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With helps of advancing CMOS technology, ISFETs have achieved great success. However, CMOS-based ISFETs are also suffering problems of scaling attenuation and threshold voltage offset. These problems mainly result from the architecture used to adapt standard CMOS process. To deal with these, we developed a novel CMOS ISFET configuration, namely, 3D-T-ISFET, by building a truncated architecture to expose CMOS process-inherent TiN thin film as the sensing interface. Due to the electrical conductivity of TiN, the signal from the environment can bypass the sensing dielectric and couple to the transistor effectively through the electrical double layer capacitance. Based on our experiments, as the footprint of 8.52 μm2, a 3.21-fold ΔID/pH improvement can be achieved by developed 3D-T-ISFET. At the same time, the 3D-T-ISFET has an about 1.65-fold improvement in SNR compared to the traditional 2D-ISFET. Compared to the 2D-ISFET in a state-of-the-art design, therefore, 3D-T-ISFET exhibits a scaling attenuation-free behavior and becomes less vulnerable to the non-idea effects brought by trapped charges.

Field Effect Transistors (FETs) have led the progress of applications measuring the acidity in aqueous solutions thanks to their accuracy, ease of miniaturization and capacity of multiplexing. The signal-to-noise ratio and linearity of the sensors are two of the most relevant figures of merit that can facilitate the improvements of these devices. In this work we present the functionalization with aminopropyltriethoxysilane (APTES) of a promising new FET design consisting of a high height-towidth aspect ratio with an efficient 2D gating architecture that improves both factors. We measured the transistor transfer and output characteristics before and after APTES functionalization, obtaining an improved sensitivity and linearity in both responses. We also compared the experimental results with a site-biding model of the surface buffering capacity of the APTES functionalized layers.

The ion-sensitive field-effect transistor (ISFET) is a popular technology utilized for pH sensing applications. In this work, we have presented the fabrication, characterization, and electrochemical modeling of an aluminum oxide (Al2O3)-gate ISFET-based pH sensor. The sensor is fabricated using well-established metal–oxide–semiconductor (MOS) unit processes with five steps of photolithography, and the sensing film is patterned using the lift-off process. The Al2O3 sensing film is deposited over the gate area using pulsed-DC magnetron-assisted reactive sputtering technique in order to improve the sensor performance. The material characterization of sensing film has been done using x-ray diffraction, field-emission scanning electron microscopy, energy-dispersive spectroscopy, and x-ray photoelectron spectroscopy techniques. The sensor has been packaged using thick-film technology and encapsulated by a dam-and-fill approach. The packaged device has been tested in various pH buffer solutions, and a sensitivity of nearly 42.1 mV/pH has been achieved. A simulation program with integrated circuit emphasis (SPICE) macromodel of the Al2O3-gate ISFET is empirically derived from the experimental results, and the extracted electrochemical parameters have been reported. The drift and hysteresis characteristics of the Al2O3-gate ISFET were also studied, and the obtained drift rates for different pH buffer solutions of 4, 7, and 10 are 0.136 μA/min, 0.124 μA/min, and 0.108 μA/min, respectively. A hysteresis of nearly 5.806 μA has been obtained. The developed sensor has high sensitivity along with low drift and hysteresis.

The ion-sensitive field-effect transistor (ISFET) is a type of electrochemical sensor with a wide range of applications. They offer advantages of being compatible with standard CMOS technology, a miniaturised form-factor, robustness, scalability and low power requirements to name a few. There are now many architectures and design strategies to construct ISFET-based systems in CMOS, and the appropriate choice of these depends heavily on the specifications of the intended application. This tutorial aims to give a designer the knowledge needed to make the best decisions for the required specifications by providing a background in theory and an overview of design trade-offs and existing approaches. Example designs which maximise performance in particular applications are discussed and practical considerations for simulation, layout and implementation are presented.

Floating-Gate-Ions-Sensitive-Field-Effect-Transistors (FG-ISFETs) are becoming the sensor’s platform for various fields such as biomedical and chemical sensors. Despite many advantages like quick response, small size as well as wide measurement range, the efficiency of the output measurement is widely affected by temperature, This requires more safety in the measured results and the analysis’s tools. This study describes a novel integrated circuit that improves the thermal stability of the output signal of the ion-sensitive field effect transistors (ISFETs). After that, we investigate the temperature dependency of the FG-ISFET using the mentioned macro model and we shows that the temperature coefficient is about of 6 mV/°C. Afterward, a new integrated interface circuit that can perform great temperature compensation was developed. This operation aims to enhance stability of readout circuit for FG-ISFET. The achieved result of the FG-ISFET under different simulations shows that the readout circuit has a good temperature compensation i.e. :2.4 〖10〗^(-9) mV/°C.

Reduction of drift in Complementary Metal Oxide-Semiconductor (CMOS) Ion-Sensitive Field-Effect Transistor (ISFET) pH sensors is demonstrated using monolayer and multilayer graphene sheets. Graphene blocks the ion penetration in the CMOS passivation layers and provides the physisorption sites needed for electrical double layer formation allowing sensing. With an in-house polymer-assisted graphene transfer (PAGT) process, monolayer and multilayer graphene sheets were manually transferred on top of the sensing membrane of CMOS ISFET sensors on a 2 by 4 mm chip. Experiments with pH buffers on five different chips were performed to extract the average performance parameters of capacitive attenuation, trapped charge, sensitivity, drift and noise. The stretched exponential function, that describes dispersion processes in amorphous solids such as silicon dioxide and silicon nitride, was modified to model the dynamic drift behaviour and analyse the effect of graphene on the performance of the sensors. The results show that on average the graphene coated ISFET sensors experience about 50% reduction in drift amplitude, up to 3 times slower surface modification and perform overall better compared to the plain unmodified devices.

