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Analytica Chimica Acta 1022 (2018) 1e19

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Analytica Chimica Acta

journal homepage: www.elsevier .com/locate/aca

Review

Synthesis and electrochemical sensing application of poly(3,4-ethylenedioxythiophene)-based materials: A review

Yun Hui 1, 2, Chao Bian 1, **, Shanhong Xia 1, *, Jianhua Tong 1, Jinfen Wang 3

1 State Key Laboratory of Transducer Technology, Institute of Electronics, Chinese Academy of Sciences, Beijing 100190, People’s Republic of China2 University of Chinese Academy of Sciences, Beijing 100190, People’s Republic of China3 CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, People’s Republic of China

h i g h l i g h t s

Abbreviation: 1-m-4-MP, 1-methyl-4-mercaptopyamperometric; AO, ascorbate oxidase; AuNPs, Au/gonanotube; CPE, carbon paste electrode; CTAB, cetyltrdifferential pulse voltammetry; EA-SPME, electroassisfluorine doped tin oxide sheets; GCE, glassy carbonperoxidase; ICP-MS, inductively coupled plasma mainorganic nanomaterials; ITO, indium tin oxide; LOD,nanotube; OCPs, organochlorine pesticides; PANI, Popolystyrene sulfonate; PTh, polythiophene; rGO/RGO,sulfonate; SPCE, screen-printed carbon electrode; SW* Corresponding author.** Corresponding author.

E-mail addresses: cbian@mail.ie.ac.cn (C. Bian), sh

https://doi.org/10.1016/j.aca.2018.02.0800003-2670/© 2018 Elsevier B.V. All rights reserved.

g r a p h i c a l a b s t r a c t

� The synthesis and composition ofPEDOT-based materials arediscussed.

� Recent advances of PEDOT-basedmaterials in electrochemical (bio)sensors are reviewed.

� Examples in different applicationfields are given and compared.

� Challenges and future developmentsare discussed.

a r t i c l e i n f o

Article history:Received 29 March 2017Received in revised form23 February 2018Accepted 24 February 2018Available online 14 March 2018

Keywords:Conducting polymersPEDOT-Based materialsNanomaterialsElectrochemical sensors

a b s t r a c t

As a significant and promising conducting polymer, poly(3,4-ethylenedioxythiophene) (PEDOT) hasattracted considerable attention in the last decade. This review aims at giving a comprehensive illus-tration about current progress on the synthesis and electrochemical sensing applications of PEDOT-basedmaterials in environmental monitoring, food and drug analysis and health care. PEDOT-based materials,such as PEDOT, functionalized PEDOT and PEDOT composites were fabricated mainly by chemicalpolymerization and electrochemical polymerization. Various nanostructures with large surface area, highconductivity, fast electron transfer rate, hydrophobic interaction and good biocompatibility were dis-played by the PEDOT-based materials. Synergetic effects were enhanced dramatically in electrochemical(bio) sensors by PEDOT composites, especially by those incorporated with versatile nanomaterials.

ridine; AAT, acetic acid thiophene; AChE-ChO, acetylcholinesterase-choline oxidase; AlcDH, alcohol oxidase; AMP,ld nanoparticles; BSA, bovine serum albumin; CFE, carbon film electrodes; cfu, colony-forming unit; CNT, carbonimethyl ammonium bromide; CV, cyclic voltammetry; DPASV, differential pulse anodic stripping voltammetry; DPV,ted solid-phase microextraction; ECL, electrochemiluminescence; EIS, electrochemical impedance spectroscopy; FTO,electrode; GNs, graphene nanosheets; GO, graphene oxide; GOx, glucose oxidase; GR, graphene; HRP, horseradishss spectrometer; IDUA, interdigitated ultramicroelectrode arrays; IDE, interdigitated electrode; IL, ionic liquid; INs,limit of detection; LSV, linear sweep voltammetry; MIP, molecularly imprinted polymers; MWCNT, multiwalled carbonlyaniline; PGE, pencil graphite electrode; PILs, poly(ionic liquids); PPO, polyphenol oxidase; PPy, polypyrrole; PSS,reduced graphene oxide; RSD, relative standard deviation; SDS, sodium dodecyl sulfate; SDBS, sodium dodecyl benzeneV, square wave voltammetry; VOCs, volatile organic compounds; XPS, X-ray photoelectron spectroscopy.

xia@mail.ie.ac.cn (S. Xia).

Y. Hui et al. / Analytica Chimica Acta 1022 (2018) 1e192

Through this paper, we hope to attract attention from a wider community and inspire researchers to takeadvantage of PEDOT in approaching scientific challenges and developments.

© 2018 Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22. Fabrication and functionalization of PEDOT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

2.1. Synthesis of PEDOT-based materials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32.2. PEDOT modified with functional groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52.3. PEDOT composites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

3. PEDOT-based materials for electrochemical sensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73.1. PEDOT-based sensors for environmental monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

3.1.1. Detection of inorganic ions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73.1.2. Detection of organic pollutants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83.1.3. Gas sensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

3.2. PEDOT-based sensors for food and drug analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103.3. PEDOT-based sensors for health care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

3.3.1. Catalytic sensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113.3.2. Affinity sensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133.3.3. Sensors without bioreceptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

4. Conclusions, challenges and future developments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

1. Introduction

Conducting organic polymers, often referred to as syntheticmetals, have attracted considerable attention. The research onconducting organic polymers goes back to the discovery ofpolyacetylene’s high electrical conductivity by H. Shirakawaet al. in 1977 [1], who won the Nobel Prize in 2000. In the pastdecades, conducting polymers, mostly linearly conjugatedpolymers such as polypyrrole (PPy), polyaniline (PANI), poly-thiophene (PTh) and their derivations, exhibited improvedelectrochemical performance for neural recording andbiochemical sensing [2,3] due to their interesting electrical andoptical properties. They impart a certain electrocatalytic activitywith good antifouling properties when modified on the elec-trodes. Undoped or slightly doped PTh films are stable [4], andthey are easily derivatized [5] and suitable for various applica-tions [6]. As a PTh derivative, poly(3, 4-ethylenedioxythiophene)(PEDT, PEDOT), was synthesized at the Bayer AG research lab-oratories in Germany during the late 1980s [7]. The chemicalstructure of PEDOT is shown in Fig. 1A. 3,4-ethylenedioxythiophene (EDOT) presents low oxidation poten-tial, good molecule symmetry, moderately low steric inhibitionof condensed rings and wide anodic potential window, thus theresultant polymer is characterized by high conductivity and avery narrow band gap [8]. It is reported that PEDOT has highelectrical conductivity [9], superior optical transparency invisible light range [10], good electrochromic characteristics [11]and better long-term electrochemical stability than PPy [12].The crucial area of doping mechanisms and polymer dynamicswas systematically explored by A. Robert Hillman et al. [13e15].

Earlier reviews [16e19] about PEDOT materials reported itssynthesis, characterizations, derivatives, copolymers and basicchemical, physical, electric properties from both a fundamental andpractical perspective. It is worth mentioning that quite a number ofscientists focused on commercially available PEDOT: PSS (Fig. 1B) in

which polystyrene sulfonate (PSS) with hydrophilic -SO3H groupact as the doping macromolecular polyanions. Recently, severalreviews of PEDOT have been published, placing particular emphasison electrical conductivity [9], energy conversion and storage de-vices [10], promising organic thermoelectric materials [20], dye-sensitized solar cells [21], and supercapacitors [22].

As a novel conducting polymer, original research of PEDOT-based materials applied in sensors were published in 1999[23,24]. According to Web of Science statistical data, there is atremendous increase of publications on PEDOT-based sensor dur-ing the past decade (Fig. 2), along with the rapid development ofnanomaterials and nanotechnology. Versatility of above materialscan be ascribed to the following aspects: the high conductivity evenwith the value of 4380 S cm�1 of PEDOT: PSS [9]; ability to offerdiverse analyte-recognizing-sites interacting with specific analytesand to generate measurable electrical signals; antifouling proper-ties to eliminate interference from electrodes’ surfaces; easy elec-trochemical or chemical deposition on many types of electrodeswith multiple functional components; good biocompatibility andstability. Thus, PEDOT-based materials have been on a large scaleapplied in the electroanalysis field.

Although fruitful accomplishments have been achieved world-wide, there has been no review particularly focusing on PEDOT-based materials for electrochemical sensors so far. This paperaims to overview current progress on the synthesis and electro-chemical sensing applications of PEDOT-based materials in envi-ronmental monitoring, food and drug analysis and health care.

2. Fabrication and functionalization of PEDOT

There is no doubt that the preparation process is of vitalimportance for morphological, electrical andmechanical propertiesof final polymer and consequently its application. Generally, thepolymerization starts with radical cations generated from EDOTmonomer, via further radicaleradical coupling reactions growing

Fig. 1. Chemical structure of PEDOT and PEDOT:PSS [10].

Fig. 2. The number of papers from 2006 to 2016 searched on Web of Science on PEDOT-based sensor.

Y. Hui et al. / Analytica Chimica Acta 1022 (2018) 1e19 3

progressively, and ends with insoluble PEDOT chain reaching asufficient length [8], during which negatively charged counter-ionsin different sizes join to maintain polymers as electrically neutral.In the past decade, as for PEDOT-based modification layers, twodistinct directions are as follows:

1) The first is involved in attempts to functionalize the PEDOTbackbone through chemical strategies introducing active groupsto combine with probes or targets.

2) Another path designed to obtain the same objective lies inPEDOT’s combination with multiple components mostly nano-materials to obtain high electrical conductivity, large surfacearea, fast electron transfer and enhancive group functionality.

The former means creating new functional compounds withsuperior properties through abundant synthetic routes or over-oxidation in different mediums [25]. It sets high demands forrelative mechanisms exploring and vast experimental verifications.The latter is established on polymer composites, providing a simpleand operable protocol for extensive analysis applications.

2.1. Synthesis of PEDOT-based materials

Many methods are available for the synthesis of PEDOT-basedmaterials such as chemical polymerization [26,27], interfacialpolymerization [28], vapor phase polymerization [29] and elec-trochemical polymerization [30e35]. As summarized in Table 1, thesynthesis procedures, reagents and solvents were tabulated, andthe products with various nanostructures, characteristics and ap-plications were compared. One of the key criteria for the synthesisof PEDOT-based materials is the precise control of the size and thecomposition. Even similar composites can present different nano-structures with distinct characteristics. In general, the as-preparedPEDOT-based materials show large surface area, high conductivity,fast electron transfer rate, hydrophobic interaction and goodbiocompatibility due to the synergic effect from the individualcomponents.

The most widely used synthesis methods include electro-chemical deposition under proper potentials and chemical poly-merization in the presence of powerful oxidants with differentcomponents in the solvent, just as described in Fig. 3. For the

Table 1Synthesis of poly(3,4-ethylenedioxythiophene)-based materials

synthesis procedure reagent solvent product nanostructure characteristic application ref

chemical polymerization sodium bis(2-ethylhexyl)sulfosuccinateand FeCl3

hexane PEDOTnanotubes

diameter of 100e300 nm,wall thickness of 40e60 nmand length greater than 5 mm

fast diffusion of molecules detecting alcoholvapors

[26]

chemical polymerization H2PdCl4 solution alcoholic solution Pd/PEDOTnanospheres

Pd nanoparticles (~4.5 nm)homogenously on surface ofPEDOT nanospheres (~60 nm)

large surface area and goodelectrocatalytic activity

hydrogenperoxide sensor

[27]

liquideliquid interfacialpolymerization

GO and FeCl3 CHCl3 PEDOT/GOnanocomposite

nanorods-like PEDOTanchored on GO nanosheets

many electro-active sites detecting Hg2þ [28]

vapor phasepolymerization thenfunctionalized withgold nanoparticles

Fe (III) tosylate 40% aqueoussolution of 1-butanol

PEDOT-AuNPfilms

rough and porous surfacecoated with goldnanoparticlesin radii ~ 50e120 nm

increased surface area andimproved conductivity

DNA sensor [29]

electrochemicalpolymerization

DNA water PEDOT/ DNAbiocompositefilms

porous microstructure withnanoparticles connected inline

high effective surface area andelectron transfer ability

dopamine sensor [30]

electrochemicalpolymerization

LiClO4 andsodium dodecylsulfate

water PC4-EDOT-COOH film

homogeneous, compact anduniform cavities

large electroactive area, COOHgroups and goodbiocompatibility

detectingbactericidecarbendazim

[31]

electrochemicalpolymerization thenclick reaction

poly(sodium 4-stryrene-sulfonate)

e ferrocene-grafted PEDOTfilms

rough and porous structure fast electron transfer rate andshow multi-color states

electrochromicdevices

[32]

electrochemicalpolymerization thenover-oxidation

LiClO4 andNa2CO3

acetonitrile/water(v/v)¼ 1:19

over-oxidizedPEDOTnanofibers

brush-like nanofibers withdiameters of 80e100 nm

increased surface area andformation of functional groups

uric acid sensor [33]

electrochemicalpolymerization thensonicate in N,N-dimethylformamide

e BMIMBF4(1-n-butyl-3-methylimidazoliumtetrafluoroborate)

PEDOTquantum dots

average thickness of~0.40± 0.17 nm and uniformin diameter of ~2.3± 0.36 nm

remarkable photo- stability,two-photon excitationproperties, and goodbiocompatibility

cellular imagingand opticalsensing of Hg2þ

[34]

electrochemicalpolymerization thenimmobilize AChE(acetylcholinesterase)

LiClO4 andf-MWCNTs(functionalizedMWCNTs)

deionized water andacetonitrile

AChE /PEDOT-f-MWCNTsnanocomposites

globule like structure improved redox properties sensingorganophosphat-es (OPs)

[35]

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preparation of multicomponent systems, combinations of variousmethods were used, which involve post functionalization of thepolymer, secondary doping by surface modified nanostructures,and polymerization on immobilized components [36]. It wasparticularly investigated that the morphological and electrical

Fig. 3. Schematic outline of synthesis of poly(3,4-ethylenedioxythiophene)-basedmaterials.

properties of polymermodified electrodes are mainly influenced bysupporting electrolytes [37], solvents [38], electropolymerizationconditions [39] and heat treatments [40].

Chemical polymerization is suitable for the large-scale produc-tion of PEDOT nanomaterials. It was facile to prepare one dimen-sional PEDOT nanomaterials with controlled morphologies rangingfrom ellipsoidal nanoparticles and nanorods to nanotubes, bycarefully adjusting the additive amount of FeCl3 in the sodiumbis(2-ethylhexyl) sulfosuccinate reverse cylindrical micelle phase[26]. Reproducible PEDOT nanoclusters were obtained by directlyadding EDOT monomer to the iron (III) chloride oxidant ethanolsolution under stirring [41]. The PEDOT nanoclusters, with the sizedistribution from 100 nm to 250 nm, showed significant porosityand large specific surface area for the extraction of sulfonamides.

Chemically induced PEDOT is usually generated in the bulk so-lution and subsequently drop-casted on the conductive surface,resulting in relatively inefficient utilization and poor adhesion. Incomparison, the above disadvantages might be eliminated to someextent by electrochemical polymerization [42], since electro-chemical polymerization offers a better control of electrodepositionparameters, and also this approach allows the production in asingle step process [43]. PEDOT in a wide variety of nanostructures(e.g. nanowire [44], nanofiber [33], quantum dots [34], etc.) wereelectrochemical polymerized by using various solvents (e.g. water[45], acetonitrile [39], 1-ethyl-3-methylimidazolium bis(per-fluoroethylsulfonyl)imide[EMI][PFSI] [46], etc.) and diverse com-ponents (e.g. surfactant [45], metal nanoparticle [47], carbonnanotube [48], graphene [49], ionic liquid [50], etc.) throughdifferent electrochemical techniques (e.g. chronoamperometry[51], chronopotentiometry [24], cyclic voltammetry [33], etc.).

