Chem Soc Rev - Xiamen University

Chem Soc RevChemical Society Reviewsrsc.li/chem-soc-rev

ISSN 0306-0012

REVIEW ARTICLEJian-Feng Li, Ricardo F. Aroca et al.Plasmon-enhanced fluorescence spectroscopy

Themed issue: Surface and tip enhanced spectroscopies

Volume 46 Number 13 7 July 2017 Pages 3857–4112

3962 | Chem. Soc. Rev., 2017, 46, 3962--3979 This journal is©The Royal Society of Chemistry 2017

Cite this: Chem. Soc. Rev., 2017,

46, 3962

Plasmon-enhanced fluorescence spectroscopy

Jian-Feng Li, *a Chao-Yu Li a and Ricardo F. Aroca*bc

Fluorescence spectroscopy with strong emitters is a remarkable tool with ultra-high sensitivity for detection

and imaging down to the single-molecule level. Plasmon-enhanced fluorescence (PEF) not only offers

enhanced emissions and decreased lifetimes, but also allows an expansion of the field of fluorescence by

incorporating weak quantum emitters, avoiding photobleaching and providing the opportunity of imaging

with resolutions significantly better than the diffraction limit. It also opens the window to a new class of

photostable probes by combining metal nanostructures and quantum emitters. In particular, the shell-

isolated nanostructure-enhanced fluorescence, an innovative new mode for plasmon-enhanced surface

analysis, is included. These new developments are based on the coupling of the fluorophores in their

excited states with localized surface plasmons in nanoparticles, where local field enhancement leads to

improved brightness of molecular emission and higher detection sensitivity. Here, we review the recent

progress in PEF with an emphasis on the mechanism of plasmon enhancement, substrate preparation, and

some advanced applications, including an outlook on PEF with high time- and spatially resolved properties.

1. Introduction

Plasmon-enhanced fluorescence (PEF) was observed1–3 andrecognized,4–6 soon after the discovery of surface-enhanced

Raman scattering (SERS),7–9 as a member of the family ofsurface-enhanced spectroscopy techniques. However, theexperimental and theoretical research of PEF has truly explodedin recent years leading to a broad spectrum of new developmentsand applications. The field has grown exponentially thanksto an extremely productive symbiosis of plasmonics10,11 andspectroscopy12,13 (spectro-plasmonics) realizing to a large extentthe ultimate goal of achieving control over spontaneous emission.

In spectroscopy, molecular fluorescence is luminescence whichoccurs only during the irradiation of a fluorophore by mono-chromatic electromagnetic radiation or white light. Molecularluminescence is formally divided into fluorescence and phos-phorescence depending on the nature of the excited state.13

a MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key

Laboratory of Physical Chemistry of Solid Surfaces, iChEM, College of Chemistry

and Chemical Engineering, Department of Physics, Research Institute for

Biomimetics and Soft Matter, Xiamen University, Xiamen 361005, China.

E-mail: [email protected] Department of Chemistry and Biochemistry, University of Windsor, Windsor,

Ontario N9B 3P4, Canadac Department of Chemistry, Faculty of Science, University of Chile, Santiago, Chile.

E-mail: [email protected]

Jian-Feng Li

Jian-Feng Li is a Professor ofChemistry at Xiamen University.He received a BSc in chemistryfrom Zhejiang University, and aPhD in chemistry from XiamenUniversity. Professor Li is theprincipal inventor of shell-isolatednanoparticle-enhanced Ramanspectroscopy (SHINERS). Hisresearch interests include surface-enhanced Raman spectroscopy,surface-enhanced fluorescence,core–shell nanostructures, surfaceplasmon resonance, electrochemis-try and surface catalysis.

Chao-Yu Li

Chao-Yu Li is now pursuing hisPhD degree under the supervisionof Prof. Zhong-Qun Tian and Prof.Jian-Feng Li at Xiamen University.His research is focused on spectro-electrochemistry, synthesis ofplasmonic nanostructures, andplasmon-enhanced single-molecule spectroscopy.

Received 6th March 2017

DOI: 10.1039/c7cs00169j

rsc.li/chem-soc-rev

Chem Soc Rev

REVIEW ARTICLE

Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM

.

View Article OnlineView Journal | View Issue

http://orcid.org/0000-0003-1598-6856

http://orcid.org/0000-0001-7809-5933

http://crossmark.crossref.org/dialog/?doi=10.1039/c7cs00169j&domain=pdf&date_stamp=2017-06-22

http://rsc.li/chem-soc-rev

https://doi.org/10.1039/c7cs00169j

https://pubs.rsc.org/en/journals/journal/CS

https://pubs.rsc.org/en/journals/journal/CS?issueid=CS046013

This journal is©The Royal Society of Chemistry 2017 Chem. Soc. Rev., 2017, 46, 3962--3979 | 3963

In contrast, metal nanoparticles such as gold or silver nano-particles when excited by monochromatic electromagneticradiation show extremely weak metal photoluminescence,14

and the dominant observed light is elastic scattering. In otherwords, the commonly shown broad plasmon spectrum isobserved for excitation with white light. However, the opticalextinction cross section (absorption + scattering) of plasmonicnanostructures can be several orders of magnitude higher thanthat of molecular fluorophores. Plasmon excitation providesenhanced optical fields in the vicinity of metal nanostructures,and these high local fields enrich optical spectroscopy withnew capabilities for photon-driven processes. The observedaugmented spectral intensity is credited to the local fieldenhancement associated with the excitation of localized surfaceplasmon resonances (LSPR) in the metal nanostructures whichcan increase the sample’s absorption and emission cross sections.Most importantly, the coupling between the frequencies emittedby the fluorophore and the resonance of the metal particle cancause the metal to radiate light (with enhanced intensity) at thesame frequency (elastic scattering) as the luminescence emittedby the fluorophore. The latter justifies the term ‘‘metal-enhancedfluorescence (MEF)’’.15

Experimentally, the overlap between the LSPR of a metalnanoparticle and the molecular absorption and emission spectraof the fluorophore is predicted to yield the highest fluorescenceenhancement factor.16 With these new developments, the objectiveis to gain control over light absorption, emission and scatteringusing plasmonic nanostructures.17 One net result is to provideenhanced optical signals for analytical techniques,18 such asSERS, surface-enhanced resonance Raman scattering (SERRS),tip-enhanced Raman scattering (TERS),19 tip-enhanced fluores-cence (TEF),20 shell-isolated nanoparticle-enhanced Ramanspectroscopy (SHINERS),21 shell-isolated nanoparticle-enhancedfluorescence (SHINEF),22 enhanced phosphorescence,23 enhancedbioluminescence,24 and enhanced chemiluminescence.25 Inparticular, fluorescence enhancement by a plasmonic nano-structure increases the sensitivity of single molecule fluorescence

and imaging resolution,26 allowing us to extend single-moleculedetection studies to weakly emitting species which are not detect-able by conventional single-molecule fluorescence techniques.27,28

Apart from fluorescence molecules, the single quantum emitterthat couples to a plasmonic nanostructure can be a fluorescentsemiconductor quantum dot (QD),29,30 with a wide range ofapplications, ranging from biological labelling to photovoltaicand optoelectronic devices. Similarly, the studies of competitiveenvironmentally friendly fluorescent carbon dots (CDs) are carriedout for potential applications in bioimaging and biomedicine.31,32

Spectro-plasmonics not only encompasses many linear and non-linear spectral techniques, but it has also opened a wide scopefor applications, for instance, enhanced photochemistry,33,34

enhanced performance of solar cells35 and organic-photovoltaicdevices,36 potential diagnostic applications in biomedicine,37

and expansion of chemi-sensors and biosensors;38,39 a list ofexamples of applications of plasmonic biosensors for detectionof chemical and biological species can be found in the reviewby Spackova et al.40 In addition, spectro-plasmonics has andwill enable the realization of new optical components41 as wellas innovative optical instrumentation.42,43

Plasmon-enhanced fluorescence studies follow a patterncommon to all enhancing techniques. For a target fluorophore,the extinction and emission spectra are first recorded in asuitable environment: gas, solution or solid state structure. Thenext step, in PEF research, is the differentiation and fabricationof the enhancing plasmonic nanostructure to be used.44 Thepeculiarity in the properties to be originated in the nanostructurecan be explored using computational techniques.45 Analyticalmethods and powerful numerical techniques like the finitedifference time domain (FDTD) method, the discrete dipoleapproximation (DDA), and the finite element method (FEM)are now routinely used by the spectro-plasmonic community,allowing us to examine the enhancing properties as a function ofnanostructure material, shape, size, the dielectric environment,and the excitation wavelength. Once the required nanostructureis identified, its fabrication and characterization will be in itselfa challenging venture, and in many instances this is the objectiveof the research project. In this review we dedicate a specialsection to the fabrication of substrates for plasmon-enhancedfluorescence, in particular, fabrication of specific nanostructureswith well-tailored enhancing properties. In addition to thecomputational work carried out to support nanostructuredesign, there is theoretical computational work aimed at under-standing the interactions or coupling between plasmonic nano-materials and individual quantum emitters; the methodology isbased on quantum electrodynamics and ab initio electronicstructure,46 and quantum plasmonics.47

PEF has also grown under different headings. Surface-enhancedfluorescence (SEF) was the first name given to PEF as one of thesurface-enhanced spectroscopy techniques.6 Metal-enhancedfluorescence15 is also now a widely used term for experimental48

and theoretical studies of PEF.23 Here, we present a review ofrecent developments in plasmon-enhanced fluorescence, under-lining the impact of PEF in stimulating new protocols in the fieldof analytical detection, single molecule detection and imaging,

Ricardo F. Aroca

Dr Ricardo Aroca is ProfessorEmeritus in the Department ofChemistry and Biochemistry atthe University of Windsor, andAdjunct Professor in the Depart-ment of Chemistry, Faculty ofScience, University of Chile. In2003 he was honoured with theGerhard Herzberg Award inrecognition of outstanding achieve-ment in the science of spectroscopy.In 2005 he was elected Fellow of theChemical Institute of Canada.Since 2009, he has also been a

Member Correspondent of the Chilean Academy of Sciences. Hisresearch is on plasmon enhanced spectroscopy.

Review Article Chem Soc Rev

Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM

. View Article Online



diagnostics and nanostructure fabrication. In particular, anattempt is made to correlate the role of different elements in thePEF experiment, such as the external excitation frequency andpolarization, the optical properties of the emitter (extinction coeffi-cient, lifetimes and quantum yield), spatial orientation, and cou-pling to localized surface plasmon resonances (LSPR) and hotspots.

A key point here is that by varying the molecule–nanoparticledistance a continuous transition from fluorescence enhancement tofluorescence quenching is observed.49 Notably, the history of fluores-cence on metal surfaces starts with the distance-dependent decayrate of a fluorophore in front of a mirror that was captured in theelegant work of Drexhage and co-workers50 in the 1960s. A classicaltheory that explains the variation of the lifetime when energytransfer is important is a fundamental reference point in thediscussion of metal-excited molecules.51 There are many specificstudies of the energy transfer from excited molecules to metal anddielectric surfaces, with the net effect of ‘‘quenching’’ the molecularemission.52,53 A molecule directly attached to the metal surface shallfacilitate the energy transfer and effective quenching, or may form asurface complex, and then a ‘‘new molecule’’ with quite differentelectronic states. This metal–molecule distance dependence is thesignature of electromagnetic origin of the plasmonic component,and has been demonstrated throughout the PEF history by variousgroups. Wokaun et al. (1983)5 studied Basic Fuchsin dye on Agislands, where the dye is separated from the metal surface by a thinlayer of SiOx. When the spacer layer thickness is increased fromd = 0, an increase in the luminescence intensity is observed reachinga maximum luminescence enhancement of 200. Aroca et al. (1988)54

controlled the radiantionless energy transfer from the excitedphthalocyanine monolayer to the nearby silver island film surfaceby using Langmuir–Blodgett (LB) spacer layers of non-fluorescentarachidic acid. The maximum enhancement obtained with spacerlayers of arachidic acid was approximately 400. Anger et al. (2006)49

discussed the enhancement and quenching in single-moleculefluorescence, demonstrating the continuous transition from fluores-cence enhancement to fluorescence quenching of a single moleculeon a gold nanoparticle. The gold particle diameter was 80 nm andthe optimal distance dependence for maximum enhancement was5 nm. In addition to specific studies of PEF distance dependence,the conditions that determine the rate of energy transfer from a dyeto a nanoparticle are also studied as part of the general problemof excitation energy transfer, as found, for example, in the workof Saini et al.55 Distance dependence studies (Geddes, 2012) inmetal-enhanced fluorescence56 are reported to be in close agree-ment with the theoretical distance-dependent decay of the localelectric field intensity of excited nanoparticles. These findingshave been extended to other emitters,23 and will be revisited inthe section of PEF mechanism.

