sensors Review Recent Advances in Electric-Double-Layer Transistors for Bio-Chemical Sensing Applications Ning Liu 1,2, Ru Chen 1 and Qing Wan 2,* 1 Nanchang Institute of Technology, Nanchang 330099, China 2 School of Electronic Science & Engineering, Nanjing University, Nanjing 210093, China * Correspondence: [email protected]; Tel.: +86-791-88126923 Received: 28 June 2019; Accepted: 1 August 2019; Published: 5 August 2019 Abstract: As promising biochemical sensors, ion-sensitive field-effect transistors (ISFETs) are used widely in the growing field of biochemical sensing applications. Recently, a new type of field-effect transistor gated by ionic electrolytes has attracted intense attention due to the extremely strong electric-double-layer (EDL) gating effect. In such devices, the carrier density of the semiconductor channel can be effectively modulated by an ion-induced EDL capacitance at the semiconductor/ electrolyte interface. With advantages of large specific capacitance, low operating voltage and sensitive interfacial properties, various EDL-based transistor (EDLT) devices have been developed for ultrasensitive portable sensing applications. In this article, we will review the recent progress of EDLT-based biochemical sensors. Starting with a brief introduction of the concepts of EDL capacitance and EDLT, we describe the material compositions and the working principle of EDLT devices. Moreover, the biochemical sensing performances of several important EDLTs are discussed in detail, including organic-based EDLTs, oxide-based EDLTs, nanomaterial-based EDLTs and neuromorphic EDLTs. Finally, the main challenges and development prospects of EDLT-based biochemical sensors are listed. Keywords: ISFET; electric-double-layer; electrolyte-gated transistor; biosensor; chemosensor 1. Introduction Biochemical species detection techniques have important applications in the area of homeland security, medical and environmental monitoring, bioscience research and also food safety. In the past decades, many kinds of energy transduction principles have been employed for chemical and biological sensing based either on optical [1], electrochemical [2], electrical [3], gravimetric [4], acoustic [5], or magnetic methods [6]. Among these, electrochemical sensors provide an attractive means to analyze the content of target species due to the direct conversion of a biochemical event into an electronic signal. Sensors based on electrochemical transduction have been developed using a variety of techniques, such as chronoamperometry [7], chronopotentiometry [8], impedance spectroscopy [9], cyclic voltammetry [10], and various field-effect transistor (FET)-based methods [11], etc. As a kind of potentiometric sensor, ion-sensitive field-effect transistors (ISFETs) are used widely in the growing field of biochemical sensing applications due to their advantages of label-free detection, easy miniaturization, integratability, robustness, etc. [12]. ISFETs were developed from metal oxide semiconductor field-effect transistors (MOSFETs) by replacing the metal gate electrode with a liquid solution and a reference electrode. In such devices, the charge carrier density in the semiconductor channel can be modulated over orders of magnitude by an electrostatic gating effect. Thus, the variation of surface potential on the sensing membrane arising from the adsorption of charged target species can be sensed by ISFETs. Due to the intrinsic property of signal amplification, ISFET devices are preferred for their low detection limits and high sensitivity, allowing them to outperform chemiresistors as Sensors 2019, 19, 3425; doi:10.3390/s19153425 www.mdpi.com/journal/sensors SensorsSensors 20192019, ,1919, ,x 3425 2 2of of 32 32 ISFET devices are preferred for their low detection limits and high sensitivity, allowing them to outperformwell as amperometric chemiresistors sensors as well [13 as]. amperometric So far, a great sensors deal of [13]. research So far, eff aort great has deal been of directed research toward effort hasthe been development directed of toward ISFETs the with development high sensitivity of andISFETs specificity. with high In addition sensitivity to sensing and specificity. performance, In additionflexible andto stretchablesensing performance, ISFET devices flexible with low and power stretchable consumption ISFET are devices also in increasingwith low demandpower consumptionin the emerging are fieldalso in of increasing biosensing demand applications in the such emerging as implantable field of biosensing chips, wearable applications electronics such and as implantablepoint-of-care chips, diagnostics wearable [14 electronics–16]. and point-of-care diagnostics [14–16]. TheThe first first generation generation of of ISFET ISFET de devices,vices, proposed