ESR1 mutations are important biomarkers in metastatic breast cancer. Specifically, p.E380Q and p.Y537S mutations arise in response to hormonal therapies given to patients with hormone receptor positive (HR+) breast cancer (BC). This paper demonstrates the efficacy of an ISFET based CMOS integrated Lab-on-Chip (LoC) system, coupled with variant-specific isothermal amplification chemistries, for detection and discrimination of wild type (WT) from mutant (MT) copies of the ESR1 gene. Hormonal resistant cancers often lead to increased chances of metastatic disease which leads to high mortality rates, especially in low-income regions and areas with low healthcare coverage. Design and optimization of bespoke primers was carried out and tested on a qPCR instrument and then benchmarked versus the LoC platform. Assays for detection of p.Y537S and p.E380Q were developed and tested on the LoC platform, achieving amplification in under 25 minutes and sensitivity of down to 1000 copies of DNA per reaction for both target assays. The LoC system hereby presented, is cheaper and smaller than other standard industry equivalent technologies such as qPCR and sequencing. The LoC platform proposed, has the potential to be used at a breast cancer point-of-care testing setting, offering mutational tracking of circulating tumour DNA in liquid biopsies to assist patient stratification and metastatic monitoring.

In this work, ISFET frontends utilising the direct tunneling current to eliminate trapped charge are proposed. The principle has been investigated and verified via silicon-imitated ISFET first, where silicon capacitors are used to imitate the passivation ones. Because the dominant tunneling components depend on the potential difference between Gate and Drain terminals, a source-follower structure could itself perform a highpass filter with time constant at 10-100 seconds level. Additionally, a time-constant regulation mechanism is presented by feeding the output signal back to the drain terminal of ISFETs, achieving a regulation factor over 50, namely from 4.7 seconds to 243.4 seconds in our implementation. Afterwards in chemical test, proposed ISFETs have been verified in terms of unit passivation capacitance, linearity, noise and sensitivity for ISFETs with 3 different top metal areas. It is found that approximately 30.12 mV/pH sensitivity can be achieved, and for the first time we managed to derive the relation between chemical flicker noise and sensing metal area.

As the CMOS-based ion-sensitive field-effect transistor (ISFET) is scaling down to achieve a compact sensing array with high spatial resolution, reduction of sensing layer capacitance attenuates capacitive coupling efficiency of environmental input signals and decreases sensitivity performance. To address this issue, a concept of three-dimensional (3D) sensing structure is proposed and examined in this study. This can increase the sensing layer capacitance for a given footprint area. Based on our designs, a series of 3D sensing structures can be implemented with a standard CMOS foundry service and CMOS-compatible post processes. Our experimental results show that an $8.5^{2}\mu \text{m}^{2}$ footprint design of the 3D sensing structure can obtain approximately 2-fold increase in transconductance compared with a traditional ISFET with the same footprint. This enables pH sensitivity to be improved 1.5-fold in current response and 1.15-fold in voltage response. Therefore, the proposed 3D-structure ISFET can pave the way toward an ISFET sensing array with high sensitivity and high spatial resolution.

Label-free detection of biomolecules using ion-sensitive field-effect transistors (ISFETs) in physiological solutions is limited by the Debye charge-screening effect of the electrical double layer. Most ISFET measurements are therefore performed in diluted ionic-strength solutions to detect the interface potential change on specific binding of biomolecules. The novel CMOS ISFETs proposed in this study have a capacitor structure in the oscillator readout to provide modulation of the surface electric field to reduce the charge screening and nonideal signal drift. Signal modulation was applied at frequencies higher than the ion-strength-dependent cut-off frequency, with the highest applied frequency being approximately 100 MHz among the four proposed designs. The measured results revealed a pH sensitivity from 52.3 to 54.4 mV/pH in terms of the floating-gate potential change. Direct DNA hybridization in a high ionic-strength solution was successfully measured with a near picomolar-level resolution.

This paper reports unique InGaAs-based ion-sensitive field-effect transistor (ISFET) sensor devices having a sensing gate in addition to the traditional floating gate with different kinds of barrier materials such as no barrier, single barrier (InP) and double barrier (InP and InAlAs), at sub-100 nm technology node. The impact of barrier layers coupled with the modified gate architecture on the sensing performance of the proposed devices has been investigated and compared thoroughly in terms of different performance metrics, e.g., threshold voltage sensitivity, ON-current sensitivity, and ON/OFF-current sensitivity. Interestingly, it has been found that the sensor device with a single barrier exhibits the highest threshold voltage sensitivity of ~ 67 mV/pH and largest ION/IOFF ratio sensitivity of 25/pH, compared to the other devices. Furthermore, it is worth mentioning that the threshold voltage sensitivity of the single-barrier sensor device crosses the conventional Nernst limit of 59 mV/pH at room temperature, by 14%. Critically analyzing the results, it is found that the sensor device with a single barrier has evolved as the most promising device for pH-sensing application, not only from the standpoint of high sensitivity parameters, but also from the fabrication point of view.

The results of a comparative literature analysis of internal electrical noises and signal-to-noise ratio for nanoscale BioFET (biological field-effect transistor) and DNA (deoxyribonucleic acid) sensors based on different architectures MIS (metal-insulator-semiconductor), EIS (electrolyte-insulator-semi-conductor) and ISFET (ion-selective field-effect transistor) are presented. Main types, models and mechanisms of internal noises of bio- & chemical field-effect based sensors are analyzed, summarized and presented. For the first time, corresponding detail electrical equivalent circuits were built to calculate the spectral densities of noises generated in the active part of a solid (semiconductor, dielectric) and in an aqueous solution for MIS, EIS and ISFET structures based sensors. Complete expressions are obtained for the rms (root mean square) value of the noise current (or voltage), as well as the noise spectral densities for the architectures under study. The miniaturization of biosensors leads to a decrease in the level of the useful signal-current. For successful operation of the sensor, it is necessary to ensure a high value of the SNR (signal-to-noise ratio). In case of weak useful signals, it is necessary to reduce the level of internal electrical noise. This work is devoted to a detailed study of the types and mechanisms of internal electrical noises in specific biosensor architectures.

