Conventional electron microscopy techniques have been crucial for studying the structure of biological specimens such as cells, tissues and macromolecules. But sample preparation of conventional electron microscopy requires complete dehydration which leads to material aggregation. Cryo-Electron Microscopy (Cryo-EM) has overcome these limitations and has recently undergone a quantum leap progression in the resolution. Due to it makes the samples without chemical fixations and heavy-metal stains, Cryo-EM has become a powerful technique in structural biology of functional complexes in their native state. Even though without crystallization, and only small amounts of sample are needed, Cryo-EM requires that samples must be very thin in order to acquire interpretable images from electron microscopes.