Extended-gate Ion-sensitive Field-effect Transistor Research Articles

A rapid and ultrasensitive cardiac troponin I aptasensor based on an ion-sensitive field-effect transistor with extended gate

Acute myocardial infarction (AMI) is a life-threatening disease with a short course and a high mortality rate. However, it is still a great challenge to achieve the on-site diagnosis of this disease within minutes, meaning there is an urgent need to develop an efficient technology for realizing the rapid diagnosis and early warning of AMI in clinical emergencies. In this study, an ultrasensitive electrochemical aptasensor based on an extended-gate ion-sensitive field-effect transistor (EGISFET) was designed to achieve the quantitative assay of cardiac troponin I (cTnI), which is a highly sensitive and specific biomarker of AMI, within only 5 min. The EGISFET exhibits extremely high detection sensitivity due to its separated structure with a large sensing area and the surface-modified Prussian blue-gold nanoparticles (PB-AuNPs) composite, which serves as a signal magnifier and DNA loading platform for good electrocatalytic ability with a large specific area. Additionally, a target-induced strand-release strategy is proposed to shorten the recognition time of cTnI using a particular DNA strand. Under optimal conditions, the as-prepared aptasensor exhibits a wide linear range of 1–1000 pg/mL, an ultralow detection limit of 0.3 pg/mL, and reliable detection results in real serum samples. It is highly anticipated that this EGISFET-based aptasensor will have broad applications in the early warning and rapid diagnosis of AMI and other acute diseases in emergency treatment.

Transparent and High-Performance Extended Gate Ion-Sensitive Field-Effect Transistors Using Electrospun Indium Tin Oxide Nanofibers

Herein, we propose a transparent high-performance extended-gate ion-sensitive field-effect transistor (EG-ISFET) using an electrospun indium-tin-oxide (ITO) nanofiber sensing membrane with a high specific surface area. Electrospinning is a simple and effective technique for forming nanofibers. Nevertheless, one-step calcination, such as conventional thermal annealing or microwave annealing, cannot sufficiently eliminate the inherent defects of nanofibers. In this study, we efficiently removed residual polymers and internal impurities from nanofibers via a two-step calcination process involving combustion and microwave annealing. Moreover, Ar plasma treatment was performed to improve the electrical characteristics of ITO nanofibers. Conformally coated thin-film sensing membranes were prepared as a comparative group and subjected to the same calcination conditions to verify the effect of the nanofiber sensing membrane. The characteristics of the ITO nanofiber and ITO thin-film sensing membranes were evaluated using scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), optical transmittance, and conductivity. Moreover, the sensor operation of the EG-ISFETs is evaluated in terms of sensitivity and non-ideal behaviors. The optimized process improves the sensor characteristics and sensing membrane quality. Therefore, the ITO nanofiber sensing membrane improves the sensitivity and stability of the EG-ISFET, suggesting its applicability as a high-performance biochemical sensor.

An Extended-Gate Ion-Sensitive Field-Effect Transistor with CMOS Technology-Intrinsic TiN Sensing Layer

