High Electron Mobility Transistor Biosensor Research Articles

Construction of AlGaN/GaN high-electron-mobility transistor-based biosensor for ultrasensitive detection of SARS-CoV-2 spike proteins and virions

The COVID-19 pandemic has highlighted the need for rapid and sensitive detection of SARS-CoV-2. Here, we report an ultrasensitive SARS-CoV-2 immunosensor by integration of an AlGaN/GaN high-electron-mobility transistor (HEMT) and anti-SARS-CoV-2 spike protein antibody. The AlGaN/GaN HEMT immunosensor has demonstrated the capability to detect SARS-CoV-2 spike proteins at an impressively low concentration of 10−22 M. The sensor was also applied to pseudoviruses and SARS-CoV-2 ΔN virions that display the Spike proteins with a single virion particle sensitivity. These features validate the potential of AlGaN/GaN HEMT biosensors for point of care tests targeting SARS-CoV-2. This research not only provides the first HEMT biosensing platform for ultrasensitive and label-free detection of SARS-CoV-2.

A salivary urea sensor based on a microsieve disposable gate AlGaN/GaN high electron mobility transistor.

The abundant bio-markers in saliva provide a new option for non-invasive testing. However, due to the presence of impurities in the saliva background, most of the existing saliva testing methods rely on pre-processing, which limits the application of saliva testing as a convenient means of testing in daily life. Herein, a disposable-gate AlGaN/GaN high electron mobility transistor (HEMT) biosensor integrated with a micro-sieve was introduced to solve the problem of signal interference caused by charged impurities in saliva for HEMT based biosensors, where the micro-sieve was utilized as a pre-treatment unit to remove large particles of impurities from saliva through the size effect and thus greatly improving the accuracy of detection. The experimental results showed that the HEMT based biosensor has excellent linearity (R2 = 0.9977) and a high sensitivity of 6.552 μA dec-1 for urea sensing from 1 fM to 100 mM in 0.1× PBS solution. When it comes to artificial saliva detection, compared to the HEMT sensor without the micro-sieve (sensitivity = 3.07432 μA dec-1), the sensitivity of the HEMT sensor integrated with the micro-sieve showed almost no change. Moreover, to verify that urea can be detected in actual saliva, urea is sensed directly in human saliva. The addition of the microsieve module provides a new way for biosensors to detect specific markers in saliva in real time, and the designed HEMT biosensor with the microsieve function has a wide range of application potential in rapid saliva detection.

Status and Prospects of Heterojunction-Based HEMT for Next-Generation Biosensors

High electron mobility transistor (HEMT) biosensors hold great potential for realizing label-free, real-time, and direct detection. Owing to their unique properties of two-dimensional electron gas (2DEG), HEMT biosensors have the ability to amplify current changes pertinent to potential changes with the introduction of any biomolecules, making them highly surface charge sensitive. This review discusses the recent advances in the use of AlGaN/GaN and AlGaAs/GaAs HEMT as biosensors in the context of different gate architectures. We describe the fundamental mechanisms underlying their operational functions, giving insight into crucial experiments as well as the necessary analysis and validation of data. Surface functionalization and biorecognition integrated into the HEMT gate structures, including self-assembly strategies, are also presented in this review, with relevant and promising applications discussed for ultra-sensitive biosensors. Obstacles and opportunities for possible optimization are also surveyed. Conclusively, future prospects for further development and applications are discussed. This review is instructive for researchers who are new to this field as well as being informative for those who work in related fields.

Antigen-Antibody Interaction-Based GaN HEMT Biosensor for C3G Detection

In this paper, we demonstrate the design and fabrication of an AlGaN/GaN High Electron Mobility Transistor (HEMT) as a bio sensing platform. Bio-compatible functionalization process with thioglycolic acid and antibody-antigen immobilization process with EDC-NHS chemistry is optimized, and the AlGaN/GaN HEMT biosensor is validated using recombinant C3G (RAPGEF1) protein and an indigenously developed mouse monoclonal antibody (clone 3F6mAb). The designed biosensor with its extended source-drain pads and inter-digital gate sensing design increases sensitivity of device to detect low concentration of biological samples. C3G protein is detected by antigen-antibody conjugation over extended functionalized sensing gate area which resulted in 36.2% change in drain current output and the corresponding antigen is detected up to 500 pg/ml. The biosensor shows a resolution in mA range, which is easily implementable by circuit due to low noise factor. It can therefore be adopted for use to detect antigens in very small biological samples, required in diagnostic assays of bio-medical applications.

