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

大脑是一个高度可塑性的器官，具有学习、记忆和适应的能力。然而，它也是一种塑料材料，具有强度、硬度和抗冲击的机械性能。神经工程学中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撞击的后果？对大脑作用力的系统研究的一个主要限制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，用于向单个神经细胞施加力。这些单细胞研究将使我们能够比较神经对力的反应的个体差异，包括细胞力学、结构、活性和基因表达的变化。该项目是产业界和多方面学术团队的合作项目，将支持两名研究生的博士工作，举办研讨会，将对这一重要社会问题感兴趣的顶尖研究人员聚集在一起，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影响。为了检查作用力对神经元的影响，设备必须在几微秒内对单个细胞施加精确的作用力。现有的设备都没有提供这些力和时间响应，而开发这样的设备将使广泛的、新的细胞测量类别成为可能。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方式向单个电池提供毫牛顿冲击力。该设备充分利用了微纳尺度转换、微流体和分析技术的最新进展，将允许对细胞进行实时监测，并在撞击后收集细胞进行分析。UHammer将实现全新的实验类别，在这些实验中，冲击加载的生物后果可以作为加载后的力幅度、方向、持续时间和时间的函数来记录和监测。重点是显著提高对冲击和压力负荷对单个神经元、神经前体细胞和脑组织的作用的理解。其技术目标是设计、制造和测试一种能够对单细胞施加生理相关负载的工具(UHammer)，优化高通量操作神经干细胞的设备，并量化冲击对单细胞力学、结构、活性、克隆形成和基因表达的影响。由工程师、神经学家、生物学家和行业领袖组成的uHammer团队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。多学科的uHammer团队有能力在考虑最终用户的情况下设计新技术，实现新的科学发现，并将其转化为疗法和治疗方法。拟议的技术将使目前不可能进行的实验成为可能，而与工业合作伙伴猫头鹰生物医疗公司的联系和承诺将使快速的商业发展成为可能。有了这些伙伴关系和目标，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

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