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

摘要：本文的目标是开发与神经系统无缝对接的生物相容性微系统。神经元通过电信号和化学信号进行交流。微机电系统（MEMS）将在生物空间和时间尺度上模拟这种细胞通信。将微电极和微流体集成到一个平台上，可以与细胞和组织进行多通道双向交互，其复杂程度是现有仪器无法实现的。这些微系统将包含聚合物，这些聚合物已被证明可以引起最小的生物反应性和生物污垢。为了实现这些目标，我的研究小组将开发以下工具：开发主动的，多通道的微流体系统，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。以及具有适当钝化和分离电极的生物相容性聚合物器件，用于支持细胞和组织切片。集成电和微流控元件，用于局部双模式刺激和记录游离细胞和完整组织切片。这些工具将促进细胞生物学和神经药理学的科学发现。此外，它们将为推进神经工程和组织工程提供新技术，其中包括：神经细胞和组织切片生物过程的体外双模式感知基于生物线索的可控和持续生长的局部生物反馈细胞、组织和共培养轴突生长和引导的体外研究植入式双模式微系统用于神经损伤和修复的体内研究中枢神经系统是最复杂的生物系统，可以说是最重要的。它也是最难与之交互的系统。该职业计划将开发复杂的双模工具，以调查和操纵局部神经微环境条件。这种能力是目前最先进的技术所不可能实现的。智力上的优点在于开发了新的工具，这些工具提高了我们对神经元通信中电信号和化学信号之间因果关系的认识。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，为再生神经回路和恢复失去的神经功能提供双向电子和化学线索。更广泛的影响中枢神经系统损伤（如创伤性脑损伤、脊髓损伤和中风）导致数百万美国人终身残疾，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，并带来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减少保健费用。南加州大学（USC）及其周边社区计划开展综合研究和教育活动，重点是增加女性和少数民族的参与。

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.