Cryoelectron tomography (CryoET)—electron microscopy of frozen tissues—allows unparalleled observations of molecular complexes in as natural a state as possible. However, current electron microscopes can only view samples to a limited depth—approximately 0.5–1 µm—which has restricted cryoET to analyses of cell surfaces, isolated organelles, or microorganisms.
To get a glimpse inside eukaryotic cells, researchers have tried freezing and then slicing them with extremely sharp diamond or glass knives—cryo-ultramicrotomy. But “cutting with a mechanical knife introduces compression artifacts, which hinder interpretation of the images,” says Jürgen Plitzko of the Max Planck Institute of Biochemistry in Germany. Another strategy, using a beam of gallium ions to erode the surface of cells from above, has also proven inadequate for imaging deeply embedded structures.
Plitzko and his team combined principles from both techniques to create thin sections of cells using a focused ion beam as a blade. The ion beam is directed at an individual ...
