Project Abstract
Light-sheet fluorescence microscopy (LSFM), through its gentle, efficient, and fast 3D
imaging capacity, has tremendous potential in biological, biomedical, and translational
applications. However, LSFM has fragmented into a myriad of specialized instruments,
each optimized for a specific class of samples and imaging regimes. As such, the
widespread use and ultimate impact of LSFM has been curtailed by its lack of adaptability.
Here we propose a universal LSFM platform that can be adapted to a wide range of
applications, ranging from sensitive live cell imaging to imaging organs and tissues that
have been rendered transparent by different clearing techniques. Further, we will improve
the spatial and temporal resolution, as well as the volumetric coverage of LSFM. These
additional improvements will be packaged in modules, which can be integrated into our
proposed platform on demand. To demonstrate its biomedical potential, we will image
human cardiomyocytes, both live and with super-resolution microscopy, to evaluate the
performance of emerging cardiac therapies on a molecular level. In its most sensitive
configuration, our LSFM platform will be able to study spatiotemporal patterns of calcium
signaling, in health and disease, which we will analyze with statistical times series
analysis methods.
Overall, our proposal will increase the capabilities and accessibility of LSFM, and as such
will spur three-dimensional imaging in biological and biomedical research.
