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

DOI: 10.1038/s41467-020-16391-6

Authors: Liqi Zhou (Nanjing University) , Jingdong Song (Chinese Center for Disease Control and Prevention) , Judy S. Kim (University of Oxford; Diamond Light Source; The Rosalind Franklin Institute) , Xudong Pei (Nanjing University) , Chen Huang (University of Oxford; Diamond Light Source) , Mark Boyce (Wellcome Trust Centre for Human Genetics, University of Oxford) , Luiza Mendonca (Wellcome Trust Centre for Human Genetics, University of Oxford) , Daniel Clare (Diamond Light Source) , Alistair Siebert (Diamond Light Source) , Christopher Allen (University of Oxford; Diamond Light Source Ltd) , Emanuela Liberti (University of Oxford; Diamond Light Source) , David Stuart (Wellcome Trust Centre for Human Genetics, University of Oxford; Diamond Light Source) , Xiaoqing Pan (University of California) , Peter Nellist (University of Oxford) , Peijun Zhang (Wellcome Trust Centre for Human Genetics, University of Oxford; Diamond Light Source) , Angus Kirkland (University of Oxford; Diamond Light Source; The Rosalind Franklin Institute) , Peng Wang (Nanjing University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 11

State: Published (Approved)
Published: June 2020
Diamond Proposal Number(s): 19243 , 20431 , 20961 , 22317

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.

Journal Keywords: Electron microscopy; Ptychography; TEM; Virus; CryoEM

Subject Areas: Physics, Biology and Bio-materials, Technique Development

Diamond Offline Facilities: Electron Physical Sciences Imaging Centre (ePSIC)
Instruments: E02-JEM ARM 300CF

Documents:
s41467-020-16391-6.pdf