Design and Implementation of a Ph Sensor for Micro Solution Based on Nanostructured Ion-Sensitive Field-Effect Transistor

Article Design and Implementation of a pH Sensor for Micro Solution Based on Nanostructured Ion-Sensitive Field-Eﬀect Transistor

Yiqing Wang * , Min Yang and Chuanjian Wu

State Key Laboratory of Materials-Oriented Chemical Engineering, College of Electrical Engineering and Control Science, Nanjing Tech University, Nanjing 211816, China; [email protected] (M.Y.); [email protected] (C.W.) * Correspondence: [email protected]; Tel.: +86-139-1597-6325

Received: 13 October 2020; Accepted: 1 December 2020; Published: 3 December 2020

Abstract: pH sensors based on a nanostructured ion-sensitive field-effect transistor have characteristics such as fast response, high sensitivity and miniaturization, and they have been widely used in biomedicine, food detection and disease monitoring. However, their performance is affected by many factors, such as gate dielectric material, channel material and channel thickness. In order to obtain a pH sensor with high sensitivity and fast response, it is necessary to determine the appropriate equipment parameters, which have high processing cost and long production time. In this study, a nanostructured ion-sensitive field-effect transistor was developed based on the SILVACO technology computer-aided design (TCAD) simulator. Through experiments, we analyzed the effects of the gate dielectric material, channel material and channel thickness on the electrical characteristics of the nanostructured field-effect transistor. Based on simulation results, silicon nitride was selected as the gate dielectric layer, while indium oxide was chosen as the channel layer. The structure and parameters of the dual channel ion-sensitive field-effect transistor were determined and discussed in detail. Finally, according to the simulation results, a pH sensor based on the nanostructured ion-sensitive field-effect transistor was fabricated. The accuracy of simulation results was verified by measuring the output, transfer and pH characteristics of the device. The fabricated pH sensor had a subthreshold swing as low as 143.19 mV/dec and obtained an actual sensitivity of 88.125 mV/pH. In addition, we also tested the oxidation reaction of hydrogen peroxide catalyzed by horseradish peroxidase, 1 1 and the sensitivity was up to 144.26 pA mol− L− , verifying that the ion-sensitive field-effect transistor (ISFET) can be used to detect the pH of micro solution, and then combine the enzyme-linked assay to detect the concentration of protein, DNA, biochemical substances, biomarkers, etc.

Keywords: ion-sensitive ﬁeld-eﬀect transistor; nanostructure; pH sensor; performance analysis

1. Introduction Biosensors based on ion-sensitive field-effect transistors (ISFETs) have wide potential applications and are expected to be the preferred devices for field diagnosis. The ISFET was first proposed by Piet Bergveld in 1970 and used for pH detection [1]. It has advantages of fast responses, high sensitivity and simple miniaturization [2]. The Honeywell Durafet is a pH-sensitive Ion-Selective Field Effect Transistor that has been successfully used for pH measurement in seawater CO2 chemistry and ocean acidification studies [3,4]. Modified Honeywell ISFETs have also been integrated into a novel solid-state sensor capable of rapid, simultaneous measurements of pH and total alkalinity in seawater [5,6]. In addition, a one-step immunoassay for the detection of influenza A virus was developed by using two different microbead types and a filter-inserted bottle [7]. The detection bead could pass through

Sensors 2020, 20, 6921; doi:10.3390/s20236921 www.mdpi.com/journal/sensors Sensors 2020, 20, 6921 2 of 16 the filter into the reaction buffer containing urea and induce a pH change, which was quantitatively measured by using phenol red and ISFET. While the one-step immunoassay could be applied to both colorimetry and ISFET assays, the detection range was wider with the ISFET-based one-step immunoassay (0–100 ng/mL). Therefore, pH detection based on ISFETs is very important in the fields of chemistry, agriculture, food processing, pharmacology, environmental science and biomedical engineering [8–11]. Given that high-performance pH sensors require extremely sensitive and stable operation, dual-gate (DG) ISFET-based pH sensors have been developed to improve their sensitivity and stability. The DG ISFETs can significantly amplify their sensitivity and stability without additional amplification circuits by inducing capacitive coupling effect between the top and back gates of the channel. With the proper combination of top gate capacitance and back gate capacitance, an ISFET with a DG structure can even exceed the Nernst limit (59 mV/pH) [12]. An amorphous-InGaZnO (a-IGZO) thin-film transistor was designed to create a biosensor that can operate with DG mode, with a pH sensitivity of 286.76 mV/pH [13]. An individually addressable back gate and a gate oxide layer directly exposed to the solution were created by using SOI (Silicon-On-Insulator) technology. When the ISFET operated in a DG mode, the response can exhibit sensitivity to pH changes beyond the Nernst limit, which was up to 107.65 mV/pH [14]. A DG silicon nanowire (SiNW) FETs pH sensor was demonstrated that can be operated in amplification mode by employing an inversed DG configuration that used the electrode immersed in a solution as the top gate and the SiNW metal gate as the back gate [15]. By integrating the sensor chip with complementary metal oxide semiconductor (CMOS) circuits, the sensitivity of dual-amplification mode obviously exceeded the Nernst limit. The DG ISFET is significantly improved in terms of sensitivity, signal-to-noise ratio, drift rate and hysteresis. This will play a strong role in promoting medical testing, environmental protection and industrial production [16–22]. In recent years, with the development of material science and photolithography technology, ISFETs have gradually become more miniaturized and integrated and can be used for pH detection of trace solutions [23]. Ion-sensitive metal oxides (MOX) with nanostructures have excellent biocompatibility. ISFET devices based on MOx are often applied to the detection of various ion concentrations. Thus, they are widely employed in the fields of electrochemical sensing, biomedical science, water and food quality monitoring, disease detection and other fields [24–26]. Among them, pH sensors used to detect the concentration of hydrogen ion (H+) are the most widely used [27,28]. An ISFET-based pH sensor utilizing a low-cost polyethylene terephthalate (PET) film coated with Au/Ta2O5 layers as the extended gate electrode was developed [29]. The extended gate structure was connected to the gate of a commercial metal–oxide–semiconductor field-effect transistor (MOSFET) integration circuit (IC) for H+ concentration measurement with the sensitivity of 24.18 mV/pH in the pH range from 1 to 13. Moreover, an ISFET biosensor based on enzyme modification was proposed [30]. Utilizing the newly prepared CMOS-compatible ISFET with Ta2O5 sensitive surface and adopting the subthreshold working mode, high sensitivity measurement was realized by reducing the influence of capacitance on the subthreshold swing value. The pH sensitivity of the prepared ISFET was 52 mV/pH. In addition, a high-sensitivity normally off MOS-ISFET pH sensor was developed by pulse electrochemistry (PEC) method. The AlGaN barrier in the sensing region was transformed into an oxide layer with a thickness of about 20 nm to achieve normally off operation. As a result, its pH sensitivity was increased to about 56.3 mV/pH [31]. It can be seen that pH sensors can improve sensitivity by improving parameters and manufacturing methods. However, pH sensors based on semiconductor field-effect transistor (FET) have high processing cost and long production time. Moreover, many researchers choose to optimize performance through simulation. An ISFET-based pH sensor model with temperature-dependent behavioral macromodel was presented [32]. The macromodel was built by using simulation program with integrated circuit emphasis (SPICE), by introducing electrochemical parameters in a MOSFET model to simulate ISFET characteristics. The framework for integration of machine learning (ML) techniques for drift compensation of ISFET chemical sensor was established to improve its performance. Moreover, a numerical simulation approach to study the electrolyte pH change of ISFET structures, SensorsSensors2020 2020, 20,, 692120, 6921 3 of3 16of 16