Real-time detection of cardiac troponin I and mechanism analysis of AlGaAs/GaAs high electron mobility transistor biosensor

The high electron mobility transistor (HEMT)-based biosensors are highly competitive in the ultimate application of portable and point-of-care testing. Herein, we have demonstrated highly sensitive and real-time detection of cardiac troponin I (cTnI), a biomarker for the diagnosis of acute myocardial infarction (AMI) using AlGaAs/GaAs HEMT-based biosensors. The device has achieved a lower detection limit of 1 pg/ml in the buffer solution and less than 30 s response time, which demonstrated significant promise in the early diagnosis and screening of AMI. In addition, our results are consistent with the enzyme-linked immunosorbent assay according to the AMI patient’s blood test results. Furthermore, by comparing the two HEMT structures, we also calculated the equilibrium dissociation constant (KD) of the cTnI and cTnI antibody and analyzed the sensing mechanism. The results show that this method is very promising for early diagnosis of AMI.

Separative extended-gate AlGaAs/GaAs HEMT biosensors based on capacitance change strategy

Separative extended-gate AlGaAs/GaAs high electron mobility transistor (HEMT) biosensors based on the capacitance change strategy are proposed and fabricated. The working mechanism underlying this strategy is clearly clarified via examining the capacitance evolution on biorecognition and the capacitance matching issue between the HEMT and the sensing pad. The fabricated biosensors demonstrate a good linear current/voltage response to a label-free prostate-specific antigen (PSA) target over a broad concentration range of 100 fg/ml to 10 ng/ml in both 0.1× and 1× phosphate buffered saline solutions. Specifically, the sensitivity variation approaches 8.7% dec−1 at the critical concentration level of 2–8 ng/ml that enters the normal PSA region in the human body. The advantages of high sensitivity, low-cost, and convenience of usage make the proposed HEMT biosensors potential candidates for prostate cancer diagnosis.

EDL Gated FET Biosensor Array for the Investigation of Ion Channels and Bioelectric Signals of Circulating Tumor Cells

This paper demonstrates a novel methodology to analyze the bioelectric signals of cells in different test media using highly sensitive Electrical Double Layer (EDL) gated AlGaN/GaN HEMT (High Electron Mobility Transistor) biosensor array. Circulating Tumor Cells (CTCs) derived from Colorectal Cancer (CRC) were the target of this experiment. Previously, we had demonstrated that our sensor can detect and count the number of captured cells with up to single cell resolution. Thereafter, we further discovered that our sensor can be used in detecting important fundamental bioelectric signals of cell. We have demonstrated that our FET (Field Effect Transistor) biosensor can dynamically monitor the changes in transmembrane potential of cells induced by high concentrations of extracellular KCl, low and high extracellular divalent cation concentrations. Additionally, cadmium ions were used to block the calcium channels present in the cell demonstrating an interesting application of bioelectric signal study. Thus, we demonstrate that our sensing methodology can replace the conventional methods to study fundamental cellular mechanisms such as ion channel gating.

Direct detection of fibrinogen in human plasma using electric-double-layer gated AlGaN/GaN high electron mobility transistors

Fibrinogen found in blood plasma is an important protein biomarker for potentially fatal diseases such as cardiovascular diseases. This study focuses on the development of an assay to detect plasmatic fibrinogen using electrical double layer gated AlGaN/GaN high electron mobility transistor biosensors without complex sample pre-treatment methods used in the traditional assays. The test results in buffer solution and clinical plasma samples show high sensitivity, specificity, and dynamic range. The sensor exhibits an ultra-low detection limit of 0.5 g/l and a detection range of 0.5–4.5 g/l in 1× PBS with 1% BSA. The concentration dependent sensor signal in human serum samples demonstrates the specificity to fibrinogen in a highly dense matrix of background proteins. The sensor does not require complicated automation, and quantitative results are obtained in 5 min with <5 μl sample volume. This sensing technique is ideal for speedy blood based diagnostics such as POC (point of care) tests, homecare tests, or personalized healthcare.

