Field Effect Transistor Biosensor Research Articles

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

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

Performance Analysis of Nanowire ISFET Biosensor Towards Bovine Serum Albumin and Liposome

Proteins are necessary to all living organisms for both structural and functional reasons. However, due to their breakdown, some proteins, including Bovine Serum Albumin (BSA) and Liposome, could cause detrimental effects on cells and tissues. Due to its high detection sensitivity, the potential for mass production, and affordable manufacture, the ion-sensitive field-effect transistor (ISFET) biosensor has become increasingly prominent in clinical research for the detection of biomolecules. BSA and Liposome are the target proteins, while collagen is the bioreceptor. ISFET biosensor with a structure of cylindrical nanowire was simulated and examined. The settling time and sensitivity of the biosensor were modeled using Nanohub BioSensorLab software. The cylindrical nanowire ISFET biosensor can be enhanced by reducing the buffer ion concentration, increasing the radius, and increasing the oxide thickness. Compared to liposomes, BSA provides a lower settling time. This is because the diffusion coefficient of liposomes is 3.6 times lower than BSA. Furthermore, settling time is reduced when the analyte concentration is increased. The results are compared with planar ISFET, considered one-dimensional (1D) architecture. The planar ISFET exhibited a quicker settling time than the cylindrical nanowire biosensor. Furthermore, as the amounts of protein and analyte increased, the settling time reduced. The cylindrical nanowire biosensor needs to be in radius of 100nm and 10nm of oxide thickness with 0.1M buffer concentration for it to achieved the highest sensitivity. These results could facilitate researchers to produce the desirable ISFET sensor for different types of proteins.

Analysis of Different Nanostructures of ISFET Biosensors Towards Liposome Detection

Proteins are needed by all living cells for structural and functional purposes. However, some proteins such as liposome instability may result in medication leaks that could harm cells. The detection of liposomes is dependent on the complex interactions between proteins, which are necessary for both their structural integrity and functional characteristics. This emphasizes the critical role that proteins play in the precise identification and examination of liposomal structures. Ion-sensitive field-effect transistor (ISFET) biosensor has gained popularity in the clinical research field for biomolecule detection due to its high detection sensitivity, mass-production capability, and low manufacturing cost. Nanohub BioSensorLab software was used to analyze the performance of different structures of ISFET (planar, cylindrical nanowire, nanosphere and double-gate FET) by simulating the settling time and selectivity of the biosensors. As the structural dimension expands from 1D to 3D, the settling time increases by three folds at the lowest analyte concentration. The fastest settling times were achieved by planar ISFET and double-gate FET. For selectivity measurements, an enhanced selectivity was achieved by increasing the concentration of the target molecule and decreasing the concentration of the parasitic molecule. A higher selectivity is determined by the higher Signal-to-Noise Ratio (SNR) value. The SNR increased linearly corresponds to the increase in the concentration of the target molecule as well as the decrease in the parasitic molecule’s concentration. The parasitic molecule's size increase of 1 nm causes a rise in SNR of 5.00×103.

Ultra-sensitive and rapid detection of Salmonella enterica and Staphylococcus aureus to single-cell level by aptamer-functionalized carbon nanotube field-effect transistor biosensors

Foodborne diseases caused by Salmonella enterica (S. enterica) and Staphylococcus aureus (S. aureus) significantly impact public health, underscoring the imperative for highly sensitive, rapid, and accurate detection technologies to ensure food safety and prevent human diseases. Nanomaterials hold great promise in the development of high-sensitivity transistor biosensors. In this work, field-effect transistor (FET) comprising high-purity carbon nanotubes (CNTs) were fabricated and modified with corresponding nucleic acid aptamers for the high-affinity and selective capture of S. enterica and S. aureus. The aptamer-functionalized CNT-FET biosensor demonstrated ultra-sensitive and rapid detection of these foodborne pathogens. Experimental results indicated that the biosensor could detect S. enterica at a limit of detection (LOD) as low as 1 CFU in PBS buffer, and S. aureus at an LOD of 1.2 CFUs, achieving single-cell level detection accuracy with exceptional specificity. The biosensor exhibited a rapid response time, completing single detections within 200 s. Even in the presence of interference from six complex food matrices, the biosensor maintained its ultra-sensitive (3.1 CFUs) and rapid response (within 200 s) characteristics for both pathogens. The developed aptamer-functionalized CNT-FET biosensor demonstrates a capability for low-cost, ultra-sensitive, label-free, and rapid detection of low-abundance S. enterica and S. aureus in both buffer solutions and complex environments. This innovation holds significant potential for applying this detection technology to on-site rapid testing scenarios, offering a promising solution to the pressing need for efficient and reliable pathogen monitoring in various settings.

