Conjugated Polymers-Based Chemical and Biological Sensors · 2020. 9. 8. · Conjugated Polymers-Based Chemical and Biological Sensors 177 6.5”*9.75” b2179-V4 Application of Nano

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Chapter 6

Conjugated Polymers-Based Chemical and Biological Sensors

Diqing Su, Yingshan Yao, Yani Chen, Jiajun Peng and Ziqi Liang

Department of Materials Science, Fudan University, Shanghai 200433, China

In this chapter, various conjugated polymers for sensing applications are fi rst discussed. Then, two device structures are introduced according to their label-required or label-free detection principles. Finally, applications of chemical and biological sensors are discussed respectively.

1. Overview

All living organisms in nature have developed the ultimate chemical and bio-logical sensors. Inspired by the incredible sensitivity and perfect specificity of signals some creatures can detect, artificial sensor devices have been fabri-cated. Owing to the increasing importance of environmental protection and resource recycling, there has been a huge demand for sensors capable of environmental monitoring, e.g. monitoring contaminants in industrial efflu-ents as well as toxic gases and vapors. Consequently, the research and devel-opment in the field of sensors have greatly expanded in many ways. Here, we will focus on conjugated polymers-based chemical and biological sensors.

The function of a sensor is known to detect events or changes in quanti-ties and generates a corresponding output, thus providing information on our

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physical, chemical and biological environment. A chemical sensor consists of a physical transducer and a chemically selective layer. A biosensor contains a biological entity such as enzyme, antibody, bacteria, tissue as a recognition agent, whereas a chemical sensor does not contain these agents.1 Among the materials used in sensor devices, π- conjugated polymers (π-CPs) have gained tremendous attention due to their potential of exhibiting collective properties that are very sensitive to minor perturbation compared to small molecules. π-CPs-based sensors can be divided into various schemes based on the kind of signal change they display in response to an analyte interaction. The changes include electrical conductivity, chemical potential, optical absorption and fluorescence — the most common one.2

The fluorescent semiconducting polymers in which π-electrons are delo-calized along the backbone have extended electronic structures, creating conduction and valence bands, respectively. The excitons transport through these energy bands by a combination of Förster (a long-range dipolar interac-tion) and Dexter (strong electronic coupling by a short range interaction) transport mechanisms. When the excitons encounter an energy trap and then are quenched at the receptor site, the fluorescence is diminished and a sensory detection event is realized. This fluorescent sensory scheme has a distinct advantage due to a combination of amplification and sensitivity resulting from efficient energy migration. It has therefore grown into a widely used and rapidly expanding method in chemical and biological sensing.

The chapter is organized as follows. Firstly, we give an overview of various classes of π-CPs for chemical and biological sensors. Secondly, we discuss vari-ous device structures based on two different transduction principles, i.e. label-requiring and label-free technologies, and in particular those employing organic field-effect transistor (OFET) structures. Finally, important applica-tions of both chemical and biological sensors are described.

2. Conducting Polymers for Sensors

2.1. Polyfluorenes

Owing to their good thermal stability and high quantum yield, Polyfluorenes (PFOs) and their related copolymers are one of the most promising blue light-emitting materials for chemo sensors. Chakraborty and coworkers syn-thesized water-soluble PFOs with sulfate ions at the terminal of the alkyl chain (PFS) (Figure 1) as a fluorescence probe to optically detect Cu (II) and cyanide (CN) ions.3 The PFS is blue emissive and can selectively detect the presence of Cu2+ with a detection limit down to 2.5 μM and CN− ions down


Conjugated Polymers-Based Chemical and Biological Sensors 177


to 6 μM. Detection of Cu2+ is based on the fluorescence “turn-off” mecha-nism. The fluorescence intensity is closely related to the concentration of Cu2+, for example, decreasing dramatically from 2.5 μM of Cu2+ to 25 μM of Cu2+, where no detectable luminescence is seen. Surprisingly, the quenched luminescence of PFS by Cu2+ could be turned on after the addition of CN−, which makes PFS a sensitive, selective and reversible cyanide probe.

A zwitterionic, boronic acid bearing a conjugated PFO polymer (PFBA) (Figure 2) was developed by the same group.4 The brilliant blue fluorescence is quenched after complexation with diol bearing biomolecules, e.g. L-DOPA, monosaccharides (D-glucose and D-fructose) and L-ascorbic acid. Because of the ground state formation of boronic ester with bio-anaytes, a static quenching is observed by photoluminescence (PL) studies in which fluores-cence of PFBA is quenched after addition of cis-dioanalytes. The maximum response with bio-analytes from aqueous solution is accomplished by PFBA at a physiological pH of 7.4, which provides a scope for PFBA to be used in biological systems.

A highly selective assay method to detect Hg2+ was developed by Lu et al. by using cationic conjugated polymer (CCP) (Figure 3).5 In the absence of Hg2+, the electrostatic interactions can help CCP form a complex with an anionic 1,3-dithiole-2-thione derivative. Due to the electron transfer process in 1, 3-dithiole-2-thione, the fluorescence of CCP was efficiently quenched. When adding Hg2+ ions, the previous 1, 3-dithiole-2-thione turned into 1,3-dithiole-2-one, which inhibited the quenching and thus led to fluorescence recovery. With detection limit as low as 0.5 μM, the assay included a distin-guishing signal amplification of CCPs and a specific Hg2+ promoted reaction.