Significantly, if the adhesion between themodified layer and theelectrode surface weakens [20], the modified layer is easy to swell,

Y. Hui et al. / Analytica Chimica Acta 1022 (2018) 1e19 5

and even badly crack off in aqueous solution. As far as the workingelectrode is concerned, carbon-based electrodes, especially glassycarbon electrode (GCE), were widely selected as substrates inelectrochemical tests due to their stronger interaction with thepolymers’ backbone. In order to promote the adhesion and bindingforce between PEDOT modified film and the electrode interface inmultiple samples, Xu and his coworkers [52,53] introduced bindingagents to the synthesis process. Both poly (vinyl alcohol) (PVA) andcarboxymethyl cellulose (CMC) have friendly biocompatibility,excellent film forming and adhesive properties. Consequently, bothPEDOT:PSSePVAeMWCNTs/GCE [52] and PEDOT:PSS-CMC-rGO@Pd/GCE [53] exhibited high conductivity, improved water-stability and synergistically enhanced electrocatalytic ability fortarget analytes. In addition, bovine serum albumin (BSA) wasintroduced as a surface buffer between the slightly hydrophobicPEDOT film and the slightly hydrophilic Pt electrode in order toimprove the durability of the electrochemically synthesized PEDOTfilm on a Pt electrode [54].

2.2. PEDOT modified with functional groups

There are two ways to obtain functionalized PEDOT layers. Onthe one hand, the monomer can be designed to synthesize groupfunctionalized EDOT derivative prior to polymerization; on theother hand, the further overoxidation upon PEDOT can also intro-duce more active groups, such as sulfones, carbonyls and terminalcarboxylic groups [25].

One path to get functionalized PEDOT lies in synthesizing EDOTmonomer derivative with active functionalities to improvelyophilic solubility and good biocompatibility. Great efforts weremade to introduce pendant groups of sulfonates [55], carboxyl[31,56], hydroxyl [31,57] and azido [58]. Xu and his coworkers [56]successfully developed a water-soluble-C4-EDOT-COOH (4-((2,3-dihydrothieno[3,4-b]dioxin-2-yl)methoxy)-4-oxobutanoic acid)monomer through an efficient five-step synthesis route. Thecarboxyl group substitution on the conjugated backbone facilitatedthe combination of PC4-EDOT-COOH with biologically active spe-cies via covalent linkage and inorganic materials via layer-by-layerself-assembly. Therefore, PC4-based films were used to developelectrochemical chemo/bio-sensors for respective determination ofcatechol, ascorbic acid, Cd2þ, acetaminophen, quercetin, epineph-rine and tryptophan with satisfactory sensing performance. Inaddition, the as-prepared PC4 has better photophysical propertiesthan PEDOT to simultaneously detect multianalytes via UVevis andfluorescence spectroscopy.

The other path lies in developing overoxidized PEDOT film(PEDOTox). When imposed upon high positive potentials, thepolymer backbone underwent partial degradation. Lang et al. [59]summarized numerous experimental techniques that are appro-priate for monitoring the degradation signals and overoxidationmechanisms in previous literature. On the one hand, both thestructural morphologies and physical/chemical properties change alot. For example, increasing potential cycles resulted in morpho-logical changes and structure evolution, particularly indicating agradual improvement of crystallinity [60]. Due to the universalbelief inmechanical degradation of polymers at lower stress / strain[61] and decreasing electronic conductivity, overoxidized PEDOTfor analytical purposes was surveyed just three years ago. Actually,several unique characteristics of PEDOT films in different over-oxidation states facilitated analytical applications. PEDOTox modi-fied screen-printed carbon electrode (SPCE) exhibits a strongadsorption to several kinds of inorganic and organic chemicals[62,63], which is largely ascribed to its hydrophobicity interaction,surface micro-porous structure and the introduction of abundantoxygen functionality such as sulphone group, carbonyl group and

even carboxylic group. According to studies [33,62], both dopaminein standard solution and uric acid in body fluids could be electro-chemically detected at submicromolar concentration by PEDOToxmodified electrodes with excellent detectability and selectivity. Anobvious distinction lay in that Lin et al. [62] recorded the voltam-mograms in blank buffer solution after electrochemical adsorptionin the mixture of ascorbic acid (AA), uric acid (UA) and dopamine(DA), in contrast with others directly detecting in DA-containingsample [64]. On the other hand, the affinity towards UA of PEDO-Tox was nearly seven-times higher than that of overoxidized PPy(PPyox) under the same preparation condition [33], probablybecause PEDOTox showed more resistance to overoxidation thanPPyox and maintained higher conductivity.

2.3. PEDOT composites

New properties immediately stand out when PEDOT associateswith one or more components, such as supporting electrolytes [65],surfactants [26], inorganic nanomaterials [66], redoxmediator [67],ionic liquids [64], polymer [68], quantum dots [69] and even bio-molecules [70], as is depicted in Fig. 3. A great many componentswhich are negatively charged are beneficial to neutralize thebackbone of PEDOT [30,66]. The specialised illustration will bedescribed in detail as follows.

Common surfactants, such as cetyltrimethyl ammonium bro-mide (CTAB) and sodium dodecyl sulfate (SDS), could not onlylower the oxidation potential of EDOT, but also increase its solu-bility in aqueous and improve the interface interaction betweenmodified electrodes and the solvent. The dispersion solution ofPEDOT blended with PSS is commercially available and plays anextremely important role in fabricating PEDOT-based electro-chemical chemo/biosensors. Besides, surfactants with relativelylarge hydrophobic tails are also suited to form aggregated micellesin water [26,71]. Various morphologies of PEDOT nanomaterialswere facilely synthesized on the basis of different input amount ofoxidizing agent in the sodium bis(2-ethylhexyl) sulfosuccinatereverse micelle systems [26].

The PEDOT-inorganic nanomaterials (INs) composites integratethe favorable advantages of organic phase and inorganic phase. Onone hand, the incorporated INs are able to adjust aggregationstructure, improve carrier transport mobility and enlarge surfacearea. On the other hand, PEDOT helps to form uniform filmwith INsand improve the conductivity and mechanical stability of the de-vice during operation. Specifically speaking, metallic nanoparticles,namely Ag, Au, and Pd nanoparticles, could be facilely deposited onthe surface of PEDOT nanostructures without any dispersing orreducing agents. The very popular composites of Au nanoparticles(AuNPs) and PEDOTare easily prepared owing to the high affinity ofAuNPs to the sulfur atom in thiophene ring. The formation ofPEDOT@AuNPs composite was shown in Fig. 4A [72]. Conversely,the dispersion inwater of carbonaceous nanomaterials, particularlyCNT and graphene recognized as a next generation electronic ma-terial, is an unavoidable problem for fabricating high-performancePEDOT nanocomposite. Hence, functionalized novel carbon nano-materials have been investigated worldwide to solve this issue.Moreover, many of them have been successfully commercialized,such as carboxylated graphene and graphene oxide (GO). Thesynthesized PEDOTeGO nanocomposites show good stability,suggesting that GO serves as a good stabilizing agent for PEDOT dueto the abundance of hydrophilic groups in GO. The formation ofPEDOTeGO nanocomposites [49] can be attributed to the pepstacking interactions and the electrostatic adsorptions betweenthe positively charged PEDOT and negatively charged GO (Fig. 4B).Due to their remarkable electrocatalytic ability, good conductivity,high adsorption capacity, excellent mechanical strength, and high

Fig. 4. A scheme (not to scale) to illustrate the formation of PEDOT composites withthe use of AuNPs [72] and GO [49].

Y. Hui et al. / Analytica Chimica Acta 1022 (2018) 1e196

thermal stability, PEDOT-INs composites were widely used aselectrochemical sensing platforms for the determination of variousanalytes.

Fig. 5. SEM images of PEDOT nanocomposites with various components (A) AuNPs (Ref [66]determination.

Redox mediators with good redox activity act as an electrontransfer between the sensor active site and the electrode surface.Mediators such as ferrocene [73], cobaltocene [67], and phthalo-cyanines [74] were immobilized by click reaction or secondaryelectrodeposition on PEDOT films. Ferrocene is covalently bondedto the polymer chain to prevent its running off the electrode surfaceand the successful immobilization was confirmed by X-ray photo-electron spectroscopy (XPS), atomic force microscope (AFM), andcyclic voltammetry (CV) [73]. Celia et al. reported that the combi-nation of PEDOT with phthalocyanines can promote electrontransfer in the active centers of biological molecules and increasethe relative activity of the enzymes [74].

Ionic liquids (ILs), recognized as a new type of molten salt,consist of asymmetrical organic cations and relative small inorganicanions [75]. Compared with traditional solvents, environmentallyfriendly ILs possess excellent properties such as good ionic con-ductivity, negligible volatilization, wide potential windows, generalsolubility at room temperature and high viscosity [76,77]. An earlierfinding [78] revealed that both electroactivity and electrome-chanical actuation of electrochemically cycled p-conjugated poly-mers in ionic liquids have long lifetimes (for 10,000 redox cycleswithout significant decrease (<1%) in either stress or strain). It isworthwhile mentioning that ILs act as not only solvents but alsodopants during the monomer polymerization process. The inter-calation of the imidazolium cation along with widely reportedanion in the polymer film matrix, affirmed by energy dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy(XPS) studies, is responsible for the formation of fibrillar PEDOTnanostructures [46].

In addition, biomolecules-doped PEDOT biocomposites alsooffer synergistic advantages: on one hand, biocomposites can be

), (B) ssDNA (Ref [30]), (C) rGO (Ref [84]) and (D) [EMIM][NTf2] (Ref [64]) for dopamine

Fig. 6. Schematic illustration for preparation of PEDOT/GO/GCE and electrochemicaldetermination of Hg2þ. Reprinted from [28] with permission.

Y. Hui et al. / Analytica Chimica Acta 1022 (2018) 1e19 7

facilely fabricated via a one-step polymerization routine withcontrollable nanostructures and high surface area since negativelycharged phosphate groups [30] or carboxyl groups [79] link withthe PEDOT main chains by electrostatic interaction; on the otherhand, biomolecules provide high catalytic activity [30] and mo-lecular recognition capabilities [70]. Based on virus-PEDOT com-posites, Penner and Weiss group have developed two types ofbiosensors: virus-PEDOT nanowires transduce target binding usingthe through-nanowire resistance [70,80]; whereas virus-PEDOTfilms use EIS without added redox species to transduce targetbinding [81e83]. Biomarkers, prostate specific membrane antigen[80,82] and human serum albumin [83], were detected at nano-molar level.

Taking the determination of dopamine as an example, differentcomponents (e.g. AuNPs [66], ssDNA [30], rGO [84] [EMIM]NTf2[64] ), were incorporated into the PEDOT matrix to enhance elec-trocatalytic activity toward the oxidation of dopamine. Forinstance, AuNPs were immobilized on the polymer matrix throughelectrostatic interactions and covalent interaction of the unchelatedAueS bond to facilitate the mass transport and weaken thecapacitive current [66]. AuNPs with average diameter of 16 nmwere uniformly distributed on PEDOT film with network-likeporous microstructure (Fig. 5A). Luo’s group [30,64,84] concen-trated on dopamine sensors based on PEDOT nanocomposites via asimple one-step electrochemical polymerization process. All thetheoretical detection limits were extrapolated at mg/L level. SEMimages showed disordered small nanoparticles (Fig. 5B), wrinkledsurface morphology (Fig. 5C) and highly porous morphology con-taining interconnected ginger-like dots (Fig. 5D), respectively. ThusPEDOT nanocomposites can be shaped into various structures withdifferent morphologies. In their further research [85], a selectiveaptamer was subsequently immobilized on the PEDOT/rGO inter-face [84]. Since chemically and mechanically robust films served torecruit and preconcentrate dopamine from solution prior to itsdirect assessment by DPV, the voltammetric aptasensor displayedan ultra-low detection limit of 78 fM and 9-generationregeneration.

3. PEDOT-based materials for electrochemical sensors

Most of the primary considerations in the fabrication of any typeof electrochemical sensors and biosensors are: (1) the preparationof effective recognition events and/or biochemical sensitive mate-rials; (2) the selection of appropriate substrate electrodes, partic-ularly in relation to patterned microelectrodes or nanoelectrodes;(3) the application of suitable electrochemical techniques (e.g.potentiometry, amperometry, impedance spectroscopy and vol-tammetry techniques are commonly applied for analytical signalassessment) [8]; (4) the establishment of efficient electron transferand amplification of measurable signals. In addition, the propertiesof analytes have an important effect on both reaction mechanismsand transducer-use patterns. Finally, the potential application insome special fields can be evaluated to a large degree.

Currently, electrochemical sensors based on conducting poly-mers have attracted considerable attention [86], especially elec-trochemical (nano) biosensors [87,88]. PPy [42], PANI [89] and PTh[8] composites for the design of electrochemical sensors havealready been reviewed. There have been two papers on PEDOT-based materials applied as chemo/biosensors so far. One paperpresented remarkable snapshots of medical biosensors [17] and theother only focused on glucose and dopamine biosensors [88].Obviously, PEDOT shows high conductivity, good antifoulingproperties, and great biocompatibility with biological media.Furthermore, synergistic effects between PEDOT and differentcomponents actually mean an optimized integration rather than a

simple sum of benefits, in the case of multicomponent systems.PEDOT composites with novel functional materials can put forwardnew proposals for satisfying urgent demands of better stability,larger surface area, faster electron transfer, higher selectivity andlower detection limits in electrochemical analysis applications. Theinherent properties of PEDOT-based materials facilitate the archi-tecture of high-performance chemo/biosensor platforms in envi-ronmental monitoring, food and drug analysis and health care.

3.1. PEDOT-based sensors for environmental monitoring

3.1.1. Detection of inorganic ionsHeavy metals universally existing in global soil and water are

admittedly environmental pollutants with high toxicity, easyaccumulation and hard degradation. It has been reported thatPEDOT/surfactants modified glassy carbon electrodes succeeded insimultaneous determination of heavy metals Zn, Cd, Pb, Cu andmetalloid As, in a pretty wide window [45]. Moreover, PEDOT-based materials were used as adsorbents in preconcentration pro-cedure prior to determination, playing an effective role in adsorb-ing and enriching heavy metals [90,91]. Mercury is particularlyinfamous for minamata disease and difficult to perform selectivedetermination, since many surface-functionalization-basedmethods usually suffer from complexity in manufacturing theelectrodes and/or the modification process or synthesis of specificreceptors [92]. PEDOT composites incorporated with AuNPs modi-fied electrodes have been popular protocols [93e95] for the strip-ping voltammetric detection of mercury (II). AuNPs can formamalgam with mercury and synergistically enhance conductivityand stability of the composite. Ding et al. synthesized Au@PEDOTnanoparticles by the chemical reduction of HAuCl4 in aqueous so-lution with EDOT as the reductant, and PSS as the stabilizer [95].Au@PEDOTmodified glassy carbon electrode shows high selectivityand reusability for mercury (II) in chloride media at micromolarlevels, thus it is very suitable for the determination of mercury (II)in seawater and wastewater samples. PEDOT nanorods/grapheneoxide nanocomposite modified glassy carbon electrode was pro-posed for sensitive detection of mercury (II) with adsorption pro-cess of mercury (II) from the solution to the surface [28]. PEDOTshowed a nanorods-like structure anchored on the surface of GOsheets with many electro-active sites. Fig. 6 shows a scheme of thefabrication procedure and the determination process. The resultingmaterial exhibited high electrocatalytical activity toward mercury(II) and long-term stability to perform successive determinationsover 30 times. Moreover, novel PEDOT-quantum dot was synthe-sized for selective detection of mercury (II) [34] due to Hg2þ-induced quantum dot aggregations via coordination interactions.

