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a n a l y t i c a c h i m i c a a c t a 6 1 4 ( 2 0 0 8 ) 1–26

avai lab le at www.sc iencedi rec t .com

journa l homepage: www.e lsev ier .com/ locate /aca

eview article

onducting polymers in chemical sensors and arrays

lrich Lange, Nataliya V. Roznyatovskaya1, Vladimir M. Mirsky ∗

nstitute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, D-93040 Regensburg, Germany

r t i c l e i n f o

rticle history:

eceived 23 December 2007

eceived in revised form

2 February 2008

ccepted 27 February 2008

ublished on line 8 March 2008

eywords:

onducting polymers

hemical sensors

a b s t r a c t

The review covers main applications of conducting polymers in chemical sensors and

biosensors. The first part is focused on intrinsic and induced receptor properties of con-

ducting polymers, such as pH sensitivity, sensitivity to inorganic ions and organic molecules

as well as sensitivity to gases. Induced receptor properties can be also formed by molecu-

larly imprinted polymerization or by immobilization of biological receptors. Immobilization

strategies are reviewed in the second part. The third part is focused on applications of con-

ducting polymers as transducers and includes usual optical (fluorescence, SPR, etc.) and

electrical (conductometric, amperometric, potentiometric, etc.) transducing techniques as

well as organic chemosensitive semiconductor devices. An assembly of stable sensing struc-

tures requires strong binding of conducting polymers to solid supports. These aspects are

lectroactive polymers

as sensors

ombinatorial techniques

lectropolymerization

discussed in the next part. Finally, an application of combinatorial synthesis and high-

throughput analysis to the development and optimization of sensing materials is described.

© 2008 Elsevier B.V. All rights reserved.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3ns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

ensor array

ontents

1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2. Conducting polymers as receptors. . . . . . . . . . . . . . . . . . . . . . . .

2.1. pH-sensitivity of conducting polymers . . . . . . . . . . . .2.2. Conducting polymers with affinity to inorganic io

2.3. Conducting polymers with affinity to organic molecul2.4. Conducting polymers with affinity to gases. . . . . . . . . . . .2.5. Molecularly imprinted conducting polymers . . . . . . . . . .

∗ Corresponding author. Fax: +49 941 9434064.E-mail address: vladimir.mirsky@chemie.uni-regensburg.de (V.M. MAbbreviations: CP, conducting polymer(s); PANI, polyaniline; PN

onic acid); PPY, polypyrrole; PTH, polythiophene; P3MTH; P3HTHolyethylenedioxythiophene; EDOT, ethylenedioxythiophene; PI, polyinoly(p-phenyleneethynylene); PMNT, poly(3-(3′-N,N,N-triethylamino-1VS, polyvinylsulfonate; PET, polyethylene terephthalate; PEG, polyeethylpropane sulfonic acid); PA, polyacrylamide; HRP, horseradish peolecular imprinting.

1 Permanent address: Department of Chemistry, Moscow State Unive003-2670/$ – see front matter © 2008 Elsevier B.V. All rights reserved.oi:10.1016/j.aca.2008.02.068

es. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

irsky).MA, poly(N-methylaniline); p-ABSA, poly(p-aminobenzene sul-; P3OTH, poly(-3-methyl-,-3-hexyl-,-3-octyl-thiophene); PEDOT,dole; PP, poly(p-phenylene); PPV, poly(p-phenylenevinylene); PPE,

′propyloxy)-4-methyl-2,5-thiophene); PSS, polystyrenesulfonate;thylenglycol; PAA, polyacrylic acid; AMPS, poly(2-acrylamido-2-roxidase; GOx, glucose oxidase; LDH, lactate dehydrogenase; MIP,

rsity, Moscow 119992, Russia.

2 a n a l y t i c a c h i m i c a a c t a 6 1 4 ( 2 0 0 8 ) 1–26

2.6. Electronic noses and tongues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83. Modification of conducting polymers by receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

3.1. Non-covalent immobilization. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123.1.1. Physical adsorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123.1.2. Langmuir–Blodgett technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123.1.3. Layer-by-layer (LbL) deposition and electrostatical doping of polymers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123.1.4. Mechanical embedding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

3.2. Covalent immobilization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133.3. Immobilization based on affinity interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

4. Conducting polymers as transducers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144.1. Conductometric and impedometric transducers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144.2. Potentiometric transducers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164.3. Voltammetric and amperometric transducers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174.4. Organic transistors and diodes as transducers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174.5. Optical transducers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

5. Attachment of conducting polymers to solid supports. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186. Application of combinatorial and high-throughput techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction

The high application potential of conducting polymers (CP)in chemical and biological sensors is one of the main rea-sons for the intensive investigation and development of thesematerials. Most CP were synthesized by modification of thestructures shown in Fig. 1.

CP show almost no conductivity in the neutral (uncharged)state. Their intrinsic conductivity results from the for-mation of charge carriers upon oxidizing (p-doping) orreducing (n-doping) their conjugated backbone. Oxidationof the neutral polymer and following relaxation processescauses the generation of localized electronic states and aso-called polaron is formed. If now an additional electronis removed, it is energetically more favourable to removethe second electron from the polaron than from anotherpart of the polymer chain. This leads to the formationof one bipolaron rather than two polarons [1]. However itis important to note that before bipolaron formation theentire CP chain would first become saturated with polarons[2].

Besides the large change in conductivity, charge injection(doping) in CP leads to some other interesting phenomenawhich can be used in various applications. The change ofthe CP electronic band structure is accompanied by a changeof the optical properties in the UV–vis and NIR-region. Thisis used in electrochromic displays and optical sensors. Fur-thermore, the electroluminescence of some CP is used inOLEDs, whereas the photoluminescence can be used in fluo-rescence sensors. Incorporation of ions leads to compensationof charges along the polymer backbone generated duringthe doping process. This property is used in ion-exchange

membranes and can be tuned by using different counterions.Films synthesized in presence of large immobile anions pos-sess cation exchange properties, whereas the use of smallmobile anions leads to films with anion exchange proper- Fig. 1 – Main classes of conductive polymers.

a n a l y t i c a c h i m i c a a c t a 6 1 4 ( 2 0 0 8 ) 1–26 3

een

tm

cbutvad

ttTvbaepceomcfifiomtat

csCeasthi

Fig. 2 – Conversion betw

ies. Swelling of CP due to oxidation can be used in artificialuscles.Doping of CP can be done either chemically or electro-

hemically. In chemical doping the oxidation is accomplishedy exposing the CP to oxidizing vapors like iodine. Anothernique chemical doping procedure is the doping of PANI dueo protonation. This leads to an internal redox reaction con-erting the semiconducting form of PANI (emeraldine base) to“metallic” form (emeraldine salt). The reactions between theifferent forms of PANI [3] are shown in the Fig. 2.

Chemical doping is effective but poor reproducible quan-itatively. Alternatively, electrochemical doping provides fineuning of the doping level by adjusting the electrical potential.he unique properties of conducting polymers are used inarious chemical and biological sensors. The polymers cane synthesized either by addition of an external agent (thispproach is often referred as “chemical synthesis” of CP) or bylectrochemical reaction. Chemical synthesis of CP is usuallyerformed by such oxidants as (NH4)2S2O7 or FeCl3 and isommonly used for the preparation of CP solutions, whilelectrochemical deposition is used mainly for depositionf CP films on conducting substrates. An advantage of thisethod is the possibility to control the film thickness by the

harge passed through the electrochemical cell during thelm growth. Other popular techniques for depositing thinlms on various substrates are spin coating by a solutionf a chemically synthesized CP, the deposition of one orore monomolecular layers of CP by Langmuir–Blodgett-

echnique, or coating of substrates by bilayers of CPnd opposed charged polymers by the layer-by-layerechnique.

In this review we discuss CP based chemical and biologi-al sensors and sensor arrays. The topic will be divided intoeveral sections taking into account different functions ofP: the use of CP as receptors, the use of CP as transduc-rs, the use of CP as immobilization matrix, etc. However,s CP are multifunctional materials, it was not always pos-

ible to make a definite separation of their functions. Finally,he application of a combinatorial approach for synthesis andigh-throughput screening of chemosensitive properties of CP

s discussed.

different states of PANI.

2. Conducting polymers as receptors

2.1. pH-sensitivity of conducting polymers

Many CP posses acidic or/and basic groups which can be pro-tonated or deprotonated. To this family of CP belong PANI,PPY, PI, polycarbazole and polyazines. Deprotonation of theseCP results in a decrease of charge carriers along the polymerchains and is accompanied by changes in the electrical andoptical properties. These changes lead to modification of redoxproperties of CP, this effect is very strong for PANI and PI butalmost not recognizable in PPY.

The protonation enhances the conductivity of PPY, whereasdeprotonation leads to a lower conductivity [4]. The pKa val-ues found for the transfer between these three pH dependentforms were in the range of 2–4 and 9–11. Similar pKa (8.7) wasdetermined from the measurements of optical absorption at650 nm [5]. Due to the deprotonation of the PPY chains, theabsorbance between 600 and 900 nm increases from pH 6 topH 12, while the minimum is shifted from 600 nm (pH 6) to500 nm (pH 12).

The influence of pH on the redox processes of PANI wasinvestigated by MacDiarmid and co-workers [6]. It was foundthat the potential of the second redox transition shifts cathod-ically with increasing of pH for 0.12 V/pH. The reason for thisbehavior is the release of protons in the redox conversion fromemeraldine salt to pernigraniline base (Fig. 2). pH and poten-tial dependencies of conductivity and optical absorption ofPANI at 420 nm were reported in [7]. Later such investigationwas extended for other spectral range and also for derivativesof PANI [8]. Due to polaron band transitions the emeraldinesalt form of PANI shows two characteristic absorbance max-ima: at 390–450 nm and at the range over 700 nm. Emeraldinebase form of PANI displays a single absorbance maximum at640–650 nm. The largest spectral changes due to deprotona-tion of emeraldine salt are observed between pH 5 and pH 8,

whereas only small changes are observed between pH 2 andpH 5. Because of hysteresis in the transfer between differentforms of PANI, the main spectral changes during decrease ofpH are observed between pH 6 to pH 3. This leads to strong

a c t

4 a n a l y t i c a c h i m i c a

limitation of the working range of such sensors [8]. Effectsof pH on PANI were also studied by Raman spectroscopy. Itwas shown that the Raman signal of the C N stretching vibra-tion of the emeraldine base form at 1439 cm−1 can be used forpH measurements between pH 3 and 6. This vibration growsconsiderably in the pH interval where the transition betweenemeraldine base and emeraldine salt takes place (pH 3–6) [9].

