Extended-gate Field-effect Transistor Research Articles

Towards monitoring of critical illness via the detection of histones with extended gate field-effect transistor sensors

Extracellular histone proteins in the blood indicate a heightened risk of morbidity after trauma or in major illnesses such as sepsis. We present the development of an aptasensor for histone detection with an extended gate field-effect transistor (EGFET) configuration, which benefits from low power consumption, rapid response, and compatibility with miniaturized gold electrodes. Histones have a high isoelectric point and charge density, which cause them to physically adsorb to non-specific elements of the sensor that have available electrostatic charges. To combat this, the sensing surface is formed with a thiol-modified, high-affinity and histone-specific RNA aptamer sequence and by co-immobilizing with poly(ethylene glycol) methyl ether thiol (PEG) as a blocking agent. Surface plasmon resonance (SPR) is used to analyze aptamer and PEG immobilization strategies, confirm histone binding, and calculate kinetic binding constants. Through comparison of different blocking agents and time-dependent preparation, the ideal equilibrium dissociation constant (KD) is estimated to be below 200 pM, which is the upper range of extracellular histone concentrations in critically ill patients with high mortality. The EGFET sensitivity of the optimized aptasensor is 6.65 mV/decade concentration change for histone H4 with a physiologically relevant 5 pM limit of detection. Selectivity tests with 100 nM bovine serum albumin (BSA) demonstrate a signal response that is 13-fold smaller than for histones. This EGFET aptasensor platform is suitable for future point-of-care monitoring of histone levels in critically ill patients, thus permitting the early detection of increased risk and the need for more aggressive interventional measures to prevent mortality.

Copper Recovery from Mobile Phone Printed Circuit Board E-Waste and Transforming into CuO@C for Electrode Material in Extended Gate Field-Effect Transistors Facilitating Non-Enzymatic Ascorbic Acid Detection

Copper Recovery from Mobile Phone Printed Circuit Board E-Waste and Transforming into CuO@C for Electrode Material in Extended Gate Field-Effect Transistors Facilitating Non-Enzymatic Ascorbic Acid Detection

Copper Recovery from Mobile Phone Printed Circuit Board E-Waste and Transforming into CuO@C for Electrode Material in Extended Gate Field-Effect Transistors Facilitating Non-Enzymatic Ascorbic Acid Detection

Copper Recovery from Mobile Phone Printed Circuit Board E-Waste and Transforming into CuO@C for Electrode Material in Extended Gate Field-Effect Transistors Facilitating Non-Enzymatic Ascorbic Acid Detection

High pH stability and detection of α-synuclein using an EGFET biosensor with an HfO2 gate deposited by high-power pulsed magnetron sputtering

In this research, hafnium oxide (HfO2) was first fabricated in an in-house-developed high-power pulsed magnetron sputtering system (HiPIMS) functionalized for application as a high-performance extended gate field-effect transistor (EGFET) for the detection of pH and proteins associated with Parkinson's disease (PD). PD is the second most common neurodegenerative disease in elderly people after Alzheimer's disease. The α-synuclein protein in patients’ blood may be a potential biomarker in the early stage of PD. Detection of α-synuclein with high sensitivity and nonspecific binding through HfO2-EGFET biosensors has the advantages of low cost and simple fabrication from disposable EGs. Among the duty cycle conditions tested, HfO2 deposited at a 25% duty cycle in HiPIMS exhibited superior pH sensitivity and linearity, with values of 56.4 mV/pH and 99.7%, respectively. The hysteresis width and drift coefficient are −3 mV and 0.3 mV/h, respectively. To overcome the Debye length limitation, 100-fold diluted phosphate buffer solution and the PMOS configuration were used to determine the α-synuclein for which the isoelectric point was 4.67. The negative gate bias in the PMOS configuration successfully causes α-synuclein to approach the surface of HfO2 EG to achieve a sensitivity of 12.1 mV/dec and a linearity of 99.5% in the range of 0.1–1000 pg/mL. The limit of detection is 0.198 pg/mL, and the immobilized surface ultimately binds specifically, resulting in low interference signals from other related biomarkers. This promising study shows that detecting various proteins involved in different diseases and performing clinical tests can be accomplished in the future.