2. Mechanism of plasmon-enhancedfluorescence2.1 The fluorescence spectrum

The most common fluorophores are organic dye molecules,characterized by aromatic rings or conjugated carbon chains.

The singlet and triplet electronic states are split into vibrationaland rotational sub-levels represented in the Jablonski diagramshown in Fig. 1. ‘‘Fluorescence emission generally results froma thermally equilibrated excited state, that is, the lowest energyvibrational state of S1’’.13 The largest cross section correspondsto the process of optical absorption, which is also very fast(in the femtosecond regime). The emission from an isolatedfluorophore is characterized in terms of two observables: thequantum yield (Q0) and the lifetime (t). Substances with thelargest quantum yields, approaching unity, such as rhodamines,display the brightest emissions. These optical quantities aredefined in terms of the radiative decay rate (kr) and the non-

radiative decay rate (knr), and Q0 ¼kr

kr þ knr. For simplicity, the

non-radiative rate knr ¼P

kd includes all processes that leadto non-radiative decay to the electronic ground state.13 The

measured lifetime is simply given by t ¼ 1

kr þ knr. The relaxa-

tion pathway (within picoseconds) involves internal conversionfrom higher vibrational states to the lowest vibrational levelof the first excited singlet state. This is followed by radiativedecay (nanoseconds) with the emission of a light which is themirror image of S0 to S1 absorption, not of the total absorptionspectrum. Since relaxation is rapid, emission spectra are usuallyindependent of the excitation frequency. Experimentally, fordilute solutions, when Beer’s law applies, the measured absor-bance is A = ebc = log P0 � log P, where e is the molar absorptioncoefficient (M�1 cm�1) of the analyte, b is the optical pathlength of the sample, c is the concentration of the analyte, andP0 is the excitation power (photons s�1). The correspondingmeasured fluorescence signal F (in photons s�1) for a givenanalyte concentration is F = QP0(1 � 10�ebc) E QP0ebc, and thefluorescence will increase linearly with the intensity of theexcitation power and concentration, before saturation. In short,for a given analyte the product P0eQ determines the sensitivityof fluorimetry. The absorption cross section is s(m2) = 3.825 �10�24e. Notice that the concrete measurement of intensitywill also depend on the collection efficiency of the opticalinstrumentation. Since light absorbance is measured as thedifference in intensity, fluorescence is more sensitive becausethe intensity is measured directly, without comparison with areference beam, and has permitted single-molecule detectionand imaging.58 Fluorescence-lifetime imaging microscopy(FLIM) provides measurements that are independent of

Fig. 1 Jablonski diagram showing the electronic and vibrational energylevels of an organic dye molecule. Reproduced with permission.57 Copy-right 2005, Nature Publishing Group.

Chem Soc Rev Review Article

Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM




fluorophore concentration, a feature that expands the realm ofapplications.

To detect non-fluorescent molecules, fluorescent tags areused with numerous applications in sensing, in particular DNAtechnology (such as DNA sequencing/hybridization).59 Thenumber of these reports continues to grow exponentially.Epifluorescence microscopy is one of the most widely usedtools in the biological sciences, and there has been a rapidgrowth in the use of microscopy due to advances in severaltechnologies, including confocal optics to provide confocallaser scanning microscopy (CLSM). There are also astonishingdevelopments in ‘super-resolution’ far-field optical microscopy(nanoscopy) techniques addressing the problem of the limitedspatial resolution of far-field optical microscopy,60 such asstimulated emission depletion (STED), ground state depletion(GSD), reversible saturated optical (fluorescence) transitions(RESOLFT), photoactivation localization microscopy (PALM),stochastic optical reconstruction microscopy (STORM), struc-tured illumination microscopy (SIM) or saturated structuredillumination microscopy (SSIM).

2.2 PEF enhancement contributions

The cartoon shown in Fig. 2 is an attempt to provide asimplified picture of PEF. P0 is the excitation power to beabsorbed by both the fluorophore and the nanoparticle leadingto an excited electronic state of the molecule and a LSPR in thenanostructure. The molecule is far enough from the metalsurface to avoid energy damping (quenching) of the exitedstate. Therefore, it can be assumed that the nonradiative decayrate (knr) is not strongly affected by the presence of the metalnanostructure. LSPRs are collective oscillations of conductionband electrons that generate intense electromagnetic local fieldsin their vicinity with exponential spatial variation on the nano-meter scale, and their coupling to the emitter could improve theabsorption and emission quantum efficiency.10,13,61 The surface

average of the near field intensity enhancement, Ej j ¼ Elocj jE0j j

, can

be easily calculated,62 leading to a new excitation power in theregion of the local field: h|E|2i�P0. Furthermore, the local fieldof the nanostructure may increase the radiative decay rate (kr)of the fluorophore.13 All experimental results have shown

consistently that enhanced intensities go together with adecrease in the lifetime t = (kr + knr)

�1 for fluorophores locatedin the near field of the nanostructure.2 The latter could lead to anew value for the quantum yield, Qloc, and the fluorophoreenhanced emission would be proportional to Fenhanced E(h|E|2i�P0)eQloc. In addition, there is the power radiated by theinduced dipole in the nanoparticle.61 In the simple case of asphere of radius a, the applied field induces a dipole moment

inside the sphere proportional to E0. p ¼ e0em4pa3e� emeþ 2em

E0,

where e, em, and e0 are the dielectric function of the metal,medium and vacuum respectively.10 The resonant enhancementtakes place under the condition that |e + 2em| is a minimum.

Therefore, to understand the sources of the enhanced fluores-cence intensity recorded in the far field it is important to keep inmind that single frequency excitation of metal nanoparticlesleads to the observation of elastic light scattering. After couplingfrequencies from emitters, this elastic scattering by plasmons isthe source of the electromagnetic enhancement contributionas was defined for SERS by Moskovits:12 ‘‘. . .The enhancedre-radiated dipolar fields excite the adsorbate, and, if theresulting molecular radiation remains at or near resonancewith the enhancing object, the scattered radiation will again beenhanced (hence the most intense SERS is really frequency-shifted elastic scattering by the metal). Under appropriatecircumstances the field enhancement will scale as E4, where Eis the local optical field.’’ Plasmon-enhanced fluorescence canonly benefit from the local field enhancement of the incidentfield and the field enhancement will scale as E2.63 Therefore,the plasmonic nanoparticle serves as a transmitting opticalantenna to transfer the near field to the far field at the fluores-cence frequency. Since nanostructures are powerful scatterers,under appropriate conditions, the re-radiation by the plasmonicstructure is the central component of the observed PEF. Itshould be pointed out that the scattering profile is specificfor each metal nanoparticle and is a sensitive function (thePurcell effect) of the environment, as can be seen in Fig. 3

Fig. 2 Cartoon of simplified plasmon enhanced fluorescence.Fig. 3 Extinction spectra of periodic particle arrays in different solvents.Reproduced with permission.64 Copyright 1999, American Chemical Society.


Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM




for silver nanoparticles in different solvents, i.e. changesin plasmon location with the dielectric constant of theenvironment.64 In fact, the dependence of LSPR wavelengthon the refractive index (nm) of the medium is approximatelylinear at optical frequencies:65 lLSPR = lp(2nm

2 + 1), where lp isthe wavelength corresponding to the plasma frequency of thebulk metal.

In addition, the scattering profile depends on the nano-particle size and shape.10 The scattering profile plays a centralrole when tuning PEF for maximum enhancement and this is acommon factor in the PEF reports. We illustrate the idea with afew examples. Work from Halas’ group:66 ‘‘Both experimentalobservations and theoretical analysis involving nanoparticlesof different plasmon resonance energies and scattering proper-ties show that fluorescence enhancement is optimizedby increasing particle scattering efficiency while tuning theplasmon resonance to the emission wavelength of the fluoro-phore’’. Work from Gedddes’ group:67 ‘‘The findings stronglysuggest that surface plasmons can radiate a fluorophore’svibrational structure’’. From the report of Ginger et al.:68

‘‘We use single-particle dark-field scattering and fluorescencemicroscopy to correlate the fluorescence intensity of the dyeswith the localized surface plasmon resonance (LSPR) spectra ofthe individual metal nanoparticles to which they are attached.For each of three different dyes, we observe a strong correlationbetween the fluorescence intensity of the dye and the degree ofspectral overlap with the plasmon resonance of the nanoparti-cle’’. From Lakowicz’s group:69 ‘‘It suggests that the opticalabsorption and scattering properties of metallic nanostructurescan be used to control the radiative decay rate and direction offluorophore emission’’. Clearly, the reradiation rate of theplasmonic nanostructure is determined by the absorptionand scattering cross sections at the emission wavelength.Under resonance conditions, LSPRs lead to light scattering thatcan be several orders of magnitude more intense than thefluorescence from efficient quantum emitters. The reradiationor elastic scattering contribution to the enhanced fluorescenceis also experimentally observed in what has been termedspectral profile modification70 or SPM. It is the modulation ofthe shape of the fluorescence spectrum by the scattering profileof the nanostructure due to reradiation.71 Although dissectingthe observed enhanced intensity into its components is not aneasy task, the basic elements are enhanced absorption,enhanced radiative decay (decrease in lifetimes and increase inquantum yield), and elastic scattering by the metal of emitter’sfrequencies.

The role of the quantum yield of the isolated molecule hasbeen investigated in many instances, and there is evidencethat fluorophores with lower Q stand to benefit the mostfrom the enhancement.72 However, a review of the literature onthe reported PEF enhancement factors does not support thegeneralization of this trend. To illustrate the point, in Table 1,we select and reproduce data from Gartia et al.73 for PEFenhancement factors of a series of molecules with differentQ values. In fact, a review of the reported experimentallydetermined PEF EFs indicates that high Q of fluorophores

is not a deterrent to achieve emission enhancements, andone should look at other factors, such as nanostructure sizeand shape, hotspot formation by aggregation or other means,fluorophore orientation and light polarization, to tune theintensity enhancement.