aided design (TCAD) tools, was proposed [33]. Additionally, transfer characteristics of a conventional using Silvaco technology computer-aided design (TCAD) tools, was proposed [33]. Additionally, ISFET device were simulated, and the ID current as a function of the reference voltage, VRef., and drain transfervoltage characteristics, VD, for different of a conventional pH scale and ISFET ID current device wereas a function simulated, of andVDS thefor IDdifferentcurrent V asRef a. functionvalues for of thespecific reference pH valuevoltage, were VRef also., and simulated. drain voltage, The V proposedD, for diff erent model pHs allow scale and accurate ID current and asefficient a function ISFET of VmodelingDS for di ff byerent trying VRef different. values for designs specific and pH further value wereoptimization also simulated. with different The proposed tools rather models than allowexpensive accurate fabrication. and efficient However, ISFET modeling they did by not trying fabricate different specific designs devices and to further verify optimization the accuracy with of the diffsimulationerent tools results rather. thanTherefore, expensive in order fabrication. to shorten However, the production they did cycle not fabricate and obtain specific a pH devices sensor towith verifyhigh the sensitivity, accuracy of fast the response simulation, low results. cost and Therefore, suited in for order detect to shortenmicro solution the production, we decided cycle and to use obtainsimulation a pH sensor software with to high design sensitivity, devices, fast analyze response, the low influence cost and of suited structure for anddetect size micro parameters solution, on wedevice decided performance, to use simulation and optimize software device to design structure devices, and analyze parameters the influencebefore processing. of structure and size parametersIn this on work device, we performance, first designed and a double optimize gate device FET device structure based and on parameters MOX. Then, before we use processing.d SILVACO TCADIn this simulation work, we firstsoftware designed to analyze a double and gate to FETcompare device the based electrical on MO characteristicsX. Then, we used of FET SILVACO devices TCADwith simulation different sensitive software film to analyze materials, and oxide to compare nanomaterials the electrical and characteristics channel size. ofWe FET further devices optimize with d difftheerent structure sensitive and film size materials, of the FET oxide device nanomaterials designed. The and feasibility channel size.of the We simulation further optimized ISFET structure the structurewas verified and size by of comparing the FET device the electricaldesigned. characteristics The feasibility of of the simulation fabricated ISFET ISFET structure device and was the verifiedsimulation by comparing device. Furthermore, the electrical characteristicscommercial pH of the solution fabricated was ISFETused to device test theand sensitivity the simulation of the device.prepared Furthermore, ISFET. Fin commercialally, it waspH used solution to detect was p usedH changes to test of the the sensitivity solution ofcaused the prepared by the hydrogen ISFET. Finally,peroxide it was oxidation used to reaction detect pH with changes horseradish of the solutionperoxidase caused to verify by the its hydrogen effectiveness peroxide and sensitivity oxidation. reaction with horseradish peroxidase to verify its effectiveness and sensitivity. 2. Structure of Device and Simulation 2. Structure of Device and Simulation The nanochannel FET was simulated by SILVACO TCAD. The cross-section of the In2O3 The nanochannel FET was simulated by SILVACO TCAD. The cross-section of the In O nanobelt nanobelt FET is shown in Figure 1a. The parameters of the nanobelt FET are shown in2 Table3 1. Figure FET is shown in Figure1a. The parameters of the nanobelt FET are shown in Table1. Figure1b 1b shows the 3D model of the In2O3 nanobelt device prepared through the simulation. Si was used as shows the 3D model of the In2O3 nanobelt device prepared through the simulation. Si was used as the the substrate, the insulating layer was Si3N4, the channel material was composed of the In2O3 nanobelt, substrate, the insulating layer was Si N , the channel material was composed of the In O nanobelt, thickness was 50 nm, w/L ratio was 39, and4 Cr/Au was used as the source–drain electrode2 material.3 thickness was 50 nm, w/L ratio was 9, and Cr/Au was used as the source–drain electrode material.

(a) (b)

FigureFigure 1. In1.2 InO32Onanobelt3 nanobelt ﬁeld-e fieldﬀ-ecteffect transistor transistor (FET): (FET (a):) ( FETa) FET cross-section cross-section of Inof2 OIn32Onanobelt3 nanobelt and and (b )(b) FETFET 3D 3D model model of Inof2 InO32Onanobelt.3 nanobelt.

TableTable 1. Parameters 1. Parameters in thein the simulation. simulation.

ParametersParameters In 2O3In2O3 Si3NSi43N4 SiSi Gate Gate permittivitypermittivity 3.7 3.7 7.57.5 11.811.8 11.8 11.8 thicknessthickness 50 nm50 nm 50 nm50 nm 600 nmnm 30 30nm nm length 400 nm 1.2 µm 1.2 µm 1.2 µm length 400 nm 1.2 μm 1.2 μm 1.2 μm

Sensors 2020, 20, 6921 4 of 16

3. Theoretical Analysis

3.1. Threshold Voltage Under normal conditions, the electric ﬁeld generated by a gate voltage controls the generation of carriers in the channel region. The threshold voltage (VT) of the device is deﬁned as the gate–source voltage when the semiconductor surface at the source end of the channel begins to be strongly inverted. At this time, it will experience a state where the surface electron concentration is equal to the hole concentration and the device is in a critical conduction state. According to the relationship between the gate–source voltage and the surface potential, the VT can be expressed as follows:

QOx QB VT = φCS + φS , (1) − Cox − Cox where φCS is the work function potential difference between the chemical film and semiconductor. φS is the surface potential of semiconductor, while QOx is the effective charge surface density of the oxide layer. Cox is the gate oxide capacitance per unit area and QB is the charge surface density of the depletion layer.

3.2. Source–Drain Current The current Equation of the FET shows the relationship between drain current and gate voltage and drain voltage. The conduction state of the device is described as follows. The voltage VDS is set to a very small value, and the electric ﬁeld intensity in the channel is assumed to be much lower than the velocity saturation electric ﬁeld. The source–drain current, IDS, can be expressed as follows: µnCoxW 1 2 I = (V VT)V V (non-saturated region), (2) DS L GS − DS − 2 DS

µnCoxW h 2i I = (V VT) (saturated region), (3) DS 2L GS − where µn is the carrier mobility while Cox is the gate oxide capacitance per unit area; VGS represents the gate–source voltage and VDS is the source–drain voltage; w/L stands for the channel width length ratio; VT is the threshold voltage. In the unsaturated region, when VDS is very small, Equation (2) can be simpliﬁed as follows:

µnCoxW I = (V VT)V , (4) DS L GS − DS At this time, a relatively uniform conductive channel is formed from the source to the drain, and the integral channel is equivalent to a resistance value, which is proportional to a resistance of 1 (VGS–VT)− . A very large value of the gate–source voltage, VGS, can result in small resistance. The current passing through the channel increases linearly with VDS, so the characteristic curve in the work area becomes linear. In the linear region, the transconductance of the device is deﬁned as follows:

∂I W g = DS = µ C V , (5) m n ox DS ∂VGS VDS L

As V increases to VDsat = V VT, the inversion charge Q = 0 of drain end reaches to 0. This DS GS − i means that the drain end cannot form an inversion layer, and the channel is clamped at the drain end. With the increase in VDS, the pinch point gradually moves from drain to source, and the increased voltage falls in the pinch oﬀ area between the pinch point and drain, forming a strong electric ﬁeld region. After the channel is clamped, there is still a conductive channel between the source and the Sensors 2020, 20, 6921 5 of 16

pinch point, because the voltage in the channel is basically maintained at VDsat. When VDsat is constant, the drain current remains unchanged and reaches the saturation value IDsat, where we get the following:

µnCoxW h 2i IDsat = (V VT) , (6) 2L GS − In the saturated region, the following relation exists:

W gm = µnCox(V VT), (7) L DS − In ideal conditions, the transconductance in the saturated region is 0. However, due to the shortening of the eﬀective channel length, there is a non-zero channel conductance in the saturated region.

