Field Effect Transistor Biosensor Research Articles

Demonstration of the enhancement of gate bias and ionic strength in electric-double-layer field-effect-transistor biosensors

Abstract In this study, we investigate the mechanism of enhanced electric-double-layer (EnEDL) field-effect-transistor (FET)-based biosensors, which can successfully detect proteins in high ionic strength solution, such as in 1XPBS. This EnEDL FET biosensor performs good sensitivity in high ionic strength solution by creating enhanced capacitance in the EDL with higher gate voltage or higher salt concentration, and operating in a large transconductance of the FET to amplify the signal. AC impedance measurement is also introduced and identifies that the imaginary part dominates the sensitivity of C-reactive protein (CRP) detection, indicating that the EnEDL capacitance plays the key role in the sensing mechanism. Extended gate connecting to the FET and a separated gate electrode is fabricated and biased with the gate voltage for the EnEDL FET biosensors. The test solution is placed between the two electrodes, and the voltage drop across the solution caused by CRP concentration was analyzed for different gate voltages and salt concentrations for the EnEDL FET biosensors. The results show that as the EDL is enhanced by higher gate bias or higher salt concentration, the sensitivity is increased, either in AC impedance analysis or voltage drop in the test solution. To utilize the enhanced EDL, the maximum transconductance of the FET should be located in a larger gate voltage. This technology can allow direct protein detection in 5 min. without complex dilution of clinical samples, which is promising for portable devices for personal healthcare.

Recent Advances of Field-Effect Transistor Technology for Infectious Diseases.

Field-effect transistor (FET) biosensors have been intensively researched toward label-free biomolecule sensing for different disease screening applications. High sensitivity, incredible miniaturization capability, promising extremely low minimum limit of detection (LoD) at the molecular level, integration with complementary metal oxide semiconductor (CMOS) technology and last but not least label-free operation were amongst the predominant motives for highlighting these sensors in the biosensor community. Although there are various diseases targeted by FET sensors for detection, infectious diseases are still the most demanding sector that needs higher precision in detection and integration for the realization of the diagnosis at the point of care (PoC). The COVID-19 pandemic, nevertheless, was an example of the escalated situation in terms of worldwide desperate need for fast, specific and reliable home test PoC devices for the timely screening of huge numbers of people to restrict the disease from further spread. This need spawned a wave of innovative approaches for early detection of COVID-19 antibodies in human swab or blood amongst which the FET biosensing gained much more attention due to their extraordinary LoD down to femtomolar (fM) with the comparatively faster response time. As the FET sensors are promising novel PoC devices with application in early diagnosis of various diseases and especially infectious diseases, in this research, we have reviewed the recent progress on developing FET sensors for infectious diseases diagnosis accompanied with a thorough discussion on the structure of Chem/BioFET sensors and the readout circuitry for output signal processing. This approach would help engineers and biologists to gain enough knowledge to initiate their design for accelerated innovations in response to the need for more efficient management of infectious diseases like COVID-19.

High-sensitivity detection of Concanavalin A using MoS2-based field effect transistor biosensor

The specific interaction between sugar and lectin plays a key role in various human diseases and projects remarkable significance to the development of a lectin biosensor for diagnosis and drug discovery. An inorganic nano MoS2 field-effect transistor (FET)-based D-Mannose biosensor was developed in this paper using a simple assembly process. First, gold nanoparticles were functionalized on the surface of MoS2. Then, the β-mercaptoethylamine was self-assembled on the gold surface via Au–S bonds to derivatize amino groups. Finally, the probe molecules D-Mannose for biological protein were immobilized on the FET via the Schiff base reaction. Results from scanning electron microscope and x-ray photoelectron spectroscopy analysis confirmed the entire assembly procedure and the feasible interaction of the FET sensor with Concanavalin A (ConA). The fabricated FET biosensors can reliably detect the target ConA with a detection limit below 105 nm. The current study shows the potential of MoS2 FET biosensors for ConA specific detection and clarifies the design of biosensors for the early diagnosis of glycomics and drug screening in medicine.

Graphene FET Sensors for Alzheimer's Disease Protein Biomarker Clusterin Detection.

