ABSTRACT
The development of rapid and ultra-sensitive detection technology of SARS-CoV-2 RNA for shortening the diagnostic window and achieving early detection of virus infections is a huge challenge to the efficient prevention and control of COVID-19. Herein, a novel ultra-sensitive surface-enhanced Raman spectroscopy (SERS) sensor powered by non-enzymatic signal amplification is proposed for rapid and reliable assay of SARS-CoV-2 RNA based on SERS-active silver nanorods (AgNRs) sensing chips and a specially designed smart unlocking-mediated target recycling signal amplification strategy. The SERS sensing was carried out by a one-pot hybridization of the lock probes (LPs), hairpin DNAs and SERS tags with SARS-CoV-2 RNA samples on an arrayed SERS sensing chip to achieve the recognition of SARS-CoV-2 RNA, the execution of nuclease-free unlocking-mediated target recycling signal amplification, and the combination of SERS tags to generate SERS signal. The SERS sensor for SARS-CoV-2 RNA can be achieved within 50 min with an ultra-high sensitivity low to 51.38 copies/mL, and has good selectivity in discriminating SARS-CoV-2 RNA against other respiratory viruses in representative clinical samples, which is well adapted for rapid, ultra-sensitive, multi-channel and point-of-care testing of viral nucleic acids, and is expected to achieve detection of SARS-CoV-2 infection in earlier detection windows for efficient COVID-19 prevention and control.