Recently, organic bioelectronics has attracted considerable interest in the scientific community. The impressive growth that it has undergone in the last 10 years has allowed the rise of the completely new field of cellular organic bioelectronics, which has now the chance to compete with consolidated approaches based on devices such as micro-electrode arrays and ISFET-based transducers both in in vitro and in vivo experimental practice. This review focuses on cellular interfaces based on organic active devices and has the intent of highlighting the recent advances and the most innovative approaches to the ongoing and everlasting challenge of interfacing living matter to the "external world" in order to unveil the hidden mechanisms governing its behavior. Device-wise, three different organic structures will be considered in this work, namely the organic electrochemical transistor (OECT), the solution-gated organic transistor (SGOFET - which is presented here in two possible different versions according to the employed active material, namely: the electrolyte-gated organic transistor - EGOFET, and the solution gated graphene transistor - gSGFET), and the organic charge modulated field effect transistor (OCMFET). Application-wise, this work will mainly focus on cellular-based biosensors employed in in vitro and in vivo cellular interfaces, with the aim of offering the reader a comprehensive retrospective of the recent past, an overview of the latest innovations, and a glance at the future prospects of this challenging, yet exciting and still mostly unexplored scientific field.

The perfect combination of biomolecules and nanomaterials is critical to achieve a biosensor with high sensitivity and selectivity. In this study, ion sensitive field effect transistor (ISFET) biosensors were fabricated based on carbon nanotube (CNT) with two different structures as the enzyme immobilization support. Laccase was immobilized over two kinds of CNT including: drop-casted single wall carbon nanotubes (SWCNTs) and forest-like multi-walled carbon nanotubes (MWCNTs) grown via Plasma-Enhanced Chemical Vapor Deposition (PECVD). The immobilization was non-covalent without any coupling agent and direct detection of 2, 2-azino-bis 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) was carried out. Hydrogen and oxygen plasma treatments were performed on both types of devices to assess their effect on the enzyme immobilization. To investigate CNT-laccase interaction, the fourier transform infrared (FTIR)-attenuated total reflection (ATR) analysis was performed before and after the laccase immobilization for pristine and plasma treated CNTs. Results showed that drop-casted SWCNT-based sensor with oxygen treatment has the highest sensitivity as high as 3.66 A. M−1.cm−2, limit of detection (LOD) of $3~\mu \text{M}$ and linear range up to $300~\mu \text{M}$ .

Introduction The deterioration of various kinds of machine lubricants and engine oils has been estimated through total acid number (TAN), and the value of TAN has been commonly measured by color-indicator titration and potentiometric titration, according to ISO standards (e.g., No. 6619 and 7537). Presently, we cannot directly monitor the TAN value on site as well as in real time, which leads the difficulty in the efficient operation of various machines and their automatic maintenance. Some kinds of devices capable of measuring nuclear magnetic resonance (NMR) [1], infrared (IR) adsorption [2], impedance [3], or electrochemical potential [3–6] of lubricants and oils to estimate their deterioration have been developed, but compact, maintenance-free, and low-cost devices capable of directly monitoring their TAN values are quite convenient for controlling mechanical systems utilized in various fields. Our group have recently attempted to develop new TAN-monitoring sensors employing a general pH meter based on ion-sensitive field-effect transistor (IS-FET) technology [7–9]. In this presentation, we would like to introduce the new concept, fundamental properties, and the operating mechanism of the sensors. Experimental Figure 1 shows schematic cross-sectional drawing of a sensor tip, which consists of an IS-FET and a reference electrode (Horiba, Ltd., ISFET pH electrode: 0040-10D, sensor chip: 0141) [10]. 1-Propanol solution containing 5.0 wt% cation-conducting polymer (Tokuyama Corp., CS-7P) was used as an original coating agent, and it was appropriately diluted with 1-propanol to form three kinds of diluted CCP solution (2.5 wt%, 1.7 wt%, and 1.3 wt%). The CCP solution (20 mm3) was dropped on the surface of the sensor tip, and then the CCP film was uniformly coated on the while surface containing the IS-FET and the reference electrode, after moderately drying at room temperature. The obtained films were expressed as CCP(m), where m stands for the concentration of the CCP solution used (wt%). Subsequently, the surface of the sensor tip was treated with 1 M NaCl aqueous solution (100 mm3) several times in order to exchange H+ for Na+ in the CCP(m) films, until the pH value reached up to ca. 6. As soon as some kinds of lubricants (20 mm3) were dropped on the surface of the obtained CCP(m) sensors, variations in pH of the lubricants measured by the CCP(m) sensors with time were measured with a pH meter (Horiba, Ltd., D-52). Results and Discussion Figure 2 shows response transients of the CCP(2.5) sensor to typical fresh and deteriorated lubricants (Oil(n), n: oxidation period for deterioration (h)) at 30°C. TAN values of the lubricants oxidized for 0, 504, 800, and 1104 h were 0.19, 0.23, 0.30, and 0.35 (mgKOH/g), respectively, and the fresh lubricant corresponds to Oil(0). After the initial pH value was controlled at ca. 6, the pH value gradually increased immediately after dropping the Oil(0) on the sensor surface (i.e., starting the pH measurement of the lubricant), and it reached a constant value of ca. 7.5. On the other hand, the pH value decreased soon after dropping other oxidized Oil(n)s on the sensor surface, and the pH value decreased with an increase in the oxidation period. Consequently, the pH value of all the Oil(n)s was largely dependent on the oxidation period and the TAN value. In addition, the response speed of the CCP(2.5) sensor to all the Oil(n)s was much faster than the deterioration rate of general lubricants under common usage conditions. These results show that the sensor is really promising as a device monitoring the deterioration of various lubricants on site as well as in real time. We will report effects of thickness of the CCP film on the response behavior and response transients of CCP(m) sensors to other kinds of lubricants and discuss their operating mechanism in this presentation. References [1] E. Förster et al., Measurement, 137 (2019) 673–682. [2] Y. Felkel et al., Chemometrics Intell. Lab. Syst., 101 (2010) 14–22. [3] M. Soleimani et al., Sens. Actuators B, 199 (2014) 247–258. [4] M. Soleimani et al., Tribol. Int., 65 (2013) 48–56. [5] K. Yang et al., Sens. Bio-Sens. Res., 23 (2019) 100273. [6] M. F. Smiechowski et al., Sens. Actuators B, 96 (2003) 261–267. [7] T. Hyodo et al., Chem. Sens., 31(B) (2015) 121–123. [8] M. Tsuruoka et al., Chem. Sens., 34(B) (2018) 19–21. [9] Y. Sakamoto et al., Abs.56th Kyushu Area Joint Meeting of Chem.-Related Soc. (2019) EC-4-005. [10] Horiba, Ltd., Catalog of Water Quality Analyzers (LAQUA Series), No. HRE-0041H. Figure 1