The extended-gate ion-sensitive field-effect transistor (EGISFET) has promising potentials in chemical and biological sensing due to flexibility for array arrangement, less light-sensitivity, and compatibility with CMOS standard fabrication process [1-2]. An EGISFET is consisted of a MOSFET and a floating-gate structure separated from analyte solutions by a sensing layer. Because charges adjacent to the sensing layer change the floating-gate potential, the channel current of the EGISFET can be modulated through the electrical field effect. In a general CMOS process, the EGISFET can be achieved by using metal/VIA/polysilicon layers as the extended gate material and the passivation nitride layer on top of the metal as the sensing layer. For the EGISFET operation, a solution gate voltage is provided in the analyte solution and a capacitive voltage divider can be obtained based on a series connection of the electrical double layer capacitance (CEDL), the sensing layer capacitance (CS) and the gate oxide capacitance (COX). Due to the capacitive coupling nature, a higher CS/(CS+COX) ratio can have a larger part of solution gate voltage transferred to COX, and thus can have a higher EGISFET transconductance [3], which promises a better sensing response, e.g. channel-current change for a given charge change. However, CS is decreasing because of scaling down for realizing high spatial resolution sensing array. Then EGISFETs become less sensitive due to a weaker capacitive coupling.In order to ameliorate this scaling effect, we developed a TiN-EGISFET based on a CMOS 0.35 mm standard fabrication process. Instead of using the 1-2 mm thick passivation/intermediate dielectric layer as the sensing layer, we took advantage of an intrinsic extra-thin TiN layer within the VIA structure as the sensing layer. To expose the TiN layer, the metal/VIA layout was placed in a special manner to form a hanging micro-structure after a one-step wet etching. Followed by sonication, the micro-structure was broken at a mechanical weak point, e.g. the metal/VIA interface, and the ultra-thin TiN was successfully exposed. To have a control group, a traditional EGISFET was also implemented on the same chip. In the EGISFET measurement, a Ag/AgCl electrode was used to provide solution gate voltage, and the electric characteristic curve for each device was measured in pH solutions with different values.Compared to the traditional EGISFET occupying the same chip area, transconductance for the TiN-exposed EGISFET was improved up to 240%. This enhancement is possibly attributed to the conductivity and chemical stability of TiN, which make CS in the TiN-exposed region disappeared, only left CEDL and COX in series. As a result, a larger portion of solution gate voltage is dropped across COX because CEDL>>COX. Furthermore, the pH sensitivity of TiN-exposed EGISFET reaches 51 mV/pH without obvious hysteresis and drift (Figure 1). This is also supported by the previous literatures [4-5]. At 0.5V overdrive voltage, the current variation of TiN-exposed EGISFET is -9.12 mA/pH, which is 275% as high as that of the traditional EGISFET (Figure 2). These results suggest that a TiN-exposed EGISFET with a smaller footprint can possess the same sensitivity of a traditional EGISFET with a larger footprint.In conclusion, we developed a method to fabricate EGISFETs with TiN sensing layers in a commercialized CMOS process. This is the first time to have the in-situ TiN EGISFET in the CMOS process without extrinsic TiN deposition. This method can be employed to realize EGISFETs with higher density in a given area without sacrificing sensitivity, thus potentially beneficial to the development of high performance and high spatial resolution ISFET sensing array.

PH Sensitivity Improvement of Vertical Silicon-Nanowire Extended-Gate Ion-Sensitive Field Effect Transistor

The extended-gate ion-sensitive field-effect transistor (EGISFET) is essential to the field of bio-chemical sensing. It has been reported that the nano-textured gate ISFET is suitable for high pH sensitivity. The small distance between each nano-structure results in the high sensitivity. However, due to the difficulties of manufacturing process, the distance between each nano-structure will no longer be shrunk, which means that it will be a challenge to keep improving sensitivity. To address this issue, we turn to make good use of the space above these nano-structures. Thus, a series of vertical silicon nanowire (SiNW) sensing membranes with different heights was developed in EGISFET pH sensors. The vertical SiNW sensing membranes were fabricated using the electroless etching technique called metal-assisted chemical etching (MACE). The ultra-thin Au nanomesh served as a catalyst in MACE process was replicated from a reusable porous anodic aluminium oxide (AAO) membrane. By photo-lithography the sensing area on the SiNW sensing membrane was defined. The transfer characteristics of such vertical SiNW EGISFET pH sensors exhibited a higher sensitivity (75.86 mV/pH) than that of the conventional planar EGISFET pH sensors (38.53 mV/pH) for the different pH solutions (pH 4, pH 7 and pH 10). The scanning electron microscopy images of SiNW with different heights are also presented.

An Extended-Gate Ion-Sensitive Field-Effect Transistor with CMOS Technology-Intrinsic TiN Sensing Layer

