Cryo Electronic Microscopy (Cryo-EM) has been extensively studied in life sciences due to it can provide the three-dimensional (3D) structure at a near-atomic resolutions. With the advance of microscope design, imaging hardware and image processing, Cryo-EM is increasingly becoming a mainstream technology for studying the structure of biological macromolecules. There is not required crystallization and only small amounts of sample are needed, Cryo-EM can present samples in a native state with imaging the sample’s intrinsic electron density, providing direct visualization of biological macromolecules, such as protein, nucleic acid, large complexes and so on.