ABSTRACT
Field-effect transistor (FET) is regarded as the most promising candidate for the next-generation biosensor, benefiting from the advantages of label-free, easy operation, low cost, easy integration, and direct detection of biomarkers in liquid environments. With the burgeoning advances in nanotechnology and biotechnology, researchers are trying to improve the sensitivity of FET biosensors and broaden their application scenarios from multiple strategies. In order to enable researchers to understand and apply FET biosensors deeply, focusing on the multidisciplinary technical details, the iteration and evolution of FET biosensors are reviewed from exploring the sensing mechanism in detecting biomolecules (research direction 1), the response signal type (research direction 2), the sensing performance optimization (research direction 3), and the integration strategy (research direction 4). Aiming at each research direction, forward perspectives and dialectical evaluations are summarized to enlighten rewarding investigations.
Subject(s)
Biosensing Techniques , Transistors, Electronic , Nanotechnology , Biosensing Techniques/methodsABSTRACT
Mass pathogen screening is critical to preventing the outbreaks and spread of infectious diseases. The large-scale epidemic of COVID-19 and the rapid mutation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have put forward new requirements for virus detection and identification techniques. Here, we report a CRISPR-based Amplification-free Viral RNA Electrical Detection platform (CAVRED) for the rapid detection and identification of SARS-CoV-2 variants. A series of CRISPR RNA assays were designed to amplify the CRISPR-Cas system's ability to discriminate between mutant and wild RNA genomes with a single-nucleotide difference. The identified viral RNA information was converted into readable electrical signals through field-effect transistor biosensors for the achievement of highly sensitive detection of single-base mutations. CAVRED can detect the SARS-CoV-2 virus genome as low as 1â cp µL-1 within 20â mins without amplification, and this value is comparable to the detection limit of real-time quantitative polymerase chain reaction. Based on the excellent RNA mutation detection ability, an 8-in-1 CAVRED array was constructed and realized the rapid identification of 40 simulated throat swab samples of SARS-CoV-2 variants with a 95.0 % accuracy. The advantages of accuracy, sensitivity, and fast speed of CAVRED promise its application in rapid and large-scale epidemic screening.
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In food safety analysis, the detection and control of foodborne pathogens and their toxins are of great importance. Monitoring of virus transmission is equally important, especially in light of recent findings that coronaviruses have been detected in frozen foods and packages during the current global epidemic of coronavirus disease 2019. In recent years, field-effect transistor (FET) biosensors have attracted considerable scholarly attention for pathogenic microorganisms and toxins detection and sensing due to their rapid response time, high sensitivity, wide dynamic range, high specificity, label-free detection, portability, and cost-effectiveness. FET-based biosensors can be modified with specific recognition elements, thus providing real-time qualitative and semiquantitative analysis. Furthermore, with advances in nanotechnology and device design, various high-performance nanomaterials are gradually applied in the detection of FET-based biosensors. In this article, we review specific detection in different biological recognition elements are immobilized on FET biosensors for the detection of pathogenic microorganisms and toxins, and we also discuss nonspecific detection by FET biosensors. In addition, there are still unresolved challenges in the development and application of FET biosensors for achieving efficient, multiplexed, in situ detection of pathogenic microorganisms and toxins. Therefore, directions for future FET biosensor research and applications are discussed.
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This work presents the sensitivity assessment of gallium nitride (GaN) material-based silicon-on-insulator fin field effect transistor by dielectric modulation in the nanocavity gap for label-free biosensing applications. The significant deflection is observed on the electrical characteristics such as drain current, transconductance, surface potential, energy band profile, electric field, sub-threshold slope, and threshold voltage in the presence of biomolecules owing to GaN material. Further, the device sensitivity is evaluated to identify the effectiveness of the proposed biosensor and its capability to detect the biomolecules with high precision or accuracy. The higher sensitivity is observed for Gelatin (k = 12) in terms of on-current, threshold voltage, and switching ratio by 104.88%, 82.12%, and 119.73%, respectively. This work is performed using a powerful tool, three-dimensional (3D) Sentaurus Technology computer-aided design using a well-calibrated structure. The results pave the way for GaN-SOI-FinFET to be a viable candidate for label-free dielectric modulated biosensor applications.
