Field Effect Transistor Biosensor Research Articles

Integrated Urinalysis Devices Based on Interface-Engineered Field-Effect Transistor Biosensors Incorporated With Electronic Circuits.

Urinalysis is attractive in non-invasive early diagnosis of bladder cancer compared with clinical gold standard cystoscopy. However, the trace bladder tumor biomarkers in urine and the particularly complex urine environment pose significant challenges for urinalysis. Here, a clinically adoptable urinalysis device that integrates molecular-specificity indium gallium zinc oxide field-effect transistor (IGZO FET) biosensor arrays, a device control panel, and an internet terminal for directly analyzing five bladder-tumor-associated proteins in clinical urine samples, is reported for bladder cancer diagnosis and classification. The IGZO FET biosensors with engineered sensing interfaces provide high sensitivity and selectivity for identification of trace proteins in the complex urine environment. Integrating with a machine-learning algorithm, this device can identify bladder cancer with an accuracy of 95.0% in a cohort of 197 patients and 75 non-bladdercancer individuals, distinguishing cancer stages with an overall accuracy of 90.0% and assessing bladder cancer recurrence after surgical treatment. The non-invasive urinalysis device defines a robust technology for remote healthcare and personalized medicine.

The Characteristics Analysis of a Microfluid-Based EGFET Biosensor with On-Chip Sensing Film for Lactic Acid Detection.

In this research, a microfluid-based extended gate field-effect transistor (EGFET) biosensor with an on-chip sensing window (OCSW) was fabricated. The detection window was composed of six metal layers, and a ruthenium dioxide (RuO2) film was spattered on the surface and functionalized with lactase to detect lactic acid (LA). To detect LA in a more diversified way, a microfluidic system was integrated with the biosensor. Moreover, a special package was used to seal the sensing window and microfluidic tube and insulate it from other parts to prevent water molecule invasion and chip damage. The sensitivity analysis of the EGFET biosensor was studied by a semiconductor parameter analyzer (SPA). The static and dynamic measurements of the EGFET with sensing windows on a chip were analyzed. The sensing characteristics of the EGFET biosensor were verified by the experimental results. The proposed biosensor is suitable for wearable applications due to the advantages of its low weight, low voltage, and simple manufacturing process.

Improvement in long-term stability of field effect transistor biosensor in aqueous environments using a combination of silane and reduced graphene oxide coating

A field-effect transistor (FET) biosensor that can directly detect target molecules is a promising diagnostic tool for healthcare and medical applications. However, the immersion of FET sensors in aqueous physiological environments for the long-term stability might damage the insulating layer of silicon dioxide, resulting in the degradation of the sensor response reproducibility. In this study, to improve the durability of the sensor response for long-term immersion in aqueous solution, we examined the effectiveness of reduced graphene oxide (rGO) coating on the gate insulator of FET sensors. The rGO coating was applied to the gate surface of the FET biosensor modified with an amino-terminated self-assembled monolayer by two steps: deposition of graphene oxide (GO) dispersion onto the monolayer-modified surface and subsequent thermal reduction of GO. The transconductance of both GO-coated and rGO-coated FETs remained unchanged after incubation under physiological conditions, suggesting that graphene prevents cations in the electrolytes from invading the gate insulator of the FET. Furthermore, functionalizing the rGO-coated FET surface enabled specific detection of target molecule.

Experimental comparison of direct and indirect aptamer-based biochemical functionalization of electrolyte-gated graphene field-effect transistors for biosensing applications