Flexible multifunctional sensors on skin or wearables are considered highly suitable for next-generation noninvasive health care devices. In this regard, the field-effect transistor (FET)-based chemical sensors such as ion-sensitive FETs (ISFETs) are attractive as, with the ultrathin complementary metal oxide semiconductor technology, they can enable a flexible or bendable sensor system. However, the bending-related stress or strain could change the output of devices on ultrathin chips (UTCs), and this has been argued as a major challenge hindering the advancement and use of this technology in applications such as wearables. This may not be always true, as with drift-free ISFETs, we show that bending could also enhance the performance of UTCs. Through fine control of bending radius in the micrometer scale, the mechanically flexible RuO2-based ISFETs on UTCs (44.76 μm thickness) are shown to reproducibly enhance the performance even after 1000 bending cycles. The 1.3 orders of magnitude improved stability (the drift rate changed from -557 nA/min to -28 ± 0.16 nA/min) is observed over a time period of 417.3 s (∼7 min) at fixed biasing and temperature conditions and under different pH conditions. Finally, a compact macromodel is developed to capture the bending-induced improvements in flexible ISFETs. The performance enhancement by controlled bending of devices could generally benefit the rapidly growing field of flexible electronics.

In this paper, a triple gate (TG) cavity based, polysilicon junctionless (JL) ion-sensitive field-effect transistor (ISFET) architecture has been proposed for the first time. The performance of the proposed device has been compared with conventionally doped ISFET. The effect of pH is investigated for different adhesion layers, device layer thickness (tsi), electrolyte thickness (te) and, channel lengths (L). Threshold voltage( $\frac {\triangle {V_{th}}}{\triangle {pH}}$ ) has been used as sensing metric for analysis and comparison. Besides, ION/IOFF ratio has also been measured for different pH. The average maximum threshold voltage sensitivity of the proposed device has been measured and found to be 72.5%, 49.5%, and 53.7% better than TG-conventional ISFET for different adhesion layers, device layer thickness, and channel lengths respectively. Furthermore, the effect of channel lenghth on threshold voltage sensitivity has also been studied. It is observed that the sensitivity increases with increase in channel length. The implementation and all the simulations have been performed by using the ATLAS device simulator.

Accurate diagnose of a disease in the early stage is critical to treat the disease properly. To this end, a multitude of biosensors with advanced technologies have been developed to detect the number of biomolecules precisely. In this work, we propose a method for extracting the Stern layer capacitance (Cstern) using the experimental data of silicon nanowire ion-sensitive field-effect transistors (ISFETs) to help improve the accurate detection of target molecules. The proposed method was applied to both pH and virus sensing scheme, and the Cstern value of pH and a virus were extracted as 32 and 26 μF/cm2, respectively. These findings indicated that the extracted Cstern was affected by the size of the ion and protein, which also was verified by a computer-aided simulation. These insights would be useful in the development of charge-based ISFET biosensors.

The sensitivity of conventional ion-sensitive field-effect transistors (ISFETs) is limited by the Nernst equation, which is not sufficient for detecting weak biological signals. In this study, we propose a silicon-on-insulator-based coplanar dual-gate (Cop-DG) ISFET pH sensor, which exhibits better performance than the conventional ISFET pH sensor. The Cop-DG ISFETs employ a Cop-DG consisting of a control gate (CG) and a sensing gate (SG) with a common gate oxide and an electrically isolated floating gate (FG). As CG and SG are capacitively coupled to FG, both these gates can efficiently modulate the conductance of the FET channel. The advantage of the proposed sensor is its ability to amplify the sensitivity effectively according to the capacitive coupling ratio between FG and coplanar gates (SG and CG), which is determined by the area of SG and CG. We obtained the pH sensitivity of 304.12 mV/pH, which is significantly larger than that of the conventional ISFET sensor (59.15 mV/pH, at 25 °C). In addition, we measured the hysteresis and drift effects to ensure the stability and reliability of the sensor. Owing to its simple structure, cost-effectiveness, and excellent sensitivity and reliability, we believe that the Cop-DG ISFET sensor provides a promising point-of-care biomedical applications.

In this paper, we discuss the effect of mismatch due to trapped charge on floating-gate ISFET sensors which constitutes one of its major limitations when fabricated in unmodified CMOS. Especially evident when designing ISFET arrays, mismatch due to trapped charge is significant and random and causes pixels to operate outside their target operating region. Here, we show a gradient descent algorithm that uses a Programmable-Gate in-pixel capacitor to reduce the mismatch across pixels in an iterative and unsupervised manner. Furthermore, we show that this algorithm can be reduced to a single iteration step by estimating in advance the total step of the GD since it depends on a capacitive ratio. We show measured results of both approaches on a ${64}\times {200}$ ISFET array which uses a parasitic capacitance across two metal layers in-pixel to obtain a very small PG capacitor. Both approaches are demonstrated across 4 chips and significantly reduce the mismatch spread with comparable performance.

The purpose of this analytical research is the capability of sensing different K+ concentrations by the ion-sensitive field effect transistor (ISFET) based on graphene. By gate voltage variation values, K+ ion concentration in the electrolyte can be measured, since there are interactions between the K+ and the gate ions. We have applied the adaptive neuro-fuzzy inference system (ANFIS) model to predict the current–voltage (I–V) characteristic which has resulted in satisfactory performance.

In this article, we present a theoretical analysis of a junctionless (JL), ion-sensitive, field-effect-transistor (ISFET), self-consistently combining the electrochemical interaction between the semiconductor-insulator interface and the surrounding electrolyte medium. Incorporating charge-based core relationships for the nanowire (NW) and planar double gate (DG) JL FETs with basic relations governing the electrolyte-insulator proton exchanges, we predict the output characteristics of the NW and DG JL ISFETs with respect to pH for all the regions of operation. This hybrid charge-based approach of JL ISFETs is fully validated by COMSOL Multiphysics simulations without the need to introduce any fitting parameters. These developments are suitable for implementation in circuit simulators as well as for fast prototyping by tuning the technological parameters and estimate their impact on the device performances, including the electrolyte medium.

