It is crucial that understanding the biological functions of macromolecules by characterizing the molecular structure. As the most effective method to obtain atomic models of proteins and nucleic acids in the 20th century, X-ray crystallography has been fundamental in the development of many scientific fields. But many samples have been proved that it is difficult to crystallize (for example membrane proteins). In addition, the biological macromolecular complexes sometimes cannot be produced in sufficient quantities of crystallization. Cryo-Electron Microscopy (Cryo-EM) has become a potential alternative to X-ray crystallography that has quickly gained popularity in structural biology.