Aptamer-based electrolyte-gated graphene field-effect transistor (EGFET) biosensors have gained considerable attention because of their rapidity and accuracy in terms of quantification of a wide range of biomarkers. Functionalization of the graphene channel of EGFETs with aptamer biorecognition elements (BREs) is a crucial step in fabrication of EGFET aptasensors. This paper presents a comprehensive comparison of commonly used biochemical functionalization approaches applied for preparation of sensing films in EGFET aptasensors, namely indirect and direct immobilization of BREs. This study is the first of its kind to experimentally compare the two BREs immobilization approaches in terms of their effects on the carrier mobility of the monolayer graphene channel and their suitability for sensing applications. Both approaches can preserve and even improve the carrier mobility of bare graphene channel and hence the sensitivity of the EGFET; however, the direct BREs immobilization method was selected to develop an aptameric EGFET biosensor as this method enables simpler and more efficient preparation of the graphene-based aptameric sensing film. The utility of the prepared EGFET aptasensor is demonstrated through detection of tumor necrosis factor-α (TNF-α), an important inflammatory biomarker. The direct BREs immobilization approach is applied to develop an EGFET aptasensor to measure TNF-α in a detection range from 10 pg/ml to 10 ng/ml, representative of its physiological level in human sweat, as a non-invasively accessible biofluid. The outstanding sensing performance of the developed TNF-α EGFET aptasensor based on direct BREs immobilization can pave the way for development of graphene biosensors.

Superhydrophobic Paper-Based Microfluidic Field-Effect Transistor Biosensor Functionalized with Semiconducting Single-Walled Carbon Nanotube and DNAzyme for Hypocalcemia Diagnosis.

Hypocalcemia is caused by a sharp decline in blood calcium concentration after dairy cow calving, which can lead to various diseases or even death. It is necessary to develop an inexpensive, easy-to-operate, reliable sensor to diagnose hypocalcemia. The cellulose-paper-based microfluidic field-effect biosensor is promising for point-of-care, but it has poor mechanical strength and a short service life after exposure to an aqueous solution. Octadecyltrichlorosilane (OTS), as a popular organosilane derivative, can improve the hydrophobicity of cellulose paper to overcome the shortage of cellulose paper. In this work, OTS was used to produce the superhydrophobic cellulose paper that enhances the mechanical strength and short service life of MFB, and a microfluidic field-effect biosensor (MFB) with semiconducting single-walled carbon nanotubes (SWNTs) and DNAzyme was then developed for the Ca2+ determination. Pyrene carboxylic acid (PCA) attached to SWNTs through a non-covalent π-π stacking interaction provided a carboxyl group that can bond with an amino group of DNAzyme. Two DNAzymes with different sensitivities were designed by changing the sequence length and cleavage site, which were functionalized with SPFET/SWNTs-PCA to form Dual-MFB, decreasing the interference of impurities in cow blood. After optimizing the detecting parameters, Dual-MFB could determine the Ca2+ concentration in the range of 25 μM to 5 mM, with a detection limit of 10.7 μM. The proposed Dual-MFB was applied to measure Ca2+ concentration in cow blood, which provided a new method to diagnose hypocalcemia after dairy cow calving.

Real-time monitoring of serotonin with highly selective aptamer-functionalized conducting polymer nanohybrids

Adequate serotonin levels are pivotal to human well-being; thus, serotonin can be used as a biomarker because it regulates a wide range of physical and psychological functions. As an imbalance of serotonin is highly likely to initiate the pathogenesis of various disorders, monitoring serotonin levels in real time is in high demand for the early detection of disease. We fabricated a field-effect transistor (FET) biosensor based on aptamer-immobilized conducting polymer nanohybrids, which showed an instantaneous response toward serotonin in solution. The mechanism of serotonin detection was based on aptamer deformation after aptamer-ligand interaction and the consequential decrease in the charge carrier density of the FET template. Docking simulations with AutoDock/Vina and PyMOL were successfully used to investigate the binding site of serotonin in the loop structure of the aptamer. The fabricated FET template showed high sensitivity toward serotonin in the range of 10 fM to 100 nM, and the limit of detection (LOD) was exceptionally low at 10 fM. Moreover, the selectivity toward serotonin was confirmed by observing no signal after the injection of structural analogs, functional analogs and excess physiological biomolecules. The potential clinical application of this sensor was confirmed because it remained consistent when the buffer solution was exchanged for artificial serum or artificial cerebrospinal fluid (CSF). † S.G.L. and S.E.S. contributed equally to this work.

Aptamer-Functionalized Carbon Nanotube Field-Effect Transistor Biosensors for Alzheimer's Disease Serum Biomarker Detection.

