Cryogenic transmission electron microscopy for materials research

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duction Transmission electron microscopy (TEM) today is the essential tool for materials characterization when site-specific chemical or structural detail is required.1,2 If you want to know the chemistry at a crack tip or the uniformity of a coating on a nanoparticle, then you must use TEM or scanning transmission electron microscopy (STEM). (S)TEM can be used to characterize all materials, from the hardest ceramics and metals to the softest polymers and the smallest nanoparticles. It can also be applied to living material, almost invariably when it is no longer living. By “living,” we mean human, animal, and vegetable, and by “no longer” we could mean after recent surgery or after mummification3 or fossilization.4 The TEM research community has tended to separate into three groups—the physical scientists, the biologists, and the instrumentalists. Modeling and software specialists tend to segregate into these same groups. Recent developments in TEM and STEM have begun to see a convergence of these different fields; the use of cryogenic techniques is one aspect where these groups have more in common than differences. The commonalities can be the instruments, the many ways we now have to prepare specimens for the TEM, or even the ways that we acquire, manipulate, and analyze experimental data. The new capabilities can be appreciated by comparing

the macroscopic appearance of cryotemplated and pressurized gas expansion cellulose nanocrystal aerogels in dry and wet states, as shown in Figure 1. The difference is clear in the macroscopic image but cryo-TEM will show the full picture.5

Method of the year and a Nobel Prize In 2017, the Nobel Prize in chemistry was awarded to J. Dubochet, J. Frank, and R. Henderson “for developing cryoelectron microscopy for the high-resolution structure determination of biomolecules in solution.”6 In this application of cryogenic (cryo)-TEM, wherein proteins are imaged, the temperature of the sample must be maintained at liquidnitrogen temperatures or below. While the low temperature not only confers radiation damage protection to samples, it also is necessary to maintain the sample in the vitreous state where proteins adopt near-native conformations. Modern automated cryo-TEMs are designed specifically to operate at liquid-nitrogen temperature. In awarding the Nobel Prize, the Royal Swedish Academy of Sciences explained that cryo-EM has “taken biochemistry into a new era.”7 (Microscopists were initially so excited to get some recognition that they forgot about the missing T, but we will include it.) The journal Nature Methods had actually named “single-particle cryo-electron microscopy (cryo-EM)”

David W. McComb, The Ohio State University, USA; [email protected] Jeffrey Lengyel, Thermo Fisher Scientific, USA; [email protected] C. Barry Carter, University of Connecticut, Storrs, and Center for Integrated Nanotechnologies, Sandia National Laboratories, USA; [email protected] doi:10.1557/mrs.2019.283

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• VOLUME 44 • DECEMBER IP • www.mrs.org/bulletin 2019 2019 Mate

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