**1. Introduction**

Biosensors are devices that incorporate biological sensing elements or bioreceptors to detect specific molecule/chemical analytes and produce a measurable signal (current, voltage, and

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color change). Enzymes are protein molecules that act as biological catalysts that bind/react highly specific to certain molecules therefore enzymes can be excellent bioreceptors. The transducer is the mechanism by which selective binding of analytes and bioreceptors is con‐ verted into a measurable signal. Common transducers are based on optical, electrochemical, and electronic signal modulations upon addition of the analyte.

Electronic devices based on polymer electrodes, organic thin‐film transistors, and organic light‐emitting diodes can be interfaced with biological moieties, i.e., cells, microorganisms, proteins, oligonucleotides, small molecules, for medical applications, and environmental and food quality control [1–7]. The scope of bioelectronics is shown in **Figure 1** [7]. Transistors, polymer electrodes, and organic light‐emitting diodes can be coupled with recognition ele‐ ment bioreceptors, i.e., enzymes, nucleic acids (DNA), or antibodies to selectively detect an analyte, i.e., proteins, complementary DNA chains, viruses, nutrients, hormones, collected from blood, urine, or saliva [8, 9]. Transistor‐based biosensors can be divided into field‐effect transistor biosensors (bio‐FETs), discussed in Section 2 and organic electrochemical transis‐ tors (OECTs), discussed in Section 3.

#### **1.1. Background of biosensors and main transducer mechanisms**

Since the introduction of insulin as a treatment for diabetes, monitoring glucose in blood became an important issue. Glucose sensors are nowadays by far the most successful com‐ mercial application of biosensors with more than 85% share of a multibillion dollar market in the USA [8, 10]. For this reason, glucose biosensors lead the path toward the development of new biosensing concepts.

The main transducer mechanisms involve optical, electrochemical, and electronic processes.

#### *1.1.1. Optical transducers*

The early glucose biosensors were based on colorimetry. Colorimetry is a technique in which the color of a solution is taken as an index of the composition of the solution. The color of the

**Figure 1.** A cartoon showing the scope of organic bioelectronics [7]. Copyright © Materials Research Society 2010.

solution can be modified by a chemical reaction and the concentration of its constituents can be revealed by comparison with a suitably prepared set of color standards in a color compara‐ tor [11]. The color comparison of the solution with its standard can be made visually or with a colorimeter. Colorimeters are devices that measure light absorption or reflection in the visible spectrum.

color change). Enzymes are protein molecules that act as biological catalysts that bind/react highly specific to certain molecules therefore enzymes can be excellent bioreceptors. The transducer is the mechanism by which selective binding of analytes and bioreceptors is con‐ verted into a measurable signal. Common transducers are based on optical, electrochemical,

Electronic devices based on polymer electrodes, organic thin‐film transistors, and organic light‐emitting diodes can be interfaced with biological moieties, i.e., cells, microorganisms, proteins, oligonucleotides, small molecules, for medical applications, and environmental and food quality control [1–7]. The scope of bioelectronics is shown in **Figure 1** [7]. Transistors, polymer electrodes, and organic light‐emitting diodes can be coupled with recognition ele‐ ment bioreceptors, i.e., enzymes, nucleic acids (DNA), or antibodies to selectively detect an analyte, i.e., proteins, complementary DNA chains, viruses, nutrients, hormones, collected from blood, urine, or saliva [8, 9]. Transistor‐based biosensors can be divided into field‐effect transistor biosensors (bio‐FETs), discussed in Section 2 and organic electrochemical transis‐

Since the introduction of insulin as a treatment for diabetes, monitoring glucose in blood became an important issue. Glucose sensors are nowadays by far the most successful com‐ mercial application of biosensors with more than 85% share of a multibillion dollar market in the USA [8, 10]. For this reason, glucose biosensors lead the path toward the development of

The main transducer mechanisms involve optical, electrochemical, and electronic processes.

The early glucose biosensors were based on colorimetry. Colorimetry is a technique in which the color of a solution is taken as an index of the composition of the solution. The color of the

**Figure 1.** A cartoon showing the scope of organic bioelectronics [7]. Copyright © Materials Research Society 2010.

and electronic signal modulations upon addition of the analyte.

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

**1.1. Background of biosensors and main transducer mechanisms**

tors (OECTs), discussed in Section 3.

new biosensing concepts.

*1.1.1. Optical transducers*

Most of the colorimetric methods to measure glucose in blood produce a color change by the reduction of an aromatic organic compound. The introduction of Dextrostix (Ames Co.) in 1964 provided a simple tool to measure blood glucose. Dextrostix is a cellulose strip with reagents that vary in color and intensity as a function of the amount of glucose present in the blood [12]. The reagents in Dextrostix are glucose oxidase, peroxidase, and a chromogen (i.e., tetramethyl‐ benzidine). Glucose in blood samples is first oxidized into gluconolactone and eventually into gluconic acid [13]. This oxidation reaction is assisted by the enzyme glucose oxidase (GOx) biological catalyst. Oxygen dissolved in blood is necessary to carry this oxidation process and the by‐product is hydrogen peroxide (H2 O2 ). Hydrogen peroxide then reacts with the chromo‐ gen system to result in a specific color pattern specific to the glucose concentration in blood.