Blood-biomarker-based tests are highly important for the early clinical diagnosis of Alzheimer's disease (AD) and the treatment and care of AD patients, but the complex serum environment and extremely low abundance of AD blood protein biomarkers present challenges. Nanomaterials are promising for constructing highly sensitive transistor-based biosensors due to their small size. However, such biosensors are difficult to fabricate on a large scale and suffer from the lack of combined optimization of reproducibility and sensitivity in complex physiological fluids. In this work, field-effect transistor (FET) biosensors based on highly uniform semiconducting carbon nanotube (CNT) thin films are mass produced to achieve highly sensitive and selective detection of the AD core blood biomarkers of β-amyloid (Aβ). The combination of the mass-produced CNT FET sensors and oligonucleotide aptamers as efficient bioreceptors enables reliable and reproducible sub-femtomolar detection in full human serum for Aβ42 and Aβ40 peptides and has outperformed other methods reported to date. The adsorption of biological substrates to the sensor was significantly reduced by multiple blocking steps, resulting in selectivity ratios of up to 730% (Aβ40) and 800% (Aβ42). The aptamer-functionalized CNT FET biosensor exhibits a large dynamic range (>104), rapid response time (several minutes), and low variation (<10%) and can be delivered as a low-cost and rapid clinical detection technology for the early diagnosis and mass screening of AD. This platform will help bring complex laboratory-based and expensive diagnostic tools to the point of care.

Rapid self-test of unprocessed viruses of SARS-CoV-2 and its variants in saliva by portable wireless graphene biosensor

We have developed a DNA aptamer-conjugated graphene field-effect transistor (GFET) biosensor platform to detect receptor-binding domain (RBD), nucleocapsid (N), and spike (S) proteins, as well as viral particles of original Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus and its variants in saliva samples. The GFET biosensor is a label-free, rapid (≤20 min), ultrasensitive handheld wireless readout device. The limit of detection (LoD) and the limit of quantitation (LoQ) of the sensor are 1.28 and 3.89 plaque-forming units (PFU)/mL for S protein and 1.45 and 4.39 PFU/mL for N protein, respectively. Cognate spike proteins of major variants of concern (N501Y, D614G, Y453F, Omicron-B1.1.529) showed sensor response ≥40 mV from the control (aptamer alone) for fM to nM concentration range. The sensor response was significantly lower for viral particles and cognate proteins of Middle East Respiratory Syndrome (MERS) compared to SARS-CoV-2, indicating the specificity of the diagnostic platform for SARS-CoV-2 vs. MERS viral proteins. During the early phase of the pandemic, the GFET sensor response agreed with RT-PCR data for oral human samples, as determined by the negative percent agreement (NPA) and positive percent agreement (PPA). During the recent Delta/Omicron wave, the GFET sensor also reliably distinguished positive and negative clinical saliva samples. Although the sensitivity is lower during the later pandemic phase, the GFET-defined positivity rate is in statistically close alignment with the epidemiological population-scale data. Thus, the aptamer-based GFET biosensor has a high level of precision in clinically and epidemiologically significant SARS-CoV-2 variant detection. This universal pathogen-sensing platform is amenable for a broad range of public health applications and real-time environmental monitoring.

High-performance dual-gate graphene pH sensors

Field-effect transistors (FETs) are versatile tools for high-precision biophysical measurements, and their measurement sensitivity and resolution can be improved by using innovative materials and device designs. Here, we report on the sensitivity and noise performance of dual-gated graphene FETs. When measuring pH, our devices exhibit a sensitivity of up to 30 V per unit change in pH, ≈500-fold greater than the Nernst value at room temperature, and noise-limited resolution of 2 × 10−4 in the biomedically relevant 0.1–10 Hz bandwidth. This level of performance is obtained due to a highly asymmetric dual-gate design utilizing an ionic liquid top-gate dielectric coupled with graphene's large intrinsic quantum capacitance (≈15 μC/cm2). Our results improve upon the sensitivity and resolution of previously demonstrated Si- and MoS2-channel FET biosensors.

Vertically Oriented Zinc Oxide Nanorod-Based Electrolyte-Gated Field-Effect Transistor for High-Performance Glucose Sensing.

