Field Effect Transistor Biosensor Research Articles

Two-Dimensional Transition Metal Dichalcogenide Tunnel Field-Effect Transistors for Biosensing Applications.

Field-effect transistor (FET) biosensors based on two-dimensional (2D) materials have drawn significant attention due to their outstanding sensitivity. However, the Boltzmann distribution of electrons imposes a physical limit on the subthreshold swing (SS), and a 2D-material biosensor with sub-60 mV/dec SS has not been realized, which hinders further increase of the sensitivity of 2D-material FET biosensors. Here, we report tunnel FETs (TFETs) based on a SnSe2/WSe2 heterostructure and observe the tunneling effect of a 2D material in aqueous solution for the first time with an ultralow SS of 29 mV/dec. A bilayer dielectric (Al2O3/HfO2) and graphene contacts, which significantly reduce the leakage current in solution and contact resistance, respectively, are crucial to the realization of the tunneling effect in solution. Then, we propose a novel biosensing method by using tunneling current as the sensing signal. The TFETs show an extremely high pH sensitivity of 895/pH due to ultralow SS, surpassing the sensitivity of FET biosensors based on a single 2D material (WSe2) by 8-fold. Specific detection of glucose is realized, and the biosensors show a superb sensitivity (3158 A/A for 5 mM), wide sensing range (from 10-9 to 10-3 M), low detection limit (10-9 M), and rapid response rate (11 s). The sensors also exhibit the ability of monitoring glucose in complex biofluid (sweat). This work provides a platform for ultrasensitive biosensing. The discovery of the tunneling effect of 2D materials in aqueous solution may stimulate further fundamental research and potential applications.

Performance Investigation of GaSb/Si Heterojunction based Gate Underlap and Overlap Vertical TFET Biosensor.

The present paper estimates the performance of vertically developed double gate GaSb/Si tunnel field-effect transistor (V-DGTFET) biosensor with source pocket. A commercially accessible tool, Silvaco-TCAD, is exploited for carrying simulations of V-DGTFET. The device's novelty is deploying a material with a small bandgap, namely GaSb, in the source region to improve the carrier tunneling in source-channel (GaSb-Si) heterojunction. Further, the present work has analysed the performance on half gate underlap and half gate overlap V-DGTFET based label-free biosensor. The performance of V-DGTFET biosensor corresponding to various biomolecules such as APTES with κ=3.57, bacteriophage-T7 with κ=6.4, apomyoglobin with κ =8.1 and gelatin with κ=12 is investigated with reference to energy band diagram, potential profile, electric field and drain characteristics. Furthermore, by considering the different values of dielectric constants from 1 to 12, the present paper computed the figure of merits (FOMs) essentially linearity and sensitivity. The results demonstrated that neutral biomolecules with higher dielectric constant values showed higher sensitivity compared with other biomolecules. Moreover, it is estimated that gelatin has to drain current sensitivity of 5.6×105, which is 13%, 20%, and 41% more in comparison to apomyoglobin (κ =8.1), bacteriophage-T7 (κ=6.4), and APTES (κ =3.57) sensitivity at 15 nm cavity length.

Recent Advances in Field Effect Transistor Biosensors: Designing Strategies and Applications for Sensitive Assay

In comparison with traditional clinical diagnosis methods, field-effect transistor (FET)-based biosensors have the advantages of fast response, easy miniaturization and integration for high-throughput screening, which demonstrates their great technical potential in the biomarker detection platform. This mini review mainly summarizes recent advances in FET biosensors. Firstly, the review gives an overview of the design strategies of biosensors for sensitive assay, including the structures of devices, functionalization methods and semiconductor materials used. Having established this background, the review then focuses on the following aspects: immunoassay based on a single biosensor for disease diagnosis; the efficient integration of FET biosensors into a large-area array, where multiplexing provides valuable insights for high-throughput testing options; and the integration of FET biosensors into microfluidics, which contributes to the rapid development of lab-on-chip (LOC) sensing platforms and the integration of biosensors with other types of sensors for multifunctional applications. Finally, we summarize the long-term prospects for the commercialization of FET sensing systems.

Emerging Technologies of Three-Dimensional Printing and Mobile Health in COVID-19 Immunity and Regenerative Dentistry.