On-site SNP discrimination of Monkeypox viral DNA at room temperature using dCas9-enhanced extended-gate field-effect transistor

During the COVID-19 pandemic, there was heightened concern about the sudden spread of viral diseases. As the threat of coronavirus transmission began to diminish, a subsequent outbreak caused by monkeypox virus (MPXV) emerged in Europe and North America. Notably, MPXV infection tends to be transmitted through sexual contact, increasing the difficulty of tracing the infection route through passive testing. As a result, there is a pressing need for cost-effective, precise, and rapid on-site screening techniques to detect MPXV. Recently, the CRISPR system, known as a genome editing tool, has been used as a rapid on-site diagnostic tool for detecting nucleic acids mostly through the use of Cas12a and Cas13a. Intriguingly, deficient Cas9 (dCas9) can recognize specific double-stranded DNA (dsDNA) sequences and bind to complementary DNA sequences. Here, we devised an innovative digital field-diagnosis platform that can be readily employed in clinical settings. This platform combines an ultrasensitive field-effect transistor (FET) with the dCas9 system, enabling quantitative analysis of biomarkers. Our dCas9-EG-FET can directly detect viral dsDNA without any amplification or pretreatment. When the dCas9 of our dCas9-EG-FET system recognizes the specific target viral DNA, the EG-FET system provides voltage differences by using FET features that measure the ion concentration on the surface of the FET sensor. Furthermore, it takes only 20 min to detect MPXV DNA using our dCas9-EG-FET system at room temperature (RT), and this system can be used to effectively distinguish single-point mutations with high sensitivity. Our findings suggest that the use of a CRISPRCas-based biosensor could lead to an effective strategy for screening for infectious diseases.

Extended-Gate FET Biosensor Based on GaN Micropillar Array and Polycrystalline Layer: Application to Hg2+ Detection in Human Urine.

Owing to the separation of field-effect transistor (FET) devices from sensing environments, extended-gate FET (EGFET) biosensor features high stability and low cost. Herein, a highly sensitive EGFET biosensor based on a GaN micropillar array and polycrystalline layer (GMP) was fabricated, which was prepared by using simple one-step low-temperature MOCVD growth. In order to improve the sensitivity and detection limit of EGFET biosensor, the surface area and the electrical conductivity of extended-gate electrode can be increased by the micropillar array and the polycrystalline layer, respectively. The designed GMP-EGFET biosensor was modified with l-cysteine and applied for Hg2+ detection with a low limit of detection (LOD) of 1 ng/L, a high sensitivity of -16.3 mV/lg(μg/L) and a wide linear range (1 ng/L-24.5 μg/L). In addition, the detection of Hg2+ in human urine was realized with an LOD of 10 ng/L, which was more than 30 times lower than that of reported sensors. To our knowledge, it is the first time that GMP was used as extended-gate of EGFET biosensor.

A simple and highly sensitive flexible sensor with extended-gate field-effect transistor for epinephrine detection utilizing InZnSnO sensing films