Conductivity of CP can be caused by ions and/or electrons.Affinity of amino groups to protons may be the reason for highproton permeability of these polymers in aqueous solutions:films of PANI [8] and PPY [10,11] on glassy carbon and platinumelectrodes show almost Nernstian behavior relative to pH. Thepotentiometric response of PPY is linear between pH 2 andpH 11. This fact as well as an electronic component of theconductivity of these polymers makes them perspective forapplications in solid state pH sensors (see Section 3.2).

The Nerstian behavior of CP can be also obtained from theanalysis of the equilibria. If polymer oxidation or reductionis not coupled with proton release/uptake (this is the casefor PPY), its behavior can be described by the same formal-ism as for traditional electrodes of the second type with theproton as a potential determining ion. The observed smalldifference from this theoretical slope may be caused by theinfluence of other ions in solution [10]. If the pKa(s) of a CP aresensitive to oxidation or reduction (this is the case for PANIand PI), the description of the equilibrium is more compli-cated [6]. The described pH dependent property changes in CPhave therefore been used to develop potentiometric [10,11],conductometric [12–15] and optical [5,9,15–22] pH sensors.Conductometric CP based pH sensors are usually preparedby depositing a thin layer of a CP film between two or fourmetallic or graphite contacts. Optical pH sensors are pre-pared by deposition of thin polymer films on the surface ofITO-electrodes, microtiterplates, cuvettes or other transparentsupport. Absorption of PANI or PANI-based polymers is mea-sured at 800–900 nm [21–23] or at 500–600 nm [16,18,19,23,24],while the measurements for optical sensors based on PPY areperformed at 650 nm [5].

2.2. Conducting polymers with affinity to inorganicions

Unmodified CP films can display some intrinsic affinity tometal ions [25,26]. Films of PI and polycarbazol provide aselective potentiometric response to Cu(II) ions [27]. Thecomplexation of Cu(II)-ions to polycarbazol enhances theconductivity of this polymer [28]. It was suggested that thecomplexation of Cu(II)-ions changes the conformation of thepolymer from a compact coil to a higher conducting expandedcoil [28]. Films of poly-3-octylthiophene (P3OTH) show aselective Nernstian response towards Ag+ ions. As UV–vismeasurements showed that P3OTH is not oxidized by Ag+ ions,it was supposed that the ions interact with the sulphur atomsand double bonds in the P3OTH-backbone [26].

Introduction of ligands leads to a modification of this ionicsensitivity. Such modification can be realized by an introduc-

tion of corresponding monomers into the polymer backbone[29–37], by using counter ions with such ligands [38–46] orby inclusion of ionophores into the polymer matrix [47].2,3-disubstituted 5-nitroquinoxalines bearing 2-pyrrolyl and

a 6 1 4 ( 2 0 0 8 ) 1–26

2-thienyl substituents have been electropolymerized (Fig. 3,1). The potentiometric response of the resulting films towardsvarious cations was tested and compared to the response ofthe monomers immobilized in a PVC membrane. It was con-cluded that the binding mechanism for the monomer and thepolymer is the same [35].

Three conjugated polymers containing 9,9-dioctylfluoreneand 2,2′-bipyridine moieties, which are alternatively linked bythe C–C single bond (2), vinylene bond (3), or ethynylene bond(4), have been synthesized and investigated [33]. All the threepolymers displayed optical sensitivity to a variety of transi-tion metal ions due to chelation between the 2,2′-bipyridylmoieties and the metal ions, but no optical response to theaddition of alkali metal ions (up to 100 ppm) and alkalineearth metal ions except Mg2+ was observed. The spectral redshift upon metal complexation was attributed to the conju-gation enhancement along the polymer backbone induced bythe bidentated coordination of metal ions to the 2,2′-bipyridylunits. For different metal ions, the differences in the changedabsorption spectra reflected different coordination ability ofmetal ions to the 2,2′-bipyridyl units. The bound metal ionsquenched the fluorescence of the polymers [33].

To get a CP which is sensitive to heavy metals, EDTA wascovalently bond to diamino-terthiophene (5), and binding ofCu2+, Pb2+, Hg2+ was detected by a technology combining anextraction and a stripping voltammetry. The ions were firstextracted from the sample by EDTA groups of this polymer,then transferred in another electrolyte, reduced at −0.9 V andreoxidized by potential increase from −0.9 V to +0.75 V [29].An introduction of ion-sensitive groups into conducting poly-mer can be also performed by copolymerization of modifiedEDTA-like pyrrole monomers with pyrrole (6) [34]. The poly-mer was used for the simultaneous determination of Cu2+,Pb2+ and Cd2+ ions by the same combination of extractionand stripping voltammetry. Notably, a polymer synthesized inthe presence of Cd2+ ions led to improved polymer selectivitytowards Cd2+ ions for short extraction times. Probably somemolecular imprinting effects (see Section 2.5) contributed intothe selectivity [34].

Salen and acetophenone groups known as selective lig-ands for divalent cations have been introduced in thiopheneand pyrrole based copolymers and suggested for applicationsin ISE [36,48]. Binding of Ca2+-ions to CP containing calix[4]-arene type groups containing crown ether moieties (10)increases conductivity of this polymer. The effect was selec-tive, K+ ions showed no effect. It was suggested that thebinding of Ca2+ ions enhances delocalisation of electrons ofthe p-diquinone in the polymer, resulting in a lower barrierfor electron hopping [49].

Crown ether modified poly(p-phenylene ethynylene)derivatives have been also used for selective determinationof K+-ions in the presence of Na+ or Li+ ions by fluorescencespectroscopy [50]. The absorbance and fluorescence spectraof the polymer (7) in solution are essentially unchanged onaddition of even a 1500-fold excess of Li+ or Na+ ions. Incontrast, an addition of K+ ions to the solution of (7) produced

a new red-shifted peak at 457 nm in the absorption spectraand quenched the fluorescence of the polymer. Probably thenew peak and the fluorescence quenching are caused by inter-polymer �-stacking induced by K+ ion bridges between two

a n a l y t i c a c h i m i c a a c t a 6 1 4 ( 2 0 0 8 ) 1–26 5

uce

1nbpmo(i

ifiaSaaPcPtattastPA

Fig. 3 – Conducting polymers with introd

5-crown-5 units on different polymer chains. The effective-ess of the interpolymer �-stacking aggregation was shown toe controlled by the side groups attached to the polymer. Theolymer (8) with two methyl groups in every second repeatingonomer unit shows the lowest resistance to the formation

f interpolymer �-stacking aggregates, whereas the polymer9) showed no response to K+ additions due to the bulkysopropyl groups which hinder interpolymer �-stacking [50].

Ionic selectivity can be also introduced in a CP by dop-ng of this material with metal complexing anions. PPYlms were doped with calcion, eriochrome black T, Kalcesnd ATP to obtain Mg2+ and Ca2+ selective membranes.ulphosalicylic acid and 4,5-dihydroxy-1,3-benzenedisulfoniccid (Tiron) were incorporated in PPY films to obtain

selective potentiometric response to Cu2+ [38,39,43].EDOT and POTH films were doped with p-sulfonatedalixarenen, p-methylsulfonated calixresocarenen, PSS,VS, silver-7,8,9,10,11,12-hexabromocarborane, potassiumetrakis[3,5-bis(trifluoromethyl)phenyl]borate and sulphon-ted thiophenes and tested as potentiometric Ag+ ion selec-ive electrodes [26,40,41,44,46,47]. However it was suggestedhat the selectivity for Ag+ results not from the incorporatednions, but due to coordination of the Ag+-ions with the

ulphur atom and the �-electrons at the polymer backbone:he selectivity of PEDOT/2-(3-thienyloxy)ethanesulfonate andEDOT/6-(3-thienyloxy)hexanesulfonate electrodes towardg+ is higher than the selectivity of Ag+-ISEs based on PEDOT

d ion binding units. See text for details.

doped with sulfonated calixarenes. Also unmodified POTHdisplays selectivity towards Ag+-ions [26]. PPY doped withEriochrome Blue Black B was suggested as a potentiometricand voltammetric Ag+ sensor. The response of the sensorswas improved by pretreatment of the CP by electrochemicaldoping/undoping in AgNO3 solution. It was proposed that thisprocess rearranges the binding sites of both PPY and ligand,and therefore generates recognition sites in the polymer[42]. PPY doped with tetraphenylborate was used as a poten-tiometric Zn2+ ionselective sensor. The sensor response isinterfered by Co2+ and Ni2+ ions, but is not influenced by Ca2+,Pb2+ or Hg2+ ions [45]. Binding of Hg2+ ions by a cryptand-222embedded in a PANI film increased the conductivity of PANI.It was suggested that binding of Hg2+ to the cryptand resultsin a proton transfer from the cryptand to PANI, leading to anincrease of its electrical conductivity [51].

2.3. Conducting polymers with affinity to organicmolecules

Sensitivity of CP to organic molecules can be based on theintrinsic affinity of the CP backbone, on affinity of side groupsor on binding to immobilized receptors. Biological (e.g. nucleic

acids, antibodies, enzymes) or synthetic (e.g. cyclodextrines,calixarenes, phenylboronic acid) receptors can be used. Mod-ification of CP with biological receptors is described in theSection 3.

6 a n a l y t i c a c h i m i c a a c t a 6 1 4 ( 2 0 0 8 ) 1–26

Table 1 – Mechanisms of interaction of different gases and vapors with conducting polymers

Interaction of gases with conducting polymers

Physical interaction Chemical interaction

CHCl3, CH2Cl2, alcohols, acetone, acetonitrile, Oxidation: NO2 [62–64], SO2 Reduction: H2 [78], N2H4 Protonation/deprotonation:

alkanes, cyclohexane, benzene, toluene[76,87,103–109]

[65], O3 [66,67]

An introduction of �-cyclodextrin into P3MTH [52] or �-cyclodextrin into PPY [53] leads to sensitivity to dopamine,l-dopa, ascorbic acid, chlorpromazine and neurotransmit-ters derived from pyrogallol and catechol (see Section 3.3).The ability of 3-amino-phenyl-boronic acid to bind diolswas used to design chemosensors for sugars based onthis receptor group. A copolymer film of PANI and poly(3-aminophenylboronic acid) can be used for reversible opticaldetection of saccharids [54]: binding of sugars results in a hyp-sochromic shift of the absorption maxima at 600 nm and to anincrease of absorption between 650 and 800 nm. Potentiomet-ric response of poly(3-aminophenylboronic acid) to sugars wasreported [55,56]. The result was explained by the stabilizationof the polyemeraldine salt form of poly(3-aminophenylboronicacid) upon binding of sugars. This leads to changes ofpKa of poly(3-aminophenylboronic acid) corresponding bychanges of H+ activity which is detected as potentio-metric response. Simultaneously, changes of resonancefrequency of quartz microbalance were measured [57]. Muchhigher effects were reported for poly(3-aminophenylboronicacid) doped with Nafion. The film resistance was mea-sured in transversal direction by impedance spectroscopy

[58] and binding of sugars increased the transversal filmresistance.