There is a growing demand for ubiquitous nitrite detection in

Y. Hui et al. / Analytica Chimica Acta 1022 (2018) 1e198

foods, water and environmental samples as the excess uptake ofnitrite cause gastric cancer and blue body [48]. Electrooxidation ofnitrite at PEDOT nanocomposites modified electrodes have beencontinuously surveyed [47e49,96e98]. Liu et al. [49] proposedheadmost interface polymerization of EDOT with GO as a stabiliz-ing agent, thus, the highly-stable aqueous dispersion of PEDOTnanorodeGO (Fig. 4B) nanocomposites were first applied in cata-lytic oxidation of nitrite. Co nanoparticles [96] were added toPEDOT-graphene films to comprehensively utilize the advantagesof two sides.The modified electrodes enable the determination ofnitrite at low potentials (~0.5 V lower than bare GCE) where thenoise level and interferences by other electro-oxidizable com-pounds are weak. The unitary PEDOT film [97] with hollow-microflower structure was developed as a nitrite sensor withbroad linear range. However, among common interferences, SO3

2�

showappreciable impact on the determination of nitrite. Extremelylow LOD (limit of detection) of 60 nM for nitrite determination wasachieved by Cu-Co/PEDOT/CNTs [98] and PEDOT/AuNP [47] com-posites modified electrodes with satisfactory catalytic activity andhigh reproducibility by the same group. The former with Cu-Cobimetal nanoparticles featured synergic enhancement effect forfast response time within 2 s while the latter with AuNPs acting asboth dopants and templates showed admirable amperometric re-sponses to nitrite without any interference from possible species.

Other inorganic ions were also detected based on PEDOT com-posites modified electrodes. Phosphomolybdate-doped-PEDOTcoated gold nanoparticles [99] were fabricated, characterized andemployed for monitoring electroreduction of bromate ions in anacidic media. The phosphomolybdate anions provide additionalstability and functionality to this new composite material. So the

Fig. 7. Schematic representation of the preparation and the use of PEDOT-b

composites modified glassy carbon electrode showed high catalyticactivity towards the reduction of BrO3

� in the concentration from0.25 to 3mM. A microfluidic impedimetric sensor [100] usingelectrospun PEDOT nanofibers (PEDOT-NFs) conjugated with bothGO nanosheets and nitrate reductase (NiR) enzyme molecules asthe bioelectrode material, was capable to accurately quantify ni-trate ions in real samples extracted from soil. Notably, the presenceof S-Au bonding between the PEDOT NFs-GO composite and Ausurface facilitated the surface modification of the workingelectrode.

3.1.2. Detection of organic pollutantsOrganic pollutants, especially persistent organic pollutants

(POPs) have severely hazardous impacts on human health andenvironment with their hard degradation, potential bio-accumulation and synergistic effects. PEDOT/MWCNT doped withCTAB or SDS were used for ultrasensitive analysis of various pyre-throids and an organochlorine pesticide (OCP) [101]. The modifiedelectrodes drastically improved the electrochemical reduction andSDS doped PEDOT/MWCNT modified electrode particularlyexhibited stable and reproducible response. The improved sensi-tivity was attributed to the enhanced adsorption of pesticides in amonolayer of surfactants and the weak hydrophobic adsorption ofsurfactants on hydrophobic and smooth surface of MWCNTs.Comparatively low LODs for cypermethrin, deltamethrin, fenval-erate and dicofol of 0.015, 0.063, 0.061, 0.01 ng/L were obtained,respectively. Another pesticide molecule, atrazine, was selectivelydetected by PEDOT-based MIP electrochemical sensor [102].Molecularly imprinted polymer (MIP) is a tailor-made, stablepolymer with molecular recognition ability. As is showed in Fig. 7,

ased MIP electrochemical sensor. Adapted from [102] with permission.

Y. Hui et al. / Analytica Chimica Acta 1022 (2018) 1e19 9

two moieties are necessary for the fabrication of such chemicallyfunctionalized, MIPs-based sensing layer, (i) a molecular sensingunit AAT to bind with atrazine, together with (ii) a hydrophiliclinker EDOT to ensure electroactivity in aqueous medium. Thedeveloped sensor presented excellent selectivity towards triazinicfamily and wide range of detection (10�9mol L�1 to1.5� 10�2mol L�1 in atrazine).

Different from drop-coating MWCNT-SDS suspension followedby electrooxidation EDOT monomer[101], chemically polymerizedPEDOT/MWCNT composite was obtained by successively addingEDOT monomer and FeCl3 to acid-treated MWCNTs suspension,and it can be applied for stable and reusable determination ofsuspected carcinogenic nitrobenzene [103]. The PEDOT/MWCNTcomposite modified carbon paste electrode significantly decreasedthe nitrobenzene reduction potential and increased the reductioncurrent due to larger surface area and excellent catalytic activity.Marek et al. developed a sulfonated PEDOT (PEDOT-S) modifiedCNTs for electrocatalytic determination of four kinds of nitro-aromatic compounds in which PEDOT-S act as a conducting poly-mer, polyelectrolyte and efficient dispersing agent [104]. BisphenolA, awidely used toxic chemical, was detected by PEDOT-ionic liquidcomposites modified SPCE [105] by flow-injection amperometrywith electrode refreshment and fast responses. Due to theadsorption capacity and antifouling features of the composites, theproposed sensor succeeded in 77 successive tests of 10 mMbisphenol A with enhancive current responses and signal stability(RSD¼ 1.95%). The detection results for bisphenol A were in goodagreement with ultra-performance liquid chromatography ultra-violet detector (HPLC-UV) analysis with relative errorbetween �2.0% and �5.1%. The developed sensor had promisingpotential in testing real samples.

3.1.3. Gas sensorsThere is an urgent demand for real-time detection of combus-

tible, explosive or toxic gas in a complex environment. PEDOT hasbeen a promising material for gas monitoring since 1999 [23],possibly due to its tunable conductivity at ambient temperaturethrough several different mechanisms including doping/dedoping,reduction/oxidationand and hydraulic conductivity [106].Compared with metal oxides doped commercial sensors, the sen-sors made of PEDOT-based materials have more advantages in

Fig. 8. Schematic diagram of the fabrication process of PEDOT/R

simple fabrication, low-power consumption and room-temperature operation. Single PEDOT nanowire sensors withtunable gas sensing performance were used for detecting watervapor and volatile organic compounds (VOCs) [44]. It was reportedthat variation in the conjugation lengths, dopant type and con-centration of the wires had significant impacts on the electrical andsensing properties of single PEDOT nanowire devices. HybridPEDOT-nanosensors incorporated with ionic liquid [107], polymer[108], metal oxide [109,110], graphene [111,112] and CNTs [113,114]also have been massively fabricated for sensitive, selective, rapidand stable detection of TNT, CO2, NO2, NH3 and VOCs.

Aguilar et al. [107] proposed an integrated electrochemical andelectrical nanosensor making full use of both the electrochemicalsignatures of the reduction of TNT and specific interactions of thereduction products with the polymer nanojunction. The highsensitivity was attributed to electrical detection of the PEDOTnanojunctions which bridged two gold electrodes separated by asmall gap (60e100 nm) on a silicon chip. Moreover, the chip wascovered with a thin layer of ionic1-butyl-3-methylimidazoliumhexafluorophosphat (BMIMPF6) which acted not only as a stableelectrolyte but also as a preconcentration medium for nitro-aromatic compounds. Finally, the sensor is capable of detectingppt-level TNT within 1e2min in the presence of various commoninterferents in ambient air. The sensing properties of PEDOT: PSScoated SWCNTs towards saturated vapors of VOCs were investi-gated over a wide range at room temperature [114]. The LOD of thesensor was calculated to be 1.3%, 5.95% and 3% for saturated vaporsof methanol, ethanol and methyl ethyl ketone, respectively.

NH3 can deprotonate the polymer and decrease its electricalconductivity. MWCNTs reinforced two types of conducting poly-mers were fabricated for NH3 determination. MWCNTePEDOT: PSScomposite was found to bemore sensitive (with sensitivity of ~16%)with less response time (~15min) and better thermal stability (upto 190 �C) than MWCNTePANI composite [113]. However, sensorrecovery posed a great problem at room temperature. Sakshi et al.applied a suitable combination of heat and DC electric field toprovide sufficient energy to desorb chemisorbed NH3 from CNTsurface completely. Recovery time was drastically reduced from48 h to 20min. Similarly, 50wt% N-doped graphene quantum dots(N-GQDs) within the polymer matrix brought about higher sensingresponse (212.32% upon exposure to 1500 ppm NH3 gas), faster

GO based gas sensor. Reprinted from [111] with permission.

Table 2PEDOT-based sensors for environmental monitoring

analyte Modified electrode technique Linearrange

LOD Sensitivity sample ref

Hg2þ Au@PEDOT/GCE ASV 0.5e20.0 mM

50 nM 7.56 mA mM�1 e [95]

Hg2þ PEDOT/GO /GCE DPSV 0.01e3.0 mM

2.78 nM 6.74 mA mM�1 tap water [28]

NO2� PEDOT hollow

microflower/FTOAMP 50-

7500 mM0.59 mM 0.38 mA mM�1 rain , river, tap

water[97]

NO2� PEDOT/AuNP/GCE AMP 0.2

e1400 mM60 nM 0.033 mA mM�1 tap water,

pickle samples[47]

BrO3� H3PMo12O40

/PEDOT/AuNP/GCECV 250

e3000 mMe 0.48 mA mM�1 e [99]

NO3� nitrate reductase/

PEDOT NFs-GOEIS 7.09

e7128 mM2.18 mM 1.06U/mM agricultural soil [100]

three pyrethroidsand an OCP

PEDOT/MWCNT/GCE CV/DPSV 0.01e50000 mg/L

cypermethrin 0.015 ng/L, deltamethrin 0.063 ng/L,fenvalerate 0.061 ng/L, dicofol 0.01 ng/L

e spiked water [101]

nitrobenzene PEDOT/MWCNT/CPE AMP 0.25e43 mM

0.083 mM 0.043 mA mM�1 wastewatersamples

[103]

nitrobenzenes(NBs)

CNTs/PEDOT-S/GCE DPV/SWV 5-55 mM e 1,2-dNB0.215 mA mM �1

1,3-dNB0.095 mA mM �1

1,4-dNB1.03 mA mM �1

e [104]

bisphenol A PEDOT /BMIMBr/SPCE

AMP 0.1e500 mM

0.02 mM 0.2661 mA mM�1

plastic waterbottles

[105]

NO2 PEDOT-PSS/TiO2

nanofiber/IDEChemiresistive 10

e130 mg L�15 mg L�1 e e [109]

VOCs PEDOT:PSS coatedSWNTs

Chemiresistive 2.5%e75% Methanol 1.3%, ethanol 5.95%, methyl ethyl ketone 3% e e [114]

Y. Hui et al. / Analytica Chimica Acta 1022 (2018) 1e1910

response time (6.8min) and higher stability than that of the PEDOT:PSS sensor [112].

Katarzyna et al. demonstrated a simple and fully electro-chemical route to fabricate a NO2 gas sensor [111]. As is shown inFig. 8, the sensing platform was equipped with gold interdigitatedelectrode (IDE) and built-in heater, and the sensing PEDOT/RGOlayer was fabricated by electropolymerization method and reduc-tion in 0.1M KCl. The factors which may have an influence on thesensing performance were investigated, including the operatingand annealing temperature, flow rate and relative humidity. Metaloxides constantly played an important role in gas sensors, espe-cially their nanocomposites with organic polymers generatingsynergetic effect. PEDOT-coated TiO2 nanofibers [109] withframework structure exhibited good, reversible and reproducibleconcentration-dependent response to NO2, and LOD in 90-s mea-surement was estimated about 5 ppb, barely suffering from varia-tions of H2O, CO2 and O2 concentrations. In addition, Lin et al.developed a fully gravure printed WO3-PEDOT: PSS sensor on apolyimide foil [110], showing good sensing response characteristicstowards 50 ppb NO2 gas at room temperature, with response andrecovery time of 45.1 and 88.7 s, respectively. It was very conve-nient in a wide variety of fields where operation at room temper-ature, light weight and mechanical flexibility are important issues.

Besides specific analytes (as summarized in Table 2), environ-mental conditions can be also monitored by using PEDOT-basedmaterials. PEDOT: PSS and its incorporation with secondarydoping agents can be utilized in monitoring relative humidity (RH)on the basis of electronic conductivity of the film. Silvia et al. [115]embedded iron oxide nanoparticles in PEDOT: PSS to prepare free-standing nanocomposite ultrathin films, which retain both mag-netic and electrical conductivity functionalities. The results fromhumidity-sensing experiments showed that, the resistance ofPEDOT: PSS/ iron oxide nanoparticles nanofilms linearly increasedwhen exposed to increasing levels of RH, in the range of 30e70%

RH. In addition, PEDOT: PSS could act as the solid electrolyte in pHelectrode applied in the environments with extreme high tem-perature[116].

3.2. PEDOT-based sensors for food and drug analysis

Food safety and drug analysis are global issues in the actualcontext of intensive development of the food and pharmaceuticalsindustry. Basically, effective constituents monitoring and fastquantification of contaminants represent two key directions forassessment of the food and drug quality. This paper summarizes thedetection of organic species in food and drug exploiting PEDOT-based materials (Table 3). In particular, studies dealing with foodadditives, pesticide residues, vitamin, antibiotics and narcoticsdeserve mentioning.

Trace amounts of ponceau 4R, an edible synthetic colorant usedin food and drinks, was successfully detected by as-prepared pol-y(EDOT-AA-co-EDOT):PSS-SWCNTs-PVA modified glassy carbonelectrode [117]. The interferences of food ingredients and additivesincluding sweeteners, preservatives and coloring agents were alsoinvestigated. Techniques like CV [118] and DPV [119] were used forthe quantification of caffeic acid in white wine and red white withsimilar sensitivity and detection limit. Vera et al. developed a thin-film miniaturized electrode for the voltammetric determination ofdiphenylamine that was listed as prior pollutant and forbiddenwithin the European Union, by immobilizing MIP particles intoPEDOT polymer membrane [120]. The thickness of the polymerlayer was optimized in order to get an adequate diffusion ofdiphenylamine and thus achieve an adequate charge transfer at theelectrode surface. The optimum membrane thickness was foundabout 50 nmwith a polymerization time of 1min. A highly selectiveand a sensitive response to diphenylamine in a range of4.95e115 mMwas obtained, compared with the bare gold electrode,and the electrode modified with PEDOT and nonimprinted polymer

Table 3PEDOT-based sensors for food and drug analysis

analyte Modified electrode technique Linear range LOD sample ref

Ponceau 4R poly(EDOT-AA-co-EDOT):PSS-SWCNTs-PVA/GCE DPSV 5.5 nM-110.6 mM 1.8 nM soft drinks [117]caffeic acid PEDOT:PSS/Pt CV 10 nM-6.5mM 3 nM white wine [118]caffeic acid AuePEDOT/rGO/GCE DPV 0.01e46 mM 4 nM red wines [119]diphenylamine PEDOT/MIP/Au DPV 4.95e115 mM 3.9 mM apple juice [120]bactericide carbendazim PC4-EDOT eCOOH/GCE DPASV 0.012e0.35 mM 3.5 nM paddy water, juice [31]organophosphates AChE/PEDOT-fMWCNTs/FTO DPV 0.001e50 mg L�1 0.001 mg L�1 lettuce [35]Vitamin K3 PEDOT:PSS-CMCrGO@Pd/GCE LSV 0.4e90 mM 14 nM animal blood, feedstaff [53]acetaminophen PEDOT/PSS/GCE LSV 0.05e1mM 10 mM medications [122]acetaminophen PEDOT/PSS/GCE DPV 5-65 mM 0.3 mM medications [122]rutin(vitamin P) PEDOT/GO/GCE DPV 0.004e1 mM and 1e60 mM 1.25 nM rutin tablets [123]penicillin PEDOTeAuNPs/GReFe3O4NPs/GCE DPV 0.1e200 mg L�1 57 ng/L milk [124]DOX MIP/AuNPs-CS/ PEDOT/Au DPV 0.4e1 mM 65 nM human serum [125]morphine MIPePEDOT/Pt AMP 0.01e0.2mM 0.3 mM e [126]morphine PEDOT/Pt SWV 8 mM-150 mM 67 nM tablets [127]

Y. Hui et al. / Analytica Chimica Acta 1022 (2018) 1e19 11

particles. In the application of detecting diphenylamine in spikedapple juice samples, values from 97% to 104% recovery were ob-tained. Enzyme inhibition-based electrochemical sensor [35] wasproposed for detecting organophosphate(OP) insecticides, whosemaximum residue levels on foods and agricultural commoditieswere strictly regulated by both Food and Agriculture Organization(FAO) and World Health Organization (WHO). PEDOT-functionalized MWCNTs matrix provided high redox propertiesand biocompatible microenvironment to retain acetylcholines-terase (AChE). The pH value of the phosphate buffer, concentrationof enzyme, substrate concentration and incubation time wereoptimized using chlorpyrifos-methyl as a model OP due to itsstrong inhibitory effect on AChE. The resultant sensor succeeded inthe analysis of chlorpyrifos-methyl in vitro as well as spiked samplewith good limit of detection (0.001 mg/L), appreciable reusability(six times) and long-term stability (one month). Interestingly, foodfreshness can be assessed by the determination of VOCs biomarkersemitted during food degradation. Quantum chemo-resistive vaporsensors were developed from the assembly of Fe3O4 decorated RGOwith poly(ionic liquid) (PIL) and PEDOT [121]. PIL functioned aspolymerization template and provided a linkage between PEDOTand Fe3O4-RGO. The interdigitated electrodesmodified by the spraylayer-by-layer method showed excellent responses at the ppm levelcompared to its each component, especially when these bio-markers were polar (ethanol, methanol and acetonitrile).

