatment of compound 2 with chloroacetic acid at 60∘Callows generating compound 3 The reaction of an excess ofthe elemental bromine in dichloromethane at 0∘C for fourhours in the dark with compound 3 produces dibromidecompound 4 Compound 5 is obtained by reaction withcompound 4 in water with the excess of sodium hydrosulfidehydrate

The synthesized bifunctional PEG linker is then conju-gated with the citrate-stabilized gold nanoparticles by simpleligand exchangeThe citrate-stabilized gold nanoparticles areknown to aggregate in the buffer containing salts Thereforethe ligand exchange from citrate to PEG should be done inpure water The PEGylated AuNPs are conjugated to mono-clonal F19 antibodies for the detection of human pancreaticcarcinoma through EDCNHS coupling reaction [129]

OHO

(2) HCl

1

2

3

4

5

Br Br

HS SH

(CH2)9

(CH2)9

(CH2)9

(CH2)9

+

NaHDMF60∘C

(OCH2CH2)n

(OCH2CH2)n

(OCH2CH2)n

OCH2COOH

OCH2COOH

(CH2)9 (OCH2CH2)n OCH2COOH

OminusNa+

Br2

(2) Acetic acid (1) NaSHH2O

60∘C(1) ClCH2-COONa

Scheme 8 Synthesis of bifunctional PEG linker using conjugationwith AuNP

(2) Hydrazide Modification According to the report by Zhiet al the hydrazide-derivatized self-assembledmonolayer ona gold surface is used for the efficient and selective anchor-ing of oligosaccharide [39] The generated oligosaccharidemicroarrays allow the fluorescence-based detection of targetproteins The use of gold as a substrate for the fluorescence-based detection suffers from the drawbacks including flu-orescence quenching and nonspecific surface adsorption ofproteins However the use of120596-thiolated fatty acid (C

16) self-

assembledmonolayer between the gold surface andhydrazide

12 Journal of Chemistry

AuC C

C

C

OHOHO O

O

O

O

O

O

O

O

O

CHR

NN

H

N

N

N

H

NH

NH

NH

H

NH

C

O

O

O NNH

NH

HNH

H

S

S

S

S

HS Au

Au

Au

Au

Au

C16 SAM

Adipic dihydrazideEDC

(Sugar)R-CHO

Binding to protein

Sugarprobe

Protein Alexafluoro 532

SAM andblocking layer

Ab 2nd Ab

NH2

NH2H2N

CH2R

Scheme 9 Application of hydrazide-derivatized SAM on a goldsurface for the fabrication of oligosaccharide microarray (adaptedfrom [39])

groups minimizes the quenching effect Moreover the effec-tive blocking of the surface with the poly(ethylene glycol)aldehyde and BSA reduces the nonspecific adsorption ofprotein on the surface

For the fabrication of the reported oligosaccharidemicroarrays the gold substrate is prepared by following amethod depicted in Scheme 9 The self-assembled mono-layer (SAM) of 16-mercaptohexadecanoic acid (MHDA) isobtained by soaking the gold coated slides in the isobutylalcohol for 2 days The slides are then washed in ethanolto remove excess reagents and are dried under the nitrogenstream The carboxyl functional groups on the SAM areconverted to the hydrazide groups by incubation of the SAMcovered slides in the dimethyl sulfoxide solution containing1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and adipicdihydrazide The ethanol-washed and dried slides are thenused for the oligosaccharide printing to obtain oligosaccha-ride microarrays

The generated oligosaccharide microarray platformallows interrogation of carbohydrate-protein interactions ina high-throughput manner

26 Silver Similar to AuNPs silver nanoparticles (AgNP) arealso used for the immobilization of proteins and enzymesThe surface of AgNP allows adsorption of proteins Henceit can be utilized as a host matrix for various biomoleculesSilver is a suitable substrate for the immobilization of wholecell or the isolated enzymes [130 131]

Texp lt Tm

Ag

AgAg

Ag

AgAg

Texp gt Tm

Figure 10 AgNPs-oligonucleotide conjugates (adapted from [36])

261 Electrostatic Modification The electrostatic interac-tions allow the physical adsorption of biomolecules on thesurface of AgNPs Shen et al reported that the AgNPs aresynthesized by reduction of silver nitrate in the presence ofsodium citrate During the reduction process the solutionis sonicated for 15min to obtain the yellow silver colloidwhich is then kept at 4∘C for several days away from lightThen isolated nanoparticles can be used for physisorption ofproteins at a pH higher than their isoelectric point [132]

262 Covalent Modification As depicted in Scheme 10the AgNPs prepared by the citrate reduction method andstabilized with citrate [133] can be functionalized with car-boxyl groups upon treatment with 3-mercaptopropanoic acid(MPA) As reported by the Petkova et al for the immobi-lization of alcohol dehydrogenase from Thermoanaerobiumbrockii (TbADH) the carboxyl-modified AgNPs were treatedwith the solution containing TbADH under continuousstirring for 7 h at 26∘C a research by [134] The AgNPsmodified with the TbADH were successfully used for thebiotransformation studies

The application of a bifunctional linker for the modifica-tion of AgNPs is reported [135 136] The bifunctional linker11-mercaptoundecanoic acid was used with 1-octanethiol in1 1 ratio to generate the mixed SAM on the surface of AgNPThe IgG antibodies are then conjugated with the mixed SAMmodified AgNPs It is reported that upon covalent conjuga-tion of biomolecules with AgNPs their stability and activityis maintained [137]

According to another report on the covalent modifi-cation AgNPs-oligonucleotide conjugates are prepared byusing DNA and triple cyclic disulfide moieties [36] Asdepicted in Figure 10 the two types ofAgNPs-oligonucleotideconjugates with complementary DNA sequences undergoDNA hybridization driven coagulation resulting in the colorchange

As depicted in Figure 11 the AgNP-DNA conjugates wereprepared by treatment of AgNPs with the cyclic disulfidemodified oligonucleotide The AgNP and oligonucleotideswere allowed to react with each other with 1 4 ratio inthe presence of 1 sodium dodecyl sulfate and NaCl Theovernight incubation of solution results in the AgNP-DNAconjugates which are collected by centrifugation and washedto remove the excess DNAs

Journal of Chemistry 13

Ag AgMPAOH

OO OH

O

HOCitrate

Citrate

Ag

COOH

COOH

TbADHAg

CONH

COOH

TbADHOminusNa+

H2N

Scheme 10 Covalent conjugation of enzymes on the surface of carboxyl-modified AgNPs

OHO

EDC HOSu Bis-amino

polyethylene glycol

NH

OO

44GMBS N

H

OO N

H44

ON

O

O3

CoA

NH

OO N

H44

ON

O

O3

SHN

O

OH

OP O

OPO

O O

OHO

NNN

N

PO

OminusOminus

OminusOminus

NH2

NH2

Scheme 11 Covalent conjugation of coenzyme A to polystyrene nanoparticles

O OOO P

OHSS

5998400 (DSP)3-A10-ATT-ATC-ACT 3998400

DSP cyclic disulfide-containingphosphate derivative =

Figure 11 Conjugation of AgNPs with oligonucleotides by usingDSP as a linker molecule (adapted from [36])

27 Polystyrene Polystyrene is an aromatic polymerobtained by polymerization of styrene monomers [138] Thepolystyrene-based NPs are widely used in the moleculardiagnostics for the detection of biomarker proteins andgenomic DNAs Polystyrene can be employed as a coating ona variety of nanoparticles as its functional groups can be easilymodified or conjugated with other molecules The otherapplication of polystyrene is in the fabrication of fluorescencebeads (FBs) The fluorescence molecules are loaded into thepolystyrene shell to produce FBs which are then used invarious sensing applications The polystyrene is also used tocoat the magnetic NPs so they can be conjugated with otherbiomolecules such as DNA and Proteins The applications ofpolystyrene include but are not limited to the detection ofE coli [139] the detection of cardiac Troponin T (cTnT) thedetection of Herpes simplex virus and many more

271 Covalent Modification Covalent modification throughcarboxyl group iswell known formodification of biomolecule

Most of the polystyrene-based nanoparticles bear large num-bers of pendant carboxyl which increases the loading amountof biomolecule

Enzyme catalyzed covalent immobilization of the pro-teins bearing a small 12-mer ldquoybbRrdquo tag onto the polystyrenenanoparticles (PSNP) is recently reported by Wong et al[140] As depicted in Scheme 11 the carboxyl-PSNPs werereacted with the bis-amino-polyethylene glycol in the pres-ence of HOSu and EDC to generate the amino-pegylatedPSNPs These PSNPs are then reacted with the g-maleimi-dobutyric acid succinimidyl (GMBS) to obtain maleimide-functionalized PSNPs The maleimide-functionalized PSNPsupon chemoligation with coenzyme A (CoA) produce theCoA-derivatized PSNPs

As depicted in Scheme 12 the protein of interest bearingybbR-tag is immobilized on the CoA-derivatized PSNPsThephosphopantetheinyl transferase (Sfp) catalyzed the reactionbetween the serine residue of the ybbR-tag and the phos-phopantetheine moiety of CoA with the simultaneous lossof 3101584051015840-adenine diphosphate results in the attachment ofproteins onto the surface of PSNPs It is reported that theenzymes immobilized by this method retain their activity

There are several reports on the use of fluoromicrobeadsfor the detection of biomarkers Primarily the fluoromi-crobeads are made up of carboxylated polystyrene as a coat-ingmaterial entrapping the fluorescentmolecules Accordingto the recent report by Song et al [37] the fluoromicrobeadswere used for the detection of the cTnT on the proteinmicroarray as depicted in Figure 12

The carboxylate modified fluoromicrobeads were conju-gated with the anti cTnI mAb through EDCNHS-mediated

14 Journal of Chemistry

HN

O

OH

OP

O

O

PO

O

OHO

N

NN

P

O

S

HN

O

Coenzyme A

Phosphopantetheine

PO

O

O

OHO

N Sfp

NN

N

P

O

ybbr-protein

HN

O

OH

OP

O

O

S

HN

O

NH2

NH2

Ominus

Ominus

Ominus

minusO

minusO

Mg2+

HO∙∙

Ominus

OminusOminus

minusO

N

O

Polystyrenenanoparticle

Scheme 12 Protein conjugation to polystyrene NP

System 1 antibody-conjugated fluoromicrobeads

System 2 avidin-conjugated fluoromicrobeads

DTSP SAM

Anti-cTnI cAb

cTnI

Figure 12 Application of the polystyrene-coated fluoromicrobeadsfor the detection of cTnI on the protein microarray (adapted from[37])

coupling reaction The use of fluoromicrobeads alloweddetecting the cTnI in plasma samples with a range of 01ndash100 ngmL

272 Affinity-Based Modification The affinity interactionsare used for the attachment of oligonucleotides with thefluoromicrobeads or polystyrene-coated magnetic beads Togenerate the oligonucleotide conjugated fluoromicrobeads ormagnetic beads respective polystyrene-coated beads are firstconjugated with the streptavidin using the EDCNHS cou-pling reaction as reported by Zhang et al [141] As depicted

B

B

MB MB

MB

BB

Magnetic bead

Streptavidin

DNA labeled biotin

Figure 13 DNA attachment to the magnetic beads

in Figure 13 the streptavidinmodified beads are then allowedto incubate with the biotinylated oligonucleotides Due to theaffinity of biotin for streptavidin the biotinylated oligonu-cleotides can be readily immobilized on the streptavidincoated beads

The binding affinity of streptavidin and biotin in solutionis up to 25 times 1013 (molL)minus1 [142] This interaction is about amillion times stronger than the antigen and antibody inter-action The antibodies directly immobilized onto the sur-face lose 90 of their biological activity [143] Howeverthe biotinylated antibodies immobilized on the streptavidincoated surface can retain their bioactivity [144]

Journal of Chemistry 15

3 Conclusions

Surface modification techniques of the materials used asplatforms in the fabrication of biosensors are reviewed inthis paper There are several reports on materials and vari-ous methods for altering their physicochemical propertiesHence one of these methods can be chosen according tothe targeted use and needed physiochemical properties Itis important to note that the performance of the biosensoris highly dependent on the substrate material used and itsmeticulous modification for particular applications There-fore it is critical to understand the principles of a biosensor toidentify the correct substrate material and its surface modifi-cation chemistry Furthermore it is important to look at thelatest advances in the materials and techniques used for thefabrication of a biosensor before the processing

Competing Interests

All authors declare that there is no conflict of interests

Acknowledgments

This research was supported by the Hallym UniversityResearch Fund (HRF-201601-010) This work was also sup-ported by the fund obtained through Industry-Academic col-laboration between Biometrix Technology Inc (ChuncheonSouth Korea) and Hallym University

References

[1] A Sassolas B D Leca-Bouvier and L J Blum ldquoDNA biosen-sors andmicroarraysrdquoChemical Reviews vol 108 no 1 pp 109ndash139 2008

[2] A Cavalcanti B Shirinzadeh M Zhang and L C KretlyldquoNanorobot hardware architecture for medical defenserdquo Sen-sors vol 8 no 5 pp 2932ndash2958 2008

[3] R-Q Zhang S-L Liu W Zhao et al ldquoA simple point-of-caremicrofluidic immunomagnetic fluorescence assay for path-ogensrdquo Analytical Chemistry vol 85 no 5 pp 2645ndash2651 2013

[4] S B Nimse K S Song M D Sonawane D R Sayyed and TS Kim ldquoImmobilization techniques for microarray challengesand applicationsrdquo Sensors vol 14 no 12 pp 22208ndash22229 2014

[5] A P F Turner ldquoBiosensors sense and sensibilityrdquo ChemicalSociety Reviews vol 42 no 8 pp 3184ndash3196 2013

[6] L Wu and X Qu ldquoCancer biomarker detection recent achieve-ments and challengesrdquoChemical Society Reviews vol 44 no 10pp 2963ndash2997 2015

[7] K Ariga Q Ji T Mori et al ldquoEnzyme nanoarchitectonicsorganization and device applicationrdquo Chemical Society Reviewsvol 42 no 15 pp 6322ndash6345 2013

[8] W-W Zhao J-J Xu and H-Y Chen ldquoPhotoelectrochemicalDNA biosensorsrdquo Chemical Reviews vol 114 no 15 pp 7421ndash7441 2014

[9] Q Liu C Wu H Cai N Hu J Zhou and P Wang ldquoCell-basedbiosensors and their application in biomedicinerdquo ChemicalReviews vol 114 no 12 pp 6423ndash6461 2014

[10] X Zhao S Nampalli A J Serino and S Kumar ldquoImmobi-lization of oligodeoxyribonucleotides with multiple anchors to

microchipsrdquo Nucleic Acids Research vol 29 no 4 pp 955ndash9592001

[11] P Kumar S K Agrawal A Misra and K C Gupta ldquoA newheterobifunctional reagent for immobilization of biomoleculeson glass surfacerdquo Bioorganic 120572Medicinal Chemistry Letters vol14 no 5 pp 1097ndash1099 2004

[12] F Secundo ldquoConformational changes of enzymes upon immo-bilisationrdquo Chemical Society Reviews vol 42 no 15 pp 6250ndash6261 2013

[13] S Lee S Kim J Malm O C Jeong H Lilja and T LaurellldquoImproved porous silicon microarray based prostate specificantigen immunoassay by optimized surface density of thecapture antibodyrdquoAnalytica Chimica Acta vol 796 pp 108ndash1142013

[14] K Jaras A A Tajudin A Ressine et al ldquoENSAM europiumnanoparticles for signal enhancement of antibody microarrayson nanoporous siliconrdquo Journal of Proteome Research vol 7 no3 pp 1308ndash1314 2008

[15] C Steinhauer A Ressine G Marko-Varga T Laurell C AK Borrebaeck and C Wingren ldquoBiocompatibility of surfacesfor antibody microarrays design of macroporous silicon sub-stratesrdquo Analytical Biochemistry vol 341 no 2 pp 204ndash2132005

[16] K Jaras B Adler A Tojo et al ldquoPorous silicon antibodymicroarrays for quantitative analysis measurement of free andtotal PSA in clinical plasma samplesrdquo Clinica Chimica Acta vol414 pp 76ndash84 2012

[17] S W Lee K Hosokawa S Kim et al ldquoA highly sensitive poroussilicon (P-Si)-based human Kallikrein 2 (hK2) immunoassayplatform toward accurate diagnosis of prostate cancerrdquo Sensorsvol 15 no 5 pp 11972ndash11987 2015

[18] C Roychaudhuri ldquoA review on porous silicon based electro-chemical biosensors beyond surface area enhancement factorrdquoSensors and Actuators B Chemical vol 210 pp 310ndash323 2015

[19] ARessine S EkstromGMarko-Varga andT Laurell ldquoMacro-nanoporous silicon as a support for high-performance proteinmicroarraysrdquo Analytical Chemistry vol 75 no 24 pp 6968ndash6974 2003

[20] S Lee E Silajdzic H Yang et al ldquoA porous silicon immunoas-say platform for fluorometric determination of 120572-synuclein inhuman cerebrospinal fluidrdquo Microchimica Acta vol 181 no 9-10 pp 1143ndash1149 2014

[21] S Belhousse N Belhaneche-Bensemra K Lasmi et alldquoModified porous silicon for electrochemical sensor of para-nitrophenolrdquo Materials Science and Engineering B vol 189 pp76ndash81 2014

[22] N Reta A Michelmore C Saint B Prieto-Simon and NH Voelcker ldquoPorous silicon membrane-modified electrodesfor label-free voltammetric detection of MS2 bacteriophagerdquoBiosensors and Bioelectronics vol 80 pp 47ndash53 2016

[23] B Guan A Magenau S Ciampi K Gaus P J Reece and J JGooding ldquoAntibody modified porous silicon microparticles forthe selective capture of cellsrdquo Bioconjugate Chemistry vol 25no 7 pp 1282ndash1289 2014

[24] S Vutti N Buch-Manson S Schoffelen N Bovet K LMartinez and M Meldal ldquoCovalent and stable CuAAC mod-ification of silicon surfaces for control of cell adhesionrdquo Chem-BioChem vol 16 no 5 pp 782ndash791 2015

[25] A M Rossi L Wang V Reipa and T E Murphy ldquoPoroussilicon biosensor for detection of virusesrdquo Biosensors andBioelectronics vol 23 no 5 pp 741ndash745 2007

16 Journal of Chemistry

[26] T L Lasseter B H Clare N L Abbott and R J HamersldquoCovalently modified silicon and diamond surfaces resistanceto nonspecific protein adsorption and optimization for biosens-ingrdquo Journal of the American Chemical Society vol 126 no 33pp 10220ndash10221 2004

[27] M Li K-G Neoh E-T Kang T Lau and E E ChiongldquoSurface modification of silicone with covalently immobilizedand crosslinked agarose for potential application in the inhibi-tion of infection and omental wrappingrdquo Advanced FunctionalMaterials vol 24 no 11 pp 1631ndash1643 2014

[28] G MacBeath and S L Schreiber ldquoPrinting proteins as microar-rays for high-throughput function determinationrdquo Science vol289 no 5485 pp 1760ndash1763 2000

[29] S B Nimse M D Sonawane K S Song and T Kim ldquoBio-marker detection technologies and future directionsrdquoThe Ana-lyst vol 141 no 3 pp 740ndash755 2016

[30] M D Sonawane S B Nimse K Song and T Kim ldquoDetectionquantification and profiling of PSA current microarray tech-nologies and future directionsrdquo RSC Advances vol 6 no 9 pp7599ndash7609 2016

[31] S B Nimse and T Kim ldquoBiological applications of function-alized calixarenesrdquo Chemical Society Reviews vol 42 no 1 pp366ndash386 2013

[32] K-S Song S B Nimse J Kim et al ldquo9GDNAChip microarraybased on the multiple interactions of 9 consecutive guaninesrdquoChemical Communications vol 47 no 25 pp 7101ndash7103 2011

[33] R J Chen S Bangsaruntip K A Drouvalakis et al ldquoNonco-valent functionalization of carbon nanotubes for highly specificelectronic biosensorsrdquo Proceedings of the National Academy ofSciences of the United States of America vol 100 no 9 pp 4984ndash4989 2003

[34] Y Lu W Shi J Qin and B Lin ldquoFabrication and characteri-zation of paper-based microfluidics prepared in nitrocellulosemembrane by wax printingrdquo Analytical Chemistry vol 82 no1 pp 329ndash335 2010

[35] P Zhang R Zhang M Gao and X Zhang ldquoNovel nitrocel-lulose membrane substrate for efficient analysis of circulatingtumor cells coupled with surface-enhanced raman scatteringimagingrdquo ACS Applied Materials and Interfaces vol 6 no 1 pp370ndash376 2014

[36] J-S Lee A K R Lytton-Jean S J Hurst and C AMirkin ldquoSil-ver nanoparticlemdasholigonucleotide conjugates based on DNAwith triple cyclic disulfide moietiesrdquo Nano Letters vol 7 no 7pp 2112ndash2115 2007

[37] S Y Song Y D Han K Kim S S Yang and H C YoonldquoA fluoro-microbead guiding chip for simple and quantifiableimmunoassay of cardiac troponin I (cTnI)rdquo Biosensors andBioelectronics vol 26 no 9 pp 3818ndash3824 2011

[38] S V Lemeshko T Powdrill Y Y Belosludtsev and M HoganldquoOligonucleotides form a duplex with non-helical properties ona positively charged surfacerdquoNucleic Acids Research vol 29 no14 pp 3051ndash3058 2001

[39] Z-L Zhi A K Powell and J E Turnbull ldquoFabrication ofcarbohydrate microarrays on gold surfaces direct attachmentof nonderivatized oligosaccharides to hydrazide-modified self-assembledmonolayersrdquoAnalytical Chemistry vol 78 no 14 pp4786ndash4793 2006

[40] S L Pan and L Rothberg ldquoChemical control of electrodefunctionalization for detection of DNA hybridization by elec-trochemical impedance spectroscopyrdquo Langmuir vol 21 no 3pp 1022ndash1027 2005

[41] Z Lu C M Li Q Zhou Q-L Bao and X Cui ldquoCovalentlylinked DNAprotein multilayered film for controlled DNAreleaserdquo Journal of Colloid and Interface Science vol 314 no 1pp 80ndash88 2007

[42] L-S Jang and H-J Liu ldquoFabrication of protein chips basedon 3-aminopropyltriethoxysilane as a monolayerrdquo BiomedicalMicrodevices vol 11 no 2 pp 331ndash338 2009

[43] F Fixe M Dufva P Telleman and C B Christensen ldquoFunc-tionalization of poly(methyl methacrylate) (PMMA) as a sub-strate for DNAmicroarraysrdquoNucleic Acids Research vol 32 no1 article e9 2004

[44] A Lueking M Horn H Eickhoff K Bussow H Lehrachand G Walter ldquoProtein microarrays for gene expression andantibody screeningrdquo Analytical Biochemistry vol 270 no 1 pp103ndash111 1999

[45] N Zammatteo L Jeanmart S Hamels et al ldquoComparisonbetween different strategies of covalent attachment of DNA toglass surfaces to build DNA microarraysrdquo Analytical Biochem-istry vol 280 no 1 pp 143ndash150 2000

[46] M Ozmen K Can I Akin et al ldquoSurface modification of glassbeads with glutaraldehyde characterization and their adsorp-tion property for metal ionsrdquo Journal of Hazardous Materialsvol 171 no 1ndash3 pp 594ndash600 2009

[47] C Funk PM Dietrich T Gross HMinW E S Unger andWWeigel ldquoEpoxy-functionalized surfaces for microarray appli-cations surface chemical analysis and fluorescence labeling ofsurface speciesrdquo Surface and Interface Analysis vol 44 no 8pp 890ndash894 2012

[48] S Mahajan P Kumar and K C Gupta ldquoOligonucleotide mic-roarrays immobilization of phosphorylated oligonucleotideson epoxylated surfacerdquo Bioconjugate Chemistry vol 17 no 5pp 1184ndash1189 2006

[49] M C Pirrung J D Davis and A L Odenbaugh ldquoNovelreagents and procedures for immobilization of DNA on glassmicrochips for primer extensionrdquo Langmuir vol 16 no 5 pp2185ndash2191 2000

[50] E Southern K Mir and M Shchepinov ldquoMolecular interac-tions on microarraysrdquo Nature Genetics vol 21 no 1 pp 5ndash91999

[51] M S Shchepinov S C Case-Green and E M SouthernldquoSteric factors influencing hybridisation of nucleic acids tooligonucleotide arraysrdquo Nucleic Acids Research vol 25 no 6pp 1155ndash1161 1997

[52] D A Tomalia A M Naylor and W A Goddard III ldquoStarbustdendrimers molecular-level control of size shape surfacechemistry topology and flexibility from atoms to macroscopicmatterrdquo Angewandte ChemiemdashInternational Edition in Englishvol 29 no 2 pp 138ndash175 1990

[53] R Benters C M Niemeyer D Drutschmann D Blohm andD Wohrle ldquoDNA microarrays with PAMAM dendritic linkersystemsrdquo Nucleic Acids Research vol 30 no 2 p e10 2002

[54] J H Moon J W Shin S Y Kim and J W Park ldquoFormationof uniform aminosilane thin layers an imine formation tomeasure relative surface density of the amine grouprdquo Langmuirvol 12 no 20 pp 4621ndash4624 1996

[55] J C Alwine D J Kemp and G R Stark ldquoMethod fordetection of specific RNAs in agarose gels by transfer to diazo-benzyloxymethyl-paper and hybridization with DNA probesrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 74 no 12 pp 5350ndash5354 1977

[56] P L Dolan Y Wu L K Ista R L Metzenberg M A Nelsonand G P Lopez ldquoRobust and efficient synthetic method for

Journal of Chemistry 17

forming DNA microarraysrdquo Nucleic Acids Research vol 29 no21 article e107 2001

[57] S B Nimse J Kim K-S Song et al ldquoSelective recognitionof the ditopic trimethylammonium cations by water-solubleaminocalix[4]arenerdquo Tetrahedron Letters vol 52 no 29 pp3751ndash3755 2011

[58] V-T Ta S B Nimse K-S Song et al ldquoCharacterization ofthe mixed self-assembled monolayer at the molecular scalerdquoChemical Communications vol 47 no 40 pp 11261ndash11263 2011

[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

[60] Y Lee E K Lee YW Cho et al ldquoProteoChip a highly sensitiveprotein microarray prepared by a novel method of proteinimmobilization for application of protein-protein interactionstudiesrdquo Proteomics vol 3 no 12 pp 2289ndash2304 2003

[61] S W Oh J D Moon H J Lim et al ldquoCalixarene derivative asa tool for highly sensitive detection and oriented immobiliza-tion of proteins in a microarray format through noncovalentmolecular interactionrdquo The FASEB Journal vol 19 no 10 pp1335ndash1337 2005

[62] S B Nimse K-S Song J Kim D R Sayyed and T Kimldquo9G DNAChip technology self-assembled monolayer (SAM)of ssDNA for ultra-sensitive detection of biomarkersrdquo Interna-tional Journal ofMolecular Sciences vol 14 no 3 pp 5723ndash57332013

[63] V-T Nguyen S B Nimse K-S Song et al ldquoHPAI 9GDNAChip discrimination of highly pathogenic influenza virusgenesrdquo Chemical Communications vol 48 no 38 pp 4582ndash4584 2012

[64] K-S Song S B Nimse J Kim D R Sayyed and T Kim ldquoAnew platform for a convenient genotyping systemrdquo ChemicalCommunications vol 49 no 26 pp 2661ndash2663 2013

[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

[67] F Hennrich C Chan VMoore M Rolandi andM OrsquoConnellCarbonNanotubes Properties and Applications Taylor amp FrancisGroup Abingdon UK 2006

[68] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

[69] C Singh M Shaffer I Kinloch and A Windle ldquoProductionof aligned carbon nanotubes by the CVD injection methodrdquoPhysica B Condensed Matter vol 323 no 1ndash4 pp 339ndash3402002

[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

[71] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Journal of Chemistry 9

O

O

O

O

R

OOCatalyst

O

O

O

O

O

O

CHHO

R

O

HC OH

R

O

H2C

O

HC OH

R

O

H2C

CH2

O

CHHO

R

O

CH2

HOHO

OHOH

+

Scheme 6 Epoxy modification of CNT

The mixture of solutions is sonicated for 1 h followedby stirring and heating at 70∘C The reaction was quenchedby addition of appropriate amount of potassium hydroxideThen the epoxilated CNT were purified and a number ofepoxy groups on the CNT surface were determined by usingthermogravimetric analysis