Aptamer Functionalized AlGaN/GaN HEMT Biosensor Array for Electrical Enumeration of Circulating Tumor Cells

This paper demonstrates a novel AlGaN/GaN HEMT (High Electron Mobility Transistor) biosensor array to count the number of circulating tumor cells (CTCs) in the sample. Due to the high sensitivity of GaN HEMT and the new sensing technique, capture of cells on the sensor can be measured electrically with a resolution of single cell binding. By using sensor array, CTC capture and detection can be enhanced. The novel sensor array fabrication technique provides flexibility and robustness, while increasing throughput. This method of electrical enumeration can also be extended to other cell lines and cell types to identify normal and abnormal cells, in the future.

Blood Based Biomarker Detection Using FET Biosensor: Towards Self-Health Management

Diseases that are the leading causes of mortality worldwide such as cardiovascular diseases (CVD), cancer and infectious diseases can be better managed and cured with early and prompt diagnosis and prognosis. Molecular biomarkers in whole blood (blood serum proteins) have predictive, diagnostic and prognostic capacity and semiconductor based electronic biosensors can be used to deliver reliable and affordable point-of-care disease monitoring. GaN High Electron Mobility Transistor (HEMT) based sensors have previously been used in a variety of applications such as ion, gas and biomolecule sensing. However, the limitations of FET biosensors set by the charge screening effect in high ionic strength solutions required additional sample processing steps, making them practically unusable in terms of point-of-care testing. With a novel biosensing technique enabling direct detection of target proteins in high salt concentration medium using GaN HEMT and innovative biosensor packaging methodology, a portable biosensor system has been designed and fabricated which can provide quantitative blood biomarker analysis in 5 minutes with less than 5 µl sample. Antibody or aptamer functionalized reference gate electrode and transistor channel form an electrical double layer (EDL) FET structure that can detect binding of target proteins with very high sensitivity. The sensing and packaging techniques have been specifically optimized to meet the requirements and convenience of a mobile diagnostic system that can be used by anyone, at all times. HEMT chip is fabricated in a 4-5 mask process: mesa isolation, ohmic metal deposition and annealing, interconnect metal deposition and device passivation. A simple and robust two step epoxy based planar HEMT chip packaging allows for easy integration with commercially available reader sockets, much like the micro-SD card. A single step surface functionalization strategy is followed for immobilizing receptors which allows for high sensitivity with a wide dynamic range of detection. Pulsed gate voltage modulates the channel conductivity which behaves as a function of the charge distribution within the EDL structure. Thus, without complex sample pre-treatments and extremely low sampling requirements, quantitative detection of protein biomarkers can be achieved. The structural design of EDL FET brings the potential to investigate the binding events that were previously undetectable in traditional FET based biosensors. Results from testing purified proteins and clinical serum samples elucidate the potential of the sensing technique to overcome the charge screening effect and offer sensing beyond Debye length in physiological salt environment, with high sensitivity and ultra-low detection limit. This diagnostic technique can be applied to all types of FET based sensors that uses immunological reactions to detect the target. Owing to standard semiconductor fabrication processes and minimal or no sampling requirements, the portable sensing system can be affordable and accessible to all. Enabled with cloud management, this diagnostic system houses the potential to be a pioneering IoT biosensor. Figure 1

Aptamer Functionalized AlGaN/GaN HEMT Biosensor Array for Electrical Enumeration of Circulating Tumor Cells