This study introduces a straightforward method for depositing InZnSnO films onto flexible polyimide substrates at room temperature, enabling their application in electrochemical pH sensing and the detection of epinephrine. A comprehensive analysis of these sensing films, spanning structural, morphological, compositional, and profiling characteristics, was conducted using diverse techniques, including X-ray diffraction, atomic force microscopy, X-ray photoelectron spectroscopy, and secondary ion mass spectroscopy. The investigation into the influence of oxygen flow rates on the performance of InZnSnO sensitive films revealed a significant correlation between their structural properties and sensing capabilities. Notably, exposure to an oxygen flow rate of 30/2 (Ar/O2) the ratio of resulted in the InZnSnO sensitive film demonstrating outstanding pH sensitivity at 59.58 mV/pH within a broad pH range of 2–12, surpassing the performance observed with other oxygen flow rates. Moreover, under this specific condition, the film exhibited excellent stability, with a minimal drift rate of 0.14 mV/h at pH 7 and a low hysteresis voltage of 1.8 mV during a pH cycle of 7 → 4→7 → 10→7. Given the critical role of epinephrine in mammalian central nervous and hormone systems, monitoring its levels is essential for assessing human health. To facilitate the detection of epinephrine, we utilized the carboxyl group of 4-formylphenylboronic acid to enable a reaction with the amino group of the 3-aminopropyltriethoxysilane-coated InZnSnO film. Through optimization, the resulting InZnSnO-based flexible sensor displayed a broad and well-defined linear relationship within the concentration range of 10−7 to 0.1 μM. In practical applications, this sensor proved effective in analyzing epinephrine in human serum, showcasing notable selectivity, stability, and reproducibility. The promising outcomes of this study underscore the potential for future applications, leveraging the advantages of electrochemical sensors, including affordability, rapid response, and user-friendly operation.

Metal-organic frameworks as sensitisers for potentiometric sensors

As an example for a metal-organic framework (MOF) sorbent acting as sensitiser in a potentiometric sensor, we introduce the metal–organic framework (MOF) UiO-66-NH2 into a bridged extended-gate field effect transistor (EGFET) design. The sensitised EGFET detects residue of the insecticide imidacloprid with a limit of detection more than 3 orders of magnitude smaller than the EU ‘Maximum Residue Limit’ (MRL) for imidacloprid. This allows decisions on MRL compliance of water at a much lower experimental footprint than with chromatographic methods. To apply the sensor to food samples, we account for possible interference from legitimate food ingredients. Interference is small or moderate for fruit juices, moderate for ‘red’ juice (containing anthocyanin dyes), and small for others. Interference is strong for tea, probably from caffeine. We propose a test protocol to make ‘accept/reject’ decisions with respect to imidacloprid residue even in the presence of small or moderate interference. The present agar-bridged EGFET design enables the wider use of MOF sorbents in potentiometric sensors.

Pyrene Derivative Incorporated Ni MOF as an Enzyme Mimic for Noninvasive Salivary Glucose Detection Toward Diagnosis of Diabetes Mellitus.

Herein, we demonstrate the detection of glucose in a noninvasive and nonenzymatic manner by utilizing an extended gate field-effect transistor (EGFET) based on the organic molecule pyrene phosphonic acid (PyP4OH8) incorporated nickel metal-organic framework (NiOM-MOF). The prepared electrode responds selectively to glucose instead of sucrose, fructose, maltose, ascorbic acid, and uric acid in a 1× phosphate buffer saline solution. Also, utilizing the scanning Kelvin probe system, the sensing electrode's work function (Φ) is measured to validate the glucose-sensing mechanism. The sensitivity, detection range, response time, limit of detection, and limit of quantification of the electrode are determined to be 24.5 μA mM-1 cm-2, 20 μM to 10 mM, less than 5 s, 2.73 μM, and 8.27 μM, respectively. Most interestingly, the developed electrode follows the Michaelis-Menten kinetics, and the calculated rate constant (km) 0.07 mM indicates a higher affinity of NiOM-MOF toward glucose. The real-time analysis has revealed that the prepared electrode is sensitive to detect glucose in real human saliva, and it can be an alternative device for the noninvasive detection of glucose. Overall, the outcomes of the EGFET studies demonstrate that the prepared electrodes are well-suited for expeditious detection of glucose levels in saliva.

An extended-gate field-effect transistor (EG-FET) signal transducing combined with epitope molecular imprinting for selective chemosensing of chosen idiopathic pulmonary fibrosis (IPF) biomarkers