Figure 1. The chemical structure of PFS.3

Figure 2. The chemical structure of PFBA.4


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2.2. Polythiophenes

Detection of metal ions requires materials with high affinity in order to achieve preconcentration at the electrode. For this purpose, Polythiophenes (PTs) having sulphur atoms in the main chain are introduced. Besides their high affinity towards metal ions, PTs can also be suitably operated in their β-position, which results in selective interaction with the analytes. Seol and his coworkers developed a kind of PTs possessing 4-formyl-3-hydroxy-1-phe-nyl side groups.10 The materials successfully demonstrate the highly selective property of PTs by illustrating its selective determination of Al(III) ions at pH 7.4, even in trace levels, and the effectiveness of the sensor can also be evalu-ated using a real standard urine sample.

An anion sensor based on semifluorinated π-conjugated diphenylbithio-phene as (Figure 4) chromophoric main chain demonstrated visually detect-able colorimetric changes as well as PL extension in response to fluoride or cyanide compared to other common anions in tetrahydrofuran (THF).6 For efficient sensing, the proper dissociation constants of 4.5 × 10−5 and 6.7 × 10−3 were determined for fluoride and cyanide, respectively, and a chromo-phore acting as a hydrogen bond donor was also required.

In the optical sensing of nitroaromatic vapors, PTs are by contrast paid less attention to because of their rather low sensory response. However, Nagarjuna et al. enhanced the interaction of polymers with 2,4 dinitrotoluene (DNT) and 2,4,6 trinitrotoluene (TNT) by adding 1,2,3-triazole moiety with appropriate alkyl side chains to PTs.11 Figure 5 displays the chemical struc-tures of three different polymers they synthesized. It was found that fluores-cent quenching of these three polymers towards DNT is in the following

Figure 3. The chemical structure of CCP.

N N

n

CCP




order: P3TzdHT > P3TzHT > P3BSiT. The quenching efficiency of P3TzdHT is 13% higher than that of P3BSiT due to the large dipole moment of 1, 2, 3-triazole, which results in a stronger ability to interact with nitroaro-matics via dipole–dipole interactions or through hydrogen bonding or both. The desired side chains can be easily attached by clicking the corresponding azides and also tuned modularly to obtain strong interactions between ana-lytes and polymers as well as lower chain packing in the thin film.

2.3. Poly(p-phenylenevinylene)s

Poly(p-phenylenevinylene)s (PPVs) are strongly luminescent conjugated polymers with high permeabilities to small molecule analytes. Chang et al. explored two such polymers (Figure 6) undergoing fluorescence quenching when exposed to DNT and TNT vapor at the ppm level.7 Different structures of poly(2-methoxy-5, 2-ethylhexyloxy-p-phenylenevinylene) (MEH-PPV) and Poly(2,3-diphenyl-1,4-phenylenevinylene)

DP10-PPV contribute to the variation of polymer response. The dialkoxy-substituted aromatic ring of MEH-PPV is richer in electron than the diphenyl-substituted aromatic ring of DP10-PPV, thus allowing for stronger coulombic interactions between electron-donating MEH-PPV and the electron-accepting analytes. Also, the planar structure of MEH-PPV

Figure 4. Chemical structure of the semifluorinated polymer with diphenylbithiophene.6

R1R2 R1

n

R1 = X-CF=CF- R2 = −90% -(p-C6H4)-C(CF3)2-(p-C6H4)-−10% chromophoreY -CH(F)-CF2-

Figure 5. The chemical structure of polymers synthesized by Nagarjuna and his coworkers.11

P3TzdHT P3TzHT P3BSiT

S S S

NN

NN

TIPS

N N

C6H13

C6H13

C6H13

n n n


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ensures more effective exciton migration along the polymer backbone. Consequently, the MEH-PPV polymer shows greater quenching efficiency than DP10-PPV.

Schimitberger and his coworkers designed an easy-to-read and smart dosimeter to detect 6 MV X-rays based on organic emissive solutions of MEH-PPV, aluminum-tris-(8-hydroxyquinoline) (Alq3) and additive components.12 During the radiation process, a change in the effective spectral overlap was observed between the emission of Alq3 solutions and the absorption of MEH-PPV, resulting in effective sensing (Figure 7). They also managed to control the degradation of MEH-PPV by adding free radicals scavengers or delivering compounds. For example, the basic degradation process can be enhanced by hindered phenolic stabilizers and reduced by benzoyl peroxide. The device can be successfully programmed to operate in doses from 0 to 100 Gy.

2.4. Poly(p-phenyleneethylene)s

Yang and Swager developed thin films of Poly(p-phenyleneethylene)s (PPEs) with remarkable nitroaromatic detection ability.8 This kind of poly-mer transducer showed rapid quenching of blue luminescence in TNT vapor at the ppm level. The PPE structure as shown in Figure 8 contains two bulky pentiptycene moieties on each alternating phenyl unit of the back-bone. The long polymer chain (Mn = 56000 g/mol) promotes the exciton delocalization, leading to exceptional sensitivity. A 25 Å film showed 50% quenching after 30 s exposure to TNT vapor, and 75% at 60 s; when exposed to DNT vapor, the quenching was up to 91% and 95% at 30 s and 60 s, respectively.

Satrijo et al. also reported an anthryl-doped, polyanionic PPE and its optical properties under different aggregation conditions.9 They found mul-ticationic amines as an effective inducer to the formation of tightly associated

Figure 6. PPVs: (A) MEH-PPV, (B) DP10-PPV.7




aggregates between PPE chains in 50:50 EtOH–H2O. The exciton migration from the blue-emitting PPE segments to the green-emitting anthryl units was largely enhanced due to the induced aggregation, which resulted in a visually detectable fluorescence color change from blue to green.

