CAREER: Biologically-Inspired Polymer Microeletromechanical Systems (MEMS) for Bi-Directional Neural Interfaces

这个提议的目标是开发生物兼容的微系统，它将与神经系统无缝对接。神经元使用电信号和化学信号进行交流。微型机电系统(MEMS)将被开发出来，在生物、空间和时间尺度上模拟这种细胞交流。将微电极和微流体集成到一个平台中，可以实现与细胞和组织的多通道双向相互作用，达到现有仪器无法达到的复杂程度。这些微系统将包含已被证明可引起最小生物反应性和生物污垢的聚合物。为了实现这些目标，我的研究小组将开发以下工具：开发用于生物流体、营养物质和药物的空间和时间精确输送和采样的有源、多通道微流控系统开发稳定、长期和生物兼容的聚合物设备，以及适当的钝化和保护电极，以支持细胞和组织切片集成用于局部双模刺激的电和微流控元素，并从分离的细胞和完整的组织切片进行记录这些工具将推动细胞生物学和神经药理学的科学发现。此外，它们还将使推进神经工程和组织工程的新技术成为可能，其中包括：对神经细胞和组织切片中的生物过程进行双模式体外检测；基于生物线索进行局部生物反馈，以进行细胞、组织和共培养中可控和可持续生长的研究；以及指导细胞、组织和共培养中的轴突生长；可植入的双模式微系统，用于在体研究神经损伤和修复。它也是最难连接的系统。这项职业规划将开发复杂的双模工具，以实现对局部神经微环境条件的调查和操作。在目前的最先进水平下，这种能力是不可能的。智能的优点在于开发了新的工具，提高了我们对神经元通讯中电信号和化学信号之间的因果关系的了解。这种微系统接口技术也将应用于其他生物系统。最终目标是开发新型生物医学植入物，为重新生长神经回路和恢复丢失的神经功能提供双向电和化学线索。BROADER IMPACT对中枢神经系统的损伤(如创伤性脑损伤、脊髓损伤和中风)在数百万美国人中导致毁灭性的终身身体残疾，目前是无法治愈的疾病。这项研究将使人们对神经损伤有新的认识，并导致促进神经修复的新疗法。对社会的直接好处包括减轻人类痛苦和降低医疗费用。计划在南加州大学(南加州大学)及其周边社区开展综合研究和教育活动，重点是增加女性和少数群体的参与。

AbstractEllis MengThe objective of this proposal is to develop biocompatible microsystems that will seamlessly interface with neural systems. Neurons communicated using both electrical and chemical signals.Microelectromechanical systems (MEMS) will be developed that mimic this cellular communication at biological spatial and temporal scales. Integration of microelectrodes and microfluidics into a single platform allows multi-channel bi-directional interaction with cells and tissue at a level of sophistication not possible with existing instrumentation. These microsystems will incorporate polymers that have been demonstrated to elicit minimal bioreactivity and biofouling. To achieve these objectives, my research group will develop the following tools:Develop active, multi-channel microfluidic systems for spatially and temporally precise delivery and sampling of biological fluids, nutrients, and drugsDevelop stable, long-term, and biocompatible polymer devices with appropriate passivation andisolation of electrodes for support of cells and tissue slices Integrate electrical and microfluidic elements for localized dual-mode stimulation and recording from dissociated cells and intact tissue slicesThese tools will advance scientific discovery in cellular biology and neuropharmacology. Additionally, they will enable new techniques for advancing neuroengineering and tissue engineering which include: Dual-mode in vitro sensing of biological processes in neural cells and tissue slices Localized biofeedback based on biological cues for controlled and sustained growth In vitro studies on axonal growth and guidance in cells, tissue, and co-cultures Implantable dual-mode microsystems for in vivo investigation of neural injury and repairINTELLECTUAL MERITThe central nervous system is the most complex biological system and arguably the most important. It is also the most difficult system to interface with. This CAREER plan will develop sophisticated dual-mode tools to enable investigation and manipulation of local neural microenvironment conditions. Such capability is not possible with the current state-of-the-art. The intellectual merit lies in the development of new tools that advance our knowledge of the cause-effect relationship between electrical and chemical signals in neurons communication. This microsystems interface technology will also be applied to other biological systems. The ultimate goal is to develop novel biomedical implants that provide bi-directional electrical and chemical cues for re-growing neural circuits and restoring lost neural functions.BROADER IMPACTInjuries to the central nervous system (e.g. traumatic brain injury, spinal cord injury, and stroke) result in devastating lifelong physical disabilities in millions of Americans and are presently incurable conditions. This research will enable new understanding of neural injury and lead to new treatments that promote neural repair. The direct benefits to society include the alleviation human suffering and reduction in health care costs. Integrated research and education activities are planned for the University of Southern California (USC) and its surrounding communities with emphasis in increased participation by females and minorities.