We propose a relatively rapid and straightforward procedure for the determination of chosen idiopathic pulmonary fibrosis (IPF) predictive protein biomarkers, vis., matrix metalloproteinase-1 (MMP-1) and surfactant-associated protein-A (SP-A), suitable for their determination in bodily fluids. IPF is a lethal lung disease, annually causing nearly as many deaths as breast cancer. Moreover, the coronavirus recently triggered acute exacerbation of patients suffering from IPF. Here, epitopes specific to the chosen IPF biomarkers were molecularly imprinted in a polymer as an alternative to imprinting fragile whole biomarkers’ molecules. A thin molecularly imprinted polymer (MIP) film-based recognition units were integrated by electropolymerization with gates of extended-gate field-effect transistors (EG-FETs) to fabricate biomarker-selective chemical sensors suitable as point-of-care testing (POCT) diagnostic devices. Either AQDDIDGIQAI or FKGNKYWAVQGQNV single-epitope imprinting allowed determining the MMP-1 biomarker in the 10 to 250 nM linear dynamic concentration range with a LOD of 7.5 or 2 nM, respectively. Simultaneous imprinting of three MMP-1 epitopes, vis., MIAHDFPGIGHK, HGYPKDIYSS, and FKGNKYWAVQGQNV, decreased this LOD to 0.1 nM, allowing for determining this biomarker in serum. Moreover, by FSSNGQSIT or YSDGTPVNYTNWYR single-epitope imprinting, chemosensors for SP-A were fabricated to show the versatility of epitope imprinting. These chemosensors selectively determined the SP-A biomarker with the LOD of 1.9 or 2.9 nM, allowing its determination in bodily fluids.

Performance Improvement of a ZnGa2O4 Extended-Gate Field-Effect Transistor pH Sensor.

ZnGa2O4 sensing films were prepared using an RF magnetron sputtering system and connected to a commercial metal oxide semiconductor field-effect transistor (MOSFET) as the extended-gate field-effect transistor (EGFET) to detect pH values. Experimental parameters were adjusted by varying the oxygen flow rate in the process chamber to produce ZnGa2O4 sensing films with different oxygen ratios. These films were then treated in a furnace tube at an annealing temperature of 700 °C. The sensitivity and linearity of the constant current mode and the constant voltage mode were measured and analyzed in the pH range of 2-12. Under the deposition conditions with an oxygen ratio of 6%, the sensitivity reached 23.14 mV/pH and 33.49 μA/pH, with corresponding linearity values of 92.1 and 96.15%, respectively. Finally, the sensing performance of the ZnGa2O4 EGFET pH sensor with and without annealing processes was analyzed and compared.

Evaluation of sensitivity of Extended Gate Field Effect Transistor -biosensor based on V2O5/GOx for glucose detection

The sensing modified electrode was prepared using glucose oxidase immobilized onto vanadium pentoxide xerogel with glass/FTO as support electrode to evaluate the possibility to construct a V2O5/GOx Extended Gate Field Effect Transistor biosensor. Previously, our studies exhibited a sensitivity of V2O5 of 58.1 mV/pH. The use of Nafion® onto V2O5/GOx caused a decrease of mass loss after several cycles compared to the modified electrode without Nafion® during the EQCM and cyclic voltammetrics studies. Electrical characterization of V2O5/GOx demonstrated a tendency to stability after 200 s as a function of applied current. In presence of glucose and in different pH, the current decreased when the glucose concentration increased due to the lower active sites of enzyme. After ten voltammetric cycles, the total charge tends to structural stability. In pH = 5.0, the modified electrode based on V2O5/GOx Extended Gate Field Effect Transistor presented more tendency to sensitivity in different concentration of glucose.

Development of Direct Electron Transfer-Type Extended Gate Field Effect Transistor Enzymatic Sensors for Metabolite Detection.

