Collaborative Research: Multimode Adaptive 3D Microscopy for Quantitative Analysis of Live-Cellular Dynamic Processes in Thick Samples

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The goal of this project is to design, develop and investigate a computational optical microscopy system to generate three-dimensional (3D) images with greatly enhanced resolution. The system will enable biologists to visualize and measure live-cellular dynamic processes in thick samples that might otherwise go undetected due to aberrations that worsen with imaging depth in conventional microscopes. The new system will overcome these limitations while providing additional benefits in terms of functionality and resolution. For example, it will be possible to simultaneously provide high accuracy fluorescent images and 3D position information, as well as phase (refractive index) and amplitude (absorption) information, so that each biological feature will be associated with quantitative information in 3D space. Another capability of the system will enable tracking moving micro-organisms accurately and even measuring the velocity of dynamic processes. The prospect of obtaining 3D information with high depth accuracy opens up myriad possibilities to address new biological applications such as studies of epithelial wound healing mechanisms and morphodynamic changes in cancer cells. The system could prove useful to detect the remodeling of cytoskeletal proteins, such as actin, during cell migration in culture or in lung tissue. The system, designed for optimized performance with respect to various imaging conditions, will provide significant advances in many biological and medical applications that critically depend on 3D resolution that is not available with current systems. Training opportunities will open for a diverse cadre of young scientists and engineers in the multi- disciplinary field of biological instrument development. A new laboratory for education, research, and interdisciplinary work at the University of Memphis will be established. Knowledge gained from the research will become part of a new graduate course in Computational Imaging at the University of Memphis and new teaching lab modules at the University of Colorado. The new multimodal microscope will be made available to other biological collaborators in both campuses.The project will also take advantage of synergistic partnerships with bio-imaging companies to transfer new discoveries into industrial applications.