This paper demonstrates a novel high sensitive FET biosensor array that can capture as well as count the number of captured Circulating Tumor Cells (CTCs) by the aptamer immobilized on the sensor. The FET used for this purpose is AlGaN/GaN HEMT (High Electron Mobility Transistor) because of its high sensitivity. Using a new and robust sensing technique the cell capture was able to be measured electrically and analyzed. The array enhances the capturing and detection capability of the sensors. The advantage of this sensor array is that the detection can be extended to any type of cells and cell lines to differentiate the normal and abnormal cells among them, and the behavior of cells can be studied in different kinds of mediums in which the cells are suspended. Biosensors can be used as point of care testing devices. In order to do so, they must be compact, portable, highly sensitive and user friendly. Along with being highly sensitive, GaN HEMT also are biocompatible, high temperature tolerant, chemically resistive and have excellent electrical properties. These properties of HEMT makes it a candidate for rapid biosensing. CTC enumeration has been used as a prognostic marker for metastatic colorectal cancer (m-CRC). CTCs are migrating cells that are shed into the blood stream from primary and metastatic tumors. But cancer patients have only 1-10 CTCs per cc of blood which makes them hard to be detected among plethora of other blood cells. The HEMT biosensor array developed by our group overcomes this drawback by capturing CTCs and counting them electrically, with an accuracy of single cell binding. The fabrication of AlGaN/GaN HEMT is done by forming mesa islands by ICP etching of epi-wafer which is followed by ohmic metal deposition, annealing and probing pad deposition. Finally individual chips of size 1mm X 1mm are embedded onto an epoxy substrate and interconnects are deposited making a planar sensing device. This fabricated chip is then passivated and only the gate electrode and channel regions are opened with an area of 10X60µm2 using photolithography. Aptamer is immobilized on the gate electrode and CTCs are allowed to be captured for 5~10 minutes. The cells bound on the aptamer are observed and the capture can be confirmed electrically by measuring the change in current gain compared to the aptamer current level and the change in current gain of HEMT sensor corresponds to the number of CTCs captured by the aptamer. In this way, CTC enumeration can be carried out using electrical measurement. This sensing technique is highly sensitive and can provide up to single cell resolution. Apart from rare migrating cells, abnormal cells and other cell based disease biomarkers can be detected and enumerated using our GaN HEMT based biosensor array. Figure 1

Electronic Biosensors Based on III-Nitride Semiconductors.

We review recent advances of AlGaN/GaN high-electron-mobility transistor (HEMT)-based electronic biosensors. We discuss properties and fabrication of III-nitride-based biosensors. Because of their superior biocompatibility and aqueous stability, GaN-based devices are ready to be implemented as next-generation biosensors. We review surface properties, cleaning, and passivation as well as different pathways toward functionalization, and critically analyze III-nitride-based biosensors demonstrated in the literature, including those detecting DNA, bacteria, cancer antibodies, and toxins. We also discuss the high potential of these biosensors for monitoring living cardiac, fibroblast, and nerve cells. Finally, we report on current developments of covalent chemical functionalization of III-nitride devices. Our review concludes with a short outlook on future challenges and projected implementation directions of GaN-based HEMT biosensors.

Ultrasensitive detection of Hg2+ using oligonucleotide-functionalized AlGaN/GaN high electron mobility transistor

An oligonucleotide-functionalized ion sensitive AlGaN/GaN high electron mobility transistor (HEMT) was fabricated to detect trace amounts of Hg2+. The advantages of ion sensitive AlGaN/GaN HEMT and highly specific binding interaction between Hg2+ and thymines were combined. The current response of this Hg2+ ultrasensitive transistor was characterized. The current increased due to the accumulation of Hg2+ ions on the surface by the highly specific thymine-Hg2+-thymine recognition. The dynamic linear range for Hg2+ detection has been determined in the concentrations from 10−14 to 10−8 M and a detection limit below 10−14 M level was estimated, which is the best result of AlGaN/GaN HEMT biosensors for Hg2+ detection till now.

Label free electrical detection of prostate specific antigen with millimeter grade biomolecule-gated AlGaN/GaN high electron mobility transistors

AlGaN/GaN high electron mobility transistor (HEMT) was successfully fabricated by complementary metal-oxide semiconductor field effect transistor-compatible fabrication method, and the label-free, electrical detection of prostate specific antigen in real time using the biomolecule-gate AlGaN/GaN HEMT sensor was presented. It shows a rapid response when target prostate biomarker in buffer solution was added to the antibody-immobilized sensing area. The linear range for target prostate specific antigen detection has been demonstrated from 0.1 pg/ml to 10.269 ng/ml and a low detection below 0.1 pg/ml level is estimated, which is the best result of AlGaN/GaN HEMT biosensor for prostate specific antigen (PSA) detection till now. The sensitivity of 0.027 % is determined for 0.1 pg/ml prostate specific antigen solution. The electrical result of the biomolecule-gated AlGaN/GaN HEMT biosensor suggested that this biosensor might be a useful tool for the prostate cancer screening.

