Field Effect Transistor-based Biosensor Research Articles

Glucose sensing by field-effect transistors based on interfacial hydrogelation of self-assembled peptide

Interfacial hydrogelation of peptides gated on the semiconductor channel has yet to be explored in surface chemistry and field-effect transistor-based biosensors (bio-FETs). This work reports the first example of peptidic hydrogel gated bio-FET by surface assisted self-assembly for label-free and real-time monitoring of the glucose with low limit of detection, excellent sensitivity, and good stability in mouse serum. The boric acid-containing peptide forms a hydrogel layer on the surface of In2O3, which interacts with glucose reversibly and generates boronate anions to influence the semiconductor's conductivity. The results also indicate the superiority of hydrogel gated bio-FET for real-time monitoring of glucose in complex environments and serve as a wearable device. This work illustrates a simple and fundamental strategy for integrating peptidic hydrogel with bio-FET for the real-time detection of analytes.

Sensitivity Assessment of Electrically Doped Cavity on Source Junctionless Tunnel Field-Effect Transistor-Based Biosensor

The tunnel field-effect transistor (TFET) has emerged as a promising device for biosensing applications due to band-to-band tunneling (BTBT) operation mechanism and a steep subthreshold swing. In this paper, an electrically doped cavity on source junctionless tunnel field-effect transistor (ED-CS-JLTFET)-based biosensor is proposed for label-free detection of biomolecules. In the proposed model, the electrically doped concept is enabled to reduce fabrication complexity and cost. In order to create a nano-cavity at the source region, some portion of the dielectric oxide of the polarity gate terminal is etched away. To perceive the presence of biomolecules, two important properties of biomolecules, such as dielectric constant and charge density, are incorporated throughout the simulation. The sensing performance of the proposed ED-CS-JLTFET-based biosensor has been analyzed in terms of transfer characteristics, threshold voltage and subthreshold swing. In addition, the sensitivity of the proposed biosensor has also been analyzed with respect to different fill factors (FFs), varying nano-cavity dimension and work-function of the control gate. It is found from the simulated results that the proposed ED-CS-JLTFET-based biosensor offers higher current sensitivities with neutral, positively charged and negatively charged biomolecules of [Formula: see text] (at k [Formula: see text]), [Formula: see text] (at [Formula: see text] and [Formula: see text] C[Formula: see text]cm[Formula: see text]) and [Formula: see text] (at k [Formula: see text] and [Formula: see text] C[Formula: see text]cm[Formula: see text]), respectively.

Earlier detection of SARS-CoV-2 infection by blood RNA signature microfluidics assay.

Earlier detection of SARS-CoV-2 infection by blood RNA signature microfluidics assay.

Detection of the O6-Carboxymethylguanine DNA Adduct in Colorectal Cancer Using a Graphene Field-Effect Transistor-Based Biosensors

Detection of the O6-Carboxymethylguanine DNA Adduct in Colorectal Cancer Using a Graphene Field-Effect Transistor-Based Biosensors

Field-Effect Transistor-Based Biosensors for Environmental and Agricultural Monitoring.

The precise monitoring of environmental contaminants and agricultural plant stress factors, respectively responsible for damages to our ecosystems and crop losses, has nowadays become a topic of uttermost importance. This is also highlighted by the recent introduction of the so-called “Sustainable Development Goals” of the United Nations, which aim at reducing pollutants while implementing more sustainable food production practices, leading to a reduced impact on all ecosystems. In this context, the standard methods currently used in these fields represent a sub-optimal solution, being expensive, laboratory-based techniques, and typically requiring trained personnel with high expertise. Recent advances in both biotechnology and material science have led to the emergence of new sensing (and biosensing) technologies, enabling low-cost, precise, and real-time detection. An especially interesting category of biosensors is represented by field-effect transistor-based biosensors (bio-FETs), which enable the possibility of performing in situ, continuous, selective, and sensitive measurements of a wide palette of different parameters of interest. Furthermore, bio-FETs offer the possibility of being fabricated using innovative and sustainable materials, employing various device configurations, each customized for a specific application. In the specific field of environmental and agricultural monitoring, the exploitation of these devices is particularly attractive as it paves the way to early detection and intervention strategies useful to limit, or even completely avoid negative outcomes (such as diseases to animals or ecosystems losses). This review focuses exactly on bio-FETs for environmental and agricultural monitoring, highlighting the recent and most relevant studies. First, bio-FET technology is introduced, followed by a detailed description of the the most commonly employed configurations, the available device fabrication techniques, as well as the specific materials and recognition elements. Then, examples of studies employing bio-FETs for environmental and agricultural monitoring are presented, highlighting in detail advantages and disadvantages of available examples. Finally, in the discussion, the major challenges to be overcome (e.g., short device lifetime, small sensitivity and selectivity in complex media) are critically presented. Despite the current limitations and challenges, this review clearly shows that bio-FETs are extremely promising for new and disruptive innovations in these areas and others.

