Emerging point-of-care biosensors for rapid diagnosis of COVID-19: current progress, challenges, and future prospects

Abstract

Coronavirus disease 2019 (COVID-19) pandemic is currently a serious global health threat. While conventional laboratory tests such as quantitative real-time polymerase chain reaction (qPCR), serology tests, and chest computerized tomography (CT) scan allow diagnosis of COVID-19, these tests are time-consuming and laborious, and are limited in resource-limited settings or developing countries. Point-of-care (POC) biosensors such as chip-based and paper-based biosensors are typically rapid, portable, cost-effective, and user-friendly, which can be used for COVID-19 in remote settings. The escalating demand for rapid diagnosis of COVID-19 presents a strong need for a timely and comprehensive review on the POC biosensors for COVID-19 that meet ASSURED criteria: Affordable, Sensitive, Specific, User-friendly, Rapid and Robust, Equipment-free, and Deliverable to end users. In the present review, we discuss the importance of rapid and early diagnosis of COVID-19 and pathogenesis of COVID-19 along with the key diagnostic biomarkers. We critically review the most recent advances in POC biosensors which show great promise for the detection of COVID-19 based on three main categories: chip-based biosensors, paper-based biosensors, and other biosensors. We subsequently discuss the key benefits of these biosensors and their use for the detection of antigen, antibody, and viral nucleic acids. The commercial POC biosensors for COVID-19 are critically compared. Finally, we discuss the key challenges and future perspectives of developing emerging POC biosensors for COVID-19. This review would be very useful for guiding strategies for developing and commercializing rapid POC tests to manage the spread of infections.Graphical abstract.

Keywords: COVID-19; Chip-based biosensors; Commercialization; Diagnostic biomarkers; Paper-based biosensors; Point-of-care biosensors.

Fig. 1

Major diagnostic markers for COVID-19. Following the infection, the number of SARS-CoV-2 RNA increases dramatically at the early stage of infections, followed by an increase in the level of antibodies. Adapted with permission from [52]

Fig. 2

Chip-based biosensors for potential antigen and antibody detection for COVID-19. a Miniaturized and high-throughput ELISA on a chip-based biosensor. The fingerstick blood is directly applied to an assay chamber. The slide is prepared by printing “stable” spots of capture antibodies (cAb) and “soluble” spots of the fluorescently tagged detection antibodies (dAb) on the polymer brush (1). dAb dissolves and binds to the analyte (2), the complexes diffuse and bind to the respective cAb spots (3), and subsequently (4) generates fluorescent signals. A mobile phone-based reader is coupled with the biosensor to provide quantitative readout. Adapted with permission from [90]. b Multiplexed detection of IgG, IgM, and the viral antigen for SARS-CoV-2 based on fluorescence immunoassay using a centrifugal chip-based biosensor (FMS: fluorescent microsphere). Adapted with permission from [91]. c A low-consumption electrochemical biosensor for antigen detection, which is powered directly by a mobile phone. Adapted with permission from [92]

Fig. 3

Paper-based biosensors for potential antigen and antibody detection for COVID-19. a Monoplexed and multiplexed paper-based biosensors or lateral flow test strips for the detection of antibodies specific to the viruses. A customized phone application records the results along with the patient data for disease management. Adapted with permission from [102]. b A paper-based biosensor which detects IgG and IgM for COVID-19. Adapted with permission from [103]. c 3D-μPAD and its simple operation for simultaneous detection of three different antibodies for medical diagnosis. Adapted with permission from [107]

Fig. 4

Other point-of-care biosensors for potential antigen and antibody detection for COVID-19. a A nanoparticle-based portable bioluminescent immunosensor (ABS). Adapted with permission from [113]. b An array of silicon nanowire biosensor for sensitive detection of disease biomarkers. Adapted with permission from [114]. c A black phosphorus-based biosensor for electrochemical detection of IgG. Adapted with permission from [115]. d A polysiloxane-modified thread-based biosensor for sensitive detection of pathogens. Adapted with permission from (196)

Fig. 5

Chip-based biosensors for potential nucleic acid detection for COVID-19. a A PDMS/paper hybrid chip-based biosensor for pathogen detection. Adapted with permission from [136]. b A chip-based biosensor integrated with loop-mediated isothermal amplification (LAMP) and portable battery-powered heater. Adapted with permission from [137]. c A lab-on-a-chip platform which consists of an array of ISFET chip-based biosensors coupled with a thermal controller. Adapted with permission from [138]

Fig. 6

Paper-based biosensors for potential nucleic acid detection for COVID-19. a A paper-based biosensor or lateral flow test strip for visualization of COVID-19 reverse transcription loop-mediated isothermal amplification (RT-LAMP) products. Adapted with permission from [148]. b An integrated paper-based sample-to-answer biosensor for the detection of pathogens. Adapted with permission from [149]. c A disposable and integrated paper-based biosensor for nucleic acid extraction, amplification, and detection. Adapted with permission from (197)

Fig. 7

Other point-of-care biosensors for potential nucleic acid detection for COVID-19. a An optomagnetic biosensor for real-time nucleic acid detection of SARS-CoV-2. Adapted with permission from [158]. b Schematic diagram of an upconverting nanoparticle-based biosensor for pathogen detection. Adapted with permission from [159]. c A cotton thread-based biosensor for nucleic acid detection for disease diagnosis. Adapted with permission from [160]