24 Nitrocellulose A PoC diagnosis system is always expe-cted to deliver final results in few minutes Though themicroarrays based on the glass and gold surfaces are usefulfor detection of multiple analytes at a time they need longertime for final data interpretation Microfluidic systems basedon paper or nitrocellulose membranes are emerging surfacesfor detection of bacteria viruses and proteins A paper isadvantageous due to its hydrophilic nature which allowsthe aqueous solutions to penetrate without the need of anyexternal force [100] The essential constituent of paper iscelluloseThe cellulose has hydroxyl functional groups whichcan be modified and changed according to surface propertiesneeded for a particular detection device [101] Due to lowcost and high availability paper is preferred for large scaleproduction Moreover the devices required for the tests areportable and disposable [102ndash105] The very first example ofpaper based detection is glucose detection in urine [106] andpregnancy test kit [107]There are different types of paper likeWhatman filter paper glossy paper [108] membrane and soforth Whatman filter is used because of its high penetrationand flow rate [109ndash112] but in some cases it does not havethe necessary characteristic for surface modification Mem-branes on the other hand are planner sheets and providelarger surface area for immobilization of biomolecules such

as DNA and protein The nitrocellulose (NC) membrane isbroadly used for immobilization of DNA [113] protein [114]and enzymes [115] due to its hydrophobic surface

241 Physical Adsorption Single-stranded DNAs are irre-versibly bound to the surface of the NCmembrane with non-covalent interactionsTheprimary interactions are hydropho-bic and electrostatic between the positively charged surfaceof the membrane and negatively charged DNAs The nitro-cellulose offers very high binding capacity for DNAs andproteins Fabrication of NC membranes can be done bydifferent methods including the photolithography The waxpatterningmethod is fast cheap and easy to process and doesnot need organic solvents The NCmembranes with the poresize of 045 120583mdo not need pretreatment for penetrationThefabrication process includesmainly printing and baking stepswhich can be finished in 10min As shown in Figure 8 firstlythe wax is printed on the surface of NCmembrane and bakedat 125∘C for 5min in the oven The melting of the wax onmembrane makes it more hydrophobic and affords surfacesuitable for the immunoassay For immunoassays Lu et alcoated the cAbs on the surface and the free area is blockedwith the 1 BSA

During baking melted wax passes through the mem-brane The 121∘ contact angle of backside membrane assuresthe melting of wax thoroughly The efficiency of wax treatedmembrane is compared with the untreated membrane byimmobilizing fluorescence labeled goat antihuman IgG Theimmobilization on wax printed surface is more uniform thanthe untreated membrane Apart from this a large volumeof liquid can be used because ring effect of protein on the

10 Journal of Chemistry

HO

OSH AuNP

AuNP-mAb

mAbEDCNHS

001M PBS

(CH2)15(CH2)11

NaBH4HAuCl4 + SH + HO

pH sim 74

Scheme 7 Immobilization on antibodies on AuNP

NC membrane

Cross section view

PrintingStep 1

Step 2 Baking

Wax patternedNC membrane

Wax is printed onto thesurface of NC membrane

Wax melts and penetratesthrough NC membrane

Nitrocellulose

Wax

Figure 8Wax printing on nitrocellulosemembranes (adapted from[34])

untreated membrane is avoided Wax printing method gen-erates 100 120583mmicrochannel which removes the micrometersize contaminants and makes the wax printed membranessuitable for the applications in microfluidic assays Apartfrom immobilization wax printing has application in dotimmunoassay and sample purifications [34]

Due to advantages of NC membrane for high bindingcapacity and good flow of solution it is also used on the chipsurfaces The glass slide can be coated with the 12 120583m layer ofNC to afford a platform with the intrinsic properties of NCThe solution of cAbs in PBS buffer containing 10 glycerolis then spotted on the modified surface After spotting theslides are incubated for one hour After incubation slides arewashed with 01 Tween 20 in PBS buffer and dried to gen-erate the platform for detection of biomarker proteins [116]

Apart from routine microarray applications NC mem-brane is also used for the detection of circulating tumor cells(CTC) as reported by Zhang et al The binding of CTCs bythe cAbs immobilized on the NC membrane is detected bySurface Enhanced Raman Scattering (SERS) as depicted inFigure 9

Usually the antibodies specific for cancer cells are usedas a capture substrate and immobilized on the surface TheNC membrane is cut into 1 cm times 1 cm pieces Then thesepieces are immersed in the ethanol and then tiled on thePMMA wafer After washing the membrane is activated byusing PBS buffer containing antibodies at 37∘C for 30minDuring this process the cAbs are avidly immobilized on theNC membrane The 1 BSA solution is loaded to block thefree surface area to avoid any background signals due tononspecific interactions Finally the membranes are washedwith PBS buffer and stored at 4∘CThe gold nanoparticle andRaman probes are used to detect the CTCs by SERS [35]

25 Gold Application of nanoparticles is amost focused areain the field of inorganic chemistry and it has also attractedimaginations of many biologists too Inorganic nanoparti-cles including gold silver and ferrous oxides have foundmany important applications in cell signaling drug deliveryand colorimetric and fluorescence-based detections Goldnanoparticles (AuNP) functionalized with proteins DNAsor Raman probes are well known in the field of biosensorsand nanobiotechnology for their applications in the molec-ular diagnostics [117ndash119] protein detection [120ndash122] generegulation [123] and cell imaging [124]

251 Covalent Modification

(1) Thiol Based Modification AuNPs are commonly usedin the electrochemical and optical detection systems Theconjugation with biomolecule does not change the opticalproperties ofAuNP [125]Di Pasqua et al reported thiolmod-ification for the detection of E coli O157H7 E coli specificantibodies were conjugated with the AuNPs [126] As shownin Scheme 7 the 10 nmAuNPs are carboxylated and then cou-pled to E coli specific monoclonal antibody (mAb) throughamide coupling

For the generation of AuNPs to the solution containing410mg of HAuCl

4sdot3H2O in 6mL of water ethanoic solutions

of 11-mercapto-1-undecanol and 16-mercaptohexadecanoicacid are added Upon addition of NaBH

4to this mixture at

0∘C the solution turns brown The product AuNP cappedwith alkanethiol pendant alcohol and carboxylic acid func-tional groups precipitate upon three hours of stirring Theprecipitated particles are then thoroughly washed with etha-nol and an ethanolic solution containing a small amountof 1M HCl The AuNPs are then dried under vacuum forten hours For the conjugation of mABs with the AuNPsthe carboxylic acid functional groups on the AuNPs are

Journal of Chemistry 11

SERSimaging

AuNPs

Raman labelNC membrane

AntibodyCancer cell

Figure 9 Detection of circulating tumor cells on NC membranes containing immobilized cAbs (adapted from [35])

activated by reacting the AuNPs with 1-ethyl-3-3(3-dimeth-ylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in the PBS buffer The mABs arethen added to this solution and the suspension is stirred atroom temperature for 30min The mAB-conjugated AuNPsare then collected by centrifugation and washing with PBSand ethanol The mAB-conjugated AuNPs successfully bindto E coli when incubated in PBS at pH 74 In other reportsthe AuNPs were found very effective in the detection ofcancerous pancreatic cells

The AuNPs are known to suffer from the problem ofaggregation upon long-term storage Therefore to solve thisissue the AuNPs are conjugated with the polyethylene glycol(PEG) to prevent their aggregation [127 128]The conjugationof PEGwith the AuNPsmakes the later hydrophilic thus pre-venting agglomeration induced by hydrophobic interactionsA PEGwith the heterobifunctional groups (dithiol at one endand a carboxyl at another end) is coated on the AuNP Thedithiol group allows stable anchoring heterobifunctional PEGligands on the surface of AuNP and the terminal carboxylgroup is used for coupling with antibodies The carboxy-terminated bifunctional PEG linker is synthesized by follow-ing a method reported by Eck et al which is depicted inScheme 8 The anionic polymerization of compound 1 withan excess of ethylene oxide allows synthesizing compound 2The treatment of compound 2 with chloroacetic acid at 60∘Callows generating compound 3 The reaction of an excess ofthe elemental bromine in dichloromethane at 0∘C for fourhours in the dark with compound 3 produces dibromidecompound 4 Compound 5 is obtained by reaction withcompound 4 in water with the excess of sodium hydrosulfidehydrate

The synthesized bifunctional PEG linker is then conju-gated with the citrate-stabilized gold nanoparticles by simpleligand exchangeThe citrate-stabilized gold nanoparticles areknown to aggregate in the buffer containing salts Thereforethe ligand exchange from citrate to PEG should be done inpure water The PEGylated AuNPs are conjugated to mono-clonal F19 antibodies for the detection of human pancreaticcarcinoma through EDCNHS coupling reaction [129]

OHO

(2) HCl

1

2

3

4

5

Br Br

HS SH

(CH2)9

(CH2)9

(CH2)9

(CH2)9

+

NaHDMF60∘C

(OCH2CH2)n

(OCH2CH2)n

(OCH2CH2)n

OCH2COOH

OCH2COOH

(CH2)9 (OCH2CH2)n OCH2COOH

OminusNa+

Br2

(2) Acetic acid (1) NaSHH2O

60∘C(1) ClCH2-COONa

Scheme 8 Synthesis of bifunctional PEG linker using conjugationwith AuNP

(2) Hydrazide Modification According to the report by Zhiet al the hydrazide-derivatized self-assembledmonolayer ona gold surface is used for the efficient and selective anchor-ing of oligosaccharide [39] The generated oligosaccharidemicroarrays allow the fluorescence-based detection of targetproteins The use of gold as a substrate for the fluorescence-based detection suffers from the drawbacks including flu-orescence quenching and nonspecific surface adsorption ofproteins However the use of120596-thiolated fatty acid (C

16) self-

assembledmonolayer between the gold surface andhydrazide

12 Journal of Chemistry

AuC C

C

C

OHOHO O

O

O

O

O

O

O

O

O

CHR

NN

H

N

N

N

H

NH

NH

NH

H

NH

C

O

O

O NNH

NH

HNH

H

S

S

S

S

HS Au

Au

Au

Au

Au

C16 SAM

Adipic dihydrazideEDC

(Sugar)R-CHO

Binding to protein

Sugarprobe

Protein Alexafluoro 532

SAM andblocking layer

Ab 2nd Ab

NH2

NH2H2N

CH2R

Scheme 9 Application of hydrazide-derivatized SAM on a goldsurface for the fabrication of oligosaccharide microarray (adaptedfrom [39])

groups minimizes the quenching effect Moreover the effec-tive blocking of the surface with the poly(ethylene glycol)aldehyde and BSA reduces the nonspecific adsorption ofprotein on the surface

For the fabrication of the reported oligosaccharidemicroarrays the gold substrate is prepared by following amethod depicted in Scheme 9 The self-assembled mono-layer (SAM) of 16-mercaptohexadecanoic acid (MHDA) isobtained by soaking the gold coated slides in the isobutylalcohol for 2 days The slides are then washed in ethanolto remove excess reagents and are dried under the nitrogenstream The carboxyl functional groups on the SAM areconverted to the hydrazide groups by incubation of the SAMcovered slides in the dimethyl sulfoxide solution containing1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and adipicdihydrazide The ethanol-washed and dried slides are thenused for the oligosaccharide printing to obtain oligosaccha-ride microarrays

The generated oligosaccharide microarray platformallows interrogation of carbohydrate-protein interactions ina high-throughput manner

26 Silver Similar to AuNPs silver nanoparticles (AgNP) arealso used for the immobilization of proteins and enzymesThe surface of AgNP allows adsorption of proteins Henceit can be utilized as a host matrix for various biomoleculesSilver is a suitable substrate for the immobilization of wholecell or the isolated enzymes [130 131]

Texp lt Tm

Ag

AgAg

Ag

AgAg

Texp gt Tm

Figure 10 AgNPs-oligonucleotide conjugates (adapted from [36])

261 Electrostatic Modification The electrostatic interac-tions allow the physical adsorption of biomolecules on thesurface of AgNPs Shen et al reported that the AgNPs aresynthesized by reduction of silver nitrate in the presence ofsodium citrate During the reduction process the solutionis sonicated for 15min to obtain the yellow silver colloidwhich is then kept at 4∘C for several days away from lightThen isolated nanoparticles can be used for physisorption ofproteins at a pH higher than their isoelectric point [132]

262 Covalent Modification As depicted in Scheme 10the AgNPs prepared by the citrate reduction method andstabilized with citrate [133] can be functionalized with car-boxyl groups upon treatment with 3-mercaptopropanoic acid(MPA) As reported by the Petkova et al for the immobi-lization of alcohol dehydrogenase from Thermoanaerobiumbrockii (TbADH) the carboxyl-modified AgNPs were treatedwith the solution containing TbADH under continuousstirring for 7 h at 26∘C a research by [134] The AgNPsmodified with the TbADH were successfully used for thebiotransformation studies

The application of a bifunctional linker for the modifica-tion of AgNPs is reported [135 136] The bifunctional linker11-mercaptoundecanoic acid was used with 1-octanethiol in1 1 ratio to generate the mixed SAM on the surface of AgNPThe IgG antibodies are then conjugated with the mixed SAMmodified AgNPs It is reported that upon covalent conjuga-tion of biomolecules with AgNPs their stability and activityis maintained [137]

According to another report on the covalent modifi-cation AgNPs-oligonucleotide conjugates are prepared byusing DNA and triple cyclic disulfide moieties [36] Asdepicted in Figure 10 the two types ofAgNPs-oligonucleotideconjugates with complementary DNA sequences undergoDNA hybridization driven coagulation resulting in the colorchange

As depicted in Figure 11 the AgNP-DNA conjugates wereprepared by treatment of AgNPs with the cyclic disulfidemodified oligonucleotide The AgNP and oligonucleotideswere allowed to react with each other with 1 4 ratio inthe presence of 1 sodium dodecyl sulfate and NaCl Theovernight incubation of solution results in the AgNP-DNAconjugates which are collected by centrifugation and washedto remove the excess DNAs

Journal of Chemistry 13

Ag AgMPAOH

OO OH

O

HOCitrate

Citrate

Ag

COOH

COOH

TbADHAg

CONH

COOH

TbADHOminusNa+

H2N

Scheme 10 Covalent conjugation of enzymes on the surface of carboxyl-modified AgNPs

OHO

EDC HOSu Bis-amino

polyethylene glycol

NH

OO

44GMBS N

H

OO N

H44

ON

O

O3

CoA

NH

OO N

H44

ON

O

O3

SHN

O

OH

OP O

OPO

O O

OHO

NNN

N

PO

OminusOminus

OminusOminus

NH2

NH2

Scheme 11 Covalent conjugation of coenzyme A to polystyrene nanoparticles

O OOO P

OHSS

5998400 (DSP)3-A10-ATT-ATC-ACT 3998400

DSP cyclic disulfide-containingphosphate derivative =

Figure 11 Conjugation of AgNPs with oligonucleotides by usingDSP as a linker molecule (adapted from [36])

27 Polystyrene Polystyrene is an aromatic polymerobtained by polymerization of styrene monomers [138] Thepolystyrene-based NPs are widely used in the moleculardiagnostics for the detection of biomarker proteins andgenomic DNAs Polystyrene can be employed as a coating ona variety of nanoparticles as its functional groups can be easilymodified or conjugated with other molecules The otherapplication of polystyrene is in the fabrication of fluorescencebeads (FBs) The fluorescence molecules are loaded into thepolystyrene shell to produce FBs which are then used invarious sensing applications The polystyrene is also used tocoat the magnetic NPs so they can be conjugated with otherbiomolecules such as DNA and Proteins The applications ofpolystyrene include but are not limited to the detection ofE coli [139] the detection of cardiac Troponin T (cTnT) thedetection of Herpes simplex virus and many more

271 Covalent Modification Covalent modification throughcarboxyl group iswell known formodification of biomolecule

Most of the polystyrene-based nanoparticles bear large num-bers of pendant carboxyl which increases the loading amountof biomolecule

Enzyme catalyzed covalent immobilization of the pro-teins bearing a small 12-mer ldquoybbRrdquo tag onto the polystyrenenanoparticles (PSNP) is recently reported by Wong et al[140] As depicted in Scheme 11 the carboxyl-PSNPs werereacted with the bis-amino-polyethylene glycol in the pres-ence of HOSu and EDC to generate the amino-pegylatedPSNPs These PSNPs are then reacted with the g-maleimi-dobutyric acid succinimidyl (GMBS) to obtain maleimide-functionalized PSNPs The maleimide-functionalized PSNPsupon chemoligation with coenzyme A (CoA) produce theCoA-derivatized PSNPs

As depicted in Scheme 12 the protein of interest bearingybbR-tag is immobilized on the CoA-derivatized PSNPsThephosphopantetheinyl transferase (Sfp) catalyzed the reactionbetween the serine residue of the ybbR-tag and the phos-phopantetheine moiety of CoA with the simultaneous lossof 3101584051015840-adenine diphosphate results in the attachment ofproteins onto the surface of PSNPs It is reported that theenzymes immobilized by this method retain their activity

There are several reports on the use of fluoromicrobeadsfor the detection of biomarkers Primarily the fluoromi-crobeads are made up of carboxylated polystyrene as a coat-ingmaterial entrapping the fluorescentmolecules Accordingto the recent report by Song et al [37] the fluoromicrobeadswere used for the detection of the cTnT on the proteinmicroarray as depicted in Figure 12

The carboxylate modified fluoromicrobeads were conju-gated with the anti cTnI mAb through EDCNHS-mediated

14 Journal of Chemistry

HN

O

OH

OP

O

O

PO

O

OHO

N

NN

P

O

S

HN

O

Coenzyme A

Phosphopantetheine

PO

O

O

OHO

N Sfp

NN

N

P

O

ybbr-protein

HN

O

OH

OP

O

O

S

HN

O

NH2

NH2

Ominus

Ominus

Ominus

minusO

minusO

Mg2+

HO∙∙

Ominus

OminusOminus

minusO

N

O

Polystyrenenanoparticle

Scheme 12 Protein conjugation to polystyrene NP

System 1 antibody-conjugated fluoromicrobeads

System 2 avidin-conjugated fluoromicrobeads

DTSP SAM

Anti-cTnI cAb

cTnI

Figure 12 Application of the polystyrene-coated fluoromicrobeadsfor the detection of cTnI on the protein microarray (adapted from[37])

coupling reaction The use of fluoromicrobeads alloweddetecting the cTnI in plasma samples with a range of 01ndash100 ngmL

272 Affinity-Based Modification The affinity interactionsare used for the attachment of oligonucleotides with thefluoromicrobeads or polystyrene-coated magnetic beads Togenerate the oligonucleotide conjugated fluoromicrobeads ormagnetic beads respective polystyrene-coated beads are firstconjugated with the streptavidin using the EDCNHS cou-pling reaction as reported by Zhang et al [141] As depicted

B

B

MB MB

MB

BB

Magnetic bead

Streptavidin

DNA labeled biotin

Figure 13 DNA attachment to the magnetic beads

in Figure 13 the streptavidinmodified beads are then allowedto incubate with the biotinylated oligonucleotides Due to theaffinity of biotin for streptavidin the biotinylated oligonu-cleotides can be readily immobilized on the streptavidincoated beads

The binding affinity of streptavidin and biotin in solutionis up to 25 times 1013 (molL)minus1 [142] This interaction is about amillion times stronger than the antigen and antibody inter-action The antibodies directly immobilized onto the sur-face lose 90 of their biological activity [143] Howeverthe biotinylated antibodies immobilized on the streptavidincoated surface can retain their bioactivity [144]

Journal of Chemistry 15

3 Conclusions

Surface modification techniques of the materials used asplatforms in the fabrication of biosensors are reviewed inthis paper There are several reports on materials and vari-ous methods for altering their physicochemical propertiesHence one of these methods can be chosen according tothe targeted use and needed physiochemical properties Itis important to note that the performance of the biosensoris highly dependent on the substrate material used and itsmeticulous modification for particular applications There-fore it is critical to understand the principles of a biosensor toidentify the correct substrate material and its surface modifi-cation chemistry Furthermore it is important to look at thelatest advances in the materials and techniques used for thefabrication of a biosensor before the processing

Competing Interests

All authors declare that there is no conflict of interests

Acknowledgments

This research was supported by the Hallym UniversityResearch Fund (HRF-201601-010) This work was also sup-ported by the fund obtained through Industry-Academic col-laboration between Biometrix Technology Inc (ChuncheonSouth Korea) and Hallym University

References

[1] A Sassolas B D Leca-Bouvier and L J Blum ldquoDNA biosen-sors andmicroarraysrdquoChemical Reviews vol 108 no 1 pp 109ndash139 2008

[2] A Cavalcanti B Shirinzadeh M Zhang and L C KretlyldquoNanorobot hardware architecture for medical defenserdquo Sen-sors vol 8 no 5 pp 2932ndash2958 2008

[3] R-Q Zhang S-L Liu W Zhao et al ldquoA simple point-of-caremicrofluidic immunomagnetic fluorescence assay for path-ogensrdquo Analytical Chemistry vol 85 no 5 pp 2645ndash2651 2013

[4] S B Nimse K S Song M D Sonawane D R Sayyed and TS Kim ldquoImmobilization techniques for microarray challengesand applicationsrdquo Sensors vol 14 no 12 pp 22208ndash22229 2014

[5] A P F Turner ldquoBiosensors sense and sensibilityrdquo ChemicalSociety Reviews vol 42 no 8 pp 3184ndash3196 2013

[6] L Wu and X Qu ldquoCancer biomarker detection recent achieve-ments and challengesrdquoChemical Society Reviews vol 44 no 10pp 2963ndash2997 2015

[7] K Ariga Q Ji T Mori et al ldquoEnzyme nanoarchitectonicsorganization and device applicationrdquo Chemical Society Reviewsvol 42 no 15 pp 6322ndash6345 2013

[8] W-W Zhao J-J Xu and H-Y Chen ldquoPhotoelectrochemicalDNA biosensorsrdquo Chemical Reviews vol 114 no 15 pp 7421ndash7441 2014

[9] Q Liu C Wu H Cai N Hu J Zhou and P Wang ldquoCell-basedbiosensors and their application in biomedicinerdquo ChemicalReviews vol 114 no 12 pp 6423ndash6461 2014

[10] X Zhao S Nampalli A J Serino and S Kumar ldquoImmobi-lization of oligodeoxyribonucleotides with multiple anchors to

microchipsrdquo Nucleic Acids Research vol 29 no 4 pp 955ndash9592001

[11] P Kumar S K Agrawal A Misra and K C Gupta ldquoA newheterobifunctional reagent for immobilization of biomoleculeson glass surfacerdquo Bioorganic 120572Medicinal Chemistry Letters vol14 no 5 pp 1097ndash1099 2004

[12] F Secundo ldquoConformational changes of enzymes upon immo-bilisationrdquo Chemical Society Reviews vol 42 no 15 pp 6250ndash6261 2013

[13] S Lee S Kim J Malm O C Jeong H Lilja and T LaurellldquoImproved porous silicon microarray based prostate specificantigen immunoassay by optimized surface density of thecapture antibodyrdquoAnalytica Chimica Acta vol 796 pp 108ndash1142013

[14] K Jaras A A Tajudin A Ressine et al ldquoENSAM europiumnanoparticles for signal enhancement of antibody microarrayson nanoporous siliconrdquo Journal of Proteome Research vol 7 no3 pp 1308ndash1314 2008

[15] C Steinhauer A Ressine G Marko-Varga T Laurell C AK Borrebaeck and C Wingren ldquoBiocompatibility of surfacesfor antibody microarrays design of macroporous silicon sub-stratesrdquo Analytical Biochemistry vol 341 no 2 pp 204ndash2132005

[16] K Jaras B Adler A Tojo et al ldquoPorous silicon antibodymicroarrays for quantitative analysis measurement of free andtotal PSA in clinical plasma samplesrdquo Clinica Chimica Acta vol414 pp 76ndash84 2012

[17] S W Lee K Hosokawa S Kim et al ldquoA highly sensitive poroussilicon (P-Si)-based human Kallikrein 2 (hK2) immunoassayplatform toward accurate diagnosis of prostate cancerrdquo Sensorsvol 15 no 5 pp 11972ndash11987 2015

[18] C Roychaudhuri ldquoA review on porous silicon based electro-chemical biosensors beyond surface area enhancement factorrdquoSensors and Actuators B Chemical vol 210 pp 310ndash323 2015

[19] ARessine S EkstromGMarko-Varga andT Laurell ldquoMacro-nanoporous silicon as a support for high-performance proteinmicroarraysrdquo Analytical Chemistry vol 75 no 24 pp 6968ndash6974 2003

[20] S Lee E Silajdzic H Yang et al ldquoA porous silicon immunoas-say platform for fluorometric determination of 120572-synuclein inhuman cerebrospinal fluidrdquo Microchimica Acta vol 181 no 9-10 pp 1143ndash1149 2014

[21] S Belhousse N Belhaneche-Bensemra K Lasmi et alldquoModified porous silicon for electrochemical sensor of para-nitrophenolrdquo Materials Science and Engineering B vol 189 pp76ndash81 2014

[22] N Reta A Michelmore C Saint B Prieto-Simon and NH Voelcker ldquoPorous silicon membrane-modified electrodesfor label-free voltammetric detection of MS2 bacteriophagerdquoBiosensors and Bioelectronics vol 80 pp 47ndash53 2016

[23] B Guan A Magenau S Ciampi K Gaus P J Reece and J JGooding ldquoAntibody modified porous silicon microparticles forthe selective capture of cellsrdquo Bioconjugate Chemistry vol 25no 7 pp 1282ndash1289 2014

[24] S Vutti N Buch-Manson S Schoffelen N Bovet K LMartinez and M Meldal ldquoCovalent and stable CuAAC mod-ification of silicon surfaces for control of cell adhesionrdquo Chem-BioChem vol 16 no 5 pp 782ndash791 2015

[25] A M Rossi L Wang V Reipa and T E Murphy ldquoPoroussilicon biosensor for detection of virusesrdquo Biosensors andBioelectronics vol 23 no 5 pp 741ndash745 2007

16 Journal of Chemistry

[26] T L Lasseter B H Clare N L Abbott and R J HamersldquoCovalently modified silicon and diamond surfaces resistanceto nonspecific protein adsorption and optimization for biosens-ingrdquo Journal of the American Chemical Society vol 126 no 33pp 10220ndash10221 2004

[27] M Li K-G Neoh E-T Kang T Lau and E E ChiongldquoSurface modification of silicone with covalently immobilizedand crosslinked agarose for potential application in the inhibi-tion of infection and omental wrappingrdquo Advanced FunctionalMaterials vol 24 no 11 pp 1631ndash1643 2014

[28] G MacBeath and S L Schreiber ldquoPrinting proteins as microar-rays for high-throughput function determinationrdquo Science vol289 no 5485 pp 1760ndash1763 2000

[29] S B Nimse M D Sonawane K S Song and T Kim ldquoBio-marker detection technologies and future directionsrdquoThe Ana-lyst vol 141 no 3 pp 740ndash755 2016

[30] M D Sonawane S B Nimse K Song and T Kim ldquoDetectionquantification and profiling of PSA current microarray tech-nologies and future directionsrdquo RSC Advances vol 6 no 9 pp7599ndash7609 2016

[31] S B Nimse and T Kim ldquoBiological applications of function-alized calixarenesrdquo Chemical Society Reviews vol 42 no 1 pp366ndash386 2013

[32] K-S Song S B Nimse J Kim et al ldquo9GDNAChip microarraybased on the multiple interactions of 9 consecutive guaninesrdquoChemical Communications vol 47 no 25 pp 7101ndash7103 2011

[33] R J Chen S Bangsaruntip K A Drouvalakis et al ldquoNonco-valent functionalization of carbon nanotubes for highly specificelectronic biosensorsrdquo Proceedings of the National Academy ofSciences of the United States of America vol 100 no 9 pp 4984ndash4989 2003

[34] Y Lu W Shi J Qin and B Lin ldquoFabrication and characteri-zation of paper-based microfluidics prepared in nitrocellulosemembrane by wax printingrdquo Analytical Chemistry vol 82 no1 pp 329ndash335 2010

[35] P Zhang R Zhang M Gao and X Zhang ldquoNovel nitrocel-lulose membrane substrate for efficient analysis of circulatingtumor cells coupled with surface-enhanced raman scatteringimagingrdquo ACS Applied Materials and Interfaces vol 6 no 1 pp370ndash376 2014

