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 了解大脑功能需要能够同时记录数千或数十个 数以千计的神经元参与基于 CMOS 的电极的动态活动。 技术是与超出这一规模和亚级的生命系统进行电交互的唯一手段。 毫秒时间分辨率，但受限于记录深度和硅片的侵入性 这可能会阻止它们在人体实验中的使用，但人们越来越意识到利用它们。 商业化的大规模 CMOS 技术可能会解决大脑绘图中的缩放挑战。 我们在此提出了一种新的设备概念，其中包含两种独特且创新的组合 广泛使用的现有技术 - 金属微线和 CMOS 电子技术 - 创造出协同效果。 在薄而可靠的 CMOS 上单片开发小直径、深穿透的金微探针 电子“路由器”，我们的目标是仅用几条 I/O 线即可实现超过 1000 个亚细胞神经探针 商业上可行的方式，可扩展性高达数万甚至更高，适用于大规模体内大脑 映射。 我们将首先开发一种可行的电化学沉积工艺来实现高纵横比的金 直径小至 10 µm，长度长达 1 mm 的无源金微探针阵列，包含 96 个探针。 首先将开发密度高达 100 个探针/mm2 的通道，同时我们将大规模开发一个通道。 SOI 衬底上的多路复用 CMOS ASIC 设计将减薄至埋氧化层，且小于 我们将在支撑 Kapton 基板上形成 3μm 的器件厚度，形成大规模多路复用穿透。 通过在减薄的植入上合成金微探针，可以形成具有多达 1000 个电极的阵列。 啮齿动物皮层中的整体结构将用于评估记录可靠性和组织反应。 金微探针的工艺将支持在厘米处放大到 10,000 - 100,000 个微探针或更高 规模。 该项目利用了材料科学家、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，以实现大 规模化、亚细胞、深穿透金微探针阵列，作为扩展到全小鼠的基础 大脑记录。