Figure 7. A set of 7 sealed glass ampoules filled with (a) MEH-PPV/Alq3: inhibitor; (b) MEH-PPV/Alq3 and; (c) MEH-PPV/Alq3: accelerator solutions obtained from exposure to 6 MV X-ray doses equal to 0, 10, 20, 40, 60, 80 and 100 Gy. All the organic materials were excited by a violet light (emitted from a violet LED with wavelength from 380 to 410 nm).12

Figure 8. The structure of PPEs: (A) PPE developed by Yang and Swager; (B) PPE devel-oped by Yang et al.8


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2.5. Polydiacetylenes

Polydiacetylenes (PDAs) have attracted much attention in sensor applications due to their unique colorimetric and fluorescence transitions. Kootery et al. spin-coated PDA films on poly(methylmethacrylate) (PMMA) and recorded special chromatic transformations.13 Specifically, the as-polymerized blue PDA layer experienced distinct transformations to purple, red and yellow phases, and a reversible red-purple PDA transition induced upon UV irradia-tion was also observed, reflecting a reversible transition from red PDA phase back to original blue phase. The chromatic properties are likely related to the specific molecular arrangement at the PDA/PMMA interface. The mixture solvents that were used for spin-coating the diacetylene monomers upon the PMMA substrate contributes to partial dissolution of the polymer surface area, thus enabling more pronounced internalization of the pendant PDA side chains within the polymer network.

Furthermore, Park et al. developed a PDA–PDMS composite sensor to overcome the difficulties in detecting saturated aliphatic hydrocarbons (SAHCs).14 The reasons lie in their extremely nonpolar nature and lack of functional groups capable of interacting with probes. The researchers observed a blue-to-red colorimetric transition on a time scale dependent on the chain length of hydrocarbon target. In addition, the development of the red color is directly proportional to the swelling ratio of the film, enabling naked-eye differentiation of a number of different linear alkanes, e.g. n-pentane and n-heptane. That is because the swelling promotes an increase of interchain distances between PDA supramolecules within crys-tals embedded in the film, and then produces a distortion of the arrayed p-orbitals of the conjugated polymer and a simultaneous blue-to-red color transition.

A novel multi-stimuli responsive fluorescence probe was developed by incorporating a spiro-pyran group into coumarin-substituted PDA vesicles.15 The probe exhibited reversible color and fluorescence changes in response to external thermal, photo and pH stimuli owing to the fluorescence energy transfer (FRET) between the red-phase PDA and the open merocyanine (MC) corm of spiro-pyran. Moreover, a set of resettable logic gate operations can be designed and realized based on the earlier system, which is capable of providing memory elements in an all-aqueous system and makes the hybrid PDA vesicles a promising candidate for multiplexed detection of analytes in biological and biomedical systems.




2.6. Dendrimers

Dendrimers are composed of multiple perfectly branched monomers that emanate from a central core with predictable 3D shapes. By designing the functional units in predetermined sites on their nanometric dimension struc-tures, the properties can be controlled, making dendrimers attractive molecu-lar probes. Kim, Vicents and others have extended a series of dendrimer-based sensors derived from pyreneamide-appended calix arenes,16 which employed calixarenes as one of the building blocks to prepare hyperbranched supramol-ecules and dendrimers. Multidentate ligands based on a tripodal tris(2-ami-noethyl)amine moiety(tren) were branched with calixarenes to build Y-shaped calix-dendrimers. As was the case with the rhodamine-dipyrenyl N-tren- di-calix fluorescent sensor for two metal cations (Al3+ and Hg2+), whose photo-properties changed through photo electron transfer (PET), FRET and other kinds of processes.

A Cy5-labeled fluorescence assay on phosphorous dendrimer derived DNA microarrays was developed for detection of DNA hybridization at pico-molar analyte concentrations.17 A five-fold improvement in the detection limit was observed for the dendrimers modified surface as compared to silanized slides. Furthermore, a four-fold increase in fluorescence was accom-plished by polyamidoamine(PAMAM)-bonded DNA probe.18 PAMAM den-drimer surface amine moieties were modified to biotin and immobilized on glass slides using biotin-avidin conjugation. The dendrimer-coated DNA chips exhibited excellent specificity for discriminating single nucleotide poly-morphism (SNP) and a broader detection dynamic range with target concen-trations from 1pM to 1nM.

2.7. Polymeric nanocomposites

Conducting polymeric materials of nanometer sizes inherit the fascinating properties of their bulk counterparts and possess further unique properties due to high surface-to-volume ratio and small dimensions. The interaction between conducting polymers and analytes is enhanced, and the response/recovery time is reduced because of the high surface area of the nanomaterials and its permission of rapid adsorption/desorption kinetics for analytes. In addition, the signal intensity can also be improved with the presence of nano-materials due to the variation of charge transport behavior in the bulk of the materials instead of only within the surface region.


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Jang et al. reported a facile technique for the synthesis of water-dispersible polyanilne (PANI) nanoparticles with poly(4-styrenesulfonate) (PSS) as an anionic polyelectrolyte, in aqueous solution (Figure 9).18 They conducted a study on the relationship between sensitivity, the surface area and thickness of the nanoparticle films. The PANI–PSS nanoparticles can be ink-jet printed on a substrate for sensor applications due to their water-dispersive property, which makes the dimensions of nanoparticle films for examining sensitivity with respect to sensing area and film thickness easy to control. It was observed that thicker films has a large sensing area and vacant volume where more analyte can absorb and diffuse into the nanoparticles, while a smaller sensing

Figure 9. (a) An atomic force microscopy image of PANI–PSS nanoparticles coated on a glass coverslip; (b) a photograph image of the emblem of Seoul National University, printed with an ink-jet printer using aqueous PANI–PSS solution as ink. The reversible and reproduc-ible responses of PANI–PSS film upon periodic exposure to NH3 vapor as a function of (c) sensing area (at a constant thickness of 1.2 mm) and; (d) film thickness (at a constant sensing area of 10 mm × 5 mm).18




area provides a shorter and more effective conducting path, both of which contribute to enhanced sensitivity in PANI–PSS nanoparticles.

