NCS-FO: A microfluidic MEMS approach to study force-induced changes in neurons

NCS-FO：一种用于研究力引起的神经元变化的微流控 MEMS 方法

• 批准号: 1631656
• 负责人: Kimberly Foster
• 金额: $ 88.5万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1631656&HistoricalAwards=false
• 关键词: NCS; FO; microfluidic; MEMS; approach

CBET - 1631656Turner, KimberlyThe brain is a highly plastic organ, capable of learning, remembering and adapting. However, it is also a plastic material with mechanical properties of strength, hardness, and impact resistance. A major challenge in neuroengineering is to understand the biophysical properties of the brain and how these differ between individuals. In particular, how do differences in the mechanical properties of the brain alter the experience of force and the consequences of impact? A major limitation in the systematic study of force on the brain has been the inability to reliably apply impacts or pressure to individual cells. The uHammer project aims to develop just such a highly engineered tool for the application of force to individual neural cells. These single cell studies will allow us to compare individual differences in neural responses to force, including changes in cell mechanics, structure, viability, and gene expression. This project, a collaboration between industry and multi-faceted academic team, will support the Ph.D. work of two graduate students, hold a workshop to bring together top researchers interested in this important societal problem, and train undergraduate research interns, while attempting to unlock some of the mysteries surrounding the brain today.The focus of this work is to probe the mechanical properties of neural tissue and the subsequent effects on function. To examine the consequences of force on neurons, a device must apply precise forces to single cells over a few microseconds. No existing devices provide these force and temporal responses, and developing such a device would enable broad, new classes of cellular measurements. The development of a MEMS based device (the uHammer) that uses time gated magnetic actuation to deliver milliNewton impact forces to single cells in a high throughput fashion, will enable these measurements. The device, capitalizing on recent advances in micro and nanoscale transduction, microfluidics, and analytical techniques, will allow cells to be monitored in real-time and collected after impact for analysis. The uHammer will enable entirely new classes of experiments, in which the biological consequences of impact loading can be recorded and monitored as a function of force amplitude, direction, duration, and time after loading. The focus is to develop a significantly improved understanding of the role of impact and pressure loading on individual neurons, neural progenitors, and brain tissue. The technical goals are to Design, fabricate and test a tool (the uHammer) able to apply physiologically relevant loads to single cell, optimize the device for high-throughput manipulation of neural stem cells, and quantify the effect of impact on single cell mechanics, structure, viability, colony formation and gene expression. The uHammer team of engineers, neuroscientists, biologists and industry leaders is able to tackle these challenging questions, while also providing a unique learning environment for undergraduates and graduate students. The multidisciplinary uHammer team has the ability to design new technology with the end user in mind, enable new scientific discovery, and transform it into therapies and treatments. The proposed technology will enable experiments that are not presently possible, and the link to and commitment from industrial partner Owl Biomedical, will enable rapid commercial developments. With these partnerships and goals in hand, UCSB is poised to make game-changing breakthroughs on problems including traumatic brain injury (TBI) and Alzheimers disease

