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Farmers aim to increase the yield of their crops by reducing their expenses. This prompts farmers to resort to smart farming practices. These practices facilitate the measurement and detection of nutrients in soil to maximize harvest with a low-cost sensor employing electrochemical and optical techniques. Potassium is a crucial macronutrient for the growth of plants. The excess or need for potassium in the soil can pose a risk to plants and the environment. Therefore, it is imperative to conduct soil monitoring to determine the quantity of soil fertilizer. ISFETs are among the most affordable and miniaturized sensors and are specific to one target ion. Although it is not time-consuming and requires an immediate response, the ISFET requires special calibration and sample preparation. This study tested ISFET on Moroccan soil potassium using a new technique of minimal sample preparation without needing a laboratory machine to extract soil using distilled water. The results indicate that the microsensor ISFET provided accurate results on solutions prepared in the laboratory with a correlation factor of 90%, and R² greater than 80% when estimating potassium levels in soil extracts. ISFET can therefore be used as an alternative method for potassium estimation. [ABSTRACT FROM AUTHOR]

Current diagnostic and prognostic tests for prostate cancer require specialised laboratories and have low specificity for prostate cancer detection. As such, recent advancements in electrochemical devices for point of care (PoC) prostate cancer detection have seen significant interest. Liquid-biopsy detection of relevant circulating and exosomal nucleic acid markers presents the potential for minimally invasive testing. In combination, electrochemical devices and circulating DNA and RNA detection present an innovative approach for novel prostate cancer diagnostics, potentially directly within the clinic. Recent research in electrochemical impedance spectroscopy, voltammetry, chronoamperometry and potentiometric sensing using field-effect transistors will be discussed. Evaluation of the PoC relevance of these techniques and their fulfilment of the WHO's REASSURED criteria for medical diagnostics is described. Further areas for exploration within electrochemical PoC testing and progression to clinical implementation for prostate cancer are assessed. [ABSTRACT FROM AUTHOR]

Farmers aim to increase the yield of their crops by reducing their expenses. This prompts farmers to resort to smart farming practices. These practices facilitate the measurement and detection of nutrients in soil to maximize harvest with a low-cost sensor employing electrochemical and optical techniques. Potassium is a crucial macronutrient for the growth of plants. The excess or need for potassium in the soil can pose a risk to plants and the environment. Therefore, it is imperative to conduct soil monitoring to determine the quantity of soil fertilizer. ISFETs are among the most affordable and miniaturized sensors specific to one target ion. Although it is not time-consuming and requires an immediate response, the ISFET requires special calibration and sample preparation. This study tested ISFET on Moroccan soil potassium using a new technique of minimal sample preparation without needing a laboratory machine to extract soil using distilled water. The results indicate that the microsensor ISFET provided accurate results on solutions prepared in the laboratory with a correlation factor of 90%, and R² greater than 80% when estimating potassium levels in soil extracts. ISFET can therefore be used as an alternative method for potassium estimation.

Study of enzyme-substrate interactions is a task of great practical and scientific importance. This paper describes the application of ion-sensitive field effect transistors in quasi-equilibrium state for examination of enzymatic reactions. A reaction occurring in the liquid gate affects the chemical potential of electrons in this gate, and this phenomenon may be used to explore biochemical interactions. This strategy can be applied to detect interactions of enzymes with substrates, inhibitors and activators regardless of their optical and electrochemical properties. Using the developed method, the reactions catalyzed by the enzymes belonging to six different EC classes were analyzed, and Michaelis constants for their substrates were determibed. Km values obtained using the proposed method were in good agreement with those obtained with standard colorimetric and fluorimentric assays. Practical potential of the described method was demonstrated by studying the interactions of a diagnostically significant enzyme α-D-galactosidase with its natural and artificial substrates and its inhibitor. Km values for α-D-galactosidase using melibiose and raffinose as substrates and IC50 value for the enzyme inhibitor 1-deoxygalactonojirimycin were determined. The described method allows rapid and label-free investigation of enzyme interactions with substrates, inhibitors and activators for a wide range of biocatalysts.

When working with a few molecules, the existing protein sequencing technologies lack the single-site amino acid (AA) precision required to detect abnormalities that escape genome analysis. We offer a new method for identifying AAs and short polypeptides using the signal from the surface potential and capacitance obtained from Field Effect Transistor (FET) sensors. Using a combination of the Site-binding and Gouy-Chapman-Stern (GCS) models, we found the signatures of every single AA and polypeptides. These fingerprints are based on orthogonal features such as the proton dissociation constants of each AA’s charging sites, the dielectric constant, and the effective length.

Significant progress has been achieved in the field of solid-state biosensors over the past 50 years. Various sensing devices with high-density integration and flexible configuration, as well as new applications for clinical diagnosis and healthcare, have been developed using blood, serum, and other body fluids such as sweat, tears, and saliva. A high-density array of ion-sensitive field effect transistors was developed by exploiting the advantages of advanced semiconductor technologies and commercialized in combination with an enzymatic primer extension reaction as a DNA sequencer in 2011. Different types of materials such as inorganic materials, metals, polymers, and biomolecules are mixed together on the surface of the gate while maintaining their own functions; therefore, compatibility among different materials has to be optimized so that the best detection performance of solid-state biosensors, including stability and reliability, is achieved as designed. Solid-state biosensors are suitable for the rapid, cost-effective, and noninvasive identification of biomarkers at various timepoints over the course of a disease.