Al2O3/ZrO2 dual-dielectric Gr/CNT nanoribbon vertical tunnel FET based biosensor for genomic classification and S-protein detection in SARS-CoV-2

The ongoing genetic mutation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) possesses the capacity to inadvertently lead to an increase in both the rates of transmission and mortality. In this study, we showcase the use of an Al2O3/ZrO2 Dual-Dielectric Gr/CNT Nanoribbon vertical tunnel field-effect transistor biosensor for the purpose of detecting spike proteins of SARS-CoV-2 in clinical samples. The proteins mentioned above are situated within the protein capsids of the virus. The effectiveness of the suggested detector has been assessed through measurements of the alteration in current drain. The present study utilizes the dielectric coefficient analogue of viral proteins as a substitute for biomolecules that exhibit internal hybridization nanogaps. The high sensitivity of the suggested detector, as evaluated on a scale ranging from 0 to 115, suggests its potential as a high-quality sensing instrument. The purpose of this study is to examine the sensitivity of DNA charge density with the aim of identifying any alterations in the virus that may impact its ability to spread and infect humans. The chromosomal composition of SARS-CoV-2 has been determined. The CMC Research Centre, situated in Vellore, Tamil Nadu, India, conducted an examination of SARS-CoV-2 samples. The scientists possess the capability to do genome sequencing on these specimens, so facilitating the examination of mutation patterns and the dispersion of different clades. A total of 250 different mutations were found out of the 600 sequences that were evaluated. The sequencing data consists of a complete collection of 250 distinct variants, including 150 missense mutations, 80 synonymous mutations, 15 mutations in noncoding regions, and 5 deletions. The comprehension of genetic variety is significantly dependent on these mutations. The proposed detector is connected to a variety of previously documented biosensors based on field-effect transistors (FETs), which are employed for the examination of genetic modifications.

ReS2-MoS2 heterojunction nanotube FET with superlattice structures for ultrasensitive detection of miRNA

Ultrasensitive detection of cancer biomarkers holds immense importance in facilitating the early diagnosis and treatment of cancer. Compared to conventional detection techniques, field-effect transistor (FET) biosensors have demonstrated substantial potential in achieving sensitive detection of cancer biomarkers. However, the ultrasensitive FET still remains great challenges due to the limited electron transport capacity and sensitivity of channel materials. Herein, we employed rhenium disulfide-molybdenum disulfide nanotube (ReS2-MoS2 NT) featuring superlattice structures as channel materials in FET biosensors for the highly sensitive detection of cancer biomarker miRNA-21. More concretely, ReS2-MoS2 NT featuring superlattice structures was synthesized using the anodic aluminum oxide (AAO) template sacrifice method and atomic layer deposition (ALD) method. The electrical properties of single ReS2-MoS2 NT FET were regulated by adjusting the total layers and number of heterojunction interfaces, and the optimal number of heterojunction interfaces of 7 was obtained. Finally, FET biosensors utilizing the network ReS2-MoS2 NT as the channel materials were fabricated and exhibited remarkable sensitivity in detecting miRNA-21 under an external light source. The linear range for detection spanned from 10 aM to 1 nM, with an exceptionally low detection limit of 2.1 aM. This study holds promise for replacing current channel materials and surpassing the detection threshold of cancer biomarkers in the future.

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

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

2D magnetic nanoporous carbon with bridge-type aptamer assembly for pesticide detection based on a regenerative field-effect transistor biosensor

Field-effect transistor (FET)-based biosensors have garnered attention due to their sensitivity to surface charge changes and advantages in real-time detection. However, these biosensors often suffer from several disadvantages such as their limited sensitivity and a high cost. Here, we reported an ultra-sensitive and reusable nanoporous-based FET biosensor hybridized with bridge-type aptamers. The sensor consisted of a two-dimensional magnetic iron-cobalt nanoparticle-embedded nanoporous carbon (Fe-Co/NPC) functionalized with bridge-type aptamers. The edges of the nanopores exhibited high surface energy and chemical activity, enabling effective interactions with the aptamers. Moreover, the nanoporous structures provided additional space, which could improve molecular recognition sites and sensor sensitivity. Our sensor could be used to detect organophosphorus pesticides (OPs) in vegetables down to 100 fM in real time and identify OPs from other pesticides. Furthermore, the magnetic properties of Fe-Co/NPC allowed us to reuse a single sensor chip up to 8 times, which significantly reduced the production cost of our sensors. In this respect, our Fe-Co/NPC-FET sensor could be a powerful tool for practical applications such as food safety detection.

