Abstract
Fast, sensitive, high-throughput detection of coronavirus antigens at physiologically relevant levels is essential for population screening that could prevent epidemics such as the current COVID-19 global pandemic. Optical methods based on surface-enhanced Raman scattering (SERS) spectroscopy are promising for this purpose because they ensure quick detection of even single biological molecules in a sample. For achieving such a high sensitivity, it is crucial to design SERS-active systems concentrating incident radiation into small sample volumes. Here, metal-dielectric cavities have been obtained through interaction of protein sulfhydryl groups with a SERS-active silver surface. The concentration of light in these cavities allows the differential detection of spike glycoprotein and nucleocapsid protein of SARS-COV-2, which are its key antigens, at physiologically relevant concentrations. The cavity Q-factor can be increased by additionally covering the dielectric protein film with a silver shell to form an ultrathin cavity, which provides an at least tenfold enhancement of the detection signal. The results could be used to design high-throughput systems for specific and sensitive detection of viral antigens and quick diagnosis of viral infections.