Field‐effect transistors have strong applications in biosensing field from pH and glucose monitoring to genomics, proteomics, cell signaling assays, and biomedical diagnostics in general. Notable advantages are the high sensitivity (thanks to intrinsic amplification), quick response (useful for real‐time monitoring), suitability for miniaturization, and compact portable read‐out systems. The initial concept of ion‐sensitive field‐effect transistors evolved with the emergence of novel classes of materials beyond traditional semiconductors. Recently, 2D nanomaterials are redesigning the field providing superior performances with large surface‐to‐volume ratio, high carrier mobility, more effective local gating, high transconductance, and operation at low voltages. Here, after a brief conceptual introduction, we review progresses and perspectives of 2D materials field‐effect‐transistor biosensors with special focus on opportunities, most recent applications, present challenges, and future perspectives. [ABSTRACT FROM AUTHOR]

Abstract Field‐effect transistors have strong applications in biosensing field from pH and glucose monitoring to genomics, proteomics, cell signaling assays, and biomedical diagnostics in general. Notable advantages are the high sensitivity (thanks to intrinsic amplification), quick response (useful for real‐time monitoring), suitability for miniaturization, and compact portable read‐out systems. The initial concept of ion‐sensitive field‐effect transistors evolved with the emergence of novel classes of materials beyond traditional semiconductors. Recently, 2D nanomaterials are redesigning the field providing superior performances with large surface‐to‐volume ratio, high carrier mobility, more effective local gating, high transconductance, and operation at low voltages. Here, after a brief conceptual introduction, we review progresses and perspectives of 2D materials field‐effect‐transistor biosensors with special focus on opportunities, most recent applications, present challenges, and future perspectives.

Precision agriculture (PA) is a type of farming that focuses on detecting, measuring, and responding to crop variability in fields. Precision agriculture research strives to increase productivity while reducing resources consumption. Nitrate is one of the most critical macronutrients in soil for plant growth. Information on the concentration of nitrate in soil is needed to optimize the amount of fertilizer required for maximum yield. As a result, many farmers rely on traditional chemical analysis to obtain this information, which is costly, time-consuming, and resource intensive. There is a high demand for the use of less expensive and more accurate sensors for nitrate analysis. One of the more affordable and miniaturized sensors is the ISFET. However, this sensor requires specific calibration procedures and sample preparation. This study (i) presents the use of ISFET for the analysis of nitrates in Moroccan soils, (ii) propose to use a new calibration method for ISFET (iii) propose a procedure for Moroccan soil sample extraction. According to laboratory analysis, the findings of this study indicate good accuracy, and the derived conclusions state that ISFET can be used, as an efficient and accurate alternative, for nitrate studies.

Ion‐sensitive field effect transistor (ISFET) sensor is a hot topic these years, playing the combined roles of signal recognizer and converter for (bio)chemical analytes. In this review article, the basic concept, origination, and history of the ISFET sensor are presented. In addition, the common fabrication processes, the most‐used working principle (potentiometric, amperometric, and impedancemetric), and the techniques of gate functionality (physical, chemical, and biological) are discussed introducing the afterward signal transfer processes from ISFET to the terminals through different types of circuits. At last, the development and recent progress (until 2021) of ions and biomolecules (DNA molecules, antibodies, enzymatic substrates, and cell‐related secretions or metabolism) were introduced together with the outlook and facing obstacles (Debye screening, the wearability of ISFET, the multiplexed detections) before the commercialization of ISFET. This review article emphasizes the advantages of the developed ISFET sensors as miniaturization, low‐cost, all‐solid, highly sensitive, and easy operation for portable and multiplexed detections. [ABSTRACT FROM AUTHOR]

Ion-sensitive field-effect transistors (ISFET) are used in various sensing applications including electrochemical biosensing. In this study, analytical models of Ta2O5, Si3N4, and SiO2-gated ISFET-based sensors were developed using MATLAB® and LTspice. The site binding, surface potential, threshold voltage, and drain current transport models were used for analysis of ISFET. This work aims to address the effect of sensing gate material, gate thickness, aspect ratio, temperature, and matrix on ISFET's performance. The thin-layer, gate degradation, and short-channel effects were also analysed. An optimum geometry of ISFET was obtained satisfying the required leakage current and gate capacitance (COX). The role of isothermal point and temperature on ISFETs were also investigated. Additionally, the efficacy of the matrix on ISFET was examined in water, blood, and urine. From the simulation results, a high current sensitivity of 1.97 (mA)1/2/pH and near-Nernstian voltage sensitivity of 56.84 mV/pH were obtained for Ta2O5-gated ISFET. However, Si3N4 and SiO2-gated ISFETs have non-uniform sensitivity characteristics to changes in the pH level. A significant change in pH sensitivity was observed for the Si3N4-gated ISFET in all matrices, whereas the Ta2O5 and SiO2-gated ISFETs were found to be less sensitive to matrix changes. Finally, this work suggests the usage of Ta2O5-gated ISFETs for sensitive sensing applications. [ABSTRACT FROM AUTHOR]

Silicon carbide is an interesting semiconductor for various electronic devices. Moreover, Ion Sensitive Field Effect Transistors (ISFETs) are used for pH detection. In this paper, a MOSFET sub-circuit has been used to model and characterize an ISFET transistor in SiC (6H-SiC) technology developed to be used as a pH sensor. Results are compared with an ISFET transistor in Si technology. The threshold voltage Vth, drain saturation current IDsat, transconductance gm and ION/IOFF ratio are found to change linearly with pH. To prove that it is material and electrical dependent, the different sensitivities in both cases are identified and compared. Interestingly, the results show that the Vth sensitivity, IDsat sensitivity, gm sensitivity and ION/IOFF sensitivity are 56 (60) mV/pH, 38.5 (8) μA/pH, 0.154 (7) μS/pH and 1.7 (7.6) × 106/pH respectively for Si (6H-SiC) ISFETs transistors. Moreover, it has been demonstrated that 6H-SiC ISFET performs better than Si ISFET which makes the SiC technology very promising for pH sensors. [ABSTRACT FROM AUTHOR]

