Light Sheet Microscope for Multi-View Imaging of Living and Optically Cleared Samples

Project Summary / Abstract This shared instrument proposal requests funding for a Zeiss Light Sheet 7 to be incorporated into the MicRoN (Microscopy Resources on the North Quad) core at Harvard Medical School. Imaging of whole organs and thick tissue samples in a more physiological context has become the next frontier in many areas of biomedical

research. Traditionally, researchers rely on extracting information about cellular components within a two- dimensional section of tissue instead of the entire volume of the sample. Because most of components in tissues and organisms are not contained in a 2D plane, quantitative volumetric imaging would enhance our

understanding of their development, structure and function. Due to its high imaging speed, light efficiency, low photo-toxicity, and inherent optical sectioning capabilities, light-sheet microscopy has emerged as a powerful tool to accomplish this mode of imaging in both live and fixed, optically cleared samples. Unlike many instruments

currently available, the one we are proposing to purchase provides a great deal of versatility and flexibility in applications, ranging from live cell imaging of organisms and organs/organoids to imaging fixed thick samples that have been optically cleared with either water-based (expansion, CLARITY, CUBIC) or solvent-based (iDisco)

methods. The proposed instrument will enhance a broad range of biomedical research, including studies of immune cell function and interactions with tissues, pathogenesis and neurodevelopmental disorders, gene therapy for hearing and balance disorders, zebrafish phenotypes and the developmental biology of new model

organisms.