Nano-biosensor for SARS-CoV-2/COVID-19 detection: methods, mechanism and interface design

The epidemic of coronavirus disease 2019 (COVID-19) was a huge disaster to human society. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which led to COVID-19, has resulted in a large number of deaths. Even though the reverse transcription-polymerase chain reaction (RT-PCR) is the most efficient method for the detection of SARS-CoV-2, the disadvantages (such as long detection time, professional operators, expensive instruments, and laboratory equipment) limit its application. In this review, the different kinds of nano-biosensors based on surface-enhanced Raman scattering (SERS), surface plasmon resonance (SPR), field-effect transistor (FET), fluorescence methods, and electrochemical methods are summarized, starting with a concise description of their sensing mechanism. The different bioprobes (such as ACE2, S protein-antibody, IgG antibody, IgM antibody, and SARS-CoV-2 DNA probes) with different bio-principles are introduced. The key structural components of the biosensors are briefly introduced to give readers an understanding of the principles behind the testing methods. In particular, SARS-CoV-2-related RNA mutation detection and its challenges are also briefly described. We hope that this review will encourage readers with different research backgrounds to design SARS-CoV-2 nano-biosensors with high selectivity and sensitivity.