In this work, we have simulated doping less tunneling field-effect transistor (DL-TFET) based pH sensor which can detect the pH variation in an aqueous (electrolyte) medium. The source-sided underlapped technique is employed to achieve better sensitivity. The simulated results were extracted with the help of the software package TCAD-Silvaco. In this work, we have compared the pH sensing capabilities of both conventionally doped TFET (C-TFET) and DL-TFET having the same configuration. Result suggests that the sensitivity of DL-TFET is equal to that of C-TFET. Since DL-TFET already exhibits superiority over C-TFET in terms of better immunity against random doping fluctuations (RDF), low fabrication cost and complexity, it can be used as a better alternative to C-TFET based ISFETs. Furthermore, in this work, we have discussed and demonstrated how the performance and sensitivity of the DL-TFET device can be further increased by the use of low energy band materials like germanium in the source region and high K dielectric materials like Al2O3 as a sensitive oxide layer underneath the underlapped region. The voltage sensitivity achieved by DL-TFET in this work is 312 mV/pH which surpasses the Nernst limits by more than 5 times. [ABSTRACT FROM AUTHOR]

Abstract Ion‐sensitive field effect transistor (ISFET) sensor is a hot topic these years, playing the combined roles of signal recognizer and converter for (bio)chemical analytes. In this review article, the basic concept, origination, and history of the ISFET sensor are presented. In addition, the common fabrication processes, the most‐used working principle (potentiometric, amperometric, and impedancemetric), and the techniques of gate functionality (physical, chemical, and biological) are discussed introducing the afterward signal transfer processes from ISFET to the terminals through different types of circuits. At last, the development and recent progress (until 2021) of ions and biomolecules (DNA molecules, antibodies, enzymatic substrates, and cell‐related secretions or metabolism) were introduced together with the outlook and facing obstacles (Debye screening, the wearability of ISFET, the multiplexed detections) before the commercialization of ISFET. This review article emphasizes the advantages of the developed ISFET sensors as miniaturization, low‐cost, all‐solid, highly sensitive, and easy operation for portable and multiplexed detections.

Methodology of electrical characterization of ISFETs has been described. It is based on a three-stage approach. First, electrical measurements of ISFET-like MOSFETs and extraction of basic parameters of the MOSFET compact model are performed. Next, mapping of the ISFET channel conductances and a number of other characteristic parameters is carried out using a semi-automatic testing setup. Finally, ISFET sensitivity to solution pH is evaluated. The methodology is applied to characterize ISFETs fabricated in the Institute of Electron Technology (IET).

High electron mobility transistor (HEMT) biosensors hold great potential for realizing label-free, real-time, and direct detection. Owing to their unique properties of two-dimensional electron gas (2DEG), HEMT biosensors have the ability to amplify current changes pertinent to potential changes with the introduction of any biomolecules, making them highly surface charge sensitive. This review discusses the recent advances in the use of AlGaN/GaN and AlGaAs/GaAs HEMT as biosensors in the context of different gate architectures. We describe the fundamental mechanisms underlying their operational functions, giving insight into crucial experiments as well as the necessary analysis and validation of data. Surface functionalization and biorecognition integrated into the HEMT gate structures, including self-assembly strategies, are also presented in this review, with relevant and promising applications discussed for ultra-sensitive biosensors. Obstacles and opportunities for possible optimization are also surveyed. Conclusively, future prospects for further development and applications are discussed. This review is instructive for researchers who are new to this field as well as being informative for those who work in related fields. [ABSTRACT FROM AUTHOR]

The ion‐sensitive field effect transistors (ISFETs), proposed little over 50 years ago, today make the most promising devices for lab‐on‐a‐chip, implantable, and point‐of‐care (POC) diagnostics. Their compatibility with CMOS (Complementary Metal Oxide Semiconductor) technology and the low cost through mass production have been the driving factors so far. Nowadays, they are also being developed in flexible form factors for new applications such as wearables and to improve the effective usage in existing applications such as implantable systems. In this regard, the CMOS ultra‐thin chip (UTC) technology and the bonding by printing are the noteworthy advances. This paper comprehensively reviews such new developments in the CMOS‐compatible ISFETs, along with their theory, readout circuitries, circuit‐based techniques for compensation of the ISFET's instabilities, such as the offset, flicker noise, and drift. The sensing mechanisms and the properties of interface between the electrolyte under test and the metal‐oxide based ion‐sensitive electrodes have been discussed along with a brief overview of the metal‐oxide based pH sensors. An overview of the reported mechanically flexible pH sensors, including ISFETs, is provided and the history of ISFET applications are also covered. Finally, established models that can be used to design flexible circuits are presented, and possible opportunities to use circuit techniques to compensate for mechanical deformation are discussed. [ABSTRACT FROM AUTHOR]

The development of an immunosensor‐based biosensor to detect the human serum albumin (HSA) was developed as a low‐cost and label‐free electrical detection through silicon nitride ion‐sensitive field‐effect transistor (Si3N4‐ISFET). This sensor was functionalized using 3‐Aminopropyltriethoxysilane (APTES). The silanized Si3N4‐ISFET surface was covalently linked with antibody against HSA (Anti‐HSA) via glutaraldehyde (GA) to function as an HSA immunosensor for detection of HSA. The interaction between HSA and Anti‐HSA on this device is monitored by changing of the gate potential at a constant drain current of 50 μA. The relationship between HSA concentration and the gate potential change of HSA immunosensor is linear up to 500 μg/ml with a detection limit of 5 μg/ml. This HSA immunosensor offers a good precision in both intra‐ and inter‐assay with a relative standard deviation of 6.61%, 7.48%, 10.69%, and 9.67%, 13.16%, 15.52% for 100, 200, and 400 μg/ml. The average percentage of recovery assay for the concentration of 32.1, 102.1, and 202.1 μg/ml is 96.55%. This sensor also provides its satisfactory selectivity when testing with Bence Jones protein solution. In addition, the results that was done by this HSA immunosensor is similar to the conventional method using immunoturbidimetric detection with a linear regression of 0.99; n = 40 with a paired sample t‐test of <0.01. Thus, this HSA immunosensor could be applied to urinary microalbumin detection because of its simplicity and satisfactory correlation value. [ABSTRACT FROM AUTHOR]

