Recent development of microfluidics-based platforms for respiratory virus detection

Abstract

With the global outbreak of SARS-CoV-2, the inadequacies of current detection technology for respiratory viruses have been recognized. Rapid, portable, accurate, and sensitive assays are needed to expedite diagnosis and early intervention. Conventional methods for detection of respiratory viruses include cell culture-based assays, serological tests, nucleic acid detection (e.g., RT-PCR), and direct immunoassays. However, these traditional methods are often time-consuming, labor-intensive, and require laboratory facilities, which cannot meet the testing needs, especially during pandemics of respiratory diseases, such as COVID-19. Microfluidics-based techniques can overcome these demerits and provide simple, rapid, accurate, and cost-effective analysis of intact virus, viral antigen/antibody, and viral nucleic acids. This review aims to summarize the recent development of microfluidics-based techniques for detection of respiratory viruses. Recent advances in different types of microfluidic devices for respiratory virus diagnostics are highlighted, including paper-based microfluidics, continuous-flow microfluidics, and droplet-based microfluidics. Finally, the future development of microfluidic technologies for respiratory virus diagnostics is discussed.

FIG. 1.

Different approaches for open/paper-based microfluidic devices for respiratory virus detection. (a) Schematic illustration of the device components and the detection principle of a label-free paper-based electrochemical biosensor for diagnosing COVID-19. Reproduced with permission from Yakoh et al., Biosens. Bioelectron. 176, 112912 (2021). Copyright 2020 Elsevier. (b) Assay procedure of a handheld, rapid, low-cost, smartphone-based paper microfluidic assay capable of directly detecting SARS-CoV-2 in the droplets/aerosols from the air. Reproduced with permission from Kim et al., Biosens. Bioelectron. 200, 113912 (2022). Copyright 2021 Elsevier. (c) Illustration of a smartphone-based PD-LAMP process to detect SARS-CoV-2. Reproduced with permission from Colbert et al., Anal. Chim. Acta 1203, 339702 (2022). Copyright 2022 Elsevier. (d) Schematic illustration of a paper-based colorimetric molecular test for SARS-CoV-2 in saliva. Reproduced with permission from Davidson et al., Biosens. Bioelectron. X 9, 100076 (2021). Copyright 2021 Author(s), licensed under a Creative Commons Attribution (CC BY-NC-ND) license. (e) The wax crayon-based μPAD using four ASO@AuNPs for colorimetric detection of viral RNA genome. Reproduced with permission from Borghei et al., Anal. Chem. 94, 13616 (2022). Copyright 2022 American Chemical Society.

FIG. 2.

Different approaches for continuous-flow microfluidic devices for respiratory virus detection. (a) A continuous-flow microfluidic chip for culture of multiple different cell lines. Reproduced with permission from Su et al., Virol. Sin. 37, 547–557 (2022). Copyright 2022 Author(s), licensed under a Creative Commons Attribution (CC BY-NC-ND) license. (b) A photograph of the fluorescence immunoassay microfluidic chip and the homemade fluorescence detection equipment for IgG/IgM/antigen detection of SARS-CoV-2. Reproduced with permission from Lin et al., Anal. Chem. 92, 9454–9458 (2020). Copyright 2020 American Chemical Society. (c) A high-throughput microfluidic nanoimmunoassay for parallel detection of an anti-SARS-CoV-2 IgG antibody in 1024 samples. Reproduced with permission from Swank et al., Proc. Natl. Acad. Sci. U.S.A. 118, e2025289118 (2021). Copyright 2021 Author(s), licensed under a Creative Commons Attribution (CC BY) license. (d) Design of the nanostructured microdevice and the portable smartphone-enabled virus detection system for colorimetric detection of an avian influenza virus (AIV). Reproduced with permission from Xia et al., ACS Sens. 4, 3298–3307 (2019). Copyright 2019 American Chemical Society. (e) A photograph and schematic of the microfluidic chip for detection of an influenza A (H1N1) virus by RT-LAMP. Reproduced with permission from Ma et al., Sens. Actuators B 296, 126647 (2019). Copyright 2019 Elsevier. (f) Overview and photograph of the microfluidic chip for multiplex nested RPA and CRISPR/Cas12a detection of respiratory viruses. Reproduced with permission from Liu et al., Small 18, 2200854 (2022). Copyright 2022 Wiley-VCH. (g) An instrument-free, hand warmer powered, self-contained microfluidic system for SARS-CoV-2 detection. Reproduced with permission from Li et al., Biosens. Bioelectron. 199, 113865 (2022). Copyright 2021 Elsevier.

FIG. 3.

Different approaches for droplet-based microfluidic devices for respiratory virus detection. (a) Overview of the Lab-in-a-Fiber device. The device consists of two modules: dispersed (disp.) phase droplets generated via flow focusing and fluorescence detection of droplets. Reproduced with permission from Parker et al., Sci. Rep. 12, 1–10 (2022). Copyright 2022 Author(s), licensed under a Creative Commons Attribution (CC BY) license. (b) A droplet microarray based on nanosensing probe patterns (MoS₂-DMA platform) for simultaneous detection of human immunodeficiency virus -1/-2 (HIV-1/-2), SARS-CoV-2 (ORFlab and N genes), and influenza A (M genes). Reproduced with permission from Oudeng et al., ACS Appl. Mater. Interfaces 12, 55614–55623 (2020). Copyright 2020 American Chemical Society. (c) Schematic of CARMEN v.1 (top) and mCARMEN (bottom) workflows. Reproduced with permission from Welch et al., Nat. Med. 28, 1083–1094 (2022). Copyright 2022 Author(s), licensed under a Creative Commons Attribution (CC BY) license.

FIG. 4.

(a) Conceptual illustration of a capacitive aptasensor coupled with microfluidic enrichment for real-time detection of trace SARS-CoV-2 nucleocapsid protein. Reproduced with permission from Qi et al., Anal. Chem. 94, 2812–2319 (2022). Copyright 2022 American Chemical Society. (b) Working principle of an electric field-mediated microfluidic assay for SARS-CoV-2 RNA detection using ITP and CRISPR-Cas12. Reproduced with permission from Ramachandran et al., Proc. Natl. Acad. Sci. U.S.A. 117, 29518 (2020). Copyright 2020 Author(s), licensed under a Creative Commons Attribution (CC BY) license. (c) POC-CRISPR detects the SARS-CoV-2 virus from unprocessed nasopharyngeal (NP) swab eluates in a sample-to-answer workflow. Reproduced with permission from Chen et al., Biosens. Bioelectron. 190, 113390 (2021). Copyright 2021 Elsevier.