Diagnostics of Tuberculosis with Single-Walled Carbon Nanotube-Based Field-Effect Transistors.

Tuberculosis (TB) is still threatening millions of people's lives, especially in developing countries. One of the major factors contributing to the ongoing epidemic of TB is the lack of a fast, efficient, and inexpensive diagnostic strategy. In this work, we developed a semiconducting single-walled carbon nanotube (SWCNT)-based field-effect transistor (FET) device functionalized with anti-Mycobacterium tuberculosis antigen 85B antibody (Ab85B) to detect the major M. tuberculosis-secreted antigen 85B (Ag85B). Through optimizing the device fabrication process by evaluating the mass of the antibody and the concentration of the gating electrolyte, our Ab85B-SWCNT FET devices achieved the detection of the Ag85B spiked in phosphate-buffered saline (calibration samples) with a limit of detection (LOD) of 0.05 fg/mL. This SWCNT FET biosensor also showed good sensing performance in biological matrices including artificial sputum and can identify Ag85B in serum after introducing bovine serum albumin (BSA) into the blocking layer. Furthermore, our BSA-blocked Ab85B-SWCNT FET devices can distinguish between TB-positive and -negative clinical samples, promising the application of SWCNT FET devices in point-of-care TB diagnostics. Moreover, the robustness of this SWCNT-based biosensor to the TB diagnosis in blood serum was enhanced by blocking SWCNT devices directly with a glutaraldehyde cross-linked BSA layer, enabling future applications of these SWCNT-based biosensors in clinical testing.

Ultrasensitive 3D Stacked Silicon Nanosheet Field-Effect Transistor Biosensor with Overcoming Debye Shielding Effect for Detection of DNA.

Silicon nanowire field effect (SiNW-FET) biosensors have been successfully used in the detection of nucleic acids, proteins and other molecules owing to their advantages of ultra-high sensitivity, high specificity, and label-free and immediate response. However, the presence of the Debye shielding effect in semiconductor devices severely reduces their detection sensitivity. In this paper, a three-dimensional stacked silicon nanosheet FET (3D-SiNS-FET) biosensor was studied for the high-sensitivity detection of nucleic acids. Based on the mainstream Gate-All-Around (GAA) fenestration process, a three-dimensional stacked structure with an 8 nm cavity spacing was designed and prepared, allowing modification of probe molecules within the stacked cavities. Furthermore, the advantage of the three-dimensional space can realize the upper and lower complementary detection, which can overcome the Debye shielding effect and realize high-sensitivity Point of Care Testing (POCT) at high ionic strength. The experimental results show that the minimum detection limit for 12-base DNA (4 nM) at 1 × PBS is less than 10 zM, and at a high concentration of 1 µM DNA, the sensitivity of the 3D-SiNS-FET is approximately 10 times higher than that of the planar devices. This indicates that our device provides distinct advantages for detection, showing promise for future biosensor applications in clinical settings.

Ultrasensitive detection of miRNA based on single-walled carbon nanotube@MoS2 field-effect transistor regulated by atomic layer deposition

MicroRNAs (miRNAs) act as diagnostic markers for various diseases, and achieving ultra-sensitive detection of miRNAs has an important effect on early disease diagnosis. Field-effect transistor (FET) biosensor exhibits superior sensitivity compared to conventional clinical detection instruments in detecting biomolecules. However, developing high-sensitive FET biosensors for detecting microRNAs remains challenging. In this study, we developed a FET biosensor using MoS2 and a network film of semiconductor single-walled carbon nanotube (SWCNT) as channel materials. The MoS2 cycles were precisely controlled and optimized by atom layer deposition (ALD), and the optimized 3-cycle device exhibited the best performance. This adjustment is beneficial for enhancing the charge transfer between SWCNT and MoS2, as well as improving the on/off ratio and mobility of FET devices. Additionally, the SWCNT@MoS2 structure offers a larger specific surface area, providing more active binding sites on the sensing interface. These two favorable factors contribute to the realization of linear detection miRNA-21 from 1 × 10−17 to 1 × 10−10 mol L−1 in biosensors. The theoretical detection limit of the biosensor is 1.9 × 10−18 mol L−1. This work develops a novel approach to achieve highly sensitive detection of miRNA for high-performance FET biosensors.