Effect of DNA Aptamer Concentration on the Conductivity of a Water-Gated Al:ZnO Thin-Film Transistor-Based Biosensor.

Field-effect transistor-based biosensors (bio-FETs) are promising candidates for the rapid high-sensitivity and high-selectivity sensing of various analytes in healthcare, clinical diagnostics, and the food industry. However, bio-FETs still have several unresolved problems that hinder their technological transfer, such as electrical stability. Therefore, it is important to develop reliable, efficient devices and establish facile electrochemical characterization methods. In this work, we have fabricated a flexible biosensor based on an Al:ZnO thin-film transistor (TFT) gated through an aqueous electrolyte on a polyimide substrate. In addition, we demonstrated techniques for establishing the operating range of such devices. The Al:ZnO-based devices with a channel length/width ratio of 12.35 and a channel thickness of 50 nm were produced at room temperature via magnetron sputtering. These Al:ZnO-based devices exhibited high field-effect mobility (μ = 6.85 cm2/Vs) and threshold voltage (Vth = 654 mV), thus showing promise for application on temperature-sensitive substrates. X-ray photoelectron spectroscopy was used to verify the chemical composition of the deposited films, while the morphological aspects of the films were assessed using scanning electron and atomic force microscopies. The gate–channel electric capacitance of 40 nF/cm2 was determined using electrochemical impedance spectroscopy, while the electrochemical window of the gate–channel system was determined as 1.8 V (from −0.6 V to +1.2 V) using cyclic voltammetry. A deionized water solution of 10 mer (CCC AAG GTC C) DNA aptamer (molar weight −2972.9 g/mol) in a concentration ranging from 1–1000 pM/μL was used as an analyte. An increase in aptamer concentration caused a proportional decrease in the TFT channel conductivity. The techniques demonstrated in this work can be applied to optimize the operating parameters of various semiconductor materials in order to create a universal detection platform for biosensing applications, such as multi-element FET sensor arrays based on various composition nanostructured films, which use advanced neural network signal processing.

Saliva-based COVID-19 detection: A rapid antigen test of SARS-CoV-2 nucleocapsid protein using an electrical-double-layer gated field-effect transistor-based biosensing system

Facing the unstopped surges of COVID-19, an insufficient capacity of diagnostic testing jeopardizes the control of disease spread. Due to a centralized setting and a long turnaround, real-time reverse transcription polymerase chain reaction (real-time RT-PCR), the gold standard of viral detection, has fallen short in timely reflecting the epidemic status quo during an urgent outbreak. As such, a rapid screening tool is necessitated to help contain the spread of COVID-19 amid the countries where the vaccine implementations have not been widely deployed. In this work, we propose a saliva-based COVID-19 antigen test using the electrical double layer (EDL)-gated field-effect transistor-based biosensor (BioFET). The detection of SARS-CoV-2 nucleocapsid (N) protein is validated with limits of detection (LoDs) of 0.34 ng/mL (7.44 pM) and 0.14 ng/mL (2.96 pM) in 1× PBS and artificial saliva, respectively. The specificity is inspected with types of antigens, exhibiting low cross-reactivity among MERS-CoV, Influenza A virus, and Influenza B virus. This portable system is embedded with Bluetooth communication and user-friendly interfaces that are fully compatible with digital health, feasibly leading to an on-site turnaround, an effective management, and a proactive response taken by medical providers and frontline health workers.

