**2.1. Surface modification of conducting polymers**

Surface modification of the CPs for incorporating biomolecules has been obtained by both physical and chemical moderations. Such modifications can be applied to create both physical and chemical guidance cues, which can be adapted for the required biomedical utilization [22]. Chemical modification has been extensively studied using biomolecules as dopants (biospecific dopants such as peptides, proteins and neurotrophins) [23, 24] or by immobilizing bioactive moieties on the surface of the material [24].

For example, neural microelectrodes are commonly used in chronic, long-term implantations. Due to the fact, highly stable materials are needed that can tolerate the implantation procedure as well as the presence of biochemical environment in living tissue. Polypyrrole, however, has a poorly defined chemical structure in which there is a notable amount of α-β′ coupling. The presence of these defect sites along the polymer chain induces structural disorder, limits the electrochemical response and has been implicated as the primary site of polymer breakdown due to over-oxidation [23]. Moreover, oxidized polypyrrole is unstable to reduction by relatively weak, but biologically relevant, reducing agents such as dithiothreitol and glutathione [23], which act as a p-dopants.

Physical modification has been investigated by enlarging surface roughness by different processes such as generating microporous layers using polystyrene sphere templates, creating composites of nanoparticles and polylactide [25], growing CPs within hydrogels [18] and mixing with biomolecules to yield "fuzzy" structures.

The electrode coatings used are rather soft [26] and can be tailored at the micrometer, nanometer and molecular scale to have fibrillary, nodular, fuzzy, tubular [27] or porous surface morphologies [25]. As a consequence, most tissue- and device-compatible surface tempering of the electrode would be bringing electrical activity, bioactivity, mechanical softness and architectural properties on a similar scale to that of cells in tissues. The surface roughness character of the conducting polymer layers can be tailored by modification of the conducting polymer synthesis temperature [22]. Exceptional adaptation of the surface roughness characteristics is important because rougher topology corresponds with increasing of surface area, which would expand the signal conduction by growing the interface with neurons. For example, polypyrrole films synthesized at a lower temperature (418°C) were rougher than the same layers achieved at 2518°C [28]. Kmecko et al. [29] presented that the introduction of carbon nanotubes as dopants to PPy and PEDOT prefers the creation of bumps and grows the surface roughness. Functionalization of CPs with biomolecules has permitted engineers to modify CPs with biological sensing elements, and to turn ON and OFF different signaling routes demanded for several cellular mechanisms to form conducting polymers that extend cell proliferation/differentiation. Moreover, dopants can be applied as intermediates to allow further modification of CPs, that is, doping with poly(glutamic acid) supplies a carboxylic acid pendent group, which can be functionalized further by covalent binding to any amino group, such as those found in polylysine and laminin [30].

The electrochemical character of the CPs can be varied by modifying the dopant concentration. Electrical conductivities can be varied by as much as 15 orders of magnitude by changing the dopant concentrations so that control is feasible over the all ranging from insulator to semiconductor and then to metal [31]. The usually used dopants contain aromatic sulphonate variants such as *p*-toluenesulphonate, styrene, sodium benzenesulphonate to dope the polymers [32]. Other appropriate dopants for oxidation polymerization contain buffer salts, I<sup>2</sup> , BF<sup>4</sup> , perchlorates and FeCl3 (**Table 3**). Biological dopants include laminin peptide sequences, hydroxyapatite or a silk-like polymer with fibronectin units and polysaccharides [22]. Nevertheless, a main disadvantage of introducing dopants is the possible diffusion of the dopant into the culture medium with effects on cytotoxicity and deterioration of the electrical characteristics of the CP layer itself. For example, dodecyl sulphate-doped PPy layers undergo structural modifications after 7 days of soaking in deionized water [23].

**2.1. Surface modification of conducting polymers**

Polypyrrole (PPy) Electrochemical and

Polythiophenes (PT) Electrochemical and

Polyaniline (PANI) Electrochemical and

Poly(3,4-ethylenedioxythiophene)

**Table 2.** Properties of the CPs.

(PEDOT)

56 Green Electronics

bioactive moieties on the surface of the material [24].

[23], which act as a p-dopants.

