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.

这项主要的研究工具（MRI）奖支持了三种商业上可用的工具的收购，这些工具将合并以创建新工具。要获得的三种仪器是共聚焦显微镜，原子力显微镜（AFM）和激光切割器。共聚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的高分辨率光学成像。 AFM将能够在这些样品上定义明确的位置施加良好的控制力，以测量其机械性能。另外，与共聚焦光显微镜相比，AFM还可以用于对样品表面进行更高分辨率的成像。激光切割器将在张力下时切割生物组织或纤维网络，以便可以通过测量切割后的后坐力来测量结构中的张力量。共同努力，这些仪器的组合将允许确定生物细胞和组织中发展的机械性能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。尽管众所周知，生物学和机械之间的相互作用在广泛的基本生物学过程中很重要，但探测不同类型的相互作用的特定工具受到限制。因此，对该工具的获取将基本上提高对生物系统和非生物系统的基本科学理解，这些系统类似于组成，结构和/或功能。获取该仪器还将推进与生物系统接口的材料的工程，以以期望的方式调整生物学反应。这将通过生物医学多个领域的进步来使社会受益。该乐器将在教育和职业的各个阶段为科学家和工程师提供新的培训和研究机会。具体的努力将集中在受益于早期研究人员和那些代表性不足的群体的成员中。高分辨率，高速共聚焦显微镜，这是一种用于与“湿”生物学和软性样本的AFM，以及将与“湿”生物学和软刀具进行工作，并将使用激光刀具组合来创建一个乐器，称为“机械学”。该仪器将用于研究机理生物学，包括表征细胞细胞骨架的纤维网络和细胞外基质，单细胞真核生物和原核生物机制（特别强调信号和分化），以及组织和有机体级的机制（具有连接性组织和形式的特定性）。该仪器还将用于研究生物生物界面的相互作用，重点是光响应动态水凝胶。此外，该仪器将用于开发新的软材料，包括活跃的软凝胶，胡椒纤维和刺激反应性软材料，这些软材料将基因工程细菌掺入了调整凝胶特性的功能成分。共聚焦显微镜将用于成像和福斯特/荧光共振能量转移（FRET）测量。 AFM将用于控制力应用，并用于测量Young的模量以及存储和损失模量。激光切割机将用于消融纤维网络，细胞细胞骨架和组织，以及作为交联动态水凝胶的照片刺激。该项目由主要的仪器研究计划（MRI）共同资助，并在公民机械和机械机械范围内（BMMB）（MRI）（MRI）（MRI）（MRI）（BMMB）（CMMB）。法定使命，并使用基金会的知识分子优点和更广泛的影响标准通过评估被认为是宝贵的支持。