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The occurrence of sudden viral outbreaks, including (Covid-19, H1N1 flu, H5N1 flu) has globally challenged the existing medical facilities and raised critical concerns about saving affected lives, especially during pandemics. The detection of viral infections at an early stage using biosensors has been proven to be the most effective, economical, and rapid way to combat their outbreak and severity. However, state-of-the-art biosensors possess bottlenecks of long detection time, delayed stage detection, and sophisticated requirements increasing the cost and complexities of biosensing strategies. Recently, using two-dimensional MXenes as a sensing material for architecting biosensors has been touted as game-changing technology in diagnosing viral diseases. The unique surface chemistries with abundant functional terminals, excellent conductivity, tunable electric and optical attributes and high specific surface area have made MXenes an ideal material for architecting virus-diagnosing biosensors. There are numerous detecting modules in MXene-based virus-detecting biosensors based on the principle of detecting various biomolecules like viruses, enzymes, antibodies, proteins, and nucleic acid. This comprehensive review critically summarizes the state-of-the-art MXene-based virus-detecting biosensors, their limitations, potential solutions, and advanced intelligent prospects with the integration of internet-of-things, artificial intelligence, 5G communications, and cloud computing technologies. It will provide a fundamental structure for future research dedicated to intelligent and point-of-care virus detection biosensors.
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The SARS‐CoV‐2 pandemic caused a public health crisis throughout the world and highlighted the need for rapid and sensitive testing as a countermeasure. A sensitive and specific biosensor platform is developed for the detection of antigen and RNA of SARS‐CoV‐2, and its variant (B1.1.529). The demonstrated biosensor platform combines unique protein catalyzed capture bioreceptors (PCCs) for antigen capture and a chimeric (RNA‐DNA) probe for RNA detection using LwaCas13a collateral cleavage activity atop graphene field effect transistors (gFETs). The reported biosensor is able to differentiate unprocessed 104 pfu m−1 samples of SARS‐CoV‐2 from Influenza and Rhinovirus. The limit of detection (LOD) calculated for SARS‐CoV‐2 antigen is 103 in buffer and 104 PFU mL−1 in 10% saliva, while LOD of ≈65 am calculated for viral RNA isolate without amplification. To provide a high reliability of detection, the role of internal and external factors with respect to gate voltage is further analyzed by Principal Component Analysis (PCA). Based on PCA analysis, the authors are able to classify the samples as pathogen positive or negative (Y > 0: Positive for pathogen, Y < 0: Negative for pathogen). The reported platform can be quickly adapted for multi‐omics and multiplexed diagnosis of continuously evolving biothreats and global pandemics. [ABSTRACT FROM AUTHOR] Copyright of Advanced Materials Technologies is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
ABSTRACT
Rapid diagnosis of coronavirus disease 2019 (COVID-19)-infected patients is urgent in making decisions on public health measures. There are different types of diagnostic tests, such as quantitative PCR assay, antibody, and antigen-based and CRISPR-based tests, which detect genetic materials, viral proteins, or human antibodies in clinical samples. However, the proper test should be highly sensitive, quick, and affordable to address this life-threatening situation. This review article highlights the advantages and disadvantages of each test and compares its different features, such as sensitivity, specificity, and limit of detection to reach a reliable conclusion. Moreover, the FDA- authorized kits and studies' approaches toward these have been compared to provide a better perspective to the researchers.Copyright © 2022 Lippincott Williams and Wilkins. All rights reserved.
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For epidemic prevention and control, molecular diagnostic techniques such as field-effect transistor (FET) biosensors is developed for rapid screening of infectious agents, including Mycobacterium tuberculosis, SARS-CoV-2, rhinovirus, and others. They obtain results within a few minutes but exhibit diminished sensitivity (<75%) in unprocessed biological samples due to insufficient recognition of low-abundance analytes. Here, an electro-enhanced strategy is developed for the precise detection of trace-level infectious agents by liquid-gate graphene field-effect transistors (LG-GFETs). The applied gate bias preconcentrates analytes electrostatically at the sensing interface, contributing to a 10-fold signal enhancement and a limit of detection down to 5 × 10−16 g mL−1 MPT64 protein in serum. Of 402 participants, sensitivity in tuberculosis, COVID-19 and human rhinovirus assays reached 97.3% (181 of 186), and specificity is 98.6% (213 of 216) with a response time of <60 s. This study solves a long-standing dilemma that response speed and result accuracy of molecular diagnostics undergo trade-offs in unprocessed biological samples, holding unique promise in high-quality and population-wide screening of infectious diseases. © 2023 Wiley-VCH GmbH.
