Massively Multiplexed Gold Microprobe Arrays for Whole-Mouse-Brain Recording

用于全小鼠大脑记录的大规模多重金微探针阵列

• 批准号: 10442207
• 负责人: Hui Fang
• 金额: $ 7.56万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10442207
• 关键词: Massively; Multiplexed; Gold; Microprobe; Arrays

Abstract Understanding brain function requires the ability to record simultaneously from thousands or tens-of- thousands of neurons contributing to the dynamic activity in a neural circuit. CMOS based electrode technology constitutes the only means to electrically interact with living systems beyond this scale and at sub- millisecond time resolution, but suffers from the limited recording depth and the invasiveness of silicon wafer which might prohibit their use in human experimentation. Still, there is a growing awareness that leveraging commercially available large-scale CMOS technologies might address the scaling challenge in brain mapping. We herein propose a new device concept which encompasses a unique and innovative combination of two widely-used existing technologies - metal microwires and CMOS electronics - to create a synergistic result. By developing small-diameter, deep-penetrating, gold microprobes monolithically on a thin yet reliable CMOS electronic ‘router’, we aim to achieve over one thousand subcellular neuro probes with only a few I/O wires in a commercially viable way, with scalability up to tens of thousands and even higher for large-scale in vivo brain mapping. We will first develop a viable electrochemical deposition process to achieve high-aspect-ratio gold microprobes with down to 10µm diameter, and up to 1mm length. A passive gold microprobe array with 96 channels will be developed first at a density up to 100 probes/mm2. In parallel, we will develop a massively multiplexed CMOS ASIC design on SOI substrates to be thinned down to the buried oxide layer with less-than- 3µm device thickness on a supporting Kapton substrate. We will form the massively multiplexed penetrating arrays with up to 1000 electrodes by synthesizing gold microprobes on the thinned-down ASIC. Implantations in rodent cortex will be used to assess recording reliability and tissue response. The monolithic fabrication process of the gold microprobes will support up-scaling to 10,000 - 100,000 microprobes or higher at the cm scale. This project leverages a vibrant collaboration between material scientists, circuit designers, device engineers and electrophysiologists at Dartmouth College and the University of Utah (Utah), to realize large- scale, subcellular, deep-penetrating gold microprobe arrays that serve as a basis to scale to whole-mouse- brain recording.

抽象的 了解大脑功能需要仅从数千或数十万中记录的能力 成千上万的神经元在神经元回路中有助于动态活性。基于CMOS的电极 技术构成与超越这种规模的生活系统电气相互作用的唯一手段 毫秒的时间分辨率，但遭受了有限的记录深度和硅晶片的侵入性 这可能禁止他们在人类实验中使用。不过，人们越来越意识到 市售的大规模CMOS技术可能会解决大脑映射中的缩放挑战。 我们在这里提出了一个新的设备概念，该概念涵盖了两个的独特而创新的组合 广泛使用的现有技术 - 金属微管和CMOS电子产品 - 创建协同结果。经过 在薄而可靠的CMOS上单拼单上开发小直径，深渗透的金微探针 电子“路由器”，我们的目标是实现超过一千多个I/O线的亚细胞神经探针 商业上可行的方式，可扩展性高达数万，甚至更高的体内大脑大脑 映射。 我们将首先开发一个可行的电化学沉积过程，以实现高光谱比率 直径至10μm的微探针，长度最高为1mm。 96 通道将首先以高达100个问题/mm2的密度开发。同时，我们将大规模发展 SOI底物上的多路复用CMOS ASIC设计将被稀释到埋在氧化物层的情况下 支撑Kapton底物上的3µm设备厚度。我们将形成大量的多重穿透 通过在稀薄的肌肉上合成金色微探针，具有多达1000个电子的阵列。植入 在啮齿动物中，皮质将用于评估记录可靠性和组织反应。整体制造 黄金微探针的过程将支持上升到10,000-100,000微探针或更高的CM。 规模。 该项目利用材料科学家，电路设计师，设备之间的充满活力的合作 达特茅斯学院和犹他大学（犹他州）的工程师和电生理学家，实现大型 比例尺，亚细胞，深渗透金微探针阵列，可作为扩展全鼠的基础 大脑记录。