Plasmonic Detection of SARS-CoV-2 Spike Protein with Polymer-Stabilized Glycosylated Gold Nanorods

[Image: see text] The COVID-19 pandemic has highlighted the need for innovative biosensing, diagnostic, and surveillance platforms. Here we report that glycosylated, polymer-stabilized, gold nanorods can bind the SARS-CoV-2 spike protein and show correlation to the presence of SARS-CoV-2 in primary COVID-19 clinical samples. Telechelic polymers were prepared by reversible addition–fragmentation chain-transfer polymerization, enabling the capture of 2,3-sialyllactose and immobilization onto gold nanorods. Control experiments with a panel of lectins and a galactosamine-terminated polymer confirmed the selective binding. The glycosylated rods were shown to give dose-dependent responses against recombinant truncated SARS-CoV-2 spike protein, and the responses were further correlated using primary patient swab samples. The essentiality of the anisotropic particles for reducing the background interference is demonstrated. This highlights the utility of polymer tethering of glycans for plasmonic biosensors of infection.