The extended-gate ion-sensitive field-effect transistor (EGISFET) has promising potentials in chemical and biological sensing due to flexibility for array arrangement, less light-sensitivity, and compatibility with CMOS standard fabrication process [1-2]. An EGISFET is consisted of a MOSFET and a floating-gate structure separated from analyte solutions by a sensing layer. Because charges adjacent to the sensing layer change the floating-gate potential, the channel current of the EGISFET can be modulated through the electrical field effect. In a general CMOS process, the EGISFET can be achieved by using metal/VIA/polysilicon layers as the extended gate material and the passivation nitride layer on top of the metal as the sensing layer. For the EGISFET operation, a solution gate voltage is provided in the analyte solution and a capacitive voltage divider can be obtained based on a series connection of the electrical double layer capacitance (CEDL), the sensing layer capacitance (CS) and the gate oxide capacitance (COX). Due to the capacitive coupling nature, a higher CS/(CS+COX) ratio can have a larger part of solution gate voltage transferred to COX, and thus can have a higher EGISFET transconductance [3], which promises a better sensing response, e.g. channel-current change for a given charge change. However, CS is decreasing because of scaling down for realizing high spatial resolution sensing array. Then EGISFETs become less sensitive due to a weaker capacitive coupling.In order to ameliorate this scaling effect, we developed a TiN-EGISFET based on a CMOS 0.35 μm standard fabrication process. Instead of using the 1-2 μm thick passivation/intermediate dielectric layer as the sensing layer, we took advantage of an intrinsic extra-thin TiN layer within the VIA structure as the sensing layer. To expose the TiN layer, the metal/VIA layout was placed in a special manner to form a hanging micro-structure after a one-step wet etching. Followed by sonication, the micro-structure was broken at a mechanical weak point, e.g. the metal/VIA interface, and the ultra-thin TiN was successfully exposed. To have a control group, a traditional EGISFET was also implemented on the same chip. In the EGISFET measurement, a Ag/AgCl electrode was used to provide solution gate voltage, and the electric characteristic curve for each device was measured in pH solutions with different values.Compared to the traditional EGISFET occupying the same chip area, transconductance for the TiN-exposed EGISFET was improved up to 240%. This enhancement is possibly attributed to the conductivity and chemical stability of TiN, which make CS in the TiN-exposed region disappeared, only left CEDL and COX in series. As a result, a larger portion of solution gate voltage is dropped across COX because CEDL>>COX. Furthermore, the pH sensitivity of TiN-exposed EGISFET reaches 51 mV/pH without obvious hysteresis and drift (Figure 1). This is also supported by the previous literatures [4-5]. At 0.5V overdrive voltage, the current variation of TiN-exposed EGISFET is -9.12 mA/pH, which is 275% as high as that of the traditional EGISFET (Figure 2). These results suggest that a TiN-exposed EGISFET with a smaller footprint can possess the same sensitivity of a traditional EGISFET with a larger footprint.In conclusion, we developed a method to fabricate EGISFETs with TiN sensing layers in a commercialized CMOS process. This is the first time to have the in-situ TiN EGISFET in the CMOS process without extrinsic TiN deposition. This method can be employed to realize EGISFETs with higher density in a given area without sacrificing sensitivity, thus potentially beneficial to the development of high performance and high spatial resolution ISFET sensing array.

High-performance extended-gate ion-sensitive field-effect transistors with multi-gate structure for transparent, flexible, and wearable biosensors

ABSTRACT In this study, we developed a high-performance extended-gate ion-sensitive field-effect transistor (EG-ISFET) sensor on a flexible polyethylene naphthalate (PEN) substrate. The EG-ISFET sensor comprises a tin dioxide (SnO2) extended gate, which acts as a detector, and an amorphous indium-gallium-zinc-oxide (a-IGZO) thin-film transistor (TFT) for a transducer. In order to self-amplify the sensitivity of the pH sensors, we designed a uniquely-structured a-IGZO TFT transducer with a high-k engineered top gate insulator consisting of a silicon dioxide/tantalum pentoxide (SiO2/Ta2O5) stack, a floating layer under the channel, and a control gate coplanar with the channel. The SiO2/Ta2O5 stacked top gate insulator and in-plane control gate significantly contribute to capacitive coupling, enabling the amplification of sensitivity to be enlarged compared to conventional dual-gate transducers. For a pH sensing method suitable for EG-ISFET sensors, we propose an in-plane control gate (IG) sensing mode, instead of conventional single-gate (SG) or dual-gate (DG) sensing modes. As a result, a pH sensitivity of 2364 mV/pH was achieved at room temperature – this is significantly superior to the Nernstian limit (59.15 mV/pH at room temperature). In addition, we found that non-ideal behavior was improved in hysteresis and drift measurements. Therefore, the proposed transparent EGISFFET sensor with an IG sensing mode is expected to become a promising platform for flexible and wearable biosensing applications.

