Optimization and Delivery of Bioactive Coating for High Yield and Stable Neural Recording

用于高产量和稳定神经记录的生物活性涂层的优化和交付

• 批准号: 10022175
• 负责人: XINYAN Tracy CUI
• 金额: $ 54.05万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10022175
• 关键词: Adopted; Aging; Animals; Astrocytes; Binding Proteins; Biological; Biomimetics; Biosensor; Brain; Cell Count; Cell Culture Techniques; Cells; Chronic; Clinical; Cognition; Communities; Development; Devices; Disease Progression; Ensure; Environment; Enzymes; Exposure to; Foreign-Body Reaction; Freeze Drying; Health; Immobilization; Immunoassay; Implant; In Vitro; Inflammatory; Learning; Light; Location; Longevity; Manufacturer Name; Maps; Mediating; Membrane; Memory; Michigan; Microglia; Modeling; Monitor; Movement; Mus; Nature; Neural Cell Adhesion Molecule L1; Neurites; Neurons; Neurosciences; Neurosciences Research; Noise; Performance; Population; Procedures; Protein Array; Proteins; Protocols documentation; Rattus; Reaction; Resolution; Rodent; Route; Shipping; Signal Transduction; Sterilization; Surface; Technology; Testing; Time; Tissues; Universities; Work; base; brain computer interface; brain machine interface; brain tissue; clinical translation; crosslink; density; experimental study; implantation; improved; in vivo; interest; medical implant; microsystems; multi-electrode arrays; nanodevice; nanoparticle; neural prosthesis; nonhuman primate; preservation; relating to nervous system; response; wound healing

Project Summary The ability to monitor activity of ensembles of neurons at single-cell resolution, chronically, over long time periods is greatly desired by neuroscientists. A variety of multi-electrode arrays (MEAs) have been developed for in vivo studies. These arrays are capable of revealing the activity of neuronal ensembles. Unfortunately, none of the devices on the market is fully capable of obtaining recordings that are simultaneously high-yield and high-quality, as well as stable and useful over months to years. This well-known challenge has greatly limited our ability to track the activity of populations of single neurons over a sufficient period of time to fully investigate circuit change during learning and memory, development and aging, or disease progression and wound healing. Additionally, the clinical use of brain machine interface (BMI), which utilize recorded neural activities to decode movement intent for controlling machine, has been hindered by the unstable and unreliable recording. We have developed a biomimetic coating composed of a brain-derived L1-cell adhesion molecule that mitigate the inflammatory host tissue reaction. In rodents, L1 coated NeuroNexas probes maintained high quality neural recording over the period of 16 weeks with significant higher single unit yield and signal to noise ratio than the uncoated control probes. Meanwhile, recordings in non-human primates (NHPs) with L1-coated Blackrock MEAs also demonstrated high quality performance in single unit yield and signal amplitude for at least 6 months. MEA manufacturers and users expressed strong interest in utilizing this technology. However, the coating made of biological protein is fragile and may lose bioactivity during the harsh environment of shipping, storage and sterilization. In order to make the L1 coating a technology that can be widely adopted by the neuroscience community, we propose to optimize the coating stability and develop practical protocols for coating preservation, storage, packaging, delivery and sterilization. The bioactivity of the coating prepared with different protocols will first be tested with cell cultures. Promising procedures will then be tested with implantation and recording in rodents at the University of Pittsburgh. Once optimum coating and procedures are determined, coated arrays will be delivered to users to evaluate the coating performance. Dr. Buzsaki (NYU) will test the L1 coated NeuroNexas arrays in freely moving rats. Dr. Schwartz (U. Pitt) and Dr. Chestek (U. Michigan) will test the L1 coated Blackrock arrays in NHPs for BMI studies. Users will work closely with us to define specific performance criteria in their recording applications, compare performance of coated and uncoated arrays, and provide user input for us to improve the packaging and delivery. Throughout the project, representatives from two MEA manufacturers, Blackrock Microsystems and NeuroNexus Technology, will serve as consultants to ensure compatibility of our procedures with their devices and guide us on the path to dissemination. The project will produce a coating technology that is both easy to adopt and generalizable to all types of state- of-art and emerging MEAs. Solving the practical issues of sterilization, packaging and delivery is a critical step toward commercial and clinical translation of the technology. High quality and stable of neural recording will greatly improve our ability to map brain activity in long-term experiments, and benefit brain-computer interfaces and other types of neural prostheses. In a broader sense, the protocols developed here for preserving immobilized protein during storage, delivery and sterilization should be applicable to other medical implants containing bioactive proteins, immunoassays, protein arrays, enzyme-based biosensors or any micro/nano devices that incorporate biological components.