2.3 PEF and the hotspots

PEF average enhancement factors for a given PEF substrate arecommonly in the order of magnitude shown in Table 1, ten to afew hundred fold. However, there is a unique class of nano-structures capable of producing super-hot local electric fieldsites or hotspots.74,75 These super-enhancing locations havebeen probed,76 and can be engineered in small nanoparticledimers and aggregates. Given the electromagnetic nature ofPEF, the highest enhancement factors have been achieved onhotspots. Using gold bowties in 2009, with excitation at 780 nm,an enhancement factor of 1340 for single molecule’s fluorescencewas reported for near-infrared dye N,N0-bis(2,6-diisopropyl-phenyl)-1,6,11,16-tetra-[4-(1,1,3,3-tetramethylbutyl)phenoxy]-quaterrylene-3,4:13,14-bis(dicarboximide) (TPQDI).77 Theauthors estimate an enhanced quantum efficiency of about 9,that multiplied by the field enhancement factor (B181) shouldaccount for the observed EF of 1340. Gill and Le Ru in 2011reported the enhancement of the fluorescence emitted fromdye-labeled DNA using Ag nanoparticle aggregates excited at532 nm.72 They observed a maximum average SEF enhance-ment factor of 740 for Atto 540Q-labeled DNA, a fluorophorewith a low quantum yield; Q = 1.6 � 10�3. The highest PEF EFreported for single molecule fluorescence was achieved whenthe fluorophore is placed in one of the many ‘‘hot spots’’engineered in a three-dimensional plasmonic nano-antenna-dots array [Disk-coupled dots-on-pillar antenna array (D2PA)];the fluorescence is enhanced by a staggering 4 � 106-fold, withexcitation at 785 nm.78

Scanning electron micrograph (SEM) of the nano-antenna-dots array used in this work is shown in Fig. 4,78 where the goldnanodots rested on the silica nanopillar sidewalls are clearlyseen. The total spacer thickness separating the fluorophorefrom the metal was 6.5 nm. The measured average fluorescenceenhancement for integrated fluorescence intensities was 7220-fold. Notably, the average fluorescence enhanced spectrum hasa much broader full-width at half-maximum (FWHM) than thefluorescence spectrum, which is consistent with the plasmonicresonance spectrum. The FWHM of the IRDye800CW fluores-cence is ca. 30 nm, while the FWHM of the plasmonic nano-structure is about 165 nm. The same nano-antenna-dots arrayD2PA was used to test the PEF of two infrared molecular dyes,

Table 1 Lifetimes, quantum yields and PEF enhancement factors73

Fluorophore t (ns) Q tmod (ns) Qmod EF

R6G 4.11 0.90 0.219 0.992 20.5Fluorescein 4.38 0.95 0.182 0.991 100Acridine orange 2.04 0.29 0.443 0.753 8.34Rhodamine-B 1.67 0.41 0.104 0.857 5.13Eosin-Y 1.31 0.32 0.277 0.845 4.3


Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM




indocyanine green (ICG) and IR800 (dimethyl f4-[1,5,5-tris(4-dimethylaminophenyl)-2,4-pentadienylidene]-2,5-cyclohexadien-1-ylideneg ammonium perchlorate).79 The SiO2 spacer thicknesswas optimum at 5 nm. The new nanoplasmonic structure, D2PA,provides a large average fluorescence integrated enhancement,of 2360 for the ICG dye molecule and 4.5 � 106 fold for thesingle molecule placed at a hotspot. The observed fluorescenceenhancement for IR800 is about 600. There is no EF reportedfor single molecule IR800. Again it is found that the observedfluorescence enhanced spectrum has a rather wide bandwidth,a spectral profile modification, which is determined by theplasmon resonance spectrum of D2PA. For work in solution, amaximum enhancement of 2530-fold for IRDye 800CW labeledstreptavidin (SAv-800CW) on citrate-stabilized Ag nanoparticleshas been reported.80 Here, the labelled carrier protein at acertain pH will interact with negatively charged Ag colloidsto form dimers, trimers, and other low order Ag aggregatescreating hotspots. The reported PEF EF value represents ensem-ble enhancement as opposed to the enhancement of individualfluorophores.

A very interesting result was attained using chemically synthe-sized single gold nanorods, where large enhancements of single-molecule fluorescence, up to 1100 times, were reported.27 Heresuch high enhancement was achieved by selecting a dye withsignificant overlap with the surface plasmon of nanorods, andexcitation at 633 nm. A follow-up detailed study was publishedrecently81 using super-resolution localization and defocusedfluorescence microscopy on resonantly coupled single-molecule,single-nanorod hybrids. The findings of this work help in theunderstanding of the PEF mechanism: ‘‘defocused microscopy onchemically labelled molecule–antenna hybrids unravelled thedominating role of the nanorod antenna in the coupled molecularemission to the optical far field. Such observations emphasizethe nanorods dual roles to enhance fluorescence signals and todominate the fluorescence emission at the far field via efficientcoupling. Our results emphasize the role of plasmonic nanostruc-tures as optical antennas in the plasmon-enhanced microscopy ona resonantly coupled optical system. The antenna effects have tobe considered in optical and spectroscopic studies of interactionsbetween molecules and metallic nanostructures, particularly insuper-resolution studies’’. Notably, the high EF is observed on anindividual nanoparticle, and the enhancement is shown to dependon molecular orientation with regard to the nanorod axis. Suchobservations highlight the fact that, via efficient coupling, thenanoparticle not only enhances fluorescence signals but alsocontrols the fluorescence emission at the far field.

3. Substrate fabrication for plasmon-enhanced fluorescence3.1 The development of substrate preparations

Motivated by the discovery of the surface-enhanced Ramanscattering (SERS) phenomenon of pyridine on a roughened Agelectrode surface,7,9 Ritchie and co-workers observed for thefirst time the fluorescence of fluorescein isothiocyanate (FITC)and rhodamine 6G (R6G) adsorbed on roughened silver islandfilms (SIFs). Previously, the luminescence of these moleculeshad been undetectable on a smooth Ag film.3,82 Later, Glassand coworkers systematically studied the relationship betweenfluorescence intensity and the degree of overlap in the absorp-tion spectrum of dye and Ag particle film.1 The authors foundemission intensity to be strongest when the plasmon resonanceof the Ag particle film overlaps with the absorption peak ofthe dye.

To explore the effect of metal surfaces on fluorophores,Barnes examined various local densities of state, which inducedvariation in the spontaneous emission rate of the fluorophoreas the emitter approached the planar metal surface.83 Alongwith developments in nanoparticle synthesis, noble metalnanoparticles with different morphologies have been designedand used as flexible substrates in plasmon-enhancedspectroscopy.84–89 To further utilize the strong electromagneticfield in wet chemically synthesized colloidal metal aggregation,Cotton and co-workers modified metal colloids on glass slidesto produce colloidal metal films (CMFs). This type of substrateexhibits a strong fluorescence enhancement with a fluorescein-labelled phospholipid.90 In 2004, Geddes and co-workers developedcore–shell nanoparticles for surface-enhanced fluorescenceexperiments, in which, they encapsulated a silver sphere in asilica shell attached to Cy3-labeled streptavidin.53 Three yearslater, the Halas group used Au shell–silica core nanoparticlesto enhance near-IR-emitting fluorophores.66 To prepare theperiodic nanoparticle array on a fixed substrate for PEF, theMoerner group adopted the micro/nano-fabrication method.Using elaborate ‘‘top-down’’ preparation techniques, they obtainedthe gold nanobowtie, nanorod, and gap-antenna-inside nano-aperture with finely controlled gap sizes to achieve a highenhancement in single-molecule detection.77,91–93 One yearafter the invention of the SHINERS method, the Aroca groupintroduced the shell-isolated mode for plasmon-enhancedfluorescence, in which the isolated-nanoparticle consists of ametal core and a compact dielectric shell.22,94 In 2014, theHalas group synthesized a gold nanomatryoshka to utilize thenear-field Fano property for emission enhancement. This nano-matryoshka consists of an Au core and a thin silica shell.Subsequently, the authors capped an outer Au shell and dopedthe silica shell with dyes.95

3.2 Synthesis and characterization of substrates in PEF

To describe the synthesis and characterization of the substratesin PEF in detail, in the subsections below we introducesubstrates including metal films with roughened surfacemorphologies, a periodic nanoparticle array prepared using

Fig. 4 SEM images of nano-antenna-dots array. Reproduced withpermission.78 Copyright 2012, American Chemical Society.


Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM




the micro/nano-fabrication method, and wet chemically synthe-sized nanoparticles with different morphologies.

3.2.1 Metal films with roughened surface morphologiesRoughened metal island films (SIFs). In their pioneering work,

Ritchie and coworkers prepared Ag island films with nanometerscale roughness by the deposition of Ag on glass slides in vacuumconditions.82,96 Following the work of Lackowicz, to prepare Agisland films, silver nitrate solution (in which a glass slide isimmersed) is mixed with 5% NaOH solution to form a precipitate.Then, ammonium hydroxide is dropped slowly to redissolve theprecipitate. After submersion in an ice bath, D-glucose is addedand the mixture is warmed to 30 1C. Upon completion of theseprocesses, the glass slide is removed and washed with H2O, readyfor the experiments.97,98 Fig. 5a shows an atomic force microscope(AFM) image of the SIFs on quartz.

Colloid coated substrates (CMFs). First, a glass slide is silanizedwith (3-mercaptopropyl)trimethoxysilane (MPS) in 2-propanol.After silanization, the glass slide is immersed in an Ag sol,prepared using the Lee–Meisel method,99 in which sodium citratesolution is added to a strongly stirred boiling AgNO3 solution, andthen stirred for B1 h. Fig. 5b and c show a scanning electronmicroscope (SEM) image and the extinction spectra of Ag colloidcoated substrates, respectively.

3.2.2 Periodic nanoparticle array prepared with the micro/nano-fabrication method. Periodic Au nanoparticle arrays onfixed substrates can be obtained using micro/nano-fabricationtechniques.77,92,93 The Moerner group prepared gold bowtienanoantennas by electro-beam lithography onto a ITO-covered

glass slide, as shown in Fig. 6a. First, a 50 nm-thick ITO layer iscoated on a quartz slide, and then a 50 nm-thick PMMA layer isspun on the slide. Subsequently, a standard E-beam exposureand a further treatment in 1 : 3 MIBK : IPA is carried out toobtain the bowtie shaped holes. A 2 nm-thick Ti along with a20 nm-thick Au layer is then deposited. In the lift-off step, thissubstrate is subjected to sonication in acetone to form thebowtie gold arrays. This substrate can be used for PEF in thenear-IR regime, due to the scattering band appearing around800 nm.77 In addition, gold nanorod (NR) arrays of different rodlengths can also be fabricated via negative-tone electron-beamlithography.92 For a novel ‘antenna-in-box’ plasmonic platform,a nanoantenna can be milled by the focused ion beam (FIB)method in a 50 nm-thick Au film (gold film can be obtainedthrough thermal evaporation) on a glass slide (as shown inFig. 6b). The gap size can be changed from 12 to 40 nm.93

3.2.3 Wet chemically synthesized nanoparticles withdifferent morphologies

Bare metal nanospheres. Gold nanospheres are commonlysynthesized using the Frens’ method, in which an amount offresh sodium citrate is added into a boiling HAuCl4 solution.Different concentration ratios of the gold precursor and citratereducing agent will yield different nanoparticle sizes. Typically,mono-dispersed nanospheres can be obtained with diameterssmaller than B50 nm, as shown in Fig. 7a.100 For a largerdiameter, a seed-mediated growth method is necessary.86 Toobtain silver nanospheres, a similar citrate reduction methoddeveloped by Lee and Meisel can be used.99 However, we notethat the dispersion of the morphology of Ag nanoparticles isrelatively poor in the absence of a strong capping agent, ascompared to that of Au nanoparticles.

Nanorods. Nanorods are mesmerizing in PEF due to theirtunable scattering band with different aspect ratios.27,92 Inthe wet chemical synthesis method, gold nanorods can beprepared using the seed-mediated growth method pioneeredby the Murphy group and the El-Sayed group.87,88 Typically, agold seed sol is obtained by reducing HAuCl4 with an ice-madeNaBH4 solution, in which the surfactant trimethylammoniumbromide (CTAB) has been introduced as a capping agent. Next, agrowth solution is used, consisting of small amounts of AgNO3,CTAB, and gold precursor. Before the addition of gold seeds,an ascorbic acid reducing agent is used to obtain intermediate

Fig. 5 (a) AFM image of SIFs on quartz. Reproduced with permission.98

Copyright 2002, Elsevier. (b and c) SEM image of the Ag colloid coatedsubstrate and the corresponding extinction spectra, respectively,when immersed in (i) benzene; (ii) hexane; (iii) 2-propanol (dotted line);(iv) water; (v) air. Reproduced with permission.90 Copyright 1995, AmericanChemical Society.

Fig. 6 SEM images of (a) gold bowtie nanoantennas on ITO slide and(b) ‘antenna-in-box’ nanoaperture. Panel (a) is reproduced with permission.77

Copyright 2009, Nature Publishing Group. Panel (b) is reproduced withpermission.93 Copyright 2012, Nature Publishing Group.

