Functional Nanomaterials for Electrochemical SRAS-CoV-2 Biosensors: a Review

The pandemic outbreak of COVID-19 has posed a threat to public health globally, and rapid and accurate identification of the viruses is crucial for controlling COVID-19. In recent years, nanomaterial-based electrochemical sensing techniques hold immense potential for molecular diagnosis with high sensitivity and specificity. In this review, we briefly introduced the structural characteristics and routine detection methods of SARS-CoV-2, then summarized the associated properties and mechanisms of the electrochemical biosensing methods. On the above basis, the research progress of electrochemical biosensors based on gold nanomaterials, oxide nanomaterials, carbon-based nanomaterials and other nanomaterials for rapid and accurate detection of virus were reviewed. Finally, the future applications of nanomaterial-based biosensors for biomolecular diagnostics were pointed out. © 2023 Science Press. All rights reserved.

Functional Nanomaterials for Electrochemical SRAS-CoV-2 Biosensors: a Review

The pandemic outbreak of COVID-19 has posed a threat to public health globally, and rapid and accurate identification of the viruses is crucial for controlling COVID-19. In recent years, nanomaterial-based electrochemical sensing techniques hold immense potential for molecular diagnosis with high sensitivity and specificity. In this review, we briefly introduced the structural characteristics and routine detection methods of SARS-CoV-2, then summarized the associated properties and mechanisms of the electrochemical biosensing methods. On the above basis, the research progress of electrochemical biosensors based on gold nanomaterials, oxide nanomaterials, carbon-based nanomaterials and other nanomaterials for rapid and accurate detection of virus were reviewed. Finally, the future applications of nanomaterial-based biosensors for biomolecular diagnostics were pointed out. © 2023 Science Press. All rights reserved.

Binding-Induced Folding of DNA Oligonucleotides Targeted to the Nucleocapsid Gene Enables Electrochemical Sensing of SARS-CoV-2.

In the wake of the COVID-19 pandemic, millions of confirmed cases and deaths have been reported around the world. COVID-19 spread can be slowed and eventually stopped by a rapid test to diagnose positive cases of the disease on the spot. It is still important to test for COVID-19 quickly regardless of the availability of the vaccine. Using the binding-induced folding principle, we developed an electrochemical test for detecting SARS-CoV-2 with no RNA extraction or nucleic acid amplification. The test showed high sensitivity with a limit of detection of 2.5 copies/µL. An electrode mounted with a capture probe and a portable potentiostat are used to conduct the test. To target the N-gene of SARS-CoV-2, a highly specific oligo-capturing probe was used. Based on the binding-induced "folding" principle, the sensor detects binding between the oligo and RNA. When the target is absent, the capture probe tends to form a hairpin as a secondary structure, retaining the redox reporter close to the surface. This can be seen as a large anodic and cathodic peak current. When the target RNA is present, the hairpin structure will open to hybridize with its complementary sequence, causing the redox reporter to pull away from the electrode. Consequently, the anodic/cathodic peak currents are reduced, indicating the presence of the SARS-CoV-2 genetic material. Validation of the test performance was performed using 122 COVID-19 clinical samples (55 positives and 67 negatives) and benchmarked to the gold standard reverse transcription-polymerase chain reaction (RT-PCR) test. As a result of our test, the accuracy, sensitivity, and specificity have been measured at 98.4%, 98.2%, and 98.5%, respectively.

Scheelite-type rare earth vanadates TVO4 (T = Ho, Y, Dy) electrocatalysts: Investigation and comparison of T site variations towards bifunctional electrochemical sensing application

In the wake of the recent COVID-19 pandemic, antibiotics are now being used in unprecedented quantities across the globe, raising major concerns regarding pharmaceutical pollution and antimicrobial resistance (AMR). In view of the incoming tide of alarming apprehensions regarding their aftermath, it is critical to investigate control strategies that can halt their spread. Rare earth vanadates notable for their fundamental and technological significance are increasingly being used as electrochemical probes for the precise quantification of various pharmaceutical compounds. However, a comprehensive study of the role of the cationic site in tailoring the response mechanism is relatively unexplored. Hence, in this work we present a facile hydrothermal synthesis route of rare earth vanadates TVO4 (T = Ho, Y, Dy) as efficient electrocatalyst for the simultaneous detection of nitrofurazone (NF) and roxarsone (RX). There appears to be a significant correlation between T site substitution, morphological and the electrochemical properties of rare earth metal based vanadates. Following a comparative study of the electrochemical activity, the three rare-earth vanadates were found to respond differently depending on their composition of T sites. The results demonstrate that Dy-based vanadate displays increased electrical conductivity and rapid charge transfer characteristics. Thus, under optimal reaction conditions DyVO4- based electrodes imparts outstanding selectivity towards the detection of NF and RX with an extensive detection window of NF = 0.01–264 µM & RX = 0.01–21 µM and 36–264 µM and low detection limit (0.002, 0.0009 µM for NF and RX, respectively). In real-time samples, the proposed sensor reveals itself to be a reliable electrode material capable of detecting residues such as NF and RX. © 2022 Elsevier B.V.

