Massively Parallel and Highly Quantitative Single-Particle Analysis on Interactions between Nanoparticles on Supported Lipid Bilayer

Observation of individual single-nanoparticle reactions provides direct information and insight for many complex chemical, physical, and biological processes, but this is utterly challenging with conventional high-resolution imaging techniques on conventional platforms. Here, we developed a photostable plasmonic nanoparticle-modified supported lipid bilayer (PNP-SLB) platform that allows for massively parallel in situ analysis of the interactions between nanoparticles with single-particle resolution on a two-dimensional (2D) fluidic surface. Each particle-by-particle PNP clustering process was monitored in real time and quantified via analysis of individual particle diffusion trajectories and single-particle-level plasmonic coupling. Importantly, the PNP-SLB-based nanoparticle cluster growth kinetics result was fitted well. As an application example, we performed a DNA detection assay, and the result suggests that our approach has very promising sensitivity and dynamic range (high attomolar to high femtomolar) without optimization, as well as remarkable single-base mismatch discrimination capability. The method shown herein can be readily applied for many different types of intermolecular and interparticle interactions and provide convenient tools and new insights for studying dynamic interactions on a highly controllable and analytical platform.