Microthread arrays for long-term and high fidelity neural interfaces

描述（由申请人提供）：该申请涉及广泛的挑战领域（13）：智能生物材料-治疗学，以及特定的挑战主题，13- ns -101：开发与神经活动接口的新型生物材料。植入式神经接口装置是新兴神经义肢和神经刺激系统的重要组成部分，无论是在研究还是临床环境中。在几乎所有情况下，系统的性能在很大程度上取决于记录和/或刺激设备在质量、稳定性和寿命要求范围内的性能。根据许多报告，记录质量、寿命和稳定性是高度可变的，植入设备后发生的反应性组织反应可能是一个关键因素。最根本的挑战是开发先进的材料和可植入的结构，使神经接口装置能够植入大脑的目标区域，并在需要的时候保持功能，有时甚至长达几年甚至几十年。该提案提供了一种创新的策略，使用领先的生物相容性聚合物来开发创新的“微线神经探针”，这种探针超小且灵活，具有生物活性表面和纳米结构电极位点，可增强信号转导。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螺纹探针。我们将重点关注慢性神经记录尖峰活动的问题，因为这被认为是神经界面材料性能最敏感的测定方法。目标1是开发用于慢性神经记录的微线程神经探针的基本版本。这一目标将为微线程神经探针建立技术基础和一套验证基准。主要任务是将碳纳米管和功能化聚合物涂层技术整合到微线程神经探针中，从而可以可靠地插入大脑并用于慢性记录。设计空间包括尺寸、柔韧性、强度、导电性、场地电气特性、绝缘涂层、插入技术和电极尺寸。目标2将开发功能化的微线程神经探针，用于慢性组织反应的靶向干预。指导假设是，固定在微线探针表面的生物分子可以有效地干预特定的反应性组织反应，包括生物污垢、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开发慢性神经探针方面具有创新性，这些探针体积小（亚细胞），柔韧性强，具有出色的电学和转导特性，并且具有为特定生物过程量身定制的复杂表面。该项目有望通过开发先进的神经探针来实现长期（永久）、高质量和选择性的神经记录，从而做出重大贡献。该项目的成果也可能建立新的生物学启发范例，用于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界（神经外科医生、神经科医生和患者），他们使用并受益于基于神经修复和神经刺激的治疗干预。该项目的公共卫生相关性是改进用于治疗神经系统疾病或损伤的神经假体和神经刺激装置。

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.