Fig. 7 SEM images of (a) Au nanospheres, (b) nanorods, (c) nanocubes,and (d) Ag nanocubes. Panel (a) is reproduced with permission.104

Copyright 2008, Wiley. Panel (b) is reproduced with permission.87

Copyright 2003, American Chemical Society. Panel (c) is reproduced withpermission.89 Copyright 2002, American Chemical Society. Panel (d) isreproduced with permission.101 Copyright 2002, American Association forthe Advancement of Science.


Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM




Au+ species. With the addition of seeds, the mixture solutiongradually changes from colourless to brownish, which indicatesthe growth of Au nanoparticles. Fig. 7b shows an SEM image ofAu nanorods.

Nanocubes. Au nanocubes with a high yield were obtained bythe Murphy group.89 Initially, gold seeds are synthesized by thereduction of HAuCl4 with NaBH4 solution. Then, an amount ofHAuCl4 is reduced by ascorbic acid to serve as the growth solution.With the addition of seeds, the gold nanocrystal begins to evolve intonanocubes in the presence of CTAB, which is introduced as thesurface capping agent to protect the Au(100) surface during thegrowth. For Ag nanocubes, silver nitrate is reduced by ethylene glycoland heated to 160 1C in the presence of poly(vinylpyrrolidone)(PVP).101 Here PVP can selectively protect the Ag(100) facetand the final morphology can be controlled by the ratio ofthe amounts of Ag precursor and PVP. Fig. 7c and d show SEMimages of as-prepared Au and Ag cubes, respectively.

Dielectric shell–metal core nanoparticles by the Stober method.To prepare dielectric shell-coated nanoparticles, the metal core canbe synthesized via a reducing Ag+ precursor with NaBH4 or sodiumcitrate. Then, the silane agent 3-aminopropyltrimethoxysilane(APS) is used to functionalize the Ag surface with siloxy groups.Subsequently, a sodium silicate solution is added for silicadeposition.85,102 Several days later, a silica shell with a controllablethickness is obtained. It should be noted that the silica shellobtained using the Stober method is porous and the ions candiffuse toward the metal core. Fig. 4a shows an SEM image ofAg@SiO2 nanoparticles. This silica shell coating method can alsobe carried out using ethanol rather than an aqueous solution,whereby the silicate solution is replaced with tetraethylorthosilicate(TEOS) solution, and amounts of NH4OH and water are used toadjust the hydrolysis rate.53

Metal shell–silica core nanoparticles (including the nanomatryoshka).To prepare metal shell–silica core nanoparticles, a silica nanoparticleis synthesized according to the Strober method. The silane agent3-aminopropyltriethoxysilane (APTES) is introduced to functionalizethe Ag surface with amino groups. Then, a suspension of very smallgold sol (diameter is B2 nm) is added. As a result, the small goldnanoparticles are covalently attached onto the silica core surface.Because the formation of the gold-nanoparticle shell is notcontinued in this step, a subsequent gold deposition is required.Hence, a mixture of HAuCl4 and K2CO3 solution is added withNaBH4 solution for the formation of a uniform gold shell. Fig. 8band c show SEM images of the gold nanoshell obtained initially andafter the shell growth is complete. With this gold nanoshell, theSPR absorption peak can be tuned to wavelengths of more than800 nm.66,103 Based on this, a fluorescent nanoparticle known asthe nanomatryoshka was developed. First, gold nanosphereswith a diameter of B40 nm are coated with silica shells ofB16 nm thickness via the Stober method. Next, the small goldnanoparticles (B2 nm) are sprinkled onto the silica shell surfacewhile dyes are doped simultaneously. Finally, the gold shell iscompleted with subsequent Au atom deposition. Fig. 8d showsan SEM image of the as-prepared nanomatryoshka.

3.2.4 Shell-isolated nanoparticles. In contrast to the morecommon Stober method, the method used to prepare compactand ultra-thin dielectric shells is known as the shell-isolatednanoparticle-enhanced Raman scattering (SHINERS) method,which was developed in 2010.38,94,105–108 For shell-isolated goldnanoparticles, the gold core is synthesized via the Frens’ method, inwhich HAuCl4 is reduced by sodium citrate. The ratio between theamounts of HAuCl4 and citrate can be tuned to obtain Au NPs withdifferent sizes. In the coating procedure with the SHINERS method,the Au NPs are modified with siloxy groups with APTES solution atroom temperature. Next, sodium silicate solution is introduced asthe silica precursor rather than TEOS. AfterB5 min stirring, the goldsol is heated in a 90 1C water bath for different time periods to yielddifferent silica shell thicknesses. Typically, a 30 min heating time willresult in a B2 nm silica shell. A longer reaction time yields a thickershell. After the silica shell growth, the gold sol is centrifuged twicewith ultrapure water and condensed in a tube. The condensedAu SHINs can be dispersed with water again and then spread as‘‘smart dusts’’ to assemble on the substrate for the followingSHINEF experiments. The schematic diagram of the synthesis ofAu SHINs and their application in SHINEF is revealed in Fig. 9.

Fig. 8 SEM images of (a) Ag@SiO2 prepared by the Stober method; (b) Aunanoshell initially obtained; (c) Au nanoshell obtained after shell growth iscomplete; (d) Au nanomatryoshka; (e) to (h) shell-isolated Au nanosphere,Au nanocube, Au nanorod, and Ag nanosphere, respectively. Panel (a) isreproduced with permission.85 Copyright 1998, American Chemical Society.Panels (b and c) are reproduced with permission.103 Copyright 1998, Elsevier.Panel (d) is reproduced with permission.95 Copyright 2014, American ChemicalSociety. Panel (e) is reproduced with permission.94 Copyright 2010, NaturePublishing Group. Panels (f and g) are reproduced with permission.105

Copyright 2013, Nature Publishing Group. Panel (h) is reproduced withpermission.38 Copyright 2015, American Chemical Society.

Fig. 9 The schematic diagram of the synthesis of Au SHINs and theapplication in SHINEF.


Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM




Concurrently, to tune the plasmon resonance band in a widervisible range, the core morphology can be changed from nano-sphere to nanocube or nanorod, and the material can bereplaced with silver, as shown in Fig. 8e–h.

4. Advanced applications of PEF

Although fluorescence spectroscopy is widely used in biologicalanalysis, the scope of its application has suffered due to theenergy quenching effect at the interface. With optimized nano-structures, the photostability, emission intensity, and radiativedecay rate are all significantly enhanced. Plasmon-mediatedfluorescence can facilitate spectroscopic analysis even down tothe single-molecule level, and exhibits excellent capabilities inmaterial characterization and active site analysis of catalysts,and in the investigation of kinetics of DNA hybridization.

4.1 Single molecule detection (SMD)

Mechanistic investigation is important for exploring andclarifying chemical reactions, single molecular behavioursand micro-environments. In addition, the materials used inthe study of bio-chemistry and genetics are at the nano-level,and the number of active sites available for catalysis is less than1% of those in bulk catalysts. As such, it is critical to developreliable single-molecule detection methods for these ultra-sensitive analyses.

Since the first report on SMD from the Moerner group in the1980s, plasmon resonance has been a matter of great interest withrespect to SMD due to its ability to confine the optic field.109–111 Inthe work by the W. E. Moerner group, the authors utilizedelectron-beam lithography to fabricate bowtie nanoantennas ona 50 nm-thick ITO-coated quartz as the substrate for plasmon-enhanced SMD.77 Fig. 10a shows schematic diagram, corres-ponding SEM image, and electromagnetic field simulation ofaspects of the gold bowtie. In the hotspot located at the bowtiegap, the electric field enhancement is more than 100-fold(as shown in Fig. 10b). Fig. 10c shows a confocal image of a16 bowtie array, in which each bright spot represents an

enhanced single molecule (SM) around the bowties. Fig. 10dshows the corresponding SM fluorescence intensity time trace,which reveals a characteristic single-step photo-bleaching property.With the greatly enhanced excitation efficiency, the authorsobtained a maximum enhancement factor of 1340-fold for a singlemolecule, which was in good agreement with the simulationresult. In the simulations, optimum PEF enhancement occurs atthe center of the bowtie nanogap, and the intensity decreasesgradually when approaching the triangle tip due to the largeenergy loss in the metal. Because strongly emitting fluorophoreswere observed only at the nanogap, this provided a potential wayfor developing a high-contrast fluorescence imaging method. Inaddition, the fluorescence decay lifetime was determined usinga time-correlated single photon counting (TCSPC) analyzer, andthe spontaneous emission rate was enhanced 428-fold. Thissubstrate provides a platform for a potentially high emission-rate, single-photon source in ambient conditions, and it shedslight on the effort to balance enhancement and energy loss inplasmonic materials.

Usually, an ultra-low analyte concentration down to the nano-mole level is necessary to perform SMD experiments. However,this condition is difficult to achieve in practice. The Michel Orritgroup reported a plasmon-enhanced single-molecule fluores-cence enhancement of up to 1100-fold.27 This PEF substrateshows excellent ability to enhance the emission process offluorophores that initially exhibit weak emission. In this simpleSMD experiment, they synthesized gold nanorods by a seed-mediated growth method and then coated them onto glass.Using a CCD imaging and time tracing strategy, they deter-mined the counts per molecule to be about 2–3, and were able togain a large enhancement of the single molecule. Specifically,rather than 1 nM, they used 100 nM CV molecules to successfullyperform the SM experiments. We note that, in this work, theconcentration of the CV molecules was higher than the concen-tration required to keep only one molecule in the focal range, butthe higher molecule concentration is more valuable in practicalanalysis, in which the concentration cannot be arbitrarilyreduced (Fig. 11).

To explore SMD with high-spatial resolution, Cang et al.76

have used the technique of single-molecule super-resolutionoptical fluorescence microscopy and reported the first directmeasurement of single hotspots as small as 15 nm with anaccuracy down to 1.2 nm. In the field of catalysis, Peng Chenand coworkers employed a series of Au rod@mSiO2 and monitored

Fig. 10 (a) Schematic diagram of the gold bowtie substrate covered withfluorophores. (b) Simulation of electric field around a single bowtie.(c) Fluorescence confocal imaging of a gold bowtie array coated withfluorophores. (d) Fluorescence intensity time trace of the single bowtie in(c). Reproduced with permission.77 Copyright 2009, Nature PublishingGroup.

Fig. 11 (a) SEM image of gold nanorods. (b) Simulation of near fieldaround a single nanorod. (c) Fluorescence imaging of SMD enhanced bynanorods. Reproduced with permission.27 Copyright 2013, Wiley.


Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM




active catalysis sites in situ in individual nanoparticles.112 Theyspread the Au@mSiO2 on the surface of a quartz slide, placed itin a microfluidic reactor cell, and flowed the reactant solutionthrough the cell, where the reaction of oxidative deacetylationof the Amplex Red (S molecule) to resorufin (P molecule) takesplace. They found that when a P molecule is observed, intensitybursts appear in the time trajectory spectrum. The location ofa single molecule can also be examined over a few pixels as apoint spread function (PSF). With the electron-multiplyingcharge-coupled image method, the authors identified differentcatalytic activities at sub-particle resolution. They also used thisconcept to consider the mechanism of the Au rods’ growth.They verified the reaction properties of the sites on the same facet,and found the reactivity to decrease gradually from the centreto the two ends of the nanorod. Hence, this single-moleculeand super-resolution catalysis imaging strategy provides greaterinsight into nanoscale catalysis (Fig. 12).

Joseph R. Lakowicz and coworkers used Cy5-labeled oligo-nucleotides to study single molecule behaviors.113 They utilizedsilver island films (SIFs) to enhance the fluorescence of Cy5molecules that had been tagged on their double-stranded DNAand the ds-DNA acted as a spacer to maintain a certain distancebetween Cy5 and SIFs. They immersed the SIFs into solutionsof ds-DNA, and then performed their experiment using a time-resolved confocal microscope. With fluorescence images andtime traces of the molecular blinking behaviors, they confirmedthat they had obtained single molecule fluorescence and theSIFs showed greater intensities than the electromagneticallyinert glass substrate. Hence, they demonstrated that the energytransfer process from a single molecule to the metal surface canbe investigated at the molecular scale.

