Biological systems operate at the nanoscale while at the same time forming complex macroscale communities. Therefore, resolving interactions and tracking key metabolic processes within living systems requires multi-scale imaging, enabling visualization of live cells at the community, cellular, subcellular, and single-molecule scales. While techniques like light sheet fluorescence microscopy (LSFM) are possible at these various scales, light sheets illuminate samples from only one side, resulting in shadowing artifacts that can obscure the view and disrupt accurate interpretation of the larger system. This Phase I STTR project will develop an innovative parabolic mirror- based imaging system that is compatible with existing inverted microscopes and that eliminates shadowing across scales—at both high and low resolution—to enable highly accurate interpretation of any specimen. The project objectives include building a prototype system and testing its functionality and benefits on a range of live cell types. The ability to visualize microbial communities without shadowing will open up new experimental space for understanding the complex energetic relationships in microbial systems. Moreover, in the longer term, the radical design change made possible by this technology will provide a platform for new innovation, enabling the development of completely new imaging techniques and expanding what is currently possible in the field of live-cell fluorescent microscopy.
