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-治疗诊断学，以及特定的挑战主题，13-NS-101：开发新型生物材料以与神经活动连接。 在研究和临床环境中，植入式神经接口设备是新兴神经假体和神经刺激系统的广泛类别的关键组件。 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，以在质量、稳定性和寿命要求内记录和/或刺激。 根据大量报告，记录质量、寿命和稳定性存在很大差异，植入后器械发生的反应性组织反应可能是一个关键影响因素。 根本的挑战是开发先进的材料和可植入的结构，使神经接口设备能够植入大脑的目标区域，并在需要的时间内保持功能，有时甚至长达数年甚至数十年。 该提案提供了一种创新策略，该策略使用领先的生物相容性聚合物来开发创新的“微线程神经探针”，该探针具有超小和灵活性，具有生物活性表面和纳米结构电极位点，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制造这些微螺纹探针。 我们将集中在尖峰活动的慢性神经记录的问题，因为这被认为是最敏感的测定神经接口材料的性能。 目的1是开发用于慢性神经记录的微线程神经探针的基础版本。 这一目标将为微线程神经探针建立一个技术基础和一套验证基准。 主要任务将是将CNT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、柔性、强度、导电性、部位电气特性、绝缘涂层、插入技术和电极尺寸。 目的二是开发功能化的微线神经探针，用于慢性组织反应的靶向干预。 指导性假设是，微线探针表面上的固定生物分子可有效地干预特定的反应性组织反应，包括生物污染、炎症和神经毒性。 该提案在其生物启发策略和使用前沿生物材料方面具有创新性，以开发小（亚细胞），灵活，坚固，具有优异的电气和转导特性的慢性神经探针，并具有针对特定生物过程定制的复杂表面。 该项目可能通过开发用于长期（永久），高质量和选择性神经记录的先进神经探针做出重大贡献。 该项目的成果也有可能建立新的生物灵感范例，用于使用仿生材料创建持久，高保真的神经接口。 该项目将影响神经科学研究界和临床社区（神经外科医生，神经学家和患者），这些社区使用并受益于基于神经假体和神经刺激的治疗干预。 该项目的公共卫生意义在于改进神经修复和神经刺激装置，以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.