To date, researchers have achieved high intensity enhance-ment and determined the possible mechanism of the chemicalaction and single molecular behavior. Future work should addressthe relevant mechanisms associated with these processes and thedesign of universal spectator fluorophores for application in manydifferent physical processes and reactions.

4.2 Detection of DNA with PEF

4.2.1 PEF with DNA origami substrates. Due to the specificityof DNA in hybridization, DNA strands have been introducedas a tool for fabricating PEF architecture, particularly DNA origami.DNA origami is a molecular self-assembly technique for designingand building ultra-fine discrete nano objects with nucleicacids.114,115 When immobilized on a two- or three-dimensional

origami structure, the interaction between plasmonic nano-particles and fluorophores can be manipulated and investi-gated with nanoscale accuracy. In the work of the P. Tinnefeldgroup, the authors used DNA origami to precisely arrangeAu NP dimers with different inter-particle gaps, and thenmanipulated the plasmonic hotspot to improve the plasmon-enhanced fluorescence.116 The length of a pillar-like DNAorigami strand is up to 220 nm and Au NPs were modified onthe origami pillar by hybridization of the DNA strands. Hence,one or two gold nanoparticles can be bound to DNA origamistructures to functionalize a single fluorescence moleculenearby one Au NP or between the NPs. A maximum 117-foldenhancement can be obtained with 100 nm dimers. Moreover,binding or unbinding events on an Au dimer-immobilized DNAorigami structure have been observed in PEF experiments.These cost-effective and versatile self-assembled plasmonicnanoantennas reveal excellent capability in DNA binding assaysand offer a way to conduct SMD experiments in biologicalmicromolar regimes.

4.2.2 Kinetics of DNA hybridization study with PEF. PEFprovides a highly sensitive platform for analyzing DNA hybridiza-tion reactions. Knoll et al.117 used plasmon-enhanced fluorescenceto investigate the kinetic parameters of DNA hybridization andmismatched DNA interactions. As shown in Fig. 14, a monolayer

Fig. 12 (a) Schematic diagram of the probing reaction catalyzed by the silicacoated gold nanorod. (b) TEM image of a single nanorod. (c) Fluorescenceintensity of SMD as a PSF. Reproduced with permission.112 Copyright 2012,Nature Publishing Group.

Fig. 13 (A) Schematic diagram of the Au dimer formed using the DNAorigami technique. The fluorophore is indicated by the red dot located onthe origami pillar between the dimer spheres. (B) Simulations of theelectric field around a single Au NP (left) and an Au NP dimer (right).(C) Simulations of emission intensity enhancement within the NP gap.Reproduced with permission.116 Copyright 2012, American Association forthe Advancement of Science.

Fig. 14 Illustration of the multilayer architecture for the plasmon-enhanced fluorescence detection of hybridization processes. Reproducedwith permission.117 Copyright 2001, Elsevier.


Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM




of binary thiol is assembled onto an Au substrate, and then amonolayer of streptavidin is introduced. Subsequently, DNA-probe oligonucleotides are coupled to the matrix through abiotin group. To generate a maximum fluorescence signal,additional 15-mer thymines in the DNA-probe oligonucleotideswere used as spacers to ensure an optimum distance betweenfluorophores and the metallic surface. The hybridization of thecomplementary DNA species in solution to these surface-modifiedoligonucleotides couples the emitter into the plasmon mode.High sensitivity is obtained by quantifying the kinetics of thehybridization and the dissociation of diverse oligonucleotides,and then detecting DNA mutations. A similar approach wasapplied to investigate the interactions of DNA–DNA and PNA–DNA by the Knoll group.118 The authors combined fluorescencedetection schemes with plasmon to achieve highly sensitivemonitoring of the hybridization process of fluorophore-labeledoligonucleotides. They found that the kinetic parameters inassociation and dissociation processes, along with the affinityvalues of base-paired hybrids, can be measured.

4.2.3 Probing the hybridization process of DNA with PEF.Specific single-stranded DNA detection by hybridization andthe use of a complementary DNA-probe have been applied inmedical, genetic disorder diagnosis, and forensic tests. Recentmetal nanotechnology has paved a new avenue in DNA detec-tion. Ag NPs and Au NPs have the unique ability to amplifyRaman scattering and fluorescence signals via surface enhance-ment effects. Miller et al.119,120 used Ag NPs as a platform toremarkably amplify the signal for label-free fluorescence-basedDNA detection. The use of nanostructured Ag substrates achieveda large (B10-fold) enhancement in the fluorescence signal uponplanar gold NP substrates for equivalent amounts of the analyte.In a related study, Tang Liang et al.120 developed an innovativegold nanorod (GNR) array biochip to systematically investigatelocalized surface plasmon resonance coupled fluorescence forsignal amplification in molecular beacon detection. As shownin Fig. 15, the authors fabricated a plasmonic substrate by anordered GNR assembly in a vertical standing array on a glasssurface, and the exposed tips in the nanoarray collectively amplifiedthe SPR signals of neighboring particles. A fluorophore-labeledhairpin probe was then attached to the GNR. Without the presenceof the target DNA, the hairpin probe is in close contact with themetal surfaces, which results in a fluorescence-quenched stateby a dominant Forster resonance energy transfer (FRET) effect.The introduction of analyte DNA results in hybridization withthe probe DNA and then the simultaneous unfolding of the DNAhairpin. It is found that the release of the attached fluorophorefrom the quenching region restores the emission intensity.Plasmon-mediated fluorescence depends on competition betweenquenching and enhancement by the metal nanostructures.Fluorescence enhancement with the gold nanoarray was reportedto significantly lower the detection limit and result in plasmon-coupled enhancement in signal amplification for ultra-sensitiveDNA analysis. The authors determined the detection limit to be10 pM. These results promise as a new paradigm in the develop-ment of a high-throughput nanobiochip with superb sensitivity forproteomics, genomics, and molecular analysis. Moreover, GNRs

can be synthesized to finely tune the LSPR band from thevisible to the NIR region for sensing and imaging applicationsin this region.

4.3 SHINEF

4.3.1 The principle of SHINEF. As pointed out in theintroduction, by varying the molecule–nanoparticle distance acontinuous transition from fluorescence enhancement tofluorescence quenching can be observed. The requirement ofan optimum molecule–metal separation to achieve enhancedfluorescence is a necessary condition that is realized using asilica layer in the shell-isolated nanoparticle enhanced fluores-cence (SHINEF) approach.22 Remarkably, the control of the shellthickness (discussed in Section 3.2.4), that empowers SHINEF,comes from the invention of shell-isolated nanoparticle enhancedRaman scattering (SHINERS),94 and for a recent review on thissubject see Ding et al.21 Plasmon enhancement has expanded itsversatility with the introduction of shell-isolated nanoparticles,and since SHINERS and SHINEF technologies can be seenas complementary, their combination in a dual mode couldprofit from the advantages of both techniques under similarconditions.121 The SHINEF discussion starts with suitablecharacterization and description of its basic properties. Themost commonly used SHINs are the SiO2 coated nanoparticles(NP) of Au and Ag with the following properties:

(i) The thickness of the SiO2 shell can be controlled with nmprecision,105 according to the application, to achieve efficientprevention of the quenching effect, and enhance the fluores-cence signal.

(ii) The silica shell provides good dispersity of the SHINs inorganic solvents and water for applications in solution.

(iii) The SiO2 shell protects the metal core from chemicalreactivity with the analytes. In addition, it can effectively reducethe potential cytotoxicity of metal nanoparticles for applicationsin living cells.

(iv) The size and the shape of the metal core can also beoptimized for specific applications. The work, so far, hasconcentrated around coated spheres and nanorods, but thedoor is open to a core of different shapes, that could lead tohigher enhancement factors. Given the role of the nanoparticlescattering in the observed SHINEF, and knowing that forspheres of radius r, the scattering scales with r6, which growsvery fast with increasing particle size, larger nanoparticleswould produce higher enhancement. The caveat is that the size

Fig. 15 Application of the ordered-GNR-array chip in probing DNAhybridization with PEF. Reproduced with permission.120 Copyright 2017,American Chemical Society.


Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM




is limited by the quality of the dipole emission, and SHINEFefficiency increases with increasing core size to a point, afterwhich the EF decreases. The size effect has been experimentallydemonstrated for both SHINERS122 and SHINEF.123 Notably,the absorption cross-section varies as r3, and consequently,absorption is more important than scattering for smallernanoparticles.

(v) SHIN nanoparticles can be tuned to ensure ideal dimen-sions for practical applications. In this respect the use of SHINsof different shapes and shell thickness can help to produceSHINEF in specific spectral regions, or target specific analytesin the visible or near infrared spectrum.

(vi) The SiO2 can be doped with a target fluorophore, as hasbeen done with Oregon Green488 isothiocyanate (OG-488),124 tofabricate a doped silica shell of variable thickness. For OG-488, afluorophore with a quantum yield higher than fluorescein, theyreport an EF of 35 fold on a gold core. On the other hand, for thegold core of different sizes (40, 60 and 80 nm), but with a silicashell of similar thickness (ca. 24 nm), the fluorescence emissionof the nanoparticles increased with the Au core size.

SHINEF based on silica coating can be extended to othermaterials, i.e., to coat Ag, Au or Cu with uniform ultrathin shellsof oxides such as Al2O3 and MnO2, for specific applications.125

The challenge is to break the limitations of SHINEF substratesand fabricate shells of appropriate materials of thickness thatcan be controlled down to nm scale without any pinhole. Forinstance, the synthesis of an ultrathin and compact MnO2 shellexpands the applications of SHINEF (or SHINERS) to alkalinesystems, where SiO2 or Al2O3 shells can easily be dissolved.

4.3.2 SHINEF + SHINERS. The dual-mode SHINERS–SHI-NEF is an emerging analytical technique expected to be a usefultool with potential applications in biomedical fields.121 Thedual-mode was used first to demonstrate with far field mea-surements in aqueous solution that by collecting SHINERS andSHINEF from the same molecular system, it is possible toconfirm that the scattering scales as the fourth power of thelocal field enhancement while the fluorescence is proportionalto the square of the local field enhancement.63 The latter isillustrated in Fig. 16, showing the SHINERS+SHINEF spectra ofcrystal violet in solution, excited with the 514.5 nm laser line.

The dual-mode applications, most likely, will require a specificadaptation of the SHINs to fit the task at hand. For instance, Leeet al. developed a nanoparticle that they call (SERS)-fluorescencedual modal nanoprobes (DMNPs),126 a nanostructure to be usedas a probe for novel biomedical imaging. The DMNP wasfabricated starting from 40 nm Au colloid. A Raman reporteris adsorbed and the first inner silica encapsulates the SERSnanoprobe. Then a fluorescent dye-labeled nanoprobe is addedwith a second outer silica encapsulation.

Zhang et al. developed a bifunctional nanostructured ensembleof quantum dot (QD)-decorated silica coated nanoparticles.127

Again an embedded Raman reporter, p-aminothiophenol (PATP),is introduced with a surface coverage of the Ag colloid (ca. 60 nmin diameter) of about 50% enough to yield strong SERS signals,and subsequently by coupling 3-mercaptopropyltrimethoxysilane(MPTMS) with a surface coverage of 50% to make the Ag NPsurfaces vitreophilic for coating with a complete silica shell.Finally, CdS QDs are covalently attached to the surfaces of thedoped SHINs. The silica shell spacer is optimized (about 9 nm) formaximum emission. The specialized SHINs are shown in Fig. 17adapted from ref. 127. SHINs with a core of Au–Ag alloy have alsobeen successfully tested.128 SHIN nanoparticles are fabricated by achemical method, and the LSPR peak is controlled by adjustingthe metal component of the alloy and shell thickness. SHINs witha Au–Ag alloy core were also fabricated with different silica shellthickness ranging from 2 to 35 nm.

