Detectors for Serial Nanocrystal Electron Diffraction

串行纳米晶体电子衍射探测器

• 批准号: RTI-2021-00517
• 负责人: Ernst, Oliver
• 金额: $ 10.93万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Research Tools and Instruments
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=718841
• 关键词: Detectors; Serial; Nanocrystal; Electron; Diffraction

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.

原子分辨结构是化学、结构生物学和材料科学的核心。有一种新的范式正在出现，以提供这一关键信息。多伦多大学开发的系列纳米晶体电子衍射仪（Serial NED）已被证明能够在室内进行高分辨率结构测定，与主要的国际X射线设备相当。通过采用连续采样与剂量分级相结合，它已被证明可以消除辐射损伤的限制结构的分辨率。电子在X射线上的散射截面高出105 - 106倍意味着只需要纳米晶体来解决结构。此外，在考虑从合成中的按比例放大确定结构的全部时间预算中，对于足够的材料来生长用于X射线分析的更大的微晶、样品纯化、访问光束线的潜在延迟等，这种新方法代表了用于结构确定的流水线中高达10倍的速度。 两个国家的最先进的透射电子显微镜（TEM）已经开发出先进的串行NED。一个TEM专用于小分子结构测定，另一个针对结构生物学进行了优化，两者都将位于化学系，以便于监督和维护。该方案要求这两个TEM采用两个基于电子计数的直接电子探测器，以消除噪声，并允许极短的有效帧读出剂量分数，以确保收集的数据没有辐射损伤。这些探测器对于串行NED的执行至关重要，并且在基本零噪声、连续读出格式的亚毫秒有效快门速度和接近单位的量子效率方面具有独特的性能。鉴于材料需求的减少和结构测定的相关高得多的吞吐量，也因为不需要去偏远的国际设施，Serial NED有望改变化学和结构生物学中的结构测定方式。 横跨化学，生物化学，物理学和材料科学系的几个小组将联手推进这一新概念。该设施将为学生培训营造一个高度跨学科的环境，直接影响超过75名学生和受训人员，为此将提供专门的研讨会，让学生亲自接触从数据收集，大数据分析到结构优化的最新方法的结构确定的各个方面。这种培训水平超出了在使用主要国际设施期间通常获得的培训水平，因为学生将成为实验各个方面的专家。他们将是下一代学生，他们将推动采用Serial NED，以帮助它充分发挥其改造结构生物学和化学的潜力。