[36] J-S Lee A K R Lytton-Jean S J Hurst and C AMirkin ldquoSil-ver nanoparticlemdasholigonucleotide conjugates based on DNAwith triple cyclic disulfide moietiesrdquo Nano Letters vol 7 no 7pp 2112ndash2115 2007

[37] S Y Song Y D Han K Kim S S Yang and H C YoonldquoA fluoro-microbead guiding chip for simple and quantifiableimmunoassay of cardiac troponin I (cTnI)rdquo Biosensors andBioelectronics vol 26 no 9 pp 3818ndash3824 2011

[38] S V Lemeshko T Powdrill Y Y Belosludtsev and M HoganldquoOligonucleotides form a duplex with non-helical properties ona positively charged surfacerdquoNucleic Acids Research vol 29 no14 pp 3051ndash3058 2001

[39] Z-L Zhi A K Powell and J E Turnbull ldquoFabrication ofcarbohydrate microarrays on gold surfaces direct attachmentof nonderivatized oligosaccharides to hydrazide-modified self-assembledmonolayersrdquoAnalytical Chemistry vol 78 no 14 pp4786ndash4793 2006

[40] S L Pan and L Rothberg ldquoChemical control of electrodefunctionalization for detection of DNA hybridization by elec-trochemical impedance spectroscopyrdquo Langmuir vol 21 no 3pp 1022ndash1027 2005

[41] Z Lu C M Li Q Zhou Q-L Bao and X Cui ldquoCovalentlylinked DNAprotein multilayered film for controlled DNAreleaserdquo Journal of Colloid and Interface Science vol 314 no 1pp 80ndash88 2007

[42] L-S Jang and H-J Liu ldquoFabrication of protein chips basedon 3-aminopropyltriethoxysilane as a monolayerrdquo BiomedicalMicrodevices vol 11 no 2 pp 331ndash338 2009

[43] F Fixe M Dufva P Telleman and C B Christensen ldquoFunc-tionalization of poly(methyl methacrylate) (PMMA) as a sub-strate for DNAmicroarraysrdquoNucleic Acids Research vol 32 no1 article e9 2004

[44] A Lueking M Horn H Eickhoff K Bussow H Lehrachand G Walter ldquoProtein microarrays for gene expression andantibody screeningrdquo Analytical Biochemistry vol 270 no 1 pp103ndash111 1999

[45] N Zammatteo L Jeanmart S Hamels et al ldquoComparisonbetween different strategies of covalent attachment of DNA toglass surfaces to build DNA microarraysrdquo Analytical Biochem-istry vol 280 no 1 pp 143ndash150 2000

[46] M Ozmen K Can I Akin et al ldquoSurface modification of glassbeads with glutaraldehyde characterization and their adsorp-tion property for metal ionsrdquo Journal of Hazardous Materialsvol 171 no 1ndash3 pp 594ndash600 2009

[47] C Funk PM Dietrich T Gross HMinW E S Unger andWWeigel ldquoEpoxy-functionalized surfaces for microarray appli-cations surface chemical analysis and fluorescence labeling ofsurface speciesrdquo Surface and Interface Analysis vol 44 no 8pp 890ndash894 2012

[48] S Mahajan P Kumar and K C Gupta ldquoOligonucleotide mic-roarrays immobilization of phosphorylated oligonucleotideson epoxylated surfacerdquo Bioconjugate Chemistry vol 17 no 5pp 1184ndash1189 2006

[49] M C Pirrung J D Davis and A L Odenbaugh ldquoNovelreagents and procedures for immobilization of DNA on glassmicrochips for primer extensionrdquo Langmuir vol 16 no 5 pp2185ndash2191 2000

[50] E Southern K Mir and M Shchepinov ldquoMolecular interac-tions on microarraysrdquo Nature Genetics vol 21 no 1 pp 5ndash91999

[51] M S Shchepinov S C Case-Green and E M SouthernldquoSteric factors influencing hybridisation of nucleic acids tooligonucleotide arraysrdquo Nucleic Acids Research vol 25 no 6pp 1155ndash1161 1997

[52] D A Tomalia A M Naylor and W A Goddard III ldquoStarbustdendrimers molecular-level control of size shape surfacechemistry topology and flexibility from atoms to macroscopicmatterrdquo Angewandte ChemiemdashInternational Edition in Englishvol 29 no 2 pp 138ndash175 1990

[53] R Benters C M Niemeyer D Drutschmann D Blohm andD Wohrle ldquoDNA microarrays with PAMAM dendritic linkersystemsrdquo Nucleic Acids Research vol 30 no 2 p e10 2002

[54] J H Moon J W Shin S Y Kim and J W Park ldquoFormationof uniform aminosilane thin layers an imine formation tomeasure relative surface density of the amine grouprdquo Langmuirvol 12 no 20 pp 4621ndash4624 1996

[55] J C Alwine D J Kemp and G R Stark ldquoMethod fordetection of specific RNAs in agarose gels by transfer to diazo-benzyloxymethyl-paper and hybridization with DNA probesrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 74 no 12 pp 5350ndash5354 1977

[56] P L Dolan Y Wu L K Ista R L Metzenberg M A Nelsonand G P Lopez ldquoRobust and efficient synthetic method for

Journal of Chemistry 17

forming DNA microarraysrdquo Nucleic Acids Research vol 29 no21 article e107 2001

[57] S B Nimse J Kim K-S Song et al ldquoSelective recognitionof the ditopic trimethylammonium cations by water-solubleaminocalix[4]arenerdquo Tetrahedron Letters vol 52 no 29 pp3751ndash3755 2011

[58] V-T Ta S B Nimse K-S Song et al ldquoCharacterization ofthe mixed self-assembled monolayer at the molecular scalerdquoChemical Communications vol 47 no 40 pp 11261ndash11263 2011

[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

[60] Y Lee E K Lee YW Cho et al ldquoProteoChip a highly sensitiveprotein microarray prepared by a novel method of proteinimmobilization for application of protein-protein interactionstudiesrdquo Proteomics vol 3 no 12 pp 2289ndash2304 2003

[61] S W Oh J D Moon H J Lim et al ldquoCalixarene derivative asa tool for highly sensitive detection and oriented immobiliza-tion of proteins in a microarray format through noncovalentmolecular interactionrdquo The FASEB Journal vol 19 no 10 pp1335ndash1337 2005

[62] S B Nimse K-S Song J Kim D R Sayyed and T Kimldquo9G DNAChip technology self-assembled monolayer (SAM)of ssDNA for ultra-sensitive detection of biomarkersrdquo Interna-tional Journal ofMolecular Sciences vol 14 no 3 pp 5723ndash57332013

[63] V-T Nguyen S B Nimse K-S Song et al ldquoHPAI 9GDNAChip discrimination of highly pathogenic influenza virusgenesrdquo Chemical Communications vol 48 no 38 pp 4582ndash4584 2012

[64] K-S Song S B Nimse J Kim D R Sayyed and T Kim ldquoAnew platform for a convenient genotyping systemrdquo ChemicalCommunications vol 49 no 26 pp 2661ndash2663 2013

[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

[67] F Hennrich C Chan VMoore M Rolandi andM OrsquoConnellCarbonNanotubes Properties and Applications Taylor amp FrancisGroup Abingdon UK 2006

[68] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

[69] C Singh M Shaffer I Kinloch and A Windle ldquoProductionof aligned carbon nanotubes by the CVD injection methodrdquoPhysica B Condensed Matter vol 323 no 1ndash4 pp 339ndash3402002

[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

[71] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

10 Journal of Chemistry

HO

OSH AuNP

AuNP-mAb

mAbEDCNHS

001M PBS

(CH2)15(CH2)11

NaBH4HAuCl4 + SH + HO

pH sim 74

Scheme 7 Immobilization on antibodies on AuNP

NC membrane

Cross section view

PrintingStep 1

Step 2 Baking

Wax patternedNC membrane

Wax is printed onto thesurface of NC membrane

Wax melts and penetratesthrough NC membrane

Nitrocellulose

Wax

Figure 8Wax printing on nitrocellulosemembranes (adapted from[34])

untreated membrane is avoided Wax printing method gen-erates 100 120583mmicrochannel which removes the micrometersize contaminants and makes the wax printed membranessuitable for the applications in microfluidic assays Apartfrom immobilization wax printing has application in dotimmunoassay and sample purifications [34]

Due to advantages of NC membrane for high bindingcapacity and good flow of solution it is also used on the chipsurfaces The glass slide can be coated with the 12 120583m layer ofNC to afford a platform with the intrinsic properties of NCThe solution of cAbs in PBS buffer containing 10 glycerolis then spotted on the modified surface After spotting theslides are incubated for one hour After incubation slides arewashed with 01 Tween 20 in PBS buffer and dried to gen-erate the platform for detection of biomarker proteins [116]

Apart from routine microarray applications NC mem-brane is also used for the detection of circulating tumor cells(CTC) as reported by Zhang et al The binding of CTCs bythe cAbs immobilized on the NC membrane is detected bySurface Enhanced Raman Scattering (SERS) as depicted inFigure 9

Usually the antibodies specific for cancer cells are usedas a capture substrate and immobilized on the surface TheNC membrane is cut into 1 cm times 1 cm pieces Then thesepieces are immersed in the ethanol and then tiled on thePMMA wafer After washing the membrane is activated byusing PBS buffer containing antibodies at 37∘C for 30minDuring this process the cAbs are avidly immobilized on theNC membrane The 1 BSA solution is loaded to block thefree surface area to avoid any background signals due tononspecific interactions Finally the membranes are washedwith PBS buffer and stored at 4∘CThe gold nanoparticle andRaman probes are used to detect the CTCs by SERS [35]

25 Gold Application of nanoparticles is amost focused areain the field of inorganic chemistry and it has also attractedimaginations of many biologists too Inorganic nanoparti-cles including gold silver and ferrous oxides have foundmany important applications in cell signaling drug deliveryand colorimetric and fluorescence-based detections Goldnanoparticles (AuNP) functionalized with proteins DNAsor Raman probes are well known in the field of biosensorsand nanobiotechnology for their applications in the molec-ular diagnostics [117ndash119] protein detection [120ndash122] generegulation [123] and cell imaging [124]

251 Covalent Modification

(1) Thiol Based Modification AuNPs are commonly usedin the electrochemical and optical detection systems Theconjugation with biomolecule does not change the opticalproperties ofAuNP [125]Di Pasqua et al reported thiolmod-ification for the detection of E coli O157H7 E coli specificantibodies were conjugated with the AuNPs [126] As shownin Scheme 7 the 10 nmAuNPs are carboxylated and then cou-pled to E coli specific monoclonal antibody (mAb) throughamide coupling

For the generation of AuNPs to the solution containing410mg of HAuCl

4sdot3H2O in 6mL of water ethanoic solutions

of 11-mercapto-1-undecanol and 16-mercaptohexadecanoicacid are added Upon addition of NaBH

4to this mixture at

0∘C the solution turns brown The product AuNP cappedwith alkanethiol pendant alcohol and carboxylic acid func-tional groups precipitate upon three hours of stirring Theprecipitated particles are then thoroughly washed with etha-nol and an ethanolic solution containing a small amountof 1M HCl The AuNPs are then dried under vacuum forten hours For the conjugation of mABs with the AuNPsthe carboxylic acid functional groups on the AuNPs are

Journal of Chemistry 11

SERSimaging

AuNPs

Raman labelNC membrane

AntibodyCancer cell

Figure 9 Detection of circulating tumor cells on NC membranes containing immobilized cAbs (adapted from [35])

activated by reacting the AuNPs with 1-ethyl-3-3(3-dimeth-ylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in the PBS buffer The mABs arethen added to this solution and the suspension is stirred atroom temperature for 30min The mAB-conjugated AuNPsare then collected by centrifugation and washing with PBSand ethanol The mAB-conjugated AuNPs successfully bindto E coli when incubated in PBS at pH 74 In other reportsthe AuNPs were found very effective in the detection ofcancerous pancreatic cells

The AuNPs are known to suffer from the problem ofaggregation upon long-term storage Therefore to solve thisissue the AuNPs are conjugated with the polyethylene glycol(PEG) to prevent their aggregation [127 128]The conjugationof PEGwith the AuNPsmakes the later hydrophilic thus pre-venting agglomeration induced by hydrophobic interactionsA PEGwith the heterobifunctional groups (dithiol at one endand a carboxyl at another end) is coated on the AuNP Thedithiol group allows stable anchoring heterobifunctional PEGligands on the surface of AuNP and the terminal carboxylgroup is used for coupling with antibodies The carboxy-terminated bifunctional PEG linker is synthesized by follow-ing a method reported by Eck et al which is depicted inScheme 8 The anionic polymerization of compound 1 withan excess of ethylene oxide allows synthesizing compound 2The treatment of compound 2 with chloroacetic acid at 60∘Callows generating compound 3 The reaction of an excess ofthe elemental bromine in dichloromethane at 0∘C for fourhours in the dark with compound 3 produces dibromidecompound 4 Compound 5 is obtained by reaction withcompound 4 in water with the excess of sodium hydrosulfidehydrate

The synthesized bifunctional PEG linker is then conju-gated with the citrate-stabilized gold nanoparticles by simpleligand exchangeThe citrate-stabilized gold nanoparticles areknown to aggregate in the buffer containing salts Thereforethe ligand exchange from citrate to PEG should be done inpure water The PEGylated AuNPs are conjugated to mono-clonal F19 antibodies for the detection of human pancreaticcarcinoma through EDCNHS coupling reaction [129]

OHO

(2) HCl

1

2

3

4

5

Br Br

HS SH

(CH2)9

(CH2)9

(CH2)9

(CH2)9

+

NaHDMF60∘C

(OCH2CH2)n

(OCH2CH2)n

(OCH2CH2)n

OCH2COOH

OCH2COOH

(CH2)9 (OCH2CH2)n OCH2COOH

OminusNa+

Br2

(2) Acetic acid (1) NaSHH2O

60∘C(1) ClCH2-COONa

Scheme 8 Synthesis of bifunctional PEG linker using conjugationwith AuNP

(2) Hydrazide Modification According to the report by Zhiet al the hydrazide-derivatized self-assembledmonolayer ona gold surface is used for the efficient and selective anchor-ing of oligosaccharide [39] The generated oligosaccharidemicroarrays allow the fluorescence-based detection of targetproteins The use of gold as a substrate for the fluorescence-based detection suffers from the drawbacks including flu-orescence quenching and nonspecific surface adsorption ofproteins However the use of120596-thiolated fatty acid (C

16) self-

assembledmonolayer between the gold surface andhydrazide

12 Journal of Chemistry

AuC C

C

C

OHOHO O

O

O

O

O

O

O

O

O

CHR

NN

H

N

N

N

H

NH

NH

NH

H

NH

C

O

O

O NNH

NH

HNH

H

S

S

S

S

HS Au

Au

Au

Au

Au

C16 SAM

Adipic dihydrazideEDC

(Sugar)R-CHO

Binding to protein

Sugarprobe

Protein Alexafluoro 532

SAM andblocking layer

Ab 2nd Ab

NH2

NH2H2N

CH2R

Scheme 9 Application of hydrazide-derivatized SAM on a goldsurface for the fabrication of oligosaccharide microarray (adaptedfrom [39])

groups minimizes the quenching effect Moreover the effec-tive blocking of the surface with the poly(ethylene glycol)aldehyde and BSA reduces the nonspecific adsorption ofprotein on the surface

For the fabrication of the reported oligosaccharidemicroarrays the gold substrate is prepared by following amethod depicted in Scheme 9 The self-assembled mono-layer (SAM) of 16-mercaptohexadecanoic acid (MHDA) isobtained by soaking the gold coated slides in the isobutylalcohol for 2 days The slides are then washed in ethanolto remove excess reagents and are dried under the nitrogenstream The carboxyl functional groups on the SAM areconverted to the hydrazide groups by incubation of the SAMcovered slides in the dimethyl sulfoxide solution containing1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and adipicdihydrazide The ethanol-washed and dried slides are thenused for the oligosaccharide printing to obtain oligosaccha-ride microarrays

The generated oligosaccharide microarray platformallows interrogation of carbohydrate-protein interactions ina high-throughput manner

26 Silver Similar to AuNPs silver nanoparticles (AgNP) arealso used for the immobilization of proteins and enzymesThe surface of AgNP allows adsorption of proteins Henceit can be utilized as a host matrix for various biomoleculesSilver is a suitable substrate for the immobilization of wholecell or the isolated enzymes [130 131]

Texp lt Tm

Ag

AgAg

Ag

AgAg

Texp gt Tm

Figure 10 AgNPs-oligonucleotide conjugates (adapted from [36])

261 Electrostatic Modification The electrostatic interac-tions allow the physical adsorption of biomolecules on thesurface of AgNPs Shen et al reported that the AgNPs aresynthesized by reduction of silver nitrate in the presence ofsodium citrate During the reduction process the solutionis sonicated for 15min to obtain the yellow silver colloidwhich is then kept at 4∘C for several days away from lightThen isolated nanoparticles can be used for physisorption ofproteins at a pH higher than their isoelectric point [132]

262 Covalent Modification As depicted in Scheme 10the AgNPs prepared by the citrate reduction method andstabilized with citrate [133] can be functionalized with car-boxyl groups upon treatment with 3-mercaptopropanoic acid(MPA) As reported by the Petkova et al for the immobi-lization of alcohol dehydrogenase from Thermoanaerobiumbrockii (TbADH) the carboxyl-modified AgNPs were treatedwith the solution containing TbADH under continuousstirring for 7 h at 26∘C a research by [134] The AgNPsmodified with the TbADH were successfully used for thebiotransformation studies

The application of a bifunctional linker for the modifica-tion of AgNPs is reported [135 136] The bifunctional linker11-mercaptoundecanoic acid was used with 1-octanethiol in1 1 ratio to generate the mixed SAM on the surface of AgNPThe IgG antibodies are then conjugated with the mixed SAMmodified AgNPs It is reported that upon covalent conjuga-tion of biomolecules with AgNPs their stability and activityis maintained [137]

According to another report on the covalent modifi-cation AgNPs-oligonucleotide conjugates are prepared byusing DNA and triple cyclic disulfide moieties [36] Asdepicted in Figure 10 the two types ofAgNPs-oligonucleotideconjugates with complementary DNA sequences undergoDNA hybridization driven coagulation resulting in the colorchange

As depicted in Figure 11 the AgNP-DNA conjugates wereprepared by treatment of AgNPs with the cyclic disulfidemodified oligonucleotide The AgNP and oligonucleotideswere allowed to react with each other with 1 4 ratio inthe presence of 1 sodium dodecyl sulfate and NaCl Theovernight incubation of solution results in the AgNP-DNAconjugates which are collected by centrifugation and washedto remove the excess DNAs

Journal of Chemistry 13

Ag AgMPAOH

OO OH

O

HOCitrate

Citrate

Ag

COOH

COOH

TbADHAg

CONH

COOH

TbADHOminusNa+

H2N

Scheme 10 Covalent conjugation of enzymes on the surface of carboxyl-modified AgNPs

OHO

EDC HOSu Bis-amino

polyethylene glycol

NH

OO

44GMBS N

H

OO N

H44

ON

O

O3

CoA

NH

OO N

H44

ON

O

O3

SHN

O

OH

OP O

OPO

O O

OHO

NNN

N

PO

OminusOminus

OminusOminus

NH2

NH2

Scheme 11 Covalent conjugation of coenzyme A to polystyrene nanoparticles

O OOO P

OHSS

5998400 (DSP)3-A10-ATT-ATC-ACT 3998400

DSP cyclic disulfide-containingphosphate derivative =

Figure 11 Conjugation of AgNPs with oligonucleotides by usingDSP as a linker molecule (adapted from [36])

27 Polystyrene Polystyrene is an aromatic polymerobtained by polymerization of styrene monomers [138] Thepolystyrene-based NPs are widely used in the moleculardiagnostics for the detection of biomarker proteins andgenomic DNAs Polystyrene can be employed as a coating ona variety of nanoparticles as its functional groups can be easilymodified or conjugated with other molecules The otherapplication of polystyrene is in the fabrication of fluorescencebeads (FBs) The fluorescence molecules are loaded into thepolystyrene shell to produce FBs which are then used invarious sensing applications The polystyrene is also used tocoat the magnetic NPs so they can be conjugated with otherbiomolecules such as DNA and Proteins The applications ofpolystyrene include but are not limited to the detection ofE coli [139] the detection of cardiac Troponin T (cTnT) thedetection of Herpes simplex virus and many more

271 Covalent Modification Covalent modification throughcarboxyl group iswell known formodification of biomolecule

Most of the polystyrene-based nanoparticles bear large num-bers of pendant carboxyl which increases the loading amountof biomolecule

Enzyme catalyzed covalent immobilization of the pro-teins bearing a small 12-mer ldquoybbRrdquo tag onto the polystyrenenanoparticles (PSNP) is recently reported by Wong et al[140] As depicted in Scheme 11 the carboxyl-PSNPs werereacted with the bis-amino-polyethylene glycol in the pres-ence of HOSu and EDC to generate the amino-pegylatedPSNPs These PSNPs are then reacted with the g-maleimi-dobutyric acid succinimidyl (GMBS) to obtain maleimide-functionalized PSNPs The maleimide-functionalized PSNPsupon chemoligation with coenzyme A (CoA) produce theCoA-derivatized PSNPs

As depicted in Scheme 12 the protein of interest bearingybbR-tag is immobilized on the CoA-derivatized PSNPsThephosphopantetheinyl transferase (Sfp) catalyzed the reactionbetween the serine residue of the ybbR-tag and the phos-phopantetheine moiety of CoA with the simultaneous lossof 3101584051015840-adenine diphosphate results in the attachment ofproteins onto the surface of PSNPs It is reported that theenzymes immobilized by this method retain their activity

There are several reports on the use of fluoromicrobeadsfor the detection of biomarkers Primarily the fluoromi-crobeads are made up of carboxylated polystyrene as a coat-ingmaterial entrapping the fluorescentmolecules Accordingto the recent report by Song et al [37] the fluoromicrobeadswere used for the detection of the cTnT on the proteinmicroarray as depicted in Figure 12

The carboxylate modified fluoromicrobeads were conju-gated with the anti cTnI mAb through EDCNHS-mediated

14 Journal of Chemistry

HN

O

OH

OP

O

O

PO

O

OHO

N

NN

P

O

S

HN

O

Coenzyme A

Phosphopantetheine

PO

O

O

OHO

N Sfp

NN

N

P

O

ybbr-protein

HN

O

OH

OP

O

O

S

HN

O

NH2

NH2

Ominus

Ominus

Ominus

minusO

minusO

Mg2+

HO∙∙

Ominus

OminusOminus

minusO

N

O

Polystyrenenanoparticle

Scheme 12 Protein conjugation to polystyrene NP

System 1 antibody-conjugated fluoromicrobeads

System 2 avidin-conjugated fluoromicrobeads

DTSP SAM

Anti-cTnI cAb

cTnI

Figure 12 Application of the polystyrene-coated fluoromicrobeadsfor the detection of cTnI on the protein microarray (adapted from[37])

coupling reaction The use of fluoromicrobeads alloweddetecting the cTnI in plasma samples with a range of 01ndash100 ngmL

272 Affinity-Based Modification The affinity interactionsare used for the attachment of oligonucleotides with thefluoromicrobeads or polystyrene-coated magnetic beads Togenerate the oligonucleotide conjugated fluoromicrobeads ormagnetic beads respective polystyrene-coated beads are firstconjugated with the streptavidin using the EDCNHS cou-pling reaction as reported by Zhang et al [141] As depicted

B

B

MB MB

MB

BB

Magnetic bead

Streptavidin

DNA labeled biotin

Figure 13 DNA attachment to the magnetic beads

in Figure 13 the streptavidinmodified beads are then allowedto incubate with the biotinylated oligonucleotides Due to theaffinity of biotin for streptavidin the biotinylated oligonu-cleotides can be readily immobilized on the streptavidincoated beads

The binding affinity of streptavidin and biotin in solutionis up to 25 times 1013 (molL)minus1 [142] This interaction is about amillion times stronger than the antigen and antibody inter-action The antibodies directly immobilized onto the sur-face lose 90 of their biological activity [143] Howeverthe biotinylated antibodies immobilized on the streptavidincoated surface can retain their bioactivity [144]

Journal of Chemistry 15

3 Conclusions

Surface modification techniques of the materials used asplatforms in the fabrication of biosensors are reviewed inthis paper There are several reports on materials and vari-ous methods for altering their physicochemical propertiesHence one of these methods can be chosen according tothe targeted use and needed physiochemical properties Itis important to note that the performance of the biosensoris highly dependent on the substrate material used and itsmeticulous modification for particular applications There-fore it is critical to understand the principles of a biosensor toidentify the correct substrate material and its surface modifi-cation chemistry Furthermore it is important to look at thelatest advances in the materials and techniques used for thefabrication of a biosensor before the processing

Competing Interests

All authors declare that there is no conflict of interests

Acknowledgments

This research was supported by the Hallym UniversityResearch Fund (HRF-201601-010) This work was also sup-ported by the fund obtained through Industry-Academic col-laboration between Biometrix Technology Inc (ChuncheonSouth Korea) and Hallym University

References

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[2] A Cavalcanti B Shirinzadeh M Zhang and L C KretlyldquoNanorobot hardware architecture for medical defenserdquo Sen-sors vol 8 no 5 pp 2932ndash2958 2008

[3] R-Q Zhang S-L Liu W Zhao et al ldquoA simple point-of-caremicrofluidic immunomagnetic fluorescence assay for path-ogensrdquo Analytical Chemistry vol 85 no 5 pp 2645ndash2651 2013

[4] S B Nimse K S Song M D Sonawane D R Sayyed and TS Kim ldquoImmobilization techniques for microarray challengesand applicationsrdquo Sensors vol 14 no 12 pp 22208ndash22229 2014

[5] A P F Turner ldquoBiosensors sense and sensibilityrdquo ChemicalSociety Reviews vol 42 no 8 pp 3184ndash3196 2013

[6] L Wu and X Qu ldquoCancer biomarker detection recent achieve-ments and challengesrdquoChemical Society Reviews vol 44 no 10pp 2963ndash2997 2015

[7] K Ariga Q Ji T Mori et al ldquoEnzyme nanoarchitectonicsorganization and device applicationrdquo Chemical Society Reviewsvol 42 no 15 pp 6322ndash6345 2013

[8] W-W Zhao J-J Xu and H-Y Chen ldquoPhotoelectrochemicalDNA biosensorsrdquo Chemical Reviews vol 114 no 15 pp 7421ndash7441 2014

[9] Q Liu C Wu H Cai N Hu J Zhou and P Wang ldquoCell-basedbiosensors and their application in biomedicinerdquo ChemicalReviews vol 114 no 12 pp 6423ndash6461 2014

[10] X Zhao S Nampalli A J Serino and S Kumar ldquoImmobi-lization of oligodeoxyribonucleotides with multiple anchors to

microchipsrdquo Nucleic Acids Research vol 29 no 4 pp 955ndash9592001

[11] P Kumar S K Agrawal A Misra and K C Gupta ldquoA newheterobifunctional reagent for immobilization of biomoleculeson glass surfacerdquo Bioorganic 120572Medicinal Chemistry Letters vol14 no 5 pp 1097ndash1099 2004

[12] F Secundo ldquoConformational changes of enzymes upon immo-bilisationrdquo Chemical Society Reviews vol 42 no 15 pp 6250ndash6261 2013

[13] S Lee S Kim J Malm O C Jeong H Lilja and T LaurellldquoImproved porous silicon microarray based prostate specificantigen immunoassay by optimized surface density of thecapture antibodyrdquoAnalytica Chimica Acta vol 796 pp 108ndash1142013

[14] K Jaras A A Tajudin A Ressine et al ldquoENSAM europiumnanoparticles for signal enhancement of antibody microarrayson nanoporous siliconrdquo Journal of Proteome Research vol 7 no3 pp 1308ndash1314 2008

[15] C Steinhauer A Ressine G Marko-Varga T Laurell C AK Borrebaeck and C Wingren ldquoBiocompatibility of surfacesfor antibody microarrays design of macroporous silicon sub-stratesrdquo Analytical Biochemistry vol 341 no 2 pp 204ndash2132005

[16] K Jaras B Adler A Tojo et al ldquoPorous silicon antibodymicroarrays for quantitative analysis measurement of free andtotal PSA in clinical plasma samplesrdquo Clinica Chimica Acta vol414 pp 76ndash84 2012