3.3. Subthreshold Swing The subthreshold swing (s) is an important parameter for switching operations. The gate voltage required to increase the drain current by an order of magnitude is defined. The swing reflects the transition steepness of the current from the off state to the on state. This corresponds specifically to the reciprocal of the slope of the subthreshold line segment in the device transfer characteristic curve using semilogarithmic coordinates, which can be expressed as follows:

dV S = GS , (8) d(log IDS)

In current development cycles, with intent to develop point-of-care test (POCT) equipment [34], whose power supply module is only about 5 V, the characteristic size of the device is constantly shrinking. It requires the device to work under low voltage and lower the threshold voltage, which is convenient for us to use ISFET for portable detection. In addition, in order to ensure a certain response speed, it is necessary to produce a steep subthreshold slope to reduce the oﬀ-state current.

4. Results and Discussion The ATLAS device simulation tool with diﬀerent parameters was used to study the performance of the proposed In2O3 nanobelt ISFET, and the optimal device structure and parameters were thereby determined. The models used to the device simulation include the concentration dependent mobility model, Shockley–Read–Hall (SRH) composite model and Fermi Dirac statistical model.

4.1. Description of Electrical Characteristics of Devices First, the output characteristics of the device were tested. As shown in Figure2a, the applied gate voltage was varied. The source–drain current varied with increase in the source–drain voltage. The gate voltage value ranged from 0.5 to 1 V with a step size of 0.1 V. The source–drain current changes as the source–drain voltage was varied from 0 to 2 V. It is revealed that large applied gate voltages can result in large corresponding source–drain currents. This follows the drain current analyzed in the previous section. The source–drain current can be enhanced with increase in gate voltage, after the source–drain voltage reaches a certain value. The source–drain current can saturate, which is consistent with the theory. When VGS = 1.0 V, the source–drain current can reach 100 µA. Figure2b shows the transfer characteristics and transconductance of the device, which clearly indicates the gate voltage’s ability to regulate source and drain current. Setting the source–drain voltage to 2.5 V, and scanning the gate voltage from 1 to 1 V, we can obtain the transfer characteristic curve, and draw − the transconductance curve according to the transconductance Equation (8) analyzed in the previous section. Through the built-in data extraction function in SILVACO TCAD, the threshold voltage can be easily obtained as 0.24 V as V = 2.5 V. In addition, according to the transfer characteristic curve, − DS Sensors 2020, 20, 6921 6 of 16

the device-switching current ratio can reach as high as 108. Figure2c shows the semilogarithmic curve of the relationship between the source and drain current of the device under the condition of VDS = 2.5 V. According to the theoretical analysis in the previous section, when the drain current rose by an order of magnitude, that is, from 0.01 to 0.1 pA, the gate–source voltage changed from 0.95 to 0.87 V. It can be concluded in terms on Equation (8) that the subthreshold swing was 81.38 − − mV/dec, which was slightly higher than theoretical value. This value was a result obtained under an Sensorsideal simulation2020, 20, 6921 environment. Realistic devices may not achieve such good performance. Actually,6 of 16 the subthreshold swing of the device fabricated in this work was 143.19 mV/dec, which would be described in Section 4.4.

-4 5x10-8 1.2x10 2.4x10-7 VDS=2.5V -4 1.0x10 4x10-8 2.0x10-7

-5 8.0x10 1.6x10-7 3x10-8

-5 6.0x10 1.2x10-7 2x10-8 4.0x10-5 8.0x10-8 V =0.5V V =0.6V GS GS 1x10-8 2.0x10-5 V =0.7V V =0.8V 4.0x10-8 GS GS Transconductance Drain-Source Current (A) VGS=0.9V VGS=1.0V Drain-Source Current (A) 0.0 0 0.0 0.0 0.5 1.0 1.5 2.0 -1.0 -0.8 -0.6 -0.4 -0.2 0.0 Drain-Source Voltage (V) Gate-Source Voltage (V)

(a) (b)

-7

-8

-9 ) -10 DS I -11

Log ( -12

-13

-14

-15 -1.0 -0.8 -0.6 -0.4 -0.2 0.0 Gate-Source Voltage (V)

(c)

FigureFigure 2. 2. InIn2O23O nanobelt3 nanobelt FET FET characteristics characteristics:: (a) d (evicea) device output output characteristic characteristic curve curve;; (b) the ( bblack) the curve black iscurve the transfer is the transfer characteristic characteristic curve curvecorresponding corresponding to the toleft the coordinate left coordinate,, and the and green the green curve curve is the is transconductancethe transconductance curve curve corresponding corresponding to the to the right right coordin coordinate;ate; (c) ( cs)emilogarithmic semilogarithmic curve curve of of the the relationshiprelationship between between source source–drain–drain current current and gate gate–voltage–voltage (푉V퐷푆DS==22.5.5 V V).) 4.2. Material Performance Analysis

4.2.4.2.1. Material Material Performance Analysis Analysis of a Gate Dielectric Layer Figure3a shows di fferent gate dielectric materials at V = 0.5 V. From the results, as the 4.2.1. Material Analysis of a Gate Dielectric Layer GS source–drain voltage was scanned from 0 to 2 V, the gate dielectric material Si3N4 had a more defined linearFigure region 3a andshows saturation different current gate dielectric than SiO materials2. This is at because 푉퐺푆 = 0 the.5 V. dielectric From the constantresults, as of the SiO source2 is 3.9,– drainwhile voltage the dielectric was scanned constant from of Si 03 toN 42 canV, the reach gate 7.5 dielectric [35,36]. Furthermore,material Si3N4 itsha bandgapd a more widthdefined is linear lower regionthan that and of saturation SiO2. Therefore, current than the large SiO2. capacitanceThis is because value the per dielectric unit area constant of Si3 Nof4 SiOcan2 resultis 3.9, while in a large the dielectriccorresponding constant source–drain of Si3N4 can current. reach 7.5 Figure [35,336b] shows. Furthermore, the application its bandgap of the width samesource–drain is lower than voltage that of SiO(VDS2. Therefore,= 2.5 V). The the semilogarithmiclarge capacitance curves value of per drain unit current area of and Si3N gate4 can voltage result ofin dia largefferent corresponding gate dielectric source–drain current. Figure 3b shows the application of the same source–drain voltage (푉퐷푆 = 2.5 V). The semilogarithmic curves of drain current and gate voltage of different gate dielectric materials can be calculated using the theory in the previous section. When the gate dielectric material was SiO2, the subthreshold swing of the device was 100.60 mV/dec, which was larger than that when the gate dielectric material was Si3N4, leading to slow work rate in the subthreshold region. As a sensitive membrane material, SiO2 has some inherent disadvantages. It is subject to diffusion of protons or hydrogen, and source–drain current, resulting in serious drift and deterioration of ISFET based on SiO2 [37–39]. Compared with other high-k sensitive film materials, Si3N4 has many advantages. For instance, it is free from interference impurities, the thickness of the film can be controlled, and no transition layer is required because of favorable conditions in the Sensors 2020, 20, 6921 7 of 16 Sensors 2020, 20, 6921 7 of 16 materialsinterface between can be calculated Si3N4 and using substrate the theory Si [40– in42 the]. Therefore, previous section.Si3N4 is preferred When the as gate the dielectric sensitivematerial layer to wasobtain SiO better2, the device subthreshold performance. swing of the device was 100.60 mV/dec, which was larger than that when the gate dielectric material was Si3N4, leading to slow work rate in the subthreshold region.

