CAREER: Multifunctional Nanostructured Electrodes for Closed-Loop Control of Neural Activity

职业：用于神经活动闭环控制的多功能纳米结构电极

• 批准号: 1454426
• 负责人: Erkin Seker
• 金额: $ 50.48万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1454426&HistoricalAwards=false
• 关键词: CAREER; Multifunctional; Nanostructured; Electrodes; Closed

PI: Seker, ErkinProposal Number: 1454426A complex network of chemical and electrical signals is the basis of how the brain works. Medical devices that can be implanted into the brain, commonly referred to as neural interfaces, are emerging as powerful tools for treating neurological disorders as well as understanding the complex network underlying the brain's operation. These devices need to be engineered with attributes to minimize adverse tissue response, enhance fidelity in recording electrical signals, and controlling brain activity by precise delivery of electrical and chemical signals. Miniaturization technology used by the microelectronics industry has shrunk the dimensions of neural interfaces down to a few hair-widths. However, the demand for integrating multiple functions on these devices requires innovations in even smaller dimensions, where novel device coatings have shown promise. The overarching goal of this project is to engineer multifunctional devices that can monitor electrical signals that precede an epileptic seizure and in response deliver anti-epileptic drugs to prevent a full-blown seizure. To that end, the investigator will develop advanced device coatings that enhance the sensitivity in monitoring electrical signals and can deliver pharmaceuticals. The engineered materials and devices will be tested on brain slices from rats, which mimic tissue response to implanted devices and epileptic activity. The scientific knowledge and technology around the novel multifunctional materials will benefit a wide-range of fields, including vascular stent and orthopedic implant coatings, catalytic fuel cells, and biosensors for pathogens. In order to train a continuum of engineers and scientist conversant across engineering and life sciences, the investigator will engage undergraduate students in a "write and execute your own research proposal" style learning experience, deliver workshops for high school teachers on lesson plan development, and prototype an online course that merges miniaturization technology and life sciences for a diverse audience. This proposal is co-funded by the Biomedical Engineering Program in the Chemical, Bioengineering, Environmental and Transport Systems Division, and by the Metals and Metallic Nanostructures Program in the Division of Materials Research.An essential component of a neural interface is the electrode, which couples the neural tissue and the electronics. A critical step in engineering materials that interface with neural tissue is to understand the relationship between material properties, electrode performance, and biological responses. Nanoporous metals, with their highly-tunable properties, are promising candidates for systematically studying these fundamental relationships. One such material is nanoporous gold (np-Au), a nanostructured metal that is synthesized by self-assembly. Np-Au offers a tunable nanostructure, a large surface area-to-volume ratio, ease of integration with miniature devices, electrical conductivity, and drug-delivery capabilities. The central goal of the project is to employ a novel material screening platform to investigate material-tissue interactions simultaneously on both histological and electrophysiological levels. This in turn will reveal the relationship between tissue response and recording fidelity as a function of systematically-tuned topographical and soluble cues. Specifically, the investigator will develop an essential framework around selective promotion of specific cell types via soluble and topographical cues, as well as on demand delivery of neuromodulator pharmaceuticals. The project will finally employ organotypic brain slices as an epilepsy model to assess the capability of the multifunctional electrode coating in monitoring and pharmaceutically modulating neural electrophysiology in a closed-loop fashion. This will establish a unique, monolithically-manufacturable technology that can be easily scaled up and integrated into implantable neural interfaces for fundamental studies of neural circuitry.

PI：Seker，Erkin提案编号：1454426一个复杂的化学和电信号网络是大脑工作的基础。可以植入大脑的医疗设备，通常被称为神经接口，正在成为治疗神经系统疾病以及了解大脑运作背后的复杂网络的强大工具。这些设备需要设计成具有属性，以最大限度地减少不良组织反应，增强记录电信号的保真度，并通过精确传递电信号和化学信号来控制大脑活动。微电子工业使用的微型化技术已经将神经接口的尺寸缩小到几根头发的宽度。然而，在这些设备上集成多种功能的需求需要在更小的尺寸上进行创新，其中新型设备涂层已经显示出前景。该项目的总体目标是设计多功能设备，可以监测癫痫发作前的电信号，并响应提供抗癫痫药物，以防止全面发作。为此，研究人员将开发先进的设备涂层，提高监测电信号的灵敏度，并可以提供药物。工程材料和设备将在大鼠脑切片上进行测试，模拟组织对植入设备和癫痫活动的反应。围绕新型多功能材料的科学知识和技术将使广泛的领域受益，包括血管支架和骨科植入物涂层，催化燃料电池和病原体生物传感器。为了培养一批精通工程和生命科学的工程师和科学家，研究人员将让本科生参与“编写和执行自己的研究提案”式的学习体验，为高中教师提供关于课程计划开发的研讨会，并为不同受众设计一个融合小型化技术和生命科学的在线课程。 该提案由化学、生物工程、环境和运输系统部的生物医学工程项目和材料研究部的金属和金属纳米结构项目共同资助。神经接口的一个重要组成部分是电极，它将神经组织和电子器件耦合起来。与神经组织接触的工程材料的关键步骤是了解材料特性、电极性能和生物反应之间的关系。 纳米多孔金属具有高度可调的性质，是系统研究这些基本关系的有希望的候选者。一种这样的材料是纳米多孔金（np-Au），一种通过自组装合成的纳米结构金属。Np-Au提供了一种可调的纳米结构，大的表面积与体积比，易于与微型设备集成，导电性和药物输送能力。该项目的中心目标是采用一种新型材料筛选平台，同时在组织学和电生理学水平上研究材料-组织相互作用。这反过来将揭示组织反应和记录保真度之间的关系，作为系统调谐的地形和可溶性线索的函数。具体而言，研究人员将通过可溶性和地形线索以及按需递送神经调节剂药物，围绕特定细胞类型的选择性促进开发一个基本框架。该项目最终将采用器官型脑切片作为癫痫模型，以评估多功能电极涂层以闭环方式监测和药物调节神经电生理学的能力。这将建立一种独特的单片制造技术，可以很容易地扩大规模并集成到植入式神经接口中，用于神经电路的基础研究。