Label-free optical quantification of material composition of suspended virus-gold nanoparticle complexes

The interaction between metallic and biological nanoparticles (NPs) is widely used in various biotechnology and biomedical applications. However, detailed characterization of this type of interaction is challenging due to a lack of high-throughput techniques that can quantify both size and composition of suspended NP complexes. Here, we introduce a technique called ``twilight nanoparticle tracking analysis'' (tNTA) and demonstrate that it provides a quantitative relationship between the measured optical signal and the composition of suspended dielectric-metal NP complexes. We assess the performance of tNTA by analyzing the selective binding of tannic acid-modified gold nanoparticles (TaAuNPs) to herpes simplex viruses (HSV). Our results show that TaAuNPs bind specifically to HSV without causing substantial changes in the size or refractive index of the virus, suggesting that the binding does not cause virus disruption. Instead, the anti-viral properties of TaAuNPs appear to stem from direct particle binding to the virus.