ATP binding to the PTH derivative poly(3-(3′-N,N,N-trimethylamino-1′-propyloxy)-4-methyl-2-5-thiophene

Fig. 4 – CP suggested for fluorescent detecti

[73–77], NH3 [70–72], H2S[72]

HCl [84–86], NH3 [76,87,88]

hydrochloride) in solution leads to changes in the absorptionspectra and to fluorescence quenching [59]. Suggestively,an electrostatic interaction of negatively charged triphos-phate group of ATP with positive charged ammonium grouppromotes planarisation of the PTH backbone resulting inefficient �–� stacking between the PTH backbones. Thisaggregation leads to fluorescence quenching and to a colourchange of the polymer chains in solution from yellow to pinkred [59].

A number of new chemosensitive CP based on deriva-tives of PANI, PPY and other heterocyclic compounds wassynthesized and studied in [60], potentiometric responsesto dicarboxylates, amino acids and ascorbic acid wereobserved.

2.4. Conducting polymers with affinity to gases

An application of CP for detection of gaseous analytes belongsto well developed field of chemosensor design [61]. Gases inter-acting with CP can be divided in two main classes: gases whichchemically react with CP and gases which physically adsorb onCP (Table 1).

Chemical reactions lead to changes in the doping level ofCP and alter therefore their physical properties like resistanceor optical absorption. Electron acceptors like NO2, I2, O3, O2

are able to oxidize partially reduced CP and therefore increase

on of nitroaromatic explosives [68,69].

a c t a

tenor

NtPbopbaplfaetf

attCrvcecoma

Po[etfig

pinTftbw[

autalas

a n a l y t i c a c h i m i c a

heir doping level. To oxidize CP, the gas should have a higherlectron affinity than the CP. NO2 was found to increase theumber of charge carriers in PANI [62] and P3HTH [63] throughxidative doping with NO2

− ions and therefore decrease theesistance.

Oppositely, an oxidation of nanofibers of emeraldine salt byO2 to pernigraniline base state leads to an increase in resis-

ance [64]. SO2 also increases the number of charge carriers inPY thus decreasing the resistance [65]. The mechanism maye similar to that proposed for NO2 and P3HTH. Ozone changesxidation and protonation states of PANI, PNMA and m-chloro-olyaniline which is detected as changes of optical absorbanceetween 500 and 800 nm [66,67]. The higher sensitivity of PANInd m-chloro-polyaniline in comparison to N-methyl-PANI isrobably caused by their ability to be oxidized to pernigrani-

ine. An electron transfer from CP to analyte can be also usedor optical detection. For example, the fluorescence of PPV, PPEnd PP (Fig. 4) is quenched in the presence of nitroaromaticxplosives. The electron deficient nitroaromatics, which bindhrough a �-complex to the polymer, act as electron acceptorsor the photoexited electrons of the polymer [68,69].

Electron donating gases like H2S, NH3 and N2H4 reducend therefore dedope CP, which leads to an increase in resis-ance. Ammonia [70,71] and H2S [72] were found to decreasehe conductivity of PTHs. A mechanism for the dedoping ofP by ammonia, explaining this result, was proposed [70]. Theeduction of PPY [73], P3HTH [74,75] and PANI [76] by hydrazineapors was also reported, but not explained in detail. Inontrast to the analytes with electron acceptor properties,lectron donating substances (hydrazine) increase fluores-ence of 1–3 (Fig. 4) [77]. The effect was explained by removalf fluorescence quenching oxidized trap sites along the poly-er backbone. The detection limit for hydrazine was as low

s 100 ppb [77].Polymer reduction by analyte is the reason for increasing

PY resistance on exposure to hydrogen [78]. Surprisingly, anpposite effect was observed for PPY/Pd composites [78], PANI

79] and PANI/PtO composites [80]. The mechanism of theseffects is not clear, however it was suggested that the conduc-ivity increase is caused by formation of water inside the CPlm. Therefore, such an exception is expected only for hydro-en.

For some gases a partial charge transfer rather than aure redox reaction is suggested. Interacting with PANI, CO

s assumed to withdraw a lone pair electron from the amineitrogen through the positive charge at the carbon atom.herefore the positive charge at the carbon atom is trans-

erred to the amine nitrogen, resulting in an increase ofhe amount of positive charge carriers along the PANI back-one [81]. Another explanation suggests that CO interactionith PANI enhances charge transfer between polymer grains

82,83].The protonation of PANI or PPY by HCl vapor leads to

n increase of the polymer conductivity [84,85]. This wassed to design a multilayer conductometric sensor based onhe subsequent polymerization of aniline and EDOT on p-

minothiophenol modified gold electrodes [86]. The PEDOTayer provides electrical contact between two sensing partsnd operates as a filter and protective layer covering the sen-or surface. The conductivity responses of PANI on exposure

6 1 4 ( 2 0 0 8 ) 1–26 7

to NH3 and HCl have been also investigated on the polymernanofibers [76]. Deprotonation of PPY or PANI by ammonialeads to an increase of the polymer resistance [76,87], for PPYthis process is reversible at low ammonia concentrations butirreversible at higher concentrations, especially under highhumidity [88].

Composites of CP with metal [78] or metaloxide[63,80,89–93] nanoparticles, carbon nanotubes [94–96], organicand metalorganic [97] compounds and insulating polymers[98–100] provide new analytical possibilities. Metaloxideparticles are assumed to form n–p hetero junctions withthe CP with a depletion region. Adsorbed gases change thedepletion region and thus modulate the conductivity of thejunction [63,89,101,102]. ZnO nanowires in composites withP3HT are assumed to reduce the P3HT and therefore enhanceits sensitivity to oxidizing gases and reduce its sensitivityto reducing gases [93]. Ferrocene was immobilized in PPY toenhance the sensitivity of a PPY based CO sensor. The CO isassumed to interact with the iron ions of ferrocene, whichthen transfers an electron to the PPy chain [97].

Weak physical interactions of non-reactive volatile organiccompounds (chloroform, acetone, aliphatic alcohols, benzene,toluene, etc.) with the polymer may lead to modification ofCP resistance. The mechanisms were not studied in details.An adsorption of ethanol and hexanol on dipentoxy substi-tuted polyterthiophene was supposed to change the potentialbarrier at the boundaries between CP grains [103]. Resistanceincreases due to adsorption of chloroform, acetone, ethanol,acetonitrile, toluene and hexane on PANI, PPY and PTH andpolythiophene derivatives were explained by CP swelling lead-ing to a higher distance between the PANI chains [76,87,104]or by modification of dielectric constant of CP [105]. Acetonewas suggested to diffuse into the intersegmental spaces inthe PPY matrices and thus destroying the dispersing interac-tions between aromatic pyrrole rings and inducing a higherdisorder [106]. For such compounds as acetone a forma-tion of hydrogen-bonds with PPY was also suggested. Theseinteractions hinder electron jumping and hence decrease theconductivity of PPY. Changes in the visible spectra of PPYdue to acetone exposure indicate a reduction of charge carri-ers, especially bipolarons [106]. Interaction of methanol withemeraldine salt of PANI increases the number of charge car-riers through hydrogen bonding of methanol with reducedamine sites in the polymer. In contrary, such interaction ofmethanol with emeraldine base leads to twisting of the poly-mer chains, resulting in a lower mobility of the charge carriersand an increase of the polymer resistance [107].

Interaction of short chain aliphatic alcohols with var-ious PANI derivatives increases the order in the polymerfilms which is accompanied by expansion of polymer chainsand conductivity increase [76,108]. Adsorption of short chainaliphatic alcohols to PANI/PSS blends is assumed to enhancethe charge transfer between adjacent PANI particles by reduc-ing of the potential barrier for hopping/tunnelling processes,or by increasing of interchain and interparticle charge mobil-ity [109]. However, an adsorption of long chain aliphatic

alcohols leads to higher film resistances, in this case a pre-vailing effect of these non-polar compounds is their insulatingproperties hindering charge transfer between polymer chains[76,108].

a c t

8 a n a l y t i c a c h i m i c a

Chiral gases can be detected by CP modified by chiral sidegroups [110]. The major drawback of CP gas sensors is theirpoor selectivity and strong interference with humidity. PPVderivatives are one of a few examples of CP which are insen-sitive to humidity [111]. Poor selectivity of CP to gaseousanalytes can be overcome by combination of different sensorsinto arrays (see Section 2.6).

2.5. Molecularly imprinted conducting polymers

The formation of artificial receptors by means of molecularlyimprinted polymerization includes the following essentialsteps:

(i) preparation of non-covalent complex or covalent conju-gate between analyte (or its analog) and polymerizablefunctional monomers,

(ii) polymerization of these functional monomers,(iii) removing of the analyte (or its analog used as the tem-

plate in the stage (i)) from the polymer.

After analyte removing, the polymer material can be usedas a polymeric receptor for sensing applications. Typically,molecularly imprinted polymers are prepared by photo- orthermally-induced radical polymerization. However, there area number of reports on MIP preparation by electropolymeriza-tion. This approach was developed independently by severalgroups in 1998–1999 [112–116] and then reproduced in manyother laboratories [117–126]. This technique was used forpreparation of insulating or conductive chemosensitive films.Films of conjugated polymers were formed by electropolymer-ization of pyrrole [114,124], aniline [125] and anilineboronicacid [127] and by polymerization of porphyrin [116] and dyes[126].

The detection of analyte binding with electropolymerizedlayers of molecularly imprinted polymers was performed bydifferent techniques. Electrical conductance of receptor lay-ers allowed to make electrochemical detection of redox activeanalytes and was applied for detection of paracetamol bind-ing to polypyrrole film [124]. This approach was successfullyapplied also for poor conducting films of CP [116,121], howevertaking into account a very limiting distance for electron tun-nelling (∼1 nm), probably only small amount of binding sitesplaced at this distance from the electrode surface can con-tribute into the measured electrical signal. Other detectiontechniques used for non-conductive as well as for conductiveelectropolymerized layers are the same as for other types ofmolecularly imprinting polymers and include mainly a moni-toring of electrical capacitance by impedance measurements[117,122,112] and changes of resonance frequency of quartzmicrobalance [115,118,128].

