Review—Thin-Film Transistors (Tfts) for Highly Sensitive Biosensing Applications: a Review

ECS Journal of Solid State Science and Technology

OPEN ACCESS Review—Thin-Film Transistors (TFTs) for Highly Sensitive Biosensing Applications: A Review

To cite this article: Ajay Kumar et al 2020 ECS J. Solid State Sci. Technol. 9 115022

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Review—Thin-Film Transistors (TFTs) for Highly Sensitive Biosensing Applications: A Review Ajay Kumar,1,z Amit Kumar Goyal,1 and Neha Gupta2,z

1ECE Department, Jaypee Institute of Information Technology, Noida, India 2Department of Applied Science and Humanities, ADGITM, New Delhi, India

This review manuscript presents Thin-Film Transistors (TFTs) for various highly sensitive biosensing applications. A low-cost, highly sensitive, early-stage diagnostic bio-sensing devices are vital for different biomedical and biological applications. Nanotechnology-based biosensor devices such as bioFET, thin-ﬁlm transistor (TFT), etc. are used to overcome the problems of conventional health diagnostic approaches. Among them, TFT based biosensors have gained a lot of attention owing to high sensitivity, high-scalability, low power consumption, rapid electrical detection, low-cost mass production, and direct electrical readouts. Further to improve the sensitivity of TFT bases biosensor, transparent materials are frequently used in current biosensing research ﬁelds and it is found that indium tin oxide (ITO) is most favorable for biosensing applications. Thus, the amalgamation of ITO on TFT paves the way with the existing CMOS technology for early-stage diagnostic of protein-related diseases such as coronary artery disease, ovarian cancer, and Alzheimer’s diseases. © 2020 The Author(s). Published on behalf of The Electrochemical Society by IOP Publishing Limited. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 License (CC BY, http://creativecommons.org/licenses/ by/4.0/), which permits unrestricted reuse of the work in any medium, provided the original work is properly cited. [DOI: 10.1149/ 2162-8777/abb2b3]

Manuscript submitted August 1, 2020; revised manuscript received August 21, 2020. Published September 7, 2020. This paper is part of the JSS Focus Issue on Solid-State Materials and Devices for Biological and Medical Applications.