Extended Gate Reference-FET (REFET) Using 2D h-BN Sensing Layer for pH Sensing Applications

Though ISFET (Ion-Sensitive Field Effect Transistor) has been widely used in measuring pH or other ions in electrolyte, one of main challenges it faces is its large volume of fluidic reference electrode. The use of REFET is one approach to address the above issue where a pH inert material such as hydrophobic polymer is used as sensing layer. However, REFETs with polymer sensing film may suffer from instability and non-uniformity. In this letter, an extended gate ISFET with 2D hexagonal boron nitride (h-BN) as sensing layer is proposed and demonstrated as a REFET. The device with as-exfoliated 2D h-BN flake shows a low pH sensitivity of less than 5 mV/pH and low drift around 0.50 mV/hour. All these suggest 2D h-BN a highly potential candidate to be used in making a stable and high performance REFET.

An Ion-Sensitive Field-Effect Transistor with Three-Dimensional Extended-Gate Architecture

Because of physically separated sensing region from field-effect region, the extended-gate ion-sensitive field-effect transistor (EG-ISFET) has many advantages over the ISFET including light insensitivity, easy fabrication, and flexibility of sensor array arrangement [1-2]. However, in the EG-ISFET configuration, there is an additional capacitance derived from the passivation layer on the top of extended gate. As a consequence, part of sensing voltages drop across the derived capacitance and the transconductance of EG-ISFET is attenuated. It should be noted that a small transconductance would result in a less current variation and lead to a poor performance in sensitivity. Increasing the capacitance by increasing the two-dimensional area of the top metal layer of the extended gate can ameliorate this issue [3]. However, it will arise other issues such as increasing the fabrication cost at the expense of larger wafer area and decreasing the pixel-resolution of sensor array because of enlargement of each sensing pixel. To address this issue, in this study we propose a lifted three-dimensional (3D) metal architecture as the extended gate for an EG-ISFET. Compared with the conventional EG-ISFET with a planar electrode surface (Fig. 1A), the proposed lifted EG-ISFET, namely the LEG-ISFET, has two metal layers lifted beyond the planar surface (Fig. 1B). Obviously, the LEG-ISFET has larger liquid/solid interface surface area than the conventional EG-ISFET does. In other words, the LEG-ISFET should have a better transconductance than the conventional EG-ISFET does. At the same time, the LEG-ISFET keeps the same wafer area as the conventional EG-ISFET. To fabricate the proposed LEG-ISFET, conventional EG-ISFETs and LEG-ISFETs with different size of top metal layer are implemented on the same chip by a standard CMOS 0.35 μm process. Then the fabricated chip undergoes wet etching to remove passivation-free metal/via layers including the oxides surrounded by them to realize the lifted 3D metal structure as shown in Fig. 2. In experiments, the ID-VG curve of each FET device is measured using Ag/AgCl reference electrode in a pH7 buffer solution. Based on the slope of the measured curves, the transconductance can be extracted. To facilitate the comparison, Table 1 shows different symbols representing different device designs. Based on the experiment, it shows that the transconductance attenuates seriously in the conventional EG-ISFET with the smallest top metal area (Fig. 3A). Compared with the MOSFET with exactly the same structure, the transconductance measured from conventional EG-ISFET is about 3 times lower than that of the MOSFET with the same structure. As the top metal area increased, the transconductance of the conventional EG-ISFET is gradually increased. On the other hand, the transconductance of each proposed LEG-ISFET is at the same level as the intrinsic MOSFET (Fig. 3B). It should be noted that the smallest LEG-ISFET has a 3D electrode surface area estimated about 3 times to the 2D top-electrode area of the smallest EG-ISFET. However, the transconductance improvement of the smallest LEG-ISFET is roughly the same as the largest EG-ISFET, which has about 600 times the top-electrode area of the smallest EG-ISFET. This finding suggests that factors other than surface area should also account for the transconductance enhancement. It is interesting to investigate the underlying mechanism to further improve the performance of ISFET. In conclusion, a high-transconductance configuration of LEG-ISFET is proposed and verified. This development has potentials for realization of sensor array with high pixel-resolution and high sensitivity. [1] Kaisti, Matti. "Detection principles of biological and chemical FET sensors." Biosensors and Bioelectronics 98 (2017): 437-448. [2] Chi, Li-Lun, et al. "Study on extended gate field effect transistor with tin oxide sensing membrane." Materials Chemistry and Physics 63.1 (2000): 19-23. [3] Sohbati, Mohammadreza, and Christofer Toumazou. "Dimension and shape effects on the ISFET performance." IEEE Sensors Journal 15.3 (2015): 1670-1679. Figure 1