The results demonstrate that molecularly imprinted elec-tropolymerization can be considered as a general technologyfor the preparation of chemosensitive surfaces. It makes itvery attractive for the fabrication of sensor arrays for artificialnoses and tongues. However, it is difficult to evaluate, if it is

really competitive with other synthetic approaches. The mainadvantage of electropolymerization is the possibility to controlthe thickness of polymer layer. Additionally, this is well com-patible with combinatorial and high-throughput approaches

a 6 1 4 ( 2 0 0 8 ) 1–26

(see Section 6 for more details) which certainly belong to cru-cial technologies for the development of molecular imprinting[129]. Electrical and optical properties of conjugated polymersmay provide interesting possibilities for binding detection.However, an application of “classical” polymers based onacrylic compounds with different functional groups provideshigher flexibility in the selection of polymerizable monomersand cross-linkers. This feature may be decisive for the choiceof technology. This was the reason why further works withmolecular imprinting technology in our group were performedby photografting technique, without electropolymerization[113,130,131].

2.6. Electronic noses and tongues

The combination of chemical sensors based on CP into arraysis motivated by a typically poor selectivity of single sensors.These arrays can be used for gaseous (artificial noses) orliquid (artificial tongues) analytes. An additional advantageof sensor arrays is the possibility to make analysis of poordefined analytes, such as aromas or taste of food products.Conductometric electronic noses based on CP were appliedfor detection of fire [132], aromatic hydrocarbons [133], bac-teria and fungi [134–140], pollutants in water [134,141], formonitoring of emissions from sewage plants [142] or for anal-ysis of wines [143], olive oils [144,145], different soils [146] andgrain quality [147] and other poor defined analytes. Surpris-ingly, instead of using of different classes of CP, derivatives ofone CP were typically used to get different selectivity of sin-gle sensors of the electronic noses. Electronic tongues wereused for analysis of different tastes [148–150], bitter solutions[151], wines [152,153] and juices [154], for the quantificationof K+ and NH4

+ in presence of Na+ [47,155], or for the detec-tion of adulterations in wines [156]. To get a higher variabilityin sensitivity of single sensors, such arrays based on electro-chemical transducing include not only the electrodes modifiedwith different CP but also uncoated noble metal electrodes andelectrodes modified with Ru(py), stearic acid, phtalocyaninesand other compounds.

3. Modification of conducting polymers byreceptors

Affinity of CP to analytes can be modified by incorporationof synthetic or natural receptors [157–162]. A set of eitherconventional multifunctional chemical agents or polymersknown and applied for the immobilization of biological ele-ments is presented in [161]. The immobilization proceduresare based on non-covalent interactions (physical adsorption,electrostatic assembly, hydrophobic interactions) or covalentbinding of a receptor to a matrix. Different CP were used forthe preparation of biosensors [159], but the main attentionwas payed to PPY [163–165]. Examples of immobilization of

receptors into CP are presented in the Tables 2 (immobiliza-tion of enzymes) and 3 (immobilization of synthetic recep-tors). Detailed analysis of advantages and disadvantages ofeach immobilization technique is presented in [159].

an

al

yt

ica

ch

imic

aa

ct

a6

14

(20

08

)1–26

9

Table 2 – Selected examples of enzymatic biosensors based on CP

Analyte Polymer/polymerization method Biological receptor Type of transducing Ref.

Immobilization by covalent cross-linking

Uric acidPANI

UricasePhotometric (UV–visspectroscopy)

[208]electrochemical polymerization

H2O2PANI/PET

HRPPhotometric (UV–visspectroscopy)

[209]chemical deposition to pretreatedPET plates

H2O2PANI

HRPPhotometric (UV–visspectroscopy)

[210]chemical polymerization

Oligo-saccaridesPANI

GlucoamilasePhotometric (UV–visspectroscopy

[211]Chemical polymerization

GlucoseThiophene derivatives copolymer

GOx Amperometric [194]Electrochemical polymerization

H2O25,2′:5′,2′ ′-Terthiophene-3-carboxylicacid

HRP Amperometric [193]

Electrochemical polymerization

Immobilization by mechanical embedding

H2O2PEDOT/PSS HRP entrapped into conducting

hydrogel matrix compositeAmperometric [187]

Colloidal dispersion, hydrogelmatrix formation

GlucosePEDOT/PEG

GOx modified by PEG Amperometric [183]Electrochemical polymerization

Phenol (diphenol)PEDOT

Tyrosinase Amperometric [212]Electrochemical polymerization

GlucosePEDOT

GOx Amperometric [213]Electro chemical polymerization

GlucosePoly(methylmethacrylate-co-thienylmethacrylate)

GOxPhotometric (UV–visspectroscopy)

[214]

Electro chemical polymerization

Organophosphate pesticidesPANI

Acetylcholinesterase Amperometric [215]Electrochemical polymerization

CholesterolPPY, PANI Cholesterol esterase and oxidase

co-immobilizedAmperometric [216,217]

Electrochemical polymerization

NADH, NAD+ p-ABSAFlavins (FAD, FMN, RF) Amperometric [218]

Electrochemical polymerization

Uric acidPANI

Uricase Amperometric [181]Electrochemical polymerization

Phenolic compoundsCopolymer: PPY/thiophenederivative

Polyphenol oxidasePhotometric (UV–visspectroscopy)

[219]

Electrochemical polymerization

10a

na

ly

tic

ac

him

ica

ac

ta

61

4(2

00

8)

1–26

Table 2 (Continued )

Analyte Polymer/polymerization method Biological receptor Type of transducing Ref.

Immobilization by electrochemical doping

GlucosePANI/o-anisidine/o-toluidinecopolymer

GOx Amperometric [220]

Electrochemical polymerization

H2O2PANI

HRP Amperometric, colourimetric [178]Electrochemical polymerization

H2O2PANI

HRP Amperometric [221]Electrochemical polymerization

H2O2PANI/carbon nanotubes

HRP Amperometric [222]Electrochemical polymerization

GlucosePANI/PVS

GOx and HRP Amperometric [223]Electropolymerization

Uric acidPANI

Uricase Amperometric [181]Electrochemical polymerization

GlucosePPY GOx modified by

AMPSAmperometric [177]

Electrochemical polymerizationImmobilization by other ways of entrappment or physical adsorption

H2O2 2-Methoxyaniline-5-sulfonicacid/poly(l-lysine)

HRP Amperometric [224]

Chemical polymerization,drop-coating

Glucose PPY/PSS/PA compositeGOx Amperometric [188]

Chemical polymerization in thedispersed phase of emulsions ofGOx and PPY

Glucose o-AnisidineGOx Amperometric [225]

Electrochemical polymerizationH2O2 PEDOT/PSS

HRP Amperometric [187]Colloidal dispersion, hydrogelmatrix formation

an

al

yt

ica

ch

imic

aa

ct

a6

14

(20

08

)1–26

11

Table 3 – Selected examples of sensors with synthetic receptors immobilized into CP

Analyte Polymer or monomer/way of polymerization Receptor Type of transducing Ref.

Immobilization by polymerization of monomer covalently modified by receptor

Anions/H2PO4− Quinoxaline Potentiometric [226]

Glycoproteins (GOx, HRP) Poly(aniline boronic acid) electrochemical polymerization Boronic acid Photometric [227]

Toluene, acetone vapor 5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrahydroxycalix[4]arene

Gravimetric, QCM electrode [228]

Li+ Substituted 14-crown-4 macrocycle Amperometric [229]

12 a n a l y t i c a c h i m i c a a c t

Tabl

e3

(Con

tin

ued

)

An

alyt

ePo

lym

eror

mon

omer

/way

ofp

olym

eriz

atio

nR

ecep

tor

Typ

eof

tran

sdu

cin

gR

ef.

Imm

obil

izat

ion

byd

opin

gor

embe

dd

ing

du

rin

gp

olym

erd

epos

itio

n

Cu

2+,E

u3+

5,17

-Bis

(4-n

itro

ph

enyl

azo)

-26,

28-

dih

ydro

xy-2

5,27

-d

i(et

hox

ycar

bon

ylm

eth

oxy)

-cal

ix[4

]are

ne

Imp

edim

etri

c[2

30]

Ag+

PED

OT

/ele

ctro

chem

ical

pol

ymer

izat

ion

p-Te

tras

ulf

onat

edca

lix[

4]ar

ene

Pote

nti

omet

ric

[44]

Na+

,K+,M

g2+,C

a2+M

n2+

,Fe3+

,Co2+

,Ni2+

,Cu

2+,Z

n2+

PPY

/ele

ctro

chem

ical

pol

ymer

izat

ion

�-C

yclo

dex

trin

,su

lfat

ed�

-cyc

lod

extr

inPo

ten

tiom

etri

c[1

75]

Dop

amin

en

euro

tran

smit

ters

Poly

(3-m

eth

ylth

iop

hen

e)/e

lect

roch

emic

alp

olym

eriz

atio

n�

-Cyc

lod

extr

inA

mp

erom

etri

c[5

2]C

atec

hol

and

pyr

ogal

loln

euro

tran

smit

ters

PPY

/ele

ctro

chem

ical

pol

ymer

izat

ion

�-C

yclo

dex

trin

Am

per

omet

ric

[53]

Na+

,K+,N

H4

+O

vero

xid

ized

PPY

/ele

ctro

chem

ical

pol

ymer

izat

ion

Non

acti

n,v

alin

omyc

in,

dib

enzo

-18-

crow

n-6

,bis

[(12

-cro

wn

-4)

met

hyl

]-2-

dod

ecyl

-2-m

eth

ylm

alon

ate,

cisd

icyc

loh

exan

o-18

-cro

wn

-6(

Imp

edim

etri

c[4

7]

Zn

2+PP

Y/e

lect

roch

emic

alp

olym

eriz

atio

nTe

trap

hen

ylbo

rate

Pote

nti

omet

ric

[45]

a 6 1 4 ( 2 0 0 8 ) 1–26

3.1. Non-covalent immobilization

3.1.1. Physical adsorptionSimple adsorption of receptors to polymer supports is rarelyused because weak bonding leads to a loss of the receptor. Fewexamples of biosensors prepared by this procedure were pro-posed for operation in non-aqueous solvents [166]: the enzymewas adsorbed on the solid support from aqueous phase andbeing insoluble in organics, it does not diffuse away from thesupport into the bulk solution [166].

3.1.2. Langmuir–Blodgett techniqueLangmuir–Blodgett technique was widely used at the endof 1980s–beginning of 1990s as a relatively simple technol-ogy to get highly ordered organic films with artificial ornatural receptors. However the system assembled by exter-nal forces does not lead to highly stable and defect freefilms. Therefore this technique was used mostly in com-bination with other immobilization procedures. A glucosesensor was prepared by embedding of GOx into a polypyr-role film consequently covered by a few lipid monolayerscontaining GOx [167]. Hydrophobic derivatives of CP (poly(3-dodecylthiophene), poly(3-hexylthiophene)) were used in amixture of stearic acid and galactose oxidase [168] or GOx[169] to be deposited by Langmuir–Blodgett technique. Duringthe last years the application of Langmuir–Blodgett approachwas almost completely replaced by the technologies of self-assembly based on layer-by-layer deposition or on binding ofthiols to some metals, modification by silanization and sub-sequent covalent immobilization.