[17] S W Lee K Hosokawa S Kim et al ldquoA highly sensitive poroussilicon (P-Si)-based human Kallikrein 2 (hK2) immunoassayplatform toward accurate diagnosis of prostate cancerrdquo Sensorsvol 15 no 5 pp 11972ndash11987 2015

[18] C Roychaudhuri ldquoA review on porous silicon based electro-chemical biosensors beyond surface area enhancement factorrdquoSensors and Actuators B Chemical vol 210 pp 310ndash323 2015

[19] ARessine S EkstromGMarko-Varga andT Laurell ldquoMacro-nanoporous silicon as a support for high-performance proteinmicroarraysrdquo Analytical Chemistry vol 75 no 24 pp 6968ndash6974 2003

[20] S Lee E Silajdzic H Yang et al ldquoA porous silicon immunoas-say platform for fluorometric determination of 120572-synuclein inhuman cerebrospinal fluidrdquo Microchimica Acta vol 181 no 9-10 pp 1143ndash1149 2014

[21] S Belhousse N Belhaneche-Bensemra K Lasmi et alldquoModified porous silicon for electrochemical sensor of para-nitrophenolrdquo Materials Science and Engineering B vol 189 pp76ndash81 2014

[22] N Reta A Michelmore C Saint B Prieto-Simon and NH Voelcker ldquoPorous silicon membrane-modified electrodesfor label-free voltammetric detection of MS2 bacteriophagerdquoBiosensors and Bioelectronics vol 80 pp 47ndash53 2016

[23] B Guan A Magenau S Ciampi K Gaus P J Reece and J JGooding ldquoAntibody modified porous silicon microparticles forthe selective capture of cellsrdquo Bioconjugate Chemistry vol 25no 7 pp 1282ndash1289 2014

[24] S Vutti N Buch-Manson S Schoffelen N Bovet K LMartinez and M Meldal ldquoCovalent and stable CuAAC mod-ification of silicon surfaces for control of cell adhesionrdquo Chem-BioChem vol 16 no 5 pp 782ndash791 2015

[25] A M Rossi L Wang V Reipa and T E Murphy ldquoPoroussilicon biosensor for detection of virusesrdquo Biosensors andBioelectronics vol 23 no 5 pp 741ndash745 2007

16 Journal of Chemistry

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[27] M Li K-G Neoh E-T Kang T Lau and E E ChiongldquoSurface modification of silicone with covalently immobilizedand crosslinked agarose for potential application in the inhibi-tion of infection and omental wrappingrdquo Advanced FunctionalMaterials vol 24 no 11 pp 1631ndash1643 2014

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[29] S B Nimse M D Sonawane K S Song and T Kim ldquoBio-marker detection technologies and future directionsrdquoThe Ana-lyst vol 141 no 3 pp 740ndash755 2016

[30] M D Sonawane S B Nimse K Song and T Kim ldquoDetectionquantification and profiling of PSA current microarray tech-nologies and future directionsrdquo RSC Advances vol 6 no 9 pp7599ndash7609 2016

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[32] K-S Song S B Nimse J Kim et al ldquo9GDNAChip microarraybased on the multiple interactions of 9 consecutive guaninesrdquoChemical Communications vol 47 no 25 pp 7101ndash7103 2011

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[34] Y Lu W Shi J Qin and B Lin ldquoFabrication and characteri-zation of paper-based microfluidics prepared in nitrocellulosemembrane by wax printingrdquo Analytical Chemistry vol 82 no1 pp 329ndash335 2010

[35] P Zhang R Zhang M Gao and X Zhang ldquoNovel nitrocel-lulose membrane substrate for efficient analysis of circulatingtumor cells coupled with surface-enhanced raman scatteringimagingrdquo ACS Applied Materials and Interfaces vol 6 no 1 pp370ndash376 2014

[36] J-S Lee A K R Lytton-Jean S J Hurst and C AMirkin ldquoSil-ver nanoparticlemdasholigonucleotide conjugates based on DNAwith triple cyclic disulfide moietiesrdquo Nano Letters vol 7 no 7pp 2112ndash2115 2007

[37] S Y Song Y D Han K Kim S S Yang and H C YoonldquoA fluoro-microbead guiding chip for simple and quantifiableimmunoassay of cardiac troponin I (cTnI)rdquo Biosensors andBioelectronics vol 26 no 9 pp 3818ndash3824 2011

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[46] M Ozmen K Can I Akin et al ldquoSurface modification of glassbeads with glutaraldehyde characterization and their adsorp-tion property for metal ionsrdquo Journal of Hazardous Materialsvol 171 no 1ndash3 pp 594ndash600 2009

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[50] E Southern K Mir and M Shchepinov ldquoMolecular interac-tions on microarraysrdquo Nature Genetics vol 21 no 1 pp 5ndash91999

[51] M S Shchepinov S C Case-Green and E M SouthernldquoSteric factors influencing hybridisation of nucleic acids tooligonucleotide arraysrdquo Nucleic Acids Research vol 25 no 6pp 1155ndash1161 1997

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[53] R Benters C M Niemeyer D Drutschmann D Blohm andD Wohrle ldquoDNA microarrays with PAMAM dendritic linkersystemsrdquo Nucleic Acids Research vol 30 no 2 p e10 2002

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Journal of Chemistry 17

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[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

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[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

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[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

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[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Journal of Chemistry 11

SERSimaging

AuNPs

Raman labelNC membrane

AntibodyCancer cell

Figure 9 Detection of circulating tumor cells on NC membranes containing immobilized cAbs (adapted from [35])

activated by reacting the AuNPs with 1-ethyl-3-3(3-dimeth-ylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) in the PBS buffer The mABs arethen added to this solution and the suspension is stirred atroom temperature for 30min The mAB-conjugated AuNPsare then collected by centrifugation and washing with PBSand ethanol The mAB-conjugated AuNPs successfully bindto E coli when incubated in PBS at pH 74 In other reportsthe AuNPs were found very effective in the detection ofcancerous pancreatic cells

The AuNPs are known to suffer from the problem ofaggregation upon long-term storage Therefore to solve thisissue the AuNPs are conjugated with the polyethylene glycol(PEG) to prevent their aggregation [127 128]The conjugationof PEGwith the AuNPsmakes the later hydrophilic thus pre-venting agglomeration induced by hydrophobic interactionsA PEGwith the heterobifunctional groups (dithiol at one endand a carboxyl at another end) is coated on the AuNP Thedithiol group allows stable anchoring heterobifunctional PEGligands on the surface of AuNP and the terminal carboxylgroup is used for coupling with antibodies The carboxy-terminated bifunctional PEG linker is synthesized by follow-ing a method reported by Eck et al which is depicted inScheme 8 The anionic polymerization of compound 1 withan excess of ethylene oxide allows synthesizing compound 2The treatment of compound 2 with chloroacetic acid at 60∘Callows generating compound 3 The reaction of an excess ofthe elemental bromine in dichloromethane at 0∘C for fourhours in the dark with compound 3 produces dibromidecompound 4 Compound 5 is obtained by reaction withcompound 4 in water with the excess of sodium hydrosulfidehydrate

The synthesized bifunctional PEG linker is then conju-gated with the citrate-stabilized gold nanoparticles by simpleligand exchangeThe citrate-stabilized gold nanoparticles areknown to aggregate in the buffer containing salts Thereforethe ligand exchange from citrate to PEG should be done inpure water The PEGylated AuNPs are conjugated to mono-clonal F19 antibodies for the detection of human pancreaticcarcinoma through EDCNHS coupling reaction [129]

OHO

(2) HCl

1

2

3

4

5

Br Br

HS SH

(CH2)9

(CH2)9

(CH2)9

(CH2)9

+

NaHDMF60∘C

(OCH2CH2)n

(OCH2CH2)n

(OCH2CH2)n

OCH2COOH

OCH2COOH

(CH2)9 (OCH2CH2)n OCH2COOH

OminusNa+

Br2

(2) Acetic acid (1) NaSHH2O

60∘C(1) ClCH2-COONa

Scheme 8 Synthesis of bifunctional PEG linker using conjugationwith AuNP

(2) Hydrazide Modification According to the report by Zhiet al the hydrazide-derivatized self-assembledmonolayer ona gold surface is used for the efficient and selective anchor-ing of oligosaccharide [39] The generated oligosaccharidemicroarrays allow the fluorescence-based detection of targetproteins The use of gold as a substrate for the fluorescence-based detection suffers from the drawbacks including flu-orescence quenching and nonspecific surface adsorption ofproteins However the use of120596-thiolated fatty acid (C

16) self-

assembledmonolayer between the gold surface andhydrazide

12 Journal of Chemistry

AuC C

C

C

OHOHO O

O

O

O

O

O

O

O

O

CHR

NN

H

N

N

N

H

NH

NH

NH

H

NH

C

O

O

O NNH

NH

HNH

H

S

S

S

S

HS Au

Au

Au

Au

Au

C16 SAM

Adipic dihydrazideEDC

(Sugar)R-CHO

Binding to protein

Sugarprobe

Protein Alexafluoro 532

SAM andblocking layer

Ab 2nd Ab

NH2

NH2H2N

CH2R

Scheme 9 Application of hydrazide-derivatized SAM on a goldsurface for the fabrication of oligosaccharide microarray (adaptedfrom [39])

groups minimizes the quenching effect Moreover the effec-tive blocking of the surface with the poly(ethylene glycol)aldehyde and BSA reduces the nonspecific adsorption ofprotein on the surface

For the fabrication of the reported oligosaccharidemicroarrays the gold substrate is prepared by following amethod depicted in Scheme 9 The self-assembled mono-layer (SAM) of 16-mercaptohexadecanoic acid (MHDA) isobtained by soaking the gold coated slides in the isobutylalcohol for 2 days The slides are then washed in ethanolto remove excess reagents and are dried under the nitrogenstream The carboxyl functional groups on the SAM areconverted to the hydrazide groups by incubation of the SAMcovered slides in the dimethyl sulfoxide solution containing1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and adipicdihydrazide The ethanol-washed and dried slides are thenused for the oligosaccharide printing to obtain oligosaccha-ride microarrays

The generated oligosaccharide microarray platformallows interrogation of carbohydrate-protein interactions ina high-throughput manner

26 Silver Similar to AuNPs silver nanoparticles (AgNP) arealso used for the immobilization of proteins and enzymesThe surface of AgNP allows adsorption of proteins Henceit can be utilized as a host matrix for various biomoleculesSilver is a suitable substrate for the immobilization of wholecell or the isolated enzymes [130 131]

Texp lt Tm

Ag

AgAg

Ag

AgAg

Texp gt Tm

Figure 10 AgNPs-oligonucleotide conjugates (adapted from [36])

261 Electrostatic Modification The electrostatic interac-tions allow the physical adsorption of biomolecules on thesurface of AgNPs Shen et al reported that the AgNPs aresynthesized by reduction of silver nitrate in the presence ofsodium citrate During the reduction process the solutionis sonicated for 15min to obtain the yellow silver colloidwhich is then kept at 4∘C for several days away from lightThen isolated nanoparticles can be used for physisorption ofproteins at a pH higher than their isoelectric point [132]

262 Covalent Modification As depicted in Scheme 10the AgNPs prepared by the citrate reduction method andstabilized with citrate [133] can be functionalized with car-boxyl groups upon treatment with 3-mercaptopropanoic acid(MPA) As reported by the Petkova et al for the immobi-lization of alcohol dehydrogenase from Thermoanaerobiumbrockii (TbADH) the carboxyl-modified AgNPs were treatedwith the solution containing TbADH under continuousstirring for 7 h at 26∘C a research by [134] The AgNPsmodified with the TbADH were successfully used for thebiotransformation studies

The application of a bifunctional linker for the modifica-tion of AgNPs is reported [135 136] The bifunctional linker11-mercaptoundecanoic acid was used with 1-octanethiol in1 1 ratio to generate the mixed SAM on the surface of AgNPThe IgG antibodies are then conjugated with the mixed SAMmodified AgNPs It is reported that upon covalent conjuga-tion of biomolecules with AgNPs their stability and activityis maintained [137]

According to another report on the covalent modifi-cation AgNPs-oligonucleotide conjugates are prepared byusing DNA and triple cyclic disulfide moieties [36] Asdepicted in Figure 10 the two types ofAgNPs-oligonucleotideconjugates with complementary DNA sequences undergoDNA hybridization driven coagulation resulting in the colorchange

As depicted in Figure 11 the AgNP-DNA conjugates wereprepared by treatment of AgNPs with the cyclic disulfidemodified oligonucleotide The AgNP and oligonucleotideswere allowed to react with each other with 1 4 ratio inthe presence of 1 sodium dodecyl sulfate and NaCl Theovernight incubation of solution results in the AgNP-DNAconjugates which are collected by centrifugation and washedto remove the excess DNAs

Journal of Chemistry 13

Ag AgMPAOH

OO OH

O

HOCitrate

Citrate

Ag

COOH

COOH

TbADHAg

CONH

COOH

TbADHOminusNa+

H2N

Scheme 10 Covalent conjugation of enzymes on the surface of carboxyl-modified AgNPs

OHO

EDC HOSu Bis-amino

polyethylene glycol

NH

OO

44GMBS N

H

OO N

H44

ON

O

O3

CoA

NH

OO N

H44

ON

O

O3

SHN

O

OH

OP O

OPO

O O

OHO

NNN

N

PO

OminusOminus

OminusOminus

NH2

NH2

Scheme 11 Covalent conjugation of coenzyme A to polystyrene nanoparticles

O OOO P

OHSS

5998400 (DSP)3-A10-ATT-ATC-ACT 3998400

DSP cyclic disulfide-containingphosphate derivative =

Figure 11 Conjugation of AgNPs with oligonucleotides by usingDSP as a linker molecule (adapted from [36])

27 Polystyrene Polystyrene is an aromatic polymerobtained by polymerization of styrene monomers [138] Thepolystyrene-based NPs are widely used in the moleculardiagnostics for the detection of biomarker proteins andgenomic DNAs Polystyrene can be employed as a coating ona variety of nanoparticles as its functional groups can be easilymodified or conjugated with other molecules The otherapplication of polystyrene is in the fabrication of fluorescencebeads (FBs) The fluorescence molecules are loaded into thepolystyrene shell to produce FBs which are then used invarious sensing applications The polystyrene is also used tocoat the magnetic NPs so they can be conjugated with otherbiomolecules such as DNA and Proteins The applications ofpolystyrene include but are not limited to the detection ofE coli [139] the detection of cardiac Troponin T (cTnT) thedetection of Herpes simplex virus and many more

271 Covalent Modification Covalent modification throughcarboxyl group iswell known formodification of biomolecule

Most of the polystyrene-based nanoparticles bear large num-bers of pendant carboxyl which increases the loading amountof biomolecule

Enzyme catalyzed covalent immobilization of the pro-teins bearing a small 12-mer ldquoybbRrdquo tag onto the polystyrenenanoparticles (PSNP) is recently reported by Wong et al[140] As depicted in Scheme 11 the carboxyl-PSNPs werereacted with the bis-amino-polyethylene glycol in the pres-ence of HOSu and EDC to generate the amino-pegylatedPSNPs These PSNPs are then reacted with the g-maleimi-dobutyric acid succinimidyl (GMBS) to obtain maleimide-functionalized PSNPs The maleimide-functionalized PSNPsupon chemoligation with coenzyme A (CoA) produce theCoA-derivatized PSNPs

As depicted in Scheme 12 the protein of interest bearingybbR-tag is immobilized on the CoA-derivatized PSNPsThephosphopantetheinyl transferase (Sfp) catalyzed the reactionbetween the serine residue of the ybbR-tag and the phos-phopantetheine moiety of CoA with the simultaneous lossof 3101584051015840-adenine diphosphate results in the attachment ofproteins onto the surface of PSNPs It is reported that theenzymes immobilized by this method retain their activity

There are several reports on the use of fluoromicrobeadsfor the detection of biomarkers Primarily the fluoromi-crobeads are made up of carboxylated polystyrene as a coat-ingmaterial entrapping the fluorescentmolecules Accordingto the recent report by Song et al [37] the fluoromicrobeadswere used for the detection of the cTnT on the proteinmicroarray as depicted in Figure 12

The carboxylate modified fluoromicrobeads were conju-gated with the anti cTnI mAb through EDCNHS-mediated

14 Journal of Chemistry

HN

O

OH

OP

O

O

PO

O

OHO

N

NN

P

O

S

HN

O

Coenzyme A

Phosphopantetheine

PO

O

O

OHO

N Sfp

NN

N

P

O

ybbr-protein

HN

O

OH

OP

O

O

S

HN

O

NH2

NH2

Ominus

Ominus

Ominus

minusO

minusO

Mg2+

HO∙∙

Ominus

OminusOminus

minusO

N

O

Polystyrenenanoparticle

Scheme 12 Protein conjugation to polystyrene NP

System 1 antibody-conjugated fluoromicrobeads

System 2 avidin-conjugated fluoromicrobeads

DTSP SAM

Anti-cTnI cAb

cTnI

Figure 12 Application of the polystyrene-coated fluoromicrobeadsfor the detection of cTnI on the protein microarray (adapted from[37])

coupling reaction The use of fluoromicrobeads alloweddetecting the cTnI in plasma samples with a range of 01ndash100 ngmL

272 Affinity-Based Modification The affinity interactionsare used for the attachment of oligonucleotides with thefluoromicrobeads or polystyrene-coated magnetic beads Togenerate the oligonucleotide conjugated fluoromicrobeads ormagnetic beads respective polystyrene-coated beads are firstconjugated with the streptavidin using the EDCNHS cou-pling reaction as reported by Zhang et al [141] As depicted

B

B

MB MB

MB

BB

Magnetic bead

Streptavidin

DNA labeled biotin

Figure 13 DNA attachment to the magnetic beads

in Figure 13 the streptavidinmodified beads are then allowedto incubate with the biotinylated oligonucleotides Due to theaffinity of biotin for streptavidin the biotinylated oligonu-cleotides can be readily immobilized on the streptavidincoated beads

The binding affinity of streptavidin and biotin in solutionis up to 25 times 1013 (molL)minus1 [142] This interaction is about amillion times stronger than the antigen and antibody inter-action The antibodies directly immobilized onto the sur-face lose 90 of their biological activity [143] Howeverthe biotinylated antibodies immobilized on the streptavidincoated surface can retain their bioactivity [144]

Journal of Chemistry 15

3 Conclusions

Surface modification techniques of the materials used asplatforms in the fabrication of biosensors are reviewed inthis paper There are several reports on materials and vari-ous methods for altering their physicochemical propertiesHence one of these methods can be chosen according tothe targeted use and needed physiochemical properties Itis important to note that the performance of the biosensoris highly dependent on the substrate material used and itsmeticulous modification for particular applications There-fore it is critical to understand the principles of a biosensor toidentify the correct substrate material and its surface modifi-cation chemistry Furthermore it is important to look at thelatest advances in the materials and techniques used for thefabrication of a biosensor before the processing

Competing Interests

All authors declare that there is no conflict of interests

Acknowledgments

This research was supported by the Hallym UniversityResearch Fund (HRF-201601-010) This work was also sup-ported by the fund obtained through Industry-Academic col-laboration between Biometrix Technology Inc (ChuncheonSouth Korea) and Hallym University

References

[1] A Sassolas B D Leca-Bouvier and L J Blum ldquoDNA biosen-sors andmicroarraysrdquoChemical Reviews vol 108 no 1 pp 109ndash139 2008

[2] A Cavalcanti B Shirinzadeh M Zhang and L C KretlyldquoNanorobot hardware architecture for medical defenserdquo Sen-sors vol 8 no 5 pp 2932ndash2958 2008

[3] R-Q Zhang S-L Liu W Zhao et al ldquoA simple point-of-caremicrofluidic immunomagnetic fluorescence assay for path-ogensrdquo Analytical Chemistry vol 85 no 5 pp 2645ndash2651 2013

[4] S B Nimse K S Song M D Sonawane D R Sayyed and TS Kim ldquoImmobilization techniques for microarray challengesand applicationsrdquo Sensors vol 14 no 12 pp 22208ndash22229 2014

[5] A P F Turner ldquoBiosensors sense and sensibilityrdquo ChemicalSociety Reviews vol 42 no 8 pp 3184ndash3196 2013

[6] L Wu and X Qu ldquoCancer biomarker detection recent achieve-ments and challengesrdquoChemical Society Reviews vol 44 no 10pp 2963ndash2997 2015

[7] K Ariga Q Ji T Mori et al ldquoEnzyme nanoarchitectonicsorganization and device applicationrdquo Chemical Society Reviewsvol 42 no 15 pp 6322ndash6345 2013

[8] W-W Zhao J-J Xu and H-Y Chen ldquoPhotoelectrochemicalDNA biosensorsrdquo Chemical Reviews vol 114 no 15 pp 7421ndash7441 2014

[9] Q Liu C Wu H Cai N Hu J Zhou and P Wang ldquoCell-basedbiosensors and their application in biomedicinerdquo ChemicalReviews vol 114 no 12 pp 6423ndash6461 2014

[10] X Zhao S Nampalli A J Serino and S Kumar ldquoImmobi-lization of oligodeoxyribonucleotides with multiple anchors to

microchipsrdquo Nucleic Acids Research vol 29 no 4 pp 955ndash9592001

[11] P Kumar S K Agrawal A Misra and K C Gupta ldquoA newheterobifunctional reagent for immobilization of biomoleculeson glass surfacerdquo Bioorganic 120572Medicinal Chemistry Letters vol14 no 5 pp 1097ndash1099 2004

[12] F Secundo ldquoConformational changes of enzymes upon immo-bilisationrdquo Chemical Society Reviews vol 42 no 15 pp 6250ndash6261 2013

[13] S Lee S Kim J Malm O C Jeong H Lilja and T LaurellldquoImproved porous silicon microarray based prostate specificantigen immunoassay by optimized surface density of thecapture antibodyrdquoAnalytica Chimica Acta vol 796 pp 108ndash1142013

[14] K Jaras A A Tajudin A Ressine et al ldquoENSAM europiumnanoparticles for signal enhancement of antibody microarrayson nanoporous siliconrdquo Journal of Proteome Research vol 7 no3 pp 1308ndash1314 2008

[15] C Steinhauer A Ressine G Marko-Varga T Laurell C AK Borrebaeck and C Wingren ldquoBiocompatibility of surfacesfor antibody microarrays design of macroporous silicon sub-stratesrdquo Analytical Biochemistry vol 341 no 2 pp 204ndash2132005

[16] K Jaras B Adler A Tojo et al ldquoPorous silicon antibodymicroarrays for quantitative analysis measurement of free andtotal PSA in clinical plasma samplesrdquo Clinica Chimica Acta vol414 pp 76ndash84 2012

[17] S W Lee K Hosokawa S Kim et al ldquoA highly sensitive poroussilicon (P-Si)-based human Kallikrein 2 (hK2) immunoassayplatform toward accurate diagnosis of prostate cancerrdquo Sensorsvol 15 no 5 pp 11972ndash11987 2015

[18] C Roychaudhuri ldquoA review on porous silicon based electro-chemical biosensors beyond surface area enhancement factorrdquoSensors and Actuators B Chemical vol 210 pp 310ndash323 2015

[19] ARessine S EkstromGMarko-Varga andT Laurell ldquoMacro-nanoporous silicon as a support for high-performance proteinmicroarraysrdquo Analytical Chemistry vol 75 no 24 pp 6968ndash6974 2003

[20] S Lee E Silajdzic H Yang et al ldquoA porous silicon immunoas-say platform for fluorometric determination of 120572-synuclein inhuman cerebrospinal fluidrdquo Microchimica Acta vol 181 no 9-10 pp 1143ndash1149 2014

[21] S Belhousse N Belhaneche-Bensemra K Lasmi et alldquoModified porous silicon for electrochemical sensor of para-nitrophenolrdquo Materials Science and Engineering B vol 189 pp76ndash81 2014

[22] N Reta A Michelmore C Saint B Prieto-Simon and NH Voelcker ldquoPorous silicon membrane-modified electrodesfor label-free voltammetric detection of MS2 bacteriophagerdquoBiosensors and Bioelectronics vol 80 pp 47ndash53 2016

[23] B Guan A Magenau S Ciampi K Gaus P J Reece and J JGooding ldquoAntibody modified porous silicon microparticles forthe selective capture of cellsrdquo Bioconjugate Chemistry vol 25no 7 pp 1282ndash1289 2014

[24] S Vutti N Buch-Manson S Schoffelen N Bovet K LMartinez and M Meldal ldquoCovalent and stable CuAAC mod-ification of silicon surfaces for control of cell adhesionrdquo Chem-BioChem vol 16 no 5 pp 782ndash791 2015

[25] A M Rossi L Wang V Reipa and T E Murphy ldquoPoroussilicon biosensor for detection of virusesrdquo Biosensors andBioelectronics vol 23 no 5 pp 741ndash745 2007

16 Journal of Chemistry

[26] T L Lasseter B H Clare N L Abbott and R J HamersldquoCovalently modified silicon and diamond surfaces resistanceto nonspecific protein adsorption and optimization for biosens-ingrdquo Journal of the American Chemical Society vol 126 no 33pp 10220ndash10221 2004

[27] M Li K-G Neoh E-T Kang T Lau and E E ChiongldquoSurface modification of silicone with covalently immobilizedand crosslinked agarose for potential application in the inhibi-tion of infection and omental wrappingrdquo Advanced FunctionalMaterials vol 24 no 11 pp 1631ndash1643 2014

[28] G MacBeath and S L Schreiber ldquoPrinting proteins as microar-rays for high-throughput function determinationrdquo Science vol289 no 5485 pp 1760ndash1763 2000

[29] S B Nimse M D Sonawane K S Song and T Kim ldquoBio-marker detection technologies and future directionsrdquoThe Ana-lyst vol 141 no 3 pp 740ndash755 2016

[30] M D Sonawane S B Nimse K Song and T Kim ldquoDetectionquantification and profiling of PSA current microarray tech-nologies and future directionsrdquo RSC Advances vol 6 no 9 pp7599ndash7609 2016

[31] S B Nimse and T Kim ldquoBiological applications of function-alized calixarenesrdquo Chemical Society Reviews vol 42 no 1 pp366ndash386 2013

[32] K-S Song S B Nimse J Kim et al ldquo9GDNAChip microarraybased on the multiple interactions of 9 consecutive guaninesrdquoChemical Communications vol 47 no 25 pp 7101ndash7103 2011

[33] R J Chen S Bangsaruntip K A Drouvalakis et al ldquoNonco-valent functionalization of carbon nanotubes for highly specificelectronic biosensorsrdquo Proceedings of the National Academy ofSciences of the United States of America vol 100 no 9 pp 4984ndash4989 2003

[34] Y Lu W Shi J Qin and B Lin ldquoFabrication and characteri-zation of paper-based microfluidics prepared in nitrocellulosemembrane by wax printingrdquo Analytical Chemistry vol 82 no1 pp 329ndash335 2010

[35] P Zhang R Zhang M Gao and X Zhang ldquoNovel nitrocel-lulose membrane substrate for efficient analysis of circulatingtumor cells coupled with surface-enhanced raman scatteringimagingrdquo ACS Applied Materials and Interfaces vol 6 no 1 pp370ndash376 2014

[36] J-S Lee A K R Lytton-Jean S J Hurst and C AMirkin ldquoSil-ver nanoparticlemdasholigonucleotide conjugates based on DNAwith triple cyclic disulfide moietiesrdquo Nano Letters vol 7 no 7pp 2112ndash2115 2007

[37] S Y Song Y D Han K Kim S S Yang and H C YoonldquoA fluoro-microbead guiding chip for simple and quantifiableimmunoassay of cardiac troponin I (cTnI)rdquo Biosensors andBioelectronics vol 26 no 9 pp 3818ndash3824 2011

[38] S V Lemeshko T Powdrill Y Y Belosludtsev and M HoganldquoOligonucleotides form a duplex with non-helical properties ona positively charged surfacerdquoNucleic Acids Research vol 29 no14 pp 3051ndash3058 2001

[39] Z-L Zhi A K Powell and J E Turnbull ldquoFabrication ofcarbohydrate microarrays on gold surfaces direct attachmentof nonderivatized oligosaccharides to hydrazide-modified self-assembledmonolayersrdquoAnalytical Chemistry vol 78 no 14 pp4786ndash4793 2006