Surface modification of the CPs for incorporating biomolecules has been obtained by both physical and chemical moderations. Such modifications can be applied to create both physical and chemical guidance cues, which can be adapted for the required biomedical utilization [22]. Chemical modification has been extensively studied using biomolecules as dopants (biospecific dopants such as peptides, proteins and neurotrophins) [23, 24] or by immobilizing

**CPs Synthesis Properties Application**

High conductivity (up to 160 S cm−1) when doped with iodine; opaque, brittle, amorphous

Biosensors, antioxidants, drug delivery, bioactuators, neural prosthetics, cardiovascular application

Biosensors, food industry

Biosensors, antioxidants, drug delivery, bioactuators, food industry, cardiovascular application

Biosensors, antioxidants, drug delivery, neural prosthetics

material

property

100 S cm−1

to 210 S cm−1

High temperature stability; ability to suppress the so-called "thermal runaway" of the capacitor; transparent conductor; moderate band gap and low redox potential; conductivity up

Good electrical conductivity and optical

Belongs to the semiflexible rod polymer family; requires simple doping/dedoping chemistry; exists as bulk films or dispersions; high conductivity up to

chemical synthesis

chemical synthesis

chemical synthesis

Electrochemical and chemical synthesis

For example, neural microelectrodes are commonly used in chronic, long-term implantations. Due to the fact, highly stable materials are needed that can tolerate the implantation procedure as well as the presence of biochemical environment in living tissue. Polypyrrole, however, has a poorly defined chemical structure in which there is a notable amount of α-β′ coupling. The presence of these defect sites along the polymer chain induces structural disorder, limits the electrochemical response and has been implicated as the primary site of polymer breakdown due to over-oxidation [23]. Moreover, oxidized polypyrrole is unstable to reduction by relatively weak, but biologically relevant, reducing agents such as dithiothreitol and glutathione

The scope of possible dopants is huge as long as the selected dopant is charged. On the other hand, covalent methods can be used to more constantly functionalize CPs. The monomer can be synthesized with required functional groups and then polymerized, or post-polymerization covalent modification is also possible. It is crucial to note that the steric effects of any introduced functional group may interrupt the planarity of the conjugated arrangement, which could in turn lower the conductivity [22].


**Table 3.** Examples of common CP dopants in biological use.

### **2.2. Conducting polymers as effective electron relays in sensor devices**

Effective electron transfer between the biorecognition species (e.g. an enzyme) and the electrode is challenging element when creating enzymatic biosensors. Classically, the distance among the active centre of the enzyme and the electrode surface is too long for direct electron transfer (DET) owing to the protective disk of the enzyme. Because electron transfer (ET) *via* a tunneling mechanism is rarely observed in classic electrodes, establishing electron relays that allow for fast ET, thus avoiding free-diffusing redox species between the electrode and the enzyme, is vital [35]. Due to the fact, organic electronic materials present very attractive expectants for molecular wiring owing to their polymeric essence and conducting character [36].

Doped PPy was the first CP presented to provide an electron relay among the surface of the electrode and the active centre of an enzyme [37, 38]. Nevertheless, owing to deficient electrochemical stability (potentially affecting long-term functionality) [39], attempts moved to other materials such as PEDOT, a polythiophene derivative which appeared as a more stable expectant owing to its low bandgap and high electrochemical stability in the oxidized state [40]. The first example of a PEDOT-based glucose sensor with potential for long-term measurements was presented by Kros et al. [41]. They physically introduced a positively charged polymer in the conducting substrate of the biosensor, permitting more effective ET as a result of the grown electrostatic interaction between the positively charged entrapped polymer and the negatively charged enzyme (**Figure 2A**). An optional procedure to enhance the electron relay in CPs postsynthesis involves intermixing with redox hydrogels, which have been presented to reveal rapid substrate and counter-ion diffusion effects with high flexibility and quick electron transfer rates. The non-conducting nature of such hydrogels hinders their effective and spatially placed immobilization on the active electrode surface, and mixing them with CPs can thus overcome this issue resulting in an ideal electron-transfer strategy. PEDOT:PSS was used to improve the deficient performance of a mediator-based biosensor by its introduction into nanocomposite enzyme electrodes, emerging in enhanced electron hopping in terms of the electron diffusion coefficient and charge transfer resistance (**Figure 2B**) [42]. Going one step further, Bao et al. investigated intrinsically conducting nanostructured polyaniline (PANI)-redox hydrogels [43]. In another strategy, a CP-based glucose-permeable redox hydrogel was created by crosslinking polymer acid-templated PANI together with glucose oxidase, leading to the electrical wiring of the enzyme and permitting electrocatalytic oxidation of glucose at low oxidation potentials (**Figure 2C**) [44]. Recently, CP hydrogels with high permeability to enzymes were utilized to produce metabolite biosensors with excellent sensing character without the need for a mediator (**Figure 2D**) [45].

