Opportunities and Challenges for Biosensors and Nanoscale Analytical Tools for Pandemics: COVID-19

Abstract

Biosensors and nanoscale analytical tools have shown huge growth in literature in the past 20 years, with a large number of reports on the topic of 'ultrasensitive', 'cost-effective', and 'early detection' tools with a potential of 'mass-production' cited on the web of science. Yet none of these tools are commercially available in the market or practically viable for mass production and use in pandemic diseases such as coronavirus disease 2019 (COVID-19). In this context, we review the technological challenges and opportunities of current bio/chemical sensors and analytical tools by critically analyzing the bottlenecks which have hindered the implementation of advanced sensing technologies in pandemic diseases. We also describe in brief COVID-19 by comparing it with other pandemic strains such as that of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) for the identification of features that enable biosensing. Moreover, we discuss visualization and characterization tools that can potentially be used not only for sensing applications but also to assist in speeding up the drug discovery and vaccine development process. Furthermore, we discuss the emerging monitoring mechanism, namely wastewater-based epidemiology, for early warning of the outbreak, focusing on sensors for rapid and on-site analysis of SARS-CoV2 in sewage. To conclude, we provide holistic insights into challenges associated with the quick translation of sensing technologies, policies, ethical issues, technology adoption, and an overall outlook of the role of the sensing technologies in pandemics.

Keywords: COVID-19; X-ray diffraction; atomic force microscopy; electron microscopy; microfluidics; nanoplasmonics; nanosensors; pandemics; point-of-care-technologies; sewage sensors.

Figure 1

Structural view of SARS-CoV2 virus and its surface protein. Reproduced with permission from ref (29) under a Creative Commons CC-BY license. Copyright 2020 StatPearls Publishing.

Figure 2

5^’ UTR and 3^’ UTR and coding region of COVID-19, SARS-CoV and MERS-CoV. Reprinted with permission from ref (34). Copyright 2020 Elsevier.

Figure 3

Transverse thin-section CT scans in patients with COVID-19 disease: (A) 56 year-old man, day 3 after symptom onset; (B) 74 year-old woman, day 10 after symptom onset; (C) 61 year-old woman, day 20 after symptom onset; and (D) 63 year-old woman, day 17 after symptom onset. Reprinted with permission from ref (45). Copyright 2020 Elsevier.

Figure 4

Contact tracing application: Using GPS contacts of individual A and all individuals using the app, infections are traced out. This is further supplemented by scanning QR-codes displayed on high-traffic public amenities where GPS is too coarse. Using this application individual A requests a test for COVID-19 infection, and their positive test result is shared as an instant notification to individuals who have been in close contact. Reproduced with permission under a Creative Commons CC-BY license from ref (52). Copyright 2020 American Association for the Advancement of Science.

Figure 5

Features of an ideal biosensor required to be developed for effective use in pandemics.

Figure 6

Detection of SARS-CoV2 using FETs: The schematic shows a collection of biological samples from a patient and its application on the graphene-based sensing area of the FET biosensor. Binding events associated with the SAR-CoV2 virus can be captured by the sensor in real time. Reprinted with permission from ref (153). Copyright 2020 American Chemical Society.

Figure 7

LSPR detection of nucleic acid sequences from SARS-CoV2 virus. The schematic shows the architecture of LSPR substrate consisting of gold nanoparticles where light is illuminated on the substrate for generation of local heat and detection of binding nucleic acid binding events. The graph also shows the LSPR response to the theroplasmonic effect and toward detection of nucleic acid sequences at low concentrations. Reprinted with permission from ref (165). Copyright 2020 American Chemical Society.

Figure 8

Imaging single viruses using a smartphone. A smartphone-based optomechanical attachment with a resolution of <50 nm for the detection of individual viruses. Reprinted with permission from ref (170). Copyright 2013 American Chemical Society.

Figure 9

High-throughput biosensor: This example shows (A) microelectrode array used for cell detection; (B) sensor layout and the addressing scheme employed in the CMOS sensor chip; (C) complete CMOS packaged biochip; and D) microphotograph showing 9000 electrodes in the chip. Reprinted with permission from ref (188). Copyright 2012 Elsevier.

Figure 10

Design of an integrated sensor for the detection of multiplex infectious disease pathogens. (a) Components of the sensor and (b) illustration of the complete sample processing from sample introduction to pathogen detection. Reprinted with permission from ref (224). Copyright 2018 American Chemical Society.

Figure 11

Visualization of SARS-CoV2 with TEM. The virus is shown in blue color. Reprinted with permission from ref (38). Copyright 2020 American Chemical Society.

Figure 12

The 3D structure of SARS-CoV2 Mpro, in two different views. One protomer of the dimeriz shown in light blue and the other one in orange. Amino acid residues of the catalytic site are indicated as yellow and blue spheres, for Cys145 and His41, respectively. Black spheres indicate the positions of Ala285 of each of the two domains III (see text). Chain termini are labeled N and C for molecule A (lightblue) and N* and C* for molecule B (orange). Reproduced with permission under a Creative Commons CC-BY license from ref (270). Copyright 2020 American Association for the Advancement of Science.

Figure 13

(A) 2D and (B) 3D AFM images and contour map (C) of a single SARS-CoV virion. Scale bar = 100 nm in (A) and (C). The corresponding cursor profiles (middle and bottom row) provide quantitative measurements of the dimensions for the spike proteins (1–15) displayed in (C). Reprinted with permission from ref (302). Copyright 2020 John Wiley and Sons.