Urea Detection Using Commercial Field Effect Transistors

We used an easy method to assemble a biosensor using simple and low cost materials. Commercial SnO2:F thin films were used as the basic sensing part of an extended-gate ion-sensitive field effect transistor. When used as a pH sensor, the oxide film showed a sensitivity of 59 ± 4 mV.pH−1, and linear response in the pH range 2.0 to 10.0. Since urea detection and quantification is important for the control of many pathologies, as proof of concept the samples were further used as platform for urea sensing by immobilizing urease protein onto the surface of the film. For urea sensing, the modified electrodes showed a linear response in the pUrea range of 2.1 to 3.0 (1.00 mM to 7.94 mM, which covers a suitable screening interval for clinical exams) and a sensitivity of 109 ± 3 mV.pUrea−1. A steady-state was reached after about 60 seconds. Varied pHs and buffer concentrations were also investigated to assess the biosensor behavior toward changes in the environmental conditions. The proposed device could be applied in clinical trials in developing countries as well as in areas hit by natural disasters.

Sensing properties of separative paper-based extended-gate ion-sensitive field-effect transistor for cost effective pH sensor applications

In this study, we developed a cost-effective ion-sensing field-effect transistor (FET) with an extended gate (EG) fabricated on a separative paper substrate. The pH sensing characteristics of the paper EG was compared with those of other EGs fabricated on silicon, glass, or polyimide substrates. The fabricated paper-based EGFET exhibited excellent sensitivity close to the Nernst response limit as well as to that of the other substrate-based EGFETs. In addition, we found that all EGFETs, regardless of the substrate, have similar non-ideal behavior, i.e., drift phenomenon and hysteresis width. To investigate the degradation and durability of the paper EG after prolonged use, aging-effect tests were carried out in terms of the hysteresis width and sensitivity over a course of 30 days. As a result, the paper EG maintained stable pH sensing characteristics after 30 days. Therefore, we expect that paper EGFETs can provide a cost-effective sensor platform.

High-performance SEGISFET pH Sensor using the structure of double-gate a-IGZO TFTs with engineered gate oxides

In this paper, we propose a high-performance separative extended gate ion-sensitive field-effect transistor (SEGISFET) that consists of a tin dioxide (SnO2) SEG sensing part and a double-gate structure amorphous indium gallium zinc oxide (a-IGZO) thin-film transistor (TFT) with tantalum pentoxide/silicon dioxide (Ta2O5/SiO2)-engineered top-gate oxide. To increase sensitivity, we maximized the capacitive coupling ratio by applying high-k dielectric at the top-gate oxide layer. As an engineered top-gate oxide, a stack of 25 nm-thick Ta2O5 and 10 nm-thick SiO2 layers was found to simultaneously satisfy a small equivalent oxide thickness (∼17.14 nm), a low leakage current, and a stable interfacial property. The threshold-voltage instability, which is a fundamental issue in a-IGZO TFTs, was improved by low-temperature post-deposition annealing (∼87 °C) using microwave irradiation. The double-gate structure a-IGZO TFTs with engineered top-gate oxide exhibited high mobility, small subthreshold swing, high drive current, and larger on/off current ratio. The a-IGZO SEGISFETs with a dual-gate sensing mode showed a pH sensitivity of 649.04 mV pH−1, which is far beyond the Nernst limit. The non-ideal behavior of ISFETs, hysteresis, and drift effect also improved. These results show that the double-gate structure a-IGZO TFTs with engineered top-gate oxide can be a good candidate for cheap and disposable SEGISFET sensors.

Non-invasive screening for Alzheimer's disease by sensing salivary sugar using Drosophila cells expressing gustatory receptor (Gr5a) immobilized on an extended gate ion-sensitive field-effect transistor (EG-ISFET) biosensor.