**Figure 2.** Organic conducting materials as effective enzyme immobilization supports and transducers for different body metabolite determination. (A) Electrostatic binding (weak and strong) of glucose oxidase (GOx) onto a PEDOT and PEDOT supplied with positively charged PMVP, poly(*N*-methyl-4-pyridine), according to [41]. (B) Schematic diagram of the working electrode coated with ferrocene-branched polyethylenimine, PEDOT:PSS and GOx for glucose detection, according to [42]. (C) Phytic acid gelated and doped PANI hydrogel according to [44]. (D) The PANI hydrogel matrix including Pt nanoparticles and the proper biocatalysts for the detection of uric acid, cholesterol and triglyceride,

Conducting Polymers as Elements of Miniature Biocompatible Sensor

http://dx.doi.org/10.5772/intechopen.75715

59

according to [45].

**2.2. Conducting polymers as effective electron relays in sensor devices**

PPY 10−2–10−3 ClO4

58 Green Electronics

PT 10–10−3 SO3

**Table 3.** Examples of common CP dopants in biological use.

Effective electron transfer between the biorecognition species (e.g. an enzyme) and the electrode is challenging element when creating enzymatic biosensors. Classically, the distance among the active centre of the enzyme and the electrode surface is too long for direct electron transfer (DET) owing to the protective disk of the enzyme. Because electron transfer (ET) *via* a tunneling mechanism is rarely observed in classic electrodes, establishing electron relays that allow for fast ET, thus avoiding free-diffusing redox species between the electrode and the enzyme, is vital [35]. Due to the fact, organic electronic materials present very attractive expectants for molecular wiring owing to their polymeric essence and conducting character [36].

**Polymer Conductivity (S cm−1) Dopant Conductivity after doping (S cm−1) Ref.** PEDOT 6 × 10−4 polystyrene sulphonate (PSS) 10 [33]

PT 10–10−3 BF<sup>4</sup> 10–20 [34]

<sup>−</sup> 10 [34]

<sup>−</sup> 10–20 [34]

Doped PPy was the first CP presented to provide an electron relay among the surface of the electrode and the active centre of an enzyme [37, 38]. Nevertheless, owing to deficient electrochemical stability (potentially affecting long-term functionality) [39], attempts moved to other materials such as PEDOT, a polythiophene derivative which appeared as a more stable expectant owing to its low bandgap and high electrochemical stability in the oxidized state [40]. The first example of a PEDOT-based glucose sensor with potential for long-term measurements was presented by Kros et al. [41]. They physically introduced a positively charged polymer in the conducting substrate of the biosensor, permitting more effective ET as a result of the grown electrostatic interaction between the positively charged entrapped polymer and the negatively charged enzyme (**Figure 2A**). An optional procedure to enhance the electron relay in CPs postsynthesis involves intermixing with redox hydrogels, which have been presented to reveal rapid substrate and counter-ion diffusion effects with high flexibility and quick electron transfer rates. The non-conducting nature of such hydrogels hinders their effective and spatially placed immobilization on the active electrode surface, and mixing them with CPs can thus overcome this issue resulting in an ideal electron-transfer strategy. PEDOT:PSS was used to improve the deficient performance of a mediator-based biosensor by its introduction into nanocomposite enzyme electrodes, emerging in enhanced electron hopping in terms of the electron diffusion coefficient and charge transfer resistance (**Figure 2B**) [42]. Going one step further, Bao et al. investigated intrinsically conducting nanostructured polyaniline (PANI)-redox hydrogels [43]. In another strategy, a CP-based glucose-permeable redox hydrogel was created by crosslinking polymer acid-templated PANI together with glucose oxidase, leading to the electrical wiring of the enzyme and permitting electrocatalytic oxidation of glucose at low oxidation potentials (**Figure 2C**) [44]. Recently, CP hydrogels with high permeability to enzymes were utilized to produce metabolite biosensors with excellent sensing character without the need for a mediator (**Figure 2D**) [45].

**Figure 2.** Organic conducting materials as effective enzyme immobilization supports and transducers for different body metabolite determination. (A) Electrostatic binding (weak and strong) of glucose oxidase (GOx) onto a PEDOT and PEDOT supplied with positively charged PMVP, poly(*N*-methyl-4-pyridine), according to [41]. (B) Schematic diagram of the working electrode coated with ferrocene-branched polyethylenimine, PEDOT:PSS and GOx for glucose detection, according to [42]. (C) Phytic acid gelated and doped PANI hydrogel according to [44]. (D) The PANI hydrogel matrix including Pt nanoparticles and the proper biocatalysts for the detection of uric acid, cholesterol and triglyceride, according to [45].
