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

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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.