Two-Dimensional Transition Metal Dichalcogenide Based Biosensors: From Fundamentals to Healthcare Applications.

There has been an exponential surge in reports on two-dimensional (2D) materials ever since the discovery of graphene in 2004. Transition metal dichalcogenides (TMDs) are a class of 2D materials where weak van der Waals force binds individual covalently bonded X-M-X layers (where M is the transition metal and X is the chalcogen), making layer-controlled synthesis possible. These individual building blocks (single-layer TMDs) transition from indirect to direct band gaps and have fascinating optical and electronic properties. Layer-dependent opto-electrical properties, along with the existence of finite band gaps, make single-layer TMDs superior to the well-known graphene that paves the way for their applications in many areas. Ultra-fast response, high on/off ratio, planar structure, low operational voltage, wafer scale synthesis capabilities, high surface-to-volume ratio, and compatibility with standard fabrication processes makes TMDs ideal candidates to replace conventional semiconductors, such as silicon, etc., in the new-age electrical, electronic, and opto-electronic devices. Besides, TMDs can be potentially utilized in single molecular sensing for early detection of different biomarkers, gas sensors, photodetector, and catalytic applications. The impact of COVID-19 has given rise to an upsurge in demand for biosensors with real-time detection capabilities. TMDs as active or supporting biosensing elements exhibit potential for real-time detection of single biomarkers and, hence, show promise in the development of point-of-care healthcare devices. In this review, we provide a historical survey of 2D TMD-based biosensors for the detection of bio analytes ranging from bacteria, viruses, and whole cells to molecular biomarkers via optical, electronic, and electrochemical sensing mechanisms. Current approaches and the latest developments in the study of healthcare devices using 2D TMDs are discussed. Additionally, this review presents an overview of the challenges in the area and discusses the future perspective of 2D TMDs in the field of biosensing for healthcare devices.

Label-free electrochemical aptasensor for the detection of SARS-CoV-2 spike protein based on carbon cloth sputtered gold nanoparticles.

The proliferation and transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or the (COVID-19) disease, has become a threat to worldwide biosecurity. Therefore, early diagnosis of COVID-19 is crucial to combat the ongoing infection spread. In this study we propose a flexible aptamer-based electrochemical sensor for the rapid, label-free detection of SARS-CoV-2 spike protein (SP). A platform made of a porous and flexible carbon cloth, coated with gold nanoparticles, to increase the conductivity and electrochemical performance of the material, was assembled with a thiol functionalized DNA aptamer via S-Au bonds, for the selective recognition of the SARS-CoV-2 SP. The various steps for the sensor preparation were followed by using scanning electron microscopy, cyclic voltammetry and differential pulse voltammetry (DPV). The proposed platform displayed good mechanical stability, revealing negligible changes on voltammetric responses to bending at various angles. Quantification of SARS-CoV-2 SP was performed by DPV and chronopotentiometry (CP), exploiting the changes of the electrical signals due the [Fe(CN)6]3-/4- redox probe, when SARS-CoV-2 SP binds to the aptamer immobilized on the electrode surface. Current density, in DPV, and square root of the transition time, in CP, varied linearly with the log[ SARS-CoV-2 SP], providing lower limits of detection (LOD) of 0.11 ng/mL and 37.8 ng/mL, respectively. The sensor displayed good selectivity, repeatability, and was tested in diluted human saliva, spiked with different SARS-CoV-2 SP concentrations, providing LODs of 0.167 ng/mL and 46.2 ng/mL for DPV and CP, respectively.

Simultaneous detection of sepsis host response biomarkers in whole blood using electrochemical biosensor.