Polyaniline blended with polyvinyle alcohol (PVA) were prepared with variable amounts of PANI in the composite for micro-humidity sensors. Low weight ratio of PANI (10%) in the nanocomposites showed high sensitivities to humidity, but the bulk resistances are too high for most practical use. A higher level of PANI contents (greater than 10%) then showed lower bulk resistance, yet the sensitivity to humidity is also dramatically reduced. Moreover, as the humidity increases, a resistance increase can be observed at 20 wt%, which is attributed to an aggregation of PANI colloid particles at these higher PANI levels. The PANI swells at high humidity levels, leading to a separation of the conducting PANI domains and resulting in an increasing in the resistance. The overall resistance is dependent on the competitive pro-cesses where the resistivity of PANI and PVA decreases and increases, at high humidity, respectively.19

3. Sensor Devices

By far, two different signal transduction principles have been reported in sen-sor detection: label-requiring technologies in which the analyte or the recog-nition element are conjugated with an optical or electroactive probe revealed by the transducer, and label-free methods where a directly-measurable change in a physical variable is produced in the recognition process.20

Label-requiring methods are widely employed and can be easily adapted in portable and miniaturized devices at low cost. Yet, their full integration into a circuit is not yet being reliably achieved, especially in electrochemical detection, which is mostly connected to their need of a reference electrode whose integration into a circuit is still a problem. By comparison, label-free technologies have a very simple detection scheme with only one captured molecule that is immobilized at the transducer detecting interface, and show great sensitivity. However, they are mostly facing with the high fabrication costs and complex detecting apparatus.

3.1. Label-requiring devices

Gaylord et al. reported a real-time DNA detection assay based on cationic blue-emitting polyfluorene and a fluorescein-labeled peptide nucleic acid (PNA) (Figure 10).21,22 PNA is employed as a probe for selective detection of target DNA, and the conjugated polyelectrolytes (CPEs) contributes to the high sensitivity due to its light harvesting properties. The positive CPEs and


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negative duplex of PNA/DNA form an electrostatic complex, which brings them into close proximity. This induces efficient FRET from the CPEs to fluorescein in the probe PNA. When there is no complementary target DNA, the CPEs will form an electrostatic complex with the sample DNA, resulting in a negligible FRET-induced fluorescein signal.

To overcome the difficulties in potassium detection caused by the inter-ference of the high concentration of sodium ions in biological media, Li et al. employed a molecular beacon aptamer (MBA) as a potassium probe. This MBA is a hairpin-shaped oligonucleotide hybridization probe where the K+-specific aptamer base sequence is incorporated in the loop part, and a fluorophore and quencher are labeled at both termini of the DNA strand.23 In the presence of K+, the addition of CPEs will not induce conformational change since the interactions between the MBA and K+ ions are stronger, which leads to a quenched FRET PL signal. In the absence of K+ ions, the MBA undergoes a conformational change to an open-chain structure through electrostatic or hydrophobic interactions or both, which induces the strong FRET-induced fluorophore emission without K+ ions. The device showed high sensitivity over a range of metal ions, and the detection limit was deter-mined to be ~1.5 nM in the presence of 100 mM Na+.

3.2. Label-free devices

Li et al. developed a label-free fluorescence sensor for the detection of adenosine triphosphate (ATP) and alkaline phosphatase (ALP) based on the water-soluble fluorescent conjugated polymer. 3 The schematic illustration of the fluorescent sen-sor is shown in Figure 11. Cu2+ could efficiently quench the PL intensity of the poly2, 5-bis(3-sulfonatopropoxy)-1,4-phenylethynylenealt-1,4-poly(phenylene

Figure 10. CPEs-based DNA detection scheme and the normalized FRET-induced PL spec-tra in the presence and absence of target DNA.21,22

1.6

1.4

1.2

0.8

0.6

0.4

0.2

0400 450 500

WAVELENGTH (nm)

(a) complementary

NO

RM

ALI

ZE

D E

MIS

SIO

N

(b) noncomplementary

550 600 650

(b)

(a)

1

Probe and AnalyteProbe and Analyte⇒ Complementary⇒ Non-complementary

Probe (PNA)CCPTarget (DNA)




ethynylene) (PPESO 3) due to the electrostatic interaction and electron transfer between PPESO3 and Cu2+. In the presence of ATP, the PPEO3–Cu2+ system would be disrupted and instead Cu2+ will form a more stable complex with ATP, leading to the recovery of the fluorescence of PPESO3. Furthermore, when ALP is introduced into the system, the Cu2+ in the ATP–Cu2+ complex would be released, quenching the fluorescence of PPESO3 again because of the hydrolysis of ATP by ALP. It was shown that the recovered PL intensity of PPESO3 has a good linear relationship with the concentration of ATP in the range of 0.05–15 μmol L−1, and the detection limit for ATP is down to 0.03 μmol L−1. For the enzyme activity of ALP, the fluorescence turn-off assay can be achieved in the range of 0.05 to 1.0 U mL−1, with detection limit down to 0.01 U mL−1.

Xu et al. developed a new DNA switch monitoring and a K+ sensor sys-tem based on the interaction between the K+-aptamer and cationic CPE (P1) in the presence of an intercalator, SYBR green (SG).24 After the addition of K+ ions, the K+ specific aptamer forms a G-quadruplex structure with K+, resulting in the intercalation of SG to G-quadruplex, producing enhanced SG emission. In the presence of P1, the polymer approaches the G-quadrupex/SG complex via electrostatic attraction, leading to efficient FRET from P1 to SG with signal amplification. In the absence of K+, it’s difficult for SG to intercalate to the aptamer, which yields inefficient FRET (Figure 12). The device showed a wide linear response of 5 to 50 mM with excellent selectivity.