• Fabrication of ISFETs. • Experimental analysis of ISFET for potassium chloride (KCl) sensing. • Sensitivity analysis for measurement methods, with one and two platinum electrodes. This work presents the fabrication and electrical characterization of the Ion Sensitive Field Effect Transistor (ISFET) exposed to potassium chloride (KCl) solutions. The focus of the study is to compare two measurements methods and verify the effects of these methods in the device threshold voltage (V TH) sensitivity to the different KCl concentrations. First, a reference electrode (a platinum needle) is placed in the sample solution over the gate area of the device, demonstrating that the threshold voltage decreases with the increase of the KCl concentration. The method shows a sensitivity of 10.44 mV/mM for the low KCl concentration range (0 to 10 mM) and 0.5 mV/mM for the higher KCl concentration range (10 to 100 mM). The second method involves inserting a second platinum electrode into the solution on the field oxide. This method proposes the KCl electrolysis to increase the selectivity for potassium ions. The result allows the next steps for potassium sensing biosensor application with selective membranes. [ABSTRACT FROM AUTHOR]

In this work, we demonstrate a wafer-scale fabrication of biologically sensitive Si nanowire FET for pH sensing and electrical detection of deoxyribonucleic acid (DNA) hybridization. Based on conventional “top-down” CMOS compatible technology, our bioFETs explore a wide range of design (nanowires (NW), nanoribbons (NR), and honeycomb (HC) structures) with opening access scaled down to only 120 nm. After device fabrication, IDS-VBG transfer and IDS-VDS output characteristics show a conventional n-type FET behavior with an ION/IOFF value higher than 105, as well as an increase of threshold voltage as the NW width is reduced. Then, using a capacitive coupling in our dually-gated Si bioFETs, the pH sensitivity is enhanced with a pH response up to 600 mV/pH. Finally, we successfully detected an increase of threshold voltage of n-type silicon nanowires (SiNWs) due to hybridized target DNA molecules.

The Ion-Sensitive Field-Effect Transistor (ISFET) is one of the most popular pH sensors traditionally using to measure hydrogen ion concentration (pH) of the electrolytic solutions. It is developed from Metal Oxide Semiconductor Field-Effect Transistor (MOSFET) by replacing gate electrode with an electrolytic solution to be tested, and a reference metal electrode immersed in that solution. Basic principle of ISFET operation is based on that of standard NMOS structure in conjunction with the insulator-electrolyte capacitor as described in this paper. The site-binding theory (generalized to two kinds of binding sites), together with the Gouy-Chapman-Stern model for the potential profile in the electrolyte, is coupled to the MOS physics. As a result, an approximate analytical model which completely describes static behavior of the ISFET is obtained. The developed description can serve as useful tool for understanding many contemporary biosensors based on original ISFET structure which has broad application in bio-medicine, biological, chemistry and environmental areas.

The demand for miniaturized point‐of‐care chemical/biochemical sensors has driven the development of field‐effect transistors (FETs) based pH sensors over the last 50 years. This paper aims to review the fabrication technologies, device structures, sensing film materials, and modeling techniques utilized for FET‐based pH sensors. We present the governing principles of potentiometric sensors, with major focus on the working principles of ion‐sensitive FETs (ISFETs). We extensively review different sensing film materials deposited by various techniques, which is critical to the sensing performance of ISFETs. The popular fabrication technologies have been presented, with special emphasis on state‐of‐the‐art silicon‐on‐insulator based technology, which can achieve high sensitivity by utilizing the dual‐gate effect. Furthermore, recent advancements in nano‐ISFETs has been elucidated. We also discuss the adoption of unmodified complementary metal‐oxide semiconductor (CMOS) ISFETs using standard CMOS processes, which has enabled the fabrication of integrated ISFET arrays, which are especially suited for ion‐imaging applications. Moreover, recent developments in extended‐gate FETs has been discussed, which have gained lot of attention due to their design flexibility and ease of fabrication, which is desirable for wearable sensing applications. In addition, recently there have been efforts to utilize nonsilicon channel materials for pH‐sensing application to obtain superior performance and various channel materials have been reviewed. Finally, we have extensively reviewed the ISFET device modeling and simulation techniques using various computer‐aided design tools, which aid in sensor design and characterization. [ABSTRACT FROM AUTHOR]

This minireview summarizes the information on the development and application of ion‐sensitive field‐effect transistors (ISFETs) with UV‐cured polyurethane ion‐selective membranes. Among the advantages of photopolymerizable polymer membranes in comparison with traditional poly(vinyl chloride) are excellent adhesion to a solid sensor surface and very fast curing time. Moreover, processes of membrane deposition and curing are compatible with ISFETs fabrication technology which is important for sensors mass production. The paper presents specific features of photopolymerizable membranes and discusses required precautions in their preparation and treatment. Examples of various analytical applications of this kind of sensors are provided. Finally, the outlook and perspectives of further development in the field of miniature solid‐state ion sensors are given. [ABSTRACT FROM AUTHOR]

Impedance spectroscopy is an electrochemical technique widely used for the electrical characterization of the behavior of biomaterials in all kinds of biosensors. Field‐effect devices, and in particular ion‐sensitive field‐effect transistors (ISFETs), have been extensively studied as transducers for biosensing. They however have not been much analyzed with impedance spectroscopy, because they typically generate non‐Faradaic capacitance measurements, since there is no charge transfer through the insulating gate in contact with the liquid solution. We have recently experimentally shown that Faradaic‐like impedance spectroscopy spectra can be obtained with ISFET devices, allowing high‐sensitivity measurements for different pH and biomarker concentrations. In this paper, we report that both Faradaic‐like and non‐Faradaic impedance behavior can be well understood by a DC and small‐signal AC model of the ISFET working in different conditions. Faradaic‐like impedance measurements are described by the operation of the ISFET in subthreshold conditions. A Nyquist plot semicircle is obtained, corresponding to the transimpedance 1/gm of the ISFET in parallel to the gate capacitances. We show that this behavior is independent of the presence of membrane material on the gate surface. In these conditions, the change in the semicircle diameter for different pH or biomarker concentrations can be understood by the change of 1/gm corresponding to a threshold voltage shift of the transistor. This description is illustrated with our recent results for pH measurements and the detection of tumor necrosis factor‐α with functionalized devices in standard solutions in the concentration range of 1–20 pg/ml. The use of the impedance spectroscopy technique takes advantage of the exponential behavior of the gm(VGS) curves in the subthreshold (weak inversion) operation of the ISFET. This results in a large signal amplification, where a small change in the threshold voltage results in a large change in the impedance spectrum, thus achieving an increased precision in the measurement of the device response to changes in the analyte concentration. [ABSTRACT FROM AUTHOR]

