Optimization of Flexible Neural Probe Arrays for Multi-Region Recordings in Rodents and Nonhuman Primates

用于啮齿动物和非人类灵长类动物多区域记录的柔性神经探针阵列的优化

• 批准号: 10401221
• 负责人: Ellis Meng
• 金额: $ 143.6万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10401221
• 关键词: Action Potentials; Active Sites; Acute; Address; Adopted; Adoption; Animal Model; Animals; Area; Atlases; BRAIN initiative; Back; Behavior; Behavioral; Brain; Brain region; Chronic; Collaborations; Communities; Computer software; Data; Development; Device Designs; Devices; Dimensions; Electrodes; Electrophysiology (science); Ensure; Evaluation; Feedback; Film; Goals; Hippocampus (Brain); Histologic; Histology; Immune response; Implantation procedure; Investigation; Length; Libraries; Link; Measures; Mechanics; Metals; Methods; Microelectrodes; Microfabrication; Modeling; Monitor; Motion; Mus; Neurosciences; Neurosciences Research; Noise; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Performance; Polymers; Rattus; Research Design; Resources; Rodent; Sepharose; Signal Transduction; Silicon; Surface; System; Techniques; Technology; Testing; Thinness; Time; Tissues; Training; Transgenic Model; Trauma; Vertebral column; Weight; Work; base; data modeling; density; design; electric impedance; experience; flexibility; implantation; improved; in vivo; in vivo evaluation; machine vision; metallicity; nonhuman primate; parylene; pre-clinical research; prototype; relating to nervous system; scale up; submicron; technology development

A core goal of the BRAIN Initiative is to link neural activity to behavior which requires technology to acquire high-quality recordings of dynamic neural activity from different brain regions over time. To achieve this core goal, this optimization proposal will address the most pressing areas of technology development to enable the dissemination of polymer microelectrode arrays with such capability and promote their integration into neuroscience research practice. Polymer-based neural interfaces can achieve high-quality recordings over a year or more which is attributed to the greater stability of the device-tissue interface compared to more rigid metallic wire and silicon-based neural interfaces. Another distinct advantage is that the same microfabrication technology can be used to produce batches of surface and penetrating electrode arrays with carefully controlled features with micron and submicron dimensional precision. Microfabricated polymer probes are already available in limited designs having shank lengths of 10 mm or less and therefore predominantly used in rats. This technology needs to be extended for access to deeper brain regions in rodents and a wide range of brain targets in larger animals, including nonhuman primates, an important model in neuroscience and preclinical research. Existing device designs such as the prototype arrays previously developed for the rat hippocampus cannot simply be scale up or down to expand access to brain regions across different species. Instead, careful design is required in collaboration with users to meet space and weight requirements as well as workflow requirements to achieve precise placement at the desired depth. Therefore, this proposal tackles the necessary optimization of the previously developed technology to enable a library of designs that will enable their use in different animal models and to target different brain regions. Another goal is to develop the appropriate insertion methods for reliably placing electrodes at the desired depth and targeted region. Once the passive recording arrays and the matching surgical insertion methods are developed and optimized at the benchtop, these will be evaluated in mice, rats, and NHPs. Overall, this proposal not only addresses optimization but further advances in polymer microelectrode array technology for neural interfaces. This will enable early dissemination of polymer array systems for large-scale monitoring and manipulation of neural activity in collaboration with early adopters and demonstration of high-quality recordings obtained in multiple species over long periods that will attract additional users. Successful demonstration will facilitate our long-term goal of realizing the wide dissemination of reliable chronic neural interfaces across different neural tissues and species.

大脑计划的核心目标是将神经活动与行为联系起来，这需要技术随着时间的推移从不同大脑区域获取动态神经活动的高质量记录。为了实现这一核心目标，该优化建议将解决技术开发最紧迫的领域，以使聚合物微电极阵列具有这种能力，并促进其整合到神经科学研究实践中。基于聚合物的神经界面可以在一年或更长时间以上获得高质量的记录，这归因于与基于刚性的金属线和基于硅的神经接口相比，设备组织界面的稳定性更高。另一个独特的优势是，相同的微加工技术可用于生产具有微观和亚微米尺寸精度的精心控制特征的表面和穿透电极阵列。 微生物的聚合物探针已经以有限的设计为10毫米或更小的柄长度，因此主要用于大鼠。需要扩展该技术，以便进入啮齿动物的更深层次的大脑区域，以及包括非人类灵长类动物在内的大型动物的广泛大脑目标，这是神经科学和临床前研究的重要模型。现有的设备设计，例如先前为大鼠海马开发的原型阵列，不能简单地扩展或向下扩展，以扩大跨不同物种的大脑区域的访问。取而代之的是，与用户合作需要仔细设计，以满足空间和重量要求以及工作流程要求，以在所需的深度下实现精确的位置。 因此，该提案应对先前开发的技术的必要优化，以使设计库可以在不同的动物模型中使用并针对不同的大脑区域。另一个目标是开发适当的插入方法，以可靠地将电极放置在所需的深度和目标区域。一旦被动记录阵列和匹配的手术插入方法在台式上开发和优化，将在小鼠，大鼠和NHP中评估这些方法。 总体而言，该提案不仅解决了优化，而且解决了神经接口的聚合物微电极阵列技术的进一步进步。这将使聚合物阵列系统的早期传播与早期采用者合作进行大规模监测和操纵神经活动，并演示长期在多个物种中获得的高质量记录，以吸引更多用户。成功的演示将有助于我们实现在不同神经组织和物种上广泛传播可靠的慢性神经界面的长期目标。