[40] S L Pan and L Rothberg ldquoChemical control of electrodefunctionalization for detection of DNA hybridization by elec-trochemical impedance spectroscopyrdquo Langmuir vol 21 no 3pp 1022ndash1027 2005

[41] Z Lu C M Li Q Zhou Q-L Bao and X Cui ldquoCovalentlylinked DNAprotein multilayered film for controlled DNAreleaserdquo Journal of Colloid and Interface Science vol 314 no 1pp 80ndash88 2007

[42] L-S Jang and H-J Liu ldquoFabrication of protein chips basedon 3-aminopropyltriethoxysilane as a monolayerrdquo BiomedicalMicrodevices vol 11 no 2 pp 331ndash338 2009

[43] F Fixe M Dufva P Telleman and C B Christensen ldquoFunc-tionalization of poly(methyl methacrylate) (PMMA) as a sub-strate for DNAmicroarraysrdquoNucleic Acids Research vol 32 no1 article e9 2004

[44] A Lueking M Horn H Eickhoff K Bussow H Lehrachand G Walter ldquoProtein microarrays for gene expression andantibody screeningrdquo Analytical Biochemistry vol 270 no 1 pp103ndash111 1999

[45] N Zammatteo L Jeanmart S Hamels et al ldquoComparisonbetween different strategies of covalent attachment of DNA toglass surfaces to build DNA microarraysrdquo Analytical Biochem-istry vol 280 no 1 pp 143ndash150 2000

[46] M Ozmen K Can I Akin et al ldquoSurface modification of glassbeads with glutaraldehyde characterization and their adsorp-tion property for metal ionsrdquo Journal of Hazardous Materialsvol 171 no 1ndash3 pp 594ndash600 2009

[47] C Funk PM Dietrich T Gross HMinW E S Unger andWWeigel ldquoEpoxy-functionalized surfaces for microarray appli-cations surface chemical analysis and fluorescence labeling ofsurface speciesrdquo Surface and Interface Analysis vol 44 no 8pp 890ndash894 2012

[48] S Mahajan P Kumar and K C Gupta ldquoOligonucleotide mic-roarrays immobilization of phosphorylated oligonucleotideson epoxylated surfacerdquo Bioconjugate Chemistry vol 17 no 5pp 1184ndash1189 2006

[49] M C Pirrung J D Davis and A L Odenbaugh ldquoNovelreagents and procedures for immobilization of DNA on glassmicrochips for primer extensionrdquo Langmuir vol 16 no 5 pp2185ndash2191 2000

[50] E Southern K Mir and M Shchepinov ldquoMolecular interac-tions on microarraysrdquo Nature Genetics vol 21 no 1 pp 5ndash91999

[51] M S Shchepinov S C Case-Green and E M SouthernldquoSteric factors influencing hybridisation of nucleic acids tooligonucleotide arraysrdquo Nucleic Acids Research vol 25 no 6pp 1155ndash1161 1997

[52] D A Tomalia A M Naylor and W A Goddard III ldquoStarbustdendrimers molecular-level control of size shape surfacechemistry topology and flexibility from atoms to macroscopicmatterrdquo Angewandte ChemiemdashInternational Edition in Englishvol 29 no 2 pp 138ndash175 1990

[53] R Benters C M Niemeyer D Drutschmann D Blohm andD Wohrle ldquoDNA microarrays with PAMAM dendritic linkersystemsrdquo Nucleic Acids Research vol 30 no 2 p e10 2002

[54] J H Moon J W Shin S Y Kim and J W Park ldquoFormationof uniform aminosilane thin layers an imine formation tomeasure relative surface density of the amine grouprdquo Langmuirvol 12 no 20 pp 4621ndash4624 1996

[55] J C Alwine D J Kemp and G R Stark ldquoMethod fordetection of specific RNAs in agarose gels by transfer to diazo-benzyloxymethyl-paper and hybridization with DNA probesrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 74 no 12 pp 5350ndash5354 1977

[56] P L Dolan Y Wu L K Ista R L Metzenberg M A Nelsonand G P Lopez ldquoRobust and efficient synthetic method for

Journal of Chemistry 17

forming DNA microarraysrdquo Nucleic Acids Research vol 29 no21 article e107 2001

[57] S B Nimse J Kim K-S Song et al ldquoSelective recognitionof the ditopic trimethylammonium cations by water-solubleaminocalix[4]arenerdquo Tetrahedron Letters vol 52 no 29 pp3751ndash3755 2011

[58] V-T Ta S B Nimse K-S Song et al ldquoCharacterization ofthe mixed self-assembled monolayer at the molecular scalerdquoChemical Communications vol 47 no 40 pp 11261ndash11263 2011

[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

[60] Y Lee E K Lee YW Cho et al ldquoProteoChip a highly sensitiveprotein microarray prepared by a novel method of proteinimmobilization for application of protein-protein interactionstudiesrdquo Proteomics vol 3 no 12 pp 2289ndash2304 2003

[61] S W Oh J D Moon H J Lim et al ldquoCalixarene derivative asa tool for highly sensitive detection and oriented immobiliza-tion of proteins in a microarray format through noncovalentmolecular interactionrdquo The FASEB Journal vol 19 no 10 pp1335ndash1337 2005

[62] S B Nimse K-S Song J Kim D R Sayyed and T Kimldquo9G DNAChip technology self-assembled monolayer (SAM)of ssDNA for ultra-sensitive detection of biomarkersrdquo Interna-tional Journal ofMolecular Sciences vol 14 no 3 pp 5723ndash57332013

[63] V-T Nguyen S B Nimse K-S Song et al ldquoHPAI 9GDNAChip discrimination of highly pathogenic influenza virusgenesrdquo Chemical Communications vol 48 no 38 pp 4582ndash4584 2012

[64] K-S Song S B Nimse J Kim D R Sayyed and T Kim ldquoAnew platform for a convenient genotyping systemrdquo ChemicalCommunications vol 49 no 26 pp 2661ndash2663 2013

[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

[67] F Hennrich C Chan VMoore M Rolandi andM OrsquoConnellCarbonNanotubes Properties and Applications Taylor amp FrancisGroup Abingdon UK 2006

[68] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

[69] C Singh M Shaffer I Kinloch and A Windle ldquoProductionof aligned carbon nanotubes by the CVD injection methodrdquoPhysica B Condensed Matter vol 323 no 1ndash4 pp 339ndash3402002

[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

[71] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

12 Journal of Chemistry

AuC C

C

C

OHOHO O

O

O

O

O

O

O

O

O

CHR

NN

H

N

N

N

H

NH

NH

NH

H

NH

C

O

O

O NNH

NH

HNH

H

S

S

S

S

HS Au

Au

Au

Au

Au

C16 SAM

Adipic dihydrazideEDC

(Sugar)R-CHO

Binding to protein

Sugarprobe

Protein Alexafluoro 532

SAM andblocking layer

Ab 2nd Ab

NH2

NH2H2N

CH2R

Scheme 9 Application of hydrazide-derivatized SAM on a goldsurface for the fabrication of oligosaccharide microarray (adaptedfrom [39])

groups minimizes the quenching effect Moreover the effec-tive blocking of the surface with the poly(ethylene glycol)aldehyde and BSA reduces the nonspecific adsorption ofprotein on the surface

For the fabrication of the reported oligosaccharidemicroarrays the gold substrate is prepared by following amethod depicted in Scheme 9 The self-assembled mono-layer (SAM) of 16-mercaptohexadecanoic acid (MHDA) isobtained by soaking the gold coated slides in the isobutylalcohol for 2 days The slides are then washed in ethanolto remove excess reagents and are dried under the nitrogenstream The carboxyl functional groups on the SAM areconverted to the hydrazide groups by incubation of the SAMcovered slides in the dimethyl sulfoxide solution containing1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and adipicdihydrazide The ethanol-washed and dried slides are thenused for the oligosaccharide printing to obtain oligosaccha-ride microarrays

The generated oligosaccharide microarray platformallows interrogation of carbohydrate-protein interactions ina high-throughput manner

26 Silver Similar to AuNPs silver nanoparticles (AgNP) arealso used for the immobilization of proteins and enzymesThe surface of AgNP allows adsorption of proteins Henceit can be utilized as a host matrix for various biomoleculesSilver is a suitable substrate for the immobilization of wholecell or the isolated enzymes [130 131]

Texp lt Tm

Ag

AgAg

Ag

AgAg

Texp gt Tm

Figure 10 AgNPs-oligonucleotide conjugates (adapted from [36])

261 Electrostatic Modification The electrostatic interac-tions allow the physical adsorption of biomolecules on thesurface of AgNPs Shen et al reported that the AgNPs aresynthesized by reduction of silver nitrate in the presence ofsodium citrate During the reduction process the solutionis sonicated for 15min to obtain the yellow silver colloidwhich is then kept at 4∘C for several days away from lightThen isolated nanoparticles can be used for physisorption ofproteins at a pH higher than their isoelectric point [132]

262 Covalent Modification As depicted in Scheme 10the AgNPs prepared by the citrate reduction method andstabilized with citrate [133] can be functionalized with car-boxyl groups upon treatment with 3-mercaptopropanoic acid(MPA) As reported by the Petkova et al for the immobi-lization of alcohol dehydrogenase from Thermoanaerobiumbrockii (TbADH) the carboxyl-modified AgNPs were treatedwith the solution containing TbADH under continuousstirring for 7 h at 26∘C a research by [134] The AgNPsmodified with the TbADH were successfully used for thebiotransformation studies

The application of a bifunctional linker for the modifica-tion of AgNPs is reported [135 136] The bifunctional linker11-mercaptoundecanoic acid was used with 1-octanethiol in1 1 ratio to generate the mixed SAM on the surface of AgNPThe IgG antibodies are then conjugated with the mixed SAMmodified AgNPs It is reported that upon covalent conjuga-tion of biomolecules with AgNPs their stability and activityis maintained [137]

According to another report on the covalent modifi-cation AgNPs-oligonucleotide conjugates are prepared byusing DNA and triple cyclic disulfide moieties [36] Asdepicted in Figure 10 the two types ofAgNPs-oligonucleotideconjugates with complementary DNA sequences undergoDNA hybridization driven coagulation resulting in the colorchange

As depicted in Figure 11 the AgNP-DNA conjugates wereprepared by treatment of AgNPs with the cyclic disulfidemodified oligonucleotide The AgNP and oligonucleotideswere allowed to react with each other with 1 4 ratio inthe presence of 1 sodium dodecyl sulfate and NaCl Theovernight incubation of solution results in the AgNP-DNAconjugates which are collected by centrifugation and washedto remove the excess DNAs

Journal of Chemistry 13

Ag AgMPAOH

OO OH

O

HOCitrate

Citrate

Ag

COOH

COOH

TbADHAg

CONH

COOH

TbADHOminusNa+

H2N

Scheme 10 Covalent conjugation of enzymes on the surface of carboxyl-modified AgNPs

OHO

EDC HOSu Bis-amino

polyethylene glycol

NH

OO

44GMBS N

H

OO N

H44

ON

O

O3

CoA

NH

OO N

H44

ON

O

O3

SHN

O

OH

OP O

OPO

O O

OHO

NNN

N

PO

OminusOminus

OminusOminus

NH2

NH2

Scheme 11 Covalent conjugation of coenzyme A to polystyrene nanoparticles

O OOO P

OHSS

5998400 (DSP)3-A10-ATT-ATC-ACT 3998400

DSP cyclic disulfide-containingphosphate derivative =

Figure 11 Conjugation of AgNPs with oligonucleotides by usingDSP as a linker molecule (adapted from [36])

27 Polystyrene Polystyrene is an aromatic polymerobtained by polymerization of styrene monomers [138] Thepolystyrene-based NPs are widely used in the moleculardiagnostics for the detection of biomarker proteins andgenomic DNAs Polystyrene can be employed as a coating ona variety of nanoparticles as its functional groups can be easilymodified or conjugated with other molecules The otherapplication of polystyrene is in the fabrication of fluorescencebeads (FBs) The fluorescence molecules are loaded into thepolystyrene shell to produce FBs which are then used invarious sensing applications The polystyrene is also used tocoat the magnetic NPs so they can be conjugated with otherbiomolecules such as DNA and Proteins The applications ofpolystyrene include but are not limited to the detection ofE coli [139] the detection of cardiac Troponin T (cTnT) thedetection of Herpes simplex virus and many more

271 Covalent Modification Covalent modification throughcarboxyl group iswell known formodification of biomolecule

Most of the polystyrene-based nanoparticles bear large num-bers of pendant carboxyl which increases the loading amountof biomolecule

Enzyme catalyzed covalent immobilization of the pro-teins bearing a small 12-mer ldquoybbRrdquo tag onto the polystyrenenanoparticles (PSNP) is recently reported by Wong et al[140] As depicted in Scheme 11 the carboxyl-PSNPs werereacted with the bis-amino-polyethylene glycol in the pres-ence of HOSu and EDC to generate the amino-pegylatedPSNPs These PSNPs are then reacted with the g-maleimi-dobutyric acid succinimidyl (GMBS) to obtain maleimide-functionalized PSNPs The maleimide-functionalized PSNPsupon chemoligation with coenzyme A (CoA) produce theCoA-derivatized PSNPs

As depicted in Scheme 12 the protein of interest bearingybbR-tag is immobilized on the CoA-derivatized PSNPsThephosphopantetheinyl transferase (Sfp) catalyzed the reactionbetween the serine residue of the ybbR-tag and the phos-phopantetheine moiety of CoA with the simultaneous lossof 3101584051015840-adenine diphosphate results in the attachment ofproteins onto the surface of PSNPs It is reported that theenzymes immobilized by this method retain their activity

There are several reports on the use of fluoromicrobeadsfor the detection of biomarkers Primarily the fluoromi-crobeads are made up of carboxylated polystyrene as a coat-ingmaterial entrapping the fluorescentmolecules Accordingto the recent report by Song et al [37] the fluoromicrobeadswere used for the detection of the cTnT on the proteinmicroarray as depicted in Figure 12

The carboxylate modified fluoromicrobeads were conju-gated with the anti cTnI mAb through EDCNHS-mediated

14 Journal of Chemistry

HN

O

OH

OP

O

O

PO

O

OHO

N

NN

P

O

S

HN

O

Coenzyme A

Phosphopantetheine

PO

O

O

OHO

N Sfp

NN

N

P

O

ybbr-protein

HN

O

OH

OP

O

O

S

HN

O

NH2

NH2

Ominus

Ominus

Ominus

minusO

minusO

Mg2+

HO∙∙

Ominus

OminusOminus

minusO

N

O

Polystyrenenanoparticle

Scheme 12 Protein conjugation to polystyrene NP

System 1 antibody-conjugated fluoromicrobeads

System 2 avidin-conjugated fluoromicrobeads

DTSP SAM

Anti-cTnI cAb

cTnI

Figure 12 Application of the polystyrene-coated fluoromicrobeadsfor the detection of cTnI on the protein microarray (adapted from[37])

coupling reaction The use of fluoromicrobeads alloweddetecting the cTnI in plasma samples with a range of 01ndash100 ngmL

272 Affinity-Based Modification The affinity interactionsare used for the attachment of oligonucleotides with thefluoromicrobeads or polystyrene-coated magnetic beads Togenerate the oligonucleotide conjugated fluoromicrobeads ormagnetic beads respective polystyrene-coated beads are firstconjugated with the streptavidin using the EDCNHS cou-pling reaction as reported by Zhang et al [141] As depicted

B

B

MB MB

MB

BB

Magnetic bead

Streptavidin

DNA labeled biotin

Figure 13 DNA attachment to the magnetic beads

in Figure 13 the streptavidinmodified beads are then allowedto incubate with the biotinylated oligonucleotides Due to theaffinity of biotin for streptavidin the biotinylated oligonu-cleotides can be readily immobilized on the streptavidincoated beads

The binding affinity of streptavidin and biotin in solutionis up to 25 times 1013 (molL)minus1 [142] This interaction is about amillion times stronger than the antigen and antibody inter-action The antibodies directly immobilized onto the sur-face lose 90 of their biological activity [143] Howeverthe biotinylated antibodies immobilized on the streptavidincoated surface can retain their bioactivity [144]

Journal of Chemistry 15

3 Conclusions

Surface modification techniques of the materials used asplatforms in the fabrication of biosensors are reviewed inthis paper There are several reports on materials and vari-ous methods for altering their physicochemical propertiesHence one of these methods can be chosen according tothe targeted use and needed physiochemical properties Itis important to note that the performance of the biosensoris highly dependent on the substrate material used and itsmeticulous modification for particular applications There-fore it is critical to understand the principles of a biosensor toidentify the correct substrate material and its surface modifi-cation chemistry Furthermore it is important to look at thelatest advances in the materials and techniques used for thefabrication of a biosensor before the processing

Competing Interests

All authors declare that there is no conflict of interests

Acknowledgments

This research was supported by the Hallym UniversityResearch Fund (HRF-201601-010) This work was also sup-ported by the fund obtained through Industry-Academic col-laboration between Biometrix Technology Inc (ChuncheonSouth Korea) and Hallym University

References

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[2] A Cavalcanti B Shirinzadeh M Zhang and L C KretlyldquoNanorobot hardware architecture for medical defenserdquo Sen-sors vol 8 no 5 pp 2932ndash2958 2008

[3] R-Q Zhang S-L Liu W Zhao et al ldquoA simple point-of-caremicrofluidic immunomagnetic fluorescence assay for path-ogensrdquo Analytical Chemistry vol 85 no 5 pp 2645ndash2651 2013

[4] S B Nimse K S Song M D Sonawane D R Sayyed and TS Kim ldquoImmobilization techniques for microarray challengesand applicationsrdquo Sensors vol 14 no 12 pp 22208ndash22229 2014

[5] A P F Turner ldquoBiosensors sense and sensibilityrdquo ChemicalSociety Reviews vol 42 no 8 pp 3184ndash3196 2013

[6] L Wu and X Qu ldquoCancer biomarker detection recent achieve-ments and challengesrdquoChemical Society Reviews vol 44 no 10pp 2963ndash2997 2015

[7] K Ariga Q Ji T Mori et al ldquoEnzyme nanoarchitectonicsorganization and device applicationrdquo Chemical Society Reviewsvol 42 no 15 pp 6322ndash6345 2013

[8] W-W Zhao J-J Xu and H-Y Chen ldquoPhotoelectrochemicalDNA biosensorsrdquo Chemical Reviews vol 114 no 15 pp 7421ndash7441 2014

[9] Q Liu C Wu H Cai N Hu J Zhou and P Wang ldquoCell-basedbiosensors and their application in biomedicinerdquo ChemicalReviews vol 114 no 12 pp 6423ndash6461 2014

[10] X Zhao S Nampalli A J Serino and S Kumar ldquoImmobi-lization of oligodeoxyribonucleotides with multiple anchors to

microchipsrdquo Nucleic Acids Research vol 29 no 4 pp 955ndash9592001

[11] P Kumar S K Agrawal A Misra and K C Gupta ldquoA newheterobifunctional reagent for immobilization of biomoleculeson glass surfacerdquo Bioorganic 120572Medicinal Chemistry Letters vol14 no 5 pp 1097ndash1099 2004

[12] F Secundo ldquoConformational changes of enzymes upon immo-bilisationrdquo Chemical Society Reviews vol 42 no 15 pp 6250ndash6261 2013

[13] S Lee S Kim J Malm O C Jeong H Lilja and T LaurellldquoImproved porous silicon microarray based prostate specificantigen immunoassay by optimized surface density of thecapture antibodyrdquoAnalytica Chimica Acta vol 796 pp 108ndash1142013

[14] K Jaras A A Tajudin A Ressine et al ldquoENSAM europiumnanoparticles for signal enhancement of antibody microarrayson nanoporous siliconrdquo Journal of Proteome Research vol 7 no3 pp 1308ndash1314 2008

[15] C Steinhauer A Ressine G Marko-Varga T Laurell C AK Borrebaeck and C Wingren ldquoBiocompatibility of surfacesfor antibody microarrays design of macroporous silicon sub-stratesrdquo Analytical Biochemistry vol 341 no 2 pp 204ndash2132005

[16] K Jaras B Adler A Tojo et al ldquoPorous silicon antibodymicroarrays for quantitative analysis measurement of free andtotal PSA in clinical plasma samplesrdquo Clinica Chimica Acta vol414 pp 76ndash84 2012

[17] S W Lee K Hosokawa S Kim et al ldquoA highly sensitive poroussilicon (P-Si)-based human Kallikrein 2 (hK2) immunoassayplatform toward accurate diagnosis of prostate cancerrdquo Sensorsvol 15 no 5 pp 11972ndash11987 2015

[18] C Roychaudhuri ldquoA review on porous silicon based electro-chemical biosensors beyond surface area enhancement factorrdquoSensors and Actuators B Chemical vol 210 pp 310ndash323 2015

[19] ARessine S EkstromGMarko-Varga andT Laurell ldquoMacro-nanoporous silicon as a support for high-performance proteinmicroarraysrdquo Analytical Chemistry vol 75 no 24 pp 6968ndash6974 2003

[20] S Lee E Silajdzic H Yang et al ldquoA porous silicon immunoas-say platform for fluorometric determination of 120572-synuclein inhuman cerebrospinal fluidrdquo Microchimica Acta vol 181 no 9-10 pp 1143ndash1149 2014

[21] S Belhousse N Belhaneche-Bensemra K Lasmi et alldquoModified porous silicon for electrochemical sensor of para-nitrophenolrdquo Materials Science and Engineering B vol 189 pp76ndash81 2014

[22] N Reta A Michelmore C Saint B Prieto-Simon and NH Voelcker ldquoPorous silicon membrane-modified electrodesfor label-free voltammetric detection of MS2 bacteriophagerdquoBiosensors and Bioelectronics vol 80 pp 47ndash53 2016

[23] B Guan A Magenau S Ciampi K Gaus P J Reece and J JGooding ldquoAntibody modified porous silicon microparticles forthe selective capture of cellsrdquo Bioconjugate Chemistry vol 25no 7 pp 1282ndash1289 2014

[24] S Vutti N Buch-Manson S Schoffelen N Bovet K LMartinez and M Meldal ldquoCovalent and stable CuAAC mod-ification of silicon surfaces for control of cell adhesionrdquo Chem-BioChem vol 16 no 5 pp 782ndash791 2015

[25] A M Rossi L Wang V Reipa and T E Murphy ldquoPoroussilicon biosensor for detection of virusesrdquo Biosensors andBioelectronics vol 23 no 5 pp 741ndash745 2007

16 Journal of Chemistry

[26] T L Lasseter B H Clare N L Abbott and R J HamersldquoCovalently modified silicon and diamond surfaces resistanceto nonspecific protein adsorption and optimization for biosens-ingrdquo Journal of the American Chemical Society vol 126 no 33pp 10220ndash10221 2004

[27] M Li K-G Neoh E-T Kang T Lau and E E ChiongldquoSurface modification of silicone with covalently immobilizedand crosslinked agarose for potential application in the inhibi-tion of infection and omental wrappingrdquo Advanced FunctionalMaterials vol 24 no 11 pp 1631ndash1643 2014

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[29] S B Nimse M D Sonawane K S Song and T Kim ldquoBio-marker detection technologies and future directionsrdquoThe Ana-lyst vol 141 no 3 pp 740ndash755 2016

[30] M D Sonawane S B Nimse K Song and T Kim ldquoDetectionquantification and profiling of PSA current microarray tech-nologies and future directionsrdquo RSC Advances vol 6 no 9 pp7599ndash7609 2016

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[32] K-S Song S B Nimse J Kim et al ldquo9GDNAChip microarraybased on the multiple interactions of 9 consecutive guaninesrdquoChemical Communications vol 47 no 25 pp 7101ndash7103 2011

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[34] Y Lu W Shi J Qin and B Lin ldquoFabrication and characteri-zation of paper-based microfluidics prepared in nitrocellulosemembrane by wax printingrdquo Analytical Chemistry vol 82 no1 pp 329ndash335 2010

[35] P Zhang R Zhang M Gao and X Zhang ldquoNovel nitrocel-lulose membrane substrate for efficient analysis of circulatingtumor cells coupled with surface-enhanced raman scatteringimagingrdquo ACS Applied Materials and Interfaces vol 6 no 1 pp370ndash376 2014

[36] J-S Lee A K R Lytton-Jean S J Hurst and C AMirkin ldquoSil-ver nanoparticlemdasholigonucleotide conjugates based on DNAwith triple cyclic disulfide moietiesrdquo Nano Letters vol 7 no 7pp 2112ndash2115 2007

[37] S Y Song Y D Han K Kim S S Yang and H C YoonldquoA fluoro-microbead guiding chip for simple and quantifiableimmunoassay of cardiac troponin I (cTnI)rdquo Biosensors andBioelectronics vol 26 no 9 pp 3818ndash3824 2011

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[40] S L Pan and L Rothberg ldquoChemical control of electrodefunctionalization for detection of DNA hybridization by elec-trochemical impedance spectroscopyrdquo Langmuir vol 21 no 3pp 1022ndash1027 2005

[41] Z Lu C M Li Q Zhou Q-L Bao and X Cui ldquoCovalentlylinked DNAprotein multilayered film for controlled DNAreleaserdquo Journal of Colloid and Interface Science vol 314 no 1pp 80ndash88 2007

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[46] M Ozmen K Can I Akin et al ldquoSurface modification of glassbeads with glutaraldehyde characterization and their adsorp-tion property for metal ionsrdquo Journal of Hazardous Materialsvol 171 no 1ndash3 pp 594ndash600 2009

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[50] E Southern K Mir and M Shchepinov ldquoMolecular interac-tions on microarraysrdquo Nature Genetics vol 21 no 1 pp 5ndash91999

[51] M S Shchepinov S C Case-Green and E M SouthernldquoSteric factors influencing hybridisation of nucleic acids tooligonucleotide arraysrdquo Nucleic Acids Research vol 25 no 6pp 1155ndash1161 1997

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[53] R Benters C M Niemeyer D Drutschmann D Blohm andD Wohrle ldquoDNA microarrays with PAMAM dendritic linkersystemsrdquo Nucleic Acids Research vol 30 no 2 p e10 2002

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Journal of Chemistry 17

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[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

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[62] S B Nimse K-S Song J Kim D R Sayyed and T Kimldquo9G DNAChip technology self-assembled monolayer (SAM)of ssDNA for ultra-sensitive detection of biomarkersrdquo Interna-tional Journal ofMolecular Sciences vol 14 no 3 pp 5723ndash57332013

[63] V-T Nguyen S B Nimse K-S Song et al ldquoHPAI 9GDNAChip discrimination of highly pathogenic influenza virusgenesrdquo Chemical Communications vol 48 no 38 pp 4582ndash4584 2012

[64] K-S Song S B Nimse J Kim D R Sayyed and T Kim ldquoAnew platform for a convenient genotyping systemrdquo ChemicalCommunications vol 49 no 26 pp 2661ndash2663 2013

[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

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[68] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

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[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

[71] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Journal of Chemistry 13

Ag AgMPAOH

OO OH

O

HOCitrate

Citrate

Ag

COOH

COOH

TbADHAg

CONH

COOH

TbADHOminusNa+

H2N

Scheme 10 Covalent conjugation of enzymes on the surface of carboxyl-modified AgNPs

OHO

EDC HOSu Bis-amino

polyethylene glycol

NH

OO

44GMBS N

H

OO N

H44

ON

O

O3

CoA

NH

OO N

H44

ON

O

O3

SHN

O

OH

OP O

OPO

O O

OHO

NNN

N

PO

OminusOminus

OminusOminus

NH2

NH2

Scheme 11 Covalent conjugation of coenzyme A to polystyrene nanoparticles

O OOO P

OHSS

5998400 (DSP)3-A10-ATT-ATC-ACT 3998400

DSP cyclic disulfide-containingphosphate derivative =

Figure 11 Conjugation of AgNPs with oligonucleotides by usingDSP as a linker molecule (adapted from [36])

27 Polystyrene Polystyrene is an aromatic polymerobtained by polymerization of styrene monomers [138] Thepolystyrene-based NPs are widely used in the moleculardiagnostics for the detection of biomarker proteins andgenomic DNAs Polystyrene can be employed as a coating ona variety of nanoparticles as its functional groups can be easilymodified or conjugated with other molecules The otherapplication of polystyrene is in the fabrication of fluorescencebeads (FBs) The fluorescence molecules are loaded into thepolystyrene shell to produce FBs which are then used invarious sensing applications The polystyrene is also used tocoat the magnetic NPs so they can be conjugated with otherbiomolecules such as DNA and Proteins The applications ofpolystyrene include but are not limited to the detection ofE coli [139] the detection of cardiac Troponin T (cTnT) thedetection of Herpes simplex virus and many more

