Micro/Nano Devices For Neuroscience Research

描述（由申请人提供）：Mynosys Cellular Devices的长期目标是开发新的半机器人微型设备，使科学家能够直接物理探测或操纵单个神经元或亚细胞过程，用于各种实验和治疗目的。这些新设备被设想为具有纳米和微米级功能特征的亚毫米级设备，使科学家能够在与神经元及其过程相同的长度尺度上操作，从而促进新的研究问题和范式，这些问题和范式迄今为止由于缺乏适当的小型化工具而一直困扰着研究人员。目前第一阶段提案的具体目标是开发两种易于使用的硅基微/纳米器件，当这些器件放在研究人员手中时，将作为轴突和树突功能，损伤和再生的广泛神经科学研究的基本微工具。这两种微尺度研究工具是一种光学透明的纳米刀，包括纳米级的锋利边缘，允许精确采集或实验损伤神经功能的基本单位，如轴突和树突。此外，我们将生产一种轴突纳米压缩器，可以将高度校准的压缩力传递到单个轴突上，以研究常见形式的挤压性神经损伤如何影响基本轴突水平的神经生物学功能。由于轴突和树突是神经系统中负责细胞通讯的基本单位，因此有大量的研究人员在健康和疾病中研究轴突和树突生物学，他们将从新的能力中受益匪浅，以收获，探测或操纵单个轴突和树突段进行研究。将受益于这些新型微尺度工具的临床相关研究领域是神经创伤，其中成年脊髓和大脑中的轴突在损伤后无法再生是一个非常重要的健康和社会经济问题，也是神经科学的主要挑战。将高度精确、可重复和校准的损伤力传递到单个轴突上的能力将有助于推进这一领域的研究。该研究计划包括工程设计，微制造，严格的设备机械和生物学测试。基本的仪器设计利用了公司早期开发的原型nanoknife，增加了关键功能，以提高用户的便利性和设备的鲁棒性。硅晶片批量制造也被用来以相对较低的成本提供两种微工具，以最大限度地减少采用的障碍。这种微型仪器的开发将为未来的设备改进奠定基础，例如集成板上驱动以自动执行切割或压缩行程。此外，从拟议项目中获得的经验和知识将有助于未来开发更多的神经微设备，以帮助推进研究。 公共卫生相关性：拟议的微型仪器为神经科学家提供了直接操纵神经细胞及其过程并与之相互作用的能力，使他们能够以前所未有的小规模测定细胞功能。由于对神经系统疾病和疾病的主要悬而未决的问题的答案将来自对神经元及其组成部分的内部工作的更深入了解，这种新颖的微型仪器将有助于促进科学调查，加深我们对疾病机制的理解，并加速寻找潜在的治疗方法。

DESCRIPTION (provided by applicant): The long-term objective of Mynosys Cellular Devices is to develop new semi-robotic microdevices that enable scientists to directly physically probe or manipulate individual neurons or subcellular processes for a variety of experimental and therapeutic purposes. Envisioned as sub- millimeter-sized devices that have nano and microscale functional features, these novel devices allow scientists to operate at the same length-scale as neurons and their processes, facilitating new research questions and paradigms that thus far have eluded investigators due to a lack of appropriate miniaturized tools. The Specific Aims of the current Phase I proposal are to develop two easy-to-use silicon-based micro/nanodevices, that when placed in the hands of researchers, will serve as fundamental microtools for a broad range of neuroscience research on axon and dendritic function, injury, and regeneration. These two microscale research tools are an optically clear nanoknife comprising of a nanoscale sharp edge that allows accurate harvesting or experimental injury of elemental units of neural function such as axons and dendrites. In addition, we will produce an axon nanocompressor that can deliver highly calibrated compressive forces onto single axons to study how common forms of crushing nerve injury affects neurobiological function at the fundamental axonal level. As axons and dendrites are the essential units responsible for cellular communication in the nervous system, there is a substantial researcher base investigating axonal and dendritic biology in health and disease, who will benefit significantly from new abilities to harvest, probe, or manipulate individual axonal and dendritic segments for study. A clinically relevant research area that will benefit from these novel microscale tools is neural trauma, where the inability of axons in the adult spinal cord and brain to regenerate after injury is a very significant health and socioeconomic problem as well as a major challenge for neuroscience. The ability to deliver highly precise, repeatable, and calibrated injury forces onto single axons will aid in advancing this area of investigation. The research plan incorporates engineering design, microfabrication, with rigorous device mechanical and biological testing. The basic instrument design leverages an earlier company-developed prototype nanoknife, with the addition of key features to enhance user convenience and device robustness. Silicon wafer batch fabrication is also exploited to deliver both microtools at a relatively low cost to minimize barriers for adoption. The development of this micro-instrumentation will lay the foundation for future device enhancements such as the integration of on-board actuation to automate execution of the cutting or compression strokes. In addition, the experience and knowledge gained from the proposed project will be useful in the future development of additional neuro-microdevices to help advance research. PUBLIC HEALTH RELEVANCE: The proposed micro-instrumentation provides neuroscientists with the ability to directly manipulate and interact with nerve cells and their processes, allowing them to assay cell function at an unprecedented small scale. As the answers to major outstanding questions of diseases and illnesses of the nervous system will come from a deeper understanding of the inner workings of the neuron and its components, this novel micro-instrumentation will help facilitate scientific investigation, deepen our understanding of disease mechanisms, and accelerate the search for potential therapies.