Nanomaterial-based biosensors are a promising fit for portable and field-deployable diagnosis sensor devices due to their mass production, miniaturization, and integration capabilities. However, the fabrication of highly stable and reproducible biosensor devices is challenging. In this work, we grow a vertically oriented architecture of zinc oxide nanorods onto the active working area (i.e., the channel between the source and drain) of a field-effect transistor (FET) using a low-temperature hydrothermal method. The glucose oxidase enzyme was immobilized on the zinc oxide nanorod surface by a physical adsorption method to fabricate the electrolyte-gated FET-based glucose biosensor. The electrical properties of the electrolyte-gated FET biosensor were measured with different glucose concentrations. We found a linear increase in current up to 80 mM glucose concentration with high sensitivity (74.78 μA/mMcm2) and a low detection limit (∼0.05 mM). We illustrate a highly reproducible fabrication process of zinc oxide nanorod-based FETs, where vertically grown nanorods with a higher surface-to-volume ratio enhance the enzyme immobilization, provide a microenvironment for longer enzyme activity, and translate to better glucose sensing parameters. Additionally, our electrolyte-gated FET biosensor showed promising application in freshly drawn mouse blood samples. These findings suggest a great opportunity to translate into practical high-performance biosensors for a broad range of analytes.

Ultrasensitive detection of exosomal miRNA with PMO-graphene quantum dots-functionalized field-effect transistor biosensor

SummaryCompared with the conventional DNA probe immobilization on the planar surface, nanoparticles-based DNA probes enable more RNA molecules to be anchored to the sensor surface, thereby improving the detection sensitivity. In this work, we report phosphorodiamidate morpholino oligomers (PMO)-graphene quantum dots (GQDs)-functionalized reduced graphene oxide (RGO) field effect transistor (FET) biosensors for ultrasensitive detection of exosomal microRNAs. After the RGO FET sensor was fabricated, polylysine (PLL) film was deposited onto the RGO surface. GQDs-PMO hybrid was prepared and covalently bound to PLL surface, enabling detection of exosomal microRNAs (miRNAs). The method achieved a detection limit as low as 85 aM and high specificity. Furthermore, the FET sensor was able to detect exosomal miRNAs in plasma samples and distinguish breast cancer samples from healthy samples. Compared with other methods, we use GQDs to further improve the sensitivity of FET, making it a potential tool for early diagnosis of breast cancer.

Qualitative and quantitative detection of microcystin-LR based on SERS-FET dual-mode biosensor

Microcystin-LR (MC-LR), a kind of hepatoxin produced by cyanobacteria blooms, can promote liver cancer through long-term exposure even at low concentrations. In this study, a novel biosensor based on surface-enhanced Raman scattering (SERS) and field effect transistor (FET) dual sensing mode was developed by using gold nanoparticles (AuNPs)/graphene composite as sensing material. Based on the SERS sensing mode, the Raman fingerprint spectrum of MC-LR was obtained through the specific combination of MC-LR aptamer and MC-LR. The SERS enhanced effect of the AuNPs was also verified by theoretical simulation. By using FET sensing mode, the graphene field effect transistor (G-FET) biosensor respectively exhibited the detection limit as low as 0.62 aM and 0.91 aM in phosphate buffered saline (PBS) and human serum, and showed a good linear relationship in a wide range of 1 × 10−18 to 1 × 10−8 M in both solutions. Meanwhile, the sensor was utilized for the detection of MC-LR in actual water samples, and the complex components in the water did not interfere with MC-LR detection, indicating a significant high specificity of the sensor. The SERS-FET dual-mode biosensor can provide more detection options and improve the reliability of measurement results, which may has a great application prospect in the field of water environment detection.

Precise and Prompt Analyte Detection via Ordered Orientation of Receptor in WSe2-Based Field Effect Transistor.

Field-effect transistors (FET) composed of transition metal dichalcogenide (TMDC) materials have gained huge importance as biosensors due to their added advantage of high sensitivity and moderate bandgap. However, the true potential of these biosensors highly depends upon the quality of TMDC material, as well as the orientation of receptors on their surfaces. The uncontrolled orientation of receptors and screening issues due to crossing the Debye screening length while functionalizing TMDC materials is a big challenge in this field. To address these issues, we introduce a combination of high-quality monolayer WSe2 with our designed Pyrene-based receptor moiety for its ordered orientation onto the WSe2 FET biosensor. A monolayer WSe2 sheet is utilized to fabricate an ideal FET for biosensing applications, which is characterized via Raman spectroscopy, atomic force microscopy, and electrical prob station. Our construct can sensitively detect our target protein (streptavidin) with 1 pM limit of detection within a short span of 2 min, through a one-step functionalizing process. In addition to having this ultra-fast response and high sensitivity, our biosensor can be a reliable platform for point-of-care-based diagnosis.

