Quantitative Phase Imaging at the Nanoscale Using Interferometric Scattering Microscope and Thermo-Optic Effect

We combine ultrasensitive microscopy with a novel, highly precise, and fast phase control to enable quantitative phase imaging of weakly scattering objects such as single microtubules. We demonstrate 3D mapping of microtubule networks and real-time 3D localization of single proteins labeled with small metallic nanoparticles. In particular, the 3D trajectories of microtubule-associated proteins acquired at the kHz rate revealed a complex trajectory of the protein diffusion on the surface of microtubules. The fast and accurate phase shaping technique combined with interferometric scattering microscopy pushes the limits of the quantitative phase imaging deep into the subdiffraction regime.