The conceptualization of biomolecule sensing accomplished by field effect transistor (FET) devices have been attracting substantial contemplation for over twenty years owing to the prospectus for ultra-high sensitivity sensing, labeling free operation, cost efficacious and possibility of miniaturization. To promote deeper backgrounds and future outlooks of biologically sensitive-FETs (BioFETs), we systematically present the extensive review of the related basic principles and technicalities from design, simulation , modeling and fabrication perspectives. The primal significance of sensing ions and molecules for point of care (POC) diagnostics has impelled the seek for ultra sensitive, specific, and robust sensors. Electronic detection exhibits the potential for miniaturized on-chip applications applications that have the possibility of being integrated into classical electronic manufacturing processes and technology. An in depth exploration of major sensing mechanisms and types of BioFETs such as ion sensitive field-effect transistor (ISFET), silicon nanowire (SiNW), organic FET (OFET), graphene FET, and compound semiconductor material based FET are discussed in this review article. BioFETs deliver sensing system that are miniaturized intrinsically suited for multiplexed and parallel detections applications. Herein we also provide the effect on figure of merits of biosensing systems from architectural perspectives of BioFETs. The underlying detection rationale governing every potentiometric sensor is also discussed in detail. Despite of the commercial application of BioFETs in pH sensing has been realized, yet their application for bio-molecular sensing at a commercial scale is obstructed by poor comprehension of how to optimize device design for enhanced figure of merits. In part, these hindrances root from the superior inter-disciplinary nature of the problem experienced in this field, where knowledge of bio-molecular binding kinetics, surface chemistry and electrical engineering is required at large. This article is an attempt to contemplate different aspects of BioFET design from various perspectives. [ABSTRACT FROM AUTHOR]

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We examined the possibility of measuring dissolved oxygen by using a potentiometric solid-state semiconductor sensor. Thin films of tin (IV) oxide (SnO2) are widely used in oxygen gas sensors. However, their ability to detect dissolved oxygen (DO) in solutions is still unknown. In this paper, we present a method for investigating the dissolved oxygen-sensing properties of SnO2 thin films in solutions by fabricating a SnO2-gate field-effect transistor (FET). A similarly structured hydrogen ion-sensitive silicon nitride (Si3N4)-gate FET was fabricated using the same method. The transfer characteristics and sensitivities were experimentally obtained and compared. The transfer characteristics of the FET show a shift in threshold voltage in response to a decrease in DO concentration. The SnO2-gate FET exhibited a sensitivity of 4 mV/ppm, whereas the Si3N4-gate FET showed no response to DO. Although the SnO2-gate FET responds to pH changes in the solution, this sensitivity issue can be eliminated by using a Si3N4-gate FET, which is capable of selectively sensing hydrogen ions without DO sensitivity. The experimental results indicate the promising properties of SnO2 thin films for multimodal sensing applications. [ABSTRACT FROM AUTHOR]

In this article, an analytical framework is put together to describe a pH Sensor based on Ion Sensitive Field-Effect Transistor (ISFET) and then simulated using Synopsys TCAD tool. In the proposed simulation work the electrolyte material and oxide surface charge density have been modeled explicitly by using experimental data available in the literature which makes this study unique from previously reported works. Furthermore, the method for adding a new material in Synopsys TCAD and using its advanced PMI feature are briefly illustrated in this work. The proposed work is validated against an available experimental work with good accuracy of 2.66% error percentage in the result. This article gives an adequate insight into the working principle of ISFET device with the objective of assisting beginners in this field before one can proceed into advanced research. [ABSTRACT FROM AUTHOR]

Abstract The demand for miniaturized point‐of‐care chemical/biochemical sensors has driven the development of field‐effect transistors (FETs) based pH sensors over the last 50 years. This paper aims to review the fabrication technologies, device structures, sensing film materials, and modeling techniques utilized for FET‐based pH sensors. We present the governing principles of potentiometric sensors, with major focus on the working principles of ion‐sensitive FETs (ISFETs). We extensively review different sensing film materials deposited by various techniques, which is critical to the sensing performance of ISFETs. The popular fabrication technologies have been presented, with special emphasis on state‐of‐the‐art silicon‐on‐insulator based technology, which can achieve high sensitivity by utilizing the dual‐gate effect. Furthermore, recent advancements in nano‐ISFETs has been elucidated. We also discuss the adoption of unmodified complementary metal‐oxide semiconductor (CMOS) ISFETs using standard CMOS processes, which has enabled the fabrication of integrated ISFET arrays, which are especially suited for ion‐imaging applications. Moreover, recent developments in extended‐gate FETs has been discussed, which have gained lot of attention due to their design flexibility and ease of fabrication, which is desirable for wearable sensing applications. In addition, recently there have been efforts to utilize nonsilicon channel materials for pH‐sensing application to obtain superior performance and various channel materials have been reviewed. Finally, we have extensively reviewed the ISFET device modeling and simulation techniques using various computer‐aided design tools, which aid in sensor design and characterization.

