Aptamer-Based Glycated Albumin Sensor for Capacitive Spectroscopy.

Glycated albumin (GA) is a candidate for glycemic indicator to control prediabetes, the half-life of which is about 2 weeks, which is neither too long nor too short, considering that there is no longer any need for daily fingerstick sampling but glucose levels can be controlled in a relatively short term. Its usefulness as a glycemic indicator must be widely recognized by developing a simple and miniaturized GA sensor for point-of-care testing (POCT) devices. In this study, we propose an aptamer-based capacitive electrode for electrochemical capacitance spectroscopy (ECS) to specifically detect GA in an enzyme-/antibody-free manner. As a component of the bioelectrical interface between the sample solution and the electrode, a densely packed capacitive polyaryl film coated on a gold electrode contributes to the detection of GA by the ECS method. In addition, the GA aptamer tethered onto the polyaryl-film-coated gold electrode is useful for not only specifically capturing GA but also inducing changes in the concentration of cations released from the cation/GA aptamer complexes by GA/GA aptamer binding. Also, hydrophilic poly(ethylene glycol) (PEG) coated on the polyaryl film electrode in parallel with the GA aptamer prevents interfering proteins such as human serum albumin (HSA) and immunoglobulin G (IgG) from nonspecifically absorbing on the polyaryl film electrode. Such a GA aptamer-based capacitive electrode produces significant signals of GA against HSA and IgG with the change in GA concentration (0.1, 1, and 10 mg/mL) detected by the ECS method. This indicates that the ECS method contributes to the evaluation of the GA level, which is based on the rate of glycation of albumin. Thus, a platform based on ECS measurement using the aptamer-based capacitive electrode is useful for protein analysis in an enzyme-/antibody-free manner.

Effect of Surface Modification on the Fundamental Electrical Characteristics of Solution-Gated Indium Tin Oxide-Based Thin-Film Transistor Fabricated by One-Step Sputtering.

Our solution-gated indium tin oxide (ITO)-based thin-film transistor (TFT) produced by single-step sputtering has great future potential in bioelectronics. In particular, chemical modifications of the ITO channel surface are expected to contribute to biomolecular recognition with ultrahigh sensitivity owing to a remarkably steep subthreshold slope (SS). In this study, we investigate the effect of a chemical modification of an aptamer as a receptor molecule at the ITO channel surface on the electrical characteristics of the solution-gated TFT. In this case, a SARS-CoV-2 aptamer is immobilized using a spacer molecule on an aryl diazonium monolayer that is electrochemically deposited with a radical scavenger. The monolayer is expected to not only passivate the ITO channel surface but also change the electron density in the ITO channel owing to the reduction reaction of aryl diazonium salts. Indeed, the electrochemical deposition of aryl diazonium salts decreases the leakage current through the ITO channel surface and provides a steep SS, which is near the thermal limit at 300 K, owing to the decrease in depletion layer capacitance. After the aptamer immobilization, the leakage current and SS unexpectedly return close to their original values before the surface modifications. This finding indicates that aptamer molecules should be carefully used because their negative charges would attract cations around the detection interface. Eventually, the solution-gated ITO-based TFT with the SARS-CoV-2 aptamer clearly responds to inactivated SARS-CoV-2 particles owing to the successful surface modification.

Hydrogel-Coated Gate Field-Effect Transistor for Real-Time and Label-Free Monitoring of ß-Amyloid Aggregation and Its Inhibition.

In this paper, we propose a hydrogel-coated gate field-effect transistor (FET) for the real-time and label-free monitoring of ß-amyloid (Aß) aggregation and its inhibition. The hydrogel used in this study is composed of poly tetramethoxysilane (TMOS), in which Aß monomers are entrapped and then aggregate, and coated on the gate insulator; that is, Aß aggregation is induced in the vicinity of the sensing surface. With the Aß hydrogel-coated gate FET, the steplike decrease in the surface potential of the Aß hydrogel-coated gate electrode is electrically monitored in real time, according to the stepwise aggregation of Aß monomers to form into fibrils through oligomers and so forth in stages. This is because the capacitance of the Aß-hydrogel membrane decreases depending on the stage of aggregation; that is, the hydrophobicity of the Aß-hydrogel membrane increases stepwise depending on the amount of Aß aggregates. The formation of Aß fibrils is also confirmed in the measurement solution using a fluorescent dye, thioflavin T, which selectively binds to the Aß fibrils. Moreover, the addition of daunomycin, an inhibitor of Aß aggregation, to the measurement solution suppresses the stepwise electrical response of the Aß hydrogel-coated gate FET. Thus, a platform based on the Aß hydrogel-coated gate FET is suitable for a simple screening system for inhibitors of Aß aggregation, which may lead the identification of potential therapeutic agents for Alzheimer's disease.

