ISFET Research Articles

Robust chemical analysis with graphene chemosensors and machine learning.

Ion-sensitive field-effect transistors (ISFETs) have emerged as indispensable tools in chemosensing applications1-4. ISFETs operate by converting changes in the composition of chemical solutions into electrical signals, making them ideal for environmental monitoring5,6, healthcare diagnostics7 and industrial process control8. Recent advancements in ISFET technology, including functionalized multiplexed arrays and advanced data analytics, have improved their performance9,10. Here we illustrate the advantages of incorporating machine learning algorithms to construct predictive models using the extensive datasets generated by ISFET sensors for both classification and quantification tasks. This integration also sheds new light on the working of ISFETs beyond what can be derived solely from human expertise. Furthermore, it mitigates practical challenges associated with cycle-to-cycle, sensor-to-sensor and chip-to-chip variations, paving the way for the broader adoption of ISFETs in commercial applications. Specifically, we use data generated bynon-functionalized graphene-based ISFET arrays to train artificial neural networks that possess a remarkable ability to discern instances of food fraud, food spoilage and food safety concerns. We anticipate that the fusion of compact, energy-efficient and reusable graphene-based ISFET technology with robust machine learning algorithms holds the potential to revolutionize the detection of subtle chemical and environmental changes, offering swift, data-driven insights applicable across a wide spectrum of applications.

Ultra-sensitive nitrate-ion detection via transconductance-enhanced graphene ion-sensitive field-effect transistors

Current potentiometric sensing methods are limited to detecting nitrate at parts-per-billion (sub-micromolar) concentrations, and there are no existing potentiometric chemical sensors with ultralow detection limits below the parts-per-trillion (picomolar) level. To address these challenges, we integrate interdigital graphene ion-sensitive field-effect transistors (ISFETs) with a nitrate ion-sensitive membrane (ISM). The work aims to maximize nitrate ion transport through the nitrate ISM, while achieving high device transconductance by evaluating graphene layer thickness, optimizing channel width-to-length ratio (RWL), and enlarging total sensing area. The captured nitrate ions by the nitrate ISM induce surface potential changes that are transduced into electrical signals by graphene, manifested as the Dirac point shifts. The device exhibits Nernst response behavior under ultralow concentrations, achieving a sensitivity of 28 mV/decade and establishing a record low limit of detection of 0.041 ppt (4.8 × 10−13 M). Additionally, the sensor showed a wide linear detection range from 0.1 ppt (1.2 × 10−12 M) to 100 ppm (1.2 × 10−3 M). Furthermore, successful detection of nitrate in tap and snow water was demonstrated with high accuracy, indicating promising applications to drinking water safety and environmental water quality control.

A method to detect enzymatic reactions with field effect transistor

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.

(Invited) Tackling Leakage, Drift, and Variation in Printed Carbon Nanotube-Based Electronic Biosensors

Semiconducting carbon nanotubes (CNTs) have been pursued for use in electronic biosensors for decades. Their all-surface molecular structure, sizeable semiconducting bandgap, and solution-phase compatibility make them highly sensitive and versatile options for transducing target bioelectrical signals. However, amid the thousands of reports on CNT-based electronic biosensors, very little attention has been given to identifying (let alone addressing) the impact of leakage current, signal drift, and device-to-device variation. This talk will present recent results focused on tackling these issues with specific emphasis on printed CNT-based biosensors. For instance, a variety of passivation strategies were studied to determine the role of leakage current for CNT transistor-based biosensors (i.e., bioFETs or ion-sensitive FETs), revealing that a bilayer epoxy/high-k dielectric stack was most effective at minimizing unwanted leakage current. The influence of signal drift will also be demonstrated, likely playing a significant role in many previous reports of CNT-based biosensors characterized by sequential concentration spikes. Finally, strategies for addressing device-to-device variation in these biosensors will be discussed, including the motivation for a printed thin-film device rather than a single-CNT configuration. Two things seem certain about this field: 1) the promise of CNT-based biosensors continues to suggest they are worth ongoing pursuit, and 2) there is much work remaining towards achieving a reproducible, reliable electronic biosensing technology from CNTs.

Sensing with Molecularly Imprinted Membranes on Two-Dimensional Solid-Supported Substrates.