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Herein, we have summarized and argued about biomarkers and indicators used for the detection of severe acute respiratory syndrome coronavirus 2. Antibody detection methods are not considered suitable to screen individuals at early stages and asymptomatic cases. The diagnosis of coronavirus disease 2019 using biomarkers and indicators at point-of-care level is much crucial. Therefore, it is urgently needed to develop rapid and sensitive detection methods which can target antigens. We have critically elaborated key role of biosensors to cope the outbreak situation. In this review, the importance of biosensors including electrochemical, surface enhanced Raman scattering, field-effect transistor, and surface plasmon resonance biosensors in the detection of severe acute respiratory syndrome coronavirus 2 has been underscored. Finally, we have outlined pros and cons of diagnostic approaches and future directions.
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In recent years, the significance of biosensors has increased rapidly due to the growing demand for rapid detection of various biomarkers with high selectivity and sensitivity. Among different biosensors, Graphene Field Effect Transistor (Gr-FET) based biosensors has emerged as a promising device and exhibited wide range of application prospects. Gr-FET biosensors are ideal for ultra-sensitive immunological diagnosis applications as it can sense surrounding changes on their surface with low noise. Recently Gr-FET based biosensors have gained profound research interest among scientific community because of its ability in detection of SARS-CoV-2 (corona virus-2). This review article highlights the sensing performance and characteristics of different Gr-FET biosensors like DNA sensor, RNA sensor, glucose sensor, lactose sensor, protein sensor, pH sensor, various bacteria and virus detecting sensors etc.This article also critically reviews the recent progress in Gr-FET based SARS- CoV-2 covid-19 virus detection bio-sensors. © 2022 Elsevier Ltd
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The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has proven the need for developing reliable and affordable technologies to detect pathogens. Particularly, the detecting the genome in wastewater could be an indicator of the transmission rate to alert on new outbreaks. However, wastewater-based epidemiology remains a technological challenge to develop affordable technologies for sensing pathogens. In this work, we introduce a label-free and portable field-effect transistor (FET)-based sensor to detect N and ORF1ab genes of the SARS-CoV-2 genome. Our sensor integrates the reverse transcription loop-mediated isothermal amplification (RT-LAMP) reaction as a cost-effective molecular detection exhibiting high specificity. The detection relies upon pH changes, due to the RT-LAMP reaction products, which are detected through a simple, but effective, extended-gate FET sensor (EGFET). We evaluate the proposed device by measuring real wastewater samples to detect the presence of SARS-CoV-2 genome, achieving a limit of detection of 0.31 × 10−3 ng/ μ L for end-point measurement. Moreover, we find the ability of the sensor to perform real-time-like analysis, showing that the RT-LAMP reaction provides a good response after 15 min for concentrations as low as 0.37 ng/ μ L. Hence, we show that our EGFET sensor offers a powerful tool to detect the presence of the SARS-CoV-2 genome with a naked-eye method, in a straightforward way than the conventional molecular methods for wastewater analysis. [Display omitted] • Label-free extended-gate field-effect transistor sensor for detect SARS-CoV-2 genome. • Portable and reliable sensing based on isothermal amplification reaction. • Detection and quantification of nucleic-acids in real wastewater samples. • End-pint and time course detection of RT-LAMP products. • The wastewater-based epidemiology can use this method in limited-resource conditions. [ FROM AUTHOR]
ABSTRACT
Low-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.