3.1.3. Layer-by-layer (LbL) deposition and electrostaticaldoping of polymersThis type of immobilization implies alternate electrostaticadsorption of receptor and opposite charged polymer layersto solid support. An exploiting of electrostatic interactionsrequires a correct choice of ionic strength and pH. Actually, LbLdeposition process is governed by a set of effects like shielding,hydrogen bonding, dispersion forces, determining film thick-ness and molecular morphology [170]. This technology canbe used also for inclusion of nanoparticles or nanoparticlesmodified with artificial or biological receptors. Deposition of alarge number of layers can be performed by using a mechan-ical robot [171] or a simple fluidic system [172]. The maindrawbacks of LbL deposition are sensitivity of the receptor-containing multilayer to variations of ionic strength, generallyleading to destabilization of an assembly and an influenceof the drying process on the multilayer structure [173]. LbLdeposition was used to incorporate GOx into a multilayer ofPSS/PPY on the surface of in-situ polymerized PPY [174].

Electrochemical doping of polymers by receptors proceedsdue to the ability of CP to exchange accompanying ions uponswitching between their redox states. Synthetic receptors likecalixarene [44], cyclodextrins [175], tetraphenylborate [45,176]were used as supporting electrolytes in polymerization mix-tures and were doped into the forming polymer (Table 3).

Doping counterions can be also of polyelectrolyte nature. Inparticular, negatively and positively charged enzymes at pHhigher than their isoelectric points are doped into polymerfilms during their oxidation or reduction, respectively. This

a c t a

aimwpaofe

dim[

3ItietprulrlcfsGsP[irmdpe[A

doeTcsticaadPTctc

a n a l y t i c a c h i m i c a

pproach is considered as postmodification of a polymer ands commonly used for polyaniline films, because its poly-

erization proceeds effectively only in strongly acidic mediahich is incompatible with most receptors. Biosensors incor-orating GOx, HRP and urease by electrochemical doping of CPre presented in the literature (Table 2). A prior modificationf GOx by polyanion (poly(2-acrylamido-2-methylpropane sul-onic acid (AMPS) via poly(ethylen oxide) spacer) allowed anffective doping of PPY by GOx [177].

The quantity of enzyme incorporated by electrochemicaloping is usually estimated by comparison of protein amount

n working solution before and after electrodeposition of poly-er. This was performed also by electrochemical technique

178].

.1.4. Mechanical embeddingf the receptor is present in the vicinity of the electrode, elec-ropolymerization leads to the entrapment of the receptornto the growing polymer layer. This incorporation proceedsffectively, if the concentration of the receptor is high andhe electrodeposition occurs under mild conditions (at lowotential, neutral pH). This procedure was used to incorpo-ate various redox enzymes into PPY, PEDOT and PANI formednder constant or cycling potential mode (Table 2). Neverthe-

ess, the amount of receptor finally embedded into the filmemains insufficient. To increase enzyme loading prior cross-inkage by glutaraldehyde and drying with mediator at thearbon paste electrode before electrocoating by PPY was per-ormed for tyrosinase [179]. High effective GOx loading due toelf entrappment into PPY nanoparticles was reported in [180]:Ox initiated pyrrole polymerization and was thereby encap-ulated into forming PPY nanoparticles. To increase loading ofANI by active uricase, a three-step procedure was proposed181]. Firstly, uricase was entrapped during electropolymer-zation of PANI, then enzyme (presumably inactivated) wasemoved from PANI film by hydrolysis under strong acidic

edia and cavities formed in PANI were electrochemicallyoped by active uricase. PEDOT, prepared by chemical vaporhase polymerization, shrinks several times being placed intothanol solution. It was exploited for immobilization of HRP182] by immersion of the polymer into ethanol solution of HRP.n incorporation of HPR was checked by UV–vis spectroscopy.

To provide stability of receptors during mechanical embed-ing, the polymerization conditions are adjusted by variationf pH, ionic strength, solvent, type of counterion, etc. How-ver, monomers are often poor soluble in aqueous media.he solubility can be increased by addition of water-solubleomplexones (cyclodextrins) or surfactants. In particular, theolubility of EDOT in aqueous solution was increased by addi-ion of surface active PEG bearing GOx, which was finallyncorporated into PEDOT [183]. Polyaniline was doped witharboxy-modified gold nanoparticles to yield layer-by-layerssembled multilayer films with extended polyaniline redoxctivity up to neutral pH values [184]. Immobilization of lactateehydrogenase (LDH) into composite films from PANI/PAA,ANI/PVS was enhanced in the presence of Ni(II) ions [185].

he immobilization proceeded by coordination of Ni(II) to thearboxy-groups of PAA and histidine of LDH. An optimiza-ion of biosensor construction proposed in [186] implied aombination of hydrogel and CP advantages. This idea has

6 1 4 ( 2 0 0 8 ) 1–26 13

been realized with HRP entrapped into conducting hydrogelmatrix [187]. An electroactive hydrogel matrix was composedfrom PEDOT and PSS with osmium as a mediator and a cross-link point to poly-4-vinylpyridine, which together with themagnesium cross-linked PEDOT/PSS gives a rigid hydrogel.A microgel of polyacrylamide containing GOx was formed inconcentrated emulsions of GOx and PPY [188]. Multilamelarvesicles were recently proposed to facilitate transport andincorporation of GOx into PPY [189].

3.2. Covalent immobilization

Chemical bonding of receptors by covalent reaction betweenfunctional groups of receptor and polymer provides thestrongest immobilization. Main steps of polymer modificationby a receptor are depicted in the Fig. 5. The simplest way isthe polymerization of derivative bearing the receptor (path1) or any function (path 2) however this is often limited bythe synthetic availability of this derivative. Various derivativesof pyrrole and thiophene modifed by ionophore units werereported (Table 3). These derivatives were electropolymerisedmostly in organic solvents.

Low solubility of modified monomers in aqueous mediaand often low conductivity of resulting polymer can be cru-cial for biomolecule immobilization. Suitable derivatives arepyrrole and thiophen bearing carboxyl function (often withalkyl spacers) at the �-position [29,190–195] or N-substitutedpyrrole [196]. Being activated by easily leaving groups like N-hydroxysuccinimide, carboxyl units react with amino groupsof the receptor. However, the efficiency of the postpolymeriza-tion modification of various poly (N-substituted pyrrole) filmswas estimated by ferrocene probe to be only 20–22% [196].Besides PPY, such polymers as polythionine are found to beconvinient for the immobilization due to the presence of freeamino functions in the polymer structure and reversible andstable behavior of the polymer film in biological compatiblemedia [197]. A sensor based on tyrosinase linked to elec-troactive poly(dicarbazole) via carboxy group was presentedin [198]. Various strategies to preparation of polymer withsynthetic (polyalkyl ether, crown ether, pyridyl-based ligands)and biological receptors are reviewed in [199]. Other chemicalagents for immobilization, detailed reactions and conditionshave been reviewed [200,201]. However, a postsynthetic mod-ification of CP can cause a detachment of CP from electrodes[202].

To overcome the problem of derivative solubility, twogeneral approaches were proposed in the literature. Post-polymerization grafting (path 3, Fig. 5) – wet chemical,organosilanization, ionized gas treatments, and UV irradia-tion were discussed [201]. Postmodification of polyaniline bythermal grafting of acrylic acid was reported [203]. Anotherapproach (path 4, Fig. 5) implies copolymerization or poly-mer deposition in the presence of polyelectrolytes [204] ormodified nanoparticles bearing functional groups of interest(path 5, Fig. 5) [184]. Besides enzymes, other biomolecules likeDNA or antibodies were immobilized to be used in biosen-

sors. A shift of cyclic voltammogramms was reported also foran antigen–antibody conducting polymer-based sensor [205].Covalent grafting of ss-DNA onto carboxy-functionalized PPYwas performed in the work [206]. Coupling of the oligonu-

14 a n a l y t i c a c h i m i c a a c t a 6 1 4 ( 2 0 0 8 ) 1–26

Fig. 5 – Formation and pretreatment of a polymer for chemical immobilization of receptor unit: polymerization of amonomer already bearing receptor unit (path 1), polymerization of functionalized derivative, followed by chemical

n of telect

immobilization (path 2). Paths 3–5 illustrate postmodificatioincorporation of the modified nanoparticles (path 4), of poly

cleotide was accompanied by a shift of the open circuitpotential of the PPY-modified gold electrode. The struc-tural conformation of the PPY backbone was changed afterhybridization reaction leading to a decrease of intrinsic con-jugation of polypyrrole [206].

Less attention was paid in literature to the immobilizationof receptors onto polymer arrays, used for sensor construc-tion. Some examples of electrode arrays based on CP withselectively immobilized receptors were discussed in [207].

3.3. Immobilization based on affinity interactions

The problem of poor compatibility of optimal polymeriza-tion conditions in CP synthesis and limited stability of(bio)receptors can be overcome by postmodifications based onaffinity interactions. The pair biotin–avidin (also streptavidin[231] or neutravidin) is the mostly used: one of these unitsshould be introduced into the polymer while another one isconjugated with the receptor. Other binding pairs are basedon his-tag or on complementary nucleotides. An additionaladvantage in the exploiting of this technology is the possibilityto exclude random immobilization and to get more homoge-neous structures. A considerable enhancement of efficiencyof chemical immobilization is provided using the specific

biotin–avidin interaction [196]. The ways of polymer or recep-tor functionalization by biotin or avidin have been elaborated[232,233] and even whole biotinilated bacteria can be immo-bilized onto electrode [234]. Other ways of immobilization can

he polymer by functional group: grafting (path 3),rolyte (path 5).

be based on the formation of coordination bonds betweencarboxyl-group of polymer and histidine [185] or by using ofpolyhistidin-tags.

Affinity based immobilization is a convenient way forpreparation of sensor arrays. Fast and simple reaction ofstreptavidin and biotin can be used for array preparationby mechanical addressing (by using a liquid handling robotor microfluidic system). Electrical addressing in synthesis ofCP (Section 6) was applied for immobilization of differentoligonucleotides to different electrodes [235,236]. Such a sys-tem can be used as a protein [237] or a DNA-array [236] orcan be converted from a DNA-array to a protein-array by bind-ing of antibodies labeled with corresponding complimentaryoligonucleotides.