Molecularly imprinted membranes (MIMs) have been a focal research interest since 1990, representing a breakthrough in the integration of target molecules into membrane structures for cutting-edge sensing applications. This paper traces the developmental history of MIMs, elucidating the diverse methodologies employed in their preparation and characterization on two-dimensional solid-supported substrates. We then explore the principles and diverse applications of MIMs, particularly in the context of emerging technologies encompassing electrochemistry, surface-enhanced Raman scattering (SERS), surface plasmon resonance (SPR), and the quartz crystal microbalance (QCM). Furthermore, we shed light on the unique features of ion-sensitive field-effect transistor (ISFET) biosensors that rely on MIMs, with the notable advancements and challenges of point-of-care biochemical sensors highlighted. By providing a comprehensive overview of the latest innovations and future trajectories, this paper aims to inspire further exploration and progress in the field of MIM-driven sensing technologies.

Assessing the performance of a robust multiparametric wearable patch integrating silicon-based sensors for real-time continuous monitoring of sweat biomarkers

The development of wearable devices for sweat analysis has experienced significant growth in the last two decades, being the main focus the monitoring of athletes health during workouts. One of the main challenges of these approaches has been to attain the continuous monitoring of sweat for time periods over 1 h. This is the main challenge addressed in this work by designing an analytical platform that combines the high performance of potentiometric sensors and a fluidic structure made of a plastic fabric into a multiplexed wearable device. The platform comprises Ion-Sensitive Field-Effect Transistors (ISFETs) manufactured on silicon, a tailor-made solid-state reference electrode, and a temperature sensor integrated into a patch-like polymeric substrate, together with the component that easily collects and drives samples under continuous capillary flow to the sensor areas. ISFET sensors for measuring pH, sodium, and potassium ions were fully characterized in artificial sweat solutions, providing reproducible and stable responses. Then, the real-time and continuous monitoring of the biomarkers in sweat with the wearable platform was assessed by comparing the ISFETs responses recorded during an 85-min continuous exercise session with the concentration values measured using commercial Ion-Selective Electrodes (ISEs) in samples collected at certain times during the session. The developed sensing platform enables the continuous monitoring of biomarkers and facilitates the study of the effects of various real working conditions, such as cycling power and skin temperature, on the target biomarker concentration levels.

Enhancement of Ion-Sensitive Field-Effect Transistors through Sol-Gel Processed Lead Zirconate Titanate Ferroelectric Film Integration and Coplanar Gate Sensing Paradigm

To facilitate the utility of field effect transistor (FET)-type sensors, achieving sensitivity enhancement beyond the Nernst limit is crucial. Thus, this study proposed a novel approach for the development of ferroelectric FETs (FeFETs) using lead zirconate titanate (PZT) ferroelectric films integrated with indium–tungsten oxide (IWO) channels synthesized via a cost-effective sol-gel process. The electrical properties of PZT-IWO FeFET devices were significantly enhanced through the strategic implementation of PZT film treatment by employing intentional annealing procedures. Consequently, key performance metrics, including the transfer curve on/off ratio and subthreshold swings, were improved. Moreover, unprecedented electrical stability was realized by eliminating the hysteresis effect during double sweeps. By leveraging a single-gate configuration as an FeFET transformation element, extended-gate (EG) detection methodologies for pH sensing were explored, thereby introducing a pioneering dimension to sensor architecture. A measurement paradigm inspired by plane gate work was adopted, and the proposed device exhibited significant resistive coupling, consequently surpassing the sensitivity thresholds of conventional ion-sensitive field-effect transistors. This achievement represents a substantial paradigm shift in the landscape of ion-sensing methodologies, surpassing the established Nernst limit (59.14 mV/pH). Furthermore, this study advances FeFET technology and paves the way for the realization of highly sensitive and reliable ion sensing modalities.

Application of Soil Testing Sensors in Agriculture: A Review

The soil whose main role is to provide nutrients in the process of plant growth is the foundation and an important part of agriculture. Soil testing is an important step for increasing agricultural production and raising farm income. Traditional soil testing methods rely on chemical processes carried out in a laboratory. Sensors play a significant role in agriculture by direct measurement of soil chemistry through tests such as pH, moisture, nutrient content, humidity and temperature. The results of soil tests are important to get high yield with good quality produce. ISE (Ion Selective Electrode) and ISEFT (ion-sensitive field effect transistor) sensors have also been used to detect the uptake of ions by plants.

Study of ISFET for KCl sensing

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 (VTH) 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.