BioFETs is the acronym used for Field-effect transistor (FET)- transducers used for biosensors. The ISFET has been introduced in based biosensors. BioFETs were first realized in 1980, and they have the 1970s for the measurement of pH and other ions concentrations witnessed great progress especially throughout the last decade.1 In as an alternative to the fragile glass electrode. ISFET has received the field of Biosensors, BioFETs are now one of the most important increasing attention in the manufacturing of ISFET-based biosensors branches. BioFETs have their extensive application in the environ- (BioFETs). There are several benefits of silicon-based ISFET: ment, agriculture, food industry, and clinical analysis. Because of (a) small size and weight; (b) low output impedance and high input this, they have received great attention in the field of research. impedance; (c) anti-breaking capability; (d) low-cost mass produc- Biosensors are made up of two main parts: the signal-transducing tion; (e) rapid response and high sensitivity. Therefore, these and biological recognition. The signal amplification and unique advantages made ISFET as an ideal tool for the manufacture of recognition abilities of the biological system make the BioFETs as a portable micro biosensors.16 prominent functional hybrid system. Therefore, the generation of In addition, catalyzed FET based biosensors17 has also been selective, specific, highly sensitive, and reliable biosensors are thus widely explored. Biocatalysts (as enzymes) are used in catalytical possible through the integration of different types of biologically BioFETs, to bind, recognize, and chemically transform biological active materials. Fast response, small size, lightweight, low cost, molecules into sensory recognizable forms. Another most studied high reliability, along with on-chip integration capability of bio- BioFETs is the ENFET (Enzyme-based ISFET). These kinds of sensor arrays for production of portable microanalysis systems are BioFETs are usually manufactured by stabilizing an enzyme on a some of the major advantages of the BioFETs.2–5 The desirable gate insulator of an ISFET. The basic working principle of an features of micro biosensors are faster response time and higher ENFET is based on catalytic activity and the enzyme’s specific sensitivity. Due to these properties, several efforts have been made binding capacity for its substrate. The extended-gate FET (EGFET) for the detection of DNA using field-effect devices.6–8 was first introduced in 1983 to improve the performance of Micro-organisms and disease markers can be potentially detected conventional ISFETs.18 The EGFET is divided into two parts, a with the help of biosensor technology in clinics. For detecting MOSFET structure, and a sensitive membrane-containing sensory biomolecular interactions such as antibody-antigen interactions, structure. Compared to traditional ISFET, this structure possesses DNA hybridization, DNA-protein binding, receptor-ligand binding, many advantages, such as flexibility of the extended gate area size, protein-protein interactions, and other types of interaction; biosen- ease to package, photo insensitivity.19,20 The MOSFET (metal- sors can serve as an effective analytical tool.9–12 As reported first by oxide-semiconductor FET) is one of the favorable devices, which is Clark and Lyon,13 in the introduction of the biosensor in 1962, widely used as a highly sensitive biosensor for the last many years. environmental, biomedical, industrial, and agricultural fields have MOSFET consists of a metal followed by an insulator and been employing biosensors in an extensive range of applications. semiconductor structure, where a metal gate electrode is applied Due to higher sensitive measurements, easy operation with a minute on top of an insulating layer of oxide.21–23 MOSFET based quantity of analyte, and high speeds, BioFETs is the most attractive biosensors are work on the principle of electrical detection of the electrical biosensors available at present.14 BioFETs are useful in the biomolecules. When the biomolecules are immobilized on the gate areas of clinical diagnosis and on-site detections due to their metal then it changes the dielectric constant of the surface. This outstanding electrical characteristics. In the BioFETs, the gate metal modifies the electric field in the channel, which further effects the is replaced by a biofilm layer material such as an enzyme, antibody, drain current and overall performance of the MOSFET device. For DNA, receptor, or another type of capturing molecule biologically specific biomolecules detection, the dielectric constant of the specific for the target analyte. When the target molecules are in the molecules is required. There are many researchers who have solution, it modulates the channel conductivity of the FET. This reported different biosensors for the detection of DNA-protein occurs because of the bio-modified gate surface, which leads to a interactions,24 diagnose Alzheimer’s diseases25–27 and caffeine change in the drain current. The ISFET (ion-sensitive field-effect detection.28 transistor)15 is the most attractive device among the variety of The label-free detection technique is frequently used for the detection of biomolecules in the different FET based biosensors such as tunnel field-effect transistor (TFET),29 transparent gate recessed 30,31 32 33 zE-mail: [email protected]; [email protected] channel MOSFET, FinFET, and thin-film transistors (TFTs), ECS Journal of Solid State Science and Technology, 2020 9 115022 etc. The label-free detection process is a plus point because of the things they provide in light of being coherent with the basic CMOS processing technology, and price-effective macro production.34 Label-free detection has included less sample setup and time of detecting along with it lessens the basic cost and complexity of the systems. FET sensors are made with the help of ISFET those works on the principle of change in the electrical characteristics (i.e., current, threshold