Label‐Free and Colorimetric Detection of Influenza A Virus via Receptor‐Mediated Viral Fusion with Plasmonic Vesicles

Abstract The rapid transmission and numerous re‐emerging human influenza virus variants that spread via the respiratory system have led to severe global damage, emphasizing the need for detection tools that can recognize active and intact virions with infectivity. Here, this work presents a plasmonic vesicle‐mediated fusogenic immunoassay (PVFIA) comprising gold nanoparticle (GNP) encapsulating fusogenic polymeric vesicles (plasmonic vesicles; PVs) for the label‐free and colorimetric detection of influenza A virus (IAV). The PVFIA combines two sequential assays: a biochip‐based immunoassay for target‐specific capture and a PV‐induced fusion assay for color change upon the IAV–PV fusion complex formation. The PVFIA demonstrates excellent specificity in capturing the target IAV, while the fusion conditions and GNP induce a significant color change, enabling visual detection. The integration of two consecutive assays results in a low detection limit (10^0.7919 EID₅₀ mL⁻¹) and good reliability (0.9901), indicating sensitivity that is 10^4.208 times higher than conventional immunoassay. Leveraging the PV viral membrane fusion activity renders the PVFIA promising for point‐of‐care diagnostics through colorimetric detection. The innovative approach addresses the critical need for detecting active and intact virions with infectivity, providing a valuable tool with which to combat the spread of the virus.