A graphene-based ion sensitive field effect transistor (GISFET) has been developed and investigated in terms of its ion sensing performance. The GISFET sensor was found to demonstrate a high detection sensitivity enabling direct measurement of K+ ion efflux from live cells. The sensing performance of the GISFET was directly compared to that of a commercial Si ISFET and very similar detection results were obtained, highlighting the promise of the GISFET sensor for ion-sensing applications. Additionally, fabrication of a GISFET array containing 25 devices using a CMOS compatible photolithographic process was demonstrated, which resulted in good uniformity across the array and high ion sensing properties of the devices, underlining their application potential for simultaneous multi-well testing with small sample volume.

Field-effect transistor (FET) sensors are attractive potentiometric (bio)chemical measurement devices because of their fast response, low output impedance, and potential for miniaturization in standard integrated circuit manufacturing technologies. Yet the wide adoption of these sensors for real-world applications is still limited, mainly due to temporal drift and cross-sensitivities that introduce considerable error in the measurements. In this paper, we demonstrate that such non-idealities can be corrected by joint use of an array of FET sensors – selective to target and major interfering ions – with machine learning (ML) methods in order to accurately predict ion concentrations continuously and in the field. We studied the predictive performance of linear regression (LR), support vector regression (SVR), and state-of-art deep neural networks (DNNs) when monitoring pH from combinatorial H+, Na+, and K+ion-sensitive FET (ISFET) sequences of readings collected over a period of 90 consecutive days in real water quality assessment conditions. The proposed ML algorithms were trained against reference online measurements obtained from a commercial pH sensor. Results show a greater capability of DNNs to provide precise pH monitoring for longer than a week, achieving a relative root-mean-square error reduction of 73% over standard two-point sensor calibration methods., The authors acknowledge funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 747848 and the SNSF-Sinergia WeCare project (No.CRSII5_177255).

The ion sensitive field effect transistor (ISFET) are being utilized in pH sensor technology to sense pH values. However, it is highly sensitive to temperature and may introduce variations in the output resulting into errors in the reading. This paper proposes a readout integrated circuit (ROIC) for temperature compensation of an ISFET based pH sensor. The resistor present in the bridge works as a thermistor and helps in stabilizing the output. The test circuit is simulated using LTSpice. The analysis is done for a temperature range of 0 − 50°C and pH range of 5.5 to 14 respectively. The performance analysis has been presented with four different type of sensing films i.e. SiO 2 , Al 2 O 3 , Ta 2 O 3 and Si 3 N 4 . The proposed circuit gave optimum results, wherein a constant output voltage is achieved throughout the temperature range 0 − 50°C with sensitivity less than 56.33mV/pH. The proposed circuit has been briefly compared with the existing circuits.

Ion-sensitive field-effect transistor (ISFET) is one of the most promising chemical sensors that has many advantages such as high integration capability, low cost, simple interface, and high productivity. ISFET has the capability to detect various molecules such as enzymes, antibodies and proteins, but pH sensing is mainly discussed in this paper. An ISFET model is developed using the TCAD tool - COMSOL Multiphysics 5.5 to study the characteristics of the ISFET as a pH sensor. The model also used to investigate the effects of gate insulator materials, other geometry consideration and operating condition on ISFET performance. The I d -Vg characteristics, threshold voltage, electric potential, and sensitivity of the ISFET were analysed. The simulated results were verified against approximated values calculated using the surface potential equation. It was observed that the tantalum pentoxide, Ta 2 O 5 dielectric material has the highest sensitivity, which is very near to the calculated Nernst limit and thinner oxide layer can result in smaller threshold voltage which may lead to lower the power consumption.

In this study, we propose a highly sensitive transparent urea enzymatic field-effect transistor (EnFET) point-of-care (POC) diagnostic test sensor using a triple-gate amorphous indium gallium zinc oxide (a-IGZO) thin-film pH ion-sensitive field-effect transistor (ISFET). The EnFET sensor consists of a urease-immobilized tin-dioxide (SnO2) sensing membrane extended gate (EG) and an a-IGZO thin film transistor (TFT), which acts as the detector and transducer, respectively. To enhance the urea sensitivity, we designed a triple-gate a-IGZO TFT transducer with a top gate (TG) at the top of the channel, a bottom gate (BG) at the bottom of the channel, and a side gate (SG) on the side of the channel. By using capacitive coupling between these gates, an extremely high urea sensitivity of 3632.1 mV/pUrea was accomplished in the range of pUrea 2 to 3.5, this is 50 times greater than the sensitivities observed in prior works. High urea sensitivity and reliability were even obtained in the low pUrea (0.5 to 2) and high pUrea (3.5 to 5) ranges. The proposed urea-EnFET sensor with a triple-gate a-IGZO TFT is therefore expected to be useful for POC diagnostic tests that require high sensitivity and high reliability.

Ion sensitive field effect transistor (ISFET) is composed of an ion selective sensing film and a transistor and is able to convert the chemical information of ion concentration into the change of current or voltage. As the oxide of the transistor of ISFET is directly contacted with the solution, it leads to unstable sensitivity and poor stability. Extended gate field effect transistor (EGFET), which separates the sensitive film and transistor, is able to greatly improve the sensing performances. This work investigates the pH sensing performance of EGFET with zinc oxide (ZnO) as the active film. The pH sensitivity and current sensitivity of ZnO are studied and analyzed. The sensitivity is excellent and the data linearity is good (0.99).

In this paper, a combined pH and impedance sensing system suitable for portable measurements is presented. The sensor outputs are converted directly to frequency or pulse width. The pH sensor is based on a voltage clamp topology that uses charging and discharging capacitors, voltage window comparators, and an SR-Latch to convert the output to frequency. The impedance to frequency sensor is based on current and voltage comparators and an SR-Latch. The pH system based on ISFET transistors is experimentally verified with on chip electrodes while the impedance sensor is characterized with discrete electronic components. The portable system is implemented with two chips and an external multi-electrode array into a portable system. Resistance, capacitance, and pH are experimentally measured using buffer solutions to simulate a water quality monitoring application. The system is implemented in a portable format and all modules, excluding the commercial microprocessor, consume an average power of 56 $ \mu W$ with an area of 0.006 mm $^{2}$ using a 180 nm technology.

