Microcrystal electron diffraction, or MicroED,[1][2] is a CryoEM method that was developed by the Gonen laboratory in late 2013 at the Janelia Research Campus of the Howard Hughes Medical Institute.
[3][4] The method is one of several modern versions of approaches to determine atomic structures using electron diffraction first demonstrated for the positions of hydrogen atoms in NH4Cl crystals by W. E. Laschkarew and I. D. Usykin in 1933,[5] which has since been used for surfaces,[6] via precession electron diffraction,[7] with much of the early work described in the work of Boris Vainshtein[8] and Douglas L.
[9] The method was developed for structure determination of proteins from nanocrystals that are typically not suitable for X-ray diffraction because of their size.
The first successful demonstration of MicroED was reported in 2013 by the Gonen laboratory[1] for the structure of lysozyme, a classic test protein in X-ray crystallography.
While some structures have been reported without freezing, radiation damage is sometimes minimized and higher resolution obtained by using cryo cooling even for small molecules.
[18][19] In these examples electron counting allowed ab initio phasing and visualization of hydrogens in proteins.
[2] Here the crystal is slowly rotated in a single direction while diffraction is recorded on a fast camera as a movie.
These methods differ slightly from MicroED: In ADT discrete steps of goniometer tilt are used to cover reciprocal space in combination with beam precession to reduce dynamical diffraction effects.
[22] ADT uses hardware and software for precession and scanning transmission electron microscopy for crystal tracking.