Micromirror total internal reflection microscopy for high-performance single particle tracking at interfaces

Single particle tracking has found broad applications in the life and
physical sciences, enabling the observation and characterisation of nano- and
microscopic motion. Fluorescence-based approaches are ideally suited for
high-background environments, such as tracking lipids or proteins in or on
cells, due to superior background rejection. Scattering-based detection is
preferable when localisation precision and imaging speed are paramount due to
the in principle infinite photon budget. Here, we show that micromirror-based
total internal reflection dark field microscopy enables background suppression
previously only reported for interferometric scattering microscopy, resulting
in nm localisation precision at 6 $\mu$s exposure time for 20 nm gold
nanoparticles with a 25 x 25 $\mu$m$^{2}$ field of view. We demonstrate the
capabilities of our implementation by characterizing sub-nm deterministic flows
of 20 nm gold nanoparticles at liquid-liquid interfaces. Our results approach
the optimal combination of background suppression, localisation precision and
temporal resolution achievable with pure scattering-based imaging and tracking
of nanoparticles at regular interfaces.