voltage, and conductance) because of the presence of charged substance between the gate dielectric and the ionic solution.35 The electric field effect, which is directed vertically down is based on Vgs, only when the gate voltage is equal or greater than the threshold voltage. The threshold voltage is the value of gate voltage for which a substantial volume of mobile holes or electron along the channel combines to give rise to a conducting channel. When the gate voltage is near to threshold or more, the NMOS starts to initiate the device. Differently, for a PMOS, the gate voltage should be lower than the threshold voltage to produce a p-type Figure 1. Schematic of the thin-film transistor as a biosensor.50 channel beneath the gate oxide layer. The analyte’s surface charge density distresses the applied gate bias of gate voltage. To detect biomolecules using a field-effect transistor, the probe objects should stick to the active sensing layer. The label-free detection technique has also been used in TFT as a biomarker for clinical applications such as children with sickle cell disease (SCD),36,37 birth asphyxia,38–41 and extracorporeal membrane oxygenation support,42 and in adults with traumatic brain injury and stroke.43,44 In this technique, a large area TFT sensor is used for the real-time detection of low concentration protein analytes.45 In this review manuscript, the different semiconductor-based biosensors, recent progress, and the applications are presented in section 1. Section 2 discusses the Thin Film Transistors (TFTs) and its effectiveness as a biosensor. Different detection techniques along with their sensing capability are also discussed in detail. In section 3, we review the different transparent materials as transparent conduc- tion oxides (TCOs) like Indium-Tin-Oxide (ITO), Zinc-Oxide (ZnO), Cadmium-Oxide (CdO) and their compounds like a thin film transparent electrode as a gate material in semiconductor devices. In section 4, we discuss the Transparent Thin Film Transistor as a biosensor and after that, the fabrication feasibility Figure 2. Schematic of the organic transistor-based label-free biosensor, and device process with flowchart has been discussed in section 5. with electric bias during DNA immobilization.51 Finally, section 6 provides a brief conclusion and possible future insight into the presented devices. interactions and these sensors are beneficial in the field by non- specialized technicians. Thin-Film Transistors (TFTs) as a Biosensor The TFTs based biosensor51 has also been used for the detection To improve the performance and to accomplish the semiconductor of DNA molecules, as shown in Fig. 2. By the incorporation of thin- technologies for the development of biosensor, thin-film transistor films organic semiconductors, the organic thin-film transistors (TFT) technology can play a vital role in this promptly expanding (OTFTs) biosensors are invented. Enhancements in biosensor field46,47 as chemical and biological sensors.48,49 TFTs exhibits peculiar innovation have been acknowledged through an improved compre- interest towards FET-based chemical and biological sensors. A TFT is a hension of the interface among science and electronics. In the MOSFET that is invented by employing entirely thin-film elements on schematic of Fig. 2, pentacene has been used as an active layer on the substrate (an insulating substrate).46 Like enhancement-mode the top contact of OTFT. During the single-stranded DNA (ssDNA) MOSFETs, normally TFTs are operated in the same principle and a immobilization processing, different biases were introduced on the very small current flows between the source and drain as Vgs (the gate source and gate contacts of OTFT to improve the immobilization voltage with respect to the source) is low due to the high resistance of efficiency of DNA molecules on the pentacene substrate. The the active layer. At the point, the charge is induced near the oxide- positive bias improves the amount of immobilized ssDNA, which – semiconductor interface when the Vgs is high, and between the source is shown by atomic force microscopy (AFM) images in Figs. 4b 4e. and drain, a channel is established. Hence the TFT operates as a switch, Organic semiconductors can be directly integrated with living disciplined by the Vgs. systems owing to excellent biocompatibility. In this analysis, three TFTs can be applied either as circuit components for molding and devices have been considered namely devices 1, 2, and 3 with the read-out of the sign of promising label-free electrical location same as shown in Fig. 2 depending on the bias voltage for 50 V, 0 V, methods or as potentiometric sensors for the identification of various and −50V respectively. The results have been extracted using these biomolecular cooperations, for example, electrochemical impedance devices and plotted in terms of output characteristics and transfer spectroscopy. The ability to detect biomolecular interactions is characteristics as shown in Figs. 3a and 3b respectively. From both essential in pharmaceutical, medical, and biotechnological applica- output characteristics and transfer characteristics, it is observed that tions. The most usually utilized strategies for the discovery of such the current is higher in all three devices due to DNA-immobilization connections depend on optical techniques, in fluorescence detection is in the saturation region. It is also observed that the current in of labeled biomolecules50 as shown in Fig. 1. Though a high level of devices 1 and 2 is higher than device 3 as shown in Fig. 3b. This success has been attained by restraining their use to specialized result reviles that the negative voltage supply is favorable to the laboratories. Due to its suitability to low-cost portable sensors, the electrical response of OTFT owing to higher on-current in device 1 highly desirable method is the electrical detection of biomolecular as compared to device 2, which reflects that the electrical response ECS Journal of Solid State Science and Technology, 2020 9 115022

