Enhancing the nanoplasmonic signal by a nanoparticle sandwiching strategy to detect viruses

Nanoparticles that can assemble and bind selectively on surfaces in intricate geometries can trigger multiple plasmonic modalities and enable wide applications in agriculture such as pesticide monitoring, in medical imaging such as targeted cancer detection, in bioengineering such as biotarget detection and biosensing, and in healthcare such as selection of drugs and their binding kinetics. However, these particles mainly rely on binding of the target to a surface to create a plasmonic resonance and subsequent shifts by binding of biotargets, which limit the flexibility to control overall sensitivity. Here, we present an unconventional way that sandwiches a virus (i.e., Hepatitis B virus: HBV) topographically between two or more nanoparticles on the top and the bottom to create a double-step shifting effect amplifying the total resonance wavelength shift on the surface by 1.53 - 1.77 times that significantly enhances the sensitivity. We successfully applied this approach to an intact HBV sensing application, which accurately quantified the viral load. This method establishes a new nanoparticle-based sandwiched nanoplasmonic approach to detect and quantify viral load using two-step sensing with broad applications in biosensing.