Using Nanomaterials for SARS-CoV-2 Sensing via Electrochemical Techniques.

Advancing low-cost and user-friendly innovations to benefit public health is an important task of scientific and engineering research. According to the World Health Organization (WHO), electrochemical sensors are being developed for low-cost SARS-CoV-2 diagnosis, particularly in resource-limited settings. Nanostructures with sizes ranging from 10 nm to a few micrometers could deliver optimum electrochemical behavior (e.g., quick response, compact size, sensitivity and selectivity, and portability), providing an excellent alternative to the existing techniques. Therefore, nanostructures, such as metal, 1D, and 2D materials, have been successfully applied in in vitro and in vivo detection of a wide range of infectious diseases, particularly SARS-CoV-2. Electrochemical detection methods reduce the cost of electrodes, provide analytical ability to detect targets with a wide variety of nanomaterials, and are an essential strategy in biomarker sensing as they can rapidly, sensitively, and selectively detect SARS-CoV-2. The current studies in this area provide fundamental knowledge of electrochemical techniques for future applications.

SARS‐CoV‐2 N Gene‐Targeted Anodic Stripping Voltammetry Sensor Using a Novel CoS‐NGQD/Pt@Pd Platform and Au‐DNA‐CdTe QD Probe

Rapid screening of individuals infected with severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) is necessary to contain contagion in a large population. Nucleic acid‐based gold standard assays are time‐consuming, and nucleic acid amplification is mandatory and expensive, impeding the containment of the coronavirus disease 2019 (COVID‐19) outbreak. To overcome the aforementioned disadvantages, this study deals with a specially designed gold (Au)‐deoxyribonucleic acid (DNA)‐cadmium telluride (CdTe) quantum dot (QD) probe to target two sections of the nucleocapsid (N) gene of SARS‐CoV‐2 ribonucleic acid (RNA) of three variants (B.1.1.529, B.1.617.2, and B.1.351). A duplex‐specific nuclease (DSN)‐assisted highly selective release of signaling probes enable higher specificity, and an Au‐supported DNA probe is incorporated to carry many CdTe QD signaling probes. After dissolution, the generated Cd2+ ions are quantified at the novel cobalt sulfide (CoS)‐nitrogen‐doped graphene QD (NGQD)/platinum (Pt)@palladium (Pd) electrode with extraordinary sensitivity through square wave anodic stripping voltammetry (SWASV). The developed sensor exhibits a wide range of detection (10 to 108 copies µL−1) and a lower detection limit (0.12 copies µL−1), without any amplification. The selectivity of the sensor is tested against MERS and HCoV‐NL63, and real‐time detection is performed on heat‐inactivated viral samples, which show excellent selectivity. [ FROM AUTHOR]

Electrochemical Impedance-Based Biosensors for the Label-Free Detection of the Nucleocapsid Protein from SARS-CoV-2.

Diagnosis of coronavirus disease (COVID-19) is important because of the emergence and global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time polymerase chain reaction (PCR) is widely used to diagnose COVID-19, but it is time-consuming and requires sending samples to test centers. Thus, the need to detect antigens for rapid on-site diagnosis rather than PCR is increasing. We quantified the nucleocapsid (N) protein in SARS-CoV-2 using an electro-immunosorbent assay (El-ISA) and a multichannel impedance analyzer with a 96-interdigitated microelectrode sensor (ToAD). The El-ISA measures impedance signals from residual detection antibodies after sandwich assays and thus offers highly specific, label-free detection of the N protein with low cross-reactivity. The ToAD sensor enables the real-time electrochemical detection of multiple samples in conventional 96-well plates. The limit of detection for the N protein was 0.1 ng/mL with a detection range up to 10 ng/mL. This system did not detect signals for the S protein. While this study focused on detecting the N protein in SARS-CoV-2, our system can also be widely applicable to detecting various biomolecules involved in antigen-antibody interactions.

Capacitive biosensor based on vertically paired electrodes for the detection of SARS-CoV-2.

Vertically paired electrodes (VPEs) with multiple electrode pairs were developed for the enhancement of capacitive measurements by optimizing the electrode gap and number of electrode pairs. The electrode was fabricated using a conductive polymer layer of PEDOT:PSS instead of Ag and Pt metal electrodes to increase the VPE fabrication yield because the PEDOT:PSS layer could be effectively etched using a reactive dry etching process. In this study, sensitivity enhancement was realized by decreasing the electrode gap and increasing the number of VPE electrode pairs. Such an increase in sensitivity according to the electrode gap and the number of electrode pairs was estimated using a model analyte for an immunoassay. Additionally, a computer simulation was performed using VPEs with different electrode gaps and numbers of VPE electrode pairs. Finally, VPEs with multiple electrode pairs were applied for SARS-CoV-2 nucleoprotein (NP) detection. The capacitive biosensor based on the VPE with immobilized anti-SARS-CoV-2 NP was applied for the specific detection of SARS-CoV-2 in viral cultures. Using viral cultures of SARS-CoV-2, SARS-CoV, MERS-CoV, and CoV-strain 229E, the limit of detection (LOD) was estimated to satisfy the cutoff value (dilution factor of 1/800) for the medical diagnosis of COVID-19, and the assay results from the capacitive biosensor were compared with commercial rapid kit based on a lateral flow immunoassay.