2.0x10-7 -8 Si3N4 Si3N4 SiO2 SiO2

1.5x10-7 -10

) DS

-7 I

1.0x10 ( -12 Log 5.0x10-8 -14

Drain-Source Current (A) Current Drain-Source 0.0 -16 0.0 0.5 1.0 1.5 2.0 -1.0 -0.9 -0.8 -0.7 -0.6 -0.5 -0.4 Gate-Source Voltage (V) Drain-Source Voltage (V) (a) (b)

Figure 3. 3. CharacteristicsCharacteristics of of di ff differenterent gate gate dielectric dielectric materials: materials (a) output: (a) o characteristicutput characteristic curve of curve different of gatedifferent dielectric gate materials dielectric in VGS materials= 0.5 V; ( inb) di푉ff퐺푆erent= 0. gate5 V; dielectric (b) different materials gate semilogarithmic dielectric materials curve of drainsemilogarithmic current versus curve gate of voltagedrain current at VDS versus= 2.5 V.gate voltage at 푉퐷푆 = 2.5 V.

4.2.2.As Analysis a sensitive of Semiconductor membrane material, Material SiO 2 has some inherent disadvantages. It is subject to diffusion of protons or hydrogen, and source–drain current, resulting in serious drift and deterioration of Zinc oxide (ZnO) and indium oxide (In2O3) are widely used as channel materials for electronic ISFET based on SiO [37–39]. Compared with other high-k sensitive film materials, Si N has many devices due to their2 chemical stability and high carrier mobility [43,44]. As a natural 3self4 -doped n- advantages. For instance, it is free from interference impurities, the thickness of the film can be type semiconductor, it is easy to crystallize, which is conducive to obtain high carrier mobility films, controlled, and no transition layer is required because of favorable conditions in the interface between and can be deposited by various coating methods. The difference in process technology also affect Si N and substrate Si [40–42]. Therefore, Si N is preferred as the sensitive layer to obtain better device3 4 performance. Taking this into consideration,3 4 we used Athena to form the structure under the device performance. same process technology and conditions, and then compared the electrical characteristics by Atlas. 4.2.2.Figure Analysis 4a,b, respectively of Semiconductor, shows the Material output and transfer characteristics of the device when the channel materials were ZnO and In2O3. The output characteristic curve was obtained by setting the gate voltageZinc to oxide0.5 V and (ZnO) scanning and indium the source oxide–drain (In2O volta3) arege widely from 0 used to 2 V. as The channel transfer materials characteristic for electronic curve deviceswas obtained due to by their setting chemical the source stability–drain and voltage high at carrier 2.5 V mobilityand scanning [43,44 the]. gate As a voltage natural from self-doped −1 to 0 n-type semiconductor, it is easy to crystallize, which is conducive to obtain high carrier mobility films, V. It can be concluded that compared with ZnO, the In2O3 film can obtain a clearer source–drain and can be deposited by various coating methods. The difference in process technology also affect current, smaller off-state current and has better performance. The on/off current ratio of In2O3 was device performance. Taking this into consideration, we used Athena to form the structure under the 108 while ZnO was 105. In2O3 also has lower process temperature and higher field mobility [45–47], same process technology and conditions, and then compared the electrical characteristics by Atlas. so we used In2O3 as the channel material in device fabrication. Figure4a,b, respectively, shows the output and transfer characteristics of the device when the channel materials were ZnO and In2O3. The output characteristic curve was obtained by setting the gate voltage to 0.5 V and scanning the source–drain voltage from 0 to 2 V. The transfer characteristic curve was obtained by setting the source–drain voltage at 2.5 V and scanning the gate voltage from 1 to 0 V. − It can be concluded that compared with ZnO, the In2O3 film can obtain a clearer source–drain current, 8 smaller off-state current and has better performance. The on/off current ratio of In2O3 was 10 while 5 ZnO was 10 . In2O3 also has lower process temperature and higher field mobility [45–47], so we used In2O3 as the channel material in device fabrication.

Sensors 2020, 20, 6921 8 of 16 Sensors 2020, 20, 6921 8 of 16

2.0x10-7 5x10-8 In2O3 In2O3 ZnO ZnO 4x10-8 -7 1.5x10 2.0x10-9

-9 5.0x10 3x10-8 1.5x10-9

-9 -7 4.0x10 1.0x10 1.0x10-9 -9 3.0x10 2x10-8 5.0x10-10 2.0x10-9 -8 -9 5.0x10 1.0x10 -8 (A) Current Drain-Source 0.0 1x10 -1.0 -0.8 -0.6 -0.4 -0.2 0.0 Drain-Source Current (A) Current Drain-Source 0.0 Gate-Source Voltage (V)

0.0 0.5 1.0 1.5 2.0 Drain-Source current (A) current Drain-Source Drain-Source Current (A) Current Drain-Source Drain-Source Gate (V) 0.0 0 0.0 0.5 1.0 1.5 2.0 -1.0 -0.8 -0.6 -0.4 -0.2 0.0 Drain-Source Voltage (V) Gate-Source Voltage (V)

(a) (b)

FigureFigure 4. CharacteristicsCharacteristics of of different different channel channel materials: materials: ( (aa)) o outpututput characteristic characteristic curve curve of of different different channelchannel mat materialserials in in 푉V퐺푆GS==00.5.5 V V;; (b (b) )transfer transfer characteristic characteristic curve curve of of different different channel channel materials materials at at 푉V퐷푆DS==22.5.5 V V..