271 Covalent Modification Covalent modification throughcarboxyl group iswell known formodification of biomolecule

Most of the polystyrene-based nanoparticles bear large num-bers of pendant carboxyl which increases the loading amountof biomolecule

Enzyme catalyzed covalent immobilization of the pro-teins bearing a small 12-mer ldquoybbRrdquo tag onto the polystyrenenanoparticles (PSNP) is recently reported by Wong et al[140] As depicted in Scheme 11 the carboxyl-PSNPs werereacted with the bis-amino-polyethylene glycol in the pres-ence of HOSu and EDC to generate the amino-pegylatedPSNPs These PSNPs are then reacted with the g-maleimi-dobutyric acid succinimidyl (GMBS) to obtain maleimide-functionalized PSNPs The maleimide-functionalized PSNPsupon chemoligation with coenzyme A (CoA) produce theCoA-derivatized PSNPs

As depicted in Scheme 12 the protein of interest bearingybbR-tag is immobilized on the CoA-derivatized PSNPsThephosphopantetheinyl transferase (Sfp) catalyzed the reactionbetween the serine residue of the ybbR-tag and the phos-phopantetheine moiety of CoA with the simultaneous lossof 3101584051015840-adenine diphosphate results in the attachment ofproteins onto the surface of PSNPs It is reported that theenzymes immobilized by this method retain their activity

There are several reports on the use of fluoromicrobeadsfor the detection of biomarkers Primarily the fluoromi-crobeads are made up of carboxylated polystyrene as a coat-ingmaterial entrapping the fluorescentmolecules Accordingto the recent report by Song et al [37] the fluoromicrobeadswere used for the detection of the cTnT on the proteinmicroarray as depicted in Figure 12

The carboxylate modified fluoromicrobeads were conju-gated with the anti cTnI mAb through EDCNHS-mediated

14 Journal of Chemistry

HN

O

OH

OP

O

O

PO

O

OHO

N

NN

P

O

S

HN

O

Coenzyme A

Phosphopantetheine

PO

O

O

OHO

N Sfp

NN

N

P

O

ybbr-protein

HN

O

OH

OP

O

O

S

HN

O

NH2

NH2

Ominus

Ominus

Ominus

minusO

minusO

Mg2+

HO∙∙

Ominus

OminusOminus

minusO

N

O

Polystyrenenanoparticle

Scheme 12 Protein conjugation to polystyrene NP

System 1 antibody-conjugated fluoromicrobeads

System 2 avidin-conjugated fluoromicrobeads

DTSP SAM

Anti-cTnI cAb

cTnI

Figure 12 Application of the polystyrene-coated fluoromicrobeadsfor the detection of cTnI on the protein microarray (adapted from[37])

coupling reaction The use of fluoromicrobeads alloweddetecting the cTnI in plasma samples with a range of 01ndash100 ngmL

272 Affinity-Based Modification The affinity interactionsare used for the attachment of oligonucleotides with thefluoromicrobeads or polystyrene-coated magnetic beads Togenerate the oligonucleotide conjugated fluoromicrobeads ormagnetic beads respective polystyrene-coated beads are firstconjugated with the streptavidin using the EDCNHS cou-pling reaction as reported by Zhang et al [141] As depicted

B

B

MB MB

MB

BB

Magnetic bead

Streptavidin

DNA labeled biotin

Figure 13 DNA attachment to the magnetic beads

in Figure 13 the streptavidinmodified beads are then allowedto incubate with the biotinylated oligonucleotides Due to theaffinity of biotin for streptavidin the biotinylated oligonu-cleotides can be readily immobilized on the streptavidincoated beads

The binding affinity of streptavidin and biotin in solutionis up to 25 times 1013 (molL)minus1 [142] This interaction is about amillion times stronger than the antigen and antibody inter-action The antibodies directly immobilized onto the sur-face lose 90 of their biological activity [143] Howeverthe biotinylated antibodies immobilized on the streptavidincoated surface can retain their bioactivity [144]

Journal of Chemistry 15

3 Conclusions

Surface modification techniques of the materials used asplatforms in the fabrication of biosensors are reviewed inthis paper There are several reports on materials and vari-ous methods for altering their physicochemical propertiesHence one of these methods can be chosen according tothe targeted use and needed physiochemical properties Itis important to note that the performance of the biosensoris highly dependent on the substrate material used and itsmeticulous modification for particular applications There-fore it is critical to understand the principles of a biosensor toidentify the correct substrate material and its surface modifi-cation chemistry Furthermore it is important to look at thelatest advances in the materials and techniques used for thefabrication of a biosensor before the processing

Competing Interests

All authors declare that there is no conflict of interests

Acknowledgments

This research was supported by the Hallym UniversityResearch Fund (HRF-201601-010) This work was also sup-ported by the fund obtained through Industry-Academic col-laboration between Biometrix Technology Inc (ChuncheonSouth Korea) and Hallym University

References

[1] A Sassolas B D Leca-Bouvier and L J Blum ldquoDNA biosen-sors andmicroarraysrdquoChemical Reviews vol 108 no 1 pp 109ndash139 2008

[2] A Cavalcanti B Shirinzadeh M Zhang and L C KretlyldquoNanorobot hardware architecture for medical defenserdquo Sen-sors vol 8 no 5 pp 2932ndash2958 2008

[3] R-Q Zhang S-L Liu W Zhao et al ldquoA simple point-of-caremicrofluidic immunomagnetic fluorescence assay for path-ogensrdquo Analytical Chemistry vol 85 no 5 pp 2645ndash2651 2013

[4] S B Nimse K S Song M D Sonawane D R Sayyed and TS Kim ldquoImmobilization techniques for microarray challengesand applicationsrdquo Sensors vol 14 no 12 pp 22208ndash22229 2014

[5] A P F Turner ldquoBiosensors sense and sensibilityrdquo ChemicalSociety Reviews vol 42 no 8 pp 3184ndash3196 2013

[6] L Wu and X Qu ldquoCancer biomarker detection recent achieve-ments and challengesrdquoChemical Society Reviews vol 44 no 10pp 2963ndash2997 2015

[7] K Ariga Q Ji T Mori et al ldquoEnzyme nanoarchitectonicsorganization and device applicationrdquo Chemical Society Reviewsvol 42 no 15 pp 6322ndash6345 2013

[8] W-W Zhao J-J Xu and H-Y Chen ldquoPhotoelectrochemicalDNA biosensorsrdquo Chemical Reviews vol 114 no 15 pp 7421ndash7441 2014

[9] Q Liu C Wu H Cai N Hu J Zhou and P Wang ldquoCell-basedbiosensors and their application in biomedicinerdquo ChemicalReviews vol 114 no 12 pp 6423ndash6461 2014

[10] X Zhao S Nampalli A J Serino and S Kumar ldquoImmobi-lization of oligodeoxyribonucleotides with multiple anchors to

microchipsrdquo Nucleic Acids Research vol 29 no 4 pp 955ndash9592001

[11] P Kumar S K Agrawal A Misra and K C Gupta ldquoA newheterobifunctional reagent for immobilization of biomoleculeson glass surfacerdquo Bioorganic 120572Medicinal Chemistry Letters vol14 no 5 pp 1097ndash1099 2004

[12] F Secundo ldquoConformational changes of enzymes upon immo-bilisationrdquo Chemical Society Reviews vol 42 no 15 pp 6250ndash6261 2013

[13] S Lee S Kim J Malm O C Jeong H Lilja and T LaurellldquoImproved porous silicon microarray based prostate specificantigen immunoassay by optimized surface density of thecapture antibodyrdquoAnalytica Chimica Acta vol 796 pp 108ndash1142013

[14] K Jaras A A Tajudin A Ressine et al ldquoENSAM europiumnanoparticles for signal enhancement of antibody microarrayson nanoporous siliconrdquo Journal of Proteome Research vol 7 no3 pp 1308ndash1314 2008

[15] C Steinhauer A Ressine G Marko-Varga T Laurell C AK Borrebaeck and C Wingren ldquoBiocompatibility of surfacesfor antibody microarrays design of macroporous silicon sub-stratesrdquo Analytical Biochemistry vol 341 no 2 pp 204ndash2132005

[16] K Jaras B Adler A Tojo et al ldquoPorous silicon antibodymicroarrays for quantitative analysis measurement of free andtotal PSA in clinical plasma samplesrdquo Clinica Chimica Acta vol414 pp 76ndash84 2012

[17] S W Lee K Hosokawa S Kim et al ldquoA highly sensitive poroussilicon (P-Si)-based human Kallikrein 2 (hK2) immunoassayplatform toward accurate diagnosis of prostate cancerrdquo Sensorsvol 15 no 5 pp 11972ndash11987 2015

[18] C Roychaudhuri ldquoA review on porous silicon based electro-chemical biosensors beyond surface area enhancement factorrdquoSensors and Actuators B Chemical vol 210 pp 310ndash323 2015

[19] ARessine S EkstromGMarko-Varga andT Laurell ldquoMacro-nanoporous silicon as a support for high-performance proteinmicroarraysrdquo Analytical Chemistry vol 75 no 24 pp 6968ndash6974 2003

[20] S Lee E Silajdzic H Yang et al ldquoA porous silicon immunoas-say platform for fluorometric determination of 120572-synuclein inhuman cerebrospinal fluidrdquo Microchimica Acta vol 181 no 9-10 pp 1143ndash1149 2014

[21] S Belhousse N Belhaneche-Bensemra K Lasmi et alldquoModified porous silicon for electrochemical sensor of para-nitrophenolrdquo Materials Science and Engineering B vol 189 pp76ndash81 2014

[22] N Reta A Michelmore C Saint B Prieto-Simon and NH Voelcker ldquoPorous silicon membrane-modified electrodesfor label-free voltammetric detection of MS2 bacteriophagerdquoBiosensors and Bioelectronics vol 80 pp 47ndash53 2016

[23] B Guan A Magenau S Ciampi K Gaus P J Reece and J JGooding ldquoAntibody modified porous silicon microparticles forthe selective capture of cellsrdquo Bioconjugate Chemistry vol 25no 7 pp 1282ndash1289 2014

[24] S Vutti N Buch-Manson S Schoffelen N Bovet K LMartinez and M Meldal ldquoCovalent and stable CuAAC mod-ification of silicon surfaces for control of cell adhesionrdquo Chem-BioChem vol 16 no 5 pp 782ndash791 2015

[25] A M Rossi L Wang V Reipa and T E Murphy ldquoPoroussilicon biosensor for detection of virusesrdquo Biosensors andBioelectronics vol 23 no 5 pp 741ndash745 2007

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[26] T L Lasseter B H Clare N L Abbott and R J HamersldquoCovalently modified silicon and diamond surfaces resistanceto nonspecific protein adsorption and optimization for biosens-ingrdquo Journal of the American Chemical Society vol 126 no 33pp 10220ndash10221 2004

[27] M Li K-G Neoh E-T Kang T Lau and E E ChiongldquoSurface modification of silicone with covalently immobilizedand crosslinked agarose for potential application in the inhibi-tion of infection and omental wrappingrdquo Advanced FunctionalMaterials vol 24 no 11 pp 1631ndash1643 2014

[28] G MacBeath and S L Schreiber ldquoPrinting proteins as microar-rays for high-throughput function determinationrdquo Science vol289 no 5485 pp 1760ndash1763 2000

[29] S B Nimse M D Sonawane K S Song and T Kim ldquoBio-marker detection technologies and future directionsrdquoThe Ana-lyst vol 141 no 3 pp 740ndash755 2016

[30] M D Sonawane S B Nimse K Song and T Kim ldquoDetectionquantification and profiling of PSA current microarray tech-nologies and future directionsrdquo RSC Advances vol 6 no 9 pp7599ndash7609 2016

[31] S B Nimse and T Kim ldquoBiological applications of function-alized calixarenesrdquo Chemical Society Reviews vol 42 no 1 pp366ndash386 2013

[32] K-S Song S B Nimse J Kim et al ldquo9GDNAChip microarraybased on the multiple interactions of 9 consecutive guaninesrdquoChemical Communications vol 47 no 25 pp 7101ndash7103 2011

[33] R J Chen S Bangsaruntip K A Drouvalakis et al ldquoNonco-valent functionalization of carbon nanotubes for highly specificelectronic biosensorsrdquo Proceedings of the National Academy ofSciences of the United States of America vol 100 no 9 pp 4984ndash4989 2003

[34] Y Lu W Shi J Qin and B Lin ldquoFabrication and characteri-zation of paper-based microfluidics prepared in nitrocellulosemembrane by wax printingrdquo Analytical Chemistry vol 82 no1 pp 329ndash335 2010

[35] P Zhang R Zhang M Gao and X Zhang ldquoNovel nitrocel-lulose membrane substrate for efficient analysis of circulatingtumor cells coupled with surface-enhanced raman scatteringimagingrdquo ACS Applied Materials and Interfaces vol 6 no 1 pp370ndash376 2014

[36] J-S Lee A K R Lytton-Jean S J Hurst and C AMirkin ldquoSil-ver nanoparticlemdasholigonucleotide conjugates based on DNAwith triple cyclic disulfide moietiesrdquo Nano Letters vol 7 no 7pp 2112ndash2115 2007

[37] S Y Song Y D Han K Kim S S Yang and H C YoonldquoA fluoro-microbead guiding chip for simple and quantifiableimmunoassay of cardiac troponin I (cTnI)rdquo Biosensors andBioelectronics vol 26 no 9 pp 3818ndash3824 2011

[38] S V Lemeshko T Powdrill Y Y Belosludtsev and M HoganldquoOligonucleotides form a duplex with non-helical properties ona positively charged surfacerdquoNucleic Acids Research vol 29 no14 pp 3051ndash3058 2001

[39] Z-L Zhi A K Powell and J E Turnbull ldquoFabrication ofcarbohydrate microarrays on gold surfaces direct attachmentof nonderivatized oligosaccharides to hydrazide-modified self-assembledmonolayersrdquoAnalytical Chemistry vol 78 no 14 pp4786ndash4793 2006

[40] S L Pan and L Rothberg ldquoChemical control of electrodefunctionalization for detection of DNA hybridization by elec-trochemical impedance spectroscopyrdquo Langmuir vol 21 no 3pp 1022ndash1027 2005

[41] Z Lu C M Li Q Zhou Q-L Bao and X Cui ldquoCovalentlylinked DNAprotein multilayered film for controlled DNAreleaserdquo Journal of Colloid and Interface Science vol 314 no 1pp 80ndash88 2007

[42] L-S Jang and H-J Liu ldquoFabrication of protein chips basedon 3-aminopropyltriethoxysilane as a monolayerrdquo BiomedicalMicrodevices vol 11 no 2 pp 331ndash338 2009

[43] F Fixe M Dufva P Telleman and C B Christensen ldquoFunc-tionalization of poly(methyl methacrylate) (PMMA) as a sub-strate for DNAmicroarraysrdquoNucleic Acids Research vol 32 no1 article e9 2004

[44] A Lueking M Horn H Eickhoff K Bussow H Lehrachand G Walter ldquoProtein microarrays for gene expression andantibody screeningrdquo Analytical Biochemistry vol 270 no 1 pp103ndash111 1999

[45] N Zammatteo L Jeanmart S Hamels et al ldquoComparisonbetween different strategies of covalent attachment of DNA toglass surfaces to build DNA microarraysrdquo Analytical Biochem-istry vol 280 no 1 pp 143ndash150 2000

[46] M Ozmen K Can I Akin et al ldquoSurface modification of glassbeads with glutaraldehyde characterization and their adsorp-tion property for metal ionsrdquo Journal of Hazardous Materialsvol 171 no 1ndash3 pp 594ndash600 2009

[47] C Funk PM Dietrich T Gross HMinW E S Unger andWWeigel ldquoEpoxy-functionalized surfaces for microarray appli-cations surface chemical analysis and fluorescence labeling ofsurface speciesrdquo Surface and Interface Analysis vol 44 no 8pp 890ndash894 2012

[48] S Mahajan P Kumar and K C Gupta ldquoOligonucleotide mic-roarrays immobilization of phosphorylated oligonucleotideson epoxylated surfacerdquo Bioconjugate Chemistry vol 17 no 5pp 1184ndash1189 2006

[49] M C Pirrung J D Davis and A L Odenbaugh ldquoNovelreagents and procedures for immobilization of DNA on glassmicrochips for primer extensionrdquo Langmuir vol 16 no 5 pp2185ndash2191 2000

[50] E Southern K Mir and M Shchepinov ldquoMolecular interac-tions on microarraysrdquo Nature Genetics vol 21 no 1 pp 5ndash91999

[51] M S Shchepinov S C Case-Green and E M SouthernldquoSteric factors influencing hybridisation of nucleic acids tooligonucleotide arraysrdquo Nucleic Acids Research vol 25 no 6pp 1155ndash1161 1997

[52] D A Tomalia A M Naylor and W A Goddard III ldquoStarbustdendrimers molecular-level control of size shape surfacechemistry topology and flexibility from atoms to macroscopicmatterrdquo Angewandte ChemiemdashInternational Edition in Englishvol 29 no 2 pp 138ndash175 1990

[53] R Benters C M Niemeyer D Drutschmann D Blohm andD Wohrle ldquoDNA microarrays with PAMAM dendritic linkersystemsrdquo Nucleic Acids Research vol 30 no 2 p e10 2002

[54] J H Moon J W Shin S Y Kim and J W Park ldquoFormationof uniform aminosilane thin layers an imine formation tomeasure relative surface density of the amine grouprdquo Langmuirvol 12 no 20 pp 4621ndash4624 1996

[55] J C Alwine D J Kemp and G R Stark ldquoMethod fordetection of specific RNAs in agarose gels by transfer to diazo-benzyloxymethyl-paper and hybridization with DNA probesrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 74 no 12 pp 5350ndash5354 1977

[56] P L Dolan Y Wu L K Ista R L Metzenberg M A Nelsonand G P Lopez ldquoRobust and efficient synthetic method for

Journal of Chemistry 17

forming DNA microarraysrdquo Nucleic Acids Research vol 29 no21 article e107 2001

[57] S B Nimse J Kim K-S Song et al ldquoSelective recognitionof the ditopic trimethylammonium cations by water-solubleaminocalix[4]arenerdquo Tetrahedron Letters vol 52 no 29 pp3751ndash3755 2011

[58] V-T Ta S B Nimse K-S Song et al ldquoCharacterization ofthe mixed self-assembled monolayer at the molecular scalerdquoChemical Communications vol 47 no 40 pp 11261ndash11263 2011

[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

[60] Y Lee E K Lee YW Cho et al ldquoProteoChip a highly sensitiveprotein microarray prepared by a novel method of proteinimmobilization for application of protein-protein interactionstudiesrdquo Proteomics vol 3 no 12 pp 2289ndash2304 2003

[61] S W Oh J D Moon H J Lim et al ldquoCalixarene derivative asa tool for highly sensitive detection and oriented immobiliza-tion of proteins in a microarray format through noncovalentmolecular interactionrdquo The FASEB Journal vol 19 no 10 pp1335ndash1337 2005

[62] S B Nimse K-S Song J Kim D R Sayyed and T Kimldquo9G DNAChip technology self-assembled monolayer (SAM)of ssDNA for ultra-sensitive detection of biomarkersrdquo Interna-tional Journal ofMolecular Sciences vol 14 no 3 pp 5723ndash57332013

[63] V-T Nguyen S B Nimse K-S Song et al ldquoHPAI 9GDNAChip discrimination of highly pathogenic influenza virusgenesrdquo Chemical Communications vol 48 no 38 pp 4582ndash4584 2012

[64] K-S Song S B Nimse J Kim D R Sayyed and T Kim ldquoAnew platform for a convenient genotyping systemrdquo ChemicalCommunications vol 49 no 26 pp 2661ndash2663 2013

[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

[67] F Hennrich C Chan VMoore M Rolandi andM OrsquoConnellCarbonNanotubes Properties and Applications Taylor amp FrancisGroup Abingdon UK 2006

[68] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

[69] C Singh M Shaffer I Kinloch and A Windle ldquoProductionof aligned carbon nanotubes by the CVD injection methodrdquoPhysica B Condensed Matter vol 323 no 1ndash4 pp 339ndash3402002

[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

[71] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

14 Journal of Chemistry

HN

O

OH

OP

O

O

PO

O

OHO

N

NN

P

O

S

HN

O

Coenzyme A

Phosphopantetheine

PO

O

O

OHO

N Sfp

NN

N

P

O

ybbr-protein

HN

O

OH

OP

O

O

S

HN

O

NH2

NH2

Ominus

Ominus

Ominus

minusO

minusO

Mg2+

HO∙∙

Ominus

OminusOminus

minusO

N

O

Polystyrenenanoparticle

Scheme 12 Protein conjugation to polystyrene NP

System 1 antibody-conjugated fluoromicrobeads

System 2 avidin-conjugated fluoromicrobeads

DTSP SAM

Anti-cTnI cAb

cTnI

Figure 12 Application of the polystyrene-coated fluoromicrobeadsfor the detection of cTnI on the protein microarray (adapted from[37])

coupling reaction The use of fluoromicrobeads alloweddetecting the cTnI in plasma samples with a range of 01ndash100 ngmL

272 Affinity-Based Modification The affinity interactionsare used for the attachment of oligonucleotides with thefluoromicrobeads or polystyrene-coated magnetic beads Togenerate the oligonucleotide conjugated fluoromicrobeads ormagnetic beads respective polystyrene-coated beads are firstconjugated with the streptavidin using the EDCNHS cou-pling reaction as reported by Zhang et al [141] As depicted

B

B

MB MB

MB

BB

Magnetic bead

Streptavidin

DNA labeled biotin

Figure 13 DNA attachment to the magnetic beads

in Figure 13 the streptavidinmodified beads are then allowedto incubate with the biotinylated oligonucleotides Due to theaffinity of biotin for streptavidin the biotinylated oligonu-cleotides can be readily immobilized on the streptavidincoated beads

The binding affinity of streptavidin and biotin in solutionis up to 25 times 1013 (molL)minus1 [142] This interaction is about amillion times stronger than the antigen and antibody inter-action The antibodies directly immobilized onto the sur-face lose 90 of their biological activity [143] Howeverthe biotinylated antibodies immobilized on the streptavidincoated surface can retain their bioactivity [144]

Journal of Chemistry 15

3 Conclusions

Surface modification techniques of the materials used asplatforms in the fabrication of biosensors are reviewed inthis paper There are several reports on materials and vari-ous methods for altering their physicochemical propertiesHence one of these methods can be chosen according tothe targeted use and needed physiochemical properties Itis important to note that the performance of the biosensoris highly dependent on the substrate material used and itsmeticulous modification for particular applications There-fore it is critical to understand the principles of a biosensor toidentify the correct substrate material and its surface modifi-cation chemistry Furthermore it is important to look at thelatest advances in the materials and techniques used for thefabrication of a biosensor before the processing

Competing Interests

All authors declare that there is no conflict of interests

Acknowledgments

This research was supported by the Hallym UniversityResearch Fund (HRF-201601-010) This work was also sup-ported by the fund obtained through Industry-Academic col-laboration between Biometrix Technology Inc (ChuncheonSouth Korea) and Hallym University

References

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[2] A Cavalcanti B Shirinzadeh M Zhang and L C KretlyldquoNanorobot hardware architecture for medical defenserdquo Sen-sors vol 8 no 5 pp 2932ndash2958 2008

[3] R-Q Zhang S-L Liu W Zhao et al ldquoA simple point-of-caremicrofluidic immunomagnetic fluorescence assay for path-ogensrdquo Analytical Chemistry vol 85 no 5 pp 2645ndash2651 2013

[4] S B Nimse K S Song M D Sonawane D R Sayyed and TS Kim ldquoImmobilization techniques for microarray challengesand applicationsrdquo Sensors vol 14 no 12 pp 22208ndash22229 2014

[5] A P F Turner ldquoBiosensors sense and sensibilityrdquo ChemicalSociety Reviews vol 42 no 8 pp 3184ndash3196 2013

[6] L Wu and X Qu ldquoCancer biomarker detection recent achieve-ments and challengesrdquoChemical Society Reviews vol 44 no 10pp 2963ndash2997 2015

[7] K Ariga Q Ji T Mori et al ldquoEnzyme nanoarchitectonicsorganization and device applicationrdquo Chemical Society Reviewsvol 42 no 15 pp 6322ndash6345 2013

[8] W-W Zhao J-J Xu and H-Y Chen ldquoPhotoelectrochemicalDNA biosensorsrdquo Chemical Reviews vol 114 no 15 pp 7421ndash7441 2014

[9] Q Liu C Wu H Cai N Hu J Zhou and P Wang ldquoCell-basedbiosensors and their application in biomedicinerdquo ChemicalReviews vol 114 no 12 pp 6423ndash6461 2014

[10] X Zhao S Nampalli A J Serino and S Kumar ldquoImmobi-lization of oligodeoxyribonucleotides with multiple anchors to

microchipsrdquo Nucleic Acids Research vol 29 no 4 pp 955ndash9592001

[11] P Kumar S K Agrawal A Misra and K C Gupta ldquoA newheterobifunctional reagent for immobilization of biomoleculeson glass surfacerdquo Bioorganic 120572Medicinal Chemistry Letters vol14 no 5 pp 1097ndash1099 2004

[12] F Secundo ldquoConformational changes of enzymes upon immo-bilisationrdquo Chemical Society Reviews vol 42 no 15 pp 6250ndash6261 2013

[13] S Lee S Kim J Malm O C Jeong H Lilja and T LaurellldquoImproved porous silicon microarray based prostate specificantigen immunoassay by optimized surface density of thecapture antibodyrdquoAnalytica Chimica Acta vol 796 pp 108ndash1142013

[14] K Jaras A A Tajudin A Ressine et al ldquoENSAM europiumnanoparticles for signal enhancement of antibody microarrayson nanoporous siliconrdquo Journal of Proteome Research vol 7 no3 pp 1308ndash1314 2008

[15] C Steinhauer A Ressine G Marko-Varga T Laurell C AK Borrebaeck and C Wingren ldquoBiocompatibility of surfacesfor antibody microarrays design of macroporous silicon sub-stratesrdquo Analytical Biochemistry vol 341 no 2 pp 204ndash2132005

[16] K Jaras B Adler A Tojo et al ldquoPorous silicon antibodymicroarrays for quantitative analysis measurement of free andtotal PSA in clinical plasma samplesrdquo Clinica Chimica Acta vol414 pp 76ndash84 2012

[17] S W Lee K Hosokawa S Kim et al ldquoA highly sensitive poroussilicon (P-Si)-based human Kallikrein 2 (hK2) immunoassayplatform toward accurate diagnosis of prostate cancerrdquo Sensorsvol 15 no 5 pp 11972ndash11987 2015

[18] C Roychaudhuri ldquoA review on porous silicon based electro-chemical biosensors beyond surface area enhancement factorrdquoSensors and Actuators B Chemical vol 210 pp 310ndash323 2015

[19] ARessine S EkstromGMarko-Varga andT Laurell ldquoMacro-nanoporous silicon as a support for high-performance proteinmicroarraysrdquo Analytical Chemistry vol 75 no 24 pp 6968ndash6974 2003

[20] S Lee E Silajdzic H Yang et al ldquoA porous silicon immunoas-say platform for fluorometric determination of 120572-synuclein inhuman cerebrospinal fluidrdquo Microchimica Acta vol 181 no 9-10 pp 1143ndash1149 2014

[21] S Belhousse N Belhaneche-Bensemra K Lasmi et alldquoModified porous silicon for electrochemical sensor of para-nitrophenolrdquo Materials Science and Engineering B vol 189 pp76ndash81 2014

[22] N Reta A Michelmore C Saint B Prieto-Simon and NH Voelcker ldquoPorous silicon membrane-modified electrodesfor label-free voltammetric detection of MS2 bacteriophagerdquoBiosensors and Bioelectronics vol 80 pp 47ndash53 2016

[23] B Guan A Magenau S Ciampi K Gaus P J Reece and J JGooding ldquoAntibody modified porous silicon microparticles forthe selective capture of cellsrdquo Bioconjugate Chemistry vol 25no 7 pp 1282ndash1289 2014