The ongoing coronavirus disease 2019 (COVID-19) pandemic highlights the importance of developing point-of-care (POC) antibody tests for monitoring the COVID-19 immune response upon viral infection or following vaccination, which requires three key aspects to achieve optimal monitoring, including three-dimensional (3D)-printed POC devices, mobile health (mHealth), and noninvasive sampling. As a critical tissue engineering concept, additive manufacturing (AM, also known as 3D printing) enables accurate control over the dimensional and architectural features of the devices. mHealth refers to the use of portable digital devices, such as smartphones, tablet computers, and fitness and medical wearables, to support health, which facilitates contact tracing, and telehealth consultations during the pandemic. Compared with invasive biosample (blood), saliva is of great importance in the spread and surveillance of COVID-19 as a noninvasive diagnostic method for virus detection and immune status monitoring. However, investigations into 3D-printed POC antibody test and mHealth using noninvasive saliva are relatively limited. Further exploration of 3D-printed antibody POC tests and mHealth applications to monitor antibody production for either disease onset or immune response following vaccination is warranted. This review briefly describes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and immune response after infection and vaccination, then discusses current widely used binding antibody tests using blood samples and enzyme-linked immunosorbent assays on two-dimensional microplates before focusing upon emerging POC technological platforms, such as field-effect transistor biosensors, lateral flow assay, microfluidics, and AM for fabricating immunoassays, and the possibility of their combination with mHealth. This review proposes that noninvasive biofluid sampling combined with 3D POC antibody tests and mHealth technologies is a promising and novel approach for POC detection and surveillance of SARS-CoV-2 immune response. Furthermore, as key concepts in dentistry, the application of 3D printing and mHealth was also included to facilitate the appreciation of cutting edge techniques in regenerative dentistry. This review highlights the potential of 3D printing and mHealth in both COVID-19 immunity monitoring and regenerative dentistry.

The design of a point of care FET biosensor to detect and screen COVID-19

Graphene field effect transistor (FET) biosensors have attracted huge attention in the point-of-care and accurate detection. With the recent spread of the new emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the need for rapid, and accurate detection & screening tools is arising. Employing these easy-to-handle sensors can offer cheap, rapid, and accurate detection. Herein, we propose the design of a reduced graphene oxide (rGO) FET biosensor for the detection of SARS-CoV-2. The main objective of this work is to detect the SARS-CoV-2 spike protein antigen on spot selectively and rapidly. The sensor consists of rGO channel, a pair of golden electrodes, and a gate underneath the channel. The channel is functionalized with COVID-19 spike protein antibodies to achieve selectivity, and with metal nanoparticles (MNPs) such as copper and silver to enhance the bio-sensing performance. The designed sensor successfully detects the SARS-CoV-2 spike protein and shows singular electrical behavior for detection. The semi-empirical modeling approach combined with none-equilibrium Green’s function were used to study the electronic transport properties of the rGO-FET biosensor before and after the addition of the target molecules. The sensor’s selectivity is also tested against other viruses. This study provides a promising guide for future practical fabrication.

Fabrication of MoS2/C60 Nanolayer Field-Effect Transistor for Ultrasensitive Detection of miRNA-155.

As a major public health issue, early cancer detection is of great significance. A field-effect transistor (FET) based on an MoS2/C60 composite nanolayer as the channel material enhances device performance by adding a light source, allowing the ultrasensitive detection of cancer-related miRNA. In this work, atomic layer deposition (ALD) was used to deposit MoS2 layer by layer, and C60 was deposited by an evaporation coater to obtain a composite nanolayer with good surface morphology as the channel material of the FET. Based on the good absorption of C60 by blue-violet light, a 405 nm laser was selected to irradiate the channel material, improving the function of FET biosensors. A linear detection window from 10 pM to 1 fM with an ultralow detection limit of 5.16 aM for miRNA-155 was achieved.