Figure 3. (a) The output characteristics and (c) the transfer characteristics of OTFT devices (reprinted from Liu et al.,51 with permission from Elsevier). can be changed by the bias voltage due to change of DNA density on Novel Materials on TFTs for Biosensing pentacene. The performance of semiconductor devices such as MOSFET is Furthermore, the on-current ratio has also been evaluated. This ratio majorly dependent on its gate controllability over the channel for is increased by applying positive voltage and reduced by applying a sensing application, and the gate controllability is dependent on device negative voltage as compared to the pristine device as shown in Fig. 4a. gate architecture and the material which is deposited on to the gate. This reflects that the positive biasing is favorable for the sensitivity of Aluminum (Al) is the commonly used gate material in the semicon- OTFT sensor. From Fig. 4a it is also observed that the density of ductor devices and it has some limitations in an application perspective. immobilized DNA increased by applying a bias voltage. The bias effects However, other materials are very frequently used now days owing to on the immobilization of ssDNA molecules have also been verified by high gate controllability and producing higher sensitivity for sensing AFM imaged of these devices as reflected in Figs. 4b–4e. The DNA applications such as biosensor and gas sensor. The gate materials are density is higher in device 1 as and lowest in device 3 which reflects that used as conducting oxide and the transparent materials are one of the the DNA molecules are more attracted to positive bias and immobilized favorable materials which are used as transparent conducting oxide for on the pentacene surface which enhances the electric response. higher performance biosensing applications. Moreover, many recent advancements in bio-molecular detection using OTFTs have proved significant promise for low-cost detection systems.52,53 The device security and biocompatibility for applications Transparent conducting oxides (TCOs).—To enhance device of identifying low groupings of biomolecules in blood or tissue present performance and interdisciplinary applications, conventional gate noteworthy difficulties.54 To overcome these difficulties two approaches material is replaced by amorphous transparent conducting oxides are widely considered. The first approach utilizes thick encapsulation (TCOs). TCOs are electrically conductive materials usually prepared layers and in the second approach, salt-free analyte solutions are with thin-film technology. TCOs are used as transparent electrodes used.55,56 Both the approaches affect the sensitivity of the sensor by for optoelectronic applications in flat panel display, optoelectrical either decreasing the Debye screeninglengthorblockingthesignal.57 interfaces, and circuitries. TCO thin films are practically used as Before organic transistor technology can be acceptable for biological transparent electrodes and exhibit average transmittance above 80% detection, two key challenges of these techniques must be overcome, in the visible region and having resistivity less than of the order of which includes: (1) selectivity toward a particular analyte with high 10−3 Ω-cm with higher carrier concentration (in the order of sensitivity, and (2) stability of transistor with variable pH in harsh media. 1020 cm−3) and bandgap (∼3 eV). Most of the TCOs are impurity- 58 Now the technology is well developed and has many commercial doped In2O3, ZnO, and SnO2. Till now, different TCO thin films applications. The detection of biomolecules in any FET devices is consisting of binary compounds (ZnO, SnO2,In2O3, CdO, etc.) have based on the gate material where the biomolecules are immobilized. been advanced with impurity-doped ZnO (ZnO:Al and ZnO:Ga), Hence there is a need to improve the electrical characteristics of impurity-doped In2O3 (In2O3:Sn) and impurity-doped SnO2 (SnO2: TFTs by using suitable gate material for higher sensing applications. Sb and SnO2:F) films. Some of the reported effective dopants The next section (Section 3) of this spotlight will discuss some novel along with their associated binary compound are listed in Table I. gate materials and their application on to the TFTs for the detection Moreover, to binary compounds, ternary compounds such as of different biomolecules with different techniques and it will also be CdSnO3,Cd2SnO4, Zn2SnO4, MgIn2O4, CdIn2O4,In4Sn3O12, and 59–64 discussed that how the indium-tin-oxide is the promising material in CdSb2O6 have been developed. These TCO films are easy to semiconductor devices for sensing applications. design owing to the use of multicomponent oxide materials (shown ECS Journal of Solid State Science and Technology, 2020 9 115022