Theoretical insight on dopamine, ascorbic acid and uric acid adsorption on graphene as material for biosensors

In the present work, the interaction of dopamine (DA), ascorbic acid (AA) and uric acid (UA) molecules with graphene, with and without divacancies, has been theoretically studied within the framework of Density Functional Theory (DFT), in particular, paying attention on those surface properties relevant for field effect transistor (FET) and electrochemical biosensor applications. Several adsorption modes for these molecules were examined, and the main sources of adsorbate–substrate bonding were considered. The electric dipole moment for these molecules, when adsorbed, suffers in some cases large modifications due to conformational changes. The perpendicular component of dipole moment has a main molecular contribution molecule and another from the adsorbate–substrate polarization. The proposed reaction models of DA, AA and UA oxidations, show a good agreement with the oxidation potential ordering obtained in electrochemical experiments, i.e., UA > DA > AA. A spreading of reaction energies is observed due to the heterogeneity in adsorption modes.

Highly sensitive, scalable, and rapid SARS-CoV-2 biosensor based on In2O3 nanoribbon transistors and phosphatase

Developing convenient and accurate SARS-CoV-2 antigen test and serology test is crucial in curbing the global COVID-19 pandemic. In this work, we report an improved indium oxide (In2O3) nanoribbon field-effect transistor (FET) biosensor platform detecting both SARS-CoV-2 antigen and antibody. Our FET biosensors, which were fabricated using a scalable and cost-efficient lithography-free process utilizing shadow masks, consist of an In2O3 channel and a newly developed stable enzyme reporter. During the biosensing process, the phosphatase enzymatic reaction generated pH change of the solution, which was then detected and converted to electrical signal by our In2O3 FETs. The biosensors applied phosphatase as enzyme reporter, which has a much better stability than the widely used urease in FET based biosensors. As proof-of-principle studies, we demonstrate the detection of SARS-CoV-2 spike protein in both phosphate-buffered saline (PBS) buffer and universal transport medium (UTM) (limit of detection [LoD]: 100 fg/mL). Following the SARS-CoV-2 antigen tests, we developed and characterized additional sensors aimed at SARS-CoV-2 IgG antibodies, which is important to trace past infection and vaccination. Our spike protein IgG antibody tests exhibit excellent detection limits in both PBS and human whole blood ((LoD): 1 pg/mL). Our biosensors display similar detection performance in different mediums, demonstrating that our biosensor approach is not limited by Debye screening from salts and can selectively detect biomarkers in physiological fluids. The newly selected enzyme for our platform performs much better performance and longer shelf life which will lead our biosensor platform to be capable for real clinical diagnosis usage.Electronic Supplementary MaterialSupplementary material (materials and methods for device fabrication, functionalization of In2O3 devices, photographs of the liquid gate measurement setup, mobilities of the nine devices labeled in Fig. 1(b), family curves of IDS-VDS with the liquid gate setup and current change after bubbling the substrate solution (current vs. time curve for S1 antigen detection)) is available in the online version of this article at 10.1007/s12274-022-4190-0.

Analysis of Electric Field Distribution for SOI-FET Sensors with Dielectrophoretic Control.

Silicon-on-insulator (SOI) nanowire or nanoribbon field-effect transistor (FET) biosensors are versatile platforms of electronic detectors for the real-time, label-free, and highly sensitive detection of a wide range of bioparticles. At a low analyte concentration in samples, the target particle diffusion transport to sensor elements is one of the main limitations in their detection. The dielectrophoretic (DEP) manipulation of bioparticles is one of the most successful techniques to overcome this limitation. In this study, TCAD modeling was used to analyze the distribution of the gradient of the electric fields E for the SOI-FET sensors with embedded DEP electrodes to optimize the conditions of the dielectrophoretic delivery of the analyte. Cases with asymmetrical and symmetrical rectangular electrodes with different heights, widths, and distances to the sensor, and with different sensor operation modes were considered. The results showed that the grad E2 factor, which determines the DEP force and affects the bioparticle movement, strongly depended on the position of the DEP electrodes and the sensor operation point. The sensor operation point allows one to change the bioparticle movement direction and, as a result, change the efficiency of the delivery of the target particles to the sensor.

