The potential of electrochemistry for the detection of coronavirus-induced infections

Abstract

Human coronaviruses (HCoV) are no stranger to the global environment. The etiology of previous outbreaks with reported symptoms of respiratory tract infections was attributed to different coronavirus strains, with the latest global pandemic in 2019 also belonging to the coronavirus family. Timely detection, effective therapeutics and future prevention are stake key holders in the management of coronavirus-induced infections. Apart from the gold standard clinical diagnostics, electrochemical techniques have also demonstrated their great potentials in the detection of different viruses and their correlated antibodies and antigens, showing high sensitivities and selectivities, and faster times for the analysis. This article aims to critically review the multifaceted electrochemical approaches, not only in the development of point-of-care portable devices but also as alternative detection strategies that can be coupled with traditional methods for the detection of various strains of coronaviruses.

Keywords: Biosensing; Biosensors; COVID-19; Coronavirus; Detection; Diagnostic; Electrochemical methods; Electrochemistry; Infections; SARS-CoV-2.

Fig. 1

Overview of the electrochemical approaches on the detection of coronavirus-induced infections: (i) Detection of proteins, (ii) Detection of viral DNA, (iii) Detection of PCR products, (iv) Detection of ROS.

Fig. 2

Experimental setups for electrochemical detection of coronavirus related proteins: (A) In₂O₃ nanowire FET modified with fibronectin for the detection of N protein. The current response is measured after the addition of increasing concentrations of N protein [30]. Reproduced with permission from Ref. [30]; (B) (i) low density CNTFET, (ii, iii) atomic force microscopy images of CNT before and after immobilization of Fn probe (scan area of 1 μm × 1 μm), (iv) plot of I_ds versus time due to addition of increasing N protein concentrations of 5, 10 and 50 nM, data points (in black), Langmuir isotherm model fitting (in red) [33]. Reproduced with permission from Ref. [33]; (C) GFET in the sensing of SARS-CoV-2 S protein [36]. Reproduced with permission from Ref. [36]; (D) (i) electrochemical immunosensor for MERS-CoV with an assembled array of gold nanoparticle-modified carbon electrodes, (ii) immunosensor fabrication, (iii) change in peak current due to addition of MERS-CoV antigen observed via square-wave voltammetry [37]. Reproduced with permission from Ref. [37].

Fig. 3

Experimental principles of label-based and label-free assays in the detection of viral DNA: (A) Schematic diagram of DNA hybridization sensor on gold films with enzymatic electrochemical detection of SARS-CoV gene sequence [42]. Adapted with permission from Ref. [42]; (B) Schematic diagram of DNA hybridization sensor using gold nanostructured screen-printed carbon electrodes for SARS-CoV virus detection [43]. Adapted with permission from Ref. [43]; (C) Schematic diagram on a screen-printed electrochemical biosensor for the detection of released purine bases of coronavirus aviair (i) immobilization of ssDNA probe onto the gold electrode, (ii) hybridization with the complementary target sequence, (iii) washing of the electrode surface, (iv) hydrolysis of dsDNA, (v) electrochemical signal detection [49]. Adapted with permission from Ref. [49]; (D) Schematic diagram on a label-free electrochemical genosensor for COVID-19 diagnosis [50]. Reproduced with permission from Ref. [50].

Fig. 4

Electrochemical detection of PCR amplification products: (A) Experimental principle of Genmark's eSensor® technology (i) hybridization of signal probe to the target DNA, (ii) reaction of target DNA/signal probe with the captured probe in the cartridge's microfluidic chamber, (iii) collection of the voltammetric response from the target DNA [53]. Adapted with permission from Ref. [53]; (B) Schematic diagram on the microarray for detection of target viral and bacterial analytes. Single-stranded biotinylated target sequence is first hybridized to the immobilized complementary probes (A, B and C) before labelling with streptavidin (SA)-horseradish peroxidase (HRP) to enable electrochemical detection [54]. Adapted with permission from Ref. [54]; (C) Electrochemical PCR scheme using graphene oxide nanoparticles as labels for DNA primers: (i) Electrochemical detection on miniaturized electrode; (ii) nanographene oxide reduction current vs PCR cycle number for positive (red) and negative control (blue) [26]. Reproduced with permission from Ref. [26].

Fig. 5

Electrochemical ROS/H₂O₂ system for the detection of SARS-CoV-2 virus: (i) production of mitochondrial ROS in human lung epithelial cells due to SARS-CoV-2 infection; (ii) fabrication of electrochemical system with three needle electrodes functionalized with MWCNTs; (iii) reduction peaks obtained due to selective responses of the released ROS on MWCNTs obtained from two hospitalized patients with COVID-19 infection (d and e in the voltammogram) versus a confirmed negative case (f in the voltammogram) where the intensities of the reduction peak currents correspond to the amount of mitochondrial ROS released as a result of the viral infection; (iv, v) CT scans of COVID-19 patients showing infected lungs; (vi) CT scan of a confirmed negative patient showing no signs of COVID-19 effect on lungs [59]. Reproduced with permission from Ref. [59].