Ultrasensitive and Selective Field-Effect Transistor-Based Biosensor Created by Rings of MoS2 Nanopores.

The ubiquitous field-effect transistor (FET) is widely used in modern digital integrated circuits, computers, communications, sensors, and other applications. However, reliable biological FET (bio-FET) is not available in real life due to the rigorous requirement for highly sensitive and selective bio-FET fabrication, which remains a challenging task. Here, we report an ultrasensitive and selective bio-FET created by the nanorings of molybdenum disulfide (MoS2) nanopores inspired by nuclear pore complexes. We characterize the nanoring of MoS2 nanopores by scanning transmission electron microscopy, Raman, and X-ray photoelectron spectroscopy spectra. After fabricating MoS2 nanopore rings-based bio-FET, we confirm edge-selective functionalization by the gold nanoparticle tethering test and the change of electrical signal of the bio-FET. Ultrahigh sensitivity of the MoS2 nanopore edge rings-based bio-FET (limit of detection of 1 ag/mL) and high selectivity are accomplished by effective coupling of the aptamers on the nanorings of the MoS2 nanopore edge for cortisol detection. We believe that MoS2 nanopore edge rings-based bio-FET would provide platforms for everyday biosensors with ultrahigh sensitivity and selectivity.

Self-assembled peptides-modified flexible field-effect transistors for tyrosinase detection

SummaryFlexible biosensors have received intensive attention for real-time, non-invasive monitoring of cancer biomarkers. Highly sensitive tyrosinase biosensors, which are important for melanoma screening, remained a hurdle. Herein, high-performance tyrosinase-sensing field-effect transistor-based biosensors (bio-FETs) have been successfully achieved by self-assembling nanostructured tetrapeptide tryptophan–valine–phenylalanine–tyrosine (WVFY) on n-type metal oxide transistors. In the presence of target tyrosinase, the phenolic hydroxyl groups in WVFY are rapidly converted to benzoquinone with the consumption of protons, which could be detected potentiometrically by bio-FETs. As a result, the WVFY-modified bio-FETs exhibited an ultra-low detection limit of 1.9 fM and an optimal detection range of 10 fM to 1 nM toward tyrosinase sensing. Furthermore, flexible devices fabricated on ∼2.9-μm-thick polyimide (PI) substrates illustrated robust mechanical flexibility, which could be attached to human skin conformally. These achievements hold promise for wearable melanoma screening and provide designing guidelines for detecting other important cancer biomarkers with bio-FETs.

Rapid Drug-Screening Platform Using Field-Effect Transistor-Based Biosensors: A Study of Extracellular Drug Effects on Transmembrane Potentials.

Ion channel-modulating drugs play an important role in treating cardiovascular diseases. Facing the demands for continuous monitoring of drug effectiveness, the conventional techniques have become limited when investigating a long-term cellular physiology. To address the challenge, we propose a drug-screening platform using the stretch-out electrical double layer (EDL)-gated field-effect transistor-based biosensors (BioFETs). In this work, BioFETs were utilized to amplify electrophysiological signals from the mammalian cardiomyocytes (H9c2). The stretch-out configuration avoided a chemical corrosion on FETs and prolonged the lifetime of a BioFET system. A physical model is presented to elucidate the signal response to a drug effect on a cell. Fibronectin and gelatin were coated on sensors and served as the adhesive layers where H9c2 cells attached. BioFETs demonstrated an ability to qualitatively distinguish a depolarization and a polarization of the cytomembranes. The signal responses to the changes of transmembrane potentials were monitored in real-time, and they were highly correlated. The effects of nifedipine and calcium ions on cellular electrophysiology were examined and discussed. Due to the capability of a rapid detection, a prolonged lifetime, and an excellent sensitivity to an electrical change, a stretch-out EDL-gated BioFET can be a drug-screening platform for ion channel modulators.