We report on the fabrication and characterisation of graphene field-effect transistor (GFET) biosensors for the detection of Clusterin, a prominent protein biomarker of Alzheimer’s disease (AD). The GFET sensors were fabricated on Si/SiO2 substrate using photolithographic patterning and metal lift-off techniques with evaporated chromium and sputtered gold contacts. Raman Spectroscopy was performed on the devices to determine the quality of the graphene. The GFETs were annealed to improve their performance before the channels were functionalized by immobilising the graphene surface with linker molecules and anti-Clusterin antibodies. Concentration of linker molecules was also independently verified by absorption spectroscopy using the highly collimated micro-beam light of Diamond B23 beamline. The detection was achieved through the binding reaction between the antibody and varying concentrations of Clusterin antigen from 1 to 100 pg/mL, as well as specificity tests using human chorionic gonadotropin (hCG), a glycoprotein risk biomarker of certain cancers. The GFETs were characterized using direct current (DC) 4-probe electrical resistance (4-PER) measurements, which demonstrated a limit of detection of the biosensors to be ∼ 300 fg/mL (4 fM). Comparison with back-gated Dirac voltage shifts with varying concentration of Clusterin show 4-PER measurements to be more accurate, at present, and point to a requirement for further optimisation of the fabrication processes for our next generation of GFET sensors. Thus, we have successfully fabricated a promising set of GFET biosensors for the detection of Clusterin protein biomarker. The developed GFET biosensors are entirely generic and also have the potential to be applied to a variety of other disease detection applications such as Parkinson’s, cancer, and cardiovascular.

Ultrasensitive and easily reproducible biosensor based on novel doped MoS2 nanowires field-effect transistor in label-free approach for detection of hepatitis B virus in blood serum

An ultrasensitive field-effect transistor (FET) for hepatitis B virus deoxyribonucleic acid (HBV DNA) detection in label free approach and easily reproducible setup was reported. The fabricated FET biosensor was materialized by ZnO doped MoS2 nanowires (NWs). This report introduced a novel structure of the MoS2 in bio-sensing approach. Because of unique electrical and structural properties of MoS2, HBV biosensor could demonstrate the high sensitivity and showed the detection limit of 1 fM. The MoS2 NWs fabrication was materialized through ZnO based vapor-liquid-solid (VLS) technique. The fabricated device could measure the DNA targets in a linear concentration range from 0.5 pM to 50 μM. The dynamic response time of FET biosensor was 25 s. The functionality of the NWs biosensor for label-free measurements could be repeated for several times without any significant malfunction and biosensor could retain 96% of its initial response after eight weeks maintenance. The HBV biosensor showed high selectivity by discrimination the complementary DNA oligonucleotides from non-complementary and the mismatch (1, 2 and 3 bases) oligonucleotides. The materialized platform was desirably reproduced for HBV concentrations in human serum. The specificity of the biosensor was evaluated against several different types of DNAs and the fabricated device showed the outstanding performance. In order to optimize the device functionality, the biosensor was checked for two different human samples and device could distinguish the samples from each other in the same manner.

A supersensitive silicon nanowire array biosensor for quantitating tumor marker ctDNA

Cancer has become one of the major diseases threatening human health and life. Circulating tumor DNA (ctDNA) testing, as a practical liquid biopsy technique, is a promising method for cancer diagnosis, targeted therapy and prognosis. Here, for the first time, a field effect transistor (FET) biosensor based on uniformly sized high-response silicon nanowire (SiNW) array was studied for real-time, label-free, super-sensitive detection of PIK3CA E542K ctDNA. High-response 120-SiNWs array was fabricated on a (111) silicon-on-insulator (SOI) by the complementary metal oxide semiconductor (CMOS)-compatible microfabrication technology. To detecting ctDNA, we modified the DNA probe on the SiNWs array through silanization. The experimental results demonstrated that the as-fabricated biosensor had significant superiority in ctDNA detection, which achieved ultralow detection limit of 10 aM and had a good linearity under the ctDNA concentration range from 0.1 fM to 100 pM. This biosensor can recognize complementary target ctDNA from one/two/full-base mismatched DNA with high selectivity. Furthermore, the fabricated SiNW-array FET biosensor successfully detected target ctDNA in human serum samples, indicating a good potential in clinical applications in the future.

Rapid β-human chorionic gonadotropin detection in urine with electric-double-layer gated field-effect transistor biosensors and a handheld device.