[24] S Vutti N Buch-Manson S Schoffelen N Bovet K LMartinez and M Meldal ldquoCovalent and stable CuAAC mod-ification of silicon surfaces for control of cell adhesionrdquo Chem-BioChem vol 16 no 5 pp 782ndash791 2015

[25] A M Rossi L Wang V Reipa and T E Murphy ldquoPoroussilicon biosensor for detection of virusesrdquo Biosensors andBioelectronics vol 23 no 5 pp 741ndash745 2007

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[26] T L Lasseter B H Clare N L Abbott and R J HamersldquoCovalently modified silicon and diamond surfaces resistanceto nonspecific protein adsorption and optimization for biosens-ingrdquo Journal of the American Chemical Society vol 126 no 33pp 10220ndash10221 2004

[27] M Li K-G Neoh E-T Kang T Lau and E E ChiongldquoSurface modification of silicone with covalently immobilizedand crosslinked agarose for potential application in the inhibi-tion of infection and omental wrappingrdquo Advanced FunctionalMaterials vol 24 no 11 pp 1631ndash1643 2014

[28] G MacBeath and S L Schreiber ldquoPrinting proteins as microar-rays for high-throughput function determinationrdquo Science vol289 no 5485 pp 1760ndash1763 2000

[29] S B Nimse M D Sonawane K S Song and T Kim ldquoBio-marker detection technologies and future directionsrdquoThe Ana-lyst vol 141 no 3 pp 740ndash755 2016

[30] M D Sonawane S B Nimse K Song and T Kim ldquoDetectionquantification and profiling of PSA current microarray tech-nologies and future directionsrdquo RSC Advances vol 6 no 9 pp7599ndash7609 2016

[31] S B Nimse and T Kim ldquoBiological applications of function-alized calixarenesrdquo Chemical Society Reviews vol 42 no 1 pp366ndash386 2013

[32] K-S Song S B Nimse J Kim et al ldquo9GDNAChip microarraybased on the multiple interactions of 9 consecutive guaninesrdquoChemical Communications vol 47 no 25 pp 7101ndash7103 2011

[33] R J Chen S Bangsaruntip K A Drouvalakis et al ldquoNonco-valent functionalization of carbon nanotubes for highly specificelectronic biosensorsrdquo Proceedings of the National Academy ofSciences of the United States of America vol 100 no 9 pp 4984ndash4989 2003

[34] Y Lu W Shi J Qin and B Lin ldquoFabrication and characteri-zation of paper-based microfluidics prepared in nitrocellulosemembrane by wax printingrdquo Analytical Chemistry vol 82 no1 pp 329ndash335 2010

[35] P Zhang R Zhang M Gao and X Zhang ldquoNovel nitrocel-lulose membrane substrate for efficient analysis of circulatingtumor cells coupled with surface-enhanced raman scatteringimagingrdquo ACS Applied Materials and Interfaces vol 6 no 1 pp370ndash376 2014

[36] J-S Lee A K R Lytton-Jean S J Hurst and C AMirkin ldquoSil-ver nanoparticlemdasholigonucleotide conjugates based on DNAwith triple cyclic disulfide moietiesrdquo Nano Letters vol 7 no 7pp 2112ndash2115 2007

[37] S Y Song Y D Han K Kim S S Yang and H C YoonldquoA fluoro-microbead guiding chip for simple and quantifiableimmunoassay of cardiac troponin I (cTnI)rdquo Biosensors andBioelectronics vol 26 no 9 pp 3818ndash3824 2011

[38] S V Lemeshko T Powdrill Y Y Belosludtsev and M HoganldquoOligonucleotides form a duplex with non-helical properties ona positively charged surfacerdquoNucleic Acids Research vol 29 no14 pp 3051ndash3058 2001

[39] Z-L Zhi A K Powell and J E Turnbull ldquoFabrication ofcarbohydrate microarrays on gold surfaces direct attachmentof nonderivatized oligosaccharides to hydrazide-modified self-assembledmonolayersrdquoAnalytical Chemistry vol 78 no 14 pp4786ndash4793 2006

[40] S L Pan and L Rothberg ldquoChemical control of electrodefunctionalization for detection of DNA hybridization by elec-trochemical impedance spectroscopyrdquo Langmuir vol 21 no 3pp 1022ndash1027 2005

[41] Z Lu C M Li Q Zhou Q-L Bao and X Cui ldquoCovalentlylinked DNAprotein multilayered film for controlled DNAreleaserdquo Journal of Colloid and Interface Science vol 314 no 1pp 80ndash88 2007

[42] L-S Jang and H-J Liu ldquoFabrication of protein chips basedon 3-aminopropyltriethoxysilane as a monolayerrdquo BiomedicalMicrodevices vol 11 no 2 pp 331ndash338 2009

[43] F Fixe M Dufva P Telleman and C B Christensen ldquoFunc-tionalization of poly(methyl methacrylate) (PMMA) as a sub-strate for DNAmicroarraysrdquoNucleic Acids Research vol 32 no1 article e9 2004

[44] A Lueking M Horn H Eickhoff K Bussow H Lehrachand G Walter ldquoProtein microarrays for gene expression andantibody screeningrdquo Analytical Biochemistry vol 270 no 1 pp103ndash111 1999

[45] N Zammatteo L Jeanmart S Hamels et al ldquoComparisonbetween different strategies of covalent attachment of DNA toglass surfaces to build DNA microarraysrdquo Analytical Biochem-istry vol 280 no 1 pp 143ndash150 2000

[46] M Ozmen K Can I Akin et al ldquoSurface modification of glassbeads with glutaraldehyde characterization and their adsorp-tion property for metal ionsrdquo Journal of Hazardous Materialsvol 171 no 1ndash3 pp 594ndash600 2009

[47] C Funk PM Dietrich T Gross HMinW E S Unger andWWeigel ldquoEpoxy-functionalized surfaces for microarray appli-cations surface chemical analysis and fluorescence labeling ofsurface speciesrdquo Surface and Interface Analysis vol 44 no 8pp 890ndash894 2012

[48] S Mahajan P Kumar and K C Gupta ldquoOligonucleotide mic-roarrays immobilization of phosphorylated oligonucleotideson epoxylated surfacerdquo Bioconjugate Chemistry vol 17 no 5pp 1184ndash1189 2006

[49] M C Pirrung J D Davis and A L Odenbaugh ldquoNovelreagents and procedures for immobilization of DNA on glassmicrochips for primer extensionrdquo Langmuir vol 16 no 5 pp2185ndash2191 2000

[50] E Southern K Mir and M Shchepinov ldquoMolecular interac-tions on microarraysrdquo Nature Genetics vol 21 no 1 pp 5ndash91999

[51] M S Shchepinov S C Case-Green and E M SouthernldquoSteric factors influencing hybridisation of nucleic acids tooligonucleotide arraysrdquo Nucleic Acids Research vol 25 no 6pp 1155ndash1161 1997

[52] D A Tomalia A M Naylor and W A Goddard III ldquoStarbustdendrimers molecular-level control of size shape surfacechemistry topology and flexibility from atoms to macroscopicmatterrdquo Angewandte ChemiemdashInternational Edition in Englishvol 29 no 2 pp 138ndash175 1990

[53] R Benters C M Niemeyer D Drutschmann D Blohm andD Wohrle ldquoDNA microarrays with PAMAM dendritic linkersystemsrdquo Nucleic Acids Research vol 30 no 2 p e10 2002

[54] J H Moon J W Shin S Y Kim and J W Park ldquoFormationof uniform aminosilane thin layers an imine formation tomeasure relative surface density of the amine grouprdquo Langmuirvol 12 no 20 pp 4621ndash4624 1996

[55] J C Alwine D J Kemp and G R Stark ldquoMethod fordetection of specific RNAs in agarose gels by transfer to diazo-benzyloxymethyl-paper and hybridization with DNA probesrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 74 no 12 pp 5350ndash5354 1977

[56] P L Dolan Y Wu L K Ista R L Metzenberg M A Nelsonand G P Lopez ldquoRobust and efficient synthetic method for

Journal of Chemistry 17

forming DNA microarraysrdquo Nucleic Acids Research vol 29 no21 article e107 2001

[57] S B Nimse J Kim K-S Song et al ldquoSelective recognitionof the ditopic trimethylammonium cations by water-solubleaminocalix[4]arenerdquo Tetrahedron Letters vol 52 no 29 pp3751ndash3755 2011

[58] V-T Ta S B Nimse K-S Song et al ldquoCharacterization ofthe mixed self-assembled monolayer at the molecular scalerdquoChemical Communications vol 47 no 40 pp 11261ndash11263 2011

[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

[60] Y Lee E K Lee YW Cho et al ldquoProteoChip a highly sensitiveprotein microarray prepared by a novel method of proteinimmobilization for application of protein-protein interactionstudiesrdquo Proteomics vol 3 no 12 pp 2289ndash2304 2003

[61] S W Oh J D Moon H J Lim et al ldquoCalixarene derivative asa tool for highly sensitive detection and oriented immobiliza-tion of proteins in a microarray format through noncovalentmolecular interactionrdquo The FASEB Journal vol 19 no 10 pp1335ndash1337 2005

[62] S B Nimse K-S Song J Kim D R Sayyed and T Kimldquo9G DNAChip technology self-assembled monolayer (SAM)of ssDNA for ultra-sensitive detection of biomarkersrdquo Interna-tional Journal ofMolecular Sciences vol 14 no 3 pp 5723ndash57332013

[63] V-T Nguyen S B Nimse K-S Song et al ldquoHPAI 9GDNAChip discrimination of highly pathogenic influenza virusgenesrdquo Chemical Communications vol 48 no 38 pp 4582ndash4584 2012

[64] K-S Song S B Nimse J Kim D R Sayyed and T Kim ldquoAnew platform for a convenient genotyping systemrdquo ChemicalCommunications vol 49 no 26 pp 2661ndash2663 2013

[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

[67] F Hennrich C Chan VMoore M Rolandi andM OrsquoConnellCarbonNanotubes Properties and Applications Taylor amp FrancisGroup Abingdon UK 2006

[68] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

[69] C Singh M Shaffer I Kinloch and A Windle ldquoProductionof aligned carbon nanotubes by the CVD injection methodrdquoPhysica B Condensed Matter vol 323 no 1ndash4 pp 339ndash3402002

[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

[71] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Journal of Chemistry 15

3 Conclusions

Surface modification techniques of the materials used asplatforms in the fabrication of biosensors are reviewed inthis paper There are several reports on materials and vari-ous methods for altering their physicochemical propertiesHence one of these methods can be chosen according tothe targeted use and needed physiochemical properties Itis important to note that the performance of the biosensoris highly dependent on the substrate material used and itsmeticulous modification for particular applications There-fore it is critical to understand the principles of a biosensor toidentify the correct substrate material and its surface modifi-cation chemistry Furthermore it is important to look at thelatest advances in the materials and techniques used for thefabrication of a biosensor before the processing

Competing Interests

All authors declare that there is no conflict of interests

Acknowledgments

This research was supported by the Hallym UniversityResearch Fund (HRF-201601-010) This work was also sup-ported by the fund obtained through Industry-Academic col-laboration between Biometrix Technology Inc (ChuncheonSouth Korea) and Hallym University

References

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[2] A Cavalcanti B Shirinzadeh M Zhang and L C KretlyldquoNanorobot hardware architecture for medical defenserdquo Sen-sors vol 8 no 5 pp 2932ndash2958 2008

[3] R-Q Zhang S-L Liu W Zhao et al ldquoA simple point-of-caremicrofluidic immunomagnetic fluorescence assay for path-ogensrdquo Analytical Chemistry vol 85 no 5 pp 2645ndash2651 2013

[4] S B Nimse K S Song M D Sonawane D R Sayyed and TS Kim ldquoImmobilization techniques for microarray challengesand applicationsrdquo Sensors vol 14 no 12 pp 22208ndash22229 2014

[5] A P F Turner ldquoBiosensors sense and sensibilityrdquo ChemicalSociety Reviews vol 42 no 8 pp 3184ndash3196 2013

[6] L Wu and X Qu ldquoCancer biomarker detection recent achieve-ments and challengesrdquoChemical Society Reviews vol 44 no 10pp 2963ndash2997 2015

[7] K Ariga Q Ji T Mori et al ldquoEnzyme nanoarchitectonicsorganization and device applicationrdquo Chemical Society Reviewsvol 42 no 15 pp 6322ndash6345 2013

[8] W-W Zhao J-J Xu and H-Y Chen ldquoPhotoelectrochemicalDNA biosensorsrdquo Chemical Reviews vol 114 no 15 pp 7421ndash7441 2014

[9] Q Liu C Wu H Cai N Hu J Zhou and P Wang ldquoCell-basedbiosensors and their application in biomedicinerdquo ChemicalReviews vol 114 no 12 pp 6423ndash6461 2014

[10] X Zhao S Nampalli A J Serino and S Kumar ldquoImmobi-lization of oligodeoxyribonucleotides with multiple anchors to

microchipsrdquo Nucleic Acids Research vol 29 no 4 pp 955ndash9592001

[11] P Kumar S K Agrawal A Misra and K C Gupta ldquoA newheterobifunctional reagent for immobilization of biomoleculeson glass surfacerdquo Bioorganic 120572Medicinal Chemistry Letters vol14 no 5 pp 1097ndash1099 2004

[12] F Secundo ldquoConformational changes of enzymes upon immo-bilisationrdquo Chemical Society Reviews vol 42 no 15 pp 6250ndash6261 2013

[13] S Lee S Kim J Malm O C Jeong H Lilja and T LaurellldquoImproved porous silicon microarray based prostate specificantigen immunoassay by optimized surface density of thecapture antibodyrdquoAnalytica Chimica Acta vol 796 pp 108ndash1142013

[14] K Jaras A A Tajudin A Ressine et al ldquoENSAM europiumnanoparticles for signal enhancement of antibody microarrayson nanoporous siliconrdquo Journal of Proteome Research vol 7 no3 pp 1308ndash1314 2008

[15] C Steinhauer A Ressine G Marko-Varga T Laurell C AK Borrebaeck and C Wingren ldquoBiocompatibility of surfacesfor antibody microarrays design of macroporous silicon sub-stratesrdquo Analytical Biochemistry vol 341 no 2 pp 204ndash2132005

[16] K Jaras B Adler A Tojo et al ldquoPorous silicon antibodymicroarrays for quantitative analysis measurement of free andtotal PSA in clinical plasma samplesrdquo Clinica Chimica Acta vol414 pp 76ndash84 2012

[17] S W Lee K Hosokawa S Kim et al ldquoA highly sensitive poroussilicon (P-Si)-based human Kallikrein 2 (hK2) immunoassayplatform toward accurate diagnosis of prostate cancerrdquo Sensorsvol 15 no 5 pp 11972ndash11987 2015

[18] C Roychaudhuri ldquoA review on porous silicon based electro-chemical biosensors beyond surface area enhancement factorrdquoSensors and Actuators B Chemical vol 210 pp 310ndash323 2015

[19] ARessine S EkstromGMarko-Varga andT Laurell ldquoMacro-nanoporous silicon as a support for high-performance proteinmicroarraysrdquo Analytical Chemistry vol 75 no 24 pp 6968ndash6974 2003

[20] S Lee E Silajdzic H Yang et al ldquoA porous silicon immunoas-say platform for fluorometric determination of 120572-synuclein inhuman cerebrospinal fluidrdquo Microchimica Acta vol 181 no 9-10 pp 1143ndash1149 2014

[21] S Belhousse N Belhaneche-Bensemra K Lasmi et alldquoModified porous silicon for electrochemical sensor of para-nitrophenolrdquo Materials Science and Engineering B vol 189 pp76ndash81 2014

[22] N Reta A Michelmore C Saint B Prieto-Simon and NH Voelcker ldquoPorous silicon membrane-modified electrodesfor label-free voltammetric detection of MS2 bacteriophagerdquoBiosensors and Bioelectronics vol 80 pp 47ndash53 2016

[23] B Guan A Magenau S Ciampi K Gaus P J Reece and J JGooding ldquoAntibody modified porous silicon microparticles forthe selective capture of cellsrdquo Bioconjugate Chemistry vol 25no 7 pp 1282ndash1289 2014

[24] S Vutti N Buch-Manson S Schoffelen N Bovet K LMartinez and M Meldal ldquoCovalent and stable CuAAC mod-ification of silicon surfaces for control of cell adhesionrdquo Chem-BioChem vol 16 no 5 pp 782ndash791 2015

[25] A M Rossi L Wang V Reipa and T E Murphy ldquoPoroussilicon biosensor for detection of virusesrdquo Biosensors andBioelectronics vol 23 no 5 pp 741ndash745 2007

16 Journal of Chemistry

[26] T L Lasseter B H Clare N L Abbott and R J HamersldquoCovalently modified silicon and diamond surfaces resistanceto nonspecific protein adsorption and optimization for biosens-ingrdquo Journal of the American Chemical Society vol 126 no 33pp 10220ndash10221 2004

[27] M Li K-G Neoh E-T Kang T Lau and E E ChiongldquoSurface modification of silicone with covalently immobilizedand crosslinked agarose for potential application in the inhibi-tion of infection and omental wrappingrdquo Advanced FunctionalMaterials vol 24 no 11 pp 1631ndash1643 2014

[28] G MacBeath and S L Schreiber ldquoPrinting proteins as microar-rays for high-throughput function determinationrdquo Science vol289 no 5485 pp 1760ndash1763 2000

[29] S B Nimse M D Sonawane K S Song and T Kim ldquoBio-marker detection technologies and future directionsrdquoThe Ana-lyst vol 141 no 3 pp 740ndash755 2016

[30] M D Sonawane S B Nimse K Song and T Kim ldquoDetectionquantification and profiling of PSA current microarray tech-nologies and future directionsrdquo RSC Advances vol 6 no 9 pp7599ndash7609 2016

[31] S B Nimse and T Kim ldquoBiological applications of function-alized calixarenesrdquo Chemical Society Reviews vol 42 no 1 pp366ndash386 2013

[32] K-S Song S B Nimse J Kim et al ldquo9GDNAChip microarraybased on the multiple interactions of 9 consecutive guaninesrdquoChemical Communications vol 47 no 25 pp 7101ndash7103 2011

[33] R J Chen S Bangsaruntip K A Drouvalakis et al ldquoNonco-valent functionalization of carbon nanotubes for highly specificelectronic biosensorsrdquo Proceedings of the National Academy ofSciences of the United States of America vol 100 no 9 pp 4984ndash4989 2003

[34] Y Lu W Shi J Qin and B Lin ldquoFabrication and characteri-zation of paper-based microfluidics prepared in nitrocellulosemembrane by wax printingrdquo Analytical Chemistry vol 82 no1 pp 329ndash335 2010

[35] P Zhang R Zhang M Gao and X Zhang ldquoNovel nitrocel-lulose membrane substrate for efficient analysis of circulatingtumor cells coupled with surface-enhanced raman scatteringimagingrdquo ACS Applied Materials and Interfaces vol 6 no 1 pp370ndash376 2014

[36] J-S Lee A K R Lytton-Jean S J Hurst and C AMirkin ldquoSil-ver nanoparticlemdasholigonucleotide conjugates based on DNAwith triple cyclic disulfide moietiesrdquo Nano Letters vol 7 no 7pp 2112ndash2115 2007

[37] S Y Song Y D Han K Kim S S Yang and H C YoonldquoA fluoro-microbead guiding chip for simple and quantifiableimmunoassay of cardiac troponin I (cTnI)rdquo Biosensors andBioelectronics vol 26 no 9 pp 3818ndash3824 2011

[38] S V Lemeshko T Powdrill Y Y Belosludtsev and M HoganldquoOligonucleotides form a duplex with non-helical properties ona positively charged surfacerdquoNucleic Acids Research vol 29 no14 pp 3051ndash3058 2001

[39] Z-L Zhi A K Powell and J E Turnbull ldquoFabrication ofcarbohydrate microarrays on gold surfaces direct attachmentof nonderivatized oligosaccharides to hydrazide-modified self-assembledmonolayersrdquoAnalytical Chemistry vol 78 no 14 pp4786ndash4793 2006

[40] S L Pan and L Rothberg ldquoChemical control of electrodefunctionalization for detection of DNA hybridization by elec-trochemical impedance spectroscopyrdquo Langmuir vol 21 no 3pp 1022ndash1027 2005

[41] Z Lu C M Li Q Zhou Q-L Bao and X Cui ldquoCovalentlylinked DNAprotein multilayered film for controlled DNAreleaserdquo Journal of Colloid and Interface Science vol 314 no 1pp 80ndash88 2007

[42] L-S Jang and H-J Liu ldquoFabrication of protein chips basedon 3-aminopropyltriethoxysilane as a monolayerrdquo BiomedicalMicrodevices vol 11 no 2 pp 331ndash338 2009

[43] F Fixe M Dufva P Telleman and C B Christensen ldquoFunc-tionalization of poly(methyl methacrylate) (PMMA) as a sub-strate for DNAmicroarraysrdquoNucleic Acids Research vol 32 no1 article e9 2004

[44] A Lueking M Horn H Eickhoff K Bussow H Lehrachand G Walter ldquoProtein microarrays for gene expression andantibody screeningrdquo Analytical Biochemistry vol 270 no 1 pp103ndash111 1999

[45] N Zammatteo L Jeanmart S Hamels et al ldquoComparisonbetween different strategies of covalent attachment of DNA toglass surfaces to build DNA microarraysrdquo Analytical Biochem-istry vol 280 no 1 pp 143ndash150 2000

[46] M Ozmen K Can I Akin et al ldquoSurface modification of glassbeads with glutaraldehyde characterization and their adsorp-tion property for metal ionsrdquo Journal of Hazardous Materialsvol 171 no 1ndash3 pp 594ndash600 2009

[47] C Funk PM Dietrich T Gross HMinW E S Unger andWWeigel ldquoEpoxy-functionalized surfaces for microarray appli-cations surface chemical analysis and fluorescence labeling ofsurface speciesrdquo Surface and Interface Analysis vol 44 no 8pp 890ndash894 2012

[48] S Mahajan P Kumar and K C Gupta ldquoOligonucleotide mic-roarrays immobilization of phosphorylated oligonucleotideson epoxylated surfacerdquo Bioconjugate Chemistry vol 17 no 5pp 1184ndash1189 2006

[49] M C Pirrung J D Davis and A L Odenbaugh ldquoNovelreagents and procedures for immobilization of DNA on glassmicrochips for primer extensionrdquo Langmuir vol 16 no 5 pp2185ndash2191 2000

[50] E Southern K Mir and M Shchepinov ldquoMolecular interac-tions on microarraysrdquo Nature Genetics vol 21 no 1 pp 5ndash91999

[51] M S Shchepinov S C Case-Green and E M SouthernldquoSteric factors influencing hybridisation of nucleic acids tooligonucleotide arraysrdquo Nucleic Acids Research vol 25 no 6pp 1155ndash1161 1997

[52] D A Tomalia A M Naylor and W A Goddard III ldquoStarbustdendrimers molecular-level control of size shape surfacechemistry topology and flexibility from atoms to macroscopicmatterrdquo Angewandte ChemiemdashInternational Edition in Englishvol 29 no 2 pp 138ndash175 1990

[53] R Benters C M Niemeyer D Drutschmann D Blohm andD Wohrle ldquoDNA microarrays with PAMAM dendritic linkersystemsrdquo Nucleic Acids Research vol 30 no 2 p e10 2002

[54] J H Moon J W Shin S Y Kim and J W Park ldquoFormationof uniform aminosilane thin layers an imine formation tomeasure relative surface density of the amine grouprdquo Langmuirvol 12 no 20 pp 4621ndash4624 1996

[55] J C Alwine D J Kemp and G R Stark ldquoMethod fordetection of specific RNAs in agarose gels by transfer to diazo-benzyloxymethyl-paper and hybridization with DNA probesrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 74 no 12 pp 5350ndash5354 1977

[56] P L Dolan Y Wu L K Ista R L Metzenberg M A Nelsonand G P Lopez ldquoRobust and efficient synthetic method for

Journal of Chemistry 17

forming DNA microarraysrdquo Nucleic Acids Research vol 29 no21 article e107 2001

[57] S B Nimse J Kim K-S Song et al ldquoSelective recognitionof the ditopic trimethylammonium cations by water-solubleaminocalix[4]arenerdquo Tetrahedron Letters vol 52 no 29 pp3751ndash3755 2011

[58] V-T Ta S B Nimse K-S Song et al ldquoCharacterization ofthe mixed self-assembled monolayer at the molecular scalerdquoChemical Communications vol 47 no 40 pp 11261ndash11263 2011

[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

[60] Y Lee E K Lee YW Cho et al ldquoProteoChip a highly sensitiveprotein microarray prepared by a novel method of proteinimmobilization for application of protein-protein interactionstudiesrdquo Proteomics vol 3 no 12 pp 2289ndash2304 2003

[61] S W Oh J D Moon H J Lim et al ldquoCalixarene derivative asa tool for highly sensitive detection and oriented immobiliza-tion of proteins in a microarray format through noncovalentmolecular interactionrdquo The FASEB Journal vol 19 no 10 pp1335ndash1337 2005

[62] S B Nimse K-S Song J Kim D R Sayyed and T Kimldquo9G DNAChip technology self-assembled monolayer (SAM)of ssDNA for ultra-sensitive detection of biomarkersrdquo Interna-tional Journal ofMolecular Sciences vol 14 no 3 pp 5723ndash57332013

[63] V-T Nguyen S B Nimse K-S Song et al ldquoHPAI 9GDNAChip discrimination of highly pathogenic influenza virusgenesrdquo Chemical Communications vol 48 no 38 pp 4582ndash4584 2012

[64] K-S Song S B Nimse J Kim D R Sayyed and T Kim ldquoAnew platform for a convenient genotyping systemrdquo ChemicalCommunications vol 49 no 26 pp 2661ndash2663 2013

[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

[67] F Hennrich C Chan VMoore M Rolandi andM OrsquoConnellCarbonNanotubes Properties and Applications Taylor amp FrancisGroup Abingdon UK 2006

[68] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

[69] C Singh M Shaffer I Kinloch and A Windle ldquoProductionof aligned carbon nanotubes by the CVD injection methodrdquoPhysica B Condensed Matter vol 323 no 1ndash4 pp 339ndash3402002

[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

[71] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

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Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

16 Journal of Chemistry

[26] T L Lasseter B H Clare N L Abbott and R J HamersldquoCovalently modified silicon and diamond surfaces resistanceto nonspecific protein adsorption and optimization for biosens-ingrdquo Journal of the American Chemical Society vol 126 no 33pp 10220ndash10221 2004

[27] M Li K-G Neoh E-T Kang T Lau and E E ChiongldquoSurface modification of silicone with covalently immobilizedand crosslinked agarose for potential application in the inhibi-tion of infection and omental wrappingrdquo Advanced FunctionalMaterials vol 24 no 11 pp 1631ndash1643 2014

[28] G MacBeath and S L Schreiber ldquoPrinting proteins as microar-rays for high-throughput function determinationrdquo Science vol289 no 5485 pp 1760ndash1763 2000

[29] S B Nimse M D Sonawane K S Song and T Kim ldquoBio-marker detection technologies and future directionsrdquoThe Ana-lyst vol 141 no 3 pp 740ndash755 2016

[30] M D Sonawane S B Nimse K Song and T Kim ldquoDetectionquantification and profiling of PSA current microarray tech-nologies and future directionsrdquo RSC Advances vol 6 no 9 pp7599ndash7609 2016

[31] S B Nimse and T Kim ldquoBiological applications of function-alized calixarenesrdquo Chemical Society Reviews vol 42 no 1 pp366ndash386 2013

[32] K-S Song S B Nimse J Kim et al ldquo9GDNAChip microarraybased on the multiple interactions of 9 consecutive guaninesrdquoChemical Communications vol 47 no 25 pp 7101ndash7103 2011

[33] R J Chen S Bangsaruntip K A Drouvalakis et al ldquoNonco-valent functionalization of carbon nanotubes for highly specificelectronic biosensorsrdquo Proceedings of the National Academy ofSciences of the United States of America vol 100 no 9 pp 4984ndash4989 2003

[34] Y Lu W Shi J Qin and B Lin ldquoFabrication and characteri-zation of paper-based microfluidics prepared in nitrocellulosemembrane by wax printingrdquo Analytical Chemistry vol 82 no1 pp 329ndash335 2010

[35] P Zhang R Zhang M Gao and X Zhang ldquoNovel nitrocel-lulose membrane substrate for efficient analysis of circulatingtumor cells coupled with surface-enhanced raman scatteringimagingrdquo ACS Applied Materials and Interfaces vol 6 no 1 pp370ndash376 2014