Electrolyte-gated carbon nanotube field-effect transistor-based biosensors: Principles and applications

Nowadays, there is a high demand for sensitive and selective real-time analytical methods suitable for a wide range of applications, from personalized telemedicine, drug discovery, food safety, and quality control, to defense, security, as well as environmental monitoring. Biosensors are analytical devices able to detect bio-chemical analytes (e.g., neurotransmitters, cancer biomarkers, bio-molecules, and ions), through the combination of a bio-recognition element and a bio-transduction device. The use of customized bio-recognition elements such as enzymes, antibodies, aptamers, and ion-selective membranes facilitates achieving high selectivity. Among the different bio-transduction devices currently available, electrolyte-gated field-effect transistors, in which the dielectric is represented by an ionic liquid buffer solution containing the targeted analyte, are gaining increasing attention. Indeed, these bio-transduction devices are characterized by superior electronic properties and intrinsic signal amplification that allow the detection of a wide range of bio-molecules with high sensitivity (down to pM concentration). A promising semiconducting material for bio-transduction devices is represented by carbon nanotubes, due to their unique electrical properties, nanosize, bio-compatibility, and their simple low-cost processability. This work provides a comprehensive and critical review of electrolyte-gated carbon nanotube field-effect transistor-based biosensors. First, an introduction to these bio-sensing devices is given. Next, the device configurations and operating principles are presented, and the most used materials and processes are reviewed with a particular focus on carbon nanotubes as the active material. Subsequently, different functionalization strategies reported in the literature, based on enzymes, antibodies, aptamers, and ion-selective membranes, are analyzed critically. Finally, present issues and challenges faced in the area are investigated, the conclusions are drawn, and a perspective outlook over the field of bio-sensing technologies, in general, is provided.

Organic Field-Effect Transistor-Based Biosensors with Enhanced Sensitivity and Reliability under Illumination for Carcinoembryonic Antigen Bioassay.

Achieving biosensors of high sensitivity and reliability is extremely significant for early diagnosis and treatment of tumor diseases. Herein, a novel organic field-effect transistor (OFET)-based biosensor was developed and applied for carcinoembryonic antigen (CEA) bioassay. This OFET-based biosensor can respond sensitively to the antigen-antibody immune-recognition reaction under illumination and darkness, respectively, thereby generating electrical signal changes of source-drain current (IDS) and threshold voltage (Vth). The OFET-based biosensor exhibits detection limits for CEA detection of 0.5 and 0.2 pM, respectively, using IDS and Vth as the response signals under darkness. When a specific intensity of light is applied, light will influence the charge-carrier transport process in the conductive channel, thus causing biosignals to turn into higher electrical signal changes of photocurrent and threshold voltage under illumination. Compared with the detection results in the dark, the biosensor exhibits higher sensitivity for CEA detection under illumination with detection limits of 13.5 and 16.9 fM. Also, multisignal outputs effectively improve the reliability of the biosensor for CEA detection. Consequently, with powerful detection functions, this OFET-based biosensor is expected to become a high-performance biosensing platform for the detection of various biological substances in the future.

A Rapid Detection of COVID-19 Viral RNA in Human Saliva Using Electrical Double Layer-Gated Field-Effect Transistor-Based Biosensors.

In light of the swift outspread and considerable mortality, coronavirus disease 2019 (COVID‐19) necessitates a rapid screening tool and a precise diagnosis. Saliva is considered as an alternative specimen to detect the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) since the viral load is comparable to what are found in a throat and a nasal cavity. The electrical double layer (EDL)‐gated field‐effect transistor‐based biosensor (BioFET) emerges as a promising candidate for salivary COVID‐19 tests due to a high sensitivity, a portable configuration, a label‐free operation, and a matrix insensitivity. In this work, the authors utilize EDL‐gated BioFETs to detect complementary DNAs (cDNAs) and viral RNAs with various testing conditions such as switches of probes, temperature treatments, and matrices. The selectivity is confirmed with cDNA and noncomplementary DNA (ncDNA), exhibiting an eightfold difference in electrical signals. The matrix insensitivity is evaluated, and BioFETs successfully validate the detection of SARS‐CoV‐2 N‐gene RNA down to 1 fm in diluted human saliva with a 95°C‐ and a 25°C‐treatment, respectively. This proposed system has a high potential to be deployed for an on‐site COVID‐19 screening, improving the disease control and benefitting frontline healthcare system.

