The team from Forschungszentrum Jülich and Heinrich Heine University Düsseldorf have combined cryo-EM with integrated differential phase contrast scanning transmission electron microscopy (iDPC-STEM).

In a study published on September 5 in the journal Nature Methods, the scientists applied iDPC-STEM to two cryo-EM test specimens: keyhole limpet hemocyanin (KLH) and tobacco mosaic virus (TMV). The micrographs showed complete contrast transfer to high resolution and enabled the cryo-EM structure determination for KLH at 6.5 Å and 3.5 Å for TMV using single-particle reconstruction methods.

The findings demonstrate that STEM imaging in general and the iDPC-STEM approach in particular can be applied to vitrified single-particle specimens to determine near-atomic resolution cryo-EM structures of biological macromolecules. This expands the possibilities for structural analysis, especially for heterogeneous, nonuniform samples or single particles when averaging capabilities are limited, the researchers noted.

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