CryoSIM: super resolution 3D structured illumination cryogenic fluorescence microscopy for correlated ultra-structural imaging

Rapid cryo-preservation of biological specimens is the gold standard for ultra-structural analysis. However, current methods for fluorescence imaging molecules under cryogenic conditions are limited to low resolutions of 400 nm. We have developed CryoSIM, a microscope for 3D super-resolution fluorescence cryo-imaging at 200 nm resolution using structured illumination microscopy. CryoSIM dramatically increases the usefulness of correlative imaging with cryo electron microscopy or cryo soft X-ray tomography by reducing the resolution gap. The microscope is easily reproducible, as it is assembled from commodity parts and controlled by the open source Python Microscope and Cockpit software.