Innovations and Challenges in Electroanalytical Tools for Rapid Biosurveillance of SARS-CoV-2

Abstract

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, preventive social paradigms and vaccine development have undergone serious renovations, which drastically reduced the viral spread and increased collective immunity. Although the technological advancements in diagnostic systems for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) detection are groundbreaking, the lack of sensitive, robust, and consumer-end point-of-care (POC) devices with smartphone connectivity are conspicuously felt. Despite its revolutionary impact on biotechnology and molecular diagnostics, the reverse transcription polymerase chain reaction technique as the gold standard in COVID-19 diagnosis is not suitable for rapid testing. Today's POC tests are dominated by the lateral flow assay technique, with inadequate sensitivity and lack of internet connectivity. Herein, the biosensing advancements in Internet of Things (IoT)-integrated electroanalytical tools as superior POC devices for SARS-CoV-2 detection will be demonstrated. Meanwhile, the impeding factors pivotal for the successful deployment of such novel bioanalytical devices, including the incongruous standards, redundant guidelines, and the limitations of IoT modules will be discussed.

Keywords: Internet of Things; biosurveillance; coronavirus disease 2019; electrochemical biosensors; rapid test.

Figure 1

Integration of standard lateral flow diagnostic tests with printed electronics and IoT modules would result in ideal diagnostic tests known as REASSURED diagnostics to fulfill the sustainable development goals of global biosurveillance. Adapted with permission.^{[ 21 ]} Copyright 2019, Springer Nature.

Figure 2

Multiplex, wireless, and graphene‐based biosensors for SARS‐CoV‐2 antigen and antibody detection (RapidPlex). a) Schematic illustration of salivary and blood viral antigen multisensing using enzyme labeled antibodies as biorecognition element. The produced current from substrate oxidation is transferred by a BLE module to a smartphone with a customized app. b) Rapid and cheap ($0.05) mass production of laser‐engraved flexible sensor arrays, c) disposable and flexible sensors, and d) rapidplex system integration with a PCB with built‐in potentiostat, signal processing, and Bluetooth communication. Adapted with permission.^{[ 44 ]} Copyright 2020, Elsevier.

Figure 3

Magnetic‐amplified SARS‐CoV‐2 biosensor. Enzyme‐linked antibody conjugation with magnetic beads can bind to the target with excellent sensitivity owing to magnetic bead's high surface area and facile magnetic preconcentration on a screen‐printed support. Adapted with permission.^{[ 45 ]} Copyright 2021, Elsevier.

Figure 4

Peptide‐based SARS‐CoV‐2 aptasensor with enhanced anifouling capability. Polyaniline nanowires‐bovine serum albumin cross‐links significantly reduces non‐specific absorption of proteins and other biomolecules. Adapted with permission.^{[ 51 ]} Copyright 2021, American Chemical Society.

Figure 5

Workflow of SARS‐CoV‐2 S and N genes detection. a) Extracted genes are isothermally amplified by RCA technique, then the amplicons are hybridized with redox‐tagged aptamers, which are subsequently detected by voltametric techniques. b) The picture of hand‐held PalmSens4 potentiostat with Bluetooth connectivity for data transfer to a personal computer. Adapted with permission.^{[ 52 ]} Copyright 2021, Springer Nature.

Figure 6

CRISPR‐based biochemical circuit combined with electrochemical biosensing. a) A heterogeneous biochemical circuit composed of paired CRISPR processor, amplification using primer exchange reaction (PER), and genetic data processor and translator into electrical signal. b) Two offset sgRNAs guide a pair of CRISPR (Cas9 D10A) to detect two PAM regions of the target, which subsequently cleaves the gene and cut it into a 3′‐overhang strand. c) Translation and amplification by PER technique. Hairpin 1 functions as a translator, only operating with the presence of the overhang target. Hairpin 2 functions as an amplifier and catalyzes concatemer formation. d) A nucleic acid‐based capture strand is immobilized on the gold electrode to bind with the produced concatemer. A redox‐tagged signal probe forms complementary binding to the concatemer and produces electrochemical signal detected by SWV technique. Adapted with permission.^{[ 63 ]} Copyright 2020, John Wiley and Sons.

Figure 7

3D‐origami‐paper‐based SARS‐CoV‐2 biosensor. A) Device components including three foldable paper‐based electrodes. B) Detection of antibodies against SARS‐CoV‐2 using RBD proteins as the biorecognition element and SWV monitoring of the electrode's response upon target binding. C) The results can be transferred wirelessly to a smartphone. Adapted with permission.^{[ 24b ]} Copyright 2021, Elsevier.

Figure 8

Reagent‐free SARS‐CoV‐2 biosensor. a) Receptor binding with viral particles increases the hydrodynamic diameter and subsequently influences the required time for the redox tag to contact the electrode's surface. b) Biosensor architecture based on immobilized DNA linker with a redox tag, conjugated with antibody against spike proteins and c) negatively charged bioreceptor swings across the electrode when a positive potential is applied, which cause a shift in the hydrodynamic drag force detected by chronoamperometric methods. Adapted with permission.^{[ 66 ]} Copyright 2021, American Chemical Society.

Figure 9

FET‐based SARS‐CoV‐2 biosensor. Anti‐spike antibodies are immobilized on the gate of a graphene‐based transistor. Target‐receptor binding causes a change in the graphene's surface charge distribution, which consequently changes the current passing through the drain. Adapted with permission.^{[ 72b ]} Copyright 2020, American Chemical Society.

Figure 10

Commercial electrochemical biosensors for SARS‐CoV‐2 detection. a) ePlex: Digital microfluidics fluid handling integrated with RT‐PCR amplification and detection via nucleic acid hybridization. The target DNA forms complementary binding to the ferrocene‐tagged signal probe then it can be transferred by digital microfluidics to a gold electrode with a DNA capture probe. The target‐receptor binding can be analyzed by voltametric methods. Adapted with permission.^{[ 72 ]} Copyright 2022, GenMark Diagnostics. b) Sampinute: a magnetic force‐assisted electrochemical sandwich immunoassay for qualitative detection of RBD spike proteins. Antibody conjugated magnetic nanobeads are utilized to target the RBD region of spike proteins, which subsequently forms a sandwich complex with the detection probe on the working electrode. Adapted with permission.^{[ 71 ]} Copyright 2022, Celltrion Group.

Figure 11

Electrochemical biosurveilance systems for real‐time monitoring of COVID‐19. IoT integrated electrochemical biosensors enable remote monitoring of patients and a cloud‐based service sets can allow patients and physicians to communicate 24/7 using smartphones, tablets, or computers.