Detection of SARS-CoV-2 RNA with a plasmonic chiral biosensor

The detection of SARS-CoV-2 infection is crucial for effective prevention and surveillance of COVID-19. In this study, we report the development of a novel detection assay named CENSOR that enables sensitive and specific detection of SARS-CoV-2 RNA using a plasmonic chiral biosensor in combination with CRISPR-Cas13a. The chiral biosensor was designed by assembling gold nanorods (AuNR) into three-dimensional plasmonic architectures of controllable chirality on a DNA origami template. This modular assembly mode enhances the flexibility and adaptability of the sensor, thereby improving its universality as a sensing platform. In the presence of SARS-CoV-2 RNA, the CRISPR-Cas13a enzyme triggers collateral cleavage of RNA molecules, resulting in a differential chiral signal readout by the biosensor compared to when there are no RNA targets present. Notably, even subtle variations in the concentration of SARS-CoV-2 RNA can provoke significant changes in chiral signals after pre-amplification of RNA targets (calculated LOD: 0.133 aM), which establishes the foundation for quantitative detection. Furthermore, CENSOR demonstrated high sensitivity and accuracy in detecting SARS-CoV-2 RNA from clinical samples, suggesting its potential application in clinical settings for viral detection beyond SARS-CoV-2.