An ultrasensitive FET biosensor based on vertically aligned MoS2 nanolayers with abundant surface active sites

Molybdenum disulfide (MoS2) nanolayers are one of the most promising two-dimensional (2D) nanomaterials for constructing next-generation field-effect transistor (FET) biosensors. In this article, we report an ultrasensitive FET biosensor that integrates a novel format of 2D MoS2, vertically-aligned MoS2 nanolayers (VAMNs), as the channel material for label-free detection of the prostate-specific antigen (PSA). The developed VAMNs-based FET biosensor shows two distinctive advantages. First, the VAMNs can be facilely grown using the conventional chemical vapor deposition (CVD) method, permitting easy fabrication and potential mass device production. Second, the unique advantage of the VAMNs for biosensor development lies in its abundant surface-exposed active edge sites that possess a high binding affinity with thiol-based linkers, which overcomes the challenge of molecule functionalization on the conventional planar MoS2 nanolayers. The high binding affinity between 11-mercaptoundecanoic acid and the VAMNs was demonstrated through experimental surface characterization and theoretical calculations via density functional theory. The FET biosensor allows rapid (within 20 min) and ultrasensitive PSA detection in human serum with simple operations (limit of detection: 800 fg mL−1). This FET biosensor offers excellent features such as ultrahigh sensitivity, ease of fabrication, and short assay time, and thereby possesses significant potential for early-stage diagnosis of life-threatening diseases.

Alanine aminotransferase assay biosensor platform using silicon nanowire field effect transistors

Frequent monitoring of serum alanine aminotransferase (ALT) activity is essential to prevent drug-induced liver injury (DILI). Current ALT assays are restricted to centralized clinical laboratories, making frequent patient monitoring logistically difficult. To address this, we demonstrated the capability of commercial foundry manufactured silicon nanowire field effect transistor (SiNW-FET) biosensors in a form factor that enables frequent near-patient monitoring. Here, we designed an ALT assay, by coupling the ALT-catalyzed production of pyruvate to the reduction of ferricyanide, enabling both spectrophotometric and electrical measurement of ALT activity. The two methods yield comparable ALT activity detection across a dynamic range wide enough to monitor patients at risk for DILI. This study demonstrates kinetic activity measurement of an endogenous enzyme using uncoupled SiNW-FETs, and commercial manufacturing of SiNW-FET sensor arrays for use in a portable biosensor platform.

Toward the Commercialization of Carbon Nanotube Field Effect Transistor Biosensors.

The development of biosensors based on field-effect transistors (FETs) using atomically thick carbon nanotubes (CNTs) as a channel material has the potential to revolutionize the related field due to their small size, high sensitivity, label-free detection, and real-time monitoring capabilities. Despite extensive research efforts to improve the sensitivity, selectivity, and practicality of CNT FET-based biosensors, their commercialization has not yet been achieved due to the non-uniform and unstable device performance, difficulties in their fabrication, the immaturity of sensor packaging processes, and a lack of reliable modification methods. This review article focuses on the practical applications of CNT-based FET biosensors for the detection of ultra-low concentrations of biologically relevant molecules. We discuss the various factors that affect the sensors' performance in terms of materials, device architecture, and sensor packaging, highlighting the need for a robust commercial process that prioritizes product performance. Additionally, we review recent advances in the application of CNT FET biosensors for the ultra-sensitive detection of various biomarkers. Finally, we examine the key obstacles that currently hinder the large-scale deployment of these biosensors, aiming to identify the challenges that must be addressed for the future industrialization of CNT FET sensors.

A micro-carbon nanotube transistor for ultra-sensitive, label-free, and rapid detection of Staphylococcal enterotoxin C in food

Staphylococcal enterotoxin C (SEC) is an enterotoxin produced by Staphylococcus aureus, which can cause intestinal diseases. Therefore, it is of great significance to develop a sensitive detection method for SEC to ensure food safety and prevent foodborne diseases in humans. A field-effect transistor (FET) based on high-purity carbon nanotubes (CNTs) was used as a transducer, and a nucleic acid aptamer with high affinity was used for recognition to capture the target. The results indicated that the biosensor achieved an ultra-low theoretical detection limit of 1.25 fg/mL in PBS, and its good specificity was verified by detecting target analogs. Three typical food homogenates were used as the solution to be measured to verify that the biosensor had a swift response time (within 5 min after sample addition). An additional study with a more significant basa fish sample response also showed excellent sensitivity (theoretical detection limit of 8.15 fg/mL) and a stable detection ratio. In summary, this CNT-FET biosensor enabled the label-free, ultra-sensitive, and fast detection of SEC in complex samples. The FET biosensors could be further used as a universal biosensor platform for the ultrasensitive detection of multiple biological toxic pollutants, thus considerably stopping the spread of harmful substances.