4. Conducting polymers as transducers

Strong and reversible influence of oxidation/reduction,protonation/deprotonation and conformational changes onelectrical and optical properties of conducting polymersallows one to use them as transducers or as components oftransducers. A list of examples of such application is shownin the Table 4.

4.1. Conductometric and impedometric transducers

The conductivity change upon interaction with analytes is oneof the mostly used transducing principles. Many processes

a n a l y t i c a c h i m i c a a c t a 6 1 4 ( 2 0 0 8 ) 1–26 15

Table 4 – Conducting polymers as transducers

Transducing principle Analyte Polymer (+receptor) Ref.

Electrochemical

Conductometric

pH PPY/PANI [13,15]HCl PANI [84,86]NH3 PANI/PPY [76,87,239,239]NO2 PANI/P3HTH [62–64]N2H4 PANI/P3HTH [75,76]Cu2+ Polycarbazole [28]Ca2+ Fig. 3 (10) [49]Hg2+ PANI + cryptand [51]

Potentiometric

pH PANI/PPY [8,10,11]Glucose, Saccharides poly(3-aminophenylboronic acid) [55,56]Ag+ P3OTH, PEDOT + sulphonated thiophenes [26,40]Zn2+ PPY + tetraphenylborate [45]Cu2+ PI, Polycarbazole [27]Ca2+, Mg2+ PPY + ATP [39]

AmperometricCr2O7

2− PANI [240]NH4

+ PPY [241]NO2

− PPY [242]

Voltammetric

Ag+ PPY + Eriochrome B [42]Cu2+, Pb2+, Cd2+, Hg2+ Fig. 3 (5,6) [29,34]AA, dopamine P3MTH, PEDOT, PANI [243–247]Morphine PEDOT + MIP polymer particle [248]NADH/NAD + PANI + FAD, [218]Serotonin, dopamine, UA Overox.PPY + Au-nanoparticle [249,250]Chlorpromazine, dopamine,l-dopa

P3MTH + cyclodextrin [52]

Impediometric K+, NH4+ in presence of Na+ PPY, PANI, PEDOT [156,47]

Optical

UV–vis

pH PANI [16,18,19,23,24]Ozone PANI; m-chloro-polyaniline [66,67]ATP poly(3-(3′-N,N,N-trimethylamino-1′-propyloxy)-4-

methyl-2-5-thiophenehydrochloride)

[59]

Near InfraredSpectroscopy

Saccharides Poly(3-aminophenylboronic acid)/PANI copolymer [54]pH PPY, PANI [5,21–23]

Fluorescence

Hydrazine Fig. 4 (1–3) [77]nitroaromatics PPEs/PPVs/PPs [68,69]K+ Fig. 3 (7–9) [50]Hg2+ PMNT = poly(3-(3′-N,N,N-triethylamino-1′propyloxy)-4-

methyl-2,5-thiophene hydrochlorid) + mercury specificoligonucleotide

[253]

ATP poly(3-(3′-N,N,N-trimethylamino-1′-propyloxy)-4-methyl-2-5-thiophenehydrochloride)

[59]

Transition metals Fig. 3 (2–4) [33]

SPRHCl PANI [252]H2S, NO2 PANI [253]H2O2 PANI + HRP [254]

I

tc

tdpce

Raman spectroscopy pH PAN

hat lead to changes in charge carrier density or mobility causehanges in conductivity.

In conductometric gas sensors, an interaction of elec-ron acceptors or donors with CP causes changes in the

oping state of the polymer due to oxidation/reduction orrotonation/deprotonation reactions, leading to changes inonductivity. Using this interaction chemosensors for differ-nt gases were developed (Section 2.4). The change of charge

[9]

carrier density due to protonation/deprotonation of CP is usednot only in gas sensors for acidic/basic gases, but also in con-ductometric pH sensors (Section 2.1).

pH changes as well as modification of the redox state

of CP can be induced by substrates, products or interme-diates of enzymatic reactions, this is the main principleof CP application as conductive transducers in enzymaticbiosensors (Section 3). An enzymatic sensor composed of

16 a n a l y t i c a c h i m i c a a c t a 6 1 4 ( 2 0 0 8 ) 1–26

Fig. 6 – Configurations for measurement of lateral (A–D) and transversal (E) resistance of conducting polymers:chemoresistors (A and C), four-point configuration upgraded for simultaneous two- and four-point measurements (s24configuration) (B and D). An introduction of reference electrode provides fixation of the redox state of the conducting

e (typ

polymer (C–E). The circle with pulses indicates an AC voltag

an interdigitated microarray electrode covered by polypyrroleand a penicillinase membrane was proposed in [255]. Theenzyme reaction acidified the polypyrrole membrane and achange of conductivity was registered. The same principlewas used in [256]. A decrease of polyaniline conductivity wasobserved during enzymatic oxidation of glucose due to for-mation of gluconolacton and its non-enzymatic hydrolysisto gluconic acid. An impedimetric response of polyaniline-alcoholdehydrogenase microlectrode array to ethanol wasreported in [257]. Electrochemically synthesized PANI formsprotrusions in a sonochemically pretreated insulating layer.The change of PANI conductivity in the presence of ethanolis not only due to local pH change, but probably also dueto chemical reaction between polyaniline and the productof enzymatic reaction (acetaldehyde) [257]. The influence ofconformational changes on polymer conductance is used insensors for Ca2+, Cu2+ and Hg2+ [28,49,51].

In most cases the simplest two-point conductivity mea-surement technique is used (Fig. 6A). Such a device was namedchemoresistor. The less used four-point conductivity mea-surement technique [84,258] can provide a higher sensitivity,especially for highly conducting polymers or essential contri-bution of polymer/contact resistance into the value measuredby two-point configuration [259]. This technique was modifiedby combining the two- and four-point techniques for simul-taneous measurements (Fig. 6) [84] and was named as s24[202].

A determination of the geometrical factor defining the ratioof polymer resistance between inner and outer electrodesmeasured by s24 technique, allowed one to separate the totalvalue of the resistance measured by two-point techniquesinto two components corresponding to the bulk and contactresistances [260]. This approach provides new analytical pos-sibilities. Both 2- or 4-contact chemoresistors (with or withouts24 approach) were used successfully for measurements ingases [76,84–87,238,239,259], but they have a common disad-

vantage: the redox state of the CP is not well defined. Thisproblem cannot be solved for CP placed directly into gasphases. In electrolytes, the redox state of the polymer can befixed by reference electrode (Fig. 6C and D). This configuration

ically, of sine or square shape) source.

was widely used for liquid analytes. Principally, one can imag-ine an application of such configuration to gases, in this caseone can use solid electrolytes or liquid electrolytes separatedfrom the gas phase by a gas-permeable membrane. Measure-ment configurations, including two-measurement electrodesand an additional reference electrode in the solution (Fig. 6C),resemble circuits for field effect transistors and were oftenreferred as organic electrochemical transistors (OECT) [261].

Although the measurements of electrical current betweenelectrodes placed on the same solid support is certainly themost practicable configuration, the low conductivity of someCP at typical conditions for bioanalytical applications (neu-tral pH, modest oxidation potential) may complicate thisapproach. In such cases, measurements of transversal resis-tance between electrode coating by CP and an electrode in thesolution are used [262] (Fig. 6E). It can be realized by the com-mon in electrochemistry two- or three-electrode circuits. Anadvantage of this configuration is due to the 105–108 higherratio of the electrode area to the layer thickness (or an effec-tive distance between electrodes placed on solid support), thevalue of the polymer resistance is correspondingly 105–108

times less than for the measurements of lateral resistance.This provides a possibility to apply this approach to polymerswith 105–108 higher specific resistance.

All the configurations drawn in Fig. 6 can be used also formeasurements in AC mode or for impedance spectroscopy.AC mode has a number of advantages because of irreversibleeffects of applied electrical potential on CP [263].

4.2. Potentiometric transducers

In potentiometric transducers CP is deposited directly on thesolid surface of electronic conductor (metal or graphite). Thisconfiguration resembles ion-selective electrodes with polymermembrane without inner solution (coated wire electrode). Thetypical problem of the coated wire electrodes is an instability

of the potential drop at the metal/polymer interface: if thereis no electrochemical reaction (and therefore no electrochem-ical equilibrium) at the interface, this potential drop cannotbe fixed. A deposition of CP having intrinsic electrochemical

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ctivity, which maintains the electrochemical equilibrium oflectrons at this interface, allows one to overcome this prob-em. This is the reason to use CP as an intermediate layeretween metal and ion selective membrane [264,265]. A poten-ial drop on the second border of CP is defined through ionxchange. But some CP films are selectively permeable forome ions or can bind some ions, therefore they can be usedot only as an intermediate layer between ion selective mem-rane and electrode but also as an ion selective membrane

tself [266,267]. The ion selectivity can be modified by intro-uction of receptors (Section 2.2). However, electrochemicalctivity of CP results in interference of ionic and electronicquilibrium on the interface with electrolyte, which may leado a strong interference in the presence of redox active com-ounds.

.3. Voltammetric and amperometric transducers

oltammetric and amperometric transducers based on CP aresed for detection of current caused by either electrocataly-is or by ion flux into/from CP during its oxidation/reduction268]. The both processes are poor selective, therefore theirypical application is an amperometric detection in chro-

atography [244,269–271]. However, differences in the redoxehavior and specific chemical interactions allow one toet required selectivity for several particular analytes. Forxample, voltammetric detection of redox active compoundsas used for the detection of dopamine [52,245,246,272–274],

scorbic acid [245,272,273,275–277], uric acid [246], NADH218,278], morphine [248], serotonin [249]. The advantage ofP modified electrodes over conventional metal or GCE elec-

rodes is provided by the electrocatalytic ability of someP. This often leads to better separation of oxidation (oreduction) peaks of the different analytes in voltammograms.he compounds are oxidized via an electron transfer from

he analytes to the oxidized polymer units. This processan be monitored by measuring the current of reoxidationf the reduced polymer units. Detection of ions can be

mproved by extraction of ions into the CP [29,34,279,280]Section 2.2).