Figure 5. Schematic of various thin-ﬁlm transparent electrodes with their TCO semiconductors.67

resistivity, the Hall mobility is 33.2 cm2(V s)−1 and the carrier concentration is 2.5 × 1021 cm−3;for9.5× 10−5 Ω-cm resistivity, the Hall mobility and the carrier concentration are 40 cm2(V s)−1 and 1.8 × 1021 cm−3 respectively, and for 8.45 × 10−5 Ω-cm resistivity, the Hall mobility and the carrier concentration are 53.5 cm2(V s)−1 and 1.38 × 1021 cm−3 respectively. ITO and ZnO are the two promising transparent electrodes used in semiconductor devices. ITO is more stable than ZnO for the oxidizing atmosphere at high temperature.85 From the characteristics of ITO and ZnO, it has been observed that both ITO and ZnO have low resistivity (10−5 Ω-cm). However, ZnO and ITO have different practical; resistivity 2–3 × 10−4 Ω-cm and 1 × 10−4 Ω-cm respectively. The energy band gap of ZnO is 3.3 eV and for ITO it is 3.7 eV but the index of refraction is the same for both ZnO and ITO. It has also been observed that the work-function of ZnO and ITO are different and have 4.6 for ZnO and 4.8–5.0 for ITO. The material properties must be very high however, it is also necessary that the cost of that material should be as low as possible for high production. It is found that ZnO is expensive however ITO is very expensive. Moreover, stability is a very important parameter for both Figure 4. (a) The bias dependence on the amounts of the particles and the ZnO and ITO and it is found that with acid solution ZnO and ITO are ratio of saturation current for devices 1, 2, and 3; (b) AFM morphology of showing less stability. For alkali solution, ZnO and ITO are also bare pentacene; AFM images of DNA immobilized on pentacene by using + − × shown low stability, and similarly for the oxidizing atmosphere at high different bias: (c) 0 V; (d) 50 V; (e) 50 V (All image sizes are 5 temperature (or oxygen plasma) ZnO and ITO show low stability. But 5/μm2) (reprinted from Liu et al.,51 with the permission from Elsevier). for reducing atmosphere at high temperature (or hydrogen plasma) ZnO and ITO show very high stability. Owing to these properties ITO in Fig. 5) for specialized applications and can be controlled by 65,66 and ZnO are promising materials for the semiconductor devices and altering the chemical composition. thereafter for sensing applications. These materials are used as a gate material for the detection of — Indium tin oxide (ITO): In2O5Sn. Obtaining a lower resistivity biomolecules on to the TFTs. Thus, section 4 discusses the different of TCO is a major challenge. In recent years, some of the impurity- transparent gate based TFTs for various biosensing applications. doped binary compound TCO films have been reported with minimum resistivity. From the reported work, it is evident that 69–76 Transparent Gate Thin Film Transistors as a Biosensor In2O3 doped TCO film i.e., indium tin oxide (ITO) has the lowest resistivity of the order of 10−5 Ω-cm as compared to ZnO Transparent gate thin film transistors (TG-TFTs) as a label- 31,75,77,78 — doped and SnO2 doped. ITO (In2O5Sn) is a solid solution of free biosensor. In the previous section is has been discussed that indium oxide (In O ; 90%) and tin oxide (SnO ; 10%), transparent TFTs are broad as a biosensor. Meanwhile less power usage and 2 3 2 86,87 and colorless thin film. ITO is the most widely used TCO owing to lower voltage in addition to sleek film circuits. For a high its electrical conductivity and optical transparency.79 The electrical sensitivity transistor-based sensor, it is required that the device properties of ITO with a resistivity of 10−5 Ω-cm have been should have high gate controllability. Thus a transparent material has summarized in Table II. From Table II it is observed that the carrier been used on to the gate of the device to improve the performance. 69–75,78,88 concentration changes with very few changes in the resistivity Indium tin oxide (ITO) is considered as the most suitable however, Hall mobility makes high changes. For 7.4 × 10−5 Ω-cm material used as transparent material owing to its electrical proper- 89 resistivity, the carrier concentration is 7.4 × 1021 cm−3,andHall ties such as higher mobility, moderate temperature fabrication, mobility is 103 cm2(V s)−1. However, For 8.9 × 10−5 Ω-cm fluent transparency, and uniform structure. The deposition of ITO 90,91 −5 resistivity, the Hall mobility is 54.1 cm2(V s)−1 and the carrier requires lower temperature, low resistivity (10 Ω-cm), with 21 −3 2 concentration is 1.3 × 1021 cm−3. Similarly for 7.2 × 10−5 Ω-cm high concentration (10 cm ) and high Hall mobility (53.5 cm ECS Journal of Solid State Science and Technology, 2020 9 115022

