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.

项目摘要 /摘要 该竞争性补充申请要求资金购买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 新的多标签，正在开发的元素探针的性能基准测试以扩展影响和 多色电子显微镜（COLOREM）的可及性。这项工作将在主动的背景下进行 正在推进采用新技术的新型方法开发新技术的研究项目 对于超高速度4D-STEM（5 R01GM138780-03）。这个资助的项目正在执行可行性研究 并克服技术挑战：1）用元素探测器制作多标签的EM标本 为色系统优化的组合（以及Colorem的所有方法可扩展）； 2）对第一次使用故障排除 用于茎检测的潜在变革性新技术以及原子数的相关能力 （z）对比成像； 3）解决处理/分析非常大的主要数据集的方法 以加速元素分化/信号解释并允许显示色系统结果。这 要求的超快速直接电子检测器将使我们能够加速并增强我们的记录能力， 比较并优化性能元件探针组合（对于信噪比和差异 对比度），并提供了对我们的定量性能的更敏感和准确的验证 数据处理例程，这些程序与标签化学物质合作，使我们能够可靠和 准确地从一个选择性标记的结构中准确地辨别出另一个选择性标记的结构的信号。 所请求的设备项目是Apollo（直接电子，LP），低噪声，高速电子计数，直接 用于传输电子显微镜的检测装置（DDD），该传输设备具有行业领先的信号 - 噪声和吞吐量规范将使我们能够更快，更准确地验证 新的元素探测器，从而加速了父母奖的目标1和3的完成。