P3MTH films have been used for the electrocatalytic oxi-ation of neurotransmitters, catechols and ascorbic acid

243,244]. In contrary to glass–carbon electrodes, these filmsffer a possibility to separate the peaks of ascorbic acid,atechol, and p-aminophenol in the voltammograms. Elec-rocatalytic properties of P3MTH films synthesized in theresence of �-cyclodextrin towards dopamine, l-dopa, ascor-ic acid and chlorpromazine have been tested. The oxidationf these compounds was catalyzed by the CP-film [272]. A

inear voltammetric response towards these compounds inhe concentration range 10−6 to 10−5 M was found. Poly[4,4 -is(butylsulfanyl)-2,2 -bithiophene] coatings provide a higherensitivity in oxidative detection of dopamine and ascorbiccid than P3MTH coatings [272]. NaPSS was found to preventlectrode fouling of PEDOT/NaPSS electrodes upon oxidationf phenols and chlorophenols [281,282]. PEDOT coated elec-

rodes also provide a separation of voltammetric peaks ofopamine and ascorbic acid. Incorporation of gold nanopar-icles in the PEDOT film improved the sensitivity of dopamineetection [245,246]. PEDOT films synthesized in the presence

6 1 4 ( 2 0 0 8 ) 1–26 17

of MIP-particles were used for the amperometric detection ofmorphine [248]. Overoxidized PPY films and overoxidized PPYfilms modified with gold nanoparticles or single wall carbonnanotubes were used for detection of dopamine, serotonin,uric acid, epinephrine and nitrite in the presence of ascor-bic acid [249,250,283,284]. The gold nanoparticles enhancethe sensitivity of the electrodes, whereas overoxidized PPYimproves the peak separation in the voltammograms.

Electrocatalytic oxidation of ascorbate at PANI modifiedelectrodes was also observed at neutral pH, despite the factthat PANI should be deprotonated at this pH and thereforeelectrochemically inactive. This observation was explainedby the fact that the oxidation of ascorbic acid is accompa-nied by proton liberation and local acidification of PANI films[247]. The mechanism of ascorbate oxidation on PANI mod-ified electrodes was studied by Raman-spectroscopy and itwas concluded that an electrocatalytic oxidation of ascorbateoccurs within the polymer film, and follows a redox catalyticmechanism. An increase of the ascorbate concentration shiftsthe reaction zone within polymer film to the underlying elec-trode/polymer interface [285].

p-ABSA/FAD modified electrodes have electrocatalyticactivity towards NADH oxidation and NAD+ reduction. NADHcan be oxidized to NAD+ using p-ABSA as a catalyst, whereasNAD+ is reduced by FADH2. Thus, p-ABSA/FAD modified elec-trode provides reversible oxidation and reduction [218], thiscan be used for design of biosensors.

High selectivity in electrocatalysis can be achieved byincorporation of enzymes into polymer matrix. Such CP mod-ified with oxidases or peroxidases are used in amperometricbiosensors (Table 2). In most cases the electron transfer fromenzyme to electrode was realized by mediatiors immobilizedin the CP matrix, and in some cases CP itself can play the role ofsuch a mediator [286,287]. In the case of peroxidases, a directelectron transfer from the CP to the enzyme was suggested[193]. Peroxidase modified electrodes are applied for detec-tion of H2O2. This can be used for amperometric transducingin competitive immunosensors with peroxidase-labeled anti-bodies or antigens [288], in DNA sensors and in enzymaticsensors based on oxygenases where H2O2 is the by-productof analyte oxidation.

4.4. Organic transistors and diodes as transducers

CP can be used as a component of diodes and transistors[261,289–291]. Chemical sensitivity of CP or a deposition ofreceptor makes these structures chemosensitive. Such appli-cations of CP in transistors can be based on the followingconfigurations: (i) CP forms a chemosensitive channel whichhas access to an analyte, the gate is not chemosensitive(Fig. 7A), CP forms a channel which is not sensitive to ana-lyte and is completely isolated from an analyte (Fig. 7B), CPforms a chemosensitive gate on inorganic field effect transis-tor (Fig. 7C). In the first case the CP has both receptor andtransducer functions [292–294]. In the second case [295,296]receptor and transducer are separated, and the CP operates

as a component of transducer. In the third case the CP canbe considered mainly as receptor. This principle was appliedmainly for gaseous analytes [297,298], but can be used also foranalytes in solutions.

18 a n a l y t i c a c h i m i c a a c t a 6 1 4 ( 2 0 0 8 ) 1–26

Fig. 7 – The structures of chemotransistors with CP: CP forms a channel which has (A) or has not (B) an access to analytes,

CP forms a chemosensitive gate (C).

In CP based Schottky-like structures, the current throughthe junction depends on the work function of the CP which canbe modified by interaction with analytes. This principle wasused for detection of NOx [299–301], ammonia [299], methane[302], alcohol and water vapors [299]. Aluminium and/or goldwere used as metals while PANI, P3OTH and PPY were used asCP in these diodes. Chemosensitive diodes formed by a junc-tion of n-doped silicium and PPY or PANI were also reportedand used as gas sensors [303,304].

4.5. Optical transducers

Changes in the redox or protonation state of a CP lead to astrong modification of its electronic band structure, thereforean interaction of analytes which oxidize/reduce or proto-nate/deprotonate CP can be measured by UV–vis spectroscopy.This was used in chemical sensors for HCl [305], NH3 [306–309],O3 [66,67] and pH [5,16,21–24]. Binding of analytes can alsochange the conformation of CP in solution which is cor-responded by modification of optical adsorption. This wasapplied to detection of divalent cations [305] and ATP [59].

More sensitive detection of optical changes in CP can berealized by application of surface plasmon resonance (SPR).The measurable parameter is in this case either refractiveindex or optical absorbance at the used wavelength. Thisapproach was used to detect changes in ultrathin films of CPupon interaction with different analytes (HCl [252], H2S, NO2

[253], H2O2 [254]). Alternatively, Raman spectroscopy can beused for transducing. A transition between emeraldine saltand emeraldine base of PANI was monitored and applied inpH sensing [9].

Modification of the optical properties of CP due to analytebinding can be detected also by fluorescence measurements.However detection schemes based on energy transfer aremore typical. Intrinsic fluorescence of some polymers causedby backbone units (e.g. PP, PPV, PPE, polyfluorene and PTHderivatives) or a fluorescence of fluorophores introduced intopolymer can be used. Fluorescence changes can be inducedby modification of self-quenching effects by interaction withanalyte or by quenching of polymer fluorescence by ana-lyte. For example, nitroaromatic explosives act as electronacceptors for photoexcited electrons of the CP and quench flu-

orescence [68]. In contrast, hydrazine enhances fluorescenceof 1–3 (Fig. 4) by reduction of oxidative traps in the polymerchains [77]. Also the binding of Hg2+ by a mercury specificoligonucleotide in solution increases fluorescence of PMNT

[251]. In comparison with single fluorescent groups, fluores-cent polymers provide a higher sensitivity: due to migration ofexcitons through the polymer chain, binding of single analytemolecule quenches fluorescence of the whole polymer chain[310]. This was demonstrated in fluorescence quenching bytransition metals in bipyridyl-containing CP (Fig. 3, 2–4) [33].

The fluorescence of fluorescent-labeled analytes can bedetected directly or by energy transfer (FRET) to/from CP. Forexample, the hybridization of a dye modified target strainwith complementary DNA immobilized on the fluorescentCP (poly(oxadiazole-co-phenylene-co-fluorene)) was detectedusing FRET between the polymer(donor) and the dye [311].

5. Attachment of conducting polymers tosolid supports

A strong adhesion of a polymer layer (either a receptor, or atransducer) to a support is an important requirement to sen-sor construction, maintaining the long-term performance andits large-scale production. The adhesion depends on manyfactors: the nature of the polymer and support (i.e. hydropho-bicity), procedure of synthesis (chemical or electrochemical,galvanostatic or potentiostatic, etc.), solvent, counter ions,etc. An electrodeposition of polyaniline with NO3

− counte-rion gives finer powder structure, which is more stronglyadhered to the electrode than a coarser structure, formed withCl−. Polymerization of aniline under cyclic voltammetry moderesults in a more adherent deposit in comparison to the filmobtained by galvanostatic and potentiostatic modes [3]. Thestability of electropolymerized films of poly-N-methylaniline(PNMA) on gold electrodes with different anions was foundto obey the series: PNMA-acetate < PNMA-chloride < PNMA-phosphate < PNMA-sulfate < PNMA-perchlorate [312].

An improvement of polymer adhesion can be performedby modification of either physical (surface area, hydrophobic-ity/hydrophility) or chemical (formation of chemical anchorgroups) properties of solid surface.

Electroplating of gold electrode in solution of Au(CN)2−

was used before electrochemical deposition of polypyrrole/PSS[313]. This increase in surface area results in improvedadhesion of the subsequently electrodeposited conducting

polymers. The morphology of the polymer layer was simi-lar to those deposited on smooth gold electrode. Washingby water and insertion into viscous medium (agar–agar gel)was used as a test for polymer adhesion [313]. Highly adher-

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victwt(nppdalipiot

uisoefp

cftma4sApamm

6h

TCeoptettap

a n a l y t i c a c h i m i c a

nt polypyrrole coatings were electrodeposited on etcheditanium and aluminium–titanium alloy in oxalic acid at aonstant potential. The substrates were etched in an alkalineeroxide solution prior to electropolymerization [314].

Special procedures were developed to synthesize CP onarious non-conductive polymers [315], inorganic compos-tes [316] and textiles [317]. An adhesion of CP obtained byhemical polymerization is often discussed in terms of effec-ive loading of porous matrix by the polymer. Polypyrroleas loaded into polypropylene by oxidative polymeriza-

ion of monomer in the presence of anionic surfactantsodium bis(2-ethylhexyl) sulfosuccinate), which providedot only doping as counterion, but also minimized theolypropylene–polypyrrole interfacial tension [318]. A com-osite of polypyrrole/PbSO4 is formed during potentiodynamiceposition of pyrrole onto lead. This composite improvesdhesion of subsequently formed pure polypyrrole film to theead support and its mechanical stability [313]. PEDOT wasntegrated into poly(methyl methacrylate), polycarbonate,oly(ethylene terephtalate), polystyrene [315]. This procedure

s based on partial dissolution of both polymers and shrinkingf the conductive layer leading to incorporation of the CP intohe support.

Simple chemical modification by organosiloxanes is widelysed to promote specific adhesion of polypyrrole and to facil-

tate its lateral growth between electrodes on solid insulatingupport [319]. An incubation of the support in ethanolic [319]r benzene [255] solutions of alkyltrichlorosilane, alkyltri-thoxysilane, (3-aminopropyl)-trimethoxysilane, etc. leads toormation of a hydrophobic or functionalized layer on the sup-ort to be covered by polymer.

In addition to improvement of the polymer adhesion,hemically bond monomolecular layers provide a possibilityor covalent binding of synthesized polymers. Thiol deriva-ives of polymerizable monomers forming self-assembled

onolayers on some metallic surfaces (Au, Pd, Ni, Cu, Agnd other) are widely used to get strong binding of polymers.-aminothiophenol was used as such sublayer for depo-ition of polyaniline and poly-N-methylaniline [84,312,320].

pyrrole monomer functionalized by thiol moiety (�-(N-yrrolyl)-alkanethiols) was attached to the electrode surfacend consequently polymerized to form a 2-D polymerizedonolayer. It was used as an anchor for subsequently poly-erized pyrrole [321].