Abstract Impedance spectroscopy is an electrochemical technique widely used for the electrical characterization of the behavior of biomaterials in all kinds of biosensors. Field‐effect devices, and in particular ion‐sensitive field‐effect transistors (ISFETs), have been extensively studied as transducers for biosensing. They however have not been much analyzed with impedance spectroscopy, because they typically generate non‐Faradaic capacitance measurements, since there is no charge transfer through the insulating gate in contact with the liquid solution. We have recently experimentally shown that Faradaic‐like impedance spectroscopy spectra can be obtained with ISFET devices, allowing high‐sensitivity measurements for different pH and biomarker concentrations. In this paper, we report that both Faradaic‐like and non‐Faradaic impedance behavior can be well understood by a DC and small‐signal AC model of the ISFET working in different conditions. Faradaic‐like impedance measurements are described by the operation of the ISFET in subthreshold conditions. A Nyquist plot semicircle is obtained, corresponding to the transimpedance 1/gm of the ISFET in parallel to the gate capacitances. We show that this behavior is independent of the presence of membrane material on the gate surface. In these conditions, the change in the semicircle diameter for different pH or biomarker concentrations can be understood by the change of 1/gm corresponding to a threshold voltage shift of the transistor. This description is illustrated with our recent results for pH measurements and the detection of tumor necrosis factor‐α with functionalized devices in standard solutions in the concentration range of 1–20 pg/ml. The use of the impedance spectroscopy technique takes advantage of the exponential behavior of the gm(VGS) curves in the subthreshold (weak inversion) operation of the ISFET. This results in a large signal amplification, where a small change in the threshold voltage results in a large change in the impedance spectrum, thus achieving an increased precision in the measurement of the device response to changes in the analyte concentration.

Abstract This minireview summarizes the information on the development and application of ion‐sensitive field‐effect transistors (ISFETs) with UV‐cured polyurethane ion‐selective membranes. Among the advantages of photopolymerizable polymer membranes in comparison with traditional poly(vinyl chloride) are excellent adhesion to a solid sensor surface and very fast curing time. Moreover, processes of membrane deposition and curing are compatible with ISFETs fabrication technology which is important for sensors mass production. The paper presents specific features of photopolymerizable membranes and discusses required precautions in their preparation and treatment. Examples of various analytical applications of this kind of sensors are provided. Finally, the outlook and perspectives of further development in the field of miniature solid‐state ion sensors are given.

A comprehensive study of the drain current drift mechanism and hysteresis phenomena in fabricated p-channel junctionless ion-sensitive field-effect transistor (JL-ISFET) has been investigated for the first time. The current drift measurements have been performed through transient analysis of drain current, under different pH and liquid-gate bias (Vlg). Further, time-dependent gate-capacitance (CG) has also been analyzed to see the effect of hydroxyl ions (OH−) in the sensing film (Al2O3). The hysteresis has also been investigated for different pH loop (7 → 3 → 7 → 11 → 7 and 7 → 11 → 7 → 3 → 7) and times (960s, 1500s, and 1920s). It has been observed that the drift of JL-ISFET occurs because of chemical modification of the sensing film, due to OH−. The proposed device exhibits a threshold voltage sensitivity of 58.2 mV/pH that is near the Nernstian limit. Further, the hysteresis width and maximum drain current drift are measured as ∼ 1.3 mV and 2.4 μ A (∼ 75%), respectively. [ABSTRACT FROM AUTHOR]

This paper describes a novel design of ISFET, which uses a hafnium oxide-coated aluminum pad surface as a floating/extended gate. The design was realized using standard CMOS technology followed by BEOL post treatment. The ISFET was designed to operate in subthreshold mode and has subthreshold slope of 108 mV/dec, pH sensitivity of 55 mV/pH and temporal stability 0.008 mV/min. Based on the ISFET, an enzymatic biosensor for detection of phenols in real samples was demonstrated. The reported design allows to significantly improve the internal characteristics of ISFET, leading to predictable high-performance biosensors formed on a basis of standard CMOS-technology. [ABSTRACT FROM AUTHOR]

This research proposes a multiple-input deep learning-driven ion-sensitive field-effect transistor (ISFET) scheme to predict the concentrations of carbaryl pesticide. In the study, the carbaryl concentrations are varied between 1 × 10−7–1 × 10−3 M, and the temperatures of solutions between 20–35 °C. To validate the multiple-input deep learning regression model, the proposed ISFET scheme is deployed onsite (a field test) to measure pesticide concentrations in the carbaryl-spiked vegetable extract. The advantage of this research lies in the use of a deep learning algorithm with an ISFET sensor to effectively predict the pesticide concentrations, in addition to improving the prediction accuracy. The results demonstrate the very high predictive ability of the proposed ISFET scheme, given an MSE, MAE, and R2 of 0.007%, 0.016%, and 0.992, respectively. The proposed multiple-input deep learning regression model with signal compensation is applicable to a wide range of solution temperatures which is convenient for onsite measurement. Essentially, the proposed multiple-input deep learning regression model could be adopted as an effective alternative to the conventional statistics-based regression to predict pesticide concentrations. [ABSTRACT FROM AUTHOR]

Fertilizers have long been used to increase crop yields; however, farmers are still having difficulties in managing fertilizers for growing crops as well as economic problems. The conventional method of soil sampling and laboratory analysis to determine soil pH is time consuming and costly; therefore, a portable pH sensor is developed to characterize spatial or temporal variability within fields via rapid and dense data acquisition. The portable pH sensor comprises an electrode unit, a portable console, and a USB connector. The soil water content (SWC) and electrical conductivity (EC) affect the electrical resistance of soil. An artificial test soil is performed to evaluate the effect of SWC and EC on soil pH. The test results show that stable pH measurements are achieved at SWCs greater than 20 mL (16.3%). Regardless of the SWC, the electric potential difference (EPD) remains at 2.5 g of NaCl. As the EC increases in the soil samples, the EPD increases. [ABSTRACT FROM AUTHOR]

