Microthread arrays for long-term and high fidelity neural interfaces

描述(由申请人提供)：本申请涉及广泛的挑战领域(13)：智能生物材料-Theranostics，以及具体的挑战主题13-NS-101：开发与神经活动接口的新型生物材料。在研究和临床环境中，植入式神经接口设备是一大类新兴的神经假体和神经刺激系统的关键组件。在几乎所有情况下，系统的性能在很大程度上取决于设备的性能，以满足质量、稳定性和寿命要求的记录和/或刺激。根据大量报道，记录质量、寿命和稳定性是高度可变的，植入设备后发生的组织反应可能是一个关键因素。根本的挑战是开发先进的材料和可植入结构，使神经接口设备能够被植入大脑的目标区域，并在需要的时间内保持功能，有时可以延伸到几年甚至几十年。这一提议提供了一种创新策略，使用尖端的生物兼容聚合物来开发创新的微线神经探针，这种探针具有超小和灵活的、具有生物活性的表面和纳米结构的电极位置，用于增强信号转导。我们将使用先进的碳纳米管(CNT)和生物活性聚合物涂层技术来制造这些微线探针。我们将重点讨论放电活动的慢性神经记录问题，因为这被认为是神经界面材料性能最敏感的测试。目标1是开发用于慢性神经记录的微线神经探针的基础版本。这一目标将为微线神经探头奠定技术基础和一套验证基准。主要任务将是将碳纳米管和功能化聚合物涂层技术集成到可以可靠地插入大脑并用于慢性记录的微线神经探针中。设计空间包括尺寸、灵活性、强度、导电性、现场电气特性、绝缘涂层、插入技术和电极尺寸。Aim 2将开发功能化微线神经探针，用于对慢性组织反应进行靶向干预。指导性假设是，固定在微线探针表面的生物分子可以有效地干预特定的组织反应，包括生物污垢、炎症和神经毒性。这一提议在其生物启发的策略和使用尖端生物材料来开发慢性神经探针方面具有创新之处，这种探针小(亚细胞)、灵活、强大，具有优异的电学和转换性能，并具有为特定生物过程量身定做的复杂表面。该项目可能会通过开发用于长期(永久)、高质量和选择性神经记录的先进神经探头来做出重大贡献。该项目的成果还可能建立新的生物启发范例，用仿生材料创建持久、高保真的神经接口。该项目将影响使用神经假体和基于神经刺激的治疗干预并从中受益的神经科学研究社区和临床社区(神经外科医生、神经病学家和患者)。该项目的公共卫生意义在于改进神经假体和神经刺激设备，用于治疗神经疾病或损伤。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (13): Smart Biomaterials - Theranostics, and specific Challenge Topic, 13-NS-101: Developing novel biomaterials to interfaces with neural activity. Implantable neural interface devices are a critical component to a broad class of emerging neuroprosthetic and neurostimulation systems, in both research and clinical settings. In almost all cases, the performance of the system hinges to a large degree on the performance of the device to record and/or stimulate within quality, stability, and longevity requirements. Recording quality, longevity and stability is highly variable according to numerous reports, and the reactive tissue response that occurs to devices following implantation is a likely key contributing factor. The fundamental challenge is to develop advanced materials and implantable structures that will enable neural interface devices to be implanted in target areas of the brain and remain functional for as long as needed, sometimes stretching into years and decades. This proposal provides an innovative strategy that uses leading-edge biocompatible polymers to develop innovative 'microthread neural probes' that are ultra-small and flexible, with bioactive surfaces and nanostructured electrode sites for enhanced signal transduction. We will create these microthread probes using advanced carbon nanotube (CNT) and bioactive polymer coating technologies. We will focus on the problem of chronic neural recording of spike activity because this is considered to be the most sensitive assay of neural interface material performance. Aim 1 is to develop base versions of microthread neural probes for chronic neural recording. This aim will establish a technology foundation and set of validation benchmarks for microthread neural probes. The primary tasks will be to integrate CNT and functionalized polymer coating technologies into microthread neural probes that can be reliably inserted into the brain and used for chronic recording. The design space includes size, flexibility, strength, conductivity, site electrical characteristics, insulating coating, insertion techniques, and electrode size. Aim 2 will develop functionalized microthread neural probes for targeted intervention in chronic tissue responses. The guiding hypothesis is that immobilized biomolecules on the microthread probe surface be effective for intervening with specific reactive tissue responses, including biofouling, inflammation, and neurotoxicity. This proposal is innovative in its biologically inspired strategies and use of leading-edge biomaterials to develop chronic neural probes that are small (sub-cellular), flexible, and strong with excellent electrical and transduction properties, and have sophisticated surfaces tailored for specific biological processes. This project is likely to make significant contributions through developing advanced neural probes for long-term (permanent), high quality and selective neural recording. The outcomes of this project are also likely to establish new biologically inspired paradigms for creating long-lasting, high-fidelity neural interfaces with biomimetic materials. This project will impact both the neuroscience research community, and clinical communities (neurosurgeons, neurologists, and patients) that use and benefit from neuroprosthetic- and neurostimulation-based treatments interventions. The public health relevance of this project is to improve neural prosthetic and neural stimulation devices for treatment of neurological diseases or injury.