MRI: Development of an Advanced Bio-Imaging Instrument: Enabling 3D quantitative multifunctional sensing at the nanoscale

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An award is made to the University of Colorado at Boulder to develop next-generation optical nano-imaging instrumentation to expand research and research training in criticalareas of science and engineering. The project will transform the microscopy capabilities at the University of Colorado at Boulder by generating a multi-functional nanoscope with unique characteristics. The instrument will be shared by investigators in the BioFrontiers Institute and departments in the colleges of Engineering and Arts and Sciences. Wide availability of next generation optical nanoscopy is critical to ensure emerging interdisciplinary research activities. This platform will bring together physicists, electrical engineers, biological engineers, biochemists, molecular biologists, cellular biologists, computer scientists, and mathematicians to work together on developing methods for increasing resolution and advancing modern microscopy in biologically relevant problems. The equipment will be the center of interdisciplinary research and a focus for the development of new ideas and technologies that cross traditional departmental boundaries. Furthermore, the platform will provide state-of-the-art optical imaging capabilities to the community through the BioFrontiers core facility.The project will advance understanding of nanoscale phenomena both at the subcellular level and within different types of materials, bringing about improvements in bioscience and advanced instrumentation. Current bioscience research is strongly dependent onthe investigators ability to characterize sub-cellular structure and function at the nanoscale. Emerging optical microscopy techniques enable imaging of cellular details and macromolecular structure previously unimaginable. Remarkably, fluorescencenanoscopy is compatible with live cells and able to multiplex labeling with high molecular specificity. While these techniques promise to create a revolution in biological research, current incarnations present significant shortcomings: limited field of view and depth of field, limited acquisition rate unsuitable for fast live cell phenomena, need for significant light dosage creating photo-damage, and unsuitability for deep imaging. The project is set to overcome these shortcomings by an integrated design of techniques such as point-spread function engineering, single-molecule localization microscopy, fast structured illumination, and adaptive microscopy.