Sizing single trapped nanoparticles with interferometric scattering fluctuations

The sizes of nanoparticles significantly influence their properties but are challenging to quantify at the single-particle level. To enable label-free single-nanoparticle detection, interferometric scattering microscopy has emerged as a sensitive modality that exhibits high-precision axial information encoded in the interferometric scattering signal. Here, we demonstrate that single nanoparticles in an interferometric scattering anti-Brownian electrokinetic (ISABEL) trap can be hydrodynamically sized by interferometric scattering contrast fluctuations. The fluctuation timescale is characterized by time autocorrelation analysis and interpreted via a Brownian Dynamics model of the ISABEL trap to provide an estimate of the hydrodynamic diameter of each trapped particle. We verify this behavior for gold and polystyrene bead standards, and demonstrate performance on single carboxysomes, nanoscale carbon fixation compartments from autotrophic bacteria. The exquisite sensitivity of interferometric scattering amplitude fluctuations further equips researchers with a label-free optical platform for increasingly sophisticated nanoparticle analysis.