Algorithm for characterizing the subcellular structures of nanometer-sized biological specimens in a solution using x-ray free-electron lasers

Jhih-Heng Yang^1*, Ning-Jung Chen¹, YeuKuang Hwu², Chien-Chun Chen^1,3,4

¹Department of Engineering and System Science, National Tsing Hua University, Hsinchu, Taiwan
²Institute of Physics, Academia Sinica, Taipei, Taiwan
³Instrument Technology Research Center, National Applied Research Laboratories, Hsinchu, Taiwan
⁴National Synchrotron Radiation Research Center, Hsinchu, Taiwan

* Presenter:Jhih-Heng Yang, email:garrygt4@gmail.com

Coherent diffraction imaging using third generation synchrotron sources and x-ray free-electron lasers has been demonstrated to be an excellent tool for revealing the inner structures of a single particle. The primary challenge in imaging pure, tiny, and isolated biological specimens is obtaining a reliable reconstruction from diffraction data that have a poor signal-to-noise ratio. Thus, we developed a robust method that yields the internal density distribution of liposome vesicles immersed in a solution. By combining the guided hybrid input-output method and a new order parameter defined by the consistency of the reconstruction, we, without prior knowledge, retrieved both pure and drug-containing liposome vesicles from individual diffraction patterns. This result is currently the smallest noncrystalline biological specimen resolved by single-shot coherent diffraction microscopy.

Keywords: coherent diffraction imaging, x-ray free-electron lasers, phase retrieval, noncrystalline biological specimen