Ions-Sensitive Field-Effect Transistors (ISFETs) have been widely used as sensor interfaces for biochemical and chemistry fields. Despite ISFET’s fast reaction (i.e. response), compact size as well as large measurement range, temperature variability is commonly impact the reliability of the measuring performance, which requires more protection in the results obtained and instruments of the study. In this article, we are introducing a new method for a CNISFET micro-sensor that uses a flexible analog circuit to perform noise reduction and temperature compensation. The circuit is developed for the common CNISFET micro sensor simulated on the TopSPICE platform. The proposed topology demonstrates a strong immunity to temperature variation and the interference of the noise.

Autologous chondrocytes are generally evaluated by mechanical, histological, and biochemical methods. However, the analyzed data are from discontinuous measurements at an end point, during which living chondrocytes are destroyed and stained. To solve the problem, we developed a label-free and noninvasive method of estimating extracellular matrix (ECM) production that results from chondrocyte metabolic activities using a cultured-chondrocyte-based gate ion-sensitive field-effect transistor (ISFET) in this study. Using the cultured-chondrocyte-based gate ISFET sensor, we found that the change in electrical signal (ΔVout), which indicated the change in interfacial pH at the chondrocyte/gate nanogap (ΔpHint), gradually increased over 3 weeks upon adding a biologically active substance, l-ascorbic acid phosphate magnesium salt n-hydrate (APM), which was attributable to chondrocyte metabolic activities. The increase in ΔVout (ΔpHint) caused by the chondrocyte metabolic activities was also confirmed by the obser...

Machine learning has become an emerging method for next-generation smart technologies. It also promotes a development-paradigm shift in sensing technologies, which are essential in various smart applications. In this paper, we develop a data-driven method for a monolithic ion-sensitive field-effect transistor (ISFET) to have both photon and pH bi-detection capabilities simultaneously. The proposed methods are executed based on sequential-bias-reconfiguration of the ISFET. Utilizing support vector machine and back-propagation neural network, the photocurrent and ion-induced current can be calculated and decoupled. To evaluate the proposed method, semi-quantification by classification methods and quantification by regression methods are both examined. This paper has experimentally demonstrated the dual-detection capability of a pH range from 5 to 9 and an intensity range from 0 to $760~\mu \text{W}$ /cm2 with prediction error less than 1.5%. To fulfill low-computation requirement for applications, we further optimize the proposed algorithm by feature reduction to balance performances between accuracy, complexity of data acquisition, and data processing. With the developed machine-learning sensing device, therefore, we successfully demonstrate potentials of data-driven sensing devices in future applications.

We developed ion-sensitive field effect transistors (ISFETs) with disposable paper extended gates (EGs). The sensing and the measuring part of conventional ISFETs are not separated and integrated on the same device. Therefore, if the sensing part is contaminated by reaction in a chemical solution, there is a problem that an expensive measuring part manufactured through a complicated process becomes also unusable. To overcome this problem and provide a cost-effective sensor platform, we constructed a high-sensitivity ISFET sensor with a measuring transistor part and a separate EG sensing part. In particular, in this experiment, a double-gate transistor capable of amplifying the sensitivity using the capacitive coupling effect between a top-gate and a bottom-gate, which differs from a general single gate transistor on an SOI substrate, was fabricated. As a result, the pH sensitivity of 1199.92 ± 32.4 mV/pH could be achieved using paper EG and dual-gate mode sensing operation, which greatly exceeds the theoretical Nernst limit (59.15 mV/pH at 25 °C) in single gate mode sensing operation. We also measured non-ideal effects such as the hysteresis and drift behavior of paper EGs, and demonstrated that they have excellent stability and reliability for long-term measurements. In addition, hysteresis and sensitivity were measured after 3, 7, 14 and 30 days to verify the aging effect of the continuous use of paper EGs. As a result, paper EGs showed stable operating characteristics for 30 days. Therefore, we expect that double-gate ISFETs with flexible paper EGs will have a significant impact on label-free, low-environmental impact, cost-effective, disposable, and flexible FET-based biosensor applications.

In this article, we study the ion-sensitive gated bipolar transistor (ISBiT) by forward biasing the source-body diode of the ion-sensitive field-effect transistor (ISFET). Based on theory, extensive TCAD device simulations, and experiments, it is shown that the ISBiT operates at lower gate-voltages with a higher transconductance ( ${g}_{m}$ ) than the ISFET both in subthreshold and near-threshold modes. In addition, overall maximum $g_{m}$ ’s have been obtained for the former when operating in saturation mode. However, in the linear superthreshold operation mode, the ISBiT shows lower $g_{m}$ ’s because of the field-induced mobility reduction. The same trends have been obtained for the pH-sensitivity expressed as $\partial {I}_{\text {D}}/\partial {\text {pH}}$ , since it is linearly dependent on the ${g}_{m}$ , as predicted by the theory. Basically, the ISBiT offers more tunability, hence, freedom in the sensor system.

We demonstrate large-area graphene based ion sensitive field effect transistors (ISFETs) with potassium ionophore sensing layers. Graphene ISFETs encapsulated with an ultra-thin hydrophobic layer, parylene C, and active areas ∼0.4 cm2 are characterized by an rms current noise as low as 5 nA in a 60 Hz electrical bandwidth, field effect mobilities up to 5000 cm2 V−1 s−1 and quantum capacitance limited coupling. Real-time sensing of K+ was achieved with a detection limit of 10−9 M K+, equivalent to 39 ng/L, and a resolution of ∼2 ×10−3 log [K+]. The ISFETs exhibit reversibility under spiking experiments and long term stability with limited drift over a course of five months. The cross-sensitivity has been measured to be 2.5 mV/decade for Na+, 4.2 mV/decade for Ca2+, 1.5 mV/decade for Mg2+ and 9.0 mV/decade for NH 4 + . Experiments with a variety of specimens, including beverages and blood, confirm the suitability of graphene ISFETs for K+ sensing in fluids with multiple solutes. The graphene ISFET design can be extended to sensing of other ionic species by substitution of alternative ionophores within the sensing membrane.