Table I. Various TCO as thin-ﬁlm transparent electrodes.67,68

Table II. Electrical properties if ITO with a resistivity of 10−5 Ω-cm.80–84

V−1 s−1).58 Owing to these properties, ITO has been used in TFT various models and equations94 are used for the simulation process. and create transparent gate TFT (TG-TFT). div()ej=- r []1 Device design and simulation methodology.—The device design for a TG-TFT is shown in Fig. 6.92,93 Figure 5a shows the ¶p 1  =+-divJppp G R []2 schematical diagram of the front view of TG-TFT and Fig. 5b ¶tq reﬂects the 3-D top view geometry of the TG-TFT. The device design parameters are represented in Table III. 94 ¶n 1  For this work, the TCAD device simulator is used. FLDMOB =+-divJnnn G R []3 and KLASRH model is considered for the simulation.94 In addition, ¶tq

Figure 6. Schematics of (a) 2-D device design of TG-TFT; (b) 3-D top view of TG-TFT.92 ECS Journal of Solid State Science and Technology, 2020 9 115022

Figure 7. (a) Transfer characteristics of TG-TFT; (b) Electric ﬁeld of TG-TFT.

Table III. TG-TFT device design parameters.92

because of the higher electric field at the source and drain side as reflected in Fig. 7b. Higher electric field improves drain current and hence the device performance for biosensing applications. Figure 8. Sensitivity of TG-TFT at different drain voltage. Sensitivity is the key parameter for the performance evaluation of a biosensor and it can be calculated by a change in threshold voltage (ΔVTH). ΔVTH is defined as the difference of threshold voltage with the analyte and without analyte. Therefore, the sensitivity of the TG- 2 pn- nie TFT biosensor has been evaluated and plotted for different drain bias RSRH = as reflected in Fig. 8. From Fig. 8, it is also observed that the tt[][]nne+++((--EkTTRAP// L )) pne ((EkT TRAP L )) pie nie sensitivity is higher at lower drain voltage and reduces with an []4 increase in drain bias, which proves that the device is suitable for low voltage supply. Further, the sensitivity performance of the 2 2 2 2 device has been evaluated by the switching ratio (I /I ) of TG-TFT RAuger =-+- AUGN()()[] pn nnie AUGP np pn ie 5 on off with and without analyte and it is increased in the presence of the analyte as compared to the absence of analyte as shown in Fig. 9a ⎡ ⎤1/b 1 owing to an increase in I and reduced I . The device sensitivity mm()E = ⎢ ⎥ []6 on off 0 ⎣ b ⎦ could be evaluated more accurately by threshold voltage change 1 + ()mu0 E sat (Vth) with and without analyte. It is found that the change in threshold voltage is 0.2 V for the TG-TFT without analyte and 0.3 V Where ɛand j are permittivity and potential and ρ is space charge for TG-TFT with the analyte and is shown in Fig. 9b. The change in density. Jp and Jn are hole and electrons current density; Gp and Gn is threshold voltage reflects the sensitivity of the device in the presence the generation rate for holes and electrons; Rp and Rn are holes and of the analyte. The sensitivity of a biosensor is defined by the change electrons recombination rates and “q” is the charge. ETRAP is change in threshold voltage when the analyte or biomolecules are present in the Fermi levels; τn is electron lifetime and τp, is the hole lifetime. and the absence of analyte or biomolecules. This is one of the easy Simulation results.—In order to investigate the electrical proper- ways to calculate the sensitivity of the device and to detect the ties of ITO based TFT, transfer characteristics and electric field have presence of a particular analyte of the biomolecule. been evaluated at 1 V gate bias as reflected in Figs. 7a and 7b respectively. Figure 7areflects the transfer characteristics and Indium-tin-oxide thin-film transistor (ITO TFT) biosensors.— plotted as a function gate voltage, and it is observed that the drain TFTs have been presented as the repetitive cause of avian influenza current is higher for a thin-film device in the nano dimension. This is (AI) which is unsafe for humans as well as economic development ECS Journal of Solid State Science and Technology, 2020 9 115022