Field-effect transistor biosensor with signal amplification by ternary initiation complexes for detection of wide-range RNA concentration

Electrical detection of RNAs using transistor-based biosensors has attracted attention as a strategy for medical diagnosis and environmental monitoring. Herein, we demonstrated a proof-of-concept for specific, sensitive, and label-free RNA detection using a field-effect transistor (FET) biosensor with signal amplification by ternary initiation complexes (SATIC), which is an isothermal one-step nucleic acid amplification initiated by the combination of target RNA, circular DNA template and DNA primer. The SATIC system-applied FET biosensor specifically and quantitatively detected the target RNA with a single-nucleotide difference via the negative charges derived from the amplification products formed by a nucleic acid amplification reaction with φ29 DNA polymerase on the gate surface. In particular, the control of the amplification time allowed the detection of target RNA molecules over a wide concentration range, resulting in a detection limit of up to 6 copies/μL. Therefore, a transistor-based bioassay using the SATIC system could be useful for simple and sensitive nucleic acid analysis.

A Drug Molecule-Modified Graphene Field-Effect Transistor Nanosensor for Rapid, Label-Free, and Ultrasensitive Detection of Estrogen Receptor α Protein.

Estrogen receptor α (ERα) is an important biomarker in breast cancer diagnosis and treatment. Sensitive and accurate detection of ERα protein expression is crucial in guiding selection of an appropriate therapeutic strategy to improve the effectiveness and prognosis of breast cancer treatment. Herein, we report a liquid-gated graphene field-effect transistor (FET) biosensor that enables rapid, sensitive, and label-free detection of the ERα protein by employing a novel drug molecule as a capture probe. The drug molecule was synthesized and subsequently immobilized onto the sensing surface of the fabricated graphene FET, which was able to distinguish the ERα-positive from the ERα-negative protein. The developed sensor not only demonstrated a low detection limit (LOD: 2.62 fM) but also achieved a fast response to ERα protein samples within 30 min. Moreover, depending on the relationship between the change of dirac point and the ERα protein concentrations, the dissociation constant (Kd) was estimated to be 7.35 ± 0.06 pM, indicating that the drug probe-modified graphene FET had a good affinity with ERα protein. The nanosensor was able to analyze ERα proteins from 36 cell samples lysates. These results show that the graphene FET sensor was able to differentiate between ERα-positive and ERα-negative cells, indicating a promising biosensor for the ultrasensitive and rapid detection of ERα protein without antibody labeling.

Phthalocyanine-functionalized field-effect transistor biosensor for in situ monitoring of cell-released hydrogen sulfide

Hydrogen sulfide (H2S) is an important endogenous gas transmitter that is closely associated with human pathological and physiological states. Therefore, the accurate and quantitative detection of H2S has attracted great research interest in the biomedical field. In this paper, we report a phthalocyanine-functionalized field-effect transistor (FET) biosensor for ultra-sensitive, in situ, real-time monitoring of H2S released from cells. The reduced graphene oxide (RGO) and cobalt phthalocyanine RGO nanocomposites (CoGPCs) were layer to layer assembled on a prefabricated FET device surface. The excellent electrical conductivity of graphene and the high catalytic property and specificity of metal phthalocyanines ensure sensitive and specific detection of H2S. The biosensor was capable of detecting H2S in the range of 10 pM to 1 mM with detection limit down to 10 pM. In addition, the sensor exhibited good selectivity and biocompatibility. The excellent performance allowed the sensor to in situ and real-time monitor H2S release from different cell lines, and investigate the effect of inhibitors on H2S release from colon cancer cells. This FET biosensor provides a new approach for in situ and real-time monitoring of H2S release, which may help us understand the function of H2S in biological and pathological processes and contribute to drug screening development studies.

Dual-Mode Graphene Field-Effect Transistor Biosensor with Isothermal Nucleic Acid Amplification.

Despite a substantial increase in testing facilities during the pandemic, access remains a major obstacle, particularly in low-resource and remote areas. This constraint emphasizes the need for high-throughput potential point-of-care diagnostic tools in environments with limited resources. Loop-mediated isothermal amplification (LAMP) is a promising technique, but improvements in sensitivity are needed for accurate detection, especially in scenarios where the virus is present in low quantities. To achieve this objective, we present a highly sensitive detection approach of a dual-mode graphene-based field-effect transistor (G-FET) biosensor with LAMP. The G-FET biosensor, which has a transparent graphene microelectrode array on a glass substrate, detects LAMP products in less than 30 min using both observable color changes and Dirac point voltage measurements, even in samples with low viral concentrations. This dual-mode G-FET biosensor emerges as a potential alternative to conventional RT-PCR for severe acute respiratory syndrome-associated coronavirus (SARS-CoV)-2 detection or point-of-care testing, particularly in resource-constrained scenarios such as developing countries. Moreover, its capacity for colorimetric detection with the naked eye enhances its applicability in diverse settings.

