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

项目总结 该项目旨在开发一种独特的新仪器，用于生物的多模式成像 具有亚细胞空间分辨率的样本。它是由扫描电子的协同组合实现的 显微镜和解吸电喷雾电离(DESI)成像质谱学的新模式。这个 一项名为BeamMap的新技术被称为束控精确映射和分子分析剖析- 其中使能射束是电子束和喷射的带电液体射束。BeamMap将 提供蛋白质、代谢物和脂肪化学的非目标表征以及与拓扑的关联 特性，使电喷雾的可实现分辨率提高了数量级 成像，化学成像分辨率为~250 nm，电子显微镜拓扑分辨率为~50 NM。这一高影响力项目的成功有可能对许多领域产生变革性的影响 生物医学科学。 研究小组将使用一种多方面的方法来开发、优化和演示BeamMap 将仪器设计和关键部件的模拟、最先进的微/纳米制造技术和 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 开发了功能齐全、优化且特性良好的原型仪器，可应用于 具有挑战性的生物医学研究问题。PI和他的研究团队为成功做好了准备，拥有 在质谱学离子源、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使能技术 生物学、医学、分析化学和生物工程。我们预计，BeamMap将假定 作为假说生成器在生物学研究中的重要作用，并将成为分子研究的关键工具 医药应用。拟议的工作将通过以下方式加强研究和教育的基础设施 推出一种新的强大的化学成像工具，用于高影响的生物和治疗应用 通过马库斯治疗细胞表征和制造中心 (https://cellmanufacturing.gatech.edu/).)广泛传播，提高科学技术水平 将通过技术论文和在科学论坛上的演讲以及使用 外部科学家的波束图。

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.