Biocompatibility characterisation of CMOS-based Lab-on-Chip electrochemical sensors for in vitro cancer cell culture applications

Lab-on-Chip electrochemical sensors, such as Ion-Sensitive Field-Effect Transistors (ISFETs), are being developed for use in point-of-care diagnostics, such as pH detection of tumour microenvironments, due to their integration with standard Complementary Metal Oxide Semiconductor (CMOS) technology. With this approach, the passivation of the CMOS process is used as a sensing layer to minimise post-processing, and Silicon Nitride (Si3N4) is the most common material at the microchip surface. ISFETs have the potential to be used for cell-based assays however, there is a poor understanding of the biocompatibility of microchip surfaces. Here, we quantitatively evaluated cell adhesion, morphogenesis, proliferation and mechano-responsiveness of both normal and cancer cells cultured on a Si3N4, sensor surface. We demonstrate that both normal and cancer cell adhesion decreased on Si3N4. Activation of the mechano-responsive transcription regulators, YAP/TAZ, are significantly decreased in cancer cells on Si3N4 in comparison to standard cell culture plastic, whilst proliferation marker, Ki67, expression markedly increased. Non-tumorigenic cells on chip showed less sensitivity to culture on Si3N4 than cancer cells. Treatment with extracellular matrix components increased cell adhesion in normal and cancer cell cultures, surpassing the adhesiveness of plastic alone. Moreover, poly-l-ornithine and laminin treatment restored YAP/TAZ levels in both non-tumorigenic and cancer cells to levels comparable to those observed on plastic. Thus, engineering the electrochemical sensor surface with treatments will provide a more physiologically relevant environment for future cell-based assay development on chip.

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

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

Detection of α-Galactosidase A Reaction in Samples Extracted from Dried Blood Spots Using Ion-Sensitive Field Effect Transistors.

Fabry disease is a lysosomal storage disorder caused by a significant decrease in the activity or absence of the enzyme α-galactosidase A. The diagnostics of Fabry disease during newborn screening are reasonable, due to the availability of enzyme replacement therapy. This paper presents an electrochemical method using complementary metal-oxide semiconductor (CMOS)-compatible ion-sensitive field effect transistors (ISFETs) with hafnium oxide-sensitive surfaces for the detection of α-galactosidase A activity in dried blood spot extracts. The capability of ISFETs to detect the reaction catalyzed by α-galactosidase A was demonstrated. The buffer composition was optimized to provide suitable conditions for both enzyme and ISFET performance. The use of ISFET structures as sensor elements allowed for the label-free detection of enzymatic reactions with melibiose, a natural substrate of α-galactosidase A, instead of a synthetic fluorogenic one. ISFET chips were packaged with printed circuit boards and microfluidic reaction chambers to enable long-term signal measurement using a custom device. The packaged sensors were demonstrated to discriminate between normal and inhibited GLA activity in dried blood spots extracts. The described method offers a promising solution for increasing the widespread distribution of newborn screening of Fabry disease.

A Portable Readout System for Biomarker Detection with Aptamer-Modified CMOS ISFET Array.

Biosensors based on ion-sensitive field effect transistors (ISFETs) combined with aptamers offer a promising and convenient solution for point-of-care testing applications due to the ability for fast and label-free detection of a wide range of biomarkers. Mobile and easy-to-use readout devices for the ISFET aptasensors would contribute to further development of the field. In this paper, the development of a portable PC-controlled device for detecting aptamer-target interactions using ISFETs is described. The device assembly allows selective modification of individual ISFETs with different oligonucleotides. Ta2O5-gated ISFET structures were optimized to minimize trapped charge and capacitive attenuation. Integrated CMOS readout circuits with linear transfer function were used to minimize the distortion of the original ISFET signal. An external analog signal digitizer with constant voltage and superimposed high-frequency sine wave reference voltage capabilities was designed to increase sensitivity when reading ISFET signals. The device performance was demonstrated with the aptamer-driven detection of troponin I in both reference voltage setting modes. The sine wave reference voltage measurement method reduced the level of drift over time and enabled a lowering of the minimum detectable analyte concentration. In this mode (constant voltage 2.4 V and 10 kHz 0.1Vp-p), the device allowed the detection of troponin I with a limit of detection of 3.27 ng/mL. Discrimination of acute myocardial infarction was demonstrated with the developed device. The ISFET device provides a platform for the multiplexed detection of different biomarkers in point-of-care testing.