In this experimental study, a portable biosensor was developed to detect β-human chorionic gonadotropin (β-hCG), which is extensively used in pregnancy tests and serves as a biomarker for ectopic pregnancy. The sensor used is an electric-double-layer field-effect transistor biosensor with the extended-gate design. Bias voltage is applied on the sensor to measure the resulting drain current signals. Gold electrode surface is functionally activated with an anti-β-hCG antibody to capture β-hCG protein. Fluorescence imaging technique is utilized to confirm the surface functionalization. The biosensor demonstrates a dynamically wide range of molecules as detection targets at very low sample concentrations, which shows the potential to detect ectopic pregnancy in very early stages and easily keep track of its periodic changes. It can be produced en masse and does not use additional labels/reagents or pre-processing techniques for the sample. This biosensor can significantly reduce the manufacturing costs and is comparable with the currently available commercial ß-hCG assays. It is suitable for early diagnosis of ectopic pregnancy with low cost and easy operation at home with urine samples.

An ultrasensitive heart-failure BNP biosensor using B/N co-doped graphene oxide gel FET

Heart failure (HF) is the number one cause of death in the world. B-type natriuretic peptide (BNP) is a recognized biomarker for HF and can be used for early detection. Field effect transistor (FET) biosensors have the ability to sense BNP in much shorter times than conventional clinical studies. The lowest limit of detection (LOD) of state-of-the-art HF FET biosensors is 100 fM and detection ranges are short, being less than 4 orders of magnitude. In this work, a B/N co-doped graphene oxide (GO) gel (BN-GO) was used as the channel material in an FET biosensor targeting BNP. The sensor was able to sense BNP in as little as 2 min, with an LOD as low as 10 aM and a wide linear detection range of 10 aM–1 μM, stretching over 11 orders of magnitude. The biosensor showed great selectivity and minimal response towards K+ and OH− ions and the human epidermal growth factor receptor (HER2) protein. This biosensor serves as a proof-of-concept of the ability of BN-GO gel FETs to be used for ultrasensitive biosensors.

DNA-based functionalization of two-dimensional MoS2 FET biosensor for ultrasensitive detection of PSA

Molybdenum disulfide (MoS2) field-effect transistor (FET) biosensors are being increasingly studied due to their highly sensitive and label-free biodetection, system-level integration and easy fabrication. However, the stability and detection ability of a pristine device deteriorate due to the absorption of H2O and CO and usually exhibit high false signals. Herein, a novel ecofriendly technology is employed to functionalize MoS2 FETs using the conjugation of a DNA tetrahedron and biotin-streptavidin (B-SA). The functionlized devices demonstrate ultrahigh sensitivity of the target protein (prostate-specific antigen, PSA) with a limit of detection of 1fg/mL and a wide linear range of 1fg/mL to 100ng/mL in a phosphate-buffered saline, which are 100 and 10,000 times higher than the reported highest values, respectively; these results are attributed to the stable immobilization provided by the DNA tetrahedron as well as the multilevel amplification and anchor system (B-SA system), which improves the antibody-antigen (Ab-Ag) binding. Real-time measurement results indicate that our proposed biosensor can also detect trace PSA (1fg/mL) in a clinically relevant sample of healthy human serum.

Potassium-regulated Immobilization of Cortisol Aptamer for Field-effect Transistor Biosensor to Detect Changes in Charge Distribution with Aptamer Transformation

Salivary cortisol concentration and its circadian variation were detected by optimizing the ionic concentration of a solution during the immobilization of aptamers on a field-effect transistor biosensor. This was achieved by modifying our previously developed technique of detecting uncharged cortisol using the transformation of negatively charged aptamers by controlling the aptamer spacing. This spacing control was achieved by synthesizing pseudo-cortisol-binding aptamers with a guanine-quadruplex during the immobilization of the aptamers in a highly concentrated solution of K+.

Graphene field effect transistor for ultrasensitive label-free detection of ATP and Adenosine

Because of unique electrical and structural properties, graphene has attracted widespread attention in biosensing applications. In this paper, a single layer of graphene was grown by chemical vapor deposition (CVD). Using graphene as the electric channel, a graphene field effect transistor (G-FET) biosensor was fabricated and used to detect adenosine triphosphate (ATP) and adenosine. Compared with traditional methods, the G-FET biosensor has the advantages of higher sensitivity and better stability. The sensor showed high performance and achieved a detection limit down to 0.5 pM for both ATP and adenosine. Moreover, the G-FET biosensor showed an excellent linear electrical response to ATP concentrations in a broad range from 0.5 pM to 50 μM. The developed graphene biosensor has high sensitivity, simple operation, and fast analysis speed, which may provide a new feasible direction to detect ATP and adenosine. Healthy sexually mature male laboratory Wistar rats, weighing 180-200 gr (“FSUE “Nursery of laboratory animals “Rappolovo”) and having been placed under quarantine not less than for 14 days, were selected for the experiment.

