Detectors for Serial Nanocrystal Electron Diffraction

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Atomically resolved structures are at the core of chemistry, structural biology, and material science. There is a new paradigm emerging to provide this critical information. Serial Nanocrystal Electron Diffraction (Serial NED) developed at the University of Toronto has been demonstrated to be capable of high resolution structure determination in house on par with major international x-ray facilities. By adopting serial sampling in combination with dose fractionation, it has been shown to eliminate radiation damage limits to structural resolution. The factor of 105 - 106 higher scattering cross section of electrons over x-rays means that only nanocrystals are needed to solve structures. Further, in considering the full time budget in determining structures from the scale up in synthesis for enough material to grow larger microcrystals for x-ray analysis, sample purification, potential delays in accessing beam lines etc, this new approach represents an up to 10-fold speed up in the pipeline for structure determination. Two state of the art Transmission Electron Microscopes (TEMs) have been developed to advance Serial NED. One TEM is dedicated to small molecule structure determination and the other is optimized for structural biology and both will be co-located in the Department of Chemistry for ease of oversight and maintenance. This proposal requests two direct electron detectors based on electron counting for these two TEMs to eliminate noise and allow extremely short effective frame readouts for dose fraction to ensure the collected data is free of radiation damage. These detectors are essential to the execution of Serial NED and are unique in performance with respect to essentially zero noise, sub-millisecond effective shutter speeds in continuous readout formats, and near unity quantum efficiency. Given the reduction in material requirements and associated much higher throughput in structure determination, also because there is no need to go to remote international facilities, Serial NED holds the promise to change how structure determination in chemistry and structural biology are done. Several groups spanning the departments of chemistry, biochemistry, physics, and material science will join forces to advance this new concept. This facility will foster a highly interdisciplinary environment for student training, directly impacting over 75 students and trainees, for which specialized workshops will be offered that will give students hands on access to all aspects of structure determination from data collection, big data analysis, to latest methods in structure refinement. This level of training goes beyond that typically acquired during the use of major international facilities in that the students will become expert in all aspects of the experiment. They will be the next generation of students who will drive the adoption of Serial NED to help it reach its full potential to transform structural biology and chemistry.