Plasmonic Nanoprobe-Enabled SERS Detection of SARS-CoV-2 Proteins and Virus Samples on Wax-Printed Paper Substrates

The development of highly sensitive detection methodologies for infectious diseases has become increasingly important, considering the recent COVID-19 pandemic. In this report, we demonstrate the use of a gold nanoprobe-based surface-enhanced Raman scattering (SERS) technique as a biosensor for the sensitive detection of SARS-CoV-2, including spike proteins, nucleocapsid proteins, as well as original or heat-inactivated patient samples. The nanoprobes are labeled with Raman reporter molecules for diagnostic detection and quantitative analysis of the protein or virus concentrations in the samples. Key to the detection is the capture of the targeted biomolecules by specific antibody-conjugated gold nanoparticles in a high-surface-area fibrous paper substrate, which facilitates the formation of "hot spots" for SERS signal amplification. The relationships between the SERS intensity and sample concentration were determined to assess diagnostic sensitivity and limits of detection. The results were also validated using the polymerase chain reaction (PCR) cycle threshold (CT) value vs the concentration of SARS-CoV-2. The nanoprobe-based and fibrous paper-assisted approach demonstrated a low-cost and portable platform technology for enhanced SERS detection of SARS-CoV-2, showing promise for expansion to the detection of various viruses.