Nanobody-based label-free photoelectrochemical immunoassay for highly sensitive detection of SARS-CoV-2 spike protein

Until now, COVID-19 caused by SARS-CoV-2 is engulfing the worldwide and still ranging to date, continuing to threaten the public health. The main challenge facing COVID-19 epidemic is short of fast-response and high-efficiency methods to determine SARS-CoV-2 viral pathogens. Herein, a nanobody-based label-free photoelectrochemical (PEC) immunosensor has been fabricated for rapidly detecting SARS-CoV-2 spike protein. As a small-size and high-stability antibody, nanobody was directly and well immobilized with Au nanoparticles and TiO 2 spheres by the interaction. Au deposited TiO 2 nanomaterial possessed 8.5 times photoelectric performance in comparison with TiO 2 in the presence of electron donor owing to surface plasma resonance effect of Au. Based on the steric hindrance effect, this immunoassay platform realized the linear detection from 0.015 to 15000 pg mL −1 , and a limit of detection was low as 5 fg mL −1 . The label-free PEC immunoassay design provides a new idea for convenient, rapid, and efficient test of SARS-CoV-2 spike protein and broadens further application of nanobody as an identification agent to specific biomarkers.