Surface Characteristics and Formation of Polyserotonin Thin Films for Bioelectrical and Biocompatible Interfaces.

In this study, we examined the fundamental surface characteristics of a polyserotonin (pST) film, which is attractive as a bioelectrical and biocompatible interface of biosensors. The pST film can easily be modified on electrode materials such as Au by self-polymerization and electropolymerization. By a simple cytotoxicity test using nonadhesive living cells, we found that the pST film is biocompatible for culturing cells on it. This finding is also supported by the fact that the surface tension of the pST film is moderate for protein adsorptions. The pST film is thinner and smoother than a poly-dopamine film, the chemical structure of which is similar to that of the pST film, depending on the polymerization time, cycle, and temperature; thus, ST as the main monomer can facilitate the precise control of the thickness and roughness of functional polymer membranes on the nanometer order. In addition, the pST film is useful as a relatively insulative interface for preventing interfering species from approaching electrode surfaces without their nonspecific adsorption, depending on the surface charges of the pST film in solutions of different pHs. The formation of the pST film self-polymerized on electrode materials is derived from the adsorption of pST nanoparticles formed by oxidative polymerization under basic conditions; therefore, the process of pST film formation should be considered in the functionalization of the pST film as a bioelectrical interface that allows biomolecular recognition (e.g., molecularly imprinted polymer membrane) for its application to wearable and biocompatible biosensors.

Technical Perspectives on Applications of Biologically Coupled Gate Field-Effect Transistors.

Biosensing technologies are required for point-of-care testing (POCT). We determine some physical parameters such as molecular charge and mass, redox potential, and reflective index for measuring biological phenomena. Among such technologies, biologically coupled gate field-effect transistor (Bio-FET) sensors are a promising candidate as a type of potentiometric biosensor for the POCT because they enable the direct detection of ionic and biomolecular charges in a miniaturized device. However, we need to reconsider some technical issues of Bio-FET sensors to expand their possible use for biosensing in the future. In this perspective, the technical issues of Bio-FET sensors are pointed out, focusing on the shielding effect, pH signals, and unique parameters of FETs for biosensing. Moreover, other attractive features of Bio-FET sensors are described in this perspective, such as the integration and the semiconductive materials used for the Bio-FET sensors.

In Situ Electrical Monitoring of Methylated DNA Based on Its Conformational Change to G-Quadruplex Using a Solution-Gated Field-Effect Transistor.

Methylated DNA is not only a diagnostic but also a prognostic biomarker for early-stage cancer. However, sodium bisulfite sequencing as a "gold standard" method for detection of methylation markers has some drawbacks such as its time-consuming and labor-intensive procedures. Therefore, simple and reliable methods are required to analyze DNA sequences with or without methylated residues. Herein, we propose a simple and direct method for detecting DNA methylation through its conformation transition to G-quadruplex using a solution-gated field-effect transistor (SG-FET) without using labeled materials. The BCL-2 gene, which is involved in the development of various human tumors, contains G-rich segments and undergoes a conformational change to G-quadruplex depending on the K+ concentration. Stacked G-quadruplex strands move close to the SG-FET sensor surface, resulting in large electrical signals based on intrinsic molecular charges. In addition, a dense hydrophilic polymer brush is grafted using surface-initiated atom transfer radical polymerization onto the SG-FET sensor surface to reduce electrical noise based on nonspecific adsorption of interfering species. In particular, control of the polymer brush thickness induces electrical signals based on DNA molecular charges in the diffusion layer, according to the Debye length limit. A platform based on the SG-FET sensor with a well-defined polymer brush is suitable for in situ monitoring of methylated DNA and realizes a point-of-care device with a high signal-to-noise ratio and without the requirement for additional processes such as bisulfite conversion and polymerase chain reaction.

Cell Adhesion Characteristics on Tantalum Pentoxide Gate Insulator for Cultured-Cell-Gate Field-Effect Transistor.