Figure 9. (a) Ion/Ioff ratio with and without analyte for TG-TFT; (b) Shift in threshold voltage with and without analyte for TG-TFT.

Figure 10. (a) Schematics of immobilized with anti-H5N1 antibodies a TFT-based sensor structure and noticing negatively charged AI H5N1 virus; (b) reaction representation for antibodies immobilized process on the ﬁlm.95 ECS Journal of Solid State Science and Technology, 2020 9 115022

Figure 11. (a) Transfer characteristics of anti-H5N1 antibodies modified ITO TFT following AI H5N1 virus and antibodies interaction. (b) Transfer characteristics of biotin-modified ITO TFT following biotin-avidin interaction. (c) Transfer characteristics of unmodified ITO TFT. (d) Transfer characteristics using BSA solution of anti-H5N1 antibodies. (reprinted from Guo et al.,95 with the permission from Elsevier). and social stability. Therefore the need of the hour is to detect the AI H9N2 virus) as reflected in transfer characteristics (red dots) of 95 highly infective avian influenza H5N1 virus. There’s a growing ITO TFT (Fig. 11a). After injecting AI H5N1 virus PBS solution, a concern over the Avian Influenza Virus. There are serious causes of shift in threshold voltage is observed owing to H5N1-antibody social stability and threatened human health due to the highly receptor-specific interaction and indicated by green dots in Fig. 11a. pathogenic avian influenza virus. The very first target by H5N1 was Figure 11b shows the transfer characteristics of biotin-modified ITO discovered in 1997 in Hong Kong, which resulted in many more TFT in which biotin-avidin interaction takes place. As compared to deaths.18,96,97 According to WHO report, 335 death has been AI H5N1 virus and antibodies interaction an opposite response is reported due to AI H5N1 virus.97,98 AI H5N1 virus spreads not observed (PBS baseline indicated by black dots) when biotin and solely among fowls however additionally among humans which may avidin interacted. Figure 11creflects unmodified transfer character- trigger a world pandemic. Furthermore, it is difficult to be cured the istics of ITO TFT and it is obtained in PBS buffer solutions that disease due to the alteration of AI H5N1 virus. H5N1 has greatly contained AI H5N1 virus is injected into the channel and indicated impacted both social wellbeing and economically. Thus, to control by black dots. But it is observed that there is no change in threshold 99 the spread of H5N1 is only possible by detecting AI H5N1. voltage after adding the virus on the device. Thus only modified ITO ITO TFTs are fabricated on a glass substrate for the detection of film surface by specific binding of AI H5N1 virus to the anti-H5 95 AI H5N1 (shown in Fig. 10). The ITO TFT is fabricated by a one- antibodies may induce the change in transfer characteristics as shadow-mask method in which a channel layer is at the same time shown in Fig. 11a. Further, the transfer characteristics of anti-H5N1 self-assembled between ITO source/drain electrodes throughout the antibodies ITO TFT is shown in Fig. 11d and plotted with respect to thermionic valve. Monoclonal anti-H5N1 immunizer (for AI H5N1 the gate voltage. Here, BSA solution instead of PBS has been used virus) was disabled on the ITO channel by (3-glycidoxypropyl) as background for the interaction of AI H5N1 virus and antibodies as trimethoxysilane through a covalent bond. The introduction of target shown in Fig. 11d. AI H5N1 caused a negative impact on the electrical characteristics of Due to the potential for mass commercial production and the ITO TFT, which causes a change in the field-effect mobility and excellent electric properties, ITO TFTs could turn out to be ideal resultant Vth (threshold voltage). Negatively charged AI H5N1 candidates for the expansion of label-free biosensors. ITO based viruses influence the ID–VG curves which consistent with an n- TFT biosensor exhibits their extensive applications in the environ- type field effect transistor behavior. Also, through the coating mental, and clinical analyte detection. It also possesses fast response, processes, these biosensors could be recursively used. small size and weight, high reliability, and the opportunity of on- Figure 11 reflects the transfer characteristics of ITO TFT, which chip integration. It can detect enzyme-linked immunosorbent assays, shows that ITO based TFT biosensor is fabricated to detect H5N1 such as biomolecules for Alzheimer’s disease, ovary tumor, and virus. A control experiment using PBS buffer solution contained AI coronary artery disease. ITO based TFT biosensor has achieved high H9N2 virus has been performed (shown by black dots). Then there is scalability, sensitivity, and low power consumption with ease of no change is observed after injecting PBS buffer solution (containing fabrication process. When ITO is used as a nano-material in ECS Journal of Solid State Science and Technology, 2020 9 115022