Purpose The purpose of this paper is to present the influence of gate dielectric etching on obtained MISFET (metal insulator semiconductor field effect transistor) structures. Because of its properties, aluminum nitride (AlN) layers can be successfully used in a large area of applications. In addition, AIN has a wide bandgap (6.2eV) and high thermal conductivity (3.2 W/cm * K). Its melting temperature is greater than 2,000°C. The relative permittivity is about 9. All these features (especially high power, high temperature and high-frequency) make AlN a useful material in the fields of electronic, optical and acoustic applications. Design/methodology/approach To fabricate n-channel transistors, silicon technology was used. The 50-nm thick AlN films were deposited using the magnetron sputtering. After preparation of SiO2/AlN stack as the gate dielectric, the optimization processes of dry etching in plasma environment by Taguchi method were realized. In the next step, three methods of AlN etching were selected and used to MISFET device fabrication. Atomic force microscopy and scanning electron microscopy allowed to surfacing of the state observation after etching process. The current–voltage (I–V) output and transfer characteristics of structures with modified etch technology were measured. Keithley SMU 236/237/238 measurement set was used. Findings In this research work, a method of AlN etching in a field effect transistor technology was developed and improved. Current−voltage characteristics of obtained MISFET structures were measured and compared. Influence of etching procedure on transistors properties was examined. Originality/value The obtained results allow improving the MISFET technology based on AlN film as a gate dielectric. The complete research work will allow using the developed technologies to implement in highly sensitive ion-sensitive field effect transistor (ISFET) structures in the future. The improvement of the etching element in the technology strongly influences the detection capabilities and operating range of the transistor.

The response of trilayer graphene nanoribbon (TGN)‐based ion‐sensitive field‐effect transistor (ISFET) to different pH solutions and adsorption effect on the sensing parameters are analytically studied in this research. The authors propose a TGN‐based sensor to electrochemically detect pH. To this end, absorption effect on the sensing area in the form of carrier concentration, carrier velocity, and conductance variations are investigated. Also, the caused electrical response on TGN as a detection element is analytically proposed, in which significant current decrease of the sensor is observed after exposure to high pH values. In order to verify the accuracy of the model, it is compared with recent reports on pH sensors. The TGN‐based pH sensor exposes higher current compared to that of carbon nanotube (CNT) counterpart for analogous ambient conditions. While, the comparative results demonstrate that the conductance of proposed model is lower than that of monolayer graphene‐counterpart for equivalent pH values. The results confirm that the conductance of the sensor is decreased and V(g‐min) is obviously right‐shifted by increasing value of pH. The authors demonstrate that although there is not the experimental evidence reported in the part of literature for TGN sensor, but the model can assist in comprehending experiments involving nanoscale pH sensors.

In this work, ion sensitive field effect transistor (ISFET) which is a device sensitive to the ions in a solution is employed. It is shown that under a fixed bias configuration, the voltage change causes a subsequent change in the surface potential of graphene thin film, which induces a detectable current change in the conducting channel between drain and source electrodes. Thus the transduction from an analog signal as an ion concentration(K+) changes to an electrical signal as current change can be achieved. For prediction purpose, the regression tree algorithm and artificial neural network (ANN) have been employed to predict the I-V characteristic, however ANN outperforms the regression tree approach and gives more accurate results.

The development of next generation medicines demand more sensitive and reliable label free sensing able to cope with increasing needs of multiplexing and shorter times to results. Field effect transistor-based biosensors emerge as one of the main possible technologies to cover the existing gap. The general trend for the sensors has been miniaturisation with the expectation of improving sensitivity and response time, but presenting issues with reproducibility and noise level. Here we propose a Fin-Field Effect Transistor (FinFET) with a high heigth to width aspect ratio for electrochemical biosensing solving the issue of nanosensors in terms of reproducibility and noise, while keeping the fast response time. We fabricated different devices and characterised their performance with their response to the pH changes that fitted to a Nernst-Poisson model. The experimental data were compared with simulations of devices with different aspect ratio, stablishing an advantage in total signal and linearity for the FinFETs with higher aspect ratio. In addition, these FinFETs promise the optimisation of reliability and efficiency in terms of limits of detection, for which the interplay of the size and geometry of the sensor with the diffusion of the analytes plays a pivotal role., Comment: Article submitted to Nano Letters

In this study, the graphene ion-sensitive field-effect transistor in an electrolyte solution with different K+ concentration has been investigated. It is found that by measuring the gate voltage changes, the K+ concentration in the electrolyte can be determined because of the interaction between the K+ ions and the gate. For prediction purpose, the artificial neural network has been employed to predict the I–V characteristic, and it demonstrated superior performance.

The reference electrode (RE), such as the widely used Ag/AgCl redox-couple electrode, is both hard to maintain and difficult to integrate as a constituent of an on-chip sensing system. Inert metals, such as Pt and Au, have been investigated as a pseudo-RE in miniaturized sensing systems. However, they generally suffer from instabilities arising from variations of ion compositions in the electrolyte. This paper presents a novel microfluidic-controlled Pt-KCl RE (PtRE) system that sets a stable potential independent of ion activities and activity changes. Assisted by extensive simulations to guide the system design, we show experimentally that the microfluidic-controlled PtRE system performs the functions of an excellent RE for ion-sensitive field-effect transistor (ISFET). The PtRE system is then implemented as an RE for an ISFET in pH sensing. Miniaturization of the PtRE system to millimeter-dimensions is shown viable by simulation, which may open the possibility for its on-chip integration.

This paper presents fabrication, characterization and modeling of aluminum nitride (AIN)-gate ion-sensitive field-effect transistor based pH sensor. The AIN sensing film is deposited using pulsed DC magnetron assisted reactive sputtering technique and the process optimization has been described. Material characterization was carried out for the deposited film by X-ray diffraction, field-emission scanning electron microscopy and energy dispersive spectroscopy and it was found that AlN film has polycrystalline structure. The fabricated device is tested in different pH buffer solutions (pH 4, 7 and 10) and a sensitivity of 33 mV/pH is obtained. A simulation program with integrated circuit emphasis (SPICE) macromodel was created by introducing electrochemical parameters in a metal-oxide field-effect transistor model for performing electrochemical simulations. We performed parametric sweep of electrochemical parameters to theoretically estimate the experimental results and we observed that the inclusion of amine sites in the SPICE macromodel is essential in determining precise sensor characteristics.