Polyethylene Glycol Functionalized Silicon Nanowire Field-Effect Transistor Biosensor for Glucose Detection.

Accurate monitoring of blood glucose levels is crucial for the diagnosis of diabetes patients. In this paper, we proposed a simple "mixed-catalyzer layer" modified silicon nanowire field-effect transistor biosensor that enabled direct detection of glucose with low-charge in high ionic strength solutions. A stable screening system was established to overcome Debye screening effect by forming a porous biopolymer layer with polyethylene glycol (PEG) modified on the surface of SiNW. The experimental results show that when the optimal ratio (APTMS:silane-PEG = 2:1) modified the surface of silicon nanowires, glucose oxidase can detect glucose in the concentration range of 10 nM to 10 mM. The sensitivity of the biosensor is calculated to be 0.47 μAcm-2mM-1, its fast response time not exceeding 8 s, and the detection limit is up to 10 nM. This glucose sensor has the advantages of high sensitivity, strong specificity and fast real-time response. Therefore, it has a potential clinical application prospect in disease diagnosis.

Highly Stable InSe-FET Biosensor for Ultra-Sensitive Detection of Breast Cancer Biomarker CA125.

Two-dimensional materials-based field-effect transistors (FETs) are promising biosensors because of their outstanding electrical properties, tunable band gap, high specific surface area, label-free detection, and potential miniaturization for portable diagnostic products. However, it is crucial for FET biosensors to have a high electrical performance and stability degradation in liquid environments for their practical application. Here, a high-performance InSe-FET biosensor is developed and demonstrated for the detection of the CA125 biomarker in clinical samples. The InSe-FET is integrated with a homemade microfluidic channel, exhibiting good electrical stability during the liquid channel process because of the passivation effect on the InSe channel. The InSe-FET biosensor is capable of the quantitative detection of the CA125 biomarker in breast cancer in the range of 0.01-1000 U/mL, with a detection time of 20 min. This work provides a universal detection tool for protein biomarker sensing. The detection results of the clinical samples demonstrate its promising application in early screenings of major diseases.

Carbon nanotube field-effect transistor based pH sensors

Field-effect transistor (FET) biosensor has received widespread attention due to their unique high-sensitivity properties. In conventional FET biosensors, the complicated interaction between the sample solution and the semiconductor channel always results in poor stability. Especially for FET-based pH sensors, the interface failure caused by the harsh acid-base working environment makes accurate, continuous, and low hysteresis pH measurement quite challenging. Here, we report a carbon nanotube (CNT)-FET pH sensor with enhanced environmental stability by introducing HfO2 film into the gate insulator. The proposed devices show desired immunity to environmental interference including various chemical and physical factors. More importantly, we verified the feasibility of this CNT-FET device for continuous pH sensing, which demonstrates a sensitivity of 67.62 mV/pH, a wide pH range of 1.34–12.68, and low hysteresis of 500 pA with pH switching loops of 4.22–10.24. This work not only realizes a high-performance pH sensor but also paves the way for the development of FET biosensors with high environmental stability, which is of great significance for FET biosensors to maintain normal working performance in complex systems.

Suspended CNTs/MoS2 heterostructure field effect transistor for high performance biosensor and its application for serum PSA detection

Field effect transistor (FET) biosensors provide highly sensitive and rapid detection of bioactive proteins and biomarkers. However, the interface scattering may degrade device performance and the supported substrate also limits the exposed area to biological analytes. Here, a suspended heterostructure field effect transistor (FET) was fabricated for the detection of prostate specific antigen (PSA) in clinical serum samples from patients with prostate cancer. First, we tested the performance of the biosensor by β-actin detection, and the suspended CNTs/MoS2 heterostructure FET showed higher mobility, conductivity and sensitivity with enhanced stability compared to the conventional supported MoS2 FET. Furthermore, the suspended device showed ultrasensitive detection of PSA with the limit of detection (LOD) as low as 10-13 μg/μL and large detection range from 10-13 to 10-4 μg/μL. The device also showed rapid response and higher stability. For clinical application, multiple serum samples were analyzed by the suspended CNTs/MoS2 FET biosensors. The PSA concentration measured by the device was highly consistent with those obtained by the enzyme-linked immunosorbent assays (ELISA) method. Taken together, the suspended CNTs/MoS2 FET showed sensitive and reliable detection capability with great potential for rapid clinical examination and biomarker monitoring.

