Utilizing Electrochemical-Based Sensing Approaches for the Detection of SARS-CoV-2 in Clinical Samples: A Review

Abstract

The development of precise and efficient diagnostic tools enables early treatment and proper isolation of infected individuals, hence limiting the spread of coronavirus disease 2019 (COVID-19). The standard diagnostic tests used by healthcare workers to diagnose severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have some limitations, including longer detection time, the need for qualified individuals, and the use of sophisticated bench-top equipment, which limit their use for rapid SARS-CoV-2 assessment. Advances in sensor technology have renewed the interest in electrochemical biosensors miniaturization, which provide improved diagnostic qualities such as rapid response, simplicity of operation, portability, and readiness for on-site screening of infection. This review gives a condensed overview of the current electrochemical sensing platform strategies for SARS-CoV-2 detection in clinical samples. The fundamentals of fabricating electrochemical biosensors, such as the chosen electrode materials, electrochemical transducing techniques, and sensitive biorecognition molecules, are thoroughly discussed in this paper. Furthermore, we summarised electrochemical biosensors detection strategies and their analytical performance on diverse clinical samples, including saliva, blood, and nasopharyngeal swab. Finally, we address the employment of miniaturized electrochemical biosensors integrated with microfluidic technology in viral electrochemical biosensors, emphasizing its potential for on-site diagnostics applications.

Keywords: COVID-19; SARS-CoV-2; diagnostic methods; electrochemical biosensor; microfluidic electrochemical devices; miniaturised electrochemical sensor; point of care (POC).

Figure 1

Schematic illustration of direct enzyme-linked immunosorbent assay (ELISA) that generates a color signal when an antibody binds to a specific antigen (protein).

Figure 2

Schematic illustration of electrochemical biosensors platform based on label-free and labelled systems with various types of biorecognition molecules and electrochemical transducing techniques for the detection of SARS-CoV-2 in clinical samples. Adapted with permission from ref. [79]. Copyright 2020 Elsevier.

Figure 3

The schematic illustration for general fabrication of electrochemical immunosensor based on label-free and labelled systems (e.g., sandwich-type immunosensor) using gold electrode substrates.

Figure 4

Schematic representation of fabrication steps for a label free impedimetric immunosensor for detection of SARS-CoV-2 in a saliva sample. (a) CV and (b) EIS measurements for each fabrication step in 0.2 mol/L PBS, pH 7.4, 0.1 mol/L KCl containing 5.0 mmol/L of [Fe(CN₆)]³⁻/⁴⁻ for the working electrodes. (c) CV measurement of the immunosensor after the incubation with different antigen concentrations. Reproduced with permission from [97]. Copyright 2021 Multidisciplinary Digital Publishing Institute (MDPI).

Figure 5

The schematic illustration for general fabrication of label-free and labelled electrochemical DNA sensors based on gold electrode substrates via self-assembly monolayer technique (thiol chemistry).

Figure 6

The fabrication of electrochemical sensors based on a labelled system using DNA aptamer-antibody conjugate as recognition elements for detection of SARS-CoV-2 virus. (a) Detection of SARS-CoV-2 viral particles by the fabricated sensor coated with gold on the electrode surface. (b) The design of the sensor consists of an analyte-specific antibody tethered to a linker composed of dsDNA that also includes the redox probe ferrocene. (c) The changes in electrical properties that occurred on the electrode sensor surface. (d–f) The peak chronoamperometric current of fabricated biosensor after exposure to target. The figure has been reproduced with permission from [100]. Copyright 2021 American Chemical Society (ACS).

Figure 7

The surface modification of miniaturized electrochemical sensors with nanomaterials such as (a) graphene, (b) gold nanoparticle (AuNPs), and (c) cobalt-functionalized TiO₂ nanotubes (Co-TNTs) together with its electrochemical measurements for rapid detection of SARS-CoV-2. (a) has been reproduced from [93] and (c) from [102] with permission from the Multidisciplinary Digital Publishing Institute (MDPI). (b) has been reproduced with permission from [108]. Copyright 2022 American Chemical Society (ACS).

Figure 8

Schematic representation of the principal detection of label-free paper-based electrochemical DNA biosensors for SARS-CoV-2 detection in nasal swabs or saliva of the patients. (a) Step 1: Samples will be collected from the nasal swab or saliva of the infected individuals. (b) Step 2: The viral RNA of SARS-CoV-2 will be extracted from samples. (c) Step 3: The extracted RNA samples will be dropped onto the paper-based electrochemical DNA biosensor and (d) incubated for 5 min. (e) Step 4: The electrochemical measurement will be performed using a potentiostat. The figure has been reproduced with permission from [108]. Copyright 2022 American Chemical Society (ACS).

Figure 9

The miniaturized label-free electrochemical sensor is integrated with smartphone-based “cloud” directory for the real-time surveillance of COVID-19 through geo-tagging. This figure has been adapted with permission from ref. [178]. Copyright 2020 Elsevier.

Figure 10

(a) A 3D-nanoprinted COVID-19 microfluidic chip (3DcC) that fabricated using PDMS. (b) The detection of 3DcC at different concentrations of SARS-CoV-2 antibodies in PBS solution using the electrical impedance spectroscopy (EIS) method. This figure has been reproduced with permission from [103]. Copyright 2022 John Wiley and Sons.