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

摘要

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.