Understanding the interaction between living cells and a tantalum pentoxide (Ta2O5) gate electrode is important for controlling cell adhesion and functions when developing a cultured-cell-gate field-effect transistor biosensor. In this study, we evaluate the cell adhesion characteristics of the Ta2O5 membrane without or with a polydopamine (pDA) coating for chondrocytes, which is expected as a treatment for improving biocompatibility. As a result, the native and pDA-modified Ta2O5 membranes are shown to have the appropriate surface tension (35-40 dyn/cm) for the adhesion of chondrocytes owing to the contribution of surface tension to not only the nonspecific adsorption of serum proteins as the scaffold of chondrocytes but also the maintenance of the conformation of serum proteins. In particular, the serum proteins adhere more efficiently to the native Ta2O5 membrane than to the pDA-modified ones owing to the relatively smaller surface tension of the native Ta2O5 membrane; as a result, the proliferation and production of extracellular matrix (ECM) proteins such as collagen and proteoglycans by chondrocytes are clearly enhanced on the native Ta2O5 membrane. Thus, the native Ta2O5 membrane shows superior performance for the chondrocyte culture on it compared with the pDA-modified ones.

Densification of Diazonium-Based Organic Thin Film as Bioelectrical Interface.

Aryl diazonium chemistry generates a covalently attached thin film on various materials. This chemistry has diverse applications owing to the stability, ease of functionalization, and versatility of the film. However, the uncontrolled growth into a polyaryl film has limited the controllability of the film's beneficial properties. In this study, we developed a multistep grafting protocol to densify the film while maintaining a thickness on the order of nanometers. This simple protocol enabled the full passivation of a nitrophenyl polyaryl film, completely eliminating the electrochemical reactions at the surface. We then applied this protocol to the grafting of phenylphosphorylcholine films, with which the densification significantly enhanced the antifouling property of the film. Together with its potential to precisely control the density of functionalized surfaces, we believe this grafting procedure will have applications in the development of bioelectrical interfaces.

Biocompatible and flexible paper-based metal electrode for potentiometric wearable wireless biosensing.

A paper-based electrode is a very attractive component for a disposable, nontoxic, and flexible biosensor. In particular, wearable biosensors, which have recently been attracting interest, not only require these characteristics of paper-based electrodes but must also be able to detect various ions and biomolecules in biological fluids. In this paper, we demonstrate the detection ability of paper-based metal electrodes for wearable biosensors as part of a wireless potentiometric measurement system, focusing on the detection of pH and sodium ions. The paper-based metal electrodes were obtained by simply coating a silicone-rubber-coated paper sheet with a Au (/Cr) thin film by sputtering then modifying it with different functional membranes such as an oxide membrane (Ta2O5) and a fluoropolysilicone (FPS)-based Na+-sensitive membrane, corresponding to the targeted ions. Satisfactory and stable detection sensitivities of the modified paper-based Au electrodes were obtained over several weeks even when they were bent to a radius of curvature in the range of 6.5 to 25 mm, assuming use in a flexible body patch biosensor. Moreover, the Na+ concentration in a sweat sample was evaluated using the paper-based Au electrode with the FPS-based Na+-sensitive membrane in a wireless and real-time manner while the electrode was bent. Thus, owing to their complex mesh structure, flexible paper sheets should be suitable for use as potentiometric electrodes for wearable wireless biosensors.

Estimation of Extracellular Matrix Production Using a Cultured-Chondrocyte-Based Gate Ion-Sensitive Field-Effect Transistor.

Autologous chondrocytes are generally evaluated by mechanical, histological, and biochemical methods. However, the analyzed data are from discontinuous measurements at an end point, during which living chondrocytes are destroyed and stained. To solve the problem, we developed a label-free and noninvasive method of estimating extracellular matrix (ECM) production that results from chondrocyte metabolic activities using a cultured-chondrocyte-based gate ion-sensitive field-effect transistor (ISFET) in this study. Using the cultured-chondrocyte-based gate ISFET sensor, we found that the change in electrical signal (ΔVout), which indicated the change in interfacial pH at the chondrocyte/gate nanogap (ΔpHint), gradually increased over 3 weeks upon adding a biologically active substance, l-ascorbic acid phosphate magnesium salt n-hydrate (APM), which was attributable to chondrocyte metabolic activities. The increase in ΔVout (ΔpHint) caused by the chondrocyte metabolic activities was also confirmed by the observation of the suppression of chondrocyte metabolism upon adding 2-deoxy-d-glucose, which was clearly monitored using the cultured-chondrocyte-based gate ISFET sensor. In particular, ΔVout increased monotonically with increasing APM concentrations, indicating that the addition of APM increased ΔVout (ΔpHint), the amount of which depended on the APM concentration. Moreover, the amounts of hydroxyproline and sulfated glycosaminoglycan (sGAG) as the main components of ECM, which were quantified by colorimetry using various APM concentrations, were found to have a linear relationship with ΔVout (ΔpHint) of the cultured-chondrocyte-based gate ISFET sensor. Therefore, a platform based on the cultured-chondrocyte-based gate ISFET is suitable for a label-free, noninvasive, and real-time measurement system to analyze ECM production by autologous chondrocytes before transplantation.