Figure 11. Schematic illustration of the fluorescence sensor for the determination of ATP and ALP.23


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Figure 12. (A) Schematic G-quadruplex assays; (B) chemical structures of P1 and SG, and; (C) fluorescence spectra with and without K+ ions. 24




3.3. OFET structures

The transduction principle of OFETs also belongs to the label-free methods, but since this kind of structure is recognized as a promising candidate for the applications in biological and chemical sensors, it will be discussed separately in this section. Typical OFET device structure is shown in Figure 13.

Tiwari et al. fabricated soluble poly(3-hexylthiophene) (P3HT) based OFETs for ammonia vapordetection.25 The chemical interaction between ammonia and P3HT can cause dedoping at a low concentration, which is confirmed in the purification process of the synthesized P3HT. When the device is not exposed to NH3, the device behaves as p-channel with majority carrier — holes participating in the conduction process as normally ON state. These positive charges are injected to the OSC material (P3HT), and a con-ducting channel is formed at the OSC/insulator surface when a negative gate voltage is applied. When ammonia interacts with P3HT, a linkage type struc-ture is formed as shown in Figure 14, and the lone pair of electrons of ammo-nia leads to a decrease in the value of ID at fixed gate voltage (VGS) of −30 V with different concentrations. In this respect, the net positive charges of the polymer are reduced, which in turn results in a decrease in current flowing through P3HT, resulting in reduced mobility and threshold voltage of the polymer. With this structure, the OFET was found to be sensitive enough to detect ammonia below 1 ppm concentration.

OFETs having oligothenylene derivative structures are evaluated as pos-sible sensors for DNT.26 When exposed to the analyte, a redox interaction

Figure 13. Scheme of a typical OFET device structure before (a); and after exposure to an analyte (b), in which the OSC stands for organic semiconductor.20


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between the organic semiconductor donor and the DNT acceptor occurs, and extra holes in the semiconductor are generated, resulting in amplified currents and a shift in the threshold voltage. The degradation of the hexyl capped tetra(thienylene–vinylene) structures based device was also studied. When left unbiased at ambient atmosphere for 2 days without DNT expo-sure, a decrease of the drain current was observed. The most probable cause of the aging is water absorption, which may create deep traps at high tem-peratures (typically > 250K). Since aging is inevitable in practical devices, the determination of DNT concentration needs either to recover the initial response or to accurately know the variation of switch-on currents as a func-tion of aging. Still, the problem remains to be solved.

4. Chemical Sensor Applications

Conducting polymers have been widely used in chemical sensor applications. In this section, several different applications of conducting polymer-based sensors will be discussed specifically including ion, PH, gas, alcohol detection and progress control.

Ion sensors have been developed by using conjugated polymers as the conductive system/component, or as a matrix for the conducting system. When such systems are in contact with analytes to be sensed, ionic exchange

Figure 14. Chemical interaction of ammonia gas molecules with P3HT.25




or interaction occurs, which in turn is transmitted as an electronic signal for display. A new Ca2+ selective sensor based on PANI membrane was developed for all-solid-state measurement of calcium activity in water samples extracted from agricultural soils.29

As such, the measurement and control of pH is very important in chem-istry, biochemistry, clinical chemistry and environmental science. de Marcos and Wolfbeis developed an optical pH sensor based on polypyrrole by oxida-tive polymerization.30 Since the polymer film has suitable optical properties for optical pH sensor, the immobilization step for an organic dye during preparation of the sensor layer was not required. Others have also developed optical pH sensors based on PANI for measurement of pH in the range of 2–12. They reported that the PANI films synthesized within a time span of 30 min are very stable in water.31–33

An optical pH sensor was reported by Jin et al. based on PANI films that are made by chemical oxidation at room temperature.34 The stability of the PANI film was improved significantly by increasing the reaction time up to 12 h. The film showed rapid reversible color change upon pH change. The pH of the solution could be determined by monitoring either absorption at a fixed wavelength or the maximum absorption wavelength of the film.

Pandey et al. developed a solid state poly(3-cyclohexyl)thiophene treated electrode as a pH sensor,35 and subsequently, an urea sensor. Later, Pandey and Singh reported the pH sensing function of polymer-modified electrode (a novel pH sensor) in both aqueous and nonaqueous mediums.36 The sensor was derived from polymer-modified electrode obtained from electrochemical polymerization of aniline in dry acetonitrile containing 0.5 M tetraphenylbo-rate at 2.0 V versus Ag/AgCl reference electrode. The light yellowish poly-mer modified electrode was characterized by scanning electron microscopy (SEM). They used weak acid (acetic acid) and weak base (ammonium hydrox-ide) as analytes. The acetic acid was analyzed in both aqueous and dry ace-tonitrile, whereas ammonium hydroxide was analyzed only in aqueous medium.

The gaseous pollutants such as SO2, NOx and toxic gases have become a serious environmental problem. Sensing technologies are needed to detect and measure the concentration of such gaseous pollutants. Now, analytical gas sensors offer a promising and inexpensive solution for problems related to hazardous gases in the environment.

Nylander et al. investigated the gas sensing properties of polypyrrole by exposing polypyrrole-impregnated filter paper to ammonia vapor.37 Persaud and Pelosi reported conducting polymer sensor arrays for gas and odor sens-ing based on substituted polymers of pyrrole, thiophene, aniline, indole.38,39


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It was observed that nucleophilic gases cause a decrease in conductivity, with electrophilic gases (NOx, PCl3, SO2) having the opposite effect.

