Light sheet fluorescence microscope for large cleared samples

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Understanding the functional principles of complex biological systems both quantitatively and mechanistically is the overarching goal of life science research at RWTH Aachen University. In this context, knowledge of cellular, systemic and organismal function is based on an in-depth understanding of the underlying morphological-anatomical structures. To map the complexity of these structures volumetrically in three dimensions and to analyze them quantitatively is therefore a mandatory prerequisite for many of the research projects pursued at RWTH Aachen. In the past decade, several new tissue clearing methods have been described, allowing light microscopy of large intact tissue volumes for the first time. Light sheet fluorescence microscopy has emerged as the optimal method for a fast and gentle analysis of such optically transparent samples. Here, the size of the samples places special demands on the microscope, and conventional light sheet microscopes usually reach their limits. Therefore, light sheet fluorescence microscopes specifically designed for imaging large, transparent samples have been developed. In this proposal, we describe the specific requirements for a suitable microscope and apply for the procurement of a light sheet fluorescence microscope engineered for imaging of large cleared samples. We intend to operate the instrument as part of the Core Facility for 3D Super-Resolution established at RWTH Aachen in 2020/2021. This way, we will make this new technology available to all life science research groups on campus.