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.
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