Performance Analysis of Nanowire ISFET Biosensor Towards Bovine Serum Albumin and Liposome

Proteins are necessary to all living organisms for both structural and functional reasons. However, due to their breakdown, some proteins, including Bovine Serum Albumin (BSA) and Liposome, could cause detrimental effects on cells and tissues. Due to its high detection sensitivity, the potential for mass production, and affordable manufacture, the ion-sensitive field-effect transistor (ISFET) biosensor has become increasingly prominent in clinical research for the detection of biomolecules. BSA and Liposome are the target proteins, while collagen is the bioreceptor. ISFET biosensor with a structure of cylindrical nanowire was simulated and examined. The settling time and sensitivity of the biosensor were modeled using Nanohub BioSensorLab software. The cylindrical nanowire ISFET biosensor can be enhanced by reducing the buffer ion concentration, increasing the radius, and increasing the oxide thickness. Compared to liposomes, BSA provides a lower settling time. This is because the diffusion coefficient of liposomes is 3.6 times lower than BSA. Furthermore, settling time is reduced when the analyte concentration is increased. The results are compared with planar ISFET, considered one-dimensional (1D) architecture. The planar ISFET exhibited a quicker settling time than the cylindrical nanowire biosensor. Furthermore, as the amounts of protein and analyte increased, the settling time reduced. The cylindrical nanowire biosensor needs to be in radius of 100nm and 10nm of oxide thickness with 0.1M buffer concentration for it to achieved the highest sensitivity. These results could facilitate researchers to produce the desirable ISFET sensor for different types of proteins.

Analysis of Different Nanostructures of ISFET Biosensors Towards Liposome Detection

Proteins are needed by all living cells for structural and functional purposes. However, some proteins such as liposome instability may result in medication leaks that could harm cells. The detection of liposomes is dependent on the complex interactions between proteins, which are necessary for both their structural integrity and functional characteristics. This emphasizes the critical role that proteins play in the precise identification and examination of liposomal structures. Ion-sensitive field-effect transistor (ISFET) biosensor has gained popularity in the clinical research field for biomolecule detection due to its high detection sensitivity, mass-production capability, and low manufacturing cost. Nanohub BioSensorLab software was used to analyze the performance of different structures of ISFET (planar, cylindrical nanowire, nanosphere and double-gate FET) by simulating the settling time and selectivity of the biosensors. As the structural dimension expands from 1D to 3D, the settling time increases by three folds at the lowest analyte concentration. The fastest settling times were achieved by planar ISFET and double-gate FET. For selectivity measurements, an enhanced selectivity was achieved by increasing the concentration of the target molecule and decreasing the concentration of the parasitic molecule. A higher selectivity is determined by the higher Signal-to-Noise Ratio (SNR) value. The SNR increased linearly corresponds to the increase in the concentration of the target molecule as well as the decrease in the parasitic molecule’s concentration. The parasitic molecule's size increase of 1 nm causes a rise in SNR of 5.00×103.

Lead ions detection using CVD-grown ReS2-FET with the facilitation of a passivation layer

Field-effect transistor (FET)-based heavy-metal detection is garnering attention due to its heightened sensitivity, affordability, convenient fabrication, and portability. Flower-like rhenium disulfide (ReS2) offers potential for high-performance FET sensors, but direct exposure of channel materials to the ionic solution without a passivation layer results in multiple signals arising from the ionic transmission, doping impact, and gating effect. Introducing a passivation layer to the channel surface enhances sensor sensitivity without compromising device performance, ensuring conductance changes are primarily due to the gating effect. Here, a large surface area of Chemical Vapor Deposition (CVD)-grown vertically aligned ReS2 is employed in the FET-based sensor, and the utilization of the HfO2 layer is to isolate analytes from the elements of the conducting channel. For real-time lead monitoring in a water environment, it exhibits strong electrical stability, an impressive LoD (≈2 nM), a rapid response time (≈1.1 sec), and notable selectivity. Additionally, sensing operations are characterized by developing a unique amplifier circuit by integrating the fabricated sensor, contributing to advancements in sensor integration to detect hazardous metals in industrial electronics. These results underscore the potential for enhancing the performance of ion-sensitive FETs through structural optimization and improvements to the fundamental sensor mechanism.

Enhanced BSA Detection Precision: Leveraging High-Performance Dual-Gate Ion-Sensitive Field-Effect-Transistor Scheme and Surface-Treated Sensing Membranes.

