Low-dose phase retrieval of biological specimens using cryo-electron ptychography

• DOI: 10.1038/s41467-020-16391-6
• Publication Date: 2020-06-02T10:05:50Z
• Authors: Liqi Zhou; Jingdong Song; Judy S. Kim; Xudong Pei; Chen Huang; Mark Boyce; Luiza Mendonça; Daniel Clare; Alistair Siebert; Christopher S. Allen; Emanuela Liberti; David Stuart; Xiaoqing Pan; Peter D. Nellist; Peijun Zhang; Angus I. Kirkland; Peng Wang
• Keywords: Image Processing; Science; Electrons; Electron; Article; 03 medical and health sciences; Computer-Assisted; Theoretical; Microscopy, Electron, Transmission; Models; Image Processing, Computer-Assisted; Transmission; Microscopy, Phase-Contrast; Microscopy; 0303 health sciences; Phase-Contrast; Q; Cryoelectron Microscopy; Virion; Models, Theoretical; Condensed Matter Physics; 3. Good health; Infectious Diseases; Physical Sciences; HIV-1

AbstractCryo-electron microscopy is an essential tool for high-resolution structural studies of biological systems. This method relies on the use of phase contrast imaging at high defocus to improve information transfer at low spatial frequencies at the expense of higher spatial frequencies. Here we demonstrate that electron ptychography can recover the phase of the specimen with continuous information transfer across a wide range of the spatial frequency spectrum, with improved transfer at lower spatial frequencies, and as such is more efficient for phase recovery than conventional phase contrast imaging. We further show that the method can be used to study frozen-hydrated specimens of rotavirus double-layered particles and HIV-1 virus-like particles under low-dose conditions (5.7 e/Å2) and heterogeneous objects in an Adenovirus-infected cell over large fields of view (1.14 × 1.14 μm), thus making it suitable for studies of many biologically important structures.