SHINEF is now a versatile analytical technique that can beused in solution, in aqueous or organic solvents, as well as onsolid surfaces. Au-SHIN nanoparticles were carefully chosen forspraying studies on Langmuir–Blodgett monolayers and Layerby Layer samples given fluorescence enhancement for high andlow quantum yield fluorophores.129 In the search to maximizethe SHINEF enhancement factor, an increase in emissionintensity was first confirmed with shell-isolated nanoparticlesof gold of about 100 nm in diameter, when, under the sameconditions, they were compared with Au-SHINs of about 40 nm,for experiments in solution and on Langmuir–Blodgett films.123

The findings are in agreement with the fact that for largerAu-SHINs, an important contributing factor comes from theincrease in nanoparticle scattering with the core size of thenanoparticle. The enhancement factor can be further increased

Fig. 16 SHINERS + SHINEF spectra of crystal violet in solution, excitedwith the 514.5 nm laser line. Reproduced with permission.63 Copyright2012, Wiley.

Fig. 17 TEM images of Ag/PATP@SiO2 with various shell thicknesses:(a) bare Ag; (b) 6 nm; (c) 9 nm; (d) 15 nm; (e) 35 nm; and (f) 60 nm.Reproduced with permission.127 Copyright, 2012. Royal Society of Chemistry.


Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM




by aggregation of Au-SHINs in solution. It was demonstratedfor crystal violet solutions and SHINs, with the addition ofdifferent volumes of NaCl solution to promote SHIN aggregation.The SHINEF results for large Au-SHINs are shown in Fig. 18. Thenon-aggregated large Au-SHINs give an EF of 47-fold, whereas theaggregated large Au-SHINs give an impressive EF of 155-fold.The results are supported by computations of local field enhance-ment of Au-SHIN dimers, a hint to hotspot contributions.

5. Conclusion and perspectives5.1 Conclusion

Plasmon-mediated fluorescence provides advanced scenariosfor nanoscale detection and imaging and is becoming a majorspectroscopic tool in biological and materials science. In parti-cular, the field is expanding by the inclusion of weak emittersand plasmonic design in a broad region of the electromagneticspectrum. The theory will continue to probe deeper into theinteractions between localized surface plasmons and nearbymolecules, where the final objective is to understand and control thecommunications between plasmonic nanomaterials and individualquantum emitters. It is evident from the ongoing research thatthe applicability of these phenomena is penetrating biological,chemical and physical science with a big impact on ultra-sensitivity and super-resolution imaging. In particular, the radia-tive decay process is found to be extraordinarily accelerated viathe Purcell effect. In the present review, we have focused onsome recent developments in the field of PEF, that given thebreadth of the field cannot be comprehensive, and we apologizefor any omission of important work. Experimentally, LSPR canbe tailored by designing plasmon-enhanced nanostructures ofdifferent architecture and materials providing great opportunityand potential applications including sensors. Particularly,plasmon-enhanced fluorescence with shell-isolated nanostruc-tures will open a wealth of flexible techniques in ultra-sensitivespectroscopic analysis.

5.2 Perspectives of PEF

5.2.1 PEF in carbon nano-materials and 2D semiconductormaterials. Due to its excellent spectroscopic properties, PEFhas exceptional prospects to be used with carbon dots andtwo-dimensional (2D) semiconductor materials, particularlyin optoelectronics. Carbon dots and 2D materials provide

textbook examples to illustrate the power of PEF. Over the pastdecade, carbon dots and 2D materials have attracted muchattention in the fields of biological imaging and nanophotonicdevices.130,131

Kim and coworkers prepared a novel solar cell with carbon-dot-supported Ag nanoparticles that takes full advantage of thecoupling of plasmons and excitons to improve the performanceof optoelectronic devices. In the design of this cell, the plasmonresonance between silver nanoparticles and carbon dotsenables additional light absorption, leading to increased powerconversion efficiency from 7.53% to 8.31% compared withcontrol devices.32 Based on these results, PEF in carbon dotscould be a versatile and effective strategy for realizing betteroptoelectronic device performance. 2D atomic layer materials,such as thin film semiconductors and graphene, currently exhibitpoor light emission and absorption and would also greatlybenefit from electromagnetic enhancement in their opticalprocesses, as determined by their nanostructures and physicalproperties. To address the problems of poor light absorptionand emission, the Koray Aydin group effectively enhanced thephotoluminescence (PL) of MoS2 by CVD over a large area byplasmonic coupling with silver nanoparticle arrays, as shown inFig. 19.132 A comparison of the intensities of light emissionsbefore and after modification by nanodisc arrays reveals thatthe light emission from large-area monolayer MoS2 usingplasmonic silver nanodisc arrays enhanced PL up to 12-fold,thus providing a valid approach for boosting light interactionwith newly emerging low-dimensional materials. In addition, itshows that perfect plasmonic nanostructures coupled withincident wavelength and emission of light have great potentialfor application in high-efficiency optoelectronic devices.Graphene, with its unusually high electron mobility, atomicthickness, broadband optical absorption, and unique flexibility,has been a popular and excellent research candidate. However,it possesses the same imperfections as other atomic layermaterials with respect to light absorption and emission, which

Fig. 18 SHINEF of CV in solution. The inset reveals the TEM image of asingle large Au SHIN. Reproduced with permission.123 Copyright 2016,American Chemical Society.

Fig. 19 Enhanced PL in plasmonic array/MoS2 heterostructures. (a) Schematicdiagram of plasmonic/MoS2 heterostructures. (b) PL intensity comparisonof selected points in each array. The inset shows the cross-section of theplasmonic/MoS2 heterostructure. (c) SEM image of fabricated nanodiscarrays. The diameter of the base unit in each array is indicated above.The scale bar is 25 mm. (d) Corresponding integrated PL map of the areadisplayed in panel (b). Reproduced with permission.132 Copyright 2015,American Chemical Society.


Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM




seriously hinders its optical applications. Resolving these pro-blems has been a challenge for scientists. Now, it is possible tomodify the surface of graphene with fluorescent group blocksvia noncovalent functionalization to enhance the light–graphene interaction.133 Although research in the plasmonused in graphene has a long way to go, it has the potential togreatly broaden optoelectrical applications in the future.

5.2.2 PEF with ultra-high spatial resolution. Due to thelimitations associated with optical diffraction, the maximumlateral resolution of optical microscopy is estimated to beabout l/2 (l, the wavelength of light). The advent of scanningnear-field microscopy (SNOM) overcame this shortcoming,achieving a resolution approaching the size of the tip. Sincebeing introduced, SNOM has been used in fluorescence imagingwith nanometer-scale resolution134 and even single moleculeresolution.135 The first imaging of single molecules and dipoleorientations at room temperature was achieved by Eric Betzigusing near-field scanning optical microscopy.136

To explore the distance dependence effect in fluorescence,PEF with SNOM is an appropriate choice. When the fluorophoreis close to a metal nanostructure, the localized electromagneticfield enhancement can enhance its excitation, radiation, andnon-radiation rates. Lukas Novotny’s group experimentally andtheoretically investigated the relation between the fluorescencerate and its distance to a gold nanoparticle modified on the endof an optical fiber attached. The authors first experimentallyrevealed the transition from emission enhancement to quench-ing by varying these distances.49 Fig. 13 shows the fluorescencerate as a function of gold NP-to-surface gap z for a verticallyoriented emitter. The maximum fluorescence enhancementoccurred at 5 nm. With this technique, a fluorescence imageof membrane proteins can also be obtained.137

Tip-enhanced Raman spectroscopy (TERS) is scanning probemicroscopy (SPM)-based Raman spectroscopy, and can simulta-neously obtain morphology and chemical information at aspatial resolution down to a single molecule, and even theinner molecular structure and conformation of an individualmolecule at sub-nanometer resolution.138,139 As shown inFig. 20c and d, chemical visualization of an individual meso-tetrakis(3,5-di-tertiarybutylphenyl)-porphyrin (H2TBPP) mole-cule has been achieved with scanning tunnelling microscopy(STM)-based TERS by Dong’s group.140 However, to scan asingle molecule with the STM technique, the distance betweenthe tip end and the molecule needs to be kept within the tunnellingregion. As a result, the fluorescence intensity is strongly quencheddue to the approaching metal tip and the metal substrate. Hence,SM fluorescence imaging with sub-nanometer resolution is difficultas compared with TERS. Recently, a breakthrough of scanningtunnelling microscopy (STM)-induced luminescence in ultra-high-vacuum conditions has been reported by Dong and co-workers.138

In virtue of the ultra-high spatial resolution in STML, the visualiza-tion of coherent dipole–dipole coupling has been realized betweena few zinc-phthalocyanine molecules. This will be of great helpfor studying intermolecular interactions at a molecular levelwith PEF. On the other hand, similar to SHINEF, an ultra-thindielectric shell coated on the tip is predicted to avoid the

quenching effect but maintain the excellent plasmonic prop-erty, which has been proved by shell-isolated tip-enhancedRaman spectroscopy (SITERS).38 Li et al. are currently extendingthis strategy to new scanning probe microscopy tip structuresfor shell-isolated tip-enhanced fluorescence spectroscopy.We can expect that, along with the high emission property ofthe fluorophore, PEF with a shell-isolated tip will definitelyfacilitate surface analysis at ultra-high spatial resolutions, suchas sub-nanometer fluorescence imaging, characterizing defectsin 2D materials and identifying active sites in catalysts.

5.2.3 PEF with ultra-high time resolution. Ordinary fluores-cence or phosphorescence occurs in timescales of nanoseconds tomilliseconds. However, in the presence of a plasmonic nanoan-tenna, both the radiative and nonradiative decays of emitters areaccelerated, and the fluorescence lifetime is reduced to hundredsof picoseconds or even shorter.141 The development of ultra-high time-resolved fluorescence methods has great potentialfor investigating ultra-fast spontaneous emission processes.The application of PEF to nanoparticles has great potentialfor achieving a large Purcell factor at room temperature.141–143

Particularly, with the highly confined optic field in nanogaps,the Purcell factor is theoretically predicted to be more than 106,which implies a lifetime shorter than B100 femtoseconds.144

Hence, it is a remarkable challenge to directly measure ultra-fast emission processes.

Time-correlated single photon counting (TCSPC) is a well-established time-domain data acquisition method for deter-mining the lifetime of an emission process and is favoured inPEF investigations.13,77,142,143,145,146 In principle, in TCSPC, theamount of detected photons is tuned to be less than one perlaser pulse. The corresponding arrival time of the photon isrecorded and stored to build up a photon distribution, whichdenotes the waveform of decay time. As illustrated in Fig. 21a,the height in the histogram represents the number of photonswhile the x axis is the time difference.13,146 However, due to thedetection limit of electronic devices, the typical time resolutionis 10–30 ps for the TCSPC technique. In the work of theMoerner group, the fluorescence lifetime of TPQDI molecules

Fig. 20 (a) Illustration of the experimental setup. The inset shows an SEMimage of an Au NP attached to the end of an optical fiber. (b) Emission rateas a function of Au NP-to-surface distance for a vertically orientedmolecule (red curve: simulated result, dotted line: experimental result).The horizontal dashed line denotes the background in the experiment.(c) Schematic diagram of STM-based TERS. (d) Chemical imaging of asingle H2TBPP molecule on the Ag(111) surface with TERS. Panels (a and b)are reproduced with permission.49 Copyright 2006, American PhysicalSociety. Panels (c and d) are reproduced with permission.140 Copyright2013, Nature Publishing Group.


Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM




close to gold bowtie nanostructures was measured by the TCSPCtechnique. As shown in Fig. 14b, magenta and green curvesdenote the lifetime of dyes in the absence and presence of thegold bowtie nanostructure, in which the lifetime is 275 and78 ps, respectively. While the excitation polarization is parallel orperpendicular to the long axis of the gold bowtie, the lifetime isshorter than the instrument response function (IRF, B10 ps).Hence, a higher time-resolution is urgent for the ultra-fastspontaneous emission in PEF. On the other hand, introducinga plasmonic nanostructure to enhance the spontaneous emis-sion rate (Purcell effect) has provided an effective approach formaking fundamental investigations of light–matter interaction andhas great significance in the field of nanophotonic engineering,such as the potential application of a single photon source at roomtemperature.147 Ultra-high time-resolved fluorescence spectroscopywill also facilitate an in-depth understanding of nano-optics inplasmonic nanocavities.