项目概要 能够以单细胞分辨率长期监测神经元群的活动 神经科学家非常渴望得到这样的周期。已开发出多种多电极阵列（MEA） 用于体内研究。这些阵列能够揭示神经元群的活动。很遗憾， 市场上没有一种设备完全能够同时获得高产量的录音 高品质，并且在数月至数年内稳定且有用。这个众所周知的挑战极大地 限制了我们在足够长的时间内追踪单个神经元群体活动的能力，以充分了解 研究学习和记忆、发育和衰老或疾病进展过程中的回路变化， 伤口愈合。此外，脑机接口（BMI）的临床应用利用记录的神经元 解码运动意图以控制机器的活动受到不稳定和不可靠的阻碍 记录。 我们开发了一种由脑源性 L1 细胞粘附分子组成的仿生涂层，可减轻 宿主组织的炎症反应。在啮齿类动物中，L1 涂层 NeuroNexas 探针保持了高质量的神经 16 周内的记录，单单位产量和信噪比明显高于 无涂层控制探头。与此同时，使用 L1 涂层 Blackrock 在非人类灵长类动物 (NHP) 中进行录音 MEA 还展示了至少 6 个单位产量和信号幅度的高质量性能 几个月。 MEA制造商和用户对利用该技术表现出浓厚的兴趣。然而， 由生物蛋白制成的涂层很脆弱，在恶劣的运输环境中可能会失去生物活性， 储存和灭菌。为了使L1涂层成为能够被广泛采用的技术 神经科学界，我们建议优化涂层稳定性并开发实用的方案 涂料的保存、储存、包装、运输和灭菌。制备的涂层的生物活性 不同的方案将首先用细胞培养物进行测试。然后将测试有前途的程序 匹兹堡大学的啮齿动物植入和记录。一旦最佳涂层和程序 确定后，涂层阵列将交付给用户以评估涂层性能。布萨基博士 （纽约大学）将在自由活动的老鼠身上测试 L1 涂层 NeuroNexas 阵列。 Schwartz 博士（皮特大学）和 Chestek 博士 （美国密歇根州）将在 NHP 中测试 L1 涂层 Blackrock 阵列，用于 BMI 研究。用户将与我们密切合作 定义其记录应用中的具体性能标准，比较涂层和 未涂层阵列，并为我们提供用户意见以改进包装和交付。在整个项目过程中， 来自 Blackrock Microsystems 和 NeuroNexus Technology 两家 MEA 制造商的代表将 担任顾问，确保我们的程序与其设备的兼容性，并指导我们走上 传播。 该项目将生产一种易于采用且可推广到所有类型国家的涂层技术。 艺术和新兴 MEA。解决灭菌、包装和运输的实际问题是关键的一步 致力于该技术的商业和临床转化。高质量和稳定的神经记录将 大大提高我们在长期实验中绘制大脑活动图谱的能力，并有利于脑机接口 和其他类型的神经假体。从更广泛的意义上讲，这里开发的协议是为了保存 储存、运输和灭菌过程中固定化的蛋白质应适用于其他医疗植入物 含有生物活性蛋白质、免疫分析、蛋白质阵列、酶基生物传感器或任何微/纳米 包含生物成分的设备。