Tsakova et al. electrodeposited EDOT monomer with variousanions and surfactants on GC electrodes, and all exhibited a goodelectrocatalytical effect for the detection of acetaminophen [122],an ingredient of numerous pharmaceutical formulations. PEDOT/PSS thin film modified electrode was found to be remarkablyeffective by investigating the type of dopant and the polymeriza-tion charge. Vitamin P [123] and Vitamin K3 [53] were detected byhierarchical nanocomposites of PEDOT/GO and PEDOT:PSS-CMC-rGO@Pd, respectively. Taking benefit from a positive synergy ofindividual properties, the designed sensors could detect Vitamin Pand Vitamin K3 at nM level without interference from many ionsand organic substances. And satisfactory recovery values are be-tween 93% and 103.4% in real sample analysis. The RSDwas 2.8% for6 successive assays at 1 mM Vitamin P [123] and 0.4% for 30 suc-cessive assays 98 mM Vitamin K3 [53]. DPV was utilized todemonstrate the electrochemical performance of the novel apta-sensor [124] and the imprinted sensor [125] for the determinationof antibiotic penicillin and doxorubicin hydrochloride (DOX),respectively. With penicillin aptamer as the specific recognitionelement assembled on a PEDOTeAuNPs/GReFe3O4NPs compositeplatform via AueN bonds, the proposed aptasensor showed highselectivity for the detection of penicillin and a low detection limit of

0.057 ngmL�1 [124]. The electrochemical sensor modified withDOX-imprinted membrane exhibited good reproducibility, satis-factory stability and excellent selectivity in the determination ofDOX in human blood serum samples with the relative standarddeviation (RSD) below 4% and recovery ranging from 96.0% to106.7% [125].

Morphine was detected by two types of PEDOT modified Ptelectrodes [126,127]. One proposed a typical microfluidic deviceusing MEMS (micro-electro-mechanical-systems) technologies,consisting of MIP films (PEDOT as the imprinting polymer withmorphine as the template), a PDMS-based microchannel, a peri-staltic micropump, microvalves and sensing microelectrodes [121].The other focused on a simple, cheap and fast quantification ofmorphine in human urine without any sample pretreatment [122].The addition of sodium dodecyl sulfate (SDS) was proved to facili-tate the electron transfer between morphine and the electrode byEIS.

3.3. PEDOT-based sensors for health care

It is essential to implement real-time and accurate detection ofcrucial biomolecules in human body. Taking glucose as an example,if blood glucose concentrations are higher than the normal range ofabout 3.9e6.2 (empty stomach) or 3.9e7.8 (2 h after food) mM, itprobably indicates the metabolic disorder resulting from insulindeficiency and hyperglycemia. Sensitivity of conducting polymersto these biochemical molecules depend on the intrinsic affinity ofthe conducting polymers’ backbone, the affinity of side groups orbinding to immobilized receptors [106]. Electrochemical sensing ofbiomolecules consists of two broad categories depending onwhether the bioreceptor is involved. Taking glucose as an example,both nonenzymatic sensing and enzymatic biosensing are widelysurveyed and used [128]. Health-care sensors utilizing novelPEDOT-basedmaterials address two goals: on one hand, to enhanceelectrochemical response to the molecular detection; on the otherhand, to simultaneously act as the immobilization matrices for thebioreceptors. Bioreceptor is the most critical part of biosensor,shouldering the responsibility for specific recognition to targets.Table 4 summarized a selection of recent publications, which arecategorized according to the recognition element: catalytic sensorsand affinity sensors. Great efforts have also focused on developingPEDOT-based healthcare sensors without bioreceptors in order todo direct detection of biomolecules, as is concluded in Table 5.

3.3.1. Catalytic sensorsCatalytic sensors usually use immobilized enzymes, cells and

tissues as biological recognition layers on the electrode surfaces.

Table 4PEDOT-based sensors for health care with bioreceptors

analyte bioelement Modified electrode technique Linear range Sensitivity LOD ref

catalytic sensorsglucose GOx PEDOT/IDUA AMP 1-20mM 0.02516 mAmM�1 800 mM [131]glucose GOx PEDOTePd/GCE AMP 0.5e30mM 0.112 mAmM�1 75 mM [129]glucose GOx CNT/PEDOT/CFE AMP 0.05e1.25mM 8.4 mAmM�1 37 mM [132]ethanol AlcDH CNT/PEDOT/CFE AMP 0.2e1.8mM 0.54 mAmM�1 100 mM [132]hydrogen peroxide HRP AuNPs/PEDOT(BSA)/Pt CV 1-15mM 186.4 mAmM�1 e [54]ascorbic acid AO grapheneePEDOT/GCE AMP 5.0 mMe0.48mM e 2 mM [130]catechol PPO Fe2O3-rGO-PEDOT-GC DPV 40 nM-62 mM e 7 nM [133]acetylcholine AChE-ChO Fe2O3/rGO/PEDOT/FTO CV 4 nM-800 mM 0.3 mA mM�1 4 nM [134]

affinity sensors

carcinoembryonic antigen carcinoembryonic antibody AuNPs/PEDOT/GR/GCE DPV 0.4 ng L�1-40 mg L�1 0.1165 (lg (ng/mL))�1

0.1 ng/L [135]

carcinoembryonic antigen Carcinoembryonic antibody PEDOT/ hyaluronic acid /GCE DPV 1 ng L�1-0.1mg L�1 e 0.3 ng/L [136]alpha fetoprotein alpha fetoprotein antibody ZnSe/AzureI/AuNPs/PEDOT/Pt CV 5� 10�5-250 mg L�1 0.2387 mA (lg (ng/

mL)) �11.1 pg L�1 [69]

alpha fetoprotein alpha fetoprotein antibody AuNPs/PEDOT/ poly(ethylene glycol)/GCE

EIS 0.001e10 pg L�1 5.2 (lg (g/mL)) �1 0.3 fg L�1 [68]

E.coliO157:H7 HRP-labeled antibody HRP-sulfonated grapheneePEDOTeAuNPs-GCE

DPV 78e7.8� 106 cfumL�1

33.68 (log (cfu/mL))�1

34 cfumL�1 [156]

C-reactive protein e poly(EDOT-co-EDOTPC)/GCE DPV 10-160 nM e 37 nM [137]prostate-specific antigen prostate-specific antibody AuNPs/PEDOT/GR/GCE ECL 1 ng L�1-10 mg L�1 1713 a.u. (log (ng/

mL)) �10.8 ng/L [138]

17b-Estradiol 76-mers sized biotinylatedaptamer

AuNP/PEDOT/Au SWV 0.1e100 nM 8.3 (log nM) �1 0.02 nM [139]

ampicillin 19-mers sized aptamer EDOT:TsO/PEDOT-OH:TsO/microelectrodes

EIS 100 pMe1mM e 10 pM [140]

kanamycin A 21-mers sized aptamer EDOT:TsO/PEDOT-OH:TsO/microelectrodes

EIS 10 nM - 1mM e e [140]

influenza A virus aptamer A22 PEDOT-OH:TsO /microelectrode EIS 10-106 pfumL�1 e e [141]DNA sequence associated with

S.aureuscomplementary strandDNA

PEDOTeAuNP/Au AMP 150 pM-1 mM 4.072 mA (lg M) �1 e [29]

27-mer DNA oligonucleotides 6-mercapto-1-hexhane HS-ssDNA

PPyePEDOTeAgNP/GCE EIS 10 fM-10 pM e 5.4± 0.3 fM [142]

DNA and DNAeMitomycin C carcinoembryonic antibody PEDOT/ chitosan /pencil graphiteelectrode

DPV 100 -1000mg L�1 e 8.41mg L�1 [143]

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Enzymes are the most commonly used because they are highlyspecific and effective for chemical reactions that they catalyze.Reaction status can be monitored using AMP, CV or DPV, if eitherthe obtained product or consumed reactant is electroactive. A widerange of small biological molecules, including glucose, hydrogenperoxide, and ascorbic acid, can be electrochemically catalyzed onthe basis of both prepared nanomaterials and immobilized en-zymes. The distinction lay in the accession of specific enzymes suchas glucose oxidases (GOx) [129], horseradish peroxidase (HRP) [54]and ascorbate oxidase (AO) [130]. Enzyme electrodes have beenextensively surveyed for high catalytic activity of inclusive enzymesand they are also available commercially. According to Michaelis-Menten equation, LOD of catalytic sensor is largely determined bythe activity of the enzyme. Thus, it is also essential to accommodateproper conditions throughout the whole experiment, such asdesirable temperature and buffer pH.

Conducting polymers have been frequently used for immobi-lizing enzymes, because enzymes can be easily entrapped withconducting polymers by physical adhesion or by an electrochemicalprocess. For instance, amperometric glucose sensors with a thinlayer of glucose oxidase covered on the electrode surfaces, wereconstituted on the basis of PEDOT and its composites [129,131,132].Although enzymes hinder electron transfer, the polymer matrixprovides good enzymatic reaction pathways for the electrode/electrolyte interactions. Santhosh et al. [129] proposed a newmethodology involving the combination of a soft template (sur-factant) and an ionic liquid (cosurfactant) for the preparation ofPEDOT nanofibers with diameters ranging from 5 to 10 nm. Elec-trodeposition of palladium nanoparticles and immobilization of

glucose oxidase are done sequentially into nanofibrous PEDOT forglucose determination in a wider linear concentration range. Nienet al. [131] electropolymerized EDOT and coexisting glucose oxi-dase by CV to modify the interdigitated ultramicroelectrode array.However, the amount of enzyme entrapped in the matrix wasmeasured spectroscopically about 0.101 U/cm2 [131]. The inefficientimmobilization of GOx led to relatively poor sensitivity comparedwith 8.4 mA/mM of CNT/PEDOT/CFE interface [132]. CNT co-immobilized with PEDOT on carbon film electrode substrates wasinvestigated as a new biosensor platform incorporating the en-zymes of glucose oxidase (GOx) and alcohol dehydrogenase(AlcDH) [132]. High sensitivity of 8.4 mAmM�1 for glucose and0.54 mAmM�1 for ethanol was obtained, respectively, by taking fulladvantages of the synergistic combination of conducting polymerand CNT.

In the case of oxidases, the sensing performance also dependson the availability of molecular oxygen and O2’s affinity to enzymes.This drawback could be avoided by purging pure nitrogen gas onthe surface of the sample solution and using dehydrogenaseswhichdo not require any oxygen as electron acceptor [54]. Besides, theaddition of oxidized nicotinamide adenine dinucleotide (NADþ), asthe electron transfer mediator in the detection solution coulddramatically enhance the sensitivity of detection by about 35.5%[54].

Lu et al. prepared enzyme electrodes by cyclic voltammetricscanning in a fresh solution containing 1.0mgmL�1 GO, 0.01MEDOT monomer, 0.01M LiClO4 and 10mgmL�1 AO [130], obtaininga cost effective biosensor for the determination of ascorbic acid(AA). For the first time a one-step electrochemical redox route was

Table 5PEDOT-based sensors for health care without bioreceptors

analyte Modified electrode technique Linear range Sensitivity LOD ref

glucose CuNPs/ PEDOT/RGO/GCE AMP 0.1 mM-1.3mM 64.34 mAmM�1 47 nM [145]hydrogen peroxide Pd NPs /PEDOT nanospheres /GCE AMP 2.5 mM-1 mM 14.05 mAmM�1 2.84 mM [27]dopamine PEDOT/RGO/GCE AMP 0.1e175 mM e 0.039 mM [84]ascorbic acid MoS2 nanosheets / PEDOT/GCE DPV 20e140 mM 8.4823 mAmM�1 5.83 mM [146]dopamine MoS2 nanosheets / PEDOT/GCE DPV 1e80 mM 257.2964 mAmM�1 0.52 mM [146]uric acid MoS2 nanosheets / PEDOT/GCE DPV 2e25 mM 743.4029 mAmM�1 0.95 mM [146]acetylcholine PEDOT/PSS/ gold wire potentiometric 10.0 mMe0.1 M 54.04± 1.70mV (lg M) �1 5.69± 1.06 mM [147]adenine ZnS NPs -PEDOT-rGO/GC-rotating disk electrode DPV 0.5e150 mM 0.2447 mA mM�1 0.141 mM [148]guanine ZnS NPs -PEDOT-rGO/GC-rotating disk electrode DPV 0.5e150 mM 0.3506 mA mM�1 0.116 mM [148]thymine ZnS NPs-PEDOT-rGO/GC-rotating disk electrode DPV 5.0e600 mM 0.0614 mA mM�1 1.57 mM [148]taurine imprinted conducting polymer based film potentiometric 0.1e10mM 53.8± 2.6mV (lg M) �1 e [149]

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proposed for the synthesis of grapheneePEDOT nanocompositefilm with large surface area, good biocompatibility and high elec-trical conductivity. Metal oxide incorporated with reduced gra-phene and PEDOT [133] showed higher loading capacity of enzymeand hence resulted in higher electron transfer efficiency. Thecatechol biosensor [133] exhibited awide sensing linear range from42 nM to 62 mM, current maxima of 92.55mA andMichaeliseMenten constant of 30.48mM. Interference from D-glucose, L-glutamic acid, AA and o-nitrophenol were negligible andthe sensor was still stable after 75 days when stored in a buffer atabout 4 �C. When similarly fabricated surface entrappedacetylcholinesterase-choline oxidase (AChE-ChO) [134], acetyl-choline was detected with a response time less than 4 s, extremelylow detection limit of 4.0 nM and high stability for long-termstorage.

3.3.2. Affinity sensorsUnlike catalytic process controlled by kinetics, the recognition

process of affinity sensor is controlled by thermodynamics, mainlydepending on the shape and size of bioreceptors and correspondinganalytes. One of the key issues when developing affinity sensors isthe immobilization of bindable bioreceptors, namely, antigens,antibodies, aptamers or DNAs, which can bind to a considerablybroad range of target species with, in many cases, high affinity andspecificity. Besides inefficient immobilization strategies, non-specific adsorptions which mostly lead to high baseline signaland delayed response, also should be taken into considerations.Generally, several highly hydrophilic compounds such as bovineserum albumin [135], horseradish peroxidase [69] and poly(-ethylene glycol) (PEG) [68] can be added to eliminate nonspecificbinding sites at the electrode/solution interface.

