High-throughput imaging of heterogeneous cell organelles with an X-ray laser

作者：Hantke Max F^*; Hasse Dirk; Maia Filipe R N C; Ekeberg Tomas; John Katja; Svenda Martin; Loh N Duane; Martin Andrew V; Timneanu Nicusor; Larsson Daniel S D; van der Schot Gijs; Carlsson Gunilla H; Ingelman Margareta; Andreasson Jakob; Westphal Daniel; Liang Mengning; Stellato Francesco; DePonte Daniel P; Hartmann Robert; Kimmel Nils; Kirian Richard A; Seibert M Marvin; Muhlig Kerstin; Schorb Sebastian; Ferguson Ken; Bostedt Christoph; Carron Sebastian

来源：Nature Photonics, 2014, 8(12): 943-949.

DOI：10.1038/NPHOTON.2014.270

We overcome two of the most daunting challenges in single-particle diffractive imaging: collecting many high-quality diffraction patterns on a small amount of sample and separating components from mixed samples. We demonstrate this on carboxysomes, which are polyhedral cell organelles that vary in size and facilitate up to 40% of Earth%26apos;s carbon fixation. A new aerosol sample-injector allowed us to record 70,000 low-noise diffraction patterns in 12 min with the Linac Coherent Light Source running at 120 Hz. We separate different structures directly from the diffraction data and show that the size distribution is preserved during sample delivery. We automate phase retrieval and avoid reconstruction artefacts caused by missing modes. We attain the highest-resolution reconstructions on the smallest single biological objects imaged with an X-ray laser to date. These advances lay the foundations for accurate, high-throughput structure determination by flash-diffractive imaging and offer a means to study structure and structural heterogeneity in biology and elsewhere.

• 出版日期2014-12