4.3.4.3. Influence Inﬂuence of of Channel Channel Parameters Parameters on on Device Device Performance Performance

ThroughThrough comparison of device performance between ZnOZnO andand InIn22O33, In 2OO33 waswas finally finally selected selected asas th thee channel material. In In order order to to explore explore the the influence influence of the thickness and length of the InIn22O3 channelchannel layer layer on on the the performance performance of of the the FET, FET, a a range range of of values values were were simulated. simulated. First, First, five five thicknesses thicknesses,, namelynamely 0.02,0.02, 0.05,0.05, 0.1, 0.1, 0.12 0.12 and and 0.15 0.1µ5m, μm were, were selected selected to compare to compare the output the output characteristics characteristics and transfer and transfercharacteristics characteristics of the device. of the Whendevice. testing When thetesting output the characteristics,output characteristics, the gate the voltage gate voltage was set was to 0.5 set V, towhile 0.5 the V, source–drainwhile the source current–drain was current scanned was from scanned 0 to 2 V. Whenfrom 0 testing to 2 V. the When transfer testing characteristics, the transfer the source–drain current was set to 2.5 V, and the gate voltage was scanned from 1 to 0 V. The simulation characteristics, the source–drain current was set to 2.5 V, and the gate voltage− was scanned from −1 toresults 0 V. The are simulation illustrated results in Figure are5 illustrateda,b. Moreover, in Figure the comparison5a,b. Moreover, of subthreshold the comparison swing of subthreshold at di fferent swingthicknesses at different are shown thicknesses in Table 2are. From shown the in Figure Table5a, 2. it From is clear the that Figure the source–drain 5a, it is clear current that the increased source– drainwith ancurrent increasing increased thickness with of an the increasing In2O3 channel. thickness As shownof the In in2O Figure3 channel.5b, the As turn-o shownff currentin Figure increased 5b, the turnsignificantly-off current when increased the thickness significantly reached when more the thanthickness 0.05 reachedµm. If the more channel than 0.05 thickness μm. If the is too channel large, thicknesscarriers still is too flow large, under carriers the action still flow of the under source–drain the action voltageof the source when–drain the device voltage is turnedwhen the off devicewhich isresulting turned off in awhich larger resulting leakage current.in a larger Moreover, leakage current. as can be Moreover, seen from as Table can2 be, the seen larger from the Table thickness 2, the largerof the the In2 Othickness3 channel, of the In greater2O3 channel, the device the greater subthreshold the device swing subthreshold and the smaller swing theand turn-on the smaller and theturn-o turnff-rate.on and Therefore, turn-off rate. considering Therefore, device considering performance device and performance manufacturing and processmanufacturing in combination, process µ inthe combination, thickness of thethe Inthickness2O3 channel of the layer In2O was3 channel defined layer as 0.05 was m.defined In addition, as 0.05 whenμm. In the addition, channel when width theis constant, channel the width diff erence is constant, in channel the difference length will in also channel cause lengthchanges will to device also cause performance. changes As to device shown performance.in Figure6a, theAs outputshown characteristicsin Figure 6a, the of output di fferent characteristics channel lengths of different 0.4 and channel 0.8 µm lengths were measured 0.4 and 0.8when μm thewere gate measured voltage when was set the to gate 0.5 voltage V. It is clearwas set that to when0.5 V. theIt is channelclear that width when is the constant, channela width short ischannel constant, length a short results channel in large length source–drain results current. in large This source also–drain satisfies current. the relationship This also satisfiesbetween the the relationshipsource–drain between current the and source the aspect–drain ratio current analyzed and the in theaspect previous ratio analyzed section, i.e.,in the the previous larger the section, aspect i.e.,ratio, the the larger greater the the aspect channel ratio length., the greater Fast carrier the channel movement length. rate Fast results carrier in largemovement source–drain rate results current. in largeFigure source6b shows–drain the current. transfer Figure characteristics 6b shows of ditheff erenttransfer channel characteristics lengths when of different the source–drain channel lengths voltage whenwas 2.5 the V. source The threshold–drain vol voltagestage was of 2.5 the V. two The were threshold similar. voltages The large of the channel-width-to-length two were similar. The large ratio channelresulted-width in a large-to-length switching ratio current resulted ratio, in a indicating large switching strong capabilitycurrent ratio, of the indicating device to strong regulate capability current. of the device to regulate current.

Sensors 2020, 20, 6921 9 of 16

Sensors 2020, 20, 6921 9 of 16 Sensors 2020, 20, 6921 9 of 16 -7 2.5x10 10-8

2.0x10-7 10-10 -7 1.5x102.5x10-7 10-8 10-12 1.0x102.0x10-7 -7 -10 In2O3 channel thickness 0.02μm 10 In O channel thickness 0.02μm 10-14 2 3 -8 -7 In O channel thickness 0.05μm 5.0x101.5x10 2 3 In2O3 channel thickness 0.05μm In2O3 channel thickness 0.1μm -12 In O channel thickness 0.1μm 10-1610 2 3 -7 In2O3 channel thickness 0.12μm 1.0x100.0 In2O3 channel thickness 0.12μm Drain-Source Current (A) Current Drain-Source In O channel thickness 0.15μm 2 3In2O3 channel thickness 0.02μm In O In channelO channel thickness thickness 0.15μm 0.02μm Drain-Source Current (A) Current Drain-Source 10-1810-14 2 3 2 3 -8 0.0 0.5 In1.0O channel1.5 thickness2.0 0.05μm 5.0x10 2 3 -1.0 -0.8 -0.6 In2O3-0.4 channel-0.2 thickness0.0 0.05μm In2O3 channel thickness 0.1μm In O channel thickness 0.1μm Drain-Source Voltage (V) 10-16 Gate-Source2 3Voltage (V) In2O3 channel thickness 0.12μm 0.0 In2O3 channel thickness 0.12μm Drain-Source Current (A) Current Drain-Source In2O3 channel thickness 0.15μm In O channel thickness 0.15μm Drain-Source Current (A) Current Drain-Source 10-18 2 3 0.0 (0.5a) 1.0 1.5 2.0 -1.0 -0.8 (b-0.6) -0.4 -0.2 0.0 Drain-Source Voltage (V) Gate-Source Voltage (V) Figure 5. Characteristics of different channel thickness: (a) output characteristic curve of different channel thickness; (b) transfer characteristic curve of different channel thickness. (a) (b)

FigureFigure 5. Characteristics5. CharacteristicsTable of diof2.ff Subthresholddifferenterent channel channel swing thickness: thickness: under ( adifferent) ( outputa) output thickness. characteristic characteristic curve curve of diofff differenterent channelchannel thickness; thickness (b); ( transferb) transfer characteristic characteristic curve curve of di offf erentdifferent channel channel thickness. thickness. Thickness (μm) 0.02 0.05 0.1 0.12 0.15 SubthresholdTable slope 2. (mSubthresholdV/dec) 67.66 swing under81.38 di fferent170 thickness..14 273.25 535.03 Table 2. Subthreshold swing under different thickness.

Thickness (Thicknessµm) (μm) 0.020.02 0.050.05 0.10.1 0.12 0.12 0.15 0.15 SubthresholdSubthreshold slope (mV/dec) slope (mV/dec 67.66) 67.66 81.3881.38 170.14170.14 273 273.25.25 535.03 535.03

1.2x10-4 3.0x10-5 In2O3 channel length 0.4 μm 1.0x10-4 2.5x10-5 In2O3 channel length 0.8 μm

-4 -5 8.0x101.2x10-5 2.0x103.0x10-5 In2O3 channel length 0.4 μm -4 -5 6.0x101.0x10-5 1.5x102.5x10-5 In2O3 channel length 0.8 μm

-5 -5 4.0x108.0x10-5 1.0x102.0x10-5

-5 6.0x10-5 -5 5.0x101.5x10-6 2.0x10 In2O3 channel length 0.4μm

-5 In2O3 channel length 0.8μm -5 Drain-Source Current (A) Current Drain-Source Drain-Source Current (A) Current Drain-Source 4.0x100.0 1.0x100.0 0.0 0.5 1.0 1.5 2.0 -1.0 -0.8 -0.6 -0.4 -0.2 0.0 -5 -6 2.0x10 Drain-Source In O Voltage channel length (V) 0.4μm 5.0x10 Gate-Source Voltage (V) 2 3

In2O3 channel length 0.8μm Drain-Source Current (A) Current Drain-Source Drain-Source Current (A) Current Drain-Source 0.0 0.0 0.0 0.5(a) 1.0 1.5 2.0 -1.0 -0.8(b) -0.6 -0.4 -0.2 0.0 Drain-Source Voltage (V) Gate-Source Voltage (V) Figure 6. 6.Characteristics Characteristics of of di ff differenterent channel channel lengths: lengths: (a) output (a) output characteristic characteristic curve of curve different of different channel channel lengths; (b) transfer characteristic curve of different channel lengths. lengths; (b) transfer characteristic(a) curve of different channel lengths. (b)