Electroactive nanocomposite ultrathin films of PANI and isopolymolyb-dic acid (PMA) for detection of NH3 and NO2 gases were fabricated by alter-nate deposition of PAN and PMA following Langmuir–Blodgett (LB) and self-assembly techniques. The process was based on doping-induced deposi-tion effect of the emeraldine base. The NH3-sensing mechanism was based on dedoping of PANI by basic ammonia, since the conductivity is strongly dependent on the doping level. In sensing of NO2 that plays the role of an oxidative dopant, an increase in the conductivity results when emeraldine base is exposed to NO2.

In addition to gas detection, the determination of alcohol is also neces-sary in industrial and clinical analyses, as well as in biochemical applications. PANI and its substituted derivatives such as poly(o-toluidine), poly(o-anisidine), poly(N-methylaniline), poly(N-ethyl aniline), poly(2, 3-dimethyl aniline), poly (2, 5-dimethyl aniline) and poly(diphenylamine) were found by Athawale and Kulkarni to be sensitive to various alcohols such as methanol, ethanol, propanol, butanol and heptanol vapors.40

5. Biological Sensor Applications

Biosensors have demonstrated great potential in biomedical research, envi-ronmental analysis, clinical diagnosis and food control. There have been enormous researches on developing highly selective, fast, reliable and low-cost versions of these devices, in which conducting polymers play an impor-tant role in the biological detection process. Different conducting polymers in biosensor applications will be introduced as follows.

5.1. Enzyme sensors

The enzyme sensor is the combination of a transducer and a thin enzymatic layer, which normally measures the concentration of a substrate. The enzy-matic reaction transforms the substrate into a reaction product detectable by a transducer. A schematic representation of an enzyme sensor is given in Figure 15. Different strategies are followed for the immobilization of molecu-lar recognition agent in sensor devices, particularly in biosensors. Polymers are the most suitable materials to immobilize the enzyme, the sensing com-ponent and hence to increase the sensor stability.

One of the most frequently performed routine analyses is the determina-tion of glucose in clinical chemistry, microbiology and in the food industries.




To treat Diabetes, the artificial pancreas was invented which has come to a reality for dynamically responding to glucose level and controlling insulin release based on the sensor’s response. Sangodkar et al.41 Fabricated PANI-based microsensors and microsensor arrays are used for the estimation of glucose, urea and triglycerides. Various copolymers of 3,4-ethylenedioxythiophene and modified EDOT containing hydroxyl groups were electrochemically prepared by Kros and coworkers.42 These copolymers have the ability to bind proteins at the surface through the covalent coupling of glucose oxidase, which were used as working electrodes and able to amperometrically detect glucose under aerobic and anaerobic conditions.

Electropolymerized pyrrole derivatives with phosphatidylcholine, 5-(1-pyrrolyl)pentyl-2-(trimethylammonium)ethyl phosphate in the presence of glucose oxidase (GOD), and an inner-membrane of Nafion or poly(o-phenylenediamine) (PPD) were developed as new hemo compatible glucose sensors.43 Schuhmann used polypyrrole/glucose oxidase electrodes,44 with the enzyme covalently bound to the outer surface of the functionalized poly-meric network, together with a similarly prepared nonenzyme electrodes to determine glucose in the presence of co-oxidizable compounds in fruit juices and wines.

A glucose biosensor based on glucose oxidase immobilized in an over-oxidized polypyrrole film was used for continuous subcutaneous monitoring of glucose in a rabbit implanted with a microdialysis probe.45 Likewise, a glucose amperometric biosensor was prepared by glutaraldehyde co-crosslink-ing with BSA was reported.46 This sensor was tested for glucose determina-tion of untreated serum samples from both normal and diabetic subjects. The

Figure 15. Diffusions of the analyte A from solution to enzyme layer and the product P via enzymatic reaction to the transducer.1


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results of amperometric assay are in good agreement with those obtained by a standard enzymatic-colorimetric method.

Urea is the end product of protein degradation in the body. The concen-tration of urea in blood is important for the assessment of kidney functioning in clinical chemistry. Osaka and coworkers constructed a highly sensitive and rapid flow injection system for urea analysis, with a composite film of elec-tropolymerized inactive polypyrrole (PPy) and a polyion complex incorporat-ing urease.47 Their system showed a sensitivity of 120 mV decade–1 and a lifetime of more than 80 assays. High sensitivity of the system is ascribed to an additional potential response of inactive PPy to ammonia or ammonium ion superimposed on the response to pH change.

A cholesterol biosensor was constructed by entrapment of cholesterol oxidase (ChOx) within a composite poly(2-hydroxyethyl methacrylate) (p(HEMA))/polypyrrole membrane. Platinum electrode-supported polymer films were prepared by UV polymerization of the hydrogel component con-taining dissolved enzyme, followed immediately by electrochemical polymeri-zation of entrapped pyrrole (Py) monomer within the performed hydrogel network.48

Cholesterol biosensors were also constructed by entrapment of choles-terol oxidase within a polypyrrole film electropolymerized in a flow system.49

This method enables adjustment of the biosensor characteristics and features low reagent consumption. The proposed cholesterol oxidase based biosensor, named Pt/PPy–ChOx, was applied for the determination of cholesterol in reference serum samples, with results consistent with certified values. Another approach is the immobilization of the enzyme and laponite particles in a polypyrrolic matrix in order to greatly enhance the sensitivity and stability of a cholesterol oxidase based biosensor.50 Such a biosensor was constructed by electropolymerization of a laponite nanoparticle-amphiphilic pyrrole deriva-tive-enzyme mixture pre-adsorbed on the electrode surface.