[36] J-S Lee A K R Lytton-Jean S J Hurst and C AMirkin ldquoSil-ver nanoparticlemdasholigonucleotide conjugates based on DNAwith triple cyclic disulfide moietiesrdquo Nano Letters vol 7 no 7pp 2112ndash2115 2007

[37] S Y Song Y D Han K Kim S S Yang and H C YoonldquoA fluoro-microbead guiding chip for simple and quantifiableimmunoassay of cardiac troponin I (cTnI)rdquo Biosensors andBioelectronics vol 26 no 9 pp 3818ndash3824 2011

[38] S V Lemeshko T Powdrill Y Y Belosludtsev and M HoganldquoOligonucleotides form a duplex with non-helical properties ona positively charged surfacerdquoNucleic Acids Research vol 29 no14 pp 3051ndash3058 2001

[39] Z-L Zhi A K Powell and J E Turnbull ldquoFabrication ofcarbohydrate microarrays on gold surfaces direct attachmentof nonderivatized oligosaccharides to hydrazide-modified self-assembledmonolayersrdquoAnalytical Chemistry vol 78 no 14 pp4786ndash4793 2006

[40] S L Pan and L Rothberg ldquoChemical control of electrodefunctionalization for detection of DNA hybridization by elec-trochemical impedance spectroscopyrdquo Langmuir vol 21 no 3pp 1022ndash1027 2005

[41] Z Lu C M Li Q Zhou Q-L Bao and X Cui ldquoCovalentlylinked DNAprotein multilayered film for controlled DNAreleaserdquo Journal of Colloid and Interface Science vol 314 no 1pp 80ndash88 2007

[42] L-S Jang and H-J Liu ldquoFabrication of protein chips basedon 3-aminopropyltriethoxysilane as a monolayerrdquo BiomedicalMicrodevices vol 11 no 2 pp 331ndash338 2009

[43] F Fixe M Dufva P Telleman and C B Christensen ldquoFunc-tionalization of poly(methyl methacrylate) (PMMA) as a sub-strate for DNAmicroarraysrdquoNucleic Acids Research vol 32 no1 article e9 2004

[44] A Lueking M Horn H Eickhoff K Bussow H Lehrachand G Walter ldquoProtein microarrays for gene expression andantibody screeningrdquo Analytical Biochemistry vol 270 no 1 pp103ndash111 1999

[45] N Zammatteo L Jeanmart S Hamels et al ldquoComparisonbetween different strategies of covalent attachment of DNA toglass surfaces to build DNA microarraysrdquo Analytical Biochem-istry vol 280 no 1 pp 143ndash150 2000

[46] M Ozmen K Can I Akin et al ldquoSurface modification of glassbeads with glutaraldehyde characterization and their adsorp-tion property for metal ionsrdquo Journal of Hazardous Materialsvol 171 no 1ndash3 pp 594ndash600 2009

[47] C Funk PM Dietrich T Gross HMinW E S Unger andWWeigel ldquoEpoxy-functionalized surfaces for microarray appli-cations surface chemical analysis and fluorescence labeling ofsurface speciesrdquo Surface and Interface Analysis vol 44 no 8pp 890ndash894 2012

[48] S Mahajan P Kumar and K C Gupta ldquoOligonucleotide mic-roarrays immobilization of phosphorylated oligonucleotideson epoxylated surfacerdquo Bioconjugate Chemistry vol 17 no 5pp 1184ndash1189 2006

[49] M C Pirrung J D Davis and A L Odenbaugh ldquoNovelreagents and procedures for immobilization of DNA on glassmicrochips for primer extensionrdquo Langmuir vol 16 no 5 pp2185ndash2191 2000

[50] E Southern K Mir and M Shchepinov ldquoMolecular interac-tions on microarraysrdquo Nature Genetics vol 21 no 1 pp 5ndash91999

[51] M S Shchepinov S C Case-Green and E M SouthernldquoSteric factors influencing hybridisation of nucleic acids tooligonucleotide arraysrdquo Nucleic Acids Research vol 25 no 6pp 1155ndash1161 1997

[52] D A Tomalia A M Naylor and W A Goddard III ldquoStarbustdendrimers molecular-level control of size shape surfacechemistry topology and flexibility from atoms to macroscopicmatterrdquo Angewandte ChemiemdashInternational Edition in Englishvol 29 no 2 pp 138ndash175 1990

[53] R Benters C M Niemeyer D Drutschmann D Blohm andD Wohrle ldquoDNA microarrays with PAMAM dendritic linkersystemsrdquo Nucleic Acids Research vol 30 no 2 p e10 2002

[54] J H Moon J W Shin S Y Kim and J W Park ldquoFormationof uniform aminosilane thin layers an imine formation tomeasure relative surface density of the amine grouprdquo Langmuirvol 12 no 20 pp 4621ndash4624 1996

[55] J C Alwine D J Kemp and G R Stark ldquoMethod fordetection of specific RNAs in agarose gels by transfer to diazo-benzyloxymethyl-paper and hybridization with DNA probesrdquoProceedings of the National Academy of Sciences of the UnitedStates of America vol 74 no 12 pp 5350ndash5354 1977

[56] P L Dolan Y Wu L K Ista R L Metzenberg M A Nelsonand G P Lopez ldquoRobust and efficient synthetic method for

Journal of Chemistry 17

forming DNA microarraysrdquo Nucleic Acids Research vol 29 no21 article e107 2001

[57] S B Nimse J Kim K-S Song et al ldquoSelective recognitionof the ditopic trimethylammonium cations by water-solubleaminocalix[4]arenerdquo Tetrahedron Letters vol 52 no 29 pp3751ndash3755 2011

[58] V-T Ta S B Nimse K-S Song et al ldquoCharacterization ofthe mixed self-assembled monolayer at the molecular scalerdquoChemical Communications vol 47 no 40 pp 11261ndash11263 2011

[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

[60] Y Lee E K Lee YW Cho et al ldquoProteoChip a highly sensitiveprotein microarray prepared by a novel method of proteinimmobilization for application of protein-protein interactionstudiesrdquo Proteomics vol 3 no 12 pp 2289ndash2304 2003

[61] S W Oh J D Moon H J Lim et al ldquoCalixarene derivative asa tool for highly sensitive detection and oriented immobiliza-tion of proteins in a microarray format through noncovalentmolecular interactionrdquo The FASEB Journal vol 19 no 10 pp1335ndash1337 2005

[62] S B Nimse K-S Song J Kim D R Sayyed and T Kimldquo9G DNAChip technology self-assembled monolayer (SAM)of ssDNA for ultra-sensitive detection of biomarkersrdquo Interna-tional Journal ofMolecular Sciences vol 14 no 3 pp 5723ndash57332013

[63] V-T Nguyen S B Nimse K-S Song et al ldquoHPAI 9GDNAChip discrimination of highly pathogenic influenza virusgenesrdquo Chemical Communications vol 48 no 38 pp 4582ndash4584 2012

[64] K-S Song S B Nimse J Kim D R Sayyed and T Kim ldquoAnew platform for a convenient genotyping systemrdquo ChemicalCommunications vol 49 no 26 pp 2661ndash2663 2013

[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

[67] F Hennrich C Chan VMoore M Rolandi andM OrsquoConnellCarbonNanotubes Properties and Applications Taylor amp FrancisGroup Abingdon UK 2006

[68] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

[69] C Singh M Shaffer I Kinloch and A Windle ldquoProductionof aligned carbon nanotubes by the CVD injection methodrdquoPhysica B Condensed Matter vol 323 no 1ndash4 pp 339ndash3402002

[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

[71] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Journal of Chemistry 17

forming DNA microarraysrdquo Nucleic Acids Research vol 29 no21 article e107 2001

[57] S B Nimse J Kim K-S Song et al ldquoSelective recognitionof the ditopic trimethylammonium cations by water-solubleaminocalix[4]arenerdquo Tetrahedron Letters vol 52 no 29 pp3751ndash3755 2011

[58] V-T Ta S B Nimse K-S Song et al ldquoCharacterization ofthe mixed self-assembled monolayer at the molecular scalerdquoChemical Communications vol 47 no 40 pp 11261ndash11263 2011

[59] S Li Y Y Chen and X R Lu ldquoSyntheses of novel tripodalcalix[n]cryptands (n= 4 6) and their extraction abilities towardcationsrdquo European Journal of Organic Chemistry vol 2000 no3 pp 485ndash490 2000

[60] Y Lee E K Lee YW Cho et al ldquoProteoChip a highly sensitiveprotein microarray prepared by a novel method of proteinimmobilization for application of protein-protein interactionstudiesrdquo Proteomics vol 3 no 12 pp 2289ndash2304 2003

[61] S W Oh J D Moon H J Lim et al ldquoCalixarene derivative asa tool for highly sensitive detection and oriented immobiliza-tion of proteins in a microarray format through noncovalentmolecular interactionrdquo The FASEB Journal vol 19 no 10 pp1335ndash1337 2005

[62] S B Nimse K-S Song J Kim D R Sayyed and T Kimldquo9G DNAChip technology self-assembled monolayer (SAM)of ssDNA for ultra-sensitive detection of biomarkersrdquo Interna-tional Journal ofMolecular Sciences vol 14 no 3 pp 5723ndash57332013

[63] V-T Nguyen S B Nimse K-S Song et al ldquoHPAI 9GDNAChip discrimination of highly pathogenic influenza virusgenesrdquo Chemical Communications vol 48 no 38 pp 4582ndash4584 2012

[64] K-S Song S B Nimse J Kim D R Sayyed and T Kim ldquoAnew platform for a convenient genotyping systemrdquo ChemicalCommunications vol 49 no 26 pp 2661ndash2663 2013

[65] Y Cui Q Wei H Park and C M Lieber ldquoNanowire nanosen-sors for highly sensitive and selective detection of biologicaland chemical speciesrdquo Science vol 293 no 5533 pp 1289ndash12922001

[66] R J Chen Y Zhang D Wang and H Dai ldquoNoncovalentsidewall functionalization of single-walled carbon nanotubesfor protein immobilizationrdquo Journal of the American ChemicalSociety vol 123 no 16 pp 3838ndash3839 2001

[67] F Hennrich C Chan VMoore M Rolandi andM OrsquoConnellCarbonNanotubes Properties and Applications Taylor amp FrancisGroup Abingdon UK 2006

[68] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

[69] C Singh M Shaffer I Kinloch and A Windle ldquoProductionof aligned carbon nanotubes by the CVD injection methodrdquoPhysica B Condensed Matter vol 323 no 1ndash4 pp 339ndash3402002

[70] H Kuzmany A Kukovecz F Simon M Holzweber C Kram-berger and T Pichler ldquoFunctionalization of carbon nanotubesrdquoSynthetic Metals vol 141 no 1-2 pp 113ndash122 2004

[71] C Journet W K Maser P Bernier et al ldquoLarge-scale pro-duction of single-walled carbon nanotubes by the electric-arctechniquerdquo Nature vol 388 no 6644 pp 756ndash758 1997

[72] AThess R Lee P Nikolaev et al ldquoCrystalline ropes of metalliccarbonnanotubesrdquo Science vol 273 no 5274 pp 483ndash487 1996

[73] M Foldvari andM Bagonluri ldquoCarbon nanotubes as functionalexcipients for nanomedicines II Drug delivery and biocompat-ibility issuesrdquo Nanomedicine vol 4 no 3 pp 183ndash200 2008

[74] Z Liu J T Robinson S M Tabakman K Yang and HDai ldquoCarbon materials for drug delivery amp cancer therapyrdquoMaterials Today vol 14 no 7-8 pp 316ndash323 2011

[75] WWei A Sethuraman C Jin N AMonteiro-Riviere and R JNarayan ldquoBiological properties of carbonnanotubesrdquo Journal ofNanoscience and Nanotechnology vol 7 no 4-5 pp 1284ndash12972007

[76] D Cui ldquoAdvances and prospects on biomolecules functional-ized carbon nanotubesrdquo Journal of Nanoscience and Nanotech-nology vol 7 no 4-5 pp 1298ndash1314 2007

[77] N Saifuddin A Z Raziah and A R Junizah ldquoCarbon nan-otubes a review on structure and their interaction with pro-teinsrdquo Journal of Chemistry vol 2013 Article ID 676815 18pages 2013

[78] S Banerjee THemraj-Benny and S SWong ldquoCovalent surfacechemistry of single-walled carbon nanotubesrdquo Advanced Mate-rials vol 17 no 1 pp 17ndash29 2005

[79] F Bomboi A Bonincontro C La Mesa and F Tardani ldquoInter-actions between single-walled carbonnanotubes and lysozymerdquoJournal of Colloid and Interface Science vol 355 no 2 pp 342ndash347 2011

[80] K Matsuura T Saito T Okazaki S Ohshima M Yumuraand S Iijima ldquoSelectivity of water-soluble proteins in single-walled carbon nanotube dispersionsrdquo Chemical Physics Lettersvol 429 no 4ndash6 pp 497ndash502 2006

[81] D Nepal and K E Geckeler ldquopH-sensitive dispersion anddebundling of single-walled carbon nanotubes lysozyme as atoolrdquo Small vol 2 no 3 pp 406ndash412 2006

[82] P Asuri S S Karajanagi H Yang T-J Yim R S Kane andJ S Dordick ldquoIncreasing protein stability through control ofthe nanoscale environmentrdquo Langmuir vol 22 no 13 pp 5833ndash5836 2006

[83] P Asuri S S Karajanagi E Sellitto D-Y Kim R S Kane andJ S Dordick ldquoWater-soluble carbon nanotube-enzyme conju-gates as functional biocatalytic formulationsrdquoBiotechnology andBioengineering vol 95 no 5 pp 804ndash811 2006

[84] E Ostuni R G Chapman R E Holmlin S Takayama and GM Whitesides ldquoA survey of structure-property relationships ofsurfaces that resist the adsorption of proteinrdquo Langmuir vol 17no 18 pp 5605ndash5620 2001

[85] R E Holmlin X Chen R G Chapman S Takayama andG M Whitesides ldquoZwitterionic SAMs that resist nonspecificadsorption of protein from aqueous bufferrdquo Langmuir vol 17no 9 pp 2841ndash2850 2001

[86] N Nakayama-Ratchford S Bangsaruntip X M Sun KWelsher and H Dai ldquoNoncovalent functionalization of carbonnanotubes by fluorescein-polyethylene glycol supramolecularconjugates with pH-dependent absorbance and fluorescencerdquoJournal of the American Chemical Society vol 129 no 9 pp2448ndash2449 2007

[87] A Satake YMiyajima and Y Kobuke ldquoPorphyrin-carbon nan-otube composites formed by noncovalent polymer wrappingrdquoChemistry of Materials vol 17 no 4 pp 716ndash724 2005

[88] J Zhang J K Lee Y Wu and R W Murray ldquoPhotolumi-nescence and electronic interaction of anthracene derivativesadsorbed on sidewalls of single-walled carbon nanotubesrdquoNano Letters vol 3 no 3 pp 403ndash407 2003

[89] W Z Yuan J Z Sun Y Dong et al ldquoWrapping carbonnanotubes in pyrene-containing poly(phenylacetylene) chainssolubility stability light emission and surface photovoltaicpropertiesrdquoMacromolecules vol 39 no 23 pp 8011ndash8020 2006

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

18 Journal of Chemistry

[90] V V Didenko V C Moore D S Baskin and R E SmalleyldquoVisualization of individual single-walled carbon nanotubes byfluorescent polymer wrappingrdquo Nano Letters vol 5 no 8 pp1563ndash1567 2005

[91] D Tasis N Tagmatarchis A Bianco and M Prato ldquoChemistryof carbon nanotubesrdquo Chemical Reviews vol 106 no 3 pp1105ndash1136 2006

[92] V Georgakilas K Kordatos M Prato D M Guldi MHolzinger and A Hirsch ldquoOrganic functionalization of carbonnanotubesrdquo Journal of the American Chemical Society vol 124no 5 pp 760ndash761 2002

[93] M W Marshall S Popa-Nita and J G Shapter ldquoMeasurementof functionalised carbon nanotube carboxylic acid groups usinga simple chemical processrdquo Carbon vol 44 no 7 pp 1137ndash11412006

[94] P D Tam N Van Hieu N D Chien A-T Le and M AnhTuan ldquoDNA sensor development based on multi-wall carbonnanotubes for label-free influenza virus (type A) detectionrdquoJournal of Immunological Methods vol 350 no 1-2 pp 118ndash1242009

[95] K Awasthi D P Singh S K Singh D Dash and O NSrivastava ldquoAttachment of biomolecules (protein and DNA) toamino-functionalized carbon nanotubesrdquo New Carbon Materi-als vol 24 no 4 pp 301ndash306 2009

[96] H Li R B Martin B A Harruff R A Carino L F Allardand Y-P Sun ldquoSingle-walled carbon nanotubes tethered withporphyrins synthesis and photophysical propertiesrdquo AdvancedMaterials vol 16 no 11 pp 896ndash900 2004

[97] Z Guo F Du D M Ren et al ldquoCovalently porphyrin-functionalized single-walled carbon nanotubes a novel pho-toactive and optical limiting donorndashacceptor nanohybridrdquo Jour-nal of Materials Chemistry vol 16 no 29 pp 3021ndash3030 2006

[98] Z Li Y Q Dong M Haussler et al ldquoSynthesis of light emissionfrom and optical power limiting in soluble single-walled car-bon nanotubes functionalized by disubstituted polyacetylenesrdquoThe Journal of Physical Chemistry B vol 110 no 5 pp 2302ndash2309 2006

[99] A Eitan K Jiang D Dukes R Andrews and L S SchadlerldquoSurfacemodification ofmultiwalled carbon nanotubes towardthe tailoring of the interface in polymer compositesrdquo Chemistryof Materials vol 15 no 16 pp 3198ndash3201 2003

[100] AWMartinez S T Phillips GMWhitesides and E CarrilholdquoDiagnostics for the developing world microfluidic paper-based analytical devicesrdquoAnalytical Chemistry vol 82 no 1 pp3ndash10 2010

[101] P J Bracher M Gupta and G M Whitesides ldquoPatterning pre-cipitates of reactions in paperrdquo Journal of Materials Chemistryvol 20 no 24 pp 5117ndash5122 2010

[102] W A Zhao and A van den Berg ldquoLab on paperrdquo Lab on a Chipvol 8 no 12 pp 1988ndash1991 2008

[103] WDungchai O Chailapakul andC SHenry ldquoA low-cost sim-ple and rapid fabricationmethod for paper-basedmicrofluidicsusing wax screen-printingrdquo Analyst vol 136 no 1 pp 77ndash822011

[104] S M Z Hossain R E Luckham A M Smith et al ldquoDevelop-ment of a bioactive paper sensor for detection of neurotoxinsusing piezoelectric inkjet printing of sol-gel-derived bioinksrdquoAnalytical Chemistry vol 81 no 13 pp 5474ndash5483 2009

[105] J Yu L Ge J Huang S Wang and S Ge ldquoMicrofluidicpaper-based chemiluminescence biosensor for simultaneousdetermination of glucose and uric acidrdquo Lab on a Chip vol 11no 7 pp 1286ndash1291 2011

[106] J P Comer ldquoSemiquantitative specific test paper for glucose inurinerdquo Analytical Chemistry vol 28 no 11 pp 1748ndash1750 1956

[107] P Von Lode ldquoPoint-of-care immunotesting approaching theanalytical performance of central laboratory methodsrdquo ClinicalBiochemistry vol 38 no 7 pp 591ndash606 2005

[108] D D Liana B Raguse J J Gooding and E Chow ldquoRecentadvances in paper-based sensorsrdquo Sensors vol 12 no 9 pp11505ndash11526 2012

[109] A K Ellerbee S T Phillips A C Siegel et al ldquoQuantifyingcolorimetric assays in paper-based microfluidic devices bymeasuring the transmission of light through paperrdquo AnalyticalChemistry vol 81 no 20 pp 8447ndash8452 2009

[110] A W Martinez S T Phillips Z Nie et al ldquoProgrammablediagnostic devices made from paper and taperdquo Lab on a Chipvol 10 no 19 pp 2499ndash2504 2010

[111] P J Bracher M Gupta and G MWhitesides ldquoPatterned paperas a template for the delivery of reactants in the fabrication ofplanarmaterialsrdquo SoftMatter vol 6 no 18 pp 4303ndash4309 2010

[112] R E Luckham and J D Brennan ldquoBioactive paper dip-stick sensors for acetylcholinesterase inhibitors based on sol-gelenzymegold nanoparticle compositesrdquoAnalyst vol 135 no8 pp 2028ndash2035 2010

[113] M Cretich V Sedini F Damin M Pelliccia L Sola andM Chiari ldquoCoating of nitrocellulose for colorimetric DNAmicroarraysrdquo Analytical Biochemistry vol 397 no 1 pp 84ndash882010

[114] E M Fenton M R Mascarenas G P Lopez and S S SibbettldquoMultiplex lateral-flow test strips fabricated by two-dimensionalshapingrdquo ACS Applied Materials and Interfaces vol 1 no 1 pp124ndash129 2009

[115] A W Martinez S T Phillips E Carrilho S W Thomas III HSindi and G M Whitesides ldquoSimple telemedicine for devel-oping regions camera phones and paper-based microfluidicdevices for real-time off-site diagnosisrdquo Analytical Chemistryvol 80 no 10 pp 3699ndash3707 2008

[116] H Li S Bergeron and D Juncker ldquoMicroarray-to-microarraytransfer of reagents by snapping of two chips for cross-reactivity-free multiplex immunoassaysrdquo Analytical Chemistryvol 84 no 11 pp 4776ndash4783 2012

[117] A P Alivisatos W Gu and C Larabell ldquoQuantum dots ascellular probesrdquo Annual Review of Biomedical Engineering vol7 pp 55ndash76 2005

[118] M Law L E Greene J C Johnson R Saykally and P YangldquoNanowire dye-sensitized solar cellsrdquo Nature Materials vol 4no 6 pp 455ndash459 2005

[119] S B Fuller E J Wilhelm and J M Jacobson ldquoInk-jetprinted nanoparticle microelectromechanical systemsrdquo JournalofMicroelectromechanical Systems vol 11 no 1 pp 54ndash60 2002

[120] D J OrsquoShannessy M Brigham-Burke and K Peck ldquoImmo-bilization chemistries suitable for use in the BIAcore surfaceplasmon resonance detectorrdquo Analytical Biochemistry vol 205no 1 pp 132ndash136 1992

[121] R W Nelson and J R Krone ldquoAdvances in surface plasmonresonance biomolecular interaction analysis mass spectrometry(BIAMS)rdquo Journal of Molecular Recognition vol 12 no 2 pp77ndash93 1999

[122] P Gomes E Giralt and D Andreu ldquoDirect single-step surfaceplasmon resonance analysis of interactions between smallpeptides and immobilized monoclonal antibodiesrdquo Journal ofImmunological Methods vol 235 no 1-2 pp 101ndash111 2000

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Journal of Chemistry 19

[123] R White C Winston M Gonen et al ldquoCurrent utility of stag-ing laparoscopy for pancreatic and peripancreatic neoplasmsrdquoJournal of the American College of Surgeons vol 206 no 3 pp445ndash450 2008

[124] J Kulig T Popiela A Zajac S Klek and P Kołodziejczyk ldquoThevalue of imaging techniques in the staging of pancreatic cancerrdquoSurgical Endoscopy and Other Interventional Techniques vol 19no 3 pp 361ndash365 2005

[125] N C Tansil and Z Gao ldquoNanoparticles in biomoleculardetectionrdquo Nano Today vol 1 no 1 pp 28ndash37 2006

[126] A J Di Pasqua R E Mishler Y-L Ship J C Dabrowiak and TAsefa ldquoPreparation of antibody-conjugated gold nanoparticlesrdquoMaterials Letters vol 63 no 21 pp 1876ndash1879 2009

[127] HOtsuka Y Akiyama Y Nagasaki andK Kataoka ldquoQuantita-tive and reversible lectin-induced association of gold nanopar-ticles modified with 120572-lactosyl-120596-mercapto-poly(ethylene gly-col)rdquo Journal of the American Chemical Society vol 123 no 34pp 8226ndash8230 2001

[128] H Liao and J H Hafner ldquoGold nanorod bioconjugatesrdquoChemistry of Materials vol 17 no 18 pp 4636ndash4641 2005

[129] W Eck G Craig A Sigdel et al ldquoPEGylated gold nanoparticlesconjugated to monoclonal F19 antibodies as targeted labelingagents for human pancreatic carcinoma tissuerdquo ACS Nano vol2 no 11 pp 2263ndash2272 2008

[130] A A Vertegel R W Siegel and J S Dordick ldquoSilica nanopar-ticle size influences the structure and enzymatic activity ofadsorbed lysozymerdquo Langmuir vol 20 no 16 pp 6800ndash68072004

[131] D D Lan B B Li and Z Z Zhang ldquoChemiluminescence flowbiosensor for glucose based on gold nanoparticle-enhancedactivities of glucose oxidase and horseradish peroxidaserdquoBiosensors and Bioelectronics vol 24 no 4 pp 940ndash944 2008

[132] X C Shen Q Yuan H Liang H Yan and X He ldquoHysteresiseffects of the interaction between serum albumins and silvernanoparticlesrdquo Science in China Series B Chemistry vol 46 pp387ndash398 2003

[133] S L Smitha KMNissamudeen D Philip andK G Gopchan-dran ldquoStudies on surface plasmon resonance and photolumi-nescence of silver nanoparticlesrdquo Spectrochimica ActamdashPart AMolecular and Biomolecular Spectroscopy vol 71 no 1 pp 186ndash190 2008

[134] G A Petkova C K Zaruba P Zvatora and V Kral ldquoGoldand silver nanoparticles for biomolecule immobilization andenzymatic catalysisrdquoNanoscale Research Letters vol 7 no 1 pp287ndash296 2012

[135] J C Riboh A J Haes A D McFarland C R Yonzon andR P Van Duyne ldquoA nanoscale optical biosensor real-timeimmunoassay in physiological buffer enabled by improvednanoparticle adhesionrdquoThe Journal of Physical Chemistry B vol107 no 8 pp 1772ndash1780 2003

[136] N Nath and A Chilkoti ldquoA colorimetric gold nanoparticlesensor to interrogate biomolecular interactions in real time on asurfacerdquo Analytical Chemistry vol 74 no 3 pp 504ndash509 2002

[137] Y Zhang R Huang X Zhu L Wang and C Wu ldquoSyn-thesis properties and optical applications of noble metalnanoparticle-biomolecule conjugatesrdquo Chinese Science Bulletinvol 57 no 2-3 pp 238ndash246 2012

[138] C Loos T Syrovets A Musyanovych et al ldquoFunctionalizedpolystyrene nanoparticles as a platform for studying bio-nanointeractionsrdquo Beilstein Journal of Nanotechnology vol 5 pp2403ndash2412 2014

[139] E G Sowers J G Wells and N A Strockbine ldquoEvaluation ofcommercial latex reagents for identification of O157 and H7antigens of Escherichia colirdquo Journal of Clinical Microbiologyvol 34 no 5 pp 1286ndash1289 1996

[140] L SWong K Okrasa and J MicKlefield ldquoSite-selective immo-bilisation of functional enzymes on to polystyrene nanoparti-clesrdquoOrganic and Biomolecular Chemistry vol 8 no 4 pp 782ndash787 2010

[141] Z Zhang H Zhu Y Tang et al ldquoPreparation and applicationof streptavidin magnetic particlesrdquo Science in China Series BChemistry vol 50 no 1 pp 127ndash134 2007

[142] E A Bayer H Ben-Hur and M Wilchek ldquoIsolation andproperties of streptavidinrdquoMethods in Enzymology vol 184 pp80ndash93 1990

[143] L Valimaa K Pettersson J Rosenberg M Karp and TLovgren ldquoQuantification of streptavidin adsorption in microti-tration wellsrdquo Analytical Biochemistry vol 331 no 2 pp 376ndash384 2004

[144] J E Butler ldquoSolid supports in enzyme-linked immunosorbentassay and other solid-phase immunoassaysrdquo Methods vol 22no 1 pp 4ndash23 2000

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Carbohydrate Chemistry

International Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Chromatography Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Applied ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Theoretical ChemistryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Spectroscopy

Analytical ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Quantum Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Organic Chemistry International

ElectrochemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CatalystsJournal of