A Novel InSe‐FET Biosensor based on Carrier‐Scattering Regulation Derived from the DNA Probe Assembly‐Determined Electrostatic Potential Distribution

AbstractLow‐dimensional material field‐effect transistor (FET)‐based biosensors have the advantages of high sensitivity, high detection speed, small size, low cost, and excellent compatibility with integrated circuits. The sensing mechanism is extremely important in the design and fabrication of high‐performance FET biosensors in practical applications. Herein, an InSe‐FET biosensor is designed and its dominant sensing mechanism during detection and (mi)RNA detection performance are investigated. Finite element analysis reveals the electrostatic potential distribution in the InSe channel with DNA probe assembly showing that Coulomb scattering is the dominant sensing mechanism for carrier scattering‐sensitive InSe. The simulation and experimental results indicate that carriers in InSe are extremely sensitive to the scattering of surface impurities because of their small electron mass. The firstly reported back‐gate bias working mode of an InSe‐FET biosensor has a linear relationship with an extra‐large detectable range of 1 fM–10 nM, high specificity for identifying 1‐nucleotide polymorphisms, and excellent repeatability and reusability. The detection of biomarker miRNAs in clinical serum samples and specific RNA in SARS‐CoV‐2 pseudovirus samples indicate promising applications of InSe‐FET biosensors in critical disease screening and the fast diagnoses of infectious diseases. This study can be useful for the design and fabrication of high‐performance FET biosensors.

Advancement in COVID-19 detection using nanomaterial-based biosensors.

Coronavirus disease 2019 (COVID-19) pandemic has exemplified how viral growth and transmission are a significant threat to global biosecurity. The early detection and treatment of viral infections is the top priority to prevent fresh waves and control the pandemic. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified through several conventional molecular methodologies that are time-consuming and require high-skill labor, apparatus, and biochemical reagents but have a low detection accuracy. These bottlenecks hamper conventional methods from resolving the COVID-19 emergency. However, interdisciplinary advances in nanomaterials and biotechnology, such as nanomaterials-based biosensors, have opened new avenues for rapid and ultrasensitive detection of pathogens in the field of healthcare. Many updated nanomaterials-based biosensors, namely electrochemical, field-effect transistor, plasmonic, and colorimetric biosensors, employ nucleic acid and antigen-antibody interactions for SARS-CoV-2 detection in a highly efficient, reliable, sensitive, and rapid manner. This systematic review summarizes the mechanisms and characteristics of nanomaterials-based biosensors for SARS-CoV-2 detection. Moreover, continuing challenges and emerging trends in biosensor development are also discussed.

Dielectric Modulated Nanotube Tunnel Field-Effect Transistor as a Label Free Biosensor: Proposal and Investigation.

Dielectric modulated (DM) field-effect transistors (FET) have gained significant popularity for label-free detection of biomolecules. However, the inherent short channel effects limit their sensitivity, scalability and energy-efficiency. Therefore, to realize the true potential of the DMFET based biosensors, in this work, we propose a highly scalable, extremely sensitive and energy-efficient DM nanotube tunnel FET (NT-TFET) biosensor for label-free detection of biomolecules by modifying the structure of the conventional NT-TFET. The modified architecture facilitates the realization of a nanocavity at the source-channel tunneling junction and also provides stability to the immobilized biomolecules. We have performed an extensive analysis of the performance of the proposed DM NT-TFET biosensor in the presence of different representative target biomolecules characterized by different dielectric constants, and/or ionized charge densities using calibrated TCAD simulations. Our results indicate that the proposed DM NT-TFET exhibits an extremely high threshold voltage sensitivity ( SVth ) of 0.44, a high selectivity exceeding four orders of magnitude, ON-state current sensitivity ( SION ) of more than five orders of magnitude and could be a promising alternative to the conventional FET based dielectric modulated biosensors. Moreover, the sensitivity of the proposed DM NT-TFET could be further improved by utilizing alternate source materials with lower bandgap or by probing the transient response of the drain current and exploiting the difference in the settling time for different biomolecules with different dielectric constant ( κ ).

