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.

项目摘要 长期以来，长期以来在单细胞分辨率下监测神经元合奏的活动的能力 神经科学家非常需要时期。已经开发了多种多电极阵列（MEA） 用于体内研究。这些阵列能够揭示神经元集合的活性。很遗憾， 市场上没有一个设备完全能够获得同时高收益的录音 和高质量的，以及数月至数年的稳定且有用的。这个著名的挑战有很大的 限制我们在足够的时间内跟踪单个神经元种群活动的能力 在学习和记忆，发展和衰老或疾病进展过程中调查电路变化 伤口愈合。此外，使用记录的神经 不稳定且不可靠的活动阻碍了解码用于控制机器的运动意图的活动 记录。 我们已经开发了一种由脑衍生的L1细胞粘附分子组成的仿生涂层，可缓解 炎症性宿主组织反应。在啮齿动物中，L1涂层神经元探针保持高质量的神经 在16周内记录，单位产量和信号比率明显高于 未涂层的对照探针。同时，用L1涂层的二十条录音在非人类灵长类动物（NHP）中 MES还表明，至少6个单位产率和信号振幅的高质量性能 月份。 MEA制造商和用户对利用这项技术表示浓厚的兴趣。但是， 由生物蛋白制成的涂层是脆弱的，在运输的恶劣环境中可能会失去生物活性， 存储和灭菌。为了使L1涂层一项技术可以广泛采用的技术 神经科学社区，我们建议优化涂料稳定性，并为 涂料保存，存储，包装，输送和灭菌。与 不同的方案将首先通过细胞培养进行测试。然后将对有希望的程序进行测试 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，涂层阵列将交付给用户以评估涂料性能。 Buzsaki博士 （NYU）将在自由移动的大鼠中测试L1涂层的神经唱阵列。 Schwartz博士（U. Pitt）和Chestek博士 （美国密歇根州）将在NHPS中测试L1涂层的贝莱克阵列进行BMI研究。用户将与我们紧密合作 要在其记录应用中定义特定的性能标准，请比较涂层的性能和 未涂层的数组，并为我们提供用户输入，以改善包装和交付。在整个项目中， 来自两个MEA制造商，贝莱德微系统和神经毒技术技术的代表将 作为顾问，以确保我们的程序与设备的兼容性，并指导我们走上通往的道路 传播。 该项目将生产既易于采用又可以推广到所有类型的国家 - Art和Art和新兴的措施。解决灭菌，包装和交付的实际问题是关键的一步 迈向该技术的商业和临床翻译。高质量和稳定的神经记录将 大大提高了我们在长期实验中绘制大脑活动的能力，并使脑部计算机界面受益 和其他类型的神经假体。从广义上讲，这里开发的协议用于保存 存储期间固定的蛋白质应适用于其他医疗植入物 含有生物活性蛋白，免疫测定，蛋白质阵列，基于酶的生物传感器或任何微/纳米 结合生物组件的设备。