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In this study, we introduced H-terminated diamond solution-gate field-effect transistor (H-diamond SGFET) to detect trace SARS-CoV-2 N-protein, which plays an important role in replication and transcription of viral RNA. 1-Pyrenebutyric acid-N-hydroxy succinimide ester (Pyr-NHS) was modified on H-diamond surface as linker, on which the specific antibody of SARS-CoV-2 N-protein was catenated. Fourier transform infrared spectrum, scanning electron microscope and energy dispersive spectrum were utilized to demonstrate the modification of H-diamond with Pyr-NHS and antibody. Shifts of IDS(max) at VGS = -500 mV in transfer characteristics of H-diamond SGFET was observed to determine N-protein concentration in phosphate buffer solution. Good linear relationship between IDS(max) and log10(N-protein) was observed from 10-14 to 10-5 g/mL with goodness of fit R2 = 0.90 and sensitivity of 1.98 µA/Log10 [concentration of N-protein] at VDS = -500 mV, VGS = -500 mV. Consequently, this prepared H-diamond SGFET biosensor may provide a new idea for diagnosis of SARS-CoV-2 due to a wide detection range from 10-14 to 10-5 g/mL and low limit of detection 10-14 g/mL.
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False detection of SARS-CoV-2 is detrimental to epidemic prevention and control. The scalar nature of the detected signal and the imperfect target recognition property of developed methods are the root causes of generating false signals. Here, we reported a collaborative system of CRISPR-Cas13a coupling with the stabilized graphene field-effect transistor, providing high-intensity vector signals for detecting SARS-CoV-2. In this collaborative system, SARS-CoV-2 RNA generates a "big subtraction" signal with a right-shifted feature, whereas any untargets cause the left-shifted characteristic signal. Thus, the false detection of SARS-CoV-2 is eliminated. High sensitivity with 0.15 copies/µL was obtained. In addition, the wide concerned instability of the graphene field-effect transistor for biosensing in solution environment was solved by the hydrophobic treatment to its substrate, which should be a milestone in advancing it's engineering application. This collaborative system characterized by the high-intensity vector signal and amazing stability significantly advances the accurate SARS-CoV-2 detection from the aspect of signal nature.
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Viral outbreaks, which include the ongoing coronavirus disease 2019 (COVID-19) pandemic provoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are a major global crisis that enormously threaten human health and social activities worldwide. Consequently, the rapid and repeated treatment and isolation of these viruses to control their spread are crucial to address the COVID-19 pandemic and future epidemics of novel emerging viruses. The application of cost-efficient, rapid, and easy-to-operate detection devices with miniaturized footprints as a substitute for the conventional optic-based polymerase chain reaction (PCR) and immunoassay tests is critical. In this context, semiconductor-based electrical biosensors are attractive sensing platforms for signal readout. Therefore, this study aimed to examine the electrical sensing of patient-derived SARS-CoV-2 samples by harnessing the activity of DNA aptamers directed against spike proteins on viral surfaces. We obtained rapid and sensitive virus detection beyond the Debye length limitation by exploiting aptamers coupled with alkaline phosphatases, which catalytically generate free hydrogen ions which can readily be measured on pH meters or ion-sensitive field-effect transistors. Furthermore, we demonstrated the detection of the viruses of approximately 100 copies/µL in 10 min, surpassing the capability of typical immunochromatographic assays. Therefore, our newly developed technology has great potential for point-of-care testing not only for SARS-CoV-2, but also for other types of pathogens and biomolecules.
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Many outbreaks of emerging disease (e.g., avian influenza, SARS, MERS, Ebola, COVID-19) are caused by viruses. In addition to direct person-to-person transfer, the movement of these viruses through environmental matrices (water, air, and food) can further disease transmission. There is a pressing need for rapid and sensitive virus detection in environmental matrices. Nanomaterial-based sensors (nanosensors), which take advantage of the unique optical, electrical, or magnetic properties of nanomaterials, exhibit significant potential for environmental virus detection. Interactions between viruses and nanomaterials (or recognition agents on the nanomaterials) can induce detectable signals and provide rapid response times, high sensitivity, and high specificity. Facile and field-deployable operations can be envisioned due to the small size of the sensing elements. In this frontier review, we summarize virus transmission via environmental pathways and then comprehensively discuss recent applications of nanosensors to detect various viruses. This review provides guidelines for virus detection in the environment through the use of nanosensors as a tool to decrease environmental transmission of current and emerging diseases.