Ultrasensitive WSe2 field-effect transistor-based biosensor for label-free detection of cancer in point-of-care applications

We demonstrate a highly sensitive tungsten diselenide (WSe2) field-effect transistor (FET) biosensor for label-free detection of early stage prostate cancer. We modified the FET channel by attaching the monoclonal antibody of prostate specific antigen (anti-PSA) through a multi-step process, followed by bovine serum albumin treatment, which ensures specific binding between anti-PSA and PSA. Our FET biosensor has a detection limit of 10 PSA, the lowest concentration detected so far by any FET sensor. At this detection limit, the sub-threshold swing is ; and the drain current () in the FET increases by 70% compared to that in a pristine device. The FET sensor exhibits linear change in threshold voltage () and drain current () over the detection range of 10 –1 PSA. Our demonstrated ultra-sensitive and fast WSe2 FET biosensors are promising for point-of-care diagnostics applications.

Monitoring Coronavirus Disease 2019: A Review of Available Diagnostic Tools.

Coronavirus disease 2019 (COVID-19) pneumonia is caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has rapidly become a global public health concern. As the new type of betacoronavirus, SARS-CoV-2 can spread across species and between populations and has a greater risk of transmission than other coronaviruses. To control the spread of SARS-CoV-2, it is vital to have a rapid and effective means of diagnosing asymptomatic SARS-CoV-2-positive individuals and patients with COVID-19, an early isolation protocol for infected individuals, and effective treatments for patients with COVID-19 pneumonia. In this review, we will summarize the novel diagnostic tools that are currently available for coronavirus, including imaging examinations and laboratory medicine by next-generation sequencing (NGS), real-time reverse transcriptase–polymerase chain reaction (rRT-PCR) analysis, immunoassay for COVID-19, cytokine and T cell immunoassays, biochemistry and microbiology laboratory parameters in the blood of the patients with COVID-19, and a field-effect transistor-based biosensor of COVID-19. Specifically, we will discuss the effective detection rate and assay time for the rRT-PCR analysis of SARS-CoV-2 and the sensitivity and specificity of different antibody detection methods, such as colloidal gold and ELISA using specimen sources obtained from the respiratory tract, peripheral serum or plasma, and other bodily fluids. Such diagnostics will help scientists and clinicians develop appropriate strategies to combat COVID-19.

Selective and electronic detection of COVID-19 (Coronavirus) using carbon nanotube field effect transistor-based biosensor: A proof-of-concept study

In this work, we propose and demonstrate a carbon nanotube (CNT) field-effect transistor (FET) based biosensor for selective detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CNT FETs were fabricated on a flexible Kapton substrate and the sensor was fabricated by immobilizing the reverse sequence of the RNA-dependent RNA polymerase gene of SARS-CoV-2 onto the CNT channel. The biosensors were tested for the synthetic positive and control target sequences. The biosensor showed a selective sensing response to the positive target sequence with a limit of detection of 10 fM. The promising results from our study suggest that the CNT FET based biosensors can be used as a diagnostic tool for the detection of SARS-CoV-2.

Ultrasensitive and Reliable Organic Field-Effect Transistor-Based Biosensors in Early Liver Cancer Diagnosis.