Acknowledgements

This work was supported by the NSFC (21522508, 21427813, and21521004), ‘‘111’’ Project (B16029 and B17027), the FundamentalResearch Funds for the Central Universities (20720150039), andthe Thousand Youth Talents Plan of China.

Notes and references

1 A. M. Glass, P. F. Liao, J. G. Bergman and D. H. Olson, Opt.Lett., 1980, 5, 368–370.

2 D. A. Weitz, S. Garoff, C. D. Hanson, T. J. Gramila andJ. I. Gersten, J. Lumin., 1981, 24–25, 83–86.

3 C. Y. Chen, I. Davoli, G. Ritchie and E. Burstein, Surf. Sci.,1980, 101, 363–366.

4 J. Gersten and A. Nitzan, J. Chem. Phys., 1981, 75, 1139–1152.5 A. Wokaun, H. P. Lutz, A. P. King, U. P. Wild and

R. R. Ernst, J. Chem. Phys., 1983, 79, 509–514.6 M. Moskovits, Rev. Mod. Phys., 1985, 57, 783–826.7 M. Fleischmann, P. J. Hendra and A. J. McQuillan, Chem.

Phys. Lett., 1974, 26, 163–166.8 M. G. Albrecht and J. A. Creighton, J. Am. Chem. Soc., 1977,

99, 5215–5217.

9 D. L. Jeanmaire and R. P. Van Duyne, J. Electroanal. Chem.,1977, 84, 1–20.

10 S. A. Maier, Plasmonics: fundamentals and applications,Springer Science + Business Media, 2007.

11 E. C. Le Ru and P. G. Etchegoin, Principles of SurfaceEnhanced Raman Spectroscopy (and related plasmoniceffects), Elsevier, Amsterdam, 2009.

12 R. Aroca, Surface-enhanced Vibrational Spectroscopy, JohnWiley & Sons, Chichester, 2006.

13 Principles of fluorescence spectroscopy, ed. J. Lakowicz,Springer, 3rd edn, 2006.

14 W. Y. Rao, Q. Li, Y. Z. Wang, T. Li and L. J. Wu, ACS Nano,2015, 9, 2783–2791.

15 C. Geddes and J. Lakowicz, J. Fluoresc., 2002, 12, 121–129.16 G. W. Lu, T. Y. Zhang, W. Q. Li, L. Hou, J. Liu and

Q. H. Gong, J. Phys. Chem. C, 2011, 115, 15822–15828.17 P. Albella, R. A. de la Osa, F. Moreno and S. A. Maier,

ACS Photonics, 2014, 1, 524–529.18 P. H. B. Aoki, C. J. L. Constantino, O. N. Oliveira Jr and

R. F. Aroca, Recent Progress in Colloid and Surface Chemistrywith Biological Applications, American Chemical Society,2015, vol. 1215, ch. 14, pp. 269–301.

19 T. Schmid, L. Opilik, C. Blum and R. Zenobi, Angew. Chem.,Int. Ed., 2013, 52, 5940–5954.

20 A. Hartschuh, Angew. Chem., Int. Ed., 2008, 47, 8178–8191.21 S. Y. Ding, J. Yi, J. F. Li, B. Ren, D. Y. Wu, R. Panneerselvam

and Z. Q. Tian, Nat. Rev. Mater., 2016, 1.22 A. R. Guerrero and R. F. Aroca, Angew. Chem., Int. Ed., 2011,

50, 665–668.23 H. Mishra, B. L. Mali, J. Karolin, A. I. Dragan and C. D.

Geddes, Phys. Chem. Chem. Phys., 2013, 15, 19538–19544.24 E. Eltzov, D. Prilutsky, A. Kushmaro, R. S. Marks and

C. D. Geddes, Appl. Phys. Lett., 2009, 94, 083901–083903.25 M. Weisenberg, Y. Zhang and C. D. Geddes, Appl. Phys.

Lett., 2010, 97, 133103.26 J. D. Flynn, B. L. Haas and J. S. Biteen, J. Phys. Chem. C,

2016, 120, 20512–20517.27 H. Yuan, S. Khatua, P. Zijlstra, M. Yorulmaz and M. Orrit,

Angew. Chem., Int. Ed., 2013, 52, 1217–1221.28 W. E. Martin, B. R. Srijanto, C. P. Collier, T. Vosch and

C. I. Richards, J. Phys. Chem. A, 2016, 120, 6719–6727.29 M. Ramırez-Maureira, V. Vargas C, A. Riveros, P. J. G. Goulet

and I. O. Osorio-Roman, Mater. Chem. Phys., 2015, 151,351–356.

30 A. J. Meixner, R. Jager, S. Jager, A. Brauer, K. Scherzinger,J. Fulmes, S. Z. Krockhaus, D. A. Gollmer, D. P. Kern andM. Fleischer, Faraday Discuss., 2015, 184, 321–337.

31 C. Y. Li, Y. H. Zhu, X. Q. Zhang, X. L. Yang and C. Z. Li, RSCAdv., 2012, 2, 1765–1768.

32 H. Choi, S. J. Ko, Y. Choi, P. Joo, T. Kim, B. R. Lee, J. W. Jung,H. J. Choi, M. Cha, J. R. Jeong, I. W. Hwang, M. H. Song,B. S. Kim and J. Y. Kim, Nat. Photonics, 2013, 7, 732–738.

33 E. S. Thrall, A. Preska Steinberg, X. Wu and L. E. Brus,J. Phys. Chem. C, 2013, 117, 26238–26247.

34 S. Impellizzeri, S. Simoncelli, G. K. Hodgson, A. E.Lanterna, C. D. McTiernan, F. M. Raymo,

Fig. 21 (a) Principle of the TCSPC technique. (b) Fluorescence lifetime ofTPQDI measured with the TCSPC technique. Panel (a) is reproduced withpermission.146 Copyright 2005, Springer. Panel (b) is reproduced withpermission.77 Copyright 2009, Nature Publishing Group.


Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM




P. F. Aramendia and J. C. Scaiano, Chem. – Eur. J., 2016, 22,7281–7287.

35 P. Mandal and S. Sharma, Renewable Sustainable EnergyRev., 2016, 65, 537–552.

36 S. Ahn, D. Rourke and W. Park, J. Opt., 2016, 18, 033001–033024.37 J. A. Webb and R. Bardhan, Nanoscale, 2014, 6, 2502–2530.38 C. Y. Li, M. Meng, S. C. Huang, L. Li, S. R. Huang, S. Chen,

L. Y. Meng, R. Panneerselvam, S. J. Zhang, B. Ren,Z. L. Yang, J. F. Li and Z. Q. Tian, J. Am. Chem. Soc.,2015, 137, 13784–13787.

39 J. N. Anker, W. P. Hall, O. Lyandres, N. C. Shah, J. Zhao andR. P. Van Duyne, Nat. Mater., 2008, 7, 442–453.

40 B. Spackova, P. Wrobel, M. Bockova and J. Homola, Proc.IEEE, 2016, 104, 2380–2408.

41 S. M. Hamidi and M. Zamani, Opt. Eng., 2015, 54,107104–107109.

42 A. Farhang, B. Abasahl, S. Dutta-Gupta, A. Lovera,P. Mandracci, E. Descrovi and O. J. F. Martin, Rev. Sci.Instrum., 2013, 84, 033107–033113.

43 S. Khatua and M. Orrit, ACS Nano, 2013, 7, 8340–8343.44 C. Forestiere, Y. Y. He, R. Wang, R. M. Kirby and L. Dal

Negro, ACS Photonics, 2016, 3, 68–78.45 J. Zhao, A. O. Pinchuk, J. M. McMahon, S. Li, L. K. Ausman,

A. L. Atkinson and G. C. Schatz, Acc. Chem. Res., 2008, 41,1710–1720.

46 D. R. Nascimento and A. E. DePrince, J. Chem. Phys., 2015,143, 214104–214112.

47 M. S. Tame, K. R. McEnery, S. K. Ozdemir, J. Lee,S. A. Maier and M. S. Kim, Nat. Phys., 2013, 9, 329–340.

48 J. Asselin, P. Legros, A. Gregoire and D. Boudreau,Plasmonics, 2016, 11, 1369–1376.

49 P. Anger, P. Bharadwaj and L. Novotny, Phys. Rev. Lett.,2006, 96, 113002.

50 K. H. Drexhage, H. Kuhn and F. P. Schafer, Ber. Bunsen-Ges., 1968, 72, 329.

51 R. R. Chance, A. Prock and R. Silbey, Adv. Chem. Phys.,1978, 37, 1–65.

52 A. P. Alivisatos, M. F. Arndt, S. Efrima, D. H. Waldeck andC. B. Harris, J. Chem. Phys., 1987, 86, 6540–6549.

53 K. Aslan, J. R. Lakowicz, H. Szmacinski and C. D. Geddes,J. Fluoresc., 2004, 14, 677–679.

54 R. Aroca, G. J. Kovacs, C. A. Jennings, R. O. Loutfy andP. S. Vincett, Langmuir, 1988, 4, 518–521.

55 S. Saini, G. Srinivas and B. Bagchi, J. Phys. Chem. B, 2009,113, 1817–1832.

56 A. I. Dragan, E. S. Bishop, J. R. Casas-Finet, R. J. Strouse,J. McGivney, M. A. Schenerman and C. D. Geddes,Plasmonics, 2012, 7, 739–744.

57 J. W. Lichtman and J.-A. Conchello, Nat. Methods, 2005, 2,910–919.

58 R. M. Dickson, A. B. Cubitt, R. Y. Tsien and W. E. Moerner,Nature, 1997, 388, 355–358.

59 M. Schena, D. Shalon, R. W. Davis and P. O. Brown,Science, 1995, 270, 467–470.

60 S. W. Hell, S. J. Sahl, M. Bates, X. W. Zhuang,R. Heintzmann, M. J. Booth, J. Bewersdorf, G. Shtengel,

H. Hess, P. Tinnefeld, A. Honigmann, S. Jakobs, I. Testa,L. Cognet, B. Lounis, H. Ewers, S. J. Davis, C. Eggeling,D. Klenerman, K. I. Willig, G. Vicidomini, M. Castello,A. Diaspro and T. Cordes, J. Phys. D: Appl. Phys., 2015, 48,443001–443035.

61 F. Emmanuel and G. Samuel, J. Phys. D: Appl. Phys., 2008,41, 013001.

62 P. Albella, F. Moreno, J. M. Saiz and F. Gonzalez, Opt.Express, 2008, 16, 12872–12879.

63 A. R. Guerrero, Y. Zhang and R. F. Aroca, Small, 2012, 8,2964–2967.

64 T. R. Jensen, M. L. Duval, K. L. Kelly, A. A. Lazarides,G. C. Schatz and R. P. Van Duyne, J. Phys. Chem. B, 1999,103, 9846–9853.

65 K. M. Mayer and J. H. Hafner, Chem. Rev., 2011, 111,3828–3857.

66 F. Tam, G. P. Goodrich, B. R. Johnson and N. J. Halas, NanoLett., 2007, 7, 496–501.

67 J. Zhang, Y. Fu, M. H. Chowdhury and J. R. Lakowicz, NanoLett., 2007, 7, 2101–2107.

68 Y. Chen, K. Munechika and D. S. Ginger, Nano Lett., 2007,7, 690–696.

69 Y. Fu, J. Zhang and J. R. Lakowicz, J. Am. Chem. Soc., 2010,132, 5540–5541.

70 E. C. Le Ru, P. G. Etchegoin, J. Grand, N. Felidj,J. Aubard and G. Levi, J. Phys. Chem. C, 2007, 111,16076–16079.

71 R. F. Aroca, G. Y. Teo, H. Mohan, A. R. Guerrero, P. Albellaand F. Moreno, J. Phys. Chem. C, 2011, 115, 20419–20424.

72 R. Gill and E. C. Le Ru, Phys. Chem. Chem. Phys., 2011, 13,16366–16372.

73 M. R. Gartia, J. P. Eichorst, R. M. Clegg and G. L. Liu, Appl.Phys. Lett., 2012, 101, 023118–023122.

74 M. Moskovits and D. H. Jeong, Chem. Phys. Lett., 2004, 397,91–95.

75 S. Chen, L. Y. Meng, H. Y. Shan, J. F. Li, L. H. Qian,C. T. Williams, Z. L. Yang and Z. Q. Tian, ACS Nano, 2016,10, 581–587.