Bovine serum albumin (BSA) is commonly incorporated in vaccines to improve stability. However, owing to potential allergic reactions in humans, the World Health Organization (WHO) mandates strict adherence to a BSA limit (≤50 ng/vaccine). BSA detection with conventional techniques is time-consuming and requires specialized equipment. Efficient alternatives such as the ion-sensitive field-effect transistor (ISFET), despite rapid detection, affordability, and portability, do not detect BSA at low concentrations because of inherent sensitivity limitations. This study proposes a silicon-on-insulator (SOI) substrate-based dual-gate (DG) ISFET platform to overcome these limitations. The capacitive coupling DG structure significantly enhances sensitivity without requiring external circuits, owing to its inherent amplification effect. The extended-gate (EG) structure separates the transducer unit for electrical signal processing from the sensing unit for biological detection, preventing chemical damage to the transducer, accommodating a variety of biological analytes, and affording easy replaceability. Vapor-phase surface treatment with (3-Aminopropyl) triethoxysilane (APTES) and the incorporation of a SnO2 sensing membrane ensure high BSA detection efficiency and sensitivity (144.19 mV/log [BSA]). This DG-FET-based biosensor possesses a simple structure and detects BSA at low concentrations rapidly. Envisioned as an effective on-site diagnostic tool for various analytes including BSA, this platform addresses prior limitations in biosensing and shows promise for practical applications.

A half-cell reaction approach for pH calculation using a solid-state chloride ion-selective electrode with a hydrogen ion-selective ion-sensitive field effect transistor

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 pHtotalEXT in molinity (mol (kg-soln)−1) concentration units. We further apply and compare pHtotalEXT 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, pHtotalEXT had root-mean squared errors ranging between ±0.0026 and ±0.0168 pH calculated using both reaction approaches relative to pHtotal of the discrete bottle samples pHtotaldisc. 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 pHtotalEXT were ≤±0.012 pH when compared to pHtotaldisc 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 pHtotalEXT 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.

Smart pH Sensing: A Self-Sensitivity Programmable Platform with Multi-Functional Charge-Trap-Flash ISFET Technology

This study presents a novel pH sensor platform utilizing charge-trap-flash-type metal oxide semiconductor field-effect transistors (CTF-type MOSFETs) for enhanced sensitivity and self-amplification. Traditional ion-sensitive field-effect transistors (ISFETs) face challenges in commercialization due to low sensitivity at room temperature, known as the Nernst limit. To overcome this limitation, we explore resistive coupling effects and CTF-type MOSFETs, allowing for flexible adjustment of the amplification ratio. The platform adopts a unique approach, employing CTF-type MOSFETs as both transducers and resistors, ensuring efficient sensitivity control. An extended-gate (EG) structure is implemented to enhance cost-effectiveness and increase the overall lifespan of the sensor platform by preventing direct contact between analytes and the transducer. The proposed pH sensor platform demonstrates effective sensitivity control at various amplification ratios. Stability and reliability are validated by investigating non-ideal effects, including hysteresis and drift. The CTF-type MOSFETs’ electrical characteristics, energy band diagrams, and programmable resistance modulation are thoroughly characterized. The results showcase remarkable stability, even under prolonged and repetitive operations, indicating the platform’s potential for accurate pH detection in diverse environments. This study contributes a robust and stable alternative for detecting micro-potential analytes, with promising applications in health management and point-of-care settings.

Ion-sensitive field effect transistor biosensors for biomarker detection: current progress and challenges.

The ion-sensitive field effect transistor (ISFET) has emerged as a crucial sensor device, owing to its numerous benefits such as label-free operation, miniaturization, high sensitivity, and rapid response time. Currently, ISFET technology excels in detecting ions, nucleic acids, proteins, and cellular components, with widespread applications in early disease screening, condition monitoring, and drug analysis. Recent advancements in sensing techniques, coupled with breakthroughs in nanomaterials and microelectronics, have significantly improved sensor performance. These developments are steering ISFETs toward a promising future characterized by enhanced sensitivity, seamless integration, and multifaceted detection capabilities. This review explores the structure and operational principles of ISFETs, highlighting recent research in ISFET biosensors for biomarker detection. It also examines the limitations of these sensors, proposes potential solutions, and anticipates their future trajectory. This review aims to provide a valuable reference for advancing ISFETs in the field of biomarker measurement.