Advancing Multi-Color EM via Direct Detector-enabled 4D-STEM

通过支持直接检测器的 4D-STEM 推进多色 EM

• 批准号: 10795540
• 负责人: Mark H Ellisman
• 金额: $ 22.4万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10795540
• 关键词: 3-Dimensional; Acceleration; Advanced Development; Award; Benchmarking; Cells; Chemistry; Color; Complex; Computer software; Data Set; Detection; Development; Devices; Electron Microscopy; Electrons; Elements; Energy-Filtering Transmission Electron Microscopy; Equipment; Feasibility Studies; Funding; Industry; Label; Methodology; Methods; Molecular; Noise; Outcome; Parents; Performance; Request for Applications; Research Project Grants; Resolution; Signal Transduction; Specific qualifier value; Specimen; Speed; Structure; Technology; Tissues; Transmission Electron Microscopy; Validation; Work; computerized data processing; contrast imaging; detector; new technology; novel; transmission process

PROJECT SUMMARY / ABSTRACT This competitive supplement application requests funds to procure a high speed direct electron counting detector for analytical Energy Filtered TEM (EFTEM). This detector will allow us to accelerate the validation and performance benchmarking of new multi-label, elemental probes under development to scale the impact and accessibility of multicolor electron microscopy (ColorEM). This work will be conducted in the context of an active research project that is advancing the development of a novel method for ColorEM, employing new technologies for ultra-high-speed 4D-STEM (5 R01GM138780-03). This funded project is performing the feasibility studies and surmounting the technical challenges to: 1) make multi-labelled EM specimens with elemental probe combinations optimized for ColorSTEM (and extensible to all methods for ColorEM); 2) troubleshoot the first use of potentially transformative new technologies for STEM detection and associated capabilities for atomic-number (Z) contrast imaging; and, 3) work out the methodology for processing/analysis of very large primary data sets so as to accelerate elemental differentiation/signal interpretation and allow for display of ColorSTEM results. The ultra-fast direct electron detector requested, will allow us to accelerate and sharpen our ability to record, compare, and optimize the performance elemental probe combinations (for both signal-to-noise and differential contrast) as well as provide for a more sensitive and accurate validation of the quantitative performance of our data processing routines, which work hand-in-hand with the labeling chemistry to allow us to reliably and accurately discern the signal recorded from one selectively labeled structure from the specific signal of another. The equipment item requested is an Apollo (Direct Electron, LP), low-noise, high-speed electron-counting, direct detection device (DDD) for transmission electron microscopy, which possesses an industry-leading signal-to- noise and throughput specification that will allow us to more rapidly and accurately validate the performance of new elemental probes, thus accelerating the completion of Aims 1 and 3 of the parent award.

项目概要/摘要 此竞争性补充申请需要资金来采购高速直接电子计数检测器 用于分析能量过滤 TEM (EFTEM)。该检测器将使我们能够加速验证和 对正在开发的新型多标签元素探针进行性能基准测试，以衡量影响和 多色电子显微镜（ColorEM）的可访问性。这项工作将在积极的背景下进行 研究项目采用新技术推进 ColorEM 新方法的开发 用于超高速 4D-STEM (5 R01GM138780-03)。该资助项目正在进行可行性研究 并克服技术挑战：1）用元素探针制作多标记电磁标本 针对 ColorSTEM 优化的组合（并可扩展到 ColorEM 的所有方法）； 2）首次使用故障排除 STEM 检测和原子序数相关功能的潜在变革性新技术 (Z)对比成像； 3）制定处理/分析非常大的原始数据集的方法 从而加速元素分化/信号解释并允许显示 ColorSTEM 结果。这 所要求的超快直接电子探测器将使我们能够加速和提高我们的记录能力， 比较并优化性能基本探头组合（对于信噪比和差分探头） 对比），并为我们的定量性能提供更灵敏和准确的验证 数据处理例程，与标记化学携手合作，使我们能够可靠和 准确地区分从一个选择性标记结构记录的信号与另一结构的特定信号。 请求的设备项目是 Apollo（直接电子，LP），低噪声，高速电子计数，直接 用于透射电子显微镜的检测装置（DDD），拥有业界领先的信号到 噪声和吞吐量规范，使我们能够更快、更准确地验证性能 新的元素探测器，从而加速完成母奖的目标1和3。