Graphene-based biosensors for detecting coronavirus: a brief review.

The coronavirus (SARS-CoV-2) disease has affected the globe with 770 437 327 confirmed cases, including about 6 956 900 deaths, according to the World Health Organization (WHO) as of September 2023. Hence, it is imperative to develop diagnostic technologies, such as a rapid cost-effective SARS-CoV-2 detection method. A typical biosensor enables biomolecule detection with an appropriate transducer by generating a measurable signal from the sample. Graphene can be employed as a component for ultrasensitive and selective biosensors based on its physical, optical, and electrochemical properties. Herein, we briefly review graphene-based electrochemical, field-effect transistor (FET), and surface plasmon biosensors for detecting the SARS-CoV-2 target. In addition, details on the surface modification, immobilization, sensitivity and limit of detection (LOD) of all three sensors with regard to SARS-CoV-2 were reported. Finally, the point-of-care (POC) detection of SARS-CoV-2 using a portable smartphone and a wearable watch is a current topic of interest.

Modular conductive MOF-gated field-effect biosensor for sensitive discrimination on the small molecular scale

Field-effect transistors (FETs) are a promising transducer for biosensors owing to their drastic signal amplification, showing a high sensitivity enough to detect ultra-low concentrations of small-molecular biomarkers in biofluids. However, the discrimination of small molecules from their structural analogues in biofluids using a FET is challenging; because of the 1) Debye screening in high-ionic-strength conditions, 2) few or no charges of the analytes, and 3) lack of target-specific receptors for small molecules. To overcome these limitations, we report a modular conductive MOF (c-MOF)-gated FET biosensor array that discriminates small-molecular neurotransmitters in biofluids. Adsorption and oxidation of analytes inside the pore of catalytic c-MOF films allow the sensitive detection of small molecules close to the clinically relevant concentration, regardless of the ionic strength of the media. The hierarchical screening ability of c-MOF attributed to their tunable pore size, surface charge, and host–guest interactions induces differentiated adsorption of small molecules. The cross-reaction intended by c-MOF design of our biosensor could provide discriminatory information of each neurotransmitter corresponding to the differences of one functional group in the molecule. Using our system, we also demonstrate discrimination capability under the interference of biologically relevant substances and artificial cerebrospinal fluid.

SARS-CoV-2 multi-variant rapid detector based on graphene transistor functionalized with an engineered dimeric ACE2 receptor

Reliable point-of-care (POC) rapid tests are crucial to detect infection and contain the spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The emergence of several variants of concern (VOC) can reduce binding affinity to diagnostic antibodies, limiting the efficacy of the currently adopted tests, while showing unaltered or increased affinity for the host receptor, angiotensin converting enzyme 2 (ACE2). We present a graphene field-effect transistor (gFET) biosensor design, which exploits the Spike-ACE2 interaction, the crucial step for SARS-CoV-2 infection. Extensive computational analyses show that a chimeric ACE2-Fragment crystallizable (ACE2-Fc) construct mimics the native receptor dimeric conformation. ACE2-Fc functionalized gFET allows in vitro detection of the trimeric Spike protein, outperforming functionalization with a diagnostic antibody or with the soluble ACE2 portion, resulting in a sensitivity of 20 pg/mL. Our miniaturized POC biosensor successfully detects B.1.610 (pre-VOC), Alpha, Beta, Gamma, Delta, Omicron (i.e., BA.1, BA.2, BA.4, BA.5, BA.2.75 and BQ.1) variants in isolated viruses and patient’s clinical nasopharyngeal swabs. The biosensor reached a Limit Of Detection (LOD) of 65 cps/mL in swab specimens of Omicron BA.5. Our approach paves the way for a new and reusable class of highly sensitive, rapid and variant-robust SARS-CoV-2 detection systems.