Solution processed low power organic field-effect transistor bio-chemical sensor of high transconductance efficiency

Developing organic field-effect transistor (OFET) biosensors for customizable detection of biomarkers for many diseases would provide a low-cost and convenient tool for both biological studies and clinical diagnosis. In this work, design principles of the OFET transducer for biosensors were derived to relate the signal-to-noise ratio (SNR) to the device-performance parameters. Steep subthreshold swing (SS), proper threshold voltage (Vth), good-enough bias-stress stability, and mechanical durability are shown to be the key prerequisites for realizing OFET bio-sensors of high transconductance efficiency (gm/ID) for large SNR. Combining a low trap-density channel and a high-k/low-k gate dielectric layer, low-temperature (<100 °C) solution-processed flexible OFETs can meet the performance requirements to maximize the gm/ID. An extended gate-structure OFET biosensor was further implemented for label-free detection of miR-21, achieving a detection limit below 10 pM with high selectivity at a low operation voltage (<1 V).

A Wearable Microneedle‐Based Extended Gate Transistor for Real‐Time Detection of Sodium in Interstitial Fluids (Adv. Mater. 10/2022)

Biosensors In article number 2108607, Miaomiao Yuan, Hossam Haick, and co-workers report an innovative, stretchable, skin-conformal, fast-response, microneedle, extended-gate field-effect transistor biosensor for real-time detection of sodium in interstitial fluids for minimally invasive health monitoring. High sensitivity, low limit of detection, excellent biocompatibility, and on-body mechanical stability are demonstrated. This platform can be integrated with a wireless-data transmitter and the Internet-of-Things cloud for real-time monitoring and long-term analysis.

Nanomaterial-Based Biosensors using Field-Effect Transistors: A Review.

Field-effect transistor biosensors (Bio-FET) have attracted great interest in recent years owing to their distinctive properties like high sensitivity, good selectivity, and easy integration into portable and wearable electronic devices. Bio-FET performance mainly relies on the constituent components such as the bio-recognition layer and the transducer, which ensures device stability, sensitivity, and lifetime. Nanomaterial-based Bio-FETs are excellent candidates for biosensing applications. This review discusses the basic concepts, function, and working principles of Bio-FETs, and focuses on the progress of recent research in Bio-FETs in the sensing of neurotransmitters, glucose, nucleic acids, proteins, viruses, and cancer biomarkers using nanomaterials. Finally, challenges in the development of Bio-FETs, as well as an outlook on the prospects of nano Bio-FET-based sensing in various fields, are discussed.

Rapid and low-cost, and disposable electrical sensor using an extended gate field-effect transistor for cardiac troponin I detection.

Field effect transistor (FET) biosensor is based on metal oxide field effect transistor that is gated by changes in the surface charges induced the reaction of biomolecules. In most cases of FET biosensor, FET biosensor is not being reused after the reaction; therefore, it is an important concept of investigate the biosensor with simplicity, cheap and reusability. However, the conventional cardiac troponin I (cTnI) sensing technique is inadequate owing to its low sensitivity and high operational time and cost. In this study, we developed a rapid and low-cost, and disposable electrical sensor using an extended gate field-effect transistor (EGFET) to detect cTnI, as a key biomarker for myocardiac infarction. We first investigated pH sensing characteristics according to the pH level, which provided a logarithmically linear sensitivity in the pH sensing buffer solution of approximately 57.9mV/pH. Subsequently, we prepared a cTnI sample and monitored the reaction between cTnI and cTnI antibodies through the changes in the drain current and transfer curves. Our results showed that the EGFET biosensor could successfully detect the cTnI levels as well as the pH with low-cost and rapid detection.