In this work, direct electron transfer (DET)-type extended gate field effect transistor (EGFET) enzymatic sensors were developed by employing DET-type or quasi-DET-type enzymes to detect glucose or lactate in both 100 mM potassium phosphate buffer and artificial sweat. The system employed either a DET-type glucose dehydrogenase or a quasi-DET-type lactate oxidase, the latter of which was a mutant enzyme with suppressed oxidase activity and modified with amine-reactive phenazine ethosulfate. These enzymes were immobilized on the extended gate electrodes. Changes in the measured transistor drain current (ID) resulting from changes to the working electrode junction potential (φ) were observed as glucose and lactate concentrations were varied. Calibration curves were generated for both absolute measured ID and ΔID (normalized to a blank solution containing no substrate) to account for variations in enzyme immobilization and conjugation to the mediator and variations in reference electrode potential. This work resulted in a limit of detection of 53.9 μM (based on ID) for glucose and 2.12 mM (based on ID) for lactate, respectively. The DET-type and Quasi-DET-type EGFET enzymatic sensor was then modeled using the case of the lactate sensor as an equivalent circuit to validate the principle of sensor operation being driven through OCP changes caused by the substrate-enzyme interaction. The model showed slight deviation from collected empirical data with 7.3% error for the slope and 8.6% error for the y-intercept.

Nonenzymatic Potentiometric Detection of Ascorbic Acid with Porphyrin/ZnO-Functionalized Laser-Induced Graphene as an Electrode of EGFET Sensors.

Laser-induced graphene (LIG) has emerged as a highly versatile material with significant potential in the development of electrochemical sensors. In this paper, we investigate the use of LIG and LIG functionalized with ZnO and porphyrins-ZnO as the gate electrodes of the extended gate field effect transistors (EGFETs). The resultant sensors exhibit remarkable sensitivity and selectivity, particularly toward ascorbic acid. The intrinsic sensitivity of LIG undergoes a notable enhancement through the incorporation of hybrid organic-inorganic materials. Among the variations tested, the LIG electrode coated with zinc tetraphenylporphyrin-capped ZnO nanoparticles demonstrates superior performance, reaching a limit of detection of approximately 3 nM. Furthermore, the signal ratio for 5 μM ascorbic acid relative to the same concentration of dopamine exceeds 250. The practical applicability of these sensors is demonstrated through the detection of ascorbic acid in real-world samples, specifically in a commercially available food supplement containing l-arginine. Notably, formulations with added vitamin C exhibit signals at least 25 times larger than those without, underscoring the sensors' capability to discern and quantify the presence of ascorbic acid in complex matrices. This research not only highlights the enhanced performance of LIG-based sensors through functionalization but also underscores their potential for practical applications in the analysis of vitamin-rich supplements.

Development of a glycated albumin sensor employing dual aptamer-based extended gate field effect transistors

Glycated albumin (GA), defined as the percentage of serum albumin glycation, is a mid-term glycemic control marker for diabetes. The concentrations of both glycated human serum albumin (GHSA) and total human serum albumin (HSA) are required to calculate GA. Here, we report the development of a GA sensor employing two albumin aptamers: anti-GHSA aptamer which is specific to GHSA and anti-HSA aptamer which recognizes both glycated and non-glycated HSA. We combine these aptamers with extended gate field effect transistors (EGFETs) to realize GA monitoring without the need to pretreat serum samples, and therefore suitable for point of care and home-testing applications. Using anti-GHSA aptamer-immobilized electrodes and EGFETs, we measured GHSA concentrations between 0.1-10 μM within 20 min. The sensor was able to measure GHSA concentration in the presence of BSA for a range of known GA levels (5–29%). With anti-HSA aptamer-immobilized electrodes and EGFETs, we measured total HSA concentrations from 1-17 μM. Furthermore, GHSA and total HSA concentrations of both healthy and diabetic-level samples were determined with GHSA and HSA sensors. The measured GHSA and total HSA concentrations in three samples were used to determine respective GA percentages, and our calculations agreed with GA levels determined by reference methods. Thus, we developed simple and rapid dual aptamer-based EGFET sensors to monitor GA through measuring GHSA and total HSA concentration, without the need for sample pretreatment, a mandatory step in the current standard of enzymatic GA monitoring.