Organic field-effect transistors (OFETs) are considered as one of the cost-effective biosensor devices with rapid detection capabilities and multiparameter responses. However, the functionalization processes on normal organic devices might impact the device performance for its further sensitive and reliable sensing applications. Herein, we develop a novel organic material, 2,6-bis(4-formylphenyl)anthracene (BFPA) for use as the protective and functional layer of OFET-based biosensors, enabling ultrasensitive determination of alpha-fetoprotein (AFP) with femtomolar accuracy in human serum. By monitoring changes of the source-drain current (Ids) and threshold voltage (Vth) electrical signals, the device exhibits improved reliability in detecting AFP biomarkers and is able to differentiate between liver cancer patients and healthy individuals. Featuring label-free determination, shorter analysis time, and lower sample volume, this ultrasensitive and reliable OFET-based biosensor displays numerous advantages over traditional strategies such as enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay, demonstrating that the proposed OFET-based biosensors have broader analytical and clinical applications for early liver cancer diagnosis.

A New Simulation Approach of Transient Response to Enhance the Selectivity and Sensitivity in Tunneling Field Effect Transistor-Based Biosensor

In this work, a new simulation approach of transient analysis on single cavity dielectric-modulated (DM) p -type of tunnel field-effect transistor (TFET) is examined for biosensing applications. The device operation and performance are investigated using the 2D device simulator and results are well-calibrated with experimental data. In this work, we have examined DC transfer characteristics, the transient response of drain current, drain current sensitivity (S), and selectivity (AS). Focussing more on the transient results, we have obtained maximum sensitivity of orders greater than 108 for APTES biomolecule with respect to air and a significant selectivity value in orders of 103 for APTES with respect to Biotin biomolecule. The performance of the device in terms of selectivity can be further improved (~10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> ) by optimizing the back-gate bias, and therefore, the impact of back-gate bias has been analysed. The results for charged biomolecules and partially filled cavity are further investigated & highlighted. The DM p-TFET biosensor shows a significant improvement in the results with the transient response for biosensing applications with the feasibility of operating at low voltages (gate voltage of -2.0 V, drain voltage of -0.5 V and back gate voltage 0 to 0.5 V).

Surface functionalized β-Bi2O3 nanofibers based flexible, field-effect transistor-biosensor (BioFET) for rapid, label-free detection of serotonin in biological fluids

In this work, we demonstrate a high-performance Field effect transistor-based biosensor (BioFET) on Al functionalized β-Bi2O3 nanofibers for highly selective and rapid detection of serotonin. The β-Bi2O3 nanofibers were synthesized using electrospinning technique and conductivity was tailored by surface functionalization using Al nanoparticles. Interdigitated silver electrodes deposited over the flexible polyimide (PI) substrate acts as contact terminals and dielectric substrate respectively while Al functionalized β-Bi2O3 nanofibers acts as n-type semiconductor channel and a thermally evaporated silver electrode beneath the PI tape as a back-gate terminal. Detailed characterization reveals the formation of β-phase monoclinic, high mobility, 1-D Bi2O3 nanofibers, and Al functionalization was validated using elemental composition studies. The fabricated FET exhibited a transconductance of 5.23 μS and mobility of 64.4 cm2 V−1s−1 with an Ion/ Ioff ratio ∼106. The BioFET exhibited an excellent sensitivity of 51.64 μA/nM towards serotonin over a wide linear detection range of 10 nM- 1 μM and a limit of detection of 0.29 nM. This can be ascribed to the excellent change in surface potential upon interaction of serotonin molecules with the electroactive surface functionalized multidimensional nanoparticle-nanofiber network and the back-gate electrode-based control of the Debye screening length. The fabricated BioFET exhibits excellent sensitivity, stability and reproducibility with a rapid response time of 0.8 s. Excellent selectivity towards serotonin in the presence of interfering analytes like ascorbic acid (AA), uric acid (UA), Glucose, Na+, K+, Dopamine (DA) is observed owing to the formation of selective binding complexes between the aromatic amine and β-Bi2O3. The real-time applicability of the sensor was successfully tested using urine samples as a test matrix thus establishing it as a promising platform for label free detection of biomolecules in point-of care diagnostics.

Fabrication and Characterization of Silk Fibroin Films by a Spin-Coating Method Toward the Application to Field-Effect Transistor-Based Biosensors

Fabrication and Characterization of Silk Fibroin Films by a Spin-Coating Method Toward the Application to Field-Effect Transistor-Based Biosensors