proposed by by Bergveld Bergveld in in 1970, 1970, were were based based on on crystaline crystaline siliconsilicon (Si) (Si) MOSFET MOSFET technology technology [17]. [17]. The The main main drawback drawback of of these these devices devices is is that that their their fabrication fabrication processesprocesses are are relatively relatively intricate intricate and and a a high high operat operatinging voltage voltage (>10 (>10 V) V) is is always always required. required. Moreover, Moreover, itit is is difficult difficult to to adapt adapt Si-based Si-based ISFE ISFETsTs to to curved curved surfaces surfaces or orflexible flexible structures structures due due to the to the rigidity rigidity of Si of substrate.Si substrate. Nowadays, Nowadays, large-area large-area deposited deposited thin-film thin-film transistor transistor (TFT) (TFT) technology, technology, which which is is well well compatiblecompatible with with flexible flexible substrates, ooffersffersa a lower lower cost cost alternative alternative to to produce produce ISFET ISFET sensors sensors [18 [18].]. On On the theother other hand, hand, according according to the to sensing the sensing mechanism mechanism of ISFET, of theISFET, change the of change surface of potential surface induced potential by inducedtarget species by target is reflected species is in reflected a modulation in a modulati of channelon current.of channel Thus, current. a strong Thus electrostatic, a strong electrostatic modulation modulationat the dielectric at /thesemiconductor dielectric/semiconductor interface is beneficial interface for theis beneficial achievement for ofthe good achievement sensing performance of good sensingand low performance power consumption. and low Reducingpower consumption. the dielectric Reducing thickness the and dielectric using a high-K thickness gate and dielectric usingare a high-Kcommon gate methods dielectric that are were common used to methods obtain large that capacitance were used ofto gate obtain dielectric, large capacitance and then to enhanceof gate dielectric,the gate modulation. and then to However, enhance duethe togate the directmodula tunnelingtion. However, of electrons, due theto the gate direct leakage tunneling current willof electrons,extremely the increase gate leakage with the current reduction will extremely of the thickness increase of with gate the dielectric. reduction Additionally, of the thickness the adoption of gate dielectric.of high-K Additionally, gate dielectrics the will adoption lead to aof decrease high-K ingate carrier dielectrics mobility will of channelslead to a owing decrease to the in electroncarrier mobilitytrapping of by channels Fröhlich owing polarons to the [19 electron]. trapping by Fröhlich polarons [19]. Recently,Recently, a a new type ofof FETFET devicesdevices gated gated by by ionic ionic electrolytes electrolytes has has attracted attracted intense intense attention attention due dueto their to gianttheir charge-carriergiant charge-carrier density accumulation density ac inducedcumulation by the induced extremely by strong the electric-double-layerextremely strong electric-double-layer(EDL) capacitive eff ect(EDL) [20 –capacitive23]. In such effect devices, [20–23]. electrolyte In such devices, ions will electrolyte migrate to ions the will gate /migrateelectrolyte to theand gate/electrolyte semiconductor and/electrolyte semiconductor/electrolyte interfaces with the interfaces application with of athe gate application voltage, functioningof a gate voltage, as two functioningnanogap EDL as two capacitors nanogap with EDL huge capa capacitancecitors with (huge>1 µF capacitancecm 2)[24]. (>1 By μ theF·cm strong−2) [24]. electrostatic By the strong EDL · − electrostaticgating effect, EDL a net gating charge effect, accumulation a net charge/depletion accumulation/depletion in the semiconductor in channel the semiconductor can be induced channel under cana low be induced gate voltage under (< 2a V).low Characteristics gate voltage (<2 of V). EDL-based Characteristics transistors of EDL-based (EDLTs), suchtransistors as large (EDLTs), specific suchcapacitance, as large specific low operating capacitance, voltage, low and operating sensitive voltage, interfacial and sensitive properties, interfacial make these properties, devices make well thesesuited devices to ultrasensitive well suited portable to ultrasensitive sensing applications. portable sensing To date, applications. much effort To has date, been much devoted effort to has the beendevelopment devoted ofto ultrasensitive the development biosensors of ultrasensiti with EDLTve configurations, biosensors with and EDLT remarkable configurations, sensing abilities and remarkablehave been demonstratedsensing abilities on varioushave been EDLT