A light-sheet microscopy (LSM)-based, spatially-resolved 3D dynamic mechanical analysis (DMA) instrument for developmental biology and physiology

康涅狄格大学（University of Connecticut）开发了一种仪器和方法，将光片显微镜（LSM）和动态力学分析（DMA）相结合，以表征活体组织和器官的动态力学特性。该仪器量化组织发育过程的能力将极大地促进发育生物学和生理学的研究。组织材料特性的测量也将为神经生物学、心血管生物学和衰老研究提供重要信息，因为任何器官系统的功能都与其结构特征相关。该仪器将建立在一个开源平台上，使科学界可以广泛使用它。本项目旨在通过对果蝇、斑马鱼和小鼠这三种生物学中广泛使用的动物模型进行分析，证明该仪器的适用性。通过该仪器实现的组织和器官发育的时间过程三维可视化将促进公众对诸如不孕症、胚胎疾病和癌症进展等健康问题的理解。该工具的开发还将导致K-12教育的低成本工具的设计，这将有利于代表性不足的种族和少数民族，他们获得工程教育的机会有限。LSM是一种新兴的技术，可以在很长一段时间内对活体生物样本进行高时间和空间分辨率的3D成像。它可以观察整个器官/组织的发育和细胞分化和迁移的高分辨率跟踪。DMA在工业、科学和工程中被广泛用于表征聚合物和生物材料的粘弹性。该项目的创新之处在于集成了微型机器人精密机械臂和基于图像的3D结构分析，结合了LSM和DMA的优点，创造了一种能够对生长组织和器官进行空间分辨动态力学分析的新型仪器。在器官发育过程中，物理力量推动或拉动组织。动态组织材料特性定义了组织如何响应这些施加的力并控制器官形状的形成。虽然细胞力的作用机制已经得到了很好的研究，但组织材料特性在形态发生中的作用还有待研究。该仪器将能够测量动态材料特性和力，为研究生物学中最基本的问题之一提供重要信息：“器官是如何形成的？”通过传统方法难以实现的全器官3D分析。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

An award is made to the University of Connecticut to develop an instrument and method that integrate light-sheet microscopy (LSM) and dynamic mechanical analysis (DMA) to characterize the dynamic mechanical properties of live tissues and organs. The instrument's capability to quantify the process of tissue development will greatly advance the study of developmental biology and physiology. The measurement of tissue material properties will also provide vital information to neurobiology, cardiovascular biology, and research on aging because the functions of any organ system are correlated to its structural characteristics. The instrument will be built on an open-source platform, making it widely accessible to the scientific community. This project aims to demonstrate the applicability of the instrument through the analysis of three animal models widely used in biology, namely, Drosophila, zebrafish, and mouse. The time-course 3D visualization of tissue and organ development enabled by the instrument will promote the public understanding of health issues such as infertility, embryonic diseases, and cancer progression. The development of the instrument will also lead to the design of low-cost tools for K-12 education, which will benefit underrepresented racial and ethnic minorities who have limited access to engineering education.LSM is an emerging technology that enables 3D imaging of live biological samples with high temporal and spatial resolution over a long time period. It allows observation of whole organ/tissue development and high-resolution tracking of cell differentiation and migration. DMA is widely used in industry, science, and engineering to characterize the viscoelastic properties of polymers and biomaterials. The project's innovation is the integration of a miniature robotic precision manipulator and image-based 3D structural analysis that combines the benefits of LSM and DMA and creates a novel instrument capable of spatially-resolved dynamic mechanical analysis of growing tissues and organs. During organ development, physical forces push or pull tissues. Dynamic tissue material properties define how tissues respond to those applied forces and control the formation of organ shapes. Although the mechanisms of cellular forces are well studied, the role of tissue material properties on morphogenesis is yet to be studied. The instrument will be capable of measuring both dynamic material properties and forces, providing vital information for studying one of the most fundamental questions in biology: "how are organs shaped?" through whole-organ 3D analysis that is difficult with conventional methodsThis award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.