**3. Organic electrochemical transistor biosensors**

No purification of virus samples was required in these measurements. **Figure 6** shows the conductance vs time recorded simultaneously for influenza A (nanowire 1) and adenovi‐ rus group III (nanowire 2) sensors set in proximity with a microfluidic system that allows the sequential flow of 1–4 adenovirus, influenza A, pure solution, and 1:1 mix solution of adenovirus and influenza A, respectively. Adenovirus is negatively charged in the solu‐ tion resulting in a positive conductance change of nanowire 2 with an on‐time duration of ca 16 s. Negative conductance change of similar duration was observed when influenza A was introduced and binded to nanowire 1. Bottom arrows in **Figure 6** indicate singulari‐ ties in which the proximity of adenovirus in device 1 resulted in a short‐lived positive change of conductance ca 0.4 s, and similarly, the proximity of influenza A resulted in a short‐lived negative change of conductance in device 2. The excellent binding selectivity, single viral particle sensitivity and selective multiplexed detection enables rapid identi‐ fication of viral samples as required for robust medical solutions, fundamental virology,

Label‐free amplified biodetection has been reported with floating‐gate transistor archi‐ tectures, **Figure 7** (left), in which the gate voltage is indirectly applied via a secondary electrolyte [33]. In such structures, the semiconductor does not need to be modified with selective bioreceptors and is not in direct contact with the analytes therefore the semicon‐ ductor can be selected on its electronic performance and doping mechanism (field‐effect vs electrochemical) and not on the ease of its chemical modification or robustness in elec‐ trolytes, thereby reducing fabrication complexity. Bioreceptors are set on one part of the floating gate coupled with a secondary electrolyte compartment and entirely separated

**Figure 6.** Conductance vs time recorded simultaneously from two silicon nanowire sensors, nanowire 1 was modified with influenza A antibody (top) and nanowire 2 was modified with adenovirus group III antibody (bottom). Arrows 1–4 correspond to the introduction of (1) adenovirus, (2) influenza A, (3) pure buffer, and (4) 1:1 mixture solution of adenovirus and influenza A. Bottom arrows highlight short‐duration conductance changes corresponding to nonspecific diffusion of viral particles. Solutions made by 40 viral particles per μl in phosphate buffer 10 μM, pH 6.0 [32]. Copyright

and drug discovery.

172 Different Types of Field-Effect Transistors - Theory and Applications

© 2014 National Academy of Sciences.

Organic electrochemical transistors (OECTs) are emerging as a promising platform for ampli‐ fied biodetection with enhanced sensitivity and low voltage (<1 V) operation [33, 40, 41]. OECTs typically consist of a polymer semiconductor included between source and drain electrodes and coupled with a gate electrode through an electrolyte. Polymer semiconductor materials are based on pi‐conjugated carbon and hydrogen backbone structures that are rela‐ tively soft, flexible, and permeable to ionic species. Polymers can be soluble in organic solvents and be printed on flexible substrates. The gate electrode and the semiconductor channel can be approached as the electrodes of a conventional electrochemical sensor (two electrodes) assign‐ ing the transistor channel together with drain and source electrodes as the working electrode and the gate electrode as the counter electrode. By modifying the channel, electrolyte or gate electrode with biochemical receptors, chemical binding events can result in large changes in conductivity in the semiconducting channel. This effect can be the basis for bioelectric signal amplification [28, 34, 42, 43].

To mitigate the reproducibility and sensibility issues related with electrochemical biosensors, a simplified electrochemical transistor architecture can be employed in which the use of high surface area activated carbon electrodes results in sub‐1 V operation and renders unnecessary presence of a reference electrode to control the applied potentials [38, 44].

Early OECTs consisted in Au microelectrodes drain‐source and gate electrodes and polypyr‐ role channels in aqueous electrolyte media, i.e., CH3 CN/0.1 M [n‐Bu4 N]ClO4 displaying typical transistor p‐type characteristics [45]. When the gate is held at negative voltages, polypyrrole is dedoped and the device is switched off. When the gate voltage is positive, polypyrrole is oxidized resulting in an increase in the channel current, the device is switched on.

Nowadays, polystyrenesulfonate‐doped poly(3,4‐ethylenedioxythiophene) (PEDOT:PSS) is the most commonly employed channel material in OECTs. PEDOT:PSS is intrinsically a p‐type conducting polymer, stable in water, and nontoxic.