Electrochemical immunosensors based on the current changesinduced by antibodyeantigen interaction appeal to a large numberof researchers. Gao et al. [135] developed a simple and sensitivelabel-free immunosensor to detect carcinoembryonic antigen (CEA)by DPV. As the addition of CEA, the DPV current signal decreasedaccordingly, because the insulating CEA protein layer acting as anonconductor obstructed the electron transfer between the elec-trolyte and electrode surface. Ternary AuNPs/PEDOT/GR nano-composite provided good electron transfer capability as well asincreased the accessibility of the antigen and antibody, whichproduced good electrochemical performance. CEA was also deter-mined in a wider linear range by PEDOT/hyaluronic acid layerwhose excellent hydrophilicity resulted in remarkable antifoulingability [136]. ZnSe/AzureI/AuNPs/PEDOT modified Pt electrode [69]was developed for the determination of alpha fetoprotein (AFP),showing a high sensitivity, rapid analysis and an especially broadlinear range. Herein, ZnSe QDs were utilized for stabilization of AFPantibody, and Azure I and nanoAu/PEDOT composite film syn-ergetically augmented electron transfer process. Comparatively

speaking, another AFP biosensor [68] presented lower detectionlimit of 0.3 fg L�1, a RSD of 2.02% among five independently fabri-cated electrodes, and negligible signal responses to BSA, humanserum albumin, hemoglobin, and DNA even at high concentrations.The fabrication process of the ultrasensitive AFP biosensor is shownin Fig. 9, first the highly biocompatible and hydrophilic PEDOT/PEGcomposite was electrodeposited on the glass carbon electrode, thenAuNPs were attached to the PEDOT/PEG substrate surface via AueSbonds, and AFP antibodies were immobilized. After antigen incu-bation, compact antibodyeantigen complexs formed and shieldedless conductive AuNPs surface, so charge-transfer resistancedecreased accordingly which was detected by EIS. Tatsuro et al.[137] developed a new EDOT derivative bearing a zwitterionicphosphorylcholine group as a biomimetic ligand for metal-free,antibody-free, and low-impedance biosensors for human C-reac-tive protein. Another sandwich-type electrochemiluminescenceimmunosensor for point-of-care testing of prostate-specific antigenwas constructed [138]. A dual amplification strategy greatlyenhanced the sensitivity, with the antibodies directly immobilizedon the AuNPs/PEDOT/GR composite film as capture probes, andthen carbon nanosphere@CdTe-labeled signal antibodies furtherintroduced as amplifying probes.

Aptamers are artificially functional oligonucleic acids and can bereproducibly synthesized in a large quantity in vitro. Aptamers havea number of well-known advantages, such as simple entrapment inthe biosensor assembly, conformational robustness compared withantibodies or enzymes and binding to a wide range of targets withhigh affinity and specificity. There has been an exponential increasein the number of their application within electrochemical sensor.An aptasensor [139] was developed for the sensitive detection of17b-estradiol, an endocrine disruptor, at low concentrations.Herein, biotinylated ssDNA aptamer was immobilized on the sur-face of PEDOT/AuNP modified Au electrode via biotin-streptavidininteraction. Noemi’s group presented the first prototype of an all-polymer electrochemical microfluidic biosensor using TopasR assubstrate and a conducting polymer bilayer as electrode materialcovalently functionalized with aptamers. PEDOT doped with tosy-late (PEDOT:TsO) and ((2,3-dihy-drothieno[3,4-b][1,4]-dioxin-2-yl)methanol) (PEDOT-OH:TsO) bilayer modifiedmicroelectrode arrayswere employed for fast, label-free and real-time detection of anti-biotics [140] and virus [141] by recording EIS in a wide dynamicrange. Furthermore, concentrations of both ampicillin in a milksample and influenza A virus in saliva were successfully detected.The authors summerized that larger targets had a stronger influ-ence on the impedance due to a greater disruption of the electro-chemical environment near the electrode.

Since DNA detection has received remarkable attention in geneanalysis, medical diagnostics and quarantine, many electrochemicalconfigurations that provide fast, low-cost, sensitive and selectiveresponses are the main goals of numerous studies. For example,

Fig. 9. Schematic illustration of the fabrication process of the AFP biosensor. Reprinted from [68] with permission.

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Spain et al. proposed a DNA sensor [29] based on vapor phasepolymerized PEDOT films functionalized with gold nanoparticles.Horseradish peroxidase (HRP) enzyme tagged probe DNA wasimmobilized to hybridize to the target oligo. The drawbacks lay inlimited tagging efficiency and complex multistep analysis. Consid-ering simple preparation and label-free DNA sensing, Radhakrishnanet al. [142] proposed Ag nanoparticles (~28± 5 nm) functionalizedbipolymer nanotubes sensing platform for the detection of DNAhybridization in phosphate buffer. Thiol capped DNA was facilelyanchored on uniform Ag nanoparticles with controlled orientation,thus, hybridization efficiency with target DNA was improved.Therefore, the developed DNA sensor provided a simple, rapidmethod to detect specific sequences of DNA. Remarkably, the abilityof polymer nanocomposite to promote electron transfer reactionallowed a detection limit for target DNA as low as 5.4± 0.3 fM. Inaddition, direct detection of DNA and DNAeanticancer drug inter-action was performed by Kuralay et al. [143]. A novel surface basedon plasma treated PEDOT coated chitosan was fabricated for the firsttime. Consequently, the modified disposable pencil graphite elec-trode succeeded in detecting DNA and DNAeMitomycin C interac-tion in a sensitive way. PEDOT: PSS membrane was also used for theion concentration polarization (ICP) -enhanced detection of DNA. Byincreasing thickness and surface charge of PEDOT:PSS membrane ina microfluidic channel, a concentration increase of DNA by 6 ordersof magnitude from an initial concentration of 100 fM within 10min[144] was achieved. As for the detection via surface hybridization onmorpholino probes, DNA target concentration as low as 10 pM wasdetected within 15min.

3.3.3. Sensors without bioreceptorsSensors without bioreceptors are mainly based on the direct

electrochemical oxidation or reduction of biomolecules. Nonenzy-matic sensor is a desirable solution to the problem of criticaloperating conditions, poor reproducibility and high cost, when theselectivity is under control to a certain degree. Hui et al. [145] in-tegrated copper nanoparticles onto the rough surface of PEDOT/graphene oxide nanocomposite modified electrode interface inorder to enhance sensing performances. The constructed sensor forsensitive detection of glucose showed a wide linear range from

0.1 mM to 1.3mM, short response time of less than 1 s, high stabilityand negligible impact from dopamine, ascorbic acid, uric acid, so-dium citrate, NaH2PO4

þ, Na2HPO4, NaNO2, and ethanol. The sensi-tivity of 64.34 mAmM�1 was higher than that of enzymatic glucosesensors. Because copper nanoparticles provided stable and activesites for the electrochemical catalytic oxidation of glucose, andPEDOT/GO nanocomposite offered a rough and conductive sub-strate for the loading of copper nanoparticles. Jiang et al. [27]elaborated a one-pot ‘green’ synthesis of Pd-decorated PEDOTnanospheres for nonenzymatic H2O2 sensing. Pd nanoparticles(~4.5 nm) were homogenously dispersed on the surface of PEDOTnanospheres, showing a good electrocatalytic reduction ofhydrogen peroxide. MoS2 nanosheets were incorporated intoPEDOT to form a nanocomposite which exhibited better electro-catalytic oxidation of ascorbic acid, dopamine and uric acid thanpure PEDOT [146]. An all-solid-state coated wire electrode [147]was fabricated for nonenzymatic determination of acetylcholine.First, the gold wire was coated with PEDOT/PSS layer. Then it wasdipped into the solution containing acetylcholine ionophore five tosix times to form an acetylcholine selective membrane. The resultsimplied that the miniaturized ion-selective electrode could beeffectively applied in detecting the acetylcholine in rat brain ho-mogenate. Nano ZnS coated PEDOT-rGO hybrids modified glassycarbon-rotating disk electrode [148] was successfully used for theassessment of guanine, adenine and thymine contents in real-lifesamples with satisfactory results. Justyna et al. [149] electro-deposited molecularly imprinted conducting polymer based film(MICP films), using EDOT as the cross-linker, acetic acid thiopheneas the monomer, flavin mononucleotide as the dopant and taurineas the template. XPS spectra verified taurine’s existence in freshlydeposited MICP films as well as taurine’s removal in the outer layerof the MICP films after extraction. Subsequently, MICP films wereutilized as a specific receptor layer for potentiometric detection oftaurine, largely insensitive toward inorganic cations like calcium,magnesium, sodium, and potassium.

4. Conclusions, challenges and future developments

As is shown above, PEDOT as an emerging and promising

Y. Hui et al. / Analytica Chimica Acta 1022 (2018) 1e19 15

conducting polymer, has incorporated with versatile components,which brings about excellent electrochemical performance due tosynergetic effects of different components. Regarding a large ma-jority of electrochemical sensors, PEDOT-basedmaterials as sensingelements demonstrated improved sensitivity, selectivity, stabilityand signal-to-noise ratio compared to each of its components. Ac-cording to the data shown in the 4 tables, linear ranges and LODs atthe level of mM to fM were obtained, which, in general, satisfy thedetection requirements in environmental monitoring, food anddrug analysis and health care. Notably, PEDOT-based materials areextensively used for the selective determination of nitrite, dopa-mine, uric acid and glucose by catalytic oxidation owing to theelectrostatic properties, biocompatibility and easy oxidase immo-bilization of the polymer matrix.

In light of ensuring high selectivity and avoiding interferencefrom other compounds in complex sample, MIP is a candidatebecause it provides artificially synthesized receptor structures withspecific recognition and high stability. Generally, MIP sensors havedifficulty in integrating highly crosslinked polymers with trans-ducers. PEDOT in combination with electrochemical transduction,with EDOT acting as the monomer [126], cross-linker [102,125,149]or entrapping membrane [120], solved this problem to somedegree.

There were still challenges as well as developments for PEDOT-based sensors due to the increasing demands for on line, in situ,real-time, in vivo, noninvasive/minimally invasive, automatic, in-tegrated and simultaneous detection. Further, incorporatingdifferent components and/or solvents into the PEDOTmatrix can beinvestigated in terms of their sensing performance towards variousanalytes. Also, it is essential to pay close attention to innovativeideas, materials and techniques in order to realize an acceptablecompromise between performance of detection and cost. A simpleprotocol of PEDOT modified neural electrodes based on flexiblesubstrate was developed for implantable recording in vivo [150].Fully integrated Au/PEDOTePteAg/AgCl electrochemical microcellswere elaborated for simultaneous determination of multi-analytes[151]. It can be presumed that MEMS electrode arrays will integratemore recognition elements on portable devices for multi-analytedetection on multiplexed systems in the foreseeable future. Theutilization of machine-learning techniques also provide a protocolto enable the single sensor to perform multivariate sensing withhigh accuracies[152]. Another strategy was developing microfluidicdevices for automation of the analytical process with minimalconsumption of reagents. And their easy combination with rearcircuits promotes the current technology closer to the “lab-on-a-chip” concept.

Specific difficulties vary from different application fields. Withrespect to environmental monitoring, it is of vital importance todevelop sensor networks and wireless signal transmitters forremote sensing. In terms of sensors used for health care, it is anurgent requirement to implement clinical monitoring in a contin-uous, convenient and harmless way. Recently, the rapid develop-ment of wearable devices enable real time non-invasive detectingof electrolytes and metabolites in more accessible sweat, tears, orsaliva instead of blood to comprehensively assess the wearer’shealth-care [153]. Due to its good transparency, thermal and me-chanical stability as well as processability, PEDOT has been used inflexible electronics like sensitive electronic skin [154]. For example,real-time monitoring of Naþ in sweat was realized by PEDOT basedfilms as solid-contact materials [155], which was integrated into adisposable microfluidic chip in connection with a wireless elec-tronic platform encased in a 3D printed wearable casing.

Currently, the protocol of species analysis significantly un-dergoes the cross-discipline impact of analytical chemistry, mate-rial science, medicine, microfluidics and electronic technology.

With the great progress of PEDOT-based materials in recent years,they are believed to play important roles in on line, in situ, realtime, in vivo, noninvasive and minimally invasive determination.

Acknowledgements

The authors would like to thank the financial support from theMajor State Basic Research Development Program of China (973Program, Grant No. 2015CB352100) and the National Natural Sci-ence Foundation of China (No.61401433).

References

[1] H. Shirakawa, E.J. Louis, A.G. MacDiarmid, C.K. Chiang, A.J. Heeger, Synthesisof electrically conducting organic polymers: halogen derivatives of poly-acetylene, (CH), J. Chem. Soc. Chem. Commun (1977) 578e580, https://doi.org/10.1039/C39770000578.

[2] M. Gerard, A. Chaubey, B.D. Malhotra, Application of conducting polymers tobiosensors, Biosens. Bioelectron 17 (2002) 345e359, https://doi.org/10.1016/S0956-5663(01)00312-8.

[3] A. Malinauskas, J. Malinauskiene, A. Ramanavi�cius, Conducting polymer-based nanostructurized materials: electrochemical aspects, Nanotech-nology 16 (2005) R51eR62, https://doi.org/10.1088/0957-4484/16/10/R01.

[4] J. Janata, M. Josowicz, Conducting polymers in electronic chemical sensors,Nat. Mater 2 (2003) 19e24, https://doi.org/10.1038/nmat768.

[5] L. Groenendaal, G. Zotti, P.H. Aubert, S.M. Waybright, J.R. Reynolds, Electro-chemistry of poly(3,4-alkylenedioxythiophene) derivatives, Adv. Mater 15(2003) 855e879, https://doi.org/10.1002/adma.200300376.

[6] T.P. Huynh, P.S. Sharma, M. Sosnowska, F. D'Souza, W. Kutner, Functionalizedpolythiophenes: recognition materials for chemosensors and biosensors ofsuperior sensitivity, selectivity, and detectability, Prog. Polym. Sci. 47 (2015)1e25, https://doi.org/10.1016/j.progpolymsci.2015.04.009.

[7] F. Jonas, L. Schrader, Conductive modifications of polymers with polypyrrolesand polythiophenes, Synth. Met 41 (1991) 831e836, https://doi.org/10.1016/0379-6779(91)91506-6.

[8] C. Zanardi, F. Terzi, R. Seeber, Polythiophenes and polythiophene-basedcomposites in amperometric sensing, Anal. Bioanal. Chem. 405 (2013)509e531, https://doi.org/10.1007/s00216-012-6318-7.

[9] H. Shi, C. Liu, Q. Jiang, J. Xu, Effective Approaches to Improve the ElectricalConductivity of PEDOT: PSS: a Review, 2015, pp. 1e16, https://doi.org/10.1002/aelm.201500017.

[10] K. Sun, S. Zhang, P. Li, Y. Xia, X. Zhang, D. Du, F.H. Isikgor, J. Ouyang, Reviewon application of PEDOTs and PEDOT: PSS in energy conversion and storagedevices, J. Mater. Sci. Mater. Electron 26 (2015) 4438e4462, https://doi.org/10.1007/s10854-015-2895-5.

[11] K.M. Blumenthal, D.A. Hanck, Electrochromic enhancement of latent fin-gerprints by poly(3,4-ethylenedioxythiophene), Phys. Chem. Chem. Phys. 14(2012) 8653e8661, https://doi.org/10.1039/C2CP40733G.

[12] H. Yamato, M. Ohwa, W. Wernet, Stability of polypyrrole and poly(3,4-ethylenedioxythiophene) for biosensor application, J. Electroanal. Chem.397 (1995) 163e170, https://doi.org/10.1016/0022-0728(95)04156-8.

[13] A.R. Hillman, I. Efimov, K.S. Ryder, Time-scale- and temperature-dependentmechanical properties of viscoelastic poly(3,4-ethylenedioxythiophene)films, J. Am. Chem. Soc. 127 (2005) 16611e16620, https://doi.org/10.1021/ja054259z.

[14] A.R. Hillman, S.J. Daisley, S. Bruckenstein, Kinetics and mechanism of theelectrochemical p-doping of PEDOT, Electrochem. Commun 9 (2007)1316e1322, https://doi.org/10.1016/j.elecom.2007.01.009.

[15] A.R. Hillman, S.J. Daisley, S. Bruckenstein, Ion and solvent transfers andtrapping phenomena during n-doping of PEDOT films, Electrochim. Acta 53(2008) 3763e3771, https://doi.org/10.1016/j.electacta.2007.10.062.

[16] L. Groenendaal, F. Jonas, D. Freitag, H. Pielartzik, J.R. Reynolds, Poly(3,4-ethylenedioxythiophene) and its derivatives: past, present, and future,Adv. Mater 12 (2000) 481e494, https://doi.org/10.1002/(SICI)1521-4095(200004)12:7<481::AID-ADMA481>3.0.CO;2-C.