High Performance NiOx Extended-Gate Field-Effect Transistor Biosensor for Detection of Uric Acid

In this paper, we developed a high performance NiOx extended-gate field-effect transistor (EGFET) biosensor for detection of uric acid. The structural and sensing properties of the NiOx sensing film deposited on a n+-type Si substrate was examined for an EGFET pH sensor. X-ray diffraction, atomic force microscope and X-ray photoelectron spectroscopy were used to analyze the film features of the NiOx sensing film. The NiOx sensing film based on EGFET exhibited a high pH sensitivity of 58.53 mV pH−1, a small hysteresis voltage of 1.4 mV and a low drift rate of 0.30 mV h−1. Moreover, the NiOx EGFET biosensor showed a high linearity in the uric acid range between 1 and 30 mg dl−1. In addition, this NiOx EGFET biosensor demonstrated a very good selectivity to uric acid over other interfering substrates (ascorbic acid, glucose, urea).

An optic-fiber graphene field effect transistor biosensor for the detection of single-stranded DNA.

Herein, a graphene field effect transistor (GFET) was constructed on an optic fiber end face to develop an integrated optical/electrical double read-out biosensor, which was used to detect target single-stranded DNA (tDNA). Two isolated Au electrodes were, respectively, prepared as the drain and source at the ends of an optic fiber and coated with a graphene film to construct a field effect transistor (FET). Probe aptamers modified with fluorophore 6'-carboxy-fluorescein (6'-FAM) were immobilized on the graphene for specific capture of tDNA. Graphene oxide (GO) was introduced to quench 6'-FAM and construct a fluorescence biosensor. Thus, a dual GFET and fluorescence biosensor was integrated on the end-face of an optic fiber. Following synchronous detection by fluorescence and FET methods, results showed satisfactory sensitivity for DNA detection. Compared with conventional biosensors using a single sensing technology, these dual sensing integrated biosensors significantly improved the reliability and accuracy of DNA detection. Furthermore, this proposed technique provides both a new biosensor for single-stranded DNA detection and a strategy for designing multi-sensing integrated biosensors.

Rapid and Label-Free Detection of the Troponin in Human Serum by a TiN-Based Extended-Gate Field-Effect Transistor Biosensor

Rapid and Label-Free Detection of the Troponin in Human Serum by a TiN-Based Extended-Gate Field-Effect Transistor Biosensor

Nano-FET-enabled biosensors: Materials perspective and recent advances in North America

Field-effect transistor (FET) is a very promising platform for biosensor applications due to its magnificent properties, including label-free detection, high sensitivity, fast response, real-time measurement capability, low running power, and the feasibility to miniaturize to a portable device. 1D (e.g. carbon nanotubes, Si nanowires, conductive polymer nanowires, 1D metal oxides, and others) and 2D (e.g. graphene materials, transition metal dichalcogenides, black phosphorus, and 2D metal oxides) materials, with their unique structural and electronic properties that are unavailable in bulk materials, have helped improve the sensitivity of FET biosensors and enabled detection down to single molecule. In this review, we give insights into the rapidly evolving field of 1D and 2D materials-based FET biosensors, with an emphasis on structure and electronic properties, synthesis, and biofunctionalization approaches of these nanomaterials. In addition, the progress in the 1D/2D-FET biosensors in North America, in the last decade, is summarized in tables. Moreover, challenges and future perspectives of 1D/2D-FET biosensors are covered.

Performance analysis of double-metal-gate dual-cavity dielectrically modulated-TFET as a label free biosensor

In this paper, a double metal gate dual cavity dielectrically modulated tunnel field effect transistor (DMG-DC-DMTFET) biosensor is proposed. The On and ambipolar currents of the device are used for detection of various biomolecules. The cavities, where biomolecules get immobilized are considered at both source-channel and drain-channel junctions of TFET in order to utilize ambipolar nature of TFET to detect the presence of biomolecules in an efficient way. Sensitivity improvement and reduction in Off current at higher dielectric constant of biomolecules are done by considering the gate metal work function engineering. The effect of charged and neutral biomolecules on band energy, transfer characteristics and electric field has been analyzed.

Narrower Nanoribbon Biosensors Fabricated by Chemical Lift-off Lithography Show Higher Sensitivity.