4.4. Device Figure Performance 6. Characteristics VerificationVerification of different channel lengths: (a) output characteristic curve of different channel lengths; (b) transfer characteristic curve of different channel lengths. According toto abovementionedabovementioned simulationsimulation andand analysisanalysis results,results, thethe InIn22OO33 nanobelt ISFET basedbased on the proposed proposed structure structure was was fabricated fabricated by by using using the the processing processing flow flow shown shown in Figure in Figure 7. First,7. First, Si3N4 4.4. Device Performance Verification Sifilm3N 4wasfilm grown was grown on Si substrate on Si substrate by radio by frequency radio frequency sputtering. sputtering. Then, a Then, photoresist a photoresist was coated was coatedon the onSi3N the4 film SiAccording3 Nfor4 formingfilm to for abovementioned source forming and source drain simulation andmasks drain after masksand photolithography. analysis after photolithography.results, Next, the In metal2O3 nanobelt was Next, deposited metal ISFET was basedby depositedelectronon the beamproposed by electron evaporation. structure beam evaporation.was After fabricated peeling After offby using the peeling ph theotoresist, processing off the photoresist,we flow formed shown wethe in formed source Figure andthe7. First, source drain. Si3 N4 andAnotherfilm drain. was photoresist Another grown on photoresist wasSi substrate coated was by continuously coated radio frequency continuously,, to create sputtering. to thecreate nanobelt Then, the nanobelt a photoresist mask. mask. Finally, was Finally, coated In2O In3 was2onO3 the wasdepositedSi deposited3N4 film by for magnetron by forming magnetron source sputtering sputtering and drain andand masks the the nanobelt after nanobelt photolithography. was was formed, formed, resultingNext, resulting metal in in was fabrication deposited of by nanostructuredelectron beam field-efield evaporation.-effectffect transistors. transistors. After peeling The The structure structure off the of ofph theotoresist, ISFET we sensing formed region the is source illustratedillustrated and drain. in FigureAnother8 8.. TheThe photoresist bandwidthbandwidth wasratioratio coated ofof InIn2O continuously3 isis 9 9 nm, nm, and and, its itsto thickness thickness create the is is 50 nanobelt50 nm. nm. mask. Finally, In2O3 was deposited by magnetron sputtering and the nanobelt was formed, resulting in fabrication of nanostructured field-effect transistors. The structure of the ISFET sensing region is illustrated in Figure 8. The bandwidth ratio of In2O3 is 9 nm, and its thickness is 50 nm.

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photoresist photoresist Si Si

Si3N4 film was grown on Si Source and drain masks Source and drain were Nanobelt mask was formed Nanobelt was formed by SubstrateSi3N4 film by was RF grown sputtering on Si weSource re formed and drainby coating masks formedSource by and electron drain beam were byNanobelt photolithography mask was formed MagnetronNanobelt was sputtering formed by Substrate by RF sputtering we re formed by coating formed by electron beam by photolithography Magnetron sputtering Photoresist on Si3N4 film evaporation Photoresist on Si3N4 film evaporation

Figure 7. Preparation process of pH-sensitive ion-sensitive field-effect transistor (ISFET). FigureFigure 7. 7.Preparation Preparation process process of of pH-sensitive pH-sensitive ion-sensitive ion-sensitive ﬁeld-e field-ﬀeffectect transistor transistor (ISFET). (ISFET).

Figure 8. Electron microscopy of ISFET sensing area.area. Figure 8. Electron microscopy of ISFET sensing area. As shownshown in FigureFigure9 9aa,b,,b, the the output output andand transfer transfer characteristicscharacteristics ofof thethe devicedevice wereweredetected detected forfor As shown in Figure 9a,b, the output and transfer characteristics of the device were detected for thethe preparedprepared InIn22O3 nanobelt ISFET through a semiconductor parametric test system (PDA, FS380),FS380), the prepared In2O3 nanobelt ISFET through a semiconductor parametric test system (PDA, FS380), whichwhich waswas consistentconsistent withwith thethe simulationsimulation results.results. When the source–drainsource–drain voltage roserose to aa certaincertain which was consistent with the simulation results. When the source–drain voltage rose to a certain value,value, thethe source–drainsource–drain currentcurrent reachedreached saturation.saturation. According toto thethe transfer characteristic curve,curve, the value, the source–drain current reached saturation. According to the transfer characteristic curve, the subthresholdsubthreshold swing swing of of the the actual actual device device can becan calculated be calculated by Equation by Equation (8) as 143.19 (8) as mV 143.19/dec. m InV addition,/dec. In subthreshold swing of the actual device can be calculated by Equation (8) as 143.19 mV/dec. In standardaddition, commercial standard commercial pH (pH 6–10) pH solutions (pH 6– were10) solutionsused to measure were used the transfer to measure characteristics. the transfer The addition, standard commercial pH (pH 6–10) solutions were used to measure the transfer detectioncharacteristics. equipment The detecti is shownon equi in Figurepment 10 isa, shown where in the Figure reaction 10a cell, where was the 2 mL. reaction The ISFET cell was was 2 ﬁxed mL. characteristics. The detection equipment is shown in Figure 10a, where the reaction cell was 2 mL. underThe ISFET the container.was fixed unde Ther Ag the/AgCl container reference. The Ag/AgCl electrode reference was placed electrode in the was solution placed as in the the topsolution gate. The ISFET was fixed under the container. The Ag/AgCl reference electrode was placed in the solution Figureas the top10b gate. shows Figure the DG10b operatingshows the method.DG operating Biased method. voltage Biased VGS = voltage4 V was VGS applied = 4 V was to the applied bottom to as the top gate. Figure 10b shows the DG operating method. Biased voltage VGS = 4 V was applied to Sithe substrate bottom Si as substrate the back gateas the while back the gate top while Ag/AgCl the top reference Ag/Ag electrodeCl reference was electrod grounded.e was The grounded voltage. the bottom Si substrate as the back gate while the top Ag/AgCl reference electrode was grounded. betweenThe voltage the between drain and the source drain V andDS was source set V toDS 1 was V. We set added to 1 V.a We 1 mL added solution a 1 m withL solution diﬀerent with pH different values The voltage between the drain and source VDS was set to 1 V. We added a 1 mL solution with different respectively.pH values respectively. The measurement The measurement results are shown results in are Figure shown 11 a. in From Figure the 11 results,a. From the the source–drain results, the pH values respectively. The measurement results are shown in Figure 11a. From the results, the currentsource– graduallydrain current increased gradually with increase increased inwit pHh increase value. Taking in pH thevalue. gate–source Taking the voltage gate– correspondingsource voltage source–drain current gradually increased with increase in pH value. Taking the gate–source voltage tocorresponding the source–drain to the current source of 8–drainµA, as current shown in of Figure8 μA, 11 asb, shown there was in a Figure linear relationship 11b, there was between a linear the corresponding to the source–drain current of 8 μA, as shown in Figure 11b, there was a linear gate–sourcerelationshipvoltage between and the pH gate from–source 6 to 10, voltage and the and regression pH from Equation 6 to 10, and was Vthe (voltage) regression= 0.088125Equation pH was+ relationship2 between the gate–source voltage and pH from 6 to 10, and the regression− Equation was 1.55375V (voltage (R )= = 0.98635).−0.088125 The pH calculated + 1.55375 sensitivity(R2 = 0.98635 of the). The In2 calculatedO3 nanobelt sensitivity ISFET can of reach the In 88.1252O3 nanobelt mV/pH. V (voltage) = −0.088125 pH + 1.55375 (R2 = 0.98635). The calculated sensitivity of the In2O3 nanobelt InISFET order ca ton furtherreach 88.125 describe mV/pH. the sensitivity In order performance to further describe of the pH the sensor, sensitivity take the performance relationship of between the pH ISFET can reach 88.125 mV/pH. In order to further describe the sensitivity performance of the pH thesensor, drain–source take the relationship current and between pH when the the drain gate–source–source current voltage and was pH 1.2 when V. As the shown gate–source in Figure voltage 11c, sensor, take the relationship between the drain–source current and pH when the gate–source voltage thewas drain–source 1.2 V. As shown current in had Figure a linear 11c, relationship the drain– withsource pH current between ha 6–10.d a li Thenear regression relationship equation with was pH was 1.2 V. As shown in Figure2 11c, the drain–source current had a linear relationship with pH Ibetween (current) 6=–10.6.55 The pH regression18.42 (R equation= 0.99534) was and I the (current) sensitivity = 6.55 was p 6.55H −µ 18.42A/ pH. (R It2 can= 0.99 be534 seen) and that the between 6–10. The − regression equation was I (current) = 6.55 pH − 18.42 (R2 = 0.99534) and the preparedsensitivity In was2O3 nanobelt6.55 μA/ ISFETpH. It cancan detect be seen the that change the ofprepared pH value In2 ofO3 trace nanobelt solution. ISFET can detect the sensitivity was 6.55 μA/ pH. It can be seen that the prepared In2O3 nanobelt ISFET can detect the change of pH value of trace solution. change of pH value of trace solution.

