Electron detector and energy filter for an high-resolution cryo-electron microscope

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We apply for a state-of-the-art direct electron detector/energy filter upgrade for our existing cryo-electron microscopy facility. The recent technological developments in cryo-electron microscopy (cryo-EM) have led to a great scientific progress with respect to improved resolution and, hence, in its applicability. Using the novel direct electron detectors, single particle analysis has routinely reached resolutions at and below 3 Å, making cryo-EM the method of choice for a broad range of questions in structural biology. Newest developments in detector/energy filter technology in combination with advanced image processing software has culminated in yet another quantitative and qualitative leap, now allowing much faster data collection, more exhaustive classification of compositional and conformational heterogeneity and a resolution limit reaching down to 1.2-1.5 Å. In order to collect sufficient amount of data to reach a resolution facilitating e.g. structure-based drug design, with our current equipment and capacity an extraordinary amount of collection time would be necessary and resolutions below 2 Å are barely possible. Although all of our cryo-EM instruments are utilized essentially 24 hours/7 days a week with very little down-time, the capacity cannot satisfy the increasing demand and worldwide shifting state of the art for data quantity and quality. The latest generation of direct electron detectors have an improved detective quantum efficiency (DQE) and exposure times are several times shorter than with its predecessor. Therefore, we apply to purchase a high-end direct electron detector and energy filter system, which is expected to increase available data collection time and, importantly, also quality. More specifically, the proposed detector/filter system is planned to be installed at our newer 300keV instrument, whereas the existing detector/filter system will be relocated to the older instrument. As a result, the data collection capacity and quality of the new setup will allow analysis of small particles, of complexes with rare conformational or compositional states and of macromolecular complexes at sufficiently high resolution for all planned applications.