Body fluids are often used as specimens for medical diagnosis. With the advent of advanced analytical techniques in biotechnology, the diagnostic potential of saliva has been the focus of many studies. We recently reported the presence of excess salivary sugars, in patients with Alzheimer’s disease (AD). In the present study, we developed a highly sensitive, cell-based biosensor to detect trehalose levels in patient saliva. The developed biosensor relies on the overexpression of sugar sensitive gustatory receptors (Gr5a) in Drosophila cells to detect the salivary trehalose. The cell-based biosensor was built on the foundation of an improved extended gate ion-sensitive field-effect transistor (EG-ISFET). Using an EG-ISFET, instead of a traditional ion-sensitive field-effect transistor (ISFET), resulted in an increase in the sensitivity and reliability of detection. The biosensor was designed with the gate terminals segregated from the conventional ISFET device. This design allows the construction of an independent reference and sensing region for simultaneous and accurate measurements of samples from controls and patients respectively. To investigate the efficacy of the cell-based biosensor for AD screening, we collected 20 saliva samples from each of the following groups: participants diagnosed with AD, participants diagnosed with Parkinson’s disease (PD), and a control group composed of healthy individuals. We then studied the response generated from the interaction of the salivary trehalose of the saliva samples and the Gr5a in the immobilized cells on an EG-ISFET sensor. The cell-based biosensor significantly distinguished salivary sugar, trehalose of the AD group from the PD and control groups. Based on these findings, we propose that salivary trehalose, might be a potential biomarker for AD and could be detected using our cell-based EG-ISFET biosensor. The cell-based EG-ISFET biosensor provides a sensitive and direct approach for salivary sugar detection and may be used in the future as a screening method for AD.

Microwave annealing effect for highly reliable biosensor: dual-gate ion-sensitive field-effect transistor using amorphous InGaZnO thin-film transistor.

We used a microwave annealing process to fabricate a highly reliable biosensor using amorphous-InGaZnO (a-IGZO) thin-film transistors (TFTs), which usually experience threshold voltage instability. Compared with furnace-annealed a-IGZO TFTs, the microwave-annealed devices showed superior threshold voltage stability and performance, including a high field-effect mobility of 9.51 cm(2)/V·s, a low threshold voltage of 0.99 V, a good subthreshold slope of 135 mV/dec, and an outstanding on/off current ratio of 1.18 × 10(8). In conclusion, by using the microwave-annealed a-IGZO TFT as the transducer in an extended-gate ion-sensitive field-effect transistor biosensor, we developed a high-performance biosensor with excellent sensing properties in terms of pH sensitivity, reliability, and chemical stability.

Flexible ISFET Biosensor Using IGZO Metal Oxide TFTs and an ITO Sensing Layer

This letter presents the fabrication details and measured performance of a prototype flexible extended-gate ion-sensitive field effect transistor (ISFET) biosensor, manufactured using a metal oxide indium-gallium-zinc oxide thin film transistor and an indium-tin oxide sensing layer on a 125- μm thick flexible plastic substrate. ISFET drain current was shown to respond correctly to the pH buffer concentration with repeatable pH sensitivity observed over multiple cycles. These results demonstrate the initial viability of directly extending flexible plastic substrate organic light emitting diode display technology to the production of low-cost, plastic ISFET biosensors.

Real-time feedback control of pH within microfluidics using integrated sensing and actuation

We demonstrate a microfluidic system which applies engineering feedback principles to control the pH of a solution with a high degree of precision. The system utilizes an extended-gate ion-sensitive field-effect transistor (ISFET) along with an integrated pseudo-reference electrode to monitor pH values within a microfluidic reaction chamber. The monitored reaction chamber has an approximate volume of 90 nL. The pH value is controlled by adjusting the flow through two input channels using a pulse-width modulated signal applied to on-chip integrated valves. We demonstrate real-time control of pH through the feedback-controlled stepping of 0.14 pH increments in both the increasing and decreasing direction. The system converges to the pH setpoint within approximately 20 seconds of a step change. The integration of feedback theory into a microfluidic environment is a necessary step for achieving complete control over the microenvironment.

Complementary Metal–Oxide–Semiconductor Ion-Sensitive Field-Effect Transistor Sensor Array with Silicon Nitride Film Formed by Catalytic Chemical Vapor Deposition as an Ion-Sensitive Membrane

Integration of 16 ×16 and 32 ×32 extended-gate ion-sensitive field-effect transistor (ISFET) arrays with a low-power consumption read-out circuitry has been reported. Si3N4 film used as a pH sensitive layer is deposited on the 4 ×4 µm2 extended-gate electrodes of ISFETs in the integrated circuit by catalytic chemical vapor deposition (Cat-CVD). The average pH sensitivity is 41 mV/pH, and the distribution obeys a Gaussian distribution with a standard deviation of 1.5–3.4 mV. The result is compared with that of pH sensitivity measurement using an Al2O3 layer formed by O2 plasma.