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.

原子解析结构是化学、结构生物学和材料科学的核心。正在出现一种新的范式来提供这些关键信息。多伦多大学开发的串行纳米晶体电子衍射 (Serial NED) 已被证明能够在室内进行高分辨率结构测定，与主要国际 X 射线设备相当。通过采用连续采样与剂量分割相结合，已证明可以消除结构分辨率的辐射损伤限制。电子散射截面比 X 射线高出 105 - 106 倍，这意味着仅需要纳米晶体即可解析结构。此外，考虑到从合成规模扩大到确定结构的全部时间预算，以获​​得足够的材料来生长更大的微晶，用于 X 射线分析、样品纯化、访问光束线等的潜在延迟，这种新方法代表了高达 10-加速管道中的结构确定。 两种最先进的透射电子显微镜 (TEM) 已被开发出来以推进串行 NED。一台 TEM 专用于小分子结构测定，另一台针对结构生物学进行优化，两者将位于化学系，以便于监督和维护。该提案要求这两个 TEM 配备两个基于电子计数的直接电子探测器，以消除噪声并允许剂量分数的极短有效帧读数，以确保收集的数据不受辐射损坏。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以及接近单位量子效率方面具有独特的性能。鉴于材料需求的减少以及结构测定中相关的更高通量，也因为无需前往远程国际设施，Serial NED 有望改变化学和结构生物学中结构测定的方式。 化学、生物化学、物理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 名学生和受训者，为此将举办专门研讨会，让学生能够接触到结构确定的各个方面，从数据收集、大数据分析到最新的结构确定。结构细化的方法。这种培训水平超出了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。他们将成为下一代学生，推动 Serial NED 的采用，帮助其充分发挥改变结构生物学和化学的潜力。