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

Abstract

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.