Wafer-scale nanoribbon field-effect transistor (FET) biosensors fabricated by straightforward top-down processes are demonstrated as sensing platforms with high sensitivity to a broad range of biological targets. Nanoribbons with 350 nm widths (700 nm pitch) were patterned by chemical lift-off lithography using high-throughput, low-cost commercial digital versatile disks (DVDs) as masters. Lift-off lithography was also used to pattern ribbons with 2 μm or 20 μm widths (4 or 40 μm pitches, respectively) using masters fabricated by photolithography. For all widths, highly aligned, quasi-one-dimensional (1D) ribbon arrays were produced over centimeter length scales by sputtering to deposit 20 nm thin-film In2O3 as the semiconductor. Compared to 20 μm wide microribbons, FET sensors with 350 nm wide nanoribbons showed higher sensitivity to pH over a broad range (pH 5 to 10). Nanoribbon FETs functionalized with a serotonin-specific aptamer demonstrated larger responses to equimolar serotonin in high ionic strength buffer than those of microribbon FETs. Field-effect transistors with 350 nm wide nanoribbons functionalized with single-stranded DNA showed greater sensitivity to detecting complementary DNA hybridization vs 20 μm microribbon FETs. In all, we illustrate facile fabrication and use of large-area, uniform In2O3 nanoribbon FETs for ion, small-molecule, and oligonucleotide detection where higher surface-to-volume ratios translate to better detection sensitivities.

Aptamer-based nanofilter interface for small-biomarker detection with potentiometric biosensor

In this paper, we report the concept of an aptamer (Ap)-based nanofilter interface for the suppression of nonspecific signals generated by interfering species in biological samples. As a model of the target small biomolecule, l-3,4-dihydroxyphenylalanine (l-DOPA) is used to demonstrate its electrical discrimination from dopamine (DA) despite their similar chemical structures using a DA–Ap nanofilter-coated Au gate field-effect transistor (FET). A Au gate electrode is employed to assess the electrical response of the FET to l-DOPA on the basis of oxidative reactions. In particular, the proposed nanofilter interface is based on the DA–Ap layer immobilized at the aryl-diazonium-based anchor monolayer, which is electrochemically grafted on the Au gate electrode via diazonium chemistry. As a result, the electrical signal from l-DOPA is clearly discriminated from that from DA at a concentration of 1 μM or higher using the DA–Ap nanofilter-coated Au gate FET. That is, DA is trapped by the DA–Ap nanofilter through the formation of complexes, the molecular charges of which are shielded by counter ions that are not in contact with the Au gate surface, whereas l-DOPA reaches and electrochemically reacts with the Au gate surface, generating an electrical signal regardless of the nanofilter. The surface properties of the DA–Ap nanofilter modified on the Au gate electrode are investigated by cyclic voltammetry, chronocoulometry, atomic force microscopy, and X-ray photoelectron spectroscopy. A platform based on the FET biosensor with the Ap-based nanofilter interface contributes to the electrical monitoring of small biomarkers while suppressing the nonspecific signals of interfering species in biological samples.

Immobilization of Target-Bound Aptamer on Field Effect Transistor Biosensor to Improve Sensitivity for Detection of Uncharged Cortisol

Immobilization of Target-Bound Aptamer on Field Effect Transistor Biosensor to Improve Sensitivity for Detection of Uncharged Cortisol

Immuno-probed graphene nanoplatelets on electrolyte-gated field-effect transistor for stable cortisol quantification in serum

Physiological and emotional stress affects the regulation of cortisol secretion, a routine process in circadian rhythm. Regular monitoring of cortisol level as a biomarker in the blood stream becomes vital to determine cortisol-related diseases. This study reports immuno-probed graphene nanoplatelets on electrolyte-gated field-effect transistor (EGFET) biosensor for cortisol determination in human serum. Solution-processed graphene nanoplatelets were evidenced on the surface by Raman spectroscopy analysis and utilized as the transducing element on the field-effect transistor. Further, confirmed the binding events of the antibody on graphene nanoplatelets using X-Ray Photoelectron Spectroscopy and characterized the electrostatic gating effect of cortisol and intermediate functionalization on graphene nanoplatelets-EGFET. The biosensor exhibited good sensitivity of 72.30 µA.(g/mL)−1 in a linear range between 1.00 pg/mL to 10.00 ng/mL, with a limit of detection (LOD) of 0.85 pg/mL. Confirmation with binding events on the biosensor was done using the relevant molecules, progesterone, cortisone, and corticosterone, and found to be selective towards cortisol. Cortisol was also successfully detected with interference by the human serum, suggesting the capability of graphene nanoplatelets-EGFET sensor for determining cortisol in a complex matrix.