Imaging Non-fluorescent Nanoparticles in Living Cells with Wavelength-Dependent Differential Interference Contrast Microscopy and Planar Illumination

Optical microscopy is a simple yet robust strategy to study live cellular processes. By changing the wavelength of the illumination light, different non-fluorescent nanoparticle probes can be identified and tracked dynamically inside crowded living cells with either differential interference contrast (DIC) microscopy or planar illumination microscopy (PIM). The translational and rotational dynamics of anisotropic nanoparticles can be readily extracted via the modified DIC microscope and the home-built PIM. In this protocol, the optimization procedures for DIC microscopy and PIM imaging are explained, and the sample preparation procedures to image non-fluorescent nanoparticles in living cells are described.