. Application of combinatorial andigh-throughput techniques

here are many factors influencing on the properties of CP.hemosensitive properties (as well as many physical prop-rties which are crucial for sensor design) depend stronglyn the type(s) of monomers and counterions [312] used forolymer synthesis and on the presence and type of addi-ional dopants. The mode of polymerization (chemical orlectrochemical) and the physical conditions of polymeriza-

ion (temperature, mode of electrochemical polymerization,he last applied potential during polymerization, etc.) as wells the solvent also effect the material properties. Mechanicalarameters, such as the thickness and porosity of polymers

6 1 4 ( 2 0 0 8 ) 1–26 19

are important too. Sensors may be based not on bulk polymerproperties, but on the properties of metal/polymer contacts.An optimization of sensing material which is sensitive to solarge number of parameters can be hardly performed withoutcombinatorial technology.

A number of experimental approaches to combinatorialsynthesis of CP were reported. Combinatorial polymerizationdriven by an introduced chemical oxidizer can be performedwith a usual liquid handling robot or with a microfluidic sys-tem. Surprisingly, much more sophisticated techniques wereusually used. A combination of a mixing of reagents by meansmicrofluidics and subsequent electropolymerization wasreported in [322]. Instead of microfluidic delivery of reagents,a mechanical robot immersing electrodes into the wellswith solution of monomers was suggested [323,324]. Anotherapproach was based on electrically addressed polymerization,this technology does not include either mechanical robotics ormicrofluidics [202,326–328].

The combinatorial synthesis based on the combination ofmicrofluidics and electropolymerization was realized with amicrochip consisting of two areas: microfluidic channels forgeneration of a gradient of two substances and a parallelelectrochemical reactor with platinum electrodes [322]. Thesystem was tested for the synthesis of polyaniline in the pres-ence of polysulfonic acid.

A general purpose set-up for combinatorial electrochem-istry was developed by a combination of a mechanical robotand electrochemical system [323,324]. The set-up can operatewith one electrode set (consisting of a classical three-electrodeconfiguration) moving it between different cells or with8-electrode set providing simultaneous 8-channel measure-ments. The electrodes geometry was adapted for the workwith microtiterplates. The system was used for automatedcharacterization of combinatorially synthesized conjugatedthiophenes [328].

Mechanical addressing can be also used for combinato-rial postsynthetical modifications of conducting polymers.Postsynthetical modification was applied to formations of dif-ferent derivates of PANI. The modification was performed bynucleophilic addition, coupling with diazonium salts and byelectrophilic aromatic substitution [329].

A system for combinatorial polymerization of conduct-ing polymers based on electrical addressation was reported[258,326]. The same approach was also used for prepara-tion of DNA- and protein-arrays [331,238]. In the case ofcombinatorial applications, it includes modules for auto-mated screening of chemosensitive properties of synthesizedmaterials. The information flow in the whole system isshown in the Fig. 8. Control of electrical potential of elec-trode groups (each consisting of four electrodes for four-pointmeasurements) on an array containing 96 such electrodegroups (each group of 400 �m × 400 �m) enables the address-able electrochemical polymer synthesis on defined electrodes.The polymerization is performed until defined polymeriza-tion charge has passed. During this time all other electrodegroups are hold at the potential below polymerization poten-

tial. Then the polymerization solution is changed. Thisprocedure is repeated for each electrode group of the elec-trode array. Afterwards, electrical characteristics of polymersand influence of potential analytes on these characteristics

20 a n a l y t i c a c h i m i c a a c t a 6 1 4 ( 2 0 0 8 ) 1–26

eriznter

Fig. 8 – The complete system for combinatorial electropolymsynthesized polymers are observed as dark points in the ce

are measured and an automated data analysis is per-formed.

An example of the completely automated set-up for combi-natorial electropolymerization described in [325–327] includesan automated dosing station, an electronic multiplexer anda socket board with electro polymerization cell. The sys-tem was first applied for the development of chemosensorsfor gaseous hydrogen chloride, polyaniline and its copoly-

mers with different derivates of aniline were used. Thena similar approach was tested in the author’s group foroptimization of amperometric biosensors for glucose basedon electrocatalytical detection of hydrogen peroxide. The

ation and high-throughput characterization. Theof the combinatorial library [330].

pigment Prussian blue was used as an electrocatalyst fordecomposition of this product of enzymatic oxidation ofglucose.

Combinatorial synthesis of conducting polymers may becoupled with further functional high-throughput multifunc-tional screening of chemosensitive properties of conductingpolymers, as it was described in [327]. The authors developed aminimal test procedure consisting of two concentration pulses

of an analyte at the same concentration and a sequence ofconcentration pulses at increased concentrations. Automatedanalysis of the materials responses has given the followinginformation:

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absolute analytical sensitivity (as d[absolute signal value]d[analyte concentration] ),

relative analytical sensitivity (as d[relative signal value]d[analyte concentration] ),

response rate; it was defined as changes of the signal duringfixed time of the analyte addition);recovery rate (if the recovery occurred because of analytedesorption at zero analyte concentration) or recovery effi-ciency (if an external influence for the signal recovery isrequired); it was defined as signal changes during the fixeddesorption time or during another defined recovery proce-dure (i.e., a temperature pulse);reversibility (was defined as the ratio of the signal val-ues before analyte adsorption and after recovery or for therecovery after the first and after the second analyte concen-tration pulses);reproducibility (was defined as the ratio of the signalchanges for the first and second analyte addition);binding constant (for sensor materials which obey Lang-muir adsorption isotherm) or response linearity (for sensormaterial which obey Henry adsorption isotherm).

This analysis technology was applied to the screening ofhemosensitive properties of polyanilines and copolymers ofnilines and aniline derivatives. Combinatorial libraries wererepared by electrically addressed polymerization [325,326]. Inemi-automated data analysis an operator can select the ana-yte concentration range for the data analysis, data for eitherwo- or four-point resistance measurement mode, initialonductance, absolute and relative changes in conductivity,inetics and trends of the sensor response, desorption effi-iencies, reversibility, reproducibility, parameters of Langmuirr Henry adsorption isotherms, etc. The authors reported [330]100 times increase of the throughput, ∼4–5 times decrease of

oxic waste and ∼100–10000 times decrease of possible expo-ure of labor personnel to hazardous substances. Convenientormat of combinatorial libraries in the form of small amountsf polymers (few �g) deposited on silicone substrate with elec-rodes allows one not only simple characterization, but alsoimple storage and organization of banks of materials withlectrical and optical access for further investigations.

The applications of high-throughput experimentationsith CP for development of gas sensors, optimization of

lectrocatalytic layer and amperometric enzymatic biosen-ors are just a few examples of this approach. A possibilityo use electrochemical polymerization for preparation of

ultilayer structures [86] indicate an application potentialor combinatorial preparation and high-throughput analy-is of complicated monolayer devices. The same approachan be certainly used for development of molecularlymprinted polymers [112,332,123] or ion-selective electrodes266]. Additionally to combinatorial electropolymerization, anlectrochemical deposition of metals or a combination of elec-rical addressing with other techniques (for example, ink-jeteposition, photopolymerization, photolithography) may bepplied. This way can be used for in-situ synthesis of combina-orial libraries of different devices for analytical applications:

hemosensitive diodes, Schottki-contacts and transistors, ion-elective electrodes, optrodes, selective filters, microsystemsor electrophoresis or chromatography containing integratedetectors.

6 1 4 ( 2 0 0 8 ) 1–26 21

Notably, the system developed for combinatorial synthesisand characterization [325–327] can be also used as an array ofchemical sensors for gases (artificial nose) and liquids (artifi-cial tongue).

7. Conclusion

The initial interest in CP was caused by their electrical con-ductivity, however further investigations evaluated a uniqueset of optical, electrical and chemical features of these com-pounds. Their wide multifunctionality leads to very differentpossibilities in applications of CP in such specialized field aschemical and biological sensors. Principally, CP can be usedfor creation of each component of a chemosensor includinga receptor layer, a transducer, a protective coating or evenan electronic circuit for data proceeding. The review demon-strates the multifunctionality of CP for design and realizationof receptors and transducers.

Using modified or unmodified CP as a receptor material oras one of the components of the receptor layer in chemicaland biological sensors offers a wide range of possible applica-tions. Insufficient selectivity of receptors can be overcome bycombining different receptors to an array (electronic noses ortongues).

Affinity properties of CP can be tuned by immobilization ofappropriate receptors. The current trend in the progress of thisdirection indicates clearly an intensive application of chemi-cal immobilization providing the most stable receptor layers.Alternatively, LbL deposition, combining advantages of softimmobilization and high experimental flexibility, as well aschemically addressed immobilization based on highly specificaffinity interactions, are developed.

Many data on analyte/polymer interactions are based onempirical information. Physical and chemical explanationsof interaction mechanisms are still relatively speculative.Detailed investigation of these processes will not only pro-vide a better understanding of these processes, but can alsoindicate a way for further improvement of chemosensitiveCP. Also an implementation of techniques of high-throughputexperimentation with subsequent data mining and analysisof empirical correlations between variation of parameters andchemosensitive properties will lead to essential accelerationof the sensor development. Notably, exactly in the case of CPthe existing high-throughput technologies allow one to makenot only an optimization of chemosensitive materials but alsoan optimization of complete sensing devices.

Signal transducing by conducting polymers is usuallybased on electrical or on optical technologies. Typical electricaltransducers include potentiometry, impedance measure-ments, potentiometry, voltammetry, amperometry or systemsbased on organic semiconductor devices, while optical tech-niques are based on UV–vis spectroscopy, surface plasmonresonance and different fluorescent techniques. An appro-priate choice of the transducing technique has strong effecton the signal-to-noise ratio and therefore on the detection

limit. Therefore, the choice of a sensor for particular appli-cations depends strongly not on the used sensing materialbut also on its compatibility with the optimal transducingtechnique.

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r

22 a n a l y t i c a c h i m i c a

Last years a commercial application of CP in organicelectronics was started. One can expect that chemical andbiological sensors will be the next application field of thesematerials. Some problems still occur in stability of sometypes of CP during storage in air or in aqueous solutions,detachment of CP from support during the storage or repet-itive drying and a strong sensitivity to small variations ofconditions during synthesis and treatment. However, thedevelopment of new materials, effective optimization of alltechnological steps as well as an implementation of combi-natorial approaches and high-throughput experimentationgive rise to a very optimistic consideration of CP applicationsin chemical and biological sensors.

Acknowledgements

The authors are thankful to Prof. O. S. Wolfbeis and to Dr. Q.Hao for fruitful discussion. N.V.R. was supported by DFG.

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