This paper presents a novel hybrid microfluidic electronic sensing platform, featuring an electronic sensor incorporated with a microfluidic structure for life science applications. This sensor with a large sensing area of 0.7 mm2 is implemented through a foundry process called Open-Gate Junction FET (OG-JFET). The proposed OG-JFET sensor with a back gate enables the charge by directly introducing the biological and chemical samples on the top of the device. This paper puts forward the design and implementation of a PDMS microfluidic structure integrated with an OG-JFET chip to direct the samples toward the sensing site. At the same time, the sensor's gain is controlled with a back gate electrical voltage. Herein, we demonstrate and discuss the functionality and applicability of the proposed sensing platform using a chemical solution with different pH values. Additionally, we introduce a mathematical model to describe the charge sensitivity of the OG-JFET sensor. Based on the results, the maximum value of transconductance gain of the sensor is ~1 mA/V at Vgs = 0, which is decreased to ~0.42 mA/V at Vgs = 1, all in Vds = 5. Furthermore, the variation of the back-gate voltage from 1.0 V to 0.0 V increases the sensitivity from ~40 mV/pH to ~55 mV/pH. As per the experimental and simulation results and discussions in this paper, the proposed hybrid microfluidic OG-JFET sensor is a reliable and high-precision measurement platform for various life science and industrial applications. [ABSTRACT FROM AUTHOR]

The method of cleaning the ISFET structures after application of a biological substance was developed. There are few references in the literature to cleaning methods of this type of structure for biological applications, but they are relatively complex and difficult to automate. We decided to use resources commonly available in technological laboratories and methods that could be relatively easily automated, which would enable the full potential of ISFET transistors to be used. During the experiments, both acetone and deionized water were tested. The cleaning method was modified and it was checked whether it is possible to use such a method on one transistor more than once and how it affects the transistor's detection capabilities. We managed to obtain an effective method of cleaning ISFETs from biological substances. This method does not allow for obtaining exactly the same state as the original state of the transistor, but it ensures its correct operation and determining the influence of the tested biological substance on the transistor based on the results.

The rapid increase of antibiotic-resistant pathogenic bacteria has become a global health threat. The development of rapid and accurate diagnostics along with the production of drugs is essential to overcome this problem. Previously reported electrochemical, mechanical, and microfluidic sensors have attempted to meet these requirements. However, the fundamental trade-off between the selectivity and sensitivity of such sensors is still the main challenging and unresolved issue. Here, we introduce a label-free and antibody-free gated device with the capability of sensitive and selective detection of bacteria. Our device with a unique operating mechanism enables us to have a fingerprint for any type of bacteria. Each type of bacteria induces unique electrical characteristics on the device according to its shape and electrostatic properties, which makes it possible to selectively detect the bacteria. Utilizing the ZnO nanorods in the structure of the sensor and using our electrical procedure of detection provide a platform for single-cell detection. [ABSTRACT FROM AUTHOR]

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 $8.5^{2} {\mu } \text{m}$ 2, a 3.21-fold ${\Delta } \text{I}_{D}$ /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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This article introduces a new foundry-based ion-sensitive field-effect transistor named open-gate junction field-effect transistor (OG-JFET), which is intended to be used for chemical and biological sensing applications. OG-JFET can be realized by removing the n-type gate in a p-type JFET to open the space for electrolyte gating. The new configuration enables applying a bias voltage via back-gate that results in more efficient channel current control. Accordingly, a $1.6 ~{\mu }\text{m}$ thick p-type conductive layer has been epitaxially grown on a $450 ~{\mu }\text{m}$ thick n-type silicon layer based on a standard foundry process. The design promotes a large sensing area including seven p-type conduction channels with dimensions of $1000\,\, {\mu }\text{m}\,\,{\times }\,\,100\,\, {\mu }\text{m}$ (W ${\times }$ L) and depth of $1.6 ~{\mu }\text{m}$. All the necessary transfer characteristics required for biosensing/ion-sensing of OG-JFET have been derived. Furthermore, we have conducted a COMSOL Multiphysics simulation on OG-JFET to verify the operation of the sensor, which helps to comprehend the functionality of the sensor in different biasing conditions. The COMSOL semiconductor simulation results showed good consistency with experimental results that make the simulations a reliable reference for optimization and customizing the chip for specific applications. OG-JFET showed a sensitivity of 55.29 mV/pH, a hysteresis of 16 mV, and drift of $3 ~{\mu }\text{A}$ /hours which are in the order of standard ISFET sensors in the literature. The simulation and experimental results in this paper, for the first time, put forward the OG-JFET as a new foundry-process-based, mass-producible ion-sensitive FET sensor for chemical and biological applications. [ABSTRACT FROM AUTHOR]

In this work, we report a novel Indium Arsenide-on-insulator (InAsOI) FinFET platform designed with record high aspect ratio that favors the use of the devices as charge sensors. InAs has very high mobility among III-V semiconductors and an intrinsic surface accumulation layer yielding good ohmic contacts thus making it an interesting choice for chemical and biological sensing platforms. Template Assisted Selective Epitaxy (TASE) enables the integration of III-V highly scaled devices, monolithically integrated on Silicon, within a fully CMOS compatible fabrication scheme hence without any catalyst-induced growth. With a new geometry, high-aspect-ratio (HAR) InAs fins and a new application of pH sensing the versatility of TASE is exhibited. HAR InAs fins, fin height to fin width in excess of 4 for fin width down to 30 nm are fabricated on a Si substrate. The HAR InAs-on-insulator fins are characterized as pH sensors. A sensitivity of 38.8 mV per pH is extracted at $6~\mu \text{A}$ drain current from a 40 nm wide 20 multi-finger array.

High electron mobility transistor (HEMT) biosensors hold great potential for realizing label-free, real-time, and direct detection. Owing to their unique properties of two-dimensional electron gas (2DEG), HEMT biosensors have the ability to amplify current changes pertinent to potential changes with the introduction of any biomolecules, making them highly surface charge sensitive. This review discusses the recent advances in the use of AlGaN/GaN and AlGaAs/GaAs HEMT as biosensors in the context of different gate architectures. We describe the fundamental mechanisms underlying their operational functions, giving insight into crucial experiments as well as the necessary analysis and validation of data. Surface functionalization and biorecognition integrated into the HEMT gate structures, including self-assembly strategies, are also presented in this review, with relevant and promising applications discussed for ultra-sensitive biosensors. Obstacles and opportunities for possible optimization are also surveyed. Conclusively, future prospects for further development and applications are discussed. This review is instructive for researchers who are new to this field as well as being informative for those who work in related fields.