To avoid the operator subjective comparison of the strips by visual inspection, the color change in Dextrostix strips can be evaluated with a simple reflectance meter or with more sophisticated spectrophotometers.

Despite the simplicity of optical transducers, its early development was hampered by the requirement of bulky and costly optical equipment or by the intrinsic inaccuracy of visual inspection [14].

One possible solution may be replacing costly reflectance meters or spectrophotometers with software algorithms to enable digital cameras in smartphones quantitative screening when fast diagnosis is needed. Common CMOS cameras found in smartphones have successfully monitored glucose, protein, and pH in artificial urine with interphone repeatability and mini‐ mal operator intervention [15].

Silicon optical photonic‐crystal waveguide arrays capable of sensing up to 128 compounds within a few millimeters of space with excellent signal‐to‐noise ratio have been recently reported [16, 17]. The operating principle is similar to that in surface plasmon resonance sen‐ sors that measure the change in reflectivity of a thin gold metal film deposited on a glass prism upon addition of the analyte. Photonic‐crystals are optical structures in which a periodic modulation of the refractive index exists for a given material. Depending on the exact periodic modulation, a given bandwidth of light cannot be transmitted through such material thus defining a photonic band gap. A given bandwidth of light can be confined in the waveguide. Since the band gap is very sensitive to the refractive index at the crystal surface, when in con‐ tact with aqueous medium, biomolecules adhere to the crystal surface and modify the refrac‐ tive index resulting in a shift in the band gap. This property can be utilized for biosensing.

Surface functionalization with a binding bioreceptor of the photonic‐crystal can be employed to improve analyte selectivity. While the requirement of additional optical and electronic components makes photonic‐crystal biosensors relatively complex they can be made ultra‐ compact in a single integrated chip embedded in an easy‐to‐use and portable device.

### *1.1.2. Electrochemical transducers*

Electrochemical sensors originally called "enzyme electrodes"emerged as highly sensitive, easy‐to‐use, portable, and user‐friendly sensing devices. Electrochemical biosensors are now‐ adays the most widespread transducers for glucose sensing [18].

Electrochemical sensors measure electrochemical processes occurring in an electrode function‐ alized with enzyme bioreceptors immersed in an electrolyte solution containing the analytes. Electrochemical processes include the measurement of tiny changes of voltage (potentiom‐ etry), current (amperometry), or resistance/conductance (conductometry) specific to the presence of an analyte. Electrochemical sensors usually involve two electrodes, the working electrode and the counter electrode under which a voltage is applied. A third reference elec‐ trode can be employed to set and monitor the potentials vs an absolute reference value.

In the absence of the reference electrode, it is somewhat difficult to measure a small current change in a reproducible way, thus the reproducibility of electrochemical sensors is generally less accurate than those employing optical transducers [19]. However, because electrochemi‐ cal sensors can be miniaturized and manufactured inexpensively, they actually dominate the biosensor market [10, 19, 20].

Electrochemical glucose sensors alike their analogue glucose optical sensors employ glucose oxi‐ dase (GOx) enzyme to bind the glucose molecule and facilitate its oxidation process. Oxygen and GOx oxidize glucose into gluconic acid and generate hydrogen peroxide as by‐product. During this process, GOx is reduced and can be regenerated (oxidized) by adding ferricyanide which in turn is reduced into ferrocyanide. A metal electrode can regenerate ferrocyanide (reduced form) into ferricyanide. The reduction‐oxidation cycle of glucose generates electrons at the metal elec‐ trode and can induce a spontaneous electric current (with no voltage applied) proportional to the glucose concentration. To obtain a quick glucose measurement, a change in the electrical current is measured as a function of a voltage applied between the electrolyte and the metal electrode.

Another popular redox system to detect glucose is based on enzyme glucose dehydrogenase as catalyzer and nicotinamide adenine dinucleotide, replacing oxygen to oxidize glucose [21, 22].

#### *1.1.3. Electronic transducers*

After the discovery of the enzyme electrode, ion‐sensitive field‐effect transistors (ISFETs), **Figure 2** (right), in which the gate electrode in a conventional metal‐organic field‐effect tran‐ sistor (MOSFET), **Figure 2** (left), is replaced by an aqueous solution and a reference electrode, emerged to measure ionic species in electrochemical and biological environments. Double lay‐ ers formed at the oxide electrolyte interface result in a different conductive state at the transistor channel proportional to the electrolyte ion concentration [23]. The gate oxide can be sensitive to specific ions similar to a glass electrode [24] or can be modified with a selective membrane or molecular receptors to filter specific ions [25, 26]. ISFETs are not strictly biosensors because they do not employ a biomolecular receptor as an active component to sense ions but they laid the foundation toward field‐effect transistor biosensors (bio‐FETs).

Electronic transducers include the field‐effect transistor and the organic electrochemical tran‐ sistor, reviewed in greater detail in the following sections.

Transistors as an Emerging Platform for Portable Amplified Biodetection in Preventive Personalized... http://dx.doi.org/10.5772/67794 169

**Figure 2.** Schematic representation of MOSFET (left) and ISFET (right) typical structures [27]. Copyright © 2002 Elsevier Science B.V.