Hin and Lowe constructed a bienzyme electrode for the detection of total cholesterol by incorporating cholesterol esterase and cholesterol oxidase in polypyrrole films.51 They claimed that in situ deposition of both enzymes during the electrochemical polymerization of pyrrole provides a simple pro-cedure for the immobilization of biomolecules at the electrodes and a fast amperometric response to cholesterol and has good storage stability. Kajiya et al. also incorporated cholesterol oxidase and ferrocenecarboxylate ions in polypyrrole films by electro-polymerization of pyrrole in an aqueous solution containing these substances.52 They obtained a remarkable amperometric response to cholesterol using such polymer films, correlating the current response with the apparent enzymatic activity of polypyrrole films.




The conventional methods of peroxides’ measurement are usually com-plicated, and suffer from various interferences. The determination of hydro-gen peroxide and organic peroxides in clinical samples and the environment is rapidly gaining practical importance. Measurement of lipid peroxides in food products and biological tissues is necessary in establishing a relationship between diseases such as breast cancer and the level and type of fat in the diet.53 García-Moreno et al. prepared a biosensor by immobilization of the horseradish peroxidase (HRP) enzyme during the electropolymerization of N-methylpyrrole for use in the determination of organic peroxides in a pre-dominantly nonaqueous medium, such as reversed micelles.54 A novel and stable amperometric biosensor was developed for the detection of hydrogen peroxide.55 The biosensor device was constructed by electrodepositing HRP/PPy membrane on the surface of ferrocenecarboxylic acid mediated sol-gel derived composite carbon electrode. The response time of this biosensor to hydrogen peroxide is a few seconds, with detection limit of 0.05 mM Lactate sensor

The determination of lactate does not only belong to frequently per-formed analyses in clinical chemistry now, but its popularity in the diagnosis of shock and myocardial infarction and in neonatology and sports medicine is increasing. Strong efforts were made to develop sensor-based lactate ana-lyzers, which might be readily used at the bedside. Chaubey et al. reported the co-immobilization of lactate oxidase and lactate dehydrogenase on con-ducting polyaniline films by physical adsorption for the estimation of l-lactate in cells and fermentation.56 Later Chaubey et al. immobilized lactate dehydro-genase (LDH) on electrochemically polymerized polypyrrole-polyvi-nylsul-phonate (PPy-PVS) composite films, via cross-linking technique using glutaraldehyde, for application to lactate biosensors.57 These PPy–PVS–LDH electrodes were shown to have a detection limit of 0.1 mM, a response time of about 40 s, and a shelf-life of about 2 weeks, which were used for L-lactate estimation from 0.5 to 6 mM.

The fructose biosensor is very useful in determination of fructose in fruits or juices or for detection of lactulose after enzymatic hydrolysis in milk sam-ples. Garcia et al. reported a new fructose biosensors utilizing a polypyrrole film and D-fructose 5-dehydrogenase immobilized by different processes.58

They employed the occlusion enzymatic immobilization technique for enzyme immobilization in the polypyrrole film and the crosslinked covalent bond method as another technique for immobilization of the enzyme in the polypyrrole film. Such biosensors were utilized for fructose determination in three different samples of dietetic products, with 200 analyses performed in 2 weeks continuously.


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An amperometric biosensor for fructose determination was fabricated by Khan et al. by co-immobilizing a pyrrolo quinoline quinone (PQQ) enzyme (fructose dehydrogenase, FDH) with the mediator in a thin polypyrrole membrane.59 They described two methods of sensor preparation. In one, FDH was potentiostatically adsorbed as a monolayer on a transducer elec-trode, and a very thin (equivalent to a monolayer of FDH) polypyrrole mem-brane containing amediator was electrodeposited on the adsorbed FDH. In the other, FDH and mediator [hexacyanoferrate (II) or ferrocene] were co-immobilized on an electrode by electrochemical polymerization of pyrrole.

5.2. DNA sensors

For the analysis of unknown or mutant genes, the diagnosis of infectious agents in various environments and the detection of drugs, pollutants, DNA sensors interacting with the structure of the double stranded DNA have attracted lots of interest.

The system developed by Dupont-Filliard et al. is based on biotin grafting-units, covalently linked to a polypyrrole matrix, able to anchor large biomolecules due to biotin/avidin affinity.60 There is a scope for regenerating the grafting-units after the “denaturation” of the biotin/avidin link, thus allow-ing the matrix for the immobilization of a new assembly (new biomolecule) with the possibility to generate a new sensor.

New biocomposite materials, based on the incorporation of nucleic acid dopants within an electronically conducting polypyrrole network, are described by Wang and Jiang.61 The growth patterns and ion-exchange prop-erties of these electropolymerized polypyrrole-oligonucleotide (PPy/ODN) films have been characterized using an in situ electrochemical quartz crystal microbalance (EQCM). Various parameters, such as the ODN length or con-centration, and the potential range, have a marked effect on the properties of the new conducting biomaterials. Very favorable growth patterns are observed for biocomposites containing 20–30-mer long ODNs, while films based on shorter ODNs or chromosomal DNA display inferior properties. The com-posite films can be prepared using low concentrations of the nucleic acid dopant, in the absence of an additional electrolyte. Such biomaterials open new opportunities, including genoelectronic devices, composite materials, bioactive interfaces, genetic analysis or probing of DNA charge transfer.

