Plasmon-enhanced single-molecule detection for femtomolar fluorescence-free biosensing

Biomolecular sensing is fundamental to our understanding of disease mechanisms, and to develop platforms toward diagnostics. Detection of low concentrations remains extremely challenging, particularly in complex biological fluids. I will present a novel plasmonic sensing platform for the fluorescence-free detection of single molecules at femtomolar concentrations directly in undiluted blood serum. The sensor is based on a nanoparticle-on-film platform that exploits the coupling between the propagating plasmon on a metallic film and the localized plasmon on a gold nanoparticle for single-molecule detection. I will discuss the fundamental signal generation mechanisms through simulations and single-particle spectroscopy. Next, I will describe how we exploit low affinity (reversible) interactions to enable the continuous monitoring of biomarkers with a 200 fM limit-of-detection and a response time of 10 minutes in undiluted serum. This platform holds great promise to monitor lowly abundant analytes in complex media, expanding the scope of continuous monitoring biosensing.