76 H. Cang, A. Labno, C. Lu, X. Yin, M. Liu, C. Gladden, Y. Liuand X. Zhang, Nature, 2011, 469, 385–388.

77 A. Kinkhabwala, Z. Yu, S. Fan, Y. Avlasevich, K. Muellenand W. E. Moerner, Nat. Photonics, 2009, 3, 654–657.

78 L. C. Zhou, F. Ding, H. Chen, W. Ding, W. H. Zhang andS. Y. Chou, Anal. Chem., 2012, 84, 4489–4495.

79 W. H. Zhang, F. Ding, W. D. Li, Y. X. Wang, J. Hu andS. Y. Chou, Nanotechnology, 2012, 23, 225301–225309.

80 M. D. Furtaw, J. P. Anderson, L. R. Middendorf andG. R. Bashford, Plasmonics, 2014, 9, 27–34.

81 L. Su, H. F. Yuan, G. Lu, S. Rocha, M. Orrit, J. Hofkens andH. Uji-I, ACS Nano, 2016, 10, 2455–2466.

82 G. Ritchie, C. Chen and E. Burstein, Bull. Am. Phys. Soc.,1980, 25, 259–260.

83 W. L. Barnes, J. Mod. Opt., 1998, 45, 661–699.84 L. M. Liz-Marzan, Langmuir, 2006, 22, 32–41.85 T. Ung, L. M. Liz-Marzan and P. Mulvaney, Langmuir, 1998,

14, 3740–3748.


Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM




86 Y. Xia, Y. Xiong, B. Lim and S. E. Skrabalak, Angew. Chem.,Int. Ed., 2009, 48, 60–103.

87 B. Nikoobakht and M. A. El-Sayed, Chem. Mater., 2003, 15,1957–1962.

88 N. R. Jana, L. Gearheart and C. J. Murphy, J. Phys. Chem. B,2001, 105, 4065–4067.

89 T. K. Sau and C. J. Murphy, J. Am. Chem. Soc., 2004, 126,8648–8649.

90 G. Chumanov, K. Sokolov, B. W. Gregory and T. M. Cotton,J. Phys. Chem., 1995, 99, 9466–9471.

91 D. P. Fromm, A. Sundaramurthy, P. J. Schuck, G. Kino andW. E. Moerner, Nano Lett., 2004, 4, 957–961.

92 E. Wientjes, J. Renger, A. G. Curto, R. Cogdell and N. F. vanHulst, Nat. Commun., 2014, 5.

93 D. Punj, M. Mivelle, S. B. Moparthi, T. S. van Zanten,H. Rigneault, N. F. van Hulst, M. F. Garcia-Parajo andJ. Wenger, Nat. Nanotechnol., 2013, 8, 512–516.

94 J. F. Li, Y. Huang, Y. Ding, Z. Yang, S. Li, X. Zhou, F. Fan,W. Zhang, Z. Zhou, D. Wu, B. Ren, Z. L. Wang andZ. Q. Tian, Nature, 2010, 464, 392–395.

95 C. Ayala-Orozco, J. G. Liu, M. W. Knight, Y. Wang, J. K. Day,P. Nordlander and N. J. Halas, Nano Lett., 2014, 14,2926–2933.

96 G. Ritchie and E. Burstein, Phys. Rev. B: Condens. MatterMater. Phys., 1981, 24, 4843–4846.

97 J. R. Lakowicz, Anal. Biochem., 2005, 337, 171–194.98 J. R. Lakowicz, Y. Shen, S. D’Auria, J. Malicka, J. Fang,

Z. Gryczynski and I. Gryczynski, Anal. Biochem., 2002, 301,261–277.

99 P. C. Lee and D. Meisel, J. Phys. Chem., 1982, 86, 3391–3395.100 G. Frens, Nature, 1973, 241, 20–22.101 Y. Sun and Y. Xia, Science, 2002, 298, 2176–2179.102 W. Stober, A. Fink and E. Bohn, J. Colloid Interface Sci.,

1968, 26, 62–69.103 S. J. Oldenburg, R. D. Averitt, S. L. Westcott and N. J. Halas,

Chem. Phys. Lett., 1998, 288, 243–247.104 P.-P. Fang, J.-F. Li, Z.-L. Yang, L.-M. Li, B. Ren and Z.-Q. Tian,

J. Raman Spectrosc., 2008, 39, 1679–1687.105 J. F. Li, X. D. Tian, S. B. Li, J. R. Anema, Z. L. Yang, Y. Ding,

Y. F. Wu, Y. M. Zeng, Q. Z. Chen, B. Ren, Z. L. Wang andZ. Q. Tian, Nat. Protoc., 2013, 8, 52–65.

106 C. Y. Li, J. C. Dong, X. Jin, S. Chen, R. Panneerselvam,A. V. Rudnev, Z. L. Yang, J. F. Li, T. Wandlowski andZ. Q. Tian, J. Am. Chem. Soc., 2015, 137, 7648–7651.

107 C.-Y. Li, S.-Y. Chen, Y.-L. Zheng, S.-P. Chen, R. Panneerselvam,S. Chen, Q.-C. Xu, Y.-X. Chen, Z.-L. Yang, D.-Y. Wu, J.-F. Li andZ.-Q. Tian, Electrochim. Acta, 2016, 199, 388–393.

108 C.-Y. Li, Z.-W. Yang, J.-C. Dong, T. Ganguly and J.-F. Li,Small, 2017, 13, 1601598.

109 W. E. Moerner and L. Kador, Phys. Rev. Lett., 1989, 62,2535–2538.

110 F. Kulzer, T. Xia and M. Orrit, Angew. Chem., Int. Ed., 2010,49, 854–866.

111 J. R. Lakowicz, K. Ray, M. Chowdhury, H. Szmacinski,Y. Fu, J. Zhang and K. Nowaczyk, Analyst, 2008, 133,1308–1346.

112 X. Zhou, N. M. Andoy, G. Liu, E. Choudhary, K.-S. Han,H. Shen and P. Chen, Nat. Nanotechnol., 2012, 7,237–241.

113 Y. Fu and J. R. Lakowicz, Anal. Chem., 2006, 78, 6238–6245.114 C. Zhou, X. Duan and N. Liu, Nat. Commun., 2015, 6.115 J. J. Funke and H. Dietz, Nat. Nanotechnol., 2015, 11,

47–52.116 G. P. Acuna, F. M. Moller, P. Holzmeister, S. Beater,

B. Lalkens and P. Tinnefeld, Science, 2012, 338, 506–510.117 T. Liebermann, W. Knoll, P. Sluka and R. Herrmann,

Colloids Surf., A, 2000, 169, 337–350.118 D. Kambhampati, P. E. Nielsen and W. Knoll, Biosens.

Bioelectron., 2001, 16, 1109–1118.119 H.-I. Peng, C. M. Strohsahl, K. E. Leach, T. D. Krauss and

B. L. Miller, ACS Nano, 2009, 3, 2265–2273.120 Z. Mei and L. Tang, Anal. Chem., 2017, 89, 633–639.121 P.-P. Fang, X. Lu, H. Liu and Y. Tong, TrAC, Trends Anal.

Chem., 2015, 66, 103–117.122 X.-D. Tian, B.-J. Liu, J.-F. Li, Z.-L. Yang, B. Ren and Z.-Q. Tian,

J. Raman Spectrosc., 2013, 44, 994–998.123 S. A. Camacho, P. H. B. Aoki, P. Albella, O. N. Oliveira,

C. J. L. Constantino and R. F. Aroca, J. Phys. Chem. C, 2016,120, 20530–20535.

124 C. Li and J. Zhu, Mater. Lett., 2013, 112, 169–172.125 X.-D. Lin, V. Uzayisenga, J.-F. Li, P.-P. Fang, D.-Y. Wu,

B. Ren and Z.-Q. Tian, J. Raman Spectrosc., 2012, 43, 40–45.126 S. Lee, H. Chon, S.-Y. Yoon, E. K. Lee, S.-I. Chang,

D. W. Lim and J. Choo, Nanoscale, 2012, 4, 124–129.127 X. Zhang, X. Kong, Z. Lv, S. Zhou and X. Du, J. Mater.

Chem. B, 2013, 1, 2198–2204.128 C. Zhang, Q. Han, C. Li, M. Zhang, L. Yan and H. Zheng,

Appl. Opt., 2016, 55, 9131–9136.129 I. O. Osorio-Roman, A. R. Guerrero, P. Albella and

R. F. Aroca, Anal. Chem., 2014, 86, 10246–10251.130 V. Strauss, J. T. Margraf, C. Dolle, B. Butz, T. J. Nacken,

J. Walter, W. Bauer, W. Peukert, E. Spiecker, T. Clark andD. M. Guldi, J. Am. Chem. Soc., 2014, 136, 17308–17316.

131 F. Xia, H. Wang, D. Xiao, M. Dubey and A. Ramasubramaniam,Nat. Photonics, 2014, 8, 899–907.

132 S. Butun, S. Tongay and K. Aydin, Nano Lett., 2015, 15,2700–2704.

133 S. Le Liepvre, P. Du, D. Kreher, F. Mathevet, A.-J. Attias,C. Fiorini-Debuisschert, L. Douillard and F. Charra, ACSPhotonics, 2016, 3, 2291–2296.

134 X.-L. Zhang, L.-G. Chen, P. Lv, H.-Y. Gao, S.-J. Wei,Z.-C. Dong and J. G. Hou, Appl. Phys. Lett., 2008,92, 223118.

135 H. G. Frey, S. Witt, K. Felderer and R. Guckenberger, Phys.Rev. Lett., 2004, 93, 200801.

136 E. Betzig and R. J. Chichester, Science, 1993, 262,1422–1425.

137 C. Hoppener and L. Novotny, Nano Lett., 2008, 8,642–646.

138 Y. Zhang, Y. Luo, Y. Zhang, Y.-J. Yu, Y.-M. Kuang, L. Zhang,Q.-S. Meng, Y. Luo, J.-L. Yang, Z.-C. Dong and J. G. Hou,Nature, 2016, 531, 623–627.


Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM




139 N. Chiang, N. Jiang, D. V. Chulhai, E. A. Pozzi,M. C. Hersam, L. Jensen, T. Seideman and R. P. VanDuyne, Nano Lett., 2015, 15, 4114–4120.

140 R. Zhang, Y. Zhang, Z. C. Dong, S. Jiang, C. Zhang,L. G. Chen, L. Zhang, Y. Liao, J. Aizpurua, Y. Luo,J. L. Yang and J. G. Hou, Nature, 2013, 498, 82–86.

141 M. Pelton, Nat. Photonics, 2015, 9, 427–435.142 G. M. Akselrod, C. Argyropoulos, T. B. Hoang, C. Ciracı,

C. Fang, J. Huang, D. R. Smith and M. H. Mikkelsen, Nat.Photonics, 2014, 8, 835–840.

143 K. J. Russell, T.-L. Liu, S. Cui and E. L. Hu, Nat. Photonics,2012, 6, 459–462.

144 R. Chikkaraddy, B. de Nijs, F. Benz, S. J. Barrow,O. A. Scherman, E. Rosta, A. Demetriadou, P. Fox, O. Hessand J. J. Baumberg, Nature, 2016, 535, 127–130.

145 M. Y. Berezin and S. Achilefu, Chem. Rev., 2010, 110, 2641–2684.146 W. Becker and A. Bergmann, in Reviews in Fluorescence

2005, ed. C. D. Geddes and J. R. Lakowicz, Springer US,Boston, MA, 2005, pp. 77–108.

147 B. Lounis and W. E. Moerner, Nature, 2000, 407, 491–493.


Publ

ishe

d on

22

June

201

7. D

ownl

oade

d by

Xia

men

Uni

vers

ity o

n 5/

27/2

019

9:42

:22

AM



Documents

Chem Soc Rev - Xiamen University