Light sheet fluorescence microscope for large cleared samples

从定量和机械两个方面理解复杂生物系统的功能原理是RWTH亚琛大学生命科学研究的首要目标。在这种情况下，对细胞、系统和生物体功能的知识是基于对潜在的形态解剖结构的深入理解。因此，绘制这些结构的三维体积图并对其进行定量分析是亚琛RWTH进行的许多研究项目的强制性先决条件。在过去的十年里，已经描述了几种新的组织清除方法，使光学显微镜第一次能够对大的完整组织体积进行观察。光片荧光显微镜已经成为快速、温和地分析这种光学透明样品的最佳方法。在这里，样品的大小对显微镜提出了特殊的要求，传统的光片显微镜通常达到了极限。因此，专门为成像大型透明样品而设计的光片荧光显微镜已经被开发出来。在这份提案中，我们描述了对合适显微镜的具体要求，并申请采购一台专为大型透明样品成像而设计的光片荧光显微镜。我们打算将该仪器作为2020/2021年在亚琛RWTH建立的3D超分辨率核心设施的一部分。这样，我们将把这项新技术提供给校园内所有的生命科学研究小组。

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.