Enzymatic glucose OECT biosensors have been reported [46–48]. Hydrophilic ionic liquids like triisobutyl‐(methyl)‐phosphonium tosylate ([P1,4,4,4][Tos]) are particularly interesting as effective enzyme immobilization medium in biological environments [49]. Sensing experi‐ ments were carried out by placing enzyme‐glucose oxidase (GOx, 500 units per mL) and fer‐ rocene mediator [bis(η‐5‐cyclopentadienyl)iron] (Fc, 10 mM) in 1.43 mL of [P1,4,4,4][Tos] and 50 mL glucose‐PBS solution.

Glucose is oxidized by the application of a gate voltage while the enzyme (GOx) is reduced. In the back cycle, oxidation of GOx is coupled with the conversion of Fc to ferricenium ion (Fc+ ) which shuttles electrons to the gate electrode (**Figure 8a**) and cations into PEDOT:PSS. PEDOT:PSS is dedoped by metal cations (M+ ) (**Figure 8b**) decreasing the drain‐source cur‐ rent as a function of glucose concentration. The measured sensitivity of such devices is in the range of 10⁻<sup>7</sup> –10⁻2 M [49].

OECTs hormone biosensors have been reported by incorporating Nafion, a material that has high specific affinity for epinephrine hormone molecules, on top of the gate electrode [50]. The sensitivity was improved by introducing gate electrodes modified with SWNTs and gra‐ phene flakes which enhanced electrocatalytic activity of the gate electrode compared to that with platinum gates thus improving the detection limit of the device. Sensitivities up to 0.1 nM were obtained.

**Figure 8.** Reactions at (a) the gate electrode and (b) the channel of the OECT [49]. Copyright © 2010, Royal Society of Chemistry.

Label‐free, flexible DNA OECT sensors have been demonstrated in flexible microfluidic sys‐ tems [51]. Single‐stranded DNA (ssDNA) probes were immobilized on gold gate electrodes and poly(dimethylsiloxane) (PDMS) microfluidic channels were fixed on top of prepatterned PEDOT:PSS channels (**Figure 9a**) set in contact with gold drain and source electrodes. The device was able to bend on both sides (**Figure 9b**) and its electric characteristics remained consistent before and after bending (**Figure 9c**). Transient curves indicate that the drain‐ source current reaches a stable plateau value after several seconds of applied gate voltages (**Figure 9d**) revealing ion permeation into the transistor channel [52]. Further investiga‐ tions revealed that the maximum bending strain was about 5% with negligible effect on the PEDOT:PSS film conductance.

To mitigate the reproducibility and sensibility issues related with electrochemical biosensors, a simplified electrochemical transistor architecture can be employed in which the use of high surface area activated carbon electrodes results in sub‐1 V operation and renders unnecessary

Early OECTs consisted in Au microelectrodes drain‐source and gate electrodes and polypyr‐

transistor p‐type characteristics [45]. When the gate is held at negative voltages, polypyrrole is dedoped and the device is switched off. When the gate voltage is positive, polypyrrole is

Nowadays, polystyrenesulfonate‐doped poly(3,4‐ethylenedioxythiophene) (PEDOT:PSS) is the most commonly employed channel material in OECTs. PEDOT:PSS is intrinsically a

Enzymatic glucose OECT biosensors have been reported [46–48]. Hydrophilic ionic liquids like triisobutyl‐(methyl)‐phosphonium tosylate ([P1,4,4,4][Tos]) are particularly interesting as effective enzyme immobilization medium in biological environments [49]. Sensing experi‐ ments were carried out by placing enzyme‐glucose oxidase (GOx, 500 units per mL) and fer‐ rocene mediator [bis(η‐5‐cyclopentadienyl)iron] (Fc, 10 mM) in 1.43 mL of [P1,4,4,4][Tos] and

Glucose is oxidized by the application of a gate voltage while the enzyme (GOx) is reduced. In the back cycle, oxidation of GOx is coupled with the conversion of Fc to ferricenium ion

rent as a function of glucose concentration. The measured sensitivity of such devices is in the

OECTs hormone biosensors have been reported by incorporating Nafion, a material that has high specific affinity for epinephrine hormone molecules, on top of the gate electrode [50]. The sensitivity was improved by introducing gate electrodes modified with SWNTs and gra‐ phene flakes which enhanced electrocatalytic activity of the gate electrode compared to that with platinum gates thus improving the detection limit of the device. Sensitivities up to 0.1

**Figure 8.** Reactions at (a) the gate electrode and (b) the channel of the OECT [49]. Copyright © 2010, Royal Society of

) which shuttles electrons to the gate electrode (**Figure 8a**) and cations into PEDOT:PSS.

oxidized resulting in an increase in the channel current, the device is switched on.