[17] N. Rozlosnik, New directions in medical biosensors employing poly(3,4-ethylenedioxy thiophene) derivative-based electrodes, Anal. Bioanal. Chem.395 (2009) 637e645, https://doi.org/10.1007/s00216-009-2981-8.

[18] M. Nikolou, G.G. Malliaras, Applications of poly (3,4-ethylenedioxythiophene) doped with poly(styrene sulfonic acid) transis-tors in chemical and biological sensors, Chem. Rec 8 (2008) 13e22, https://doi.org/10.1002/tcr.20133.

[19] S. Kirchmeyer, K. Reuter, Scientific importance, properties and growing ap-plications of poly(3,4-ethylenedioxythiophene), J. Mater. Chem. 15 (2005)2077, https://doi.org/10.1039/b417803n.

[20] R. Yue, J. Xu, Poly(3,4-ethylenedioxythiophene) as promising organic ther-moelectric materials: a mini-review, Synth. Met. 162 (2012) 912e917,https://doi.org/10.1016/j.synthmet.2012.04.005.

[21] H.W, Y.H.H. Wei Wei, A review on PEDOT-based counter electrodes for dye-sensitized solar cells, Int. J. Energy Res. 38 (2014) 1099e1111, https://doi.org/10.1002/er.

Y. Hui et al. / Analytica Chimica Acta 1022 (2018) 1e1916

[22] Z. Zhao, G.F. Richardson, Q. Meng, S. Zhu, H.C. Kuan, J. Ma, PEDOT-basedcomposites as electrode materials for supercapacitors, Nanotechnology 27(2016) 42001, https://doi.org/10.1088/0957-4484/27/4/042001.

[23] P. Schottland, M. Bouguettaya, C. Chevrot, Soluble polythiophene derivativesfor NO2 sensing applications, Synth. Met 102 (1999) 1325, https://doi.org/10.1016/S0379-6779(98)01043-1.

[24] J. Bobacka, Potential stability of all-solid-state ion-selective electrodes usingconducting polymers as ion-to-electron transducers, Anal. Chem. 71 (1999)4932e4937, https://doi.org/10.1021/ac990497z.

[25] P. Tehrani, A. Kanciurzewska, X. Crispin, N.D. Robinson, M. Fahlman,M. Berggren, The effect of pH on the electrochemical over-oxidation inPEDOT: PSS films, Solid State Ionics 177 (2007) 3521e3527, https://doi.org/10.1016/j.ssi.2006.10.008.

[26] H. Yoon, M. Chang, J. Jang, Formation of 1D poly(3,4-ethylenedioxythiophene) nanomaterials in reverse microemulsions andtheir application to chemical sensors, Adv. Funct. Mater 17 (2007) 431e436,https://doi.org/10.1002/adfm.200600106.

[27] F. Jiang, R. Yue, Y. Du, J. Xu, P. Yang, A one-pot “green” synthesis of Pd-decorated PEDOT nanospheres for nonenzymatic hydrogen peroxidesensing, Biosens. Bioelectron 44 (2013) 127e131, https://doi.org/10.1016/j.bios.2013.01.003.

[28] Y. Zuo, J. Xu, X. Zhu, X. Duan, L. Lu, Y. Gao, H. Xing, T. Yang, G. Ye, Y. Yu,Poly(3,4-ethylenedioxythiophene) nanorods/graphene oxide nanocompositeas a new electrode material for the selective electrochemical detection ofmercury (II), Synth. Met 220 (2016) 14e19, https://doi.org/10.1016/j.synthmet.2016.05.022.

[29] E. Spain, T.E. Keyes, R.J. Forster, DNA sensor based on vapour polymerisedpedot films functionalised with gold nanoparticles, Biosens. Bioelectron 41(2013) 65e70, https://doi.org/10.1016/j.bios.2012.06.046.

[30] G. Xu, W. Wang, B. Li, Z. Luo, X. Luo, A dopamine sensor based on a carbonpaste electrode modified with DNA-doped poly(3,4-ethylenedioxythiophene), Microchim. Acta 182 (2015) 679e685, https://doi.org/10.1007/s00604-014-1373-8.

[31] Y. Yao, Y. Wen, L. Zhang, Z. Wang, H. Zhang, J. Xu, Electrochemical recog-nition and trace-level detection of bactericide carbendazim using carboxylicgroup functionalized poly(3,4-ethylenedioxythiophene) mimic electrode,Anal. Chim. Acta 831 (2014) 38e49, https://doi.org/10.1016/j.aca.2014.04.059.

[32] J. Xu, Y. Tian, R. Peng, Y. Xian, Q. Ran, L. Jin, Electrochemistry Communica-tions Ferrocene clicked poly ( 3, 4-ethylenedioxythiophene ) conductingpolymer : characterization, electrochemical and electrochromic properties,Electrochem. Commun 11 (2009) 1972e1975, https://doi.org/10.1016/j.elecom.2009.08.031.

[33] A. €Ozcan, S. Ilkbas, Preparation of poly(3,4-ethylenedioxythiophene) nano-fibers modified pencil graphite electrode and investigation of over-oxidationconditions for the selective and sensitive determination of uric acid in bodyfluids, Anal. Chim. Acta 891 (2015) 312e320, https://doi.org/10.1016/j.aca.2015.08.015.

[34] K.P. Prasad, Y. Chen, M.A. Sk, A. Than, Y. Wang, H. Sun, K. Lim, X. Dong,P. Chen, Fluorescent quantum dots derived from PEDOT and their applica-tions in optical imaging and sensing, Mater. Horizons 1 (2014) 529e534,https://doi.org/10.1039/c4mh00066h.

[35] N. Kaur, H. Thakur, R. Kumar, N. Prabhakar, An electrochemical sensormodified with poly(3,4-ethylenedioxythiophene)-wrapped multi-walledcarbon nanotubes for enzyme inhibition-based determination of organo-phosphates, Microchim. Acta 183 (2016) 2307e2315, https://doi.org/10.1007/s00604-016-1871-y.

[36] C. Jan�aky, C. Visy, Conducting polymer-based hybrid assemblies for elec-trochemical sensing: a materials science perspective, Anal. Bioanal. Chem.405 (2013) 3489e3511, https://doi.org/10.1007/s00216-013-6702-y.

[37] A. Lakshmi, J. Anandha Raj, G. Gopu, P. Arumugam, C. Vedhi, Electrochemical,electrochromic behaviour and effects of supporting electrolyte on nano-thinfilm of poly (3,4-ethylenedioxy thiophene), Electrochim. Acta 92 (2013)452e459, https://doi.org/10.1016/j.electacta.2013.01.069.

[38] E. Poverenov, M. Li, A. Bitler, M. Bendikov, Major effect of electro-polymerization solvent on morphology and electrochromic properties ofPEDOT films, Chem. Mater 22 (2010) 4019e4025, https://doi.org/10.1021/cm100561d.

[39] K.C. (nee Włodarczyk), J. Karczewski, P. Jasi�nski, Influence of electro-polymerization conditions on the morphological and electrical properties ofPEDOT film, Electrochim. Acta 176 (2015) 156e161, https://doi.org/10.1016/j.electacta.2015.07.006.

[40] Z.A. King, C.M. Shaw, S.A. Spanninga, D.C. Martin, Structural, chemical andelectrochemical characterization of poly ( 3, 4-Ethylenedioxythiophene ) (PEDOT ) prepared with various counter-ions and heat treatments, Polymer(Guildf) 52 (2011) 1302e1308, https://doi.org/10.1016/j.polymer.2011.01.042.

[41] T. Tian, S. Zheng, B. Ye, B. Qu, Y. Zhao, X. Kang, Z. Gu, Poly-3, 4-ethylenedioxythiophene nanoclusters for high effective solid phase extrac-tion, J. Chromatogr. A. 1275 (2013) 17e24, https://doi.org/10.1016/j.chroma.2012.12.025.

[42] A. Ramanavi�cius, A. Ramanavi�ciene, A. Malinauskas, Electrochemical sensorsbased on conducting polymer-polypyrrole, Electrochim. Acta 51 (2006)6025e6037, https://doi.org/10.1016/j.electacta.2005.11.052.

[43] M.A. Valle, L.A. Hern�andez, F.R. Díaz, A. Ramos, Electrosynthesis and

characterization of poly ( 3, 4- ethylenedioxythiophene), Nanowires 10(2015) 5152e5163.

[44] C.M. Hangarter, S.C. Hernandez, X. He, N. Chartuprayoon, Y.H. Choa,N.V. Myung, Tuning the gas sensing performance of single PEDOT nanowiredevices, Analyst 136 (2011) 2350e2358, https://doi.org/10.1039/c0an01000f.

[45] P. Manisankar, C. Vedhi, G. Selvanathan, P. Arumugam, Differential pulsestripping voltammetric determination of heavy metals simultaneously usingnew polymer modified glassy carbon electrodes, Microchim. Acta (2008)289e295, https://doi.org/10.1007/s00604-008-0013-6.

[46] S. Ahmad, M. Deepa, S. Singh, Electrochemical synthesis and surface char-acterization of poly ( 3, 4-ethylenedioxythiophene ) films grown in an ionicliquid, Langmuir (2007) 11430e11433.

[47] P. Lin, F. Chai, R. Zhang, G. Xu, X. Fan, Electrochemical synthesis of poly ( 3, 4-ethylenedioxythiophene ) doped with gold nanoparticles, and its applicationto nitrite sensing, Microchim. Acta 183 (2016) 1235e1241, https://doi.org/10.1007/s00604-016-1751-5.

[48] C.Y. Lin, V.S. Vasantha, K.C. Ho, Detection of nitrite using poly(3,4-ethylenedioxythiophene) modified SPCEs, Sensors Actuators, B Chem. 140(2009) 51e57, https://doi.org/10.1016/j.snb.2009.04.047.

[49] S. Liu, J. Tian, L. Wang, Y. Luo, X. Sun, Production of stable aqueous dispersionof poly(3,4-ethylenedioxythiophene) nanorods using graphene oxide as astabilizing agent and their application for nitrite detection, Analyst 136(2011) 4898e4902, https://doi.org/10.1039/c1an15799j.

[50] M. Wu, H. Zhang, F. Zhao, B. Zeng, A novel poly(3,4-ethylenedioxythiophene)-ionic liquid composite coating for the headspacesolid-phase microextraction and gas chromatography determination ofseveral alcohols in soft drinks, Anal. Chim. Acta 850 (2014) 41e48, https://doi.org/10.1016/j.aca.2014.08.029.

[51] O. Zhang, Y. Wen, J. Xu, L. Lu, X. Duan, H. Yu, One-step synthesis of poly(3,4-ethylenedioxythiophene)-Au composites and their application for thedetection of nitrite, Synth. Met 164 (2013) 47e51, https://doi.org/10.1016/j.synthmet.2012.11.013.

[52] Z. Wang, J. Xu, Y. Yao, L. Zhang, Y. Wen, Sensors and Actuators B: chemicalFacile preparation of highly water-stable and flexible PEDOT: PSS organic /inorganic composite materials and their application in electrochemicalsensors, Sensors Actuators B. Chem. 196 (2014) 357e369, https://doi.org/10.1016/j.snb.2014.02.035.

[53] Z. Zhang, J. Zhang, H. Zhang, J. Xu, Y. Wen, W. Ding, Characterization ofPEDOT: PSS-reduced graphene oxide@Pd composite electrode and itsapplication in voltammetric determination of vitamin K3, J. Electroanal.Chem. 775 (2016) 258e266, https://doi.org/10.1016/j.jelechem.2016.06.005.

[54] F. Xu, S. Ren, Y. Gu, A novel conductive poly (3, 4-ethylenedioxythiophene)-BSA film for the construction of a durable HRP biosensor modified withNanoAu particles, Sensors (Switzerland) 16 (2016) 374, https://doi.org/10.3390/s16030374.

[55] M. Yamada, N. Ohnishi, M. Watanabe, Y. Hino, Prussian blue nanoparticlesprotected by the water-soluble pi-conjugated polymer PEDOT-S: synthesisand multiple-color pH-sensing with a redox reaction, Chem. Commun.(Camb) (2009) 7203e7205, https://doi.org/10.1039/b917552k.

[56] L. Zhang, Y. Wen, Y. Yao, J. Xu, X. Duan, G. Zhang, Synthesis and character-ization of PEDOT derivative with carboxyl group and its chemo/bio sensingapplication as nanocomposite, immobilized biological and enhanced opticalmaterials, Electrochim. Acta 116 (2014) 343e354, https://doi.org/10.1016/j.electacta.2013.11.042.

[57] Y. Yao, L. Zhang, Y. Wen, Z. Wang, H. Zhang, D. Hu, J. Xu, X. Duan, Voltam-metric determination of catechin using single-walled carbon nanotubes/poly(hydroxymethylated-3,4-ethylenedioxythiophene) composite modifiedelectrode, Ionics (Kiel) 21 (2015) 2927e2936, https://doi.org/10.1007/s11581-015-1494-z.

[58] T. Gal�an, B. Prieto-sim�on, M. Alvira, R. Eritja, G. G€otz, P. B€auerle, J. Samitier,Label-free electrochemical DNA sensor using “ click ” -functionalized, Bio-sens. Bioelectron 74 (2015) 751e756, https://doi.org/10.1016/j.bios.2015.07.037.

[59] G.G. L�ang, M. Ujv�ari, S. Vesztergom, V. Kondratiev, J. Gubicza, K.J. Szekeres,The electrochemical degradation of poly(3,4-ethylenedioxythiophene) filmselectrodeposited from aqueous solutions, Zeitschrift Für Phys. Chemie 230(2016) 1e22, https://doi.org/10.1515/zpch-2016-0752.

[60] M.U.G.K.J. Szekeres, G.G. L�ang, Morphological changes in electrochemicallydeposited poly(3,4-ethylenedioxythiophene) films during overoxidation,J. Solid State Electrochem 19 (2015) 1247e1252, https://doi.org/10.1007/s10008-015-2746-6.

[61] J. Moulton, P. Smith, Electrical and mechanical properties of oriented poly (3-alkylthiophenes): 2. Effect of side-chain length, Polymer (Guildf) 33 (1992)2340e2347.

[62] J.M. Lin, Y.L. Su, W.T. Chang, W.Y. Su, S.H. Cheng, Strong adsorption char-acteristics of a novel overoxidized poly(3,4-ethylenedioxythiophene) filmand application for dopamine sensing, Electrochim. Acta 149 (2014) 65e75,https://doi.org/10.1016/j.electacta.2014.10.030.

[63] Y. Hui, C. Bian, J. Wang, J. Tong, S. Xia, Comparison of two types of over-oxidized PEDOT films and their application in sensor fabrication, Sensors 17(2017) 628, https://doi.org/10.3390/s17030628.

[64] G. Sheng, G. Xu, S. Xu, S. Wang, X. Luo, Cost-effective preparation and sensingapplication of conducting polymer PEDOT/ionic liquid nanocomposite withexcellent electrochemical properties, RSC Adv 5 (2015) 20741e20746,

Y. Hui et al. / Analytica Chimica Acta 1022 (2018) 1e19 17

https://doi.org/10.1039/C4RA15755A.[65] X. Ling, W. Zhang, Z. Chen, Electrochemically modified carbon fiber bundles

as selective sorbent for online solid-phase microextraction of sulfonamides,Microchim. Acta 183 (2016) 813e820, https://doi.org/10.1007/s00604-015-1726-y.

[66] K. Liu, H. Pang, J. Zhang, H. Huang, Q. Liu, Y. Chu, Synthesis and character-ization of a highly stable poly (3,4-ethylenedioxythiophene)-gold nano-particles composite film and its application to electrochemical dopaminesensors, RSC Adv 4 (2014) 8415, https://doi.org/10.1039/c3ra45859h.

[67] N.F. Atta, A. Galal, S.M. Ali, S.H. Hassan, Electrochemistry and detection ofdopamine at a poly ( 3, 4-ethylenedioxythiophene ) electrode modified withferrocene and cobaltocene, Ionics (Kiel) 21 (2015) 2371e2382, https://doi.org/10.1007/s11581-015-1417-z.