Sepsis is a silent killer, caused by a syndromic reaction of the body's immune system to an infection that is typically the ultimate pathway to mortality due to numerous infectious diseases, including COVID-19 across the world. In the United States alone, sepsis claims 220,000 lives, with a dangerously high fatality rate between 25% and 50%. Early detection and treatment can avert 80% of sepsis mortality which is currently unavailable in most healthcare institutions. The novelty in this work is the ability to simultaneously detect eight (IL-6, IL-8, IL-10, IP-10, TRAIL, d-dimer, CRP, and G-CSF) heterogeneous immune response biomarkers directly in whole blood without the need for dilution or sample processing. The DETecT sepsis (Direct Electrochemical Technique Targeting Sepsis) 2.0 sensor device leverages electrochemical impedance spectroscopy as a technique to detect subtle binding interactions at the metal/semi-conductor sensor interface and reports results within 5 min using only two drops (~100 µl) of blood. The device positively (r >0.87) correlated with lab reference standard LUMINEX for clinical translation using 40 patient samples. The developed device showed diagnostic accuracy greater than 80% (AUC >0.8) establishing excellent specific and sensitive response. Portable handheld user-friendly feature coupled with precise quantification of immune biomarkers makes the device amenable in a versatile setting providing insights on patient's immune response. This work highlights an innovative solution of enhancing sepsis care and management in the absence of a decision support device in the continuum of sepsis care.

Sensing of C-Reactive Protein Using an Extended-Gate Field-Effect Transistor with a Tungsten Disulfide-Doped Peptide-Imprinted Conductive Polymer Coating.

C-reactive protein (CRP) is a non-specific biomarker of inflammation and may be associated with cardiovascular disease. In recent studies, systemic inflammatory responses have also been observed in cases of coronavirus disease 2019 (COVID-19). Molecularly imprinted polymers (MIPs) have been developed to replace natural antibodies with polymeric materials that have low cost and high stability and could thus be suitable for use in a home-care system. In this work, a MIP-based electrochemical sensing system for measuring CRP was developed. Such a system can be integrated with microfluidics and electronics for lab-on-a-chip technology. MIP composition was optimized using various imprinting template (CRP peptide) concentrations. Tungsten disulfide (WS2) was doped into the MIPs. Doping not only enhances the electrochemical response accompanying the recognition of the template molecules but also raises the top of the sensing range from 1.0 pg/mL to 1.0 ng/mL of the imprinted peptide. The calibration curve of the WS2-doped peptide-imprinted polymer-coated electrodes in the extended-gate field-effect transistor platform was obtained and used for the measurement of CRP concentration in real human serum.

Nanobiotechnology enabled approaches for wastewater based epidemiology.

The impacts of the ongoing coronavirus pandemic highlight the importance of environmental monitoring to inform public health safety. Wastewater based epidemiology (WBE) has drawn interest as a tool for analysis of biomarkers in wastewater networks. Wide scale implementation of WBE requires a variety of field deployable analytical tools for real-time monitoring. Nanobiotechnology enabled sensing platforms offer potential as biosensors capable of highly efficient and sensitive detection of target analytes. This review provides an overview of the design and working principles of nanobiotechnology enabled biosensors and recent progress on the use of biosensors in detection of biomarkers. In addition, applications of biosensors for analysis of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus are highlighted as they relate to the potential expanded use of biosensors for WBE-based monitoring. Finally, we discuss the opportunities and challenges in future applications of biosensors in WBE for effective monitoring and investigation of public health threats.

Rapid SARS-CoV-2 Detection Using Electrochemical Immunosensor.

The outbreak of the coronavirus disease (COVID-19) pandemic caused by the novel coronavirus (SARS-CoV-2) has been declared an international public health crisis. It is essential to develop diagnostic tests that can quickly identify infected individuals to limit the spread of the virus and assign treatment options. Herein, we report a proof-of-concept label-free electrochemical immunoassay for the rapid detection of SARS-CoV-2 virus via the spike surface protein. The assay consists of a graphene working electrode functionalized with anti-spike antibodies. The concept of the immunosensor is to detect the signal perturbation obtained from ferri/ferrocyanide measurements after binding of the antigen during 45 min of incubation with a sample. The absolute change in the [Fe(CN)6]3-/4- current upon increasing antigen concentrations on the immunosensor surface was used to determine the detection range of the spike protein. The sensor was able to detect a specific signal above 260 nM (20 µg/mL) of subunit 1 of recombinant spike protein. Additionally, it was able to detect SARS-CoV-2 at a concentration of 5.5 × 105 PFU/mL, which is within the physiologically relevant concentration range. The novel immunosensor has a significantly faster analysis time than the standard qPCR and is operated by a portable device which can enable on-site diagnosis of infection.