Control of Potential Response to Small Biomolecules with Electrochemically Grafted Aryl-Based Monolayer in Field-Effect Transistor-Based Sensors.

In this paper, we demonstrate the use of a monolayer film electrografted via diazonium chemistry for controlling the potential response of a field-effect transistor (FET)-based sensor. 4-Nitrobenzenediazonium salt is electrografted on an extended-Au-gate FET (EG-Au-FET) with or without using a radical scavenger by cyclic voltammetry (CV), resulting in the formation of a monolayer or multilayer. In particular, the surface coverage of the aryl-derivative monolayer on the Au gate electrode gradually increases with increasing number of potential cycles in CV. Here, Au exhibits a strong catalytic action, resulting in the oxidation of organic compounds. Uric acid is used as a low-molecular-weight biomolecule for interference. The denser the surface coverage of the grafted monolayer, the smaller the potential response of the EG-Au-FET because the redox reaction of uric acid with the Au gate surface is suppressed. On the other hand, the effect of the aryl-derivative multilayer on the suppression of the potential response was smaller than that of the monolayer because the electrogenerated aryl radicals did not react with the Au surface but with the grafted species, resulting in an exposed part of the Au surface among the grafted aryl molecules. Thus, a platform based on such a monolayer film electrografted via diazonium chemistry is suitable for controlling the potential response based on the interference of low-molecular-weight biomolecules in biosamples.

Biocompatible and Na+-sensitive thin-film transistor for biological fluid sensing.

In this study, we develop a Na+-sensitive thin-film transistor (TFT) for a biocompatible ion sensor and investigate its cytotoxicity. A transparent amorphous oxide semiconductor composed of amorphous In-Ga-Zn-oxide (a-InGaZnO) is utilized as a channel of the Na+-sensitive TFT, which includes an indium tin oxide (ITO) film as the source and drain electrodes and a Ta2O5 thin-film gate, onto which a Na+-sensitive membrane is coated. As one of the Na+-sensitive membranes, the polyvinyl chloride (PVC) membrane with bis(12-crown-4) as the ionophore used on the TFT sensors shows good sensitivity and selectivity to changes in Na+ concentration but has high cytotoxicity owing to the leaching of its plasticizer to the solution; the plasticizer is added to solve and entrap the ionophore in the PVC membrane. On the other hand, a plasticizer-free Na+-sensitive membrane, the fluoropolysilicone (FPS) membrane with the bis(12-crown-4) ionophore, also reduces cell viability owing to the leaching of the ionophore. However, the FPS membrane with calix[4]arene as the ionophore on the gate of TFT sensors exhibits not only favorable electrical properties but also the lack of cytotoxicity. Thus, considering structural flexibility of TFTs, a platform based on TFT sensors coated with the Na+-sensitive FPS membrane containing calix[4]arene is suitable as a biocompatible Na+ sensing system for the continuous monitoring of ionic components in biological fluids such as sweat and tears.

Molecular-Charge-Contact-Based Ion-Sensitive Field-Effect Transistor Sensor in Microfluidic System for Protein Sensing.

In this paper, we demonstrate the possibility of direct protein sensing beyond the Debye length limit using a molecular-charge-contact (MCC)-based ion-sensitive field-effect transistor (ISFET) sensor combined with a microfluidic device. Different from the MCC method previously reported, biotin-coated magnetic beads are set on the gate insulator of an ISFET using a button magnet before the injection of target molecules such as streptavidin. Then, the streptavidin-a biotin interaction, used as a model of antigen-antibody reaction is expected at the magnetic beads/gate insulator nanogap interface, changing the pH at the solution/dielectric interface owing to the weak acidity of streptavidin. In addition, the effect of the pH or ionic strength of the measurement solutions on the electrical signals of the MCC-based ISFET sensor is investigated. Furthermore, bound/free (B/F) molecule separation with a microfluidic device is very important to obtain an actual electrical signal based on the streptavidin-biotin interaction. Platforms based on the MCC method are suitable for exploiting the advantages of ISFETs as pH sensors, that is, direct monitoring systems for antigen-antibody reactions in the field of in vitro diagnostics.