[68] M. Cui, Z. Song, Y. Wu, B. Guo, X. Fan, X. Luo, A highly sensitive biosensor fortumor maker alpha fetoprotein based on poly(ethylene glycol) doped con-ducting polymer PEDOT, Biosens. Bioelectron 79 (2016) 736e741, https://doi.org/10.1016/j.bios.2016.01.012.

[69] K. Liu, J. Zhang, Q. Liu, H. Huang, Electrochemical immunosensor for alpha-fetoprotein determination based on ZnSe quantum dots/Azure I/gold nano-particles/poly (3,4-ethylenedioxythiophene) modified Pt electrode, Electro-chim. Acta 114 (2013) 448e454, https://doi.org/10.1016/j.electacta.2013.10.018.

[70] J.A. Arter, D.K. Taggart, T.M. McIntire, R.M. Penner, G.A. Weiss, Virus-PEDOTnanowires for biosensing, Nano Lett. 10 (2010) 4858e4862, https://doi.org/10.1021/nl1025826.

[71] M.G. Han, S.H. Foulger, Facile synthesis of poly(3,4-ethylenedioxythiophene)nanofibers from an aqueous surfactant solution, Small 2 (2006) 1164e1169,https://doi.org/10.1002/smll.200600135.

[72] L. Yang, J. Zhang, F. Zhao, B. Zeng, Electrodeposition of self-assembledpoly(3,4-ethylenedioxythiophene) @gold nanoparticles on stainless steelwires for the headspace solid-phase microextraction and gas chromato-graphic determination of several polycyclic aromatic hydrocarbons,J. Chromatogr. A. 1471 (2016) 80e86, https://doi.org/10.1016/j.chroma.2016.10.041.

[73] E. Scavetta, R. Mazzoni, F. Mariani, R.G. Margutta, A. Bonfiglio, M. Demelas,S. Fiorilli, M. Marzocchi, B. Fraboni, Dopamine amperometric detection at aferrocene clicked PEDOT: PSS coated electrode, J. Mater. Chem. B 2 (2014)2861, https://doi.org/10.1039/c4tb00169a.

[74] C. García-Hern�andez, C. García-Cabez�on, F. Martín-Pedrosa, J.A. De Saja,M.L. Rodríguez-M�endez, Layered composites of PEDOT/PSS/nanoparticlesand PEDOT/PSS/phthalocyanines as electron mediators for sensors and bio-sensors, Beilstein J. Nanotechnol 7 (2016) 1948e1959, https://doi.org/10.3762/bjnano.7.186.

[75] M.J.A. Shiddiky, A.A.J. Torriero, Application of ionic liquids in electrochemicalsensing systems, Biosens. Bioelectron 26 (2011) 1775e1787, https://doi.org/10.1016/j.bios.2010.08.064.

[76] D. Wei, A. Ivaska, Applications of ionic liquids in electrochemical sensors,Anal. Chim. Acta 607 (2008) 126e135, https://doi.org/10.1016/j.aca.2007.12.011.

[77] A. Abo-Hamad, M.A.H. AlSaadi, M. Hayyan, I. Juneidi, M.A. Hashim, Ionicliquid-carbon nanomaterial hybrids for electrochemical sensor applications:a review, Electrochim. Acta 193 (2015) 321e343, https://doi.org/10.1016/j.electacta.2016.02.044.

[78] W. Lu, W. Lu, A.G. Fadeev, B. Qi, E. Smela, B.R. Mattes, J. Ding, G.M. Spinks,J. Mazurkiewicz, D. Zhou, G.G. Wallace, D.R. Macfarlane, S.A. Forsyth,M. Forsyth, Use of ionic liquids for p-conjugated polymer electrochemicaldevices, Science (80-. ) 983 (2002), https://doi.org/10.1126/science.1072651.

[79] Z. Guo, H. Liu, C. Jiang, Y. Zhu, M. Wan, L. Dai, L. Jiang, Biomolecule-dopedPEDOT with three-dimensional nanostructures as efficient catalyst for oxy-gen reduction reaction, Small 10 (2014) 2087e2095, https://doi.org/10.1002/smll.201303642.

[80] J.A. Arter, J.E. Diaz, K.C. Donavan, T. Yuan, R.M. Penner, G.A. Weiss, Virus-polymer hybrid nanowires tailored to detect prostate-specific membraneantigen, Anal. Chem. 84 (2012) 2776e2783, https://doi.org/10.1021/ac203143y.

[81] K.C. Donavan, J.A. Arter, R. Pilolli, N. Cioffi, G.A. Weiss, R.M. Penner, Virus-poly(3,4-ethylenedioxythiophene) composite films for impedance-basedbiosensing, Anal. Chem. 83 (2011) 2420e2424, https://doi.org/10.1021/ac2000835.

[82] K. Mohan, K.C. Donavan, J.A. Arter, R.M. Penner, G.A. Weiss, Sub-nanomolardetection of prostate-specific membrane antigen in synthetic urine by syn-ergistic, dual-ligand phage, J. Am. Chem. Soc. 135 (2013) 7761e7767, https://doi.org/10.1021/ja4028082.

[83] A.F. Ogata, J.M. Edgar, S. Majumdar, J.S. Briggs, S.V. Patterson, M.X. Tan,S.T. Kudlacek, C.A. Schneider, G.A. Weiss, R.M. Penner, Virus-enabledbiosensor for human serum albumin, Anal. Chem. 89 (2017) 1373e1381,https://doi.org/10.1021/acs.analchem.6b04840.

[84] W. Wang, G. Xu, X.T. Cui, G. Sheng, X. Luo, Enhanced catalytic and dopaminesensing properties of electrochemically reduced conducting polymer nano-composite doped with pure graphene oxide, Biosens. Bioelectron 58 (2014)153e156, https://doi.org/10.1016/j.bios.2014.02.055.

[85] W. Wang, W. Wang, J.J. Davis, X. Luo, Ultrasensitive and selective voltam-metric aptasensor for dopamine based on a conducting polymer nano-composite doped with graphene oxide, Microchim. Acta 182 (2015)1123e1129, https://doi.org/10.1007/s00604-014-1418-z.

[86] S. Shrivastava, N. Jadon, R. Jain, Next-generation polymer nanocomposite-based electrochemical sensors and biosensors: a review, TrAC - TrendsAnal. Chem. 82 (2016) 55e67, https://doi.org/10.1016/j.trac.2016.04.005.

[87] M. Ates, A review study of (bio)sensor systems based on conducting poly-mers, Mater. Sci. Eng. C 33 (2013) 1853e1859, https://doi.org/10.1016/j.msec.2013.01.035.

[88] C. Park, C. Lee, O. Kwon, Conducting polymer based nanobiosensors, Poly-mers (Basel) 8 (2016) 249, https://doi.org/10.3390/polym8070249.

[89] T. Sen, S. Mishra, N.G. Shimpi, Synthesis and sensing applications of poly-aniline nanocomposites: a review, RSC Adv 6 (2016) 42196e42222, https://doi.org/10.1039/C6RA03049A.

[90] M.R. Nabid, R. Sedghi, R. Hajimirza, H.A. Oskooie, M.M. Heravi,A nanocomposite made from conducting organic polymers and multi-walledcarbon nanotubes for the adsorption and separation of gold(III) ions,Microchim. Acta 175 (2011) 315e322, https://doi.org/10.1007/s00604-011-0680-6.

[91] J. Qiu, X. Kang, L. Ma, W. Huang, Q. Ge, Preparation and application of poly 3,4-ethylenedioxythiophene (PEDOT) nanofibers in the pretreatment of sam-ples before the determination of elements in children fingernails, Mater. Sci.Eng. 87 (2015) 012093, https://doi.org/10.1088/1757-899X/87/1/012093.

[92] C. Gao, X. Huang, Trends in analytical chemistry voltammetric determinationof mercury ( ii ), Trends Anal. Chem. 51 (2013) 1e12, https://doi.org/10.1016/j.trac.2013.05.010.

[93] M. Giannetto, G. Mori, F. Terzi, C. Zanardi, R. Seeber, Composite PEDOT/Aunanoparticles modified electrodes for determination of mercury at tracelevels by anodic stripping voltammetry, Electroanalysis 23 (2011) 456e462,https://doi.org/10.1002/elan.201000469.

[94] S. Anandhakumar, J. Mathiyarasu, K.L.N. Phani, Anodic stripping voltam-metric detection of mercury(ii) using Au-PEDOT modified carbon pasteelectrode, Anal. Methods 4 (2012) 2486, https://doi.org/10.1039/c2ay25170a.

[95] L. Ding, J. Zhai, A.M. Bond, J. Zhang, Polystyrenesulfonate doped poly(-Hydroxymethyl 3,4-Ethylenedioxythiophene) stabilized Au nanoparticlemodified glassy carbon electrode as a reusable sensor for mercury(II)detection in chloride media, J. Electroanal. Chem. 704 (2013) 96e101,https://doi.org/10.1016/j.jelechem.2013.06.014.

[96] Q. Wang, Y. Yun, A nanomaterial composed of cobalt nanoparticles, poly(3,4-ethylenedioxythiophene) and graphene with high electrocatalytic activityfor nitrite oxidation, Microchim. Acta 177 (2012) 411e418, https://doi.org/10.1007/s00604-012-0794-5.

[97] Y.H. Cheng, C.W. Kung, L.Y. Chou, R. Vittal, K.C. Ho, Poly(3,4-ethylenedioxythiophene) (PEDOT) hollow microflowers and their applica-tion for nitrite sensing, Sensors Actuators, B Chem. 192 (2014) 762e768,https://doi.org/10.1016/j.snb.2013.10.126.

[98] J. Wang, G. Xu, W. Wang, S. Xu, X. Luo, Nitrite oxidation with copper-cobaltnanoparticles on carbon nanotubes doped conducting polymer PEDOTcomposite, Chem. - An Asian J 10 (2015) 1892e1897, https://doi.org/10.1002/asia.201500579.

[99] S.S. Hassan, Y. Liu, Sirajuddin, A.R. Solangi, A.M. Bond, J. Zhang, Phospho-molybdate-doped-poly(3,4-ethylenedioxythiophene) coated gold nano-particles: synthesis, characterization and electrocatalytic reduction ofbromate, Anal. Chim. Acta 803 (2013) 41e46, https://doi.org/10.1016/j.aca.2013.04.036.

[100] M.A. Ali, H. Jiang, N.K. Mahal, R.J. Weber, R. Kumar, M.J. Castellano, L. Dong,Microfluidic impedimetric sensor for soil nitrate detection using grapheneoxide and conductive nanofibers enabled sensing interface, Sensors Actua-tors B Chem. 239 (2017) 1289e1299, https://doi.org/10.1016/j.snb.2016.09.101.

[101] P.L. Abirama Sundari, P. Manisankar, Development of ultrasensitive surfac-tants doped poly(3,4- ethylenedioxythiophene)/multiwalled carbon nano-tube sensor for the detection of pyrethroids and an organochlorine pesticide,J. Appl. Electrochem 41 (2011) 29e37, https://doi.org/10.1007/s10800-010-0204-9.

[102] E. Pardieu, H. Cheap, C. Vedrine, M. Lazerges, Y. Lattach, F. Garnier, S. Remita,C. Pernelle, Molecularly imprinted conducting polymer based electro-chemical sensor for detection of atrazine, Anal. Chim. Acta 649 (2009)236e245, https://doi.org/10.1016/j.aca.2009.07.029.

[103] G. Xu, B. Li, X. Wang, X. Luo, Electrochemical sensor for nitrobenzene basedon carbon paste electrode modified with a poly(3,4-ethylenedioxythiophene) and carbon nanotube nanocomposite, Microchim.Acta 181 (2014) 463e469, https://doi.org/10.1007/s00604-013-1136-y.

[104] M. Sobkowiak, T. Rebis, G. Milczarek, Electrocatalytic sensing of poly-nitroaromatic compounds on multiwalled carbon nanotubes modified withalkoxysulfonated derivative of PEDOT, Mater. Chem. Phys (2016), https://doi.org/10.1016/j.matchemphys.2016.10.035.

[105] J.Y. Wang, Y.L. Su, B.H. Wu, S.H. Cheng, Reusable electrochemical sensor forbisphenol A based on ionic liquid functionalized conducting polymer plat-form, Talanta 147 (2016) 103e110, https://doi.org/10.1016/j.talanta.2015.09.035.

[106] X. Li, Y. Wang, X. Yang, J. Chen, H. Fu, T. Cheng, Y. Wang, Conducting poly-mers in environmental analysis, TrAC - Trends Anal. Chem. 39 (2012)163e179, https://doi.org/10.1016/j.trac.2012.06.003.

[107] A.D. Aguilar, E.S. Forzani, M. Leright, F. Tsow, A. Cagan, R.A. Iglesias,L.A. Nagahara, I. Amlani, R. Tsui, N.J. Tao, A hybrid nanosensor for TNT vapordetection, Nano Lett. 10 (2010) 380e384, https://doi.org/10.1021/nl902382s.

Y. Hui et al. / Analytica Chimica Acta 1022 (2018) 1e1918

[108] C.J. Chiang, K.T. Tsai, Y.H. Lee, H.W. Lin, Y.L. Yang, C.C. Shih, C.Y. Lin, H.A. Jeng,Y.H. Weng, Y.Y. Cheng, K.C. Ho, C.A. Dai, In situ fabrication of conductingpolymer composite film as a chemical resistive CO2 gas sensor, Micro-electron. Eng 111 (2013) 409e415, https://doi.org/10.1016/j.mee.2013.04.014.

[109] E. Zampetti, S. Pantalei, A. Muzyczuk, A. Bearzotti, F. De Cesare, C. Spinella,A. Macagnano, A high sensitive NO2 gas sensor based on PEDOTePSS/TiO2nanofibres, Sensors Actuators B Chem. 176 (2013) 390e398, https://doi.org/10.1016/j.snb.2012.10.005.

[110] Y. Lin, L. Huang, L. Chen, J. Zhang, L. Shen, Q. Chen, W. Shi, Fully gravure-printed NO2 gas sensor on a polyimide foil using WO3-PEDOT: PSS nano-composites and Ag electrodes, Sensors Actuators, B Chem. 216 (2015)176e183, https://doi.org/10.1016/j.snb.2015.04.045.

[111] K. Dunst, D. Jurk�ow, P. Jasi�nski, Laser patterned platform with PEDOT-graphene composite film for NO2 sensing, Sensors Actuators, B Chem. 229(2016) 155e165, https://doi.org/10.1016/j.snb.2016.01.093.

[112] M. Hakimi, A. Salehi, F.A. Boroumand, Fabrication and characterization of anammonia gas sensor based on pedot-pss with N-Doped graphene quantumdots dopant, IEEE Sens. J. 16 (2016) 6149e6154, https://doi.org/10.1109/JSEN.2016.2585461.

[113] S. Sharma, S. Hussain, S. Singh, S.S. Islam, MWCNT-conducting polymercomposite based ammonia gas sensors: a new approach for complete re-covery process, Sensors Actuators, B Chem. 194 (2014) 213e219, https://doi.org/10.1016/j.snb.2013.12.050.

[114] S. Badhulika, N.V. Myung, A. Mulchandani, Conducting polymer coatedsingle-walled carbon nanotube gas sensors for the detection of volatileorganic compounds, Talanta 123 (2014) 109e114, https://doi.org/10.1016/j.talanta.2014.02.005.

[115] G. Campo, C. Sangregorio, B. Mazzolai, V. Mattoli, Characterization of free-standing PEDOT: PSS/Iron oxide nanoparticle composite thin films andapplication as conformable humidity sensors, ACS Appl. Mater. Interfaces(2013).

[116] J. Zhang, Y. Guo, S. Li, H. Xu, A solid-contact pH-selective electrode based ontridodecylamine as hydrogen neutral ionophore, Meas. Sci. Technol 27(2016) 105101, https://doi.org/10.1088/0957-0233/27/10/105101.

