MRI: Track 1 Acquisition of a System for Integrated Confocal Microscopy and Mechanical Interrogation

MRI：轨道 1 获取集成共焦显微镜和机械询问系统

• 批准号: 2320311
• 负责人: Vernita Gordon
• 金额: $ 138.7万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2320311&HistoricalAwards=false
• 关键词: MRI; Track; Acquisition; System; Integrated

This Major Research Instrumentation (MRI) award supports the acquisition of three commercially-available instruments that will be combined to create a new instrument. The three instruments to be acquired are a confocal microscope, an atomic force microscope (AFM), and a laser cutter. The confocal microscope will be able to do fast, high-resolution optical imaging of living cells and tissues as well as soft gels and other soft materials. The AFM will be able to apply well-controlled forces at well-defined locations on these samples, to measure their mechanical properties. Additionally, the AFM can also be used to do higher-resolution imaging of sample surfaces than the confocal light microscope. The laser cutter will be used to cut biological tissues or fiber networks while they are under tension, so that the amount of tension in the structure can be measured by measuring the recoil following the cut. Working together, the combination of these instruments will allow determination of the mechanical properties that develop in biological cells and tissues and how biological cells and tissues respond to a range of mechanical inputs from their environments. Although it is well-known that the interplay between biology and mechanics is important in a wide range of essential biological processes, specific tools for probing the different types of interplay have been limited. Therefore, the acquisition of this instrument will substantially advance basic scientific understanding of biological systems and of non-biological systems that resemble biological systems in composition, structure, and/or function. Acquisition of this instrument will also advance the engineering of materials that interface with biological systems to tune biological response in the desired way. This will benefit society through advances in multiple areas of biomedicine. The instrument will offer new training and research opportunities to scientists and engineers at all stages of their education and career. Specific efforts will be focused on benefiting early-career researchers and those who are members of under-represented groups.A high-resolution, high-speed confocal microscope, an AFM designed for work with “wet” biological and soft-matter samples, and a laser cutter will be combined to create one instrument, termed the “mechanoscope.” This instrument will be used to investigate mechanobiology, including the fiber networks that characterize the cellular cytoskeleton and the extracellular matrix, single-cell eukaryotic and prokaryotic mechanobiology (with a particular emphasis on signaling and differentiation), and tissue- and organism-level mechanobiology (with a particular emphasis on connective tissue and morphogenesis). This instrument will also be used to investigate interactions at the biotic-abiotic interface, focusing on photo-responsive dynamic hydrogels. Further, the instrument will be used in the development of new soft materials, including active soft gels, peptide fibrils, and stimuli-responsive soft materials that incorporate genetically engineered bacteria as a functional component for tuning gel properties. Confocal microscopy will be used for imaging and Forster/fluorescence resonance energy transfer (FRET) measurements. AFM will be used for controlled force application and for measurement of Young’s moduli and storage and loss moduli. The laser cutter will be used for ablation of fiber networks, cellular cytoskeletons, and tissues, and as a photo-stimulus for crosslinking dynamic hydrogels.This project is jointly funded by the Major Instrumentation Research Program (MRI) and the Biomechanics and Mechanobiology Program (BMMB) in the division of Civil, Mechanical and Manufacturing Innovation (CMMI).This 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.

该重大研究仪器 (MRI) 奖项支持购买三台商用仪器，将它们组合起来创建一台新仪器。这三台仪器是共焦显微镜、原子力显微镜 (AFM) 和激光切割机。共焦显微镜将能够对活细胞和组织以及软凝胶和其他软材料进行快速、高分辨率的光学成像，AFM 将能够在这些样品上明确的位置施加良好控制的力。测量此外，与共焦光学显微镜相比，AFM 还可用于对样品表面进行更高分辨率的成像。激光切割机可用于在张力作用下切割生物组织或纤维网络，从而减少张力。可以通过测量切割后的反冲来测量结构，这些仪器的组合将能够确定生物细胞和组织中产生的机械特性以及生物细胞和组织如何响应来自其环境的一系列机械输入。虽然是众所周知的。生物学和力学之间的相互作用在广泛的基本生物过程中很重要，但用于探测不同类型相互作用的特定工具却很有限，因此，获得该仪器将大大促进对生物系统和非生物系统的基本科学理解。 -在组成、结构和/或功能上类似于生物系统的生物系统也将推进与生物系统接口的材料工程，以期望的方式调整生物反应，这将通过多个方面的进步造福社会。该仪器将提供生物医学领域。为处于教育和职业生涯各个阶段的科学家和工程师提供新的培训和研究机会，具体努力将集中于使早期职业研究人员和代表性不足群体的成员受益。高分辨率、高速共聚焦显微镜。 ，一种设计用于处理“湿”生物和软物质样品的原子力显微镜和激光切割机将被组合起来创建一种仪器，称为“机械镜”。该仪器将用于研究机械生物学，包括表征的光纤网络。该仪器还将包括细胞骨架和细胞外基质、单细胞真核和原核力学生物学（特别强调信号传导和分化）以及组织和生物体水平的力学生物学（特别强调结缔组织和形态发生）。该仪器将用于研究生物-非生物界面的相互作用，重点关注光响应动态水凝胶。此外，该仪器将用于开发新型软材料，包括活性软材料。凝胶、肽原纤维和刺激响应软材料，通过基因工程改造细菌作为调节凝胶特性的功能成分，将用于成像，福斯特/荧光共振能量转移（FRET）将用于受控力测量。激光切割机将用于光纤网络、细胞骨架和组织的消融，并用作杨氏模量、储能模量和损耗模量的测量。用于交联动态水凝胶的光刺激。该项目由土木、机械和制造创新 (CMMI) 部门的主要仪器研究计划 (MRI) 和生物力学和力学生物学计划 (BMMB) 联合资助。该奖项反映了 NSF 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。