Sperm-Cultured Gate Ion-Sensitive Field-Effect Transistor for Non-Optical and Live Monitoring of Sperm Capacitation.

We have successfully monitored the effect of progesterone and Ca2+ on artificially induced sperm capacitation in a real-time, noninvasive and label-free manner using an ion-sensitive field-effect transistor (ISFET) sensor. The sperm activity can be electrically detected as a change in pH generated by sperm respiration based on the principle of the ISFET sensor. Upon adding mouse sperm to the gate of the ISFET sensor in the culture medium with progesterone, the pH decreases with an increasing concentration of progesterone from 1 to 40 µM. This is because progesterone induces Ca2+ influx into spermatozoa and triggers multiple Ca2+-dependent physiological responses, which subsequently activates sperm respiration. Moreover, this pH response of the ISFET sensor is not observed for a Ca2+-free medium even when progesterone is introduced, which means that Ca2+ influx is necessary for sperm activation that results in sperm capacitation. Thus, a platform based on the ISFET sensor system can provide a simple method of evaluating artificially induced sperm capacitation in the field of male infertility treatment.

Live Monitoring of Microenvironmental pH Based on Extracellular Acidosis around Cancer Cells with Cell-Coupled Gate Ion-Sensitive Field-Effect Transistor.

We demonstrated the live monitoring of cellular respiration using an ion-sensitive field-effect transistor (ISFET), focusing on different types of living cells, namely cancer and normal cells. In particular, we realized the label-free, real-time, and noninvasive monitoring of microenvironmental pH behavior based on extracellular acidosis around cancer cells in the long term and in situ. The change in interfacial pH (ΔpHint), which was analyzed based on the change in interfacial potential (Δ Vout) at the cell/gate nanogap interface gradually decreased for every cell-based ISFET. Moreover, the ΔpHint for cancer cells shifted by a factor of 5 to 6, which was larger than that for normal cells. This is because cancer cells cause dysbolism and are activated, thereby suppressing oxidative phosphorylation in mitochondria so as not to induce their apoptosis. Therefore, cancer cellular respiration proceeds via the glycolysis pathway, through which lactic acid is eventually released. Additionally, the pH sensitivity of the ISFET device was maintained even when the device was immersed into a cell culture medium for 24 h and 1 w; thus, the effect of nonspecific adsorption of proteins contained in the medium on the pH sensitivity of the ISFET device was negligible in the live monitoring of cellular respiration.

In situ electrical monitoring of cancer cells invading vascular endothelial cells with semiconductor-based biosensor.

Cellular dynamics is very closely related to ionic behaviors, most of which have been hardly monitored in real time, whereas semiconductor-based biosensors have the unique advantage of direct detection of ionic charges in a real-time and noninvasive manner. In this study, we monitored the invasion process of cancer cells into the vascular endothelial layer in real time by a label-free method using a field-effect transistor (FET) biosensor. Endothelial cells were cultured on the sensing surface of the FET gate, to form a basement membrane between the endothelial cells and the sensing surface. When invasive cancer cells (HeLa cells) approached the endothelial cell-coated gate FET biosensor, a change in the surface potential was clearly detected using the FET biosensor. This is because HeLa cells, which invaded the endothelial cell layer, reduced the molecular charge density in the basement membrane by decomposing it. A platform based on the cell-coated gate FET biosensor is suitable for real-time and noninvasive monitoring of cellular dynamics based on intrinsic ionic charges.

Dysregulation of a potassium channel, THIK-1, targeted by caspase-8 accelerates cell shrinkage.