CBET -1631656特纳，金伯利大脑是一个高度可塑的器官，能够学习，记忆和适应。然而，它也是一种塑料材料，具有强度，硬度和抗冲击性的机械性能。神经工程的一个主要挑战是了解大脑的生物物理特性以及这些特性在个体之间的差异。特别是，大脑机械特性的差异如何改变力的体验和冲击的后果？对大脑受力的系统研究的一个主要局限是无法可靠地对单个细胞施加冲击或压力。uHammer项目旨在开发这样一种高度工程化的工具，用于对单个神经细胞施加力。这些单细胞研究将使我们能够比较对力的神经反应的个体差异，包括细胞力学，结构，活力和基因表达的变化。 该项目是工业界和多方面学术团队之间的合作，将支持博士学位。两名研究生的工作，举办一个研讨会，汇集对这一重要社会问题感兴趣的顶尖研究人员，并培训本科生研究实习生，同时试图解开当今围绕大脑的一些谜团。这项工作的重点是探索神经组织的机械特性及其对功能的后续影响。为了研究力对神经元的影响，设备必须在几微秒内对单个细胞施加精确的力。没有现有的设备提供这些力和时间响应，开发这样的设备将使广泛的，新类别的细胞测量。基于MEMS的设备（uHammer）的开发将使这些测量成为可能，该设备使用时间门控磁致动以高通量的方式向单个细胞传递毫牛顿冲击力。该设备利用了微和纳米级转导，微流体和分析技术的最新进展，将允许实时监测细胞并在撞击后收集用于分析。uHammer将实现全新类型的实验，其中可以记录和监测冲击载荷的生物后果，作为载荷后力振幅、方向、持续时间和时间的函数。重点是发展一个显着改善的理解的作用，影响和压力负荷对个别神经元，神经祖细胞和脑组织。技术目标是设计、制造和测试一种工具（uHammer），该工具能够向单细胞施加生理相关载荷，优化用于神经干细胞高通量操作的装置，并量化对单细胞力学、结构、活力、集落形成和基因表达的影响。uHammer团队的工程师，神经科学家，生物学家和行业领袖能够解决这些具有挑战性的问题，同时也为本科生和研究生提供了一个独特的学习环境。多学科uHammer团队有能力在设计新技术时考虑到最终用户，实现新的科学发现，并将其转化为疗法和治疗方法。这项技术将使目前不可能的实验成为可能，而与工业合作伙伴Owl Biomedical的联系和承诺将使商业发展迅速。有了这些伙伴关系和目标在手，UCSB准备在创伤性脑损伤（TBI）和阿尔茨海默病等问题上取得改变游戏规则的突破

项目成果

Controlled Single-Cell Compression With a High-Throughput MEMS Actuator

使用高通量 MEMS 致动器控制单细胞压缩

• DOI: 10.1109/jmems.2020.3005514
• 发表时间: 2020
• 期刊: Journal of Microelectromechanical Systems
• 影响因子: 2.7
• 作者: Walker, Jennifer L.;Patterson, Luke H.;Rodriguez-Mesa, Evelyn;Shields, Kevin;Foster, John S.;Valentine, Megan T.;Doyle, Adele M.;Foster, Kimberly L.
• 通讯作者: Foster, Kimberly L.

THE μHAMMER: INVESTIGATING CELLULAR RESPONSE TO IMPACT WITH A HIGH THROUGHPUT MICROFLUIDIC MEMS DEVICE

μHAMMER：利用高通量微流控 MEMS 设备研究细胞对冲击的反应

• DOI: 10.31438/trf.hh2018.47
• 发表时间: 2018
• 期刊: SC
• 作者: Patterson, L.H.C.;Walker, J.L.;Rodriguez-Mesa, E.;Shields, K.;Foster, J.S.;Valentine, M.T.;Doyle, A.M.;Foster, K.L.
• 通讯作者: Foster, K.L.

Inertial flow focusing: a case study in optimizing cellular trajectory through a microfluidic MEMS device for timing-critical applications

• DOI: 10.1007/s10544-020-00508-1
• 发表时间: 2020-08
• 期刊: Biomedical Microdevices
• 影响因子: 2.8
• 作者: Luke H. C. Patterson;Jennifer L. Walker;Mark A. Naivar;E. Rodriguez-Mesa;M. R. Hoonejani;K. Shields;J. Foster;A. Doyle;M. Valentine;K. Foster

Investigating Cellular Response to Impact With a Microfluidic MEMS Device

使用微流控 MEMS 设备研究细胞对冲击的响应

• DOI: 10.1109/jmems.2019.2948895
• 发表时间: 2020
• 期刊: Journal of Microelectromechanical Systems
• 影响因子: 2.7
• 作者: Patterson, Luke H. C.;Walker, Jennifer L.;Rodriguez-Mesa, Evelyn;Shields, Kevin;Foster, John S.;Valentine, Megan T.;Doyle, Adele M.;Foster, Kimberly L.
• 通讯作者: Foster, Kimberly L.