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

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 () and Peng Wang ()
Additional contact information
Liqi Zhou: Nanjing University
Jingdong Song: Chinese Center for Disease Control and Prevention
Judy S. Kim: University of Oxford, Parks Road
Xudong Pei: Nanjing University
Chen Huang: University of Oxford, Parks Road
Mark Boyce: University of Oxford
Luiza Mendonça: University of Oxford
Daniel Clare: Harwell Science and Innovation Campus
Alistair Siebert: Harwell Science and Innovation Campus
Christopher S. Allen: University of Oxford, Parks Road
Emanuela Liberti: University of Oxford, Parks Road
David Stuart: University of Oxford
Xiaoqing Pan: University of California
Peter D. Nellist: University of Oxford, Parks Road
Peijun Zhang: University of Oxford
Angus I. Kirkland: University of Oxford, Parks Road
Peng Wang: Nanjing University

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: Abstract Cryo-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.

Date: 2020
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DOI: 10.1038/s41467-020-16391-6

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