Activation of caspases is crucial for the execution of apoptosis. Although the caspase cascade associated with activation of the initiator caspase-8 (CASP8) has been investigated in molecular and biochemical detail, the physiological role of CASP8 is not fully understood. Here, we identified a two-pore domain potassium channel, tandem-pore domain halothane-inhibited K+ channel 1 (THIK-1), as a novel CASP8 substrate. The intracellular region of THIK-1 was cleaved by CASP8 in apoptotic cells. Overexpression of THIK-1, but not its mutant lacking the CASP8-target sequence in the intracellular portion, accelerated cell shrinkage in response to apoptotic stimuli. In contrast, knockdown of endogenous THIK-1 by RNA interference resulted in delayed shrinkage and potassium efflux. Furthermore, a truncated THIK-1 mutant lacking the intracellular region, which mimics the form cleaved by CASP8, led to a decrease of cell volume of cultured cells without apoptotic stimulation and excessively promoted irregular development of Xenopus embryos. Taken together, these results indicate that THIK-1 is involved in the acceleration of cell shrinkage. Thus, we have demonstrated a novel physiological role of CASP8: creating a cascade that advances the cell to the next stage in the apoptotic process.

Ion Sensitive Transparent-Gate Transistor for Visible Cell Sensing.

In this study, we developed an ion-sensitive transparent-gate transistor (IS-TGT) for visible cell sensing. The gate sensing surface of the IS-TGT is transparent in a solution because a transparent amorphous oxide semiconductor composed of amorphous In-Ga-Zn-oxide (a-IGZO) with a thin SiO2 film gate that includes an indium tin oxide (ITO) film as the source and drain electrodes is utilized. The pH response of the IS-TGT was found to be about 56 mV/pH, indicating approximately Nernstian response. Moreover, the potential signals of the IS-TGT for sodium and potassium ions, which are usually included in biological environments, were evaluated. The optical and electrical properties of the IS-TGT enable cell functions to be monitored simultaneously with microscopic observation and electrical measurement. A platform based on the IS-TGT can be used as a simple and cost-effective plate-cell-sensing system based on thin-film fabrication technology in the research field of life science.

Nonoptical Detection of Allergic Response with a Cell-Coupled Gate Field-Effect Transistor.

In this study, we report the label-free and reliable detection of allergic response using a cell-coupled gate field-effect transistor (cell-based FET). Rat basophilic leukemia (RBL-2H3) cells were cultured as a signal transduction interface to induce allergic reaction on the gate oxide surface of the FET, because IgE antibodies, which bind to Fcε receptors at the RBL-2H3 cell membrane, are specifically cross-linked by allergens, resulting in the allergic response of RBL-2H3 cells. In fact, the surface potential at the FET gate decreased owing to secretions such as histamine from the IgE-bound RBL-2H3 cells, which reacted with the allergen. This is because histamine, as one of the candidate secretions, shows basicity, resulting in a change in pH around the cell/gate interface. That is, the RBL-2H3-cell-based FET used in this study was originally from an ion-sensitive FET (ISFET), whose oxide surface (Ta2O5) with hydroxyl groups is fully responsive to pH on the basis of the equilibrium reaction. The allergic response of RBL-2H3 cells on the gate was also confirmed by estimating the amount of ß-hexosaminidase released together with histamine and was analyzed using the electrical properties based on an inflammatory response of secreted histamine with the vascular endothelial cell-based FET. Thus, the allergic responses were monitored in a nonoptical and real-time manner using the cell-based FETs with the cellular layers on the gate, which reproduced the in vivo system and were useful for the reliable detection of the allergic reaction.

Glucose-responsive hydrogel electrode for biocompatible glucose transistor.

In this paper, we propose a highly sensitive and biocompatible glucose sensor using a semiconductor-based field effect transistor (FET) with a functionalized hydrogel. The principle of the FET device contributes to the easy detection of ionic charges with high sensitivity, and the hydrogel coated on the electrode enables the specific detection of glucose with biocompatibility. The copolymerized hydrogel on the Au gate electrode of the FET device is optimized by controlling the mixture ratio of biocompatible 2-hydroxyethylmethacrylate (HEMA) as the main monomer and vinylphenylboronic acid (VPBA) as a glucose-responsive monomer. The gate surface potential of the hydrogel FETs shifts in the negative direction with increasing glucose concentration from 10 µM to 40 mM, which results from the increase in the negative charges on the basis of the diol-binding of PBA derivatives with glucose molecules in the hydrogel. Moreover, the hydrogel coated on the gate suppresses the signal noise caused by the nonspecific adsorption of proteins such as albumin. The hydrogel FET can serve as a highly sensitive and biocompatible glucose sensor in in vivo or ex vivo applications such as eye contact lenses and sheets adhering to the skin.