Tin disulfide nanoflowers and nitrogen doped graphene oxide based extended gate field effect transistor as immunosensors

Miniaturized biosensor design is widely preferred for its application in integrated platform to provide rapid and sensitive diagnosis. However, there are only few reports which employ extended gate field effect transistors (EG-FET) for immunosensing application. Herein, we designed EG-FET using four level lithography techniques. Further, the gate layer (Au/Ti) of device has been modified with Tin disulfide nanoflowers (SnS2) and nitrogen doped graphene oxide (N-GO) hybrid composite for enhanced electrical sensing. The as-prepared SnS2 and N-GO based nanocomposite (SnS2/N-GO) was characterized by various techniques. The designed SnS2/N-GO based EG-FET was employed as an immunosensor to detect HIgG using anti-HIgG antibody. Under optimum conditions, our miniaturized immunosensor demonstrated the detection of HIgG as low as 4.81 ng/mL. The proposed immunosensor exhibited excellent sensitivity, selectivity and reproducibility towards HIgG detection, thereby suitable for a reliable integrated biosensing platform which can detect protein concentration in real samples for clinical diagnostics.

High Sensitivity of Extended-Gate Field-Effect Transistors Based on 1-D ZnO:Ag Nanomaterials through a Cheap Photochemical Synthesis as pH Sensors at Room Temperature

High Sensitivity of Extended-Gate Field-Effect Transistors Based on 1-D ZnO:Ag Nanomaterials through a Cheap Photochemical Synthesis as pH Sensors at Room Temperature

A 'Frugal' EGFET Sensor for Waterborne H2S.

Hydrogen sulphide (H2S) is a toxic gas soluble in water, H2Saq, as a weak acid. Since H2Saq usually originates from the decomposition of faecal matter, its presence also indicates sewage dumping and possible parallel waterborne pathogens associated with sewage. We here present a low footprint ('frugal') H2Saq sensor as an accessible resource for water quality monitoring. As a sensing mechanism, we find the chemical affinity of thiols to gold (Au) translates to H2Saq. When an Au electrode is used as a control gate (CG) or floating gate (FG) electrode in the electric double layer (EDL) pool of an extended gate field effect transistor (EGFET) sensor, EGFET transfer characteristics shift along the CG voltage axis in response to H2Saq. We rationalise this by the interface potential from the adsorption of polar H2S molecules to the electrode. The sign of the shift changes between Au CG and Au FG, and cancels when both electrodes are Au. The sensor is selective for H2Saq over the components of urine, nor does urine suppress the sensor's ability to detect H2Saq. Electrodes can be recovered for repeated use by washing in 1M HCl. Quantitatively, CG voltage shift is fitted by a Langmuir-Freundlich (LF) model, supporting dipole adsorption over an ionic (Nernstian) response mechanism. We find a limit-of-detection of 14.9 nM, 100 times below potability.

Ultrasensitive sensing urinary cystatin C via an interface-engineered graphene extended-gate field-effect transistor for non-invasive diagnosis of chronic kidney disease

Early chronic kidney disease (CKD) has strong concealment and lacks an efficient, non-invasive, and lable-free detection platform. Cystatin C (Cys C) in urine is closely related to the progress of CKD (especially at the early stage), which is an ideal endogenous marker to evaluate the impairment of renal function. Thus, the accurate detection of urinary Cys C (u-Cys C) is great significant for early prevention and treatment and delaying the course of the disease of CKD patients. Herein, we developed an extended-gate field-effect transistor (EG-FET) sensor for ultrasensitive detection of u-Cys C, which consists of a monolithic interface-engineered graphene EG electrode array and a commercially available MOSFET. Laser-induced graphene (LIG) loaded with sputtered Au NPs in the presence of adhesive Cr (Au NPs/Cr/LIG) boosts the electrical performance of the EG electrode. Meanwhile, Au NPs also serve as linkers to immobilize papain that can selectively form protein complexes with Cys C. Supported by the synergistic effect of multilevel interface-engineered graphene, our sensor exhibits a good linear correlation within the u-Cys C concentration range of 5 ag/μL to 50 ng/μL with low detection limit of 0.05 ag/μL. Our work makes accurate, specific and rapid detection of u-Cys C feasible and promising for early screening for CKD.

Optimizing Sensitivity and Dimensions in CMOS Extended Gate FET Biosensors

Optimizing Sensitivity and Dimensions in CMOS Extended Gate FET Biosensors