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. [ABSTRACT FROM AUTHOR]

Monitoring of pH is crucial for several chemical and biochemical processes. ISFET (Ion-Sensitive Field-Effect Transistors)-based pH sensors are promising candidates for pH monitoring applications. However, ISFET devices are prone to temporal and temperature drifts, which severely affects the precision of pH measurements. In this work, we collect experimental data of temporal and temperature drifts in an ISFET sensor to formulate an accurate SPICE macro model, incorporating both temporal and temperature non-idealities. The developed macro model is utilized for generating training data for state-of-the-art machine learning models for drift compensation, with a primary focus on the temporal characteristics. We utilize recurrent neural networks (RNNs) to model the temporal characteristics of ISFET, and thus, compensate the non-ideality. The sensor data is collected in various pH buffer solutions and a data set of sequences containing time-dependent voltage readings are generated by the device and the RNNs are trained to learn the crucial features from the data and map them to the precise pH of the solution. We compare two variants of RNNs, i.e. LSTM (long short-term memory) and GRU (gated recurrent unit), and their bidirectional low computational cost variants - biLSTM and biGRU. Each model is tested in a memory-constrained environment with the availability of a 32-bit and 64-bit floating-point number. Empirically, we find biLSTMs to perform best, where the achieved root mean square error (RMSE) between the model predicted pH and the true pH of the test solution is less than 0.212 pH, with an average RMSE of 0.126 pH. For temperature drift compensation, we collect data for four different temperatures and adapt well-established MLPs (Multi-layer Perceptrons) to compensate the intrinsic temperature drift in the sensor. We observe an average RMSE of the model predicted pH to the true pH to be less than 0.286 pH. The developed RNN models were implemented on Xilinx ZCU104 FPGA development kit using PYNQ framework, which demonstrates low power consumption. The proposed framework establishes the efficacy of Machine Learning (ML) techniques for drift compensation in ISFET-based pH sensors for deployment in IoT applications. [ABSTRACT FROM AUTHOR]

We examined the possibility of measuring dissolved oxygen by using a potentiometric solid-state semiconductor sensor. Thin films of tin (IV) oxide (SnO2) are widely used in oxygen gas sensors. However, their ability to detect dissolved oxygen (DO) in solutions is still unknown. In this paper, we present a method for investigating the dissolved oxygen-sensing properties of SnO2 thin films in solutions by fabricating a SnO2-gate field-effect transistor (FET). A similarly structured hydrogen ion-sensitive silicon nitride (Si3N4)-gate FET was fabricated using the same method. The transfer characteristics and sensitivities were experimentally obtained and compared. The transfer characteristics of the FET show a shift in threshold voltage in response to a decrease in DO concentration. The SnO2-gate FET exhibited a sensitivity of 4 mV/ppm, whereas the Si3N4-gate FET showed no response to DO. Although the SnO2-gate FET responds to pH changes in the solution, this sensitivity issue can be eliminated by using a Si3N4-gate FET, which is capable of selectively sensing hydrogen ions without DO sensitivity. The experimental results indicate the promising properties of SnO2 thin films for multimodal sensing applications.

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. [ABSTRACT FROM AUTHOR]

This paper studies royal inscriptions of the Eighteenth Dynasty—a period of extensive military activity in Nubia and the Levant—to examine the prevailing assumption that earthly wars were conceived as mirroring a cosmic struggle between order and chaos. Instead, the sources suggest a more intricate picture, in which royal prerogative and divine will are at play, often ambiguously intertwined. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Here, we explicitly define a half-cell reaction approach for pH calculation using the electrode couple comprised of the solid-state chloride ion-selective electrode (Cl-ISE) as the reference electrode and the hydrogen ion-selective ion-sensitive field effect transistor (ISFET) of the Honeywell Durafet as the hydrogen ion H + -sensitive measuring or working electrode. This new approach splits and isolates the independent responses of the Cl-ISE to the chloride ion Cl − (and salinity) and the ISFET to H + (and pH), and calculates pH directly on the total scale pH total EXT in molinity (mol (kg-soln)−1) concentration units. We further apply and compare pH total EXT calculated using the half-cell and the existing complete cell reaction (defined by Martz et al. (2010)) approaches using measurements from two SeapHOx sensors deployed in a test tank. Salinity (on the Practical Salinity Scale) and pH oscillated between 1 and 31 and 6.9 and 8.1, respectively, over a six-day period. In contrast to established Sensor Best Practices, we employ a new calibration method where the calibration of raw pH sensor timeseries are split out as needed according to salinity. When doing this, pH total EXT had root-mean squared errors ranging between ±0.0026 and ±0.0168 pH calculated using both reaction approaches relative to pH total of the discrete bottle samples pH total disc. Our results further demonstrate the rapid response of the Cl-ISE reference to variable salinity with changes up to ±12 (30 min)−1. Final calculated pH total EXT were ≤±0.012 pH when compared to pH total disc following salinity dilution or concentration. These results are notably in contrast to those of the few in situ field deployments over similar environmental conditions that demonstrated pH total EXT calculated using the Cl-ISE as the reference electrode had larger uncertainty in nearshore waters. Therefore, additional work beyond the correction of variable temperature and salinity conditions in pH calculation using the Cl-ISE is needed to examine the effects of other external stimuli on in situ electrode response. Furthermore, whereas past work has focused on in situ reference electrode response, greater scrutiny of the ISFET as the H + -sensitive measuring electrode for pH measurement in natural waters is also needed. • Electrode responses are split out and isolated using half reactions. • A new approach for pH calculation using half reactions is explicitly defined. • pH calculation uses single ion activity coefficients for the chloride and hydrogen ions. • This new pH calculation approach is optimized for salinities between 0.105 and 35. • pH can now be calculated directly on the total scale in molinity (mol (kg soln)−1). [ABSTRACT FROM AUTHOR]