Label-free, ultrasensitive, ultrahigh-speed scattering-based interferometric imaging

Label-free microscope imaging techniques allow direct visualization of biological substances in their most native forms. This review article provides an overview of recent advancements of scattering-based, interferometric laser microscopy and their applications to ultrasensitive and ultrahigh-speed biological imaging. In particular, common-path, widefield interferometric laser microscopy, namely interferometric scattering (iSCAT) microscopy and coherent brightfield (COBRI) microscopy, are discussed in details. Using these simple yet powerful optical techniques, single proteins and individual endogenous biological nanoparticles can be imaged and tracked without any label at ultrahigh spatiotemporal resolution. The development of ultrasensitive and ultrahigh-speed scattering-based interferometric microscope imaging enables investigation of biophysical and biochemical processes with minimal perturbation and unprecedented clarity.