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Sensors 2020, 20, 6921 11 of 16 Sensors 2020, 20, 6921 11 of 16 Sensors 202014, 20, 6921 100 11 of 16 VDS=-0.5V

1412 10080 14 100 VDS=-0.5V V =-0.5V 1210 8060 DS 12 80 108 6040 10 60

8 6 Vgs=-0.5V Vgs=-0.6V 4020 8 Vgs=-0.7V Vgs=-0.8V 40

Vgs=-0.9V Vgs=-1V Drain-Source Current (nA) Current Drain-Source Drain-Source Current (μA) Current Drain-Source 6 4 Vgs=-0.5V Vgs=-0.6V 200 -4 -3 -2 -1 0 0.0 0.5 1.0 1.5 2.0 6 Vgs=-0.7V Vgs=-0.5V Vgs=-0.8V Vgs=-0.6V 20

Gate-Source Vgs=-0.9V Vgs=-0.7V Voltage Vgs=-1V Vgs=-0.8V(V) Gate-Source Voltage (V) Drain-Source Current (nA) Current Drain-Source Drain-Source Current (μA) Current Drain-Source 4 0 Vgs=-0.9V Vgs=-1V

-4 -3 -2 -1 0 0.0 0.5 1.0 1.5 2.0 Drain-Source Current (nA) Current Drain-Source Drain-Source Current (μA) Current Drain-Source 4 0 -4 Gate-Source-3 (a)-2 Voltage-1 (V) 0 0.0 Gate-Source0.5 (b1.0) Voltage1.5 (V) 2.0 Gate-Source Voltage (V) Gate-Source Voltage (V) Figure 9. ISFET characteristics of In2O3 nanobelt: (a) ISFET output characteristic curve of In2O3 (a) (b) nanobelt; (b) ISFET transfer(a) characteristic curve of In2O3 nanobelt. (b) Figure 9. ISFET characteristics of In2O3 nanobelt: (a) ISFET output characteristic curve of In2O3 Figure 9. ISFET characteristics of In2O3 nanobelt: (a) ISFET output characteristic curve of In2O3 nanobelt;Figure 9. (bISFET) ISFET characteristics transfer characteristic of In2O3 curvenanobelt: of In2 (Oa)3 nanobelt ISFET output. characteristic curve of In2O3 nanobelt;nanobelt; ((bb)) ISFETISFET transfertransfer characteristiccharacteristic curve curve of of In In22OO33 nanobelt.nanobelt.

(a) (b)

Figure 10. pH detection for micro solution: (a) p hysical map of testing equipment; (b) dual-gate ( DG) (a) (b) mode electrical connection(a) diagram. (b) FigureFigure 10. 10. pHpH detection detection for for micro micro solution solution:: (a (a) )p physicalhysical map map of of testing testing equipment; equipment; ( (bb)) dual dual-gate-gate ( (DG)DG) Figure 10. pH detection for micro solution: (a) physical map of testing equipment; (b) dual-gate (DG) modemode electrical electrical connection connection diagram diagram.. mode electrical connection diagram. 50 pH6 1.1 pH7 5040 pH8 1.0 50 pH6 pH9 1.1 pH7 pH6pH10 1.1 4030 pH8 pH7 1.00.9 40 pH9 pH8 1.0 2 pH10 pH9 R =0.98635 3020 pH10 0.8 30 0.9 0.9 R2=0.98635 2010 0.7 R2=0.98635 20 0.8 0.8

Drain-Source Current (μA) Current Drain-Source 0

10 (V) Voltage Gate-Source 0.0 0.2 0.4 0.6 0.8 1.0 1.2 0.70.6 10 6 7 8 9 10 Gate-Source Voltage (V) 0.7

Drain-Source Current (μA) Current Drain-Source 0 pH 0.0 0.2 0.4 0.6 0.8 1.0 1.2 (V) Voltage Gate-Source 0.6 Drain-Source Current (μA) Current Drain-Source 0 v (V) Voltage Gate-Source 0.0 Gate-Source0.2 0.4 0.6 Voltage0.8 1.0 (V) 1.2 0.66 7 8 9 10 6 7 pH8 9 10 Gate-Source(a) Voltage (V) (b) v pH v (a) Figure 11. Cont. (b) (a) (b)

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35 R2=0.99534 30

20 Drain-Source Current (μA) Current Drain-Source 6 7 8 9 10 pH

(c)

2 3 DS GS FigureFigure 11. 11.In In2OO3 nanobelt nanobelt ISFET ISFET pH pH detection: detection: (a ()Ia)DS I -V-VGS curve curve family family with with pH pH from from 6 6 to to 10; 10; (b ()b linear) linear GS DS curvecurve of of V GSV -pH-pH from from 6 6 to to 10; 10 (;c ()c linear) linear curve curve of of IDS I -pH-pH from from 6 6 to to 10. 10.

