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亚毫米大小的设备，具有纳米和微尺度的功能特征，使科学家能够在与神经元及其过程相同的长度尺度上进行操作，从而促进了迄今为止由于缺乏适当的小型化工具而使研究人员无法解决的新研究问题和范式。当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/纳米设备，当它们被置于研究人员手中时，将作为广泛的神经科学研究的基本微工具，用于轴突和树突功能，损伤和再生。这两种微尺度的研究工具是光学清晰的纳米刀，由纳米级的锋利边缘组成，可以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，它可以向单个轴突提供高度校准的压缩力，以研究常见的压迫性神经损伤如何在基本轴突水平上影响神经生物学功能。由于轴突和树突是神经系统中负责细胞通讯的基本单位，因此有大量研究人员研究健康和疾病中的轴突和树突生物学，他们将从收集、探测或操纵单个轴突和树突片段的新能力中获益良多。从这些新型微型工具中受益的一个临床相关研究领域是神经创伤，成人脊髓和大脑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、微制造以及严格的设备机械和生物测试。基本的仪器设计利用了公司早期开发的原型纳米刀，并增加了一些关键功能，以增强用户的便利性和设备的稳健性。硅晶圆批量制造也被用于以相对较低的成本提供这两种微工具，以最大限度地减少采用障碍。这种微型仪器的发展将为未来的设备增强奠定基础，例如集成板载驱动以自动执行切割或压缩冲程。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型装置，以帮助推进研究。

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.