Imaging live cells at a resolution higher than achieved using optical microscopy is a challenge. Ultra-fast coherent diffractive imaging with X-ray free-electron lasers (XFELs) has the potential to achieve sub-nanometer resolution on micron-sized living cells. Our container-free injection method can introduce a beam of live cyanobacteria into the micron-sized focus of the Linac Coherent Light Source (LCLS) to record of diffraction patterns from individual cells, with very low noise at high hit rates (millions of cells/day). We used iterative phase retrieval to derive two-dimensional projection images directly from the diffraction patterns. In a first experiment, we collected diffraction patterns to 33-46 nm full-period resolution, and reconstructed the exit wave front to 76 nm full-period resolution. In a second experiment, we demonstrate that it is indeed possible to record diffraction data to nanometer resolution on live cells with an intense, ultra-short X-ray pulse as predicted earlier. These results are encouraging, and future developments to the XFELs and improvements to the X-ray area-detectors will bring sub-nanometer resolution reconstructions of living cells within reach. Utilizing this type of diffraction data will require the development of new analysis methods and algorithms for studying structure and structural variability in large populations of cells and to create abstract models. Such studies will allow us to understand living cells and populations of cells in new ways.
Gijs van der Schot, Tomas Ekeberg, and Janos Hajdu, "Imaging heterogeneity using an x-ray free-electron laser (Conference Presentation)," Proc. SPIE 10076, High-Speed Biomedical Imaging and Spectroscopy: Toward Big Data Instrumentation and Management II, 100760Y (Presented at SPIE BiOS: January 31, 2017; Published: 24 April 2017); https://doi.org/10.1117/12.2249771.5381802499001.
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