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

PI：Seker，Erkin Proposal Number：1454426化学和电信号的复杂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将不良组织反应降至最低的属性，提高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宽。然而，在这些设备上集成多种功能的需求需要在更小尺寸上进行创新，在这些领域，新型设备涂层已经显示出希望。该项目的总体目标是设计多功能设备，能够监测癫痫发作之前的电信号，并相应地提供抗癫痫药物，以防止癫痫全面发作。为此，研究人员将开发先进的设备涂层，以提高监测电信号的灵敏度，并能够输送药物。这些工程材料和设备将在大鼠的脑切片上进行测试，这些切片模拟组织对植入设备的反应和癫痫活动。围绕新型多功能材料的科学知识和技术将造福于广泛的领域，包括血管支架和整形外科植入涂层、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学和生命科学的工程师和科学家，研究人员将让本科生参与一种“编写并执行自己的研究计划”式的学习体验，为高中教师提供关于教案制定的研讨会，并为不同的受众制作一门融合微型化技术和生命科学的在线课程的原型。这项提议由化学、生物工程、环境和运输系统部门的生物医学工程计划和材料研究部门的金属和金属纳米结构计划共同资助。神经接口的一个基本组件是电极，它连接神经组织和电子设备。在设计与神经组织接口的材料时，关键的一步是了解材料特性、电极性能和生物响应之间的关系。纳米多孔金属具有高度可调谐的性质，是系统研究这些基本关系的有希望的候选者。其中一种材料是纳米多孔金(NP-Au)，这是一种通过自组装合成的纳米结构金属。NP-Au具有可调的纳米结构、较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使用一种新的材料筛选平台来同时在组织学和电生理水平上研究材料与组织之间的相互作用。这反过来将揭示组织反应和记录保真度之间的关系，作为系统调整的地形和可溶线索的函数。具体地说，研究人员将围绕通过可溶和局部线索选择性促进特定细胞类型，以及按需提供神经调节剂药物，开发一个基本框架。该项目最终将使用器官型脑片作为癫痫模型，以评估多功能电极涂层在闭环方式监测和药物调制神经电生理方面的能力。这将建立一种独特的、可单芯片制造的技术，可以很容易地放大并集成到可植入的神经接口中，用于神经电路的基础研究。

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.