WhenWhen the the enzyme enzyme substrate substrate undergoes undergoes oxidation oxidation or or hydrolysis hydrolysis under under the the action action of of the the enzyme, enzyme, − thethe OH OH− concentration concentration in in the the solution solution will will change, change, which which will causewill cause a change a change in pH. in Therefore, pH. Therefore, in order in toorder verify to that verify the devicethat the can devi detectce can the detect pH change the pH of change micro solution of micro furtherly, solution we further usedly the, we hydrogen used the peroxidehydrogen oxidation peroxide reaction oxidation under reaction the catalyze under the of horseradishcatalyze of horseradish peroxidase peroxidase to change theto change pH value the ofpH microvalue solution. of micro The solution reaction. The proceeded reaction proceeded as follows: as follows: HRP − HHRP2O2 → H2O + OH , (9) H O H O + OH−, (9) 2 2 → 2 The 30 U horseradish peroxidase was immobilized on the surface of ISFET and placed at 4 °C for The24 h. 30 Different U horseradish amounts peroxidase of hydrogen was peroxide immobilized (100 onμL, the 200 surface, 300, 400 of and ISFET 500 and μL) placed at a concentration at 4 ◦C for 24of h. 0.1 Di ffmolerent L−1 amounts was added of hydrogen in 0.01 × phosphate peroxide (100 bufferµL, saline 200, 300, (PBS 400), andthe total 500 µ volumeL) at a concentrationwas 1 mL. When of 1 0.1 mol L was added in 0.01 phosphate buffer saline (PBS),− the total volume was 1 mL. When the the hydrogen− peroxide oxidation× reaction proceeded, OH ions were released into the solution, as hydrogenshown in peroxide Equation oxidation (9), and reactionthe pH value proceeded, of the OHsolution− ions increase were releasedd. As the into hydrogen the solution, peroxide as shown content in Equationincrease (9),d, the and drain the pH–source value current of the solutiongradually increased. increased As. The the curve hydrogen is shown peroxide in Figure content 12a. increased, As shown thein drain–source Figure 12b, current the source gradually leakage increased. current The gradually curve is increase shown ind Figurewith the 12a. increase As shown of in the Figure hydrogen 12b, theperoxide source leakage content. current There graduallywas a linear increased relationship with the between increase the of the source hydrogen leakage peroxide current content. and the Therehydrogen was a linear peroxide relationship content between from 100 the to source 500 μL, leakage and current the regression and the hydrogen equation peroxidewas I (current) content = from0.144265 100 toC (hydrogen 500 µL, and peroxide) the regression + 12.83788 equation (R2 = 0.9 was9738 I (current)). The calculated= 0.144265C sensitivity (hydrogen of urea peroxide) detection 2 1 1 + was12.83788 144.26 (R pA= mol0.99738).−1 L−1. The The above calculated experiment sensitivity prove ofd ureathat the detection ISFET wasdeveloped 144.26 in pA this mol work− L −can. Thedetect above the experiment pH change proved caused that by the the ISFET oxidation developed reaction in thisof enzyme work can substrate detect the in pH the change trace solution. caused byBased the oxidation on this reaction conclusion, of enzyme labeling substrate the inantigen the trace or solution. antibody Based with on enzyme this conclusion, and adding labeling the thecorresponding antigen or antibody enzyme with substrate, enzyme the and prepared adding the ISFET corresponding can be used enzyme for enzyme substrate,-linked the rpreparedeaction to ISFETdetect can the be concentration used for enzyme-linked of protein, reactionDNA, biochemical to detect the substances, concentration biomarkers, of protein, et DNA,c. In conclusion, biochemical the substances,simulated biomarkers, device structure etc. In model conclusion, used the to simulated develop thedevice device structure has modelsignificant used potential to develop in the the deviceapplication has significant of pH sensors. potential in the application of pH sensors.

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6 0 100μL 5

-2 200μL (μA) 300μL 4 -4 400μL 500μL 3 R2=0.99738 -6 2 -8

Drain-Source Current Drain-Source 1 D -10

Drain-Source Voltage(μA) Drain-Source 0 0 20 40 60 80 100 120 140 100 200 300 400 500 Time (s) H O Contents (μL) 2 2 (a) (b)

FigureFigure 12. 12. InIn22O3 nanobelt ISFET hydrogen peroxide detection: (a)) thethe reaction curve of of hydrogen hydrogen −11 peroxideperoxide andand horseradishhorseradish peroxidase,peroxidase, respectivelyrespectively addadd 100,100, 200,200, 300,300, 400400 andand 500500µ μLL ofof 0.1 0.1 mol mol L L− hydrogenhydrogen peroxideperoxide andand immobilizedimmobilized horseradishhorseradish peroxidaseperoxidase inin 0.010.01 × PBSPBS environment;environment; ((bb)) linearlinear × curvecurve ofof thethe didifferenceﬀerence betweenbetween thethe drain–sourcedrain–source currentcurrent ofof thethe reactionreaction ofof hydrogenhydrogen peroxideperoxide andand horseradishhorseradish peroxidase.peroxidase.

5.5. Conclusions InIn thisthis paper,paper, thethe two-dimensionaltwo-dimensional simulationsimulation ofof aa nanochannelnanochannel FETFET waswas studiedstudied byby usingusing thethe SILVACOSILVACO TCADTCAD simulationsimulation software.software. ByBy analyzinganalyzing thethe thresholdthreshold voltage,voltage, source–drainsource–drain currentcurrent andand subthresholdsubthreshold swingswing model,model, thethe influencesinfluences ofof gategate dielectricdielectric material,material, channelchannel materialmaterial andand channelchannel size on device performance were systematically considered. For final fabricated device, Si N was size on device performance were systematically considered. For final fabricated device, Si33N44 was selected as the sensitive film material, In O was used as channel material, the channel thickness was selected as the sensitive film material, In22O33 was used as channel material, the channel thickness was determineddetermined toto bebe 5050 nmnm andand thethe width-to-lengthwidth-to-length ratioratio waswas 9.9. ByBy comparingcomparing thethe measuredmeasured devicedevice characteristicscharacteristics with with the the simulated simulated data, data, the accuracy the accuracy of the simulation of the simulation structure structure was verified. was Moreover, verified. theMoreover, structure the can structure be used for can pH be detection used for with pH a detection sensitivity with of 88.125 a sensitivity mV/pH and of 88.125 hydrogen mV/pH peroxide and 1 1 oxidationhydrogen reaction peroxide with oxidation a sensitivity reaction of 144.26 with pAa sensitivity mol− L− of. In 144.26 conclusion, pA mol the−1 proposedL−1. In conclusion, structure canthe beproposed used to structure detect biomolecules can be used based to detect on pH biomolecules detection and based has promisingon pH detection applications and has for waterpromising and foodapplications quality control,for water chronic and food disease quality treatment control, and chronic industrial disease production. treatment and industrial production.

Author Contributions: Conceptualization, Y.W. and M.Y.; methodology, Y.W. and M.Y.; software, M.Y. and C.W.; validation,Author Contributions: Y.W., M.Y. and Conceptuali C.W.; formalzation analysis,, Y.W Y.W.. and and M C.W.;.Y.; methodology, investigation, Y Y.W.,.W. and M.Y. M. andY. C.W.;; software, resources, M.Y. Y.W.; and dataC.W. curation,; validation, M.Y. Y.W., and C.W.;M.Y. writing—originaland C.W.; formal draftanalysis, preparation, Y.W. and Y.W. C.W. and; investigation, M.Y.; writing—review Y.W., M.Y. and and editing, C.W.; Y.W.;resources, visualization, Y.W.; data M.Y. curation, and C.W.; M.Y. supervision, and C.W.; Y.W.;writing project—original administration, draft preparati Y.W.;on, funding Y.W. acquisition,and M.Y.; writing Y.W. All— authorsreview and have editing, read and Y.W. agreed; visualization, to the published M.Y. and version C.W.;of supervision, the manuscript. Y.W.; project administration, Y.W.; funding Funding:acquisition,This Y.W research. All authors was fundedhave read by and the agreed Jiangsu to Province the published Natural version Science of the Foundation manuscript. for the Youth (No. BK20180687) and Postgraduate Research & Practice Innovation Program of Jiangsu Province (No. SJCX20_0348). Funding: This research was funded by the Jiangsu Province Natural Science Foundation for the Youth (No. ConﬂictsBK20180687) of Interest: and PostgraduateThe authors Research declare & no Practice conﬂict Innovation of interest. Program of Jiangsu Province (No. SJCX20_0348).

Conflicts of Interest: The authors declare no conflict of interest. References

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