State of the Art on the SARS-CoV-2 Toolkit for Antigen Detection: One Year Later

Abstract

The recent global events of COVID-19 in 2020 have alerted the world to the risk of viruses and their impacts on human health, including their impacts in the social and economic sectors. Rapid tests are urgently required to enable antigen detection and thus to facilitate rapid and simple evaluations of contagious individuals, with the overriding goal to delimitate spread of the virus among the population. Many efforts have been achieved in recent months through the realization of novel diagnostic tools for rapid, affordable, and accurate analysis, thereby enabling prompt responses to the pandemic infection. This review reports the latest results on electrochemical and optical biosensors realized for the specific detection of SARS-CoV-2 antigens, thus providing an overview of the available diagnostics tested and marketed for SARS-CoV-2 antigens as well as their pros and cons.

Keywords: SARS-CoV-2 detection; droplets; nasopharyngeal swab; saliva; serum.

Figure 1

(A) Timeline of virus-based diseases. Reprinted with permission from [1], 2021 Elsevier. (B) different diagnostic methods for COVID-19. Reprinted with permission from [4], 2020 Elsevier. (C) different strategies for biosensing tool development in the COVID-19 outbreak. Reprinted with permission from [5], 2020 American Chemical Society and (D) features of an ideal biosensor for pandemics. Reprinted with permission from [16], 2020 American Chemical Society.

Figure 2

Different matrices used for the development of antigen biosensors at an academic level vs. commercially available antigen kits.

Figure 3

SARS-CoV-2 antigen detection in a nasopharyngeal swab. (A) S protein detection with a field-effect transistor-based immunosensor. Reprinted with permission from [26], 2020 American Chemical Society; (B) lateral-flow assay fabricated using the scFv-Fc antibody for N protein detection. Reprinted with permission from [34], 2021 Elsevier; (C) molecularly imprinted polymer-based electrochemical sensor for the detection of N protein. Reprinted with permission from [35], 2021 Elsevier.

Figure 4

SARS-CoV-2 antigen detection in saliva: (A) magnetic beads combined with a nanomaterial-based-printed electrode for the development of two immunosensors for the detection of S and N proteins. Reprinted with permission from [38], 2021 Elsevier; (B) magnetic beads for the development of a cheap aptamer assay for the detection of S and N protein antigens, exploiting an off-the-shelf glucometer. Reprinted with permission from [39], 2021 Elsevier; (C) a reagent-free electrochemical immunosensor for directly reading out viral particles in 5 min. Reprinted with permission from [40], 2020 American Chemical Society; (D) an electrochemical biosensing system for the detection of N protein, IgM and IgG antibodies, and inflammatory biomarker C-reactive protein using the same hand-held device. Reprinted with permission from [41], 2020 Elsevier.

Figure 5

SARS-CoV-2 antigen detection in serum and droplets. (A) Microfluidic device for the high-sensitivity measurement of N protein in undiluted and 5× diluted serum. Reprinted with permission from [43], 2021 American Chemical Society; (B) immunosensor for the detection of SARS-CoV-2 in droplets by exploiting the surface of the face mask to collect and enrich the respiratory droplets. Reprinted with permission from [47], 2021 Elsevier.