Interferometric scattering for label-free electrokinetic trapping of single nanoparticles

Anti-Brownian ELectrokinetic (ABEL) trapping is a technique to trap single particles in solution, enabling extended characterization of their properties. It utilizes photon-by-photon fluorescence to estimate a particle’s position, and fast electrophoretic and electroosmotic feedback forces to counteract Brownian motion and confine a particle to the center of a nanofluidic chamber. This enables the observation of photophysical properties, diffusion constants, and electrokinetic mobility. However, trapping is limited to particles that are either tagged with a fluorescent label, or have bright native fluorescence. Here we present the Interferometric Scattering Anti-Brownian ELectrokinetic trap (ISABEL trap), which uses interferometric scattering to enable fast detection and trapping of non-fluorescent particles. The weak scattered light from a nanoparticle is enhanced by interference with a strong reflection from a nearby interface. This enables direct and extended-duration study of single particles that do not fluoresce, or which exhibit intermittent fluorescence or photobleaching.