[117] Z. Wang, H. Zhang, Z. Wang, J. Zhang, X. Duan, J. Xu, Y. Wen, Trace analysis ofPonceau 4R in soft drinks using differential pulse stripping voltammetry atSWCNTs composite electrodes based on PEDOT: PSS derivatives, Food Chem.180 (2015) 186e193, https://doi.org/10.1016/j.foodchem.2015.02.043.

[118] C. Bianchini, A. Curulli, M. Pasquali, D. Zane, Determination of caffeic acid inwine using PEDOT film modified electrode, Food Chem. 156 (2014) 81e86,https://doi.org/10.1016/j.foodchem.2014.01.074.

[119] Z. Liu, J. Xu, R. Yue, T. Yang, L. Gao, Facile one-pot synthesis of Au-PEDOT/rGOnanocomposite for highly sensitive detection of caffeic acid in red winesample, Electrochim. Acta 196 (2016) 1e12, https://doi.org/10.1016/j.electacta.2016.02.178.

[120] V.L.V. Granado, M. Guti�errez-Capit�an, C. Fern�andez-S�anchez, M.T.S.R. Gomes,A. Rudnitskaya, C. Jimenez-Jorquera, Thin-film electrochemical sensor fordiphenylamine detection using molecularly imprinted polymers, Anal. Chim.Acta 809 (2014) 141e147, https://doi.org/10.1016/j.aca.2013.11.038.

[121] T.T. Tung, M. Castro, I. Pillin, T.Y. Kim, K.S. Suh, J.F. Feller, Graphene-Fe3O4/PIL-PEDOT for the design of sensitive and stable quantum chemo-resistiveVOC sensors, Carbon N. Y. 74 (2014) 104e112, https://doi.org/10.1016/j.carbon.2014.03.009.

[122] V. Tsakova, G. Ilieva, D. Filjova, Role of the anionic dopant of poly(3,4-ethylenedioxythiophene) for the electroanalytical performance: electro-oxidation of acetaminophen, Electrochim. Acta 179 (2015) 343e349, https://doi.org/10.1016/j.electacta.2015.02.062.

[123] K. Zhang, J. Xu, X. Zhu, L. Lu, X. Duan, D. Hu, L. Dong, H. Sun, Y. Gao, Y. Wu,Poly(3,4-ethylenedioxythiophene) nanorods grown on graphene oxidesheets as electrochemical sensing platform for rutin, J. Electroanal. Chem.739 (2015) 66e72, https://doi.org/10.1016/j.jelechem.2014.12.013.

[124] J. Zhao, W. Guo, M. Pei, F. Ding, GReFe 3 O 4 NPs and PEDOTeAuNPs com-posite based electrochemical aptasensor for the sensitive detection ofpenicillin, Anal. Methods 8 (2016) 4391e4397, https://doi.org/10.1039/C6AY00555A.

[125] M.G.Y. Zhang, J. Zheng, J. Wang, Preparation and properties of doxorubicinhydrochloride sensor based on molecularly imprinted polymer, Chem. J.Chinese Univ. 37 (2016) 860e866.

[126] C.H. Weng, W.M. Yeh, K.C. Ho, G. Bin Lee, A microfluidic system utilizingmolecularly imprinted polymer films for amperometric detection ofmorphine, Sensors Actuators, B Chem. 121 (2007) 576e582, https://doi.org/10.1016/j.snb.2006.04.111.

[127] N.F. Atta, A. Galal, R.A. Ahmed, Direct and simple electrochemical determi-nation of morphine at PEDOT modified Pt electrode, Electroanalysis 23(2011) 737e746, https://doi.org/10.1002/elan.201000600.

[128] C. Chen, Q. Xie, D. Yang, H. Xiao, Y. Fu, Y. Tan, S. Yao, Recent advances inelectrochemical glucose biosensors: a review, RSC Adv 3 (2013) 4473,https://doi.org/10.1039/c2ra22351a.

[129] P. Santhosh, K.M. Manesh, S. Uthayakumar, S. Komathi, A.I. Gopalan, K. Lee,Fabrication of enzymatic glucose biosensor based on palladium nano-particles dispersed onto poly (3 ,4-ethylenedioxythiophene) nanofibers,Bioelectrochemistry 75 (2009) 61e66, https://doi.org/10.1016/j.bioelechem.2008.12.001.

[130] L. Lu, O. Zhang, J. Xu, Y. Wen, X. Duan, H. Yu, L. Wu, T. Nie, A facile one-step

redox route for the synthesis of graphene/poly (3,4-ethylenedioxythiophene) nanocomposite and their applications in bio-sensing, Sensors Actuators, B Chem. 181 (2013) 567e574, https://doi.org/10.1016/j.snb.2013.02.024.

[131] P.C. Nien, M.C. Huang, F.Y. Chang, K.C. Ho, Integrating an enzyme-entrappedconducting polymer electrode and a prereactor in a microfluidic system forsensing glucose, Electroanalysis 20 (2008) 635e642, https://doi.org/10.1002/elan.200704123.

[132] M.M. Barsan, V. Pifferi, L. Falciola, C.M.A. Brett, New CNT/poly(brilliant green)and CNT/poly(3,4-ethylenedioxythiophene) based electrochemical enzymebiosensors, Anal. Chim. Acta 927 (2016) 35e45, https://doi.org/10.1016/j.aca.2016.04.049.

[133] V. Sethuraman, P. Muthuraja, J. Anandha Raj, P. Manisankar, A highly sen-sitive electrochemical biosensor for catechol using conducting polymerreduced graphene oxide-metal oxide enzyme modified electrode, Biosens.Bioelectron 84 (2015) 112e119, https://doi.org/10.1016/j.bios.2015.12.074.

[134] N. Chauhan, S. Chawla, C.S. Pundir, U. Jain, An electrochemical sensor fordetection of neurotransmitter-acetylcholine using metal nanoparticles, 2Dmaterial and conducting polymer modified electrode, Biosens. Bioelectron.(2016) 1e7, https://doi.org/10.1016/j.bios.2016.06.047.

[135] Y. Gao, J. Xu, L. Lu, X. Zhu, W. Wang, T. Yang, K. Zhang, Y. Yu, A label-freeelectrochemical immunosensor for carcinoembryonic antigen detection on agraphene platform doped with poly(3,4-ethylenedioxythiophene)/Aunanoparticles, RSC Adv 5 (2015) 86910e86918, https://doi.org/10.1039/C5RA16618G.

[136] W. Wang, M. Cui, Z. Song, X. Luo, An antifouling electrochemical immuno-sensor for carcinoembryonic antigen based on hyaluronic acid doped con-ducting polymer PEDOT, RSC Adv 6 (2016) 88411e88416, https://doi.org/10.1039/C6RA19169J.

[137] T. Goda, M. Toya, A. Matsumoto, Y. Miyahara, Poly(3,4-ethylenedioxythiophene) bearing phosphorylcholine groups for metal-free,antibody-free, and low-impedance biosensors specific for C-Reactive pro-tein, ACS Appl. Mater. Interfaces 7 (2015) 27440e27448, https://doi.org/10.1021/acsami.5b09325.

[138] W. Li, W. Dai, L. Ge, S. Ge, M. Yan, J. Yu, Electropolymerized poly(3,4-ethylendioxythiophene)/graphene composite film and its application inquantum dots electrochemiluminescence immunoassay, J. Inorg. Organomet.Polym. Mater 23 (2013) 719e725, https://doi.org/10.1007/s10904-013-9838-5.

[139] R.A. Olowu, O. Arotiba, S.N. Mailu, T.T. Waryo, P. Baker, E. Iwuoha, Electro-chemical aptasensor for endocrine disrupting 17b-estradiol based on aPoly(3,4-ethylenedioxylthiopene)-gold nanocomposite platform, Sensors(Switzerland) 10 (2010) 9872e9890, https://doi.org/10.3390/s101109872.

[140] J. Dapr�a, L.H. Lauridsen, A.T. Nielsen, N. Rozlosnik, Comparative study onaptamers as recognition elements for antibiotics in a label-free all-polymerbiosensor, Biosens. Bioelectron 43 (2013) 315e320, https://doi.org/10.1016/j.bios.2012.12.058.

[141] K. Kiilerich-Pedersen, J. Dapr�a, S. Cherr�e, N. Rozlosnik, High sensitivity point-of-care device for direct virus diagnostics, Biosens. Bioelectron 49 (2013)374e379, https://doi.org/10.1016/j.bios.2013.05.046.

[142] S. Radhakrishnan, C. Sumathi, A. Umar, S. Jae Kim, J. Wilson, V. Dharuman,Polypyrrole-poly(3,4-ethylenedioxythiophene)-Ag (PPy-PEDOT-Ag) nano-composite films for label-free electrochemical DNA sensing, Biosens. Bio-electron. 47 (2013) 133e140, https://doi.org/10.1016/j.bios.2013.02.049.

[143] F. Kuralay, S. Demirci, M. Kiristi, L. Oksuz, A.U. Oksuz, Poly(3,4-ethylenedioxythiophene) coated chitosan modified disposable electrodesfor DNA and DNA-drug interaction sensing, Colloids Surfaces B Biointerfaces123 (2014) 825e830, https://doi.org/10.1016/j.colsurfb.2014.10.021.

[144] X. Wei, P. Panindre, Q. Zhang, Y.-A. Song, Increasing the detection sensitivityfor dna-morpholino hybridization in sub-nanomolar regime by enhancingthe surface ion conductance of PEDOT: PSS membrane in a microchannel,Acs Sensors (2016), https://doi.org/10.1021/acssensors.6b00169.

[145] N. Hui, W. Wang, G. Xu, X. Luo, Graphene oxide doped poly(3,4-ethylenedioxythiophene) modified with copper nanoparticles for high per-formance nonenzymatic sensing of glucose, J. Mater. Chem. B 3 (2015)556e561, https://doi.org/10.1039/C4TB01831A.

[146] Y. Li, H. Lin, H. Peng, R. Qi, C. Luo, A glassy carbon electrode modified withMoS2 nanosheets and poly(3,4-ethylenedioxythiophene) for simultaneouselectrochemical detection of ascorbic acid, dopamine and uric acid, Micro-chim. Acta 183 (2016) 2517e2523, https://doi.org/10.1007/s00604-016-1897-1.

[147] C. He, Z. Wang, Y. Wang, R. Hu, G. Li, Nonenzymatic all-solid-state coatedwire electrode for acetylcholine determination in vitro, Biosens. Bioelectron85 (2016) 679e683, https://doi.org/10.1016/j.bios.2016.05.077.

[148] X. Ye, Y. Du, K. Duan, D. Lu, C. Wang, X. Shi, Fabrication of nano-ZnS coatedPEDOT-reduced graphene oxide hybrids modified glassy carbon-rotatingdisk electrode and its application for simultaneous determination ofadenine, guanine, and thymine, Sensors Actuators, B Chem. 203 (2014)271e281, https://doi.org/10.1016/j.snb.2014.06.135.

[149] J. Kupis-Rozmysłowicz, M. Wagner, J. Bobacka, A. Lewenstam, J. Migdalski,Biomimetic membranes based on molecularly imprinted conducting poly-mers as a sensing element for determination of taurine, Electrochim. Acta188 (2016) 537e544, https://doi.org/10.1016/j.electacta.2015.12.007.

[150] V. Castagnola, E. Descamps, A. Lecestre, L. Dahan, J. Remaud, L.G. Nowak,C. Bergaud, Parylene-based flexible neural probes with PEDOT coated surface

Y. Hui et al. / Analytica Chimica Acta 1022 (2018) 1e19 19

for brain stimulation and recording, Biosens. Bioelectron 67 (2015) 450e457,https://doi.org/10.1016/j.bios.2014.09.004.

[151] F.S. Belaidi, A. Civ�elas, V. Castagnola, A. Tsopela, L. Mazenq, Sensors andActuators B: chemical PEDOT-modified integrated microelectrodes for thedetection of ascorbic acid, dopamine and uric acid, Sensors Actuators B.Chem. 214 (2015) 1e9, https://doi.org/10.1016/j.snb.2015.03.005.

[152] E.S. Muckley, J. Lynch, R. Kumar, B. Sumpter, I.N. Ivanov, PEDOT: PSS/QCM-based multimodal humidity and pressure sensor, Sensors Actuators, BChem. 236 (2016) 91e98, https://doi.org/10.1016/j.snb.2016.05.054.

[153] A.J. Bandodkar, J. Wang, Non-invasive wearable electrochemical sensors: areview, Trends Biotechnol 32 (2014) 363e371, https://doi.org/10.1016/j.tibtech.2014.04.005.

[154] J.W. Park, J. Jang, Fabrication of graphene/free-standing nanofibrillar PEDOT/P(VDF-HFP) hybrid device for wearable and sensitive electronic skin appli-cation, Carbon N. Y. 87 (2016) 275e281, https://doi.org/10.1016/j.carbon.2015.02.039.

[155] T.G, D.D.G. Matzeu, C. O'Quigley, E. McNamara, C. Zuliani, C. Fay, An inte-grated sensing and wireless communications platform for sensing sodium insweat, Anal. Methods 8 (2016) 64e71, https://doi.org/10.1039/C5AY02254A.

[156] Y. Guo, Y. Wang, S. Liu, J. Yu, H. Wang, M. Cui, J. Huang, Electrochemicalimmunosensor assay (EIA) for sensitive detection of E. coli O157:H7 withsignal amplification on a SGePEDOTeAuNPs electrode interface, Analyst 140(2015) 551e559, https://doi.org/10.1039/C4AN01463D.

Yun Hui received her BS degree from Southeast University(Nanjing) in 2014. Currently she is working towards the Ph.D.degree under the supervision of Dr. Shanhong Xia at theInstitute of Electronics, Chinese Academy of Sciences (IECAS).Her research focuses on poly(3,4-ethylenedioxythiophene)composite, microfabrications, electrochemical microsensor,fluorescence detection and water quality monitoring.

Chao Bian received the Ph.D. degree in physical electronicsfrom IECSA in 2006 and worked as a visiting scholar inUniversity of British Columbia in 2013. She is an associateprofessor with the State Key Laboratory of Transducer Tech-nology, IECSA, engaged in biochemical microsensor andmicro-electro-mechanical system (MEMS). Her research in-terests include sensors and systems, micro system

technology, integrated sensor system-on-chip and so on.Currently her researches focus on microsensors and systemsfor water quality monitoring. Dr. Bian has published 37 SCIpapers and 32 EI papers and obtained more than 10 patents.

Shanhong Xia received the Ph.D. degree in electrical engi-neering from Cambridge University, in 1994. She worked asa visiting scholar at the Berkeley Sensor and Actuator Centerfor several short periods. She is now a Professor at IECAS, aswell as vice-president of the Sensor Society and CouncilMember of the China Instrument and Control Society. Shewas the general chair at the 16th International Conferenceon Solid-State Sensors, Actuators and Microsystems. Herresearch interests include sensors and microsystems,system-on-chip, wireless sensor network, micro/nanofabri-cations, water quality monitoring. Dr. Xia has publishedover 300 papers and obtained more than 30 patents.

Jianhua Tong received the Ph.D degrees from Dalian Universityof Technology in 2005. He worked as a postdoctoral researchassociate with the Advanced Micro and Nanosystems Labora-tory, University of Toronto, from 2005 to 2008, and worked as avisiting scholar at Massachusetts Institute of Technology in2015. He is currently with IECSA, as an associate professor. Hisresearch interests include integrated microfluidic devices forwater quality monitoring, microreactor for digestion of totalphosphate and total nitrogen, carbon nanotube-based micro-sensors, MEMS-based device arrays, and piezoelectric micro-sensors and microactuators. Dr. Tong has published over 30SCI papers and obtained over 10 patents.

Jinfen Wang received the Ph.D. degree in bioelectronics fromIECAS in 2013 and worked as a Postdoctoral Research Associatewith the State Key Laboratory of Transducer Technology inIECAS from 2013 to 2016, engaged in biochemical microsensorfor water quality monitoring. She is currently with CAS Centerfor Excellence in Nanoscience, National Center for Nanoscienceand Technology, as a Research Associate. Her research interestsinclude MEMS-based biochemical sensor for water qualitymonitoring, flexible devices and eletroneurophilogy moni-toring. Dr. Wang has published over 20 SCI papers.

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