The paper presents a novel optical microscopy method for directly detecting infectious SARS-CoV-2 viral particles in clinical samples by counting spike proteins on individual virions. Traditional virus detection techniques often measure viral genomes or specific proteins but cannot differentiate between infectious particles and non-infectious debris. We address this limitation by using wide-field optical microscopy combined with advanced fluorescent mesoscopic labels formed by plasmonic core–shell nanoparticles coupled to fluorescent dye molecules. These labels allow rapid (<20 minutes) imaging of whole virus particles without pre-concentration steps and enable to distinguish between infectious and non-infectious virus strains based on the number of spikes present on their lipid envelopes. This approach could improve virus diagnostics by providing not just detection but also infection potential assessment at the level of single viral particles.
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