Abstract
Transmission electron microscopy offers structural and compositional information with atomic resolution, but its use is restricted to thin, solid samples. Liquid samples, particularly those involving water, have been challenging because of the need to form a thin liquid layer that is stable within the microscope vacuum. Liquid cell electron microscopy is a developing technique that allows us to apply the powerful capabilities of the electron microscope to imaging and analysis of liquid specimens. We describe its impact in materials science and biology. We discuss how its applications have expanded via improvements in equipment and experimental techniques, enabling new capabilities and stimuli for samples in liquids, and offering the potential to solve grand challenge problems.
Highlights
Transmission electron microscopy offers structural and compositional information with atomic resolution, but its use is restricted to thin, solid samples
As microscopists become increasingly familiar with beam effects in liquids, the low-dose techniques developed for biological cryo-electron microscopy are becoming standard, and the benefits of high-sensitivity detectors in reducing the dose required per image are being exploited
The pioneering demonstrations that labeled biological structures can be resolved through micrometers of water using scanning TEM (STEM) [47, 97], and that biological processes can be stimulated in situ by injecting nutrients [30], showed that liquid cell microscopy can provide high-resolution information while circumventing some of the sample preparation issues
Summary
Transmission electron microscopy offers structural and compositional information with atomic resolution, but its use is restricted to thin, solid samples. Liquid samples, those involving water, have been challenging because of the need to form a thin liquid layer that is stable within the microscope vacuum. Made of silicon nitride on a silicon support, these liquid cells perform two jobs: They separate the liquid from the microscope vacuum while confining it into a layer that is thin enough for imaging with transmitted electrons. Because the equipment is not too expensive and works in existing electron microscopes, liquid cell microscopy programs have developed around the world
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