BeamMap: Ultra-High Resolution Topological and Chemical Imaging with Synergistic Liquid and Electron Beams

BeamMap：使用协同液体和电子束进行超高分辨率拓扑和化学成像

• 批准号: 10029717
• 负责人: ANDREI G FEDOROV
• 金额: $ 40.68万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10029717
• 关键词: Affect; Analytical Chemistry; Area; Atmospheric Pressure; Benchmarking; Biochemical; Biochemical Process; Biological; Biological Models; Biological Response Modifier Therapy; Biology; Biomedical Engineering; Biomedical Research; Cells; Cellular biology; Characteristics; Charge; Chemicals; Clinical; Cytometry; Detection; Development; Devices; Disease; Education; Electron Beam; Electron Microscope; Electron Microscopy; Electrospray Ionization; Electrostatics; Ensure; Excision; Gases; Goals; High Pressure Liquid Chromatography; Image; Imaging Device; Interdisciplinary Study; Investments; Ion Transport; Ions; Islets of Langerhans; Label; Lipid Chemistry; Liquid substance; Mass Spectrum Analysis; Measures; Medicine; Molecular; Molecular Medicine; Multimodal Imaging; Names; Paper; Performance; Play; Production; Proteins; Research; Research Infrastructure; Resolution; Risk Management; Role; Sampling; Scanning Electron Microscopy; Science; Scientist; Solvents; Spectrometry, Mass, Electrospray Ionization; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectrometry, Mass, Secondary Ion; Stains; System; Technology; Therapeutic; Time; Ultrafine; Vacuum; Validation; Variant; Work; base; biological research; biological systems; biomarker discovery; design; experimental study; imaging capabilities; imaging system; improved; innovation; insight; instrument; ion source; mass analyzer; mass spectrometer; multimodality; nanofabrication; new technology; operation; pancreas imaging; pressure; protein metabolite; prototype; risk mitigation; sensor; simulation; statistics; success; technology development; tool; ultra high resolution; voltage

PROJECT SUMMARY The proposed project aims to develop a unique new instrument for multi-mode imaging of biological samples with sub-cellular spatial resolution. It is enabled by a synergistic combination of Scanning Electron Microscopy and a new mode of Desorption Electrospray Ionization (DESI) imaging mass spectrometry. The new technology is called BeamMap for Beam Enabled Accurate Mapping & Molecular Analyte Profiling – where the enabling beams are the electron beam and the sprayed electrified liquid beam. BeamMap will provide untargeted characterization of protein, metabolite and lipid chemistry and correlation with topological features, yielding an order of magnitude improvement in the achievable resolution for electrospray based imaging, with chemical imaging resolution of ~ 250 nm and electron microscopy topological resolution of ~ 50 nm. Success in this high impact project has potential to bring about a transformative effect on many areas of biomedical sciences. The research team will develop, optimize and demonstrate BeamMap using a multifaceted approach that combines instrument design and simulation of critical components, state of the art micro/nanofabrication, and validation through carefully controlled experiments. As a result of this work, the research team will have be developed a fully functional, optimized, and well characterized prototype instrument, ready for application to challenging biomedical research questions. The PI and his research team are well situated for success, with a track record of high impact interdisciplinary research in mass spectrometry ion sources, bio-analytical devices, micro and nano-fabrication, and sensors development. This research will provide a new enabling technology for research endeavors in fundamental and clinical biology, medicine, analytical chemistry, and bioengineering. We expect that BeamMap will assume an important role in biological research as a hypothesis generator, and will become a key tool in molecular medicine applications. The proposed work will enhance the infrastructure for research and education by introducing a new powerful chemical imaging tool for use in high impact biological and therapeutic applications through the Marcus Center of Therapeutic Cell Characterization and Manufacturing (https://cellmanufacturing.gatech.edu/). Broad dissemination to enhance scientific and technological understanding will be achieved through technical papers and presentations in scientific forums and the use of the BeamMap by external scientists.

项目摘要 拟议项目旨在开发一种独特的新仪器，用于生物成像的多模式成像。 具有亚细胞空间分辨率的样本。它是由扫描电子显微镜的协同组合， 显微镜和一种新的解吸电喷雾电离（DESI）成像质谱模式。的 一项名为BeamMap的新技术，用于射束精确绘图和分子分析物分析- 其中使能束是电子束和喷射的带电液体束。BeamMap将 提供蛋白质、代谢物和脂质化学的非靶向表征以及与拓扑结构的相关性 特征，产生基于电喷雾的可实现分辨率的数量级改进。 成像，化学成像分辨率约250 nm，电子显微镜拓扑分辨率约50 nm.这一影响巨大的项目的成功有可能对许多领域产生变革性影响， 生物医学科学 研究团队将使用多方面的方法开发，优化和演示BeamMap， 结合了仪器设计和关键组件的模拟，最先进的微/纳米纤维， 通过精心控制的实验进行验证。作为这项工作的结果，研究小组将不得不 开发了一个功能齐全，优化和良好的特点原型仪器，准备应用于 挑战生物医学研究问题。PI和他的研究团队处于成功的有利位置， 在质谱离子源，生物分析设备， 微纳米制造和传感器开发。 这项研究将为基础和临床研究工作提供一种新的技术 生物学、医学、分析化学和生物工程。我们预计BeamMap将假设 在生物学研究中作为假设生成器的重要作用，并将成为分子生物学中的关键工具。 医药应用。拟议的工作将加强研究和教育的基础设施， 介绍一种新的强大的化学成像工具，用于高影响力的生物和治疗应用 马库斯治疗细胞表征和制造中心（Marcus Center of Therapeutic Cell Characterization and Manufacturing） （https：//cellmanufacturing.gatech.edu/）。广泛传播以加强科学和技术 将通过技术文件和在科学论坛上的介绍以及利用 外部科学家的BeamMap