Nano assembly of plasmonic probe-virus particles enabled rapid and ultrasensitive point-of-care SARS-CoV-2 detection

The current COVID-19 global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus has become a major public health concern. The ability to identify the viruss presence in infected hosts with sufficient speed and sensitivity is critical to control the epidemic timely. Here, we use self-assembly of arrayed gold nanoparticles (AuNPs) on the coronavirus, which we call the "plasmo-virus particle," to achieve a rapid, sensitive, sample preparation-free assay enabling direct detection of SARS-CoV-2 in a point-of-care (POC) setting. The AuNPs of the plasmo-virus particle serve as plasmonic nanoprobes that specifically bind to the spike protein (S-protein) sites on the surface of SARS-CoV-2. Optical interactions between the self-assembled plasmonic nanoprobes generate multiple modes of highly enhanced plasmonic coupling. Measuring changes of the multimode plasmonic coupling-induced extinction peaks allows for quantifying SARS-CoV-2 at low titers with a limit of detection (LOD) of 1.4 x 101 pfu/mL. Using a miniaturized standalone biochip reading device, we further demonstrate the nano assembly assay for smartphone-operated SARS-CoV-2 detection for viral transport medium (VTM) samples within 10 min without any sample purification steps. We anticipate that the high sensitivity and speed of the POC detection performance of this biosensor technology could be broadly accepted for timely personalized diagnostics of infectious agents under low-resource settings.