A conjugated polymer is regarded as a 3D network of intrinsically con-ducting macromolecular wires, able to transport electrical signals. Further functionalization of such molecules with prosthetic groups show recognition properties and such polymer architectures mimic the nervous system in living




systems. With this idea, Garnier et al. developed new electrochemical sensors based on electroactive polypyrrole functionalized with ODN.62 They analyzed the experimental conditions for building such a modified electrode, showing a high electroactivity in aqueous medium. The functionalization of polypyr-role involved a precursor polypyrrole bearing an easy leaving ester group, on which an amino-labeled ODN could be directly substituted. The electro-chemical response of this polypyrrole electrode functionalized with an ODN probe was analyzed in various aqueous media, containing either complemen-tary or noncomplementary ODN targets. The results showed that the func-tionalized polypyrroles act as macromolecular wires, able to transduce biological information intomolecular signals.

Livache et al. described an ODN array constructed on a silicon device bearing a matrix of addressable 50-micronmicroelectrodes. Each electrode was covered by a conducting polymer (polypyrrole) grafted with ODN.63 The DNA chip was prepared by successive electrochemically addressed copolym-erizations of 50 pyrrole-labeled ODN and pyrrole. This technology found successful application in the genotyping of hepatitis C virus in blood samples, with results that showed good sensitivity and a high dimensional resolution.

5.3. Other applications

Sensor arrays coupled with pattern recognition are useful in the discrimina-tion of the aromas of certain foods and beverages. Several examples are avail-able in the literature, demonstrating the success of using polymeric array of sensors for the detection of food and beverage odors.

Guadarrama et al. described a sensor array based on thin films of conduct-ing polymers with an objective to discriminate among different virgin olive oils.64 They constructed an array using eight polymeric sensors deposited electrochemically using monomers such as 3-methylthiophene, pyrrole and aniline and doping agents. In a later publication, they reported an electronic nose for the organoleptic characterization of olive oil. The instrument con-sists of an array of electrodeposited conducting polymer-based sensors not only able to distinguish among olive oils of different qualities (extra virgin, virgin, ordinary and lampante) but also among Spanish olive oils prepared from different varieties of olives and even of different geographic origins.

For the identification of wines, Guadarrama and collaborators tested a set of 12 polymeric sensors as an artificial olfactory system. A set of sensors were prepared by electrochemical deposition of various conducting polymers, such as polypyrrole, poly-3-methylthiophene and polyaniline. The array of 12 sen-sors, which were located in a stainless steel chamber, was exposed to the


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aromas of Spanish white and red wines from different regions, and the system was able to differentiate among the tested samples.

In another development by Meijerink and his coworkers, PANI dispersion was used to prepare chemo resistors by spin-coating on a wafer, with an inter-digited electrode array (IDA).65 The array was successfully used for recogni-tion of a series of diluted organic vapors over a period of 8 weeks.

Immunosensors are based on the recognition involved in the coupling of an antigen with an antibody, with immune agents immobilized in a polymer matrix such as PVC, polyacrylamide gel, etc. Either an immobilized antigen detects an antibody, or an immobilized antibody detects an antigen. Due to the interaction between an antibody and an antigen, a variation in electric charge, mass or optical properties, is detected directly with a variety of transducers.

Kim and coworkers reported a conductimetric membrane strip immu-nosensor with polyaniline-bound gold colloids as signal generators.66 They introduced polyaniline as a conductivity-modulating agent on the gold sur-face after immobilizing an antibody specific to human albumin as a model analyte. This novel signal generator amplified the conductimetric signal 4.7 times compared with the plain gold, and the signal was also a maximum of 2.3-fold higher than that for the photometric system under the same analyti-cal conditions.

Conducting polymers can also be employed in taste sensors. Lipid mem-branes used in combination within electrodes have been utilized to mimic some of the functionality of mammalian taste bud cells. It is generally assumed that the primary process of chemoreception in the mammalian olfactory sys-tem takes place at the cell membrane of sensory neurons. The mammalian sense of taste occurs as a result of complex chemical analyses that are com-pleted in parallel at a series of chemically active sites called taste buds. These taste buds are located in depressions in the tongue, where th emolecular and ionic analytes become restricted to allow time for their identification.67 There are five primary tastes: sweet (carbohydrate based), sour (acidity), salty (ionic), umami or savory (amino acids) and bitter (quinine and other alkaloids).

Sangodkar et al. described the fabrication of PANI-based microsensor and microsensor arrays for the estimation of glucose, urea and triglycerides. Polymer deposition and enzyme immobilization were done electrochemi-cally.68 The enzyme was directly immobilized to the chosen microelectrodes by controlling the electrochemical potential, avoiding any contact of the enzyme solution to other microelectrodes. This enabled immobilization of a different enzyme on each of the three closely spaced microelectrodes, result-ing in a sensor array for the analysis of a sample containing a mixture of




glucose, urea and triolein in a single measurement using a few microliters of the sample.

6. Conclusions and Perspectives

In this chapter, we reviewed a variety of conjugated polymers and their appli-cations in chemical and biological sensors, and different device structures based on their detection principles. The excitation energy along the π-backbone, while transferring to lower energy, electron/energy accepter sites over long distances leads to an amplified fluorescence signal. Importantly, polymers are easily processed, can be tailored for particular properties, and may be chosen to be inert in the environment containing the analyte. With all of these prop-erties, conjugated polymers are recognized as promising materials in sensing devices. Furthermore, combining different sensing concepts, based on more than one analyte-recognition principle, appears to be a better- practiced way of improving the sensor performance. However, the filed of conjugated polymer-based sensors is far from mature, the issues of device stability and cost remain to be resolved. Therefore, synergistic collaborations between polymer scientists and technologists are highly needed in sensor research to accelerate the availability of durable and cheap chemical and biological sensors for human consumption.

Acknowledgments

The authors acknowledge the support of the Recruitment Program by the Global Experts in China and the start-up funds from Fudan University.

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