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During the COVID'19 outbreak, biosensing devices won increasing relevance, demonstrating their potential in the medical diagnostic field. Hence, the present review reports on the main advances in 2D-ZnO nanostructure-based biosensors. So far, bulk ZnO has shown potential for biosensing, optical, and power electronic applications, mainly based on its wide band gap. In the post graphene era, its 2-D allotropes like ZnO sheets and ZnO nanoribbons have outperformed the bulk ZnO structures for specific applications. ZnO demonstrates various stable and feasible morphologies: nanotubes, nanowires, nanorods, nanosheets, nanoparticles, and nanobelts. As a matrix layer in biosensing applications, ZnO strongly binds to biomolecules due to its high isoelectric point (IEP) and shows a strong sensitivity due to the high surface-to-volume ratio. Further, ZnO nanostructures used as a matrix layer play an important role in inhibiting specific biological interactions and hence improve the sensitivity of sensing devices. Further, bioselective layers are typically immobilized onto ZnO either by direct adsorption or by covalent binding. ZnO based biosensors are categorized into optical, piezoelectric, and electrochemical biosensors, among others, based on their biosensing mechanism. In particular, electrochemical sensors produce signals via an electrical pathway for detecting and monitoring the target molecules. Optical sensors produce signals based on luminescence or reflectance, among others. Piezoelectric biosensors produce signals by mass loading of the piezoelectric material. ZnO-based FET biosensors are also reported, showing sensing application by the change in the channel's conductance. Further, recent literature on the detection of COVID-19 using ZnO nanostructures is presented.
ABSTRACT
The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has proven the need for developing reliable and affordable technologies to detect pathogens. Particularly, the detecting the genome in wastewater could be an indicator of the transmission rate to alert on new outbreaks. However, wastewater-based epidemiology remains a technological challenge to develop affordable technologies for sensing pathogens. In this work, we introduce a label-free and portable field-effect transistor (FET)-based sensor to detect N and ORF1ab genes of the SARS-CoV-2 genome. Our sensor integrates the reverse transcription loop-mediated isothermal amplification (RT-LAMP) reaction as a cost-effective molecular detection exhibiting high specificity. The detection relies upon pH changes, due to the RT-LAMP reaction products, which are detected through a simple, but effective, extended-gate FET sensor (EGFET). We evaluate the proposed device by measuring real wastewater samples to detect the presence of SARS-CoV-2 genome, achieving a limit of detection of 0.31 × 10−3 ng/μL for end-point measurement. Moreover, we find the ability of the sensor to perform real-time-like analysis, showing that the RT-LAMP reaction pro-vides a good response after 15 min for concentrations as low as 0.37 ng/μL. Hence, we show that our EGFET sensor offers a powerful tool to detect the presence of the SARS- CoV-2 genome with a naked-eye method, in a straightforward way than the conventional molecular methods for wastewater analysis.
ABSTRACT
Rapid and accurate identification of a pathogen is crucial for disease control and prevention of the epidemic of emerging infectious like SARS-CoV-2. However, no foolproof gold standard assay exists to date. Nucleic acid-based molecular diagnostic tests have been established for identifying COVID-19. However, viral RNAs are highly unstable in handling with poor laboratory procedures, leading to a false negative that accelerates the spread of the disease. Detection of the spike protein (S1) of the SARS-CoV-2 virus through a proper receptor, commonly used in antigen-based rapid testing kits, also suffers from false-negative predictions due to decreasing viral titers in clinical specimens. Organic field-effect transistor (OFET)-based sensors can be highly sensitive upon properly integrating receptors in the conducting channel. This work demonstrates how angiotensin-converting enzyme 2 (ACE2) molecules can be used as receptor molecules of the SARS-CoV-2 virus in the OFET platform. Integration of ACE2 molecules into pentacene grain boundaries has been studied through the statistical analysis of rough surfaces in terms of lateral correlation length and interface width. The uniform coating of ACE2 molecules has been confirmed through growth studies to achieve better ingress of the receptors into the conducting channel at the semiconductor/dielectric interface of OFETs. We have observed less than a minute detection time with 94% sensitivity, which is the highest reported value. The sensor works with a saliva sample, requiring no sample preparation or virus transfer medium. A prototype module developed for remote monitoring confirms the suitability for point-of-care (POC) application at large-scale testing in more crowded areas like airports, railway stations, shopping malls, etc.