CN/0.1 M [n‐Bu4

N]ClO4

) (**Figure 8b**) decreasing the drain‐source cur‐

displaying typical

presence of a reference electrode to control the applied potentials [38, 44].

role channels in aqueous electrolyte media, i.e., CH3

174 Different Types of Field-Effect Transistors - Theory and Applications

p‐type conducting polymer, stable in water, and nontoxic.

50 mL glucose‐PBS solution.

–10⁻2

PEDOT:PSS is dedoped by metal cations (M+

M [49].

(Fc+

range of 10⁻<sup>7</sup>

nM were obtained.

Chemistry.

Biocompatible materials have been investigated due to the rapid development of OECTs and their potential use in biological applications. Skin itself can be utilized as a noncon‐ ventional gate electrode to sense heart beatings, **Figure 10a**. Campana et al. demonstrated transparent transistors fabricated on biodegradable poly(lactic‐co‐glycolic acid) substrates to sense heart beatings [53]. Traditional electrocardiograms utilize Ag/AgCl to estab‐ lish a Faradaic contact between the skin and the electrodes and to sense small voltage

**Figure 9.** (a) Schematic diagram of the OECT integrated with a flexible microfluidic system and gate gold electrodes before (control) and after DNA modification and DNA hybridization. (b) Photographs of a device bent on both sides. (c) Transfer characteristics (Ids vs Vgs) of the OECT measured before and after bending it on both sides, inset shows the output characteristics (Ids vs Vgs). (d) Time‐dependent channel current of the OECT measured after applying different gate voltages. The drain‐source voltage (Vds) in the transfer and time‐dependent characteristics was −0.1 V [51]. Copyright © 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

**Figure 10.** ECG recording with a bioresorbable OECT operated in direct contact with the skin. (a) Wiring diagram of the experiment. (b) Measured drain‐source current (bottom, left axis) as obtained during transistor recording (Vgs = 0.5 V, Vds = −0.3 V) and comparison with a normal electrocardiogram potentiometric recording with standard disposable leads (top, right axis) [53]. Copyright © 2014 WILEY VCH Verlag GmbH & Co. KGaA, Weinheim.

perturbations that exist on the skin per heart beatings [54]. To reduce the skin's impedance, an electroconductive gel was employed between the skin and PEDOT:PSS channels. The OECTs recorded heartbeats with Ids amplitude of ca 0.1 μA equivalent to measuring signals at the gate with amplitudes of ca 50 μV whereas traditional electrocardiograms monitor spikes at ca 500 μV, **Figure 10b**.

Wearable electrochemical transistors as a platform for real‐time detection of biomarkers in external biological fluids was demonstrated with a simple device structure [55]. Drain, source, and gate PEDOT:PSS electrodes were screen printed on textile fabrics. Adrenaline, dopamine, and ascorbic acid in artificial sweet were sensed in the order of tenths of μM concentrations. The device operation was stable despite several hand‐washing cycles and deformations.

Flexible lactate sensors with ionogel solid‐state electrolytes have been developed [56]. The concentration of lactate in blood can indicate circulatory effectiveness of anaerobic metabo‐ lism. The ionogel was prepared by dissolving ferrocene mediator (Fc) in hydrophilic ionic liquid 1‐ethyl‐3‐methylimidazolium ethylsulfate [C2 mIm][EtSO4 ] followed by mixing it with monomer N‐isopropylacrylamide (NIPAAm) cross‐linker N,N'‐methylenebis(acrylamide) (MBAAm) and photoinitiator (dimethoxyphenyl)acetophenone DMPA. Under application of a gate voltage, lactic acid was oxidized to pyruvate and Fc was converted to ferricenium ion (Fc+ ). Fc+ transduce electrons to the gate electrode and the PEDOT:PSS channel is dedoped with cations from the solution which leads to a decrease in the drain‐source current.

A disposable alcohol breath sensor, to estimate the content of alcohol in the blood, was demonstrated using organic electrochemical transistors [57]. Alcohol dehydrogenase and nicotinamide adenine dinucleotide (NAD+ ) enzymes were immobilized on a collagen‐based gel. PEDOT:PSS was employed as drain, source, and gate electrodes. When NAD+ is in con‐ tact with ethanol and alcohol dehydrogenase, it can get reduced to NADH and oxidized back to NAD+ , freeing two electrodes that can change the conductivity state of PEDOT:PSS.
