Plasmonic nanostructure-enhanced Raman scattering for detection of SARS-CoV-2 nucleocapsid protein and spike protein variants

Abstract

Epidemiological control and public health monitoring during the outbreaks of infectious viral diseases rely on the ability to detect viral pathogens. Here we demonstrate a rapid, sensitive, and selective nanotechnology-enhanced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection based on the surface-enhanced Raman scattering (SERS) responses from the plasma-engineered, variant-specific antibody-functionalized silver microplasma-engineered nanoassemblies (AgMEN) interacting with the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins. The three-dimensional (3D) porous AgMEN with plasmonic-active nanostructures provide a high sensitivity to virus detection via the remarkable SERS signal collection. Moreover, the variant-specific antibody-functionalization on the SERS-active AgMEN enabled the high selectivity of the SARS-CoV-2 S variants, including wild-type, Alpha, Delta, and Omicron, under the simulated human saliva conditions. The exceptional ultrahigh sensitivity of our SERS biosensor was demonstrated via SARS-CoV-2 S and N proteins at the detection limit of 1 fg mL−1 and 0.1 pg mL−1, respectively. Our work demonstrates a versatile SERS-based detection platform can be applied for the ultrasensitive detection of virus variants, infectious diseases, and cancer biomarkers.