In this study, we fabricated extended-gate (EG) field-effect transistor (FET) pH sensors with dualgate (DG) structures, using a range of dielectric sensing membranes (SiO₂, Si₃N₄, HfO₂ and Ta₂O5) to vary their sensitivity. The fabricated EGFETs consisted of a silicon-on-insulator (SOI)-based metal-oxide semiconductor field-effect transistor (MOSFET) transducer and an EG sensor. We amplified the sensitivity of the device far beyond the Nernst limit (59 mV/pH), which is the theoretical maximum of conventional ion-selective FET (ISFET) sensing, by applying capacitive coupling. Among the evaluated dielectric sensing membranes, we obtained the highest sensitivity (478 mV/pH), low hysteresis (100.2 mV) and drift rate (24.6 mV/h) from the pH sensor with a Ta₂O5 membrane. Hence, we expect DG FET configurations using Ta₂O5 films as EG sensing membranes to be useful for high performance biosensor applications, as they satisfy the requirements for sensitivity, stability and reliability.

This paper demonstrates and compares three configurations for ISFET arrays fabricated in unmodified CMOS that facilitate chemical imaging with linear pH-to-output conversion. Specifically, the typical voltage-mode source-follower configuration is compared against our recently proposed current-mode approach using an ISFET in velocity saturation. These two topologies are also compared against an extension of the current-mode topology to include a programmable-gate capacitor inside the pixel stack for offset compensation. Various performance metrics, such as linearity, speed, power consumption, size, attenuation, and noise have been experimentally measured to quantify the performance of each approach and a figure-of-merit (FoM) has been defined to capture the overall performance. Using this FoM, the current-mode approach results in the best overall performance. Through this paper, however, the relative merits and limitations of each approach are identified to be used as a guide for future designs which are usually application-specific. Furthermore, we illustrate methods used to obtain standard ISFET performance metrics in order to standardize the comparison of ISFET arrays using the figure-of-merit.

This paper presents a USB 3.0 based readout platform for real-time ion imaging applications. The front end utilizes an ion-imaging array containing 16 k ISFET pixels to capture ion diffusion at 6100 fps. Operating at 200 MHz, the chip streams ion information at a data rate of 762.94 Mb/s. The backend readout system employs a FIFO-to-USB bridge (FT601Q) that supports Super Speed (5Gbps) to perform real-time data streaming and operates in bulk transfer mode to ensure data integrity. Implemented on a Xilinx Virtex UltraScale+ FPGA, the system involves a high-throughput data path through the on-board DDR4 SDRAMs, based on which a ring buffer is designed to provide the 2 GB buffering capacity. The readout system can operate in real time regardless of the USB glitches encountered on the Windows OS when involving data polling. In addition, a simple differencing algorithm with threshold detection is integrated into the back end for dynamic frame rate operation. The proposed readout system performs real-time ion imaging at high speed as well as streams the collected images for visualization within a latency of 25 ms, achieving state-of-the-art performance for high-speed Lab-on-Chip applications.

We have developed a CMOS System-on-Chip capable of concurrent DNA detection and actuation towards ultrafast and accurate molecular diagnostics. The system relies on a sensor array to perform electrochemical imaging by combining potentiometric ion-sensitive field-effect transistor (ISFET) sensing with impedance spectroscopy to concurrently detect DNA molecules and protons generated during an amplification reaction at high resolution. The impedance sensing electrodes are also used to conduct DNA manipulation using dielectrophoresis (DEP), further improving performance. The system achieves a maximum electric field strength of 2.5MV/m, generated with an AC voltage input of 1.8V, which is suitable for a battery supplied portable device. The sensing system made of EIS and ISFET front-ends are implemented in 0.18 µm CMOS technology. The ISFET sensing system presents a readout sensitivity of up to 129 mV (with a gain of 15 dB) with programmable controlled gate voltage to compensate non-idealities. Lastly, the EIS system is able to detect an impedance up to 100 MO within a frequency range between 100Hz-100kHz, presenting a dynamic range of 84.1 dB. The integrated systems achieve dual sensing and actuation for electrochemical DNA sensing with improved performance.

This paper presents a multi-sensing pixel capable of sensing ion concentration, temperature, moisture and light from the same spatial point. The presented pixel is composed of an ISFET chemical sensor, a light sensor, a moisture sensor and a temperature sensor, all implemented in standard CMOS technology in a compact pixel. All sensing modalities are acquired simultaneously and modulated onto a single waveform using multi-frequency PWM modulation, overcoming the associated transmission overhead. Furthermore, ISFET non-idealities such as trapped charge are compensated through a global DAC, balancing the input linear OTA, while the light sensor dark current is mitigated in-pixel by subtracting its influence using a reference photodiode. The proposed pixel occupies 50x50 μτη2, and it is integrated as part of a 4x4 multi-sensing array, along with on-chip biasing, instrumentation and digital control. To the best of our knowledge, this architecture represents the first multi- sensing architecture capable of extracting four features from the same spatial point simultaneously, enabling ISFET-based platforms to sense both the chemical signal and the external conditions influencing its measurement.

The use of deoxyribonucleic acid (DNA) hybridization to detect disease-related gene expression is a valuable diagnostic tool. An ion-sensitive field-effect transistor (ISFET) with a graphene layer has been utilized for detecting DNA hybridization. Silicene is a two-dimensional silicon allotrope with structural properties similar to graphene. Thus, it has recently experienced intensive scientific research interest due to its unique electrical, mechanical, and sensing characteristics. In this paper, we proposed an ISFET structure with silicene and electrolyte layers for the label-free detection of DNA hybridization. When DNA hybridization occurs, it changes the ion concentration in the surface layer of the silicene and the pH level of the electrolyte solution. The process also changes the quantum capacitance of the silicene layer and the electrical properties of the ISFET device. The quantum capacitance and the corresponding resonant frequency readout of the silicene and graphene are compared. The performance evaluation found that the changes in quantum capacitance, resonant frequency, and tuning ratio indicate that the sensitivity of silicene is much more effective than graphene.