Clinical Utility of Biosensing Platforms for Confirmation of SARS-CoV-2 Infection.

Despite collaborative efforts from all countries, coronavirus disease 2019 (COVID-19) pandemic has been continuing to spread globally, forcing the world into social distancing period, making a special challenge for public healthcare system. Before vaccine widely available, the best approach to manage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is to achieve highest diagnostic accuracy by improving biosensor efficacy. For SARS-CoV-2 diagnostics, intensive attempts have been made by many scientists to ameliorate the drawback of current biosensors of SARS-CoV-2 in clinical diagnosis to offer benefits related to platform proposal, systematic analytical methods, system combination, and miniaturization. This review assesses ongoing research efforts aimed at developing integrated diagnostic tools to detect RNA viruses and their biomarkers for clinical diagnostics of SARS-CoV-2 infection and further highlights promising technology for SARS-CoV-2 specific diagnosis. The comparisons of SARS-CoV-2 biomarkers as well as their applicable biosensors in the field of clinical diagnosis were summarized to give scientists an advantage to develop superior diagnostic platforms. Furthermore, this review describes the prospects for this rapidly growing field of diagnostic research, raising further interest in analytical technology and strategic plan for future pandemics.

Trending Technology of Glucose Monitoring during COVID-19 Pandemic: Challenges in Personalized Healthcare.

The COVID-19 pandemic has continued to spread rapidly, and patients with diabetes are at risk of experiencing rapid progression and poor prognosis for appropriate treatment. Continuous glucose monitoring (CGM), which includes accurately tracking fluctuations in glucose levels without raising the risk of coronavirus exposure, becomes an important strategy for the self-management of diabetes during this pandemic, efficiently contributing to the diabetes care and the fight against COVID-19. Despite being less accurate than direct blood glucose monitoring, wearable noninvasive systems can encourage patient adherence by guaranteeing reliable results through high correlation between blood glucose levels and glucose concentrations in various other biofluids. This review highlights the trending technologies of glucose sensors during the ongoing COVID-19 pandemic (2019-2020) that have been developed to make a significant contribution to effective management of diabetes and prevention of coronavirus spread, from off-body systems to wearable on-body CGM devices, including nanostructure and sensor performance in various biofluids. The advantages and disadvantages of various human biofluids for use in glucose sensors are also discussed. Furthermore, the challenges faced by wearable CGM sensors with respect to personalized healthcare during and after the pandemic are deliberated to emphasize the potential future directions of CGM devices for diabetes management.

Electrochemical Immunosensor for the Early Detection of Rheumatoid Arthritis Biomarker: Anti-Cyclic Citrullinated Peptide Antibody in Human Serum Based on Avidin-Biotin System.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that produces a progressive inflammatory response that leads to severe pain, swelling, and stiffness in the joints of hands and feet, followed by irreversible damage of the joints. The authors developed a miniaturized, label-free electrochemical impedimetric immunosensor for the sensitive and direct detection of arthritis Anti-CCP-ab biomarker. An interdigitated-chain-shaped microelectrode array (ICE) was fabricated by taking the advantage of microelectromechanical systems. The fabricated ICE was modified with a self-assembled monolayer (SAM) of Mercaptohexanoic acid (MHA) for immobilization of the synthetic peptide bio-receptor (B-CCP). The B-CCP was attached onto the surface of SAM modified ICE through a strong avidin-biotin bio-recognition system. The modified ICE surface with the SAM and bio-molecules (Avidin, B-CCP, Anti-CCP-ab and BSA) was morphologically and electrochemically characterized. The change in the sensor signal upon analyte binding on the electrode surface was probed through the electrochemical impedance spectroscopy (EIS) property of charge-transfer resistance (Rct) of the modified electrodes. EIS measurements were target specific and the sensor response was linearly increased with step wise increase in target analyte (Anti-CCP-ab) concentrations. The developed sensor showed a linear range for the addition of Anti-CCP-ab between 1 IU mL-1 → 800 IU mL-1 in phosphate buffered saline (PBS) and Human serum (HS), respectively. The sensor showed a limit of detection of 0.60 IU mL-1 and 0.82 IU mL-1 in the PBS and HS, respectively. The develop bio-electrode showed a good reproducibility (relative standard deviation (RSD), 1.52%), selectivity and stability (1.5% lost at the end of 20th day) with an acceptable recovery rate (98.0% → 101.18%) and % RSD's for the detection of Anti-CCP-ab in spiked HS samples.