This study explores the application of integrated differential phase contrast scanning transmission electron microscopy (IDPC-STEM) for cryo-electron microscopy (cryo-EM) structure determination. Using keyhole limpet hemocyanin (KLH) and tobacco mosaic virus (TMV) as test specimens, the authors demonstrate that IDPC-STEM can produce high-resolution images suitable for single-particle reconstruction. Near-atomic resolution structures were obtained for KLH (6.5 Å) and TMV (3.5 Å), matching results from conventional transmission electron microscopy (CTEM). This work establishes IDPC-STEM as a viable technique for high-resolution cryo-EM structure determination of biological macromolecules.

Ivan Lazić, Maarten Wirix, Max Leo Leidl, Felix de Haas, Daniel Mann, Maximilian Beckers, Evgeniya V. Pechnikova, Knut Müller-Caspary, Ricardo Egoavil, Eric G. T. Bosch, Carsten Sachse