Detection of prostate-specific antigen with biomolecule-gated AlGaN/GaN high electron mobility transistors

In order to improve the sensitivity of AlGaN/GaN high electron mobility transistor (HEMT) biosensors, a simple biomolecule-gated AlGaN/GaN HEMT structure was designed and successfully fabricated for prostate specific antigen (PSA) detection. UV/ozone was used to oxidize the GaN surface and then a 3-aminopropyl trimethoxysilane (APTES) self-assembled monolayer was bound to the sensing region. This monolayer serves as a binding layer for attachment of the prostate specific antibody (anti-PSA). The biomolecule-gated AlGaN/GaN HEMT sensor shows a rapid and sensitive response when the target prostate-specific antigen in buffer solution was added to the antibody-immobilized sensing area. The current change showed a logarithm relationship against the PSA concentration from 0.1 pg/ml to 0.993 ng/ml. The sensitivity of 0.215% is determined for 0.1 pg/ml PSA solution. The above experimental result of the biomolecule-gated AlGaN/GaN HEMT biosensor suggested that this biosensor might be a useful tool for prostate cancer screening.

Direct label-free electrical immunodetection of transplant rejection protein biomarker in physiological buffer using floating gate AlGaN/GaN high electron mobility transistors.

Monokine induced by interferon gamma (MIG/CXCL9) is used as an immune biomarker for early monitoring of transplant or allograft rejection. This paper demonstrates a direct electrical, label-free detection method of recombinant human MIG with anti-MIG IgG molecules in physiologically relevant buffer environment. The sensor platform used is a biologically modified GaN-based high electron mobility transistor (HEMT) device. Biomolecular recognition capability was provided by using high affinity anti-MIG monoclonal antibody to form molecular affinity interface receptors on short N-hydroxysuccinimide-ester functionalized disulphide (DSP) self-assembled monolayers (SAMs) on the gold sensing gate of the HEMT device. A floating gate configuration has been adopted to eliminate the influences of external gate voltage. Preliminary test results with the proposed chemically treated GaN HEMT biosensor show that MIG can be detected for a wide range of concentration varying from 5 ng/mL to 500 ng/mL.

Research on biomolecule-gate AlGaN/GaN high-electron-mobility transistor biosensors

In order to enhance the performance of AlGaN/GaN high electron mobility transistor (HEMT) biosensor, millimeter grade AlGaN/GaN HEMT structure have been designed and successfully fabricated. Factors influencing the capability of the AlGaN/GaN HEMT biosensor are analyzed. UV/ozone is used to oxidize GaN surface and then 3-aminopropyl trimethoxysilane (APTES) self-assembled monolayer can be bound to the sensing region. This serves as a binding layer in the attachment of prostate specific antibody (anti-PSA) for prostate specific antigen detection. The millimeter grade biomolecule-gated GaN/AlGaN HEMT sensor shows a quick response when the target prostate specific antigen in a buffer solution is added to the antibody-immobilized sensing area. The detection capability of this biomolecule-gate sensor estimated to be below 0.1 pg/ml level using a 21.5 mm2 sensing area, which is the best result of GaN/AlGaN HEMT biosensor for PSA detection till now. The electrical result of the biomolecule-gated GaN/AlGaN HEMT biosensor suggests that this biosensor might be a useful tool for the prostate cancer screening.

An excellent enzymatic lactic acid biosensor with ZnO nanowires-gated AlGaAs/GaAs high electron mobility transistor

An excellent biosensor with ZnO nanowires-gated AlGaAs/GaAs high electron mobility transistor (HEMT) was used to detect lactic acid. Due to the new structure, addition of the Si-doped GaAs cap layer, the HEMT biosensor could detect a wide range of lactic acid concentrations from 0.03 nM to 300 mM. The novel biosensor exhibiting good performance along with fast response, high sensitivity, wide detection range, and long-term stability, can be integrated with a commercially available transmitter to realize lactic acid detection.