Cryogenic electron microscopy

Cryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample solution is applied to a grid-mesh and plunge-frozen in liquid ethane or a mixture of liquid ethane and propane.[1] While development of the technique began in the 1970s, recent advances in detector technology and software algorithms have allowed for the determination of biomolecular structures at near-atomic resolution.[2] This has attracted wide attention to the approach as an alternative to X-ray crystallography or NMR spectroscopy for macromolecular structure determination without the need for crystallization.[3]

In 2017, the Nobel Prize in Chemistry was awarded to Jacques Dubochet, Joachim Frank, and Richard Henderson "for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution."[4] Nature Methods also named cryo-EM as the "Method of the Year" in 2015.[5]

The Federal Institute of Technology, the University of Lausanne and the University of Geneva opened the Dubochet Center For Imaging (DCI) at the end of November 2021, for the purposes of applying and further developing cryo-EM.[6] Less than a month after the first identification of the SARS-CoV-2 Omicron variant, researchers at the DCI were able to define its structure, identify the crucial mutations to circumvent individual vaccines and provide insights for new therapeutic approaches.[7]

The Danish National cryo-EM Facility also known as EMBION was inaugurated on December 1st 2016. EMBION is a cryo-EM consortium between Danish Universities (Aarhus University host and University of Copenhagen co-host).

Cryogenic transmission electron microscopy (cryo-TEM) is a transmission electron microscopy technique that is used in structural biology and materials science.

• Cryogenic electron tomography (cryo-ET), a specialized application where samples are imaged as they are tilted
• Electron crystallography, method to determine the arrangement of atoms in solids using a TEM
• MicroED,[8] method to determine the structure of proteins, peptides, organic molecules, and inorganic compounds using electron diffraction from 3D crystals[9][10][11]
• Single particle analysis cryo-EM, an averaging method to determine protein structure from monodisperse samples[12]

• 
  Cryo-TEM image of GroEL suspended in amorphous ice at 50000× magnification
• Structure of alcohol oxidase from Pichia pastoris by Cryo-TEM
• 
  Cryogenic transmission electron microscopy (cryoTEM) image of an intact ARMAN cell from an Iron Mountain biofilm. Image width is 576 nm.
• 
  Cryo-electron micrograph of the CroV giant marine virus
  (scale bar represents 200 nm)[13]