- Rodriguez, Jose A;
- Xu, Rui;
- Chen, Chien-Chun;
- Huang, Zhifeng;
- Jiang, Huaidong;
- Chen, Allan L;
- Raines, Kevin S;
- Pryor, Alan;
- Nam, Daewoong;
- Wiegart, Lutz;
- Song, Changyong;
- Madsen, Anders;
- Chushkin, Yuriy;
- Zontone, Federico;
- Bradley, Peter J;
- Miao, Jianwei
A structural understanding of whole cells in three dimensions at high spatial resolution remains a significant challenge and, in the case of X-rays, has been limited by radiation damage. By alleviating this limitation, cryogenic coherent diffractive imaging (cryo-CDI) can in principle be used to bridge the important resolution gap between optical and electron microscopy in bio-imaging. Here, the first experimental demonstration of cryo-CDI for quantitative three-dimensional imaging of whole frozen-hydrated cells using 8 keV X-rays is reported. As a proof of principle, a tilt series of 72 diffraction patterns was collected from a frozen-hydrated Neospora caninum cell and the three-dimensional mass density of the cell was reconstructed and quantified based on its natural contrast. This three-dimensional reconstruction reveals the surface and internal morphology of the cell, including its complex polarized sub-cellular structure. It is believed that this work represents an experimental milestone towards routine quantitative three-dimensional imaging of whole cells in their natural state with spatial resolutions in the tens of nanometres.