Enhancing graphene field-effect transistor biosensors with DNA-mediated protein orientation

Enhancing graphene field-effect transistor biosensors with DNA-mediated protein orientation

Solution-Induced Degradation of the Silicon Nanobelt Field-Effect Transistor Biosensors.

Field-effect transistor (FET)-based biosensors are powerful analytical tools for detecting trace-specific biomolecules in diverse sample matrices, especially in the realms of pandemics and infectious diseases. The primary concern in applying these biosensors is their stability, a factor directly impacting the accuracy and reliability of sensing over extended durations. The risk of biosensor degradation is substantial, potentially jeopardizing the sensitivity and selectivity and leading to inaccurate readings, including the possibility of false positives or negatives. This paper delves into the documented degradation of silicon nanobelt FET (NBFET) biosensors induced by buffer solutions. The results highlight a positive correlation between immersion time and the threshold voltage of NBFET devices. Secondary ion mass spectrometry analysis demonstrates a gradual increase in sodium and potassium ion concentrations within the silicon as immersion days progress. This outcome is ascribed to the nanobelt's exposure to the buffer solution during the biosensing period, enabling ion penetration from the buffer into the silicon. This study emphasizes the critical need to address buffer-solution-induced degradation to ensure the long-term stability and performance of FET-based biosensors in practical applications.

Asymmetric Schottky Barrier-Generated MoS2/WTe2 FET Biosensor Based on a Rectified Signal.

Field-effect transistor (FET) biosensors can be used to measure the charge information carried by biomolecules. However, insurmountable hysteresis in the long-term and large-range transfer characteristic curve exists and affects the measurements. Noise signal, caused by the interference coefficient of external factors, may destroy the quantitative analysis of trace targets in complex biological systems. In this report, a "rectified signal" in the output characteristic curve, instead of the "absolute value signal" in the transfer characteristic curve, is obtained and analyzed to solve these problems. The proposed asymmetric Schottky barrier-generated MoS2/WTe2 FET biosensor achieved a 105 rectified signal, sufficient reliability and stability (maintained for 60 days), ultra-sensitive detection (10 aM) of the Down syndrome-related DYRK1A gene, and excellent specificity in base recognition. This biosensor with a response range of 10 aM-100 pM has significant application potential in the screening and rapid diagnosis of Down syndrome.

An integrated wearable sticker based on extended-gate AlGaN/GaN high electron mobility transistors for real-time cortisol detection in human sweat.

Cortisol hormone imbalances can be detected through non-invasive sweat monitoring using field-effect transistor (FET) biosensors, which provide rapid and sensitive detection. However, challenges like skin compatibility and integration with sweat collection have hindered FET biosensors as wearable sensing platforms. In this study, we present an integrated wearable sticker for real-time cortisol detection based on an extended-gate AlGaN/GaN high electron mobility transistor (HEMT) combined with a soft bottom substrate and flexible channel for sweat collection. The developed devices exhibit excellent linearity (R2 = 0.990) and a high sensitivity of 1.245 μA dec-1 for cortisol sensing from 1 nM to 100 μM in high-ionic-strength solution, with successful cortisol detection demonstrated using authentic human sweat samples. Additionally, the chip's microminiature design effectively reduces bending impact during the wearable process of traditional soft binding sweat sensors. The extendedgate structure design of the HEMT chip enhances both width-to-length ratio and active sensing area, resulting in an exceptionally low detection limit of 100 fM. Futhermore, due to GaN material's inherent stability, this device exhibits long-term stability with sustained performance within a certain attenuation range even after 60 days. These stickers possess small, lightweight, and portable features that enable real-time cortisol detection within 5 minutes through direct sweat collection. The application of this technology holds great potential in the field of personal health management, facilitating users to conveniently monitor their mental and physical conditions.

Applications of Graphene Field Effect Biosensors for Biological Sensing.

This chapter provides a comprehensive overview of the principles, applications, and advancements in graphene field-effect transistor (gFET) biosensors for biological sensing. The unique properties of graphene that make it ideal for biosensing, including its high conductivity, chemical stability, and ability to facilitate label-free detection, will be discussed. The chapter also explores various applications of gFET biosensors, from detecting pH and salinity changes to complex protein-protein interactions and DNA/RNA sensing. It also addresses the challenges and future directions in gFET biosensor technology, emphasizing the need for scalable manufacturing, sophisticated surface chemistry, and the integration of multiomics approaches to enhance biosensing capabilities.