103 Figure 12. Schematic structure of the electrolyte-gated In2O3 TFT. biosensor technology then it increases the detection capability with enhanced speciﬁcity and less amount of analyte requirement. ITO based TFT biosensors can sense analytes in pico/femto levels. Moreover, by using composites composed of several nanomaterials such as nanoparticles, conductive polymers and graphene can improve the analytical performance in the fabrication of these biosensors which improves analytical performance such as repeat- ability, reproducibility and detection limit.100,101

Indium oxide thin film transistor with electrolyte-gated based biosensor.—In this part of the review, we explore an In2O3-electrolyte gated thin film transistor to be a label-free biosensor as reflected in Fig. 12. Through surface modification, a receptor molecule is created, where the In2O3 channel is covered by streptavidin, then, the target biomolecules of biotin to be discovered are occupied by the receptor molecules. The electrical performance of the EGTFT has been changed when the target biomolecules would bring about a change in the surface potential of charges in the In2O3 channel. The MOCVD (metal-organic chemical vapor deposition) grown In2O3 in the high background carrier concentration in and huge EDL (electric double layer) capacitance in liquid gate can produce ultra-low operation voltage. With ultralow operation voltage of VG = 0 V and VDS = 50 mV, high sensitivity is achieved when positive charges are observed in biotin. The detection limit is −1 ∼50 ng ml . This study displays the feasibility of In2O3-EGTFT as a biosensor, even though the discovered limit should be improved. In2O3 EGTFT biosensor has been looked into to detect the biotin using streptavidin as a receptor. This binding system (streptavidin- –biotin-binding) is globally utilized as a molecular linker.102 The detections of biotin are very beneficial as the detection in solution is critical to tumor-targeted cancer therapeutics and clinical diagnostic applications.103 Biotin and streptavidin act as models where the streptavidin- biotin interaction takes place for receptor and target molecules and the bio-functionalization steps of the In2O3 surface. Naturally, the surface of the In2O3 carries hydroxyl groups. Thereafter, for 12 h at a suitable temperature under room conditions, immersing in an ethanol solution of APTES (3-aminopropyltrieth-oxysilane), the In2O3 surface is altered by NH2 (the amino functional group). For 2 h to obtain CHO on the In2O3 surface, the In2O3 is then dipped in a glutaraldehyde solution. For the next hour, the streptavidin biomolecules are then immobilized on the aldehyde-functionalized In2O3 surface by exposing in a solution of streptavidin. Finally, at room temperature for 30 min, biotin with four different concentrations is moved onto the In2O3 surface then the biotin would be received by the streptavidin receptor. As a comparison, the In2O3 surfaces Figure 13. Fabrication flowchart of ITO TFT at room temperature. ECS Journal of Solid State Science and Technology, 2020 9 115022

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