What Is a Cryogenic Electron Microscope?
A cryogenic electron microscope (CryoEM) is a type of transmission electron microscopy that can observe the three-dimensional structure of biomolecules such as proteins by freezing samples in liquid nitrogen (-350°F).
Analytical methods using CryoEMs have developed rapidly in recent years, and in 2017, the Nobel Prize in Chemistry was awarded to three researchers involved in their development. As a new analysis technique that has been put to practical use in recent years, it is expected to make a significant contribution to the development of various fields in the future, including drug discovery, medicine, and life sciences.
Uses of Cryogenic Electron Microscopes
CryoEMs were developed to analyze the three-dimensional structure of biomolecules, such as proteins with high resolution. Conventional X-ray crystallography is difficult to analyze due to the difficulty of crystallizing proteins. However, cryo-electron microscopes make it possible to analyze proteins in solution. It is also possible to analyze high-molecular-weight proteins, which has been difficult with nuclear magnetic resonance (NMR) analysis.
Recent active research and development has dramatically improved the resolution, enabling analysis at the atomic level down to 1.5 Å (1 Å (angstrom) = 10 to the minus tenth power of a meter).
Principle of Cryogenic Electron Microscopes
With transmission electron microscopes, which are the basis of CryoEMs, it is difficult to observe the structure of a sample containing water molecules, such as a protein, while maintaining its structure, because the sample is irradiated with electron beams in a vacuum. CryoEMs, therefore, allow observation while preserving the structure of the sample by rapidly freezing it in liquid nitrogen (-350 ºF).
When observing the molecular structure of a protein or other molecule with a CryoEM, a weak electron beam is irradiated to minimize damage to the molecular structure of the protein or other molecule by the electron beam. As a result, the resulting image is very noisy. Therefore, we take numerous photographs of the same protein and reconstruct the three-dimensional structure of the protein by averaging a large number of image data. Such an analysis method is called single-particle analysis.
Behind the practical application and performance improvement of CryoEMs are, of course, improvements in the performance of the instruments themselves, such as the electron gun, lens, and camera, including the cooling mechanism, but also many technological innovations, such as new image analysis techniques based on deep learning and improved computing power of computers.