Interferometric scattering enables fluorescence-free electrokinetic trapping of single nanoparticles in free solution

Anti-Brownian traps confine single particles in free solution by closed-loop feedback forces that directly counteract Brownian motion. The extended-duration measurement of trapped objects allows detailed characterization of photophysical and transport properties, as well as observation of infrequent or rare dynamics. However, this approach has been generally limited to particles that can be tracked by fluorescent emission. Here we present the Interferometric Scattering Anti-Brownian ELectrokinetic trap (ISABEL trap), which uses interferometric scattering rather than fluorescence to monitor particle position. By decoupling the ability to track (and therefore trap) a particle from collection of its spectroscopic data, the ISABEL trap enables confinement and extended study of single particles that do not fluoresce, that only weakly fluoresce, or which exhibit intermittent fluorescence or photobleaching. This new technique significantly expands the range of nanoscale objects that may be investigated at the single-particle level in free solution.