Novel Transparent, Ultra-soft Neuroelectrode Arrays Based on Nanomeshing Conventional Electrode Materials

摘要 人们对大规模有效地将光学方法与电生理学结合的兴趣与日俱增 并以极高的精确度充分利用 两种技术都有。人们还广泛认识到，设备的柔软性和合规性是 显著降低组织损伤和刺激，并随着时间的推移保持信号质量。我们的长期目标是(一) 将电生理学与光学脑记录/刺激大规模无缝融合，实现 高时空分辨率的脑活动图，捕捉到了 神经元回路和神经元通讯的最快时间动力学以及(Ii)整合电极阵列 与脑组织无缝连接。此R01应用程序的目标是实现以下目标的第一步 目标是开发和验证一种新的神经电子工具，它提供最先进的 电生理能力，同时允许光学和慢性生物兼容性， 通过整个MEA的光学透明度和机械超柔软实现关键，以及 其他工程方面的努力。我们非常雄心勃勃地应对这两大挑战，因为 统一技术理念，纳米级常规电极材料。 在我们以前的工作中，我们提出了这个新的电极概念，它导致了 透明、灵活的电极，具有高性能，尺寸可达15×15微米，并具有记录能力 单个单位的峰值。在这个应用中，我们的目的是证明：这种纳米切割的概念可以导致100s-电极- 大规模、高密度、透明和超软电极阵列，同时允许 (I)有效地将电记录/刺激与体内光学成像相结合，以及(Ii)慢性稳定性 单单元录音。这一概念的证明将容易地实现稳定、并行的电/光 在毫米到厘米的尺度上对大脑进行研究，具有进一步的可扩展性，同时还提供独特的 通过可持续的神经假体提供下一代治疗干预的机会。在三个月内- 相关目标，我们将开发和验证概念验证、基于纳米网格的微电极、透明的 超软、高密度(纳米网格)阵列，具有至少256个高性能纳米网格微电极和 通过整合创新技术的跨学科三年计划拒绝无线数据链路 基础神经科学测试的发展。我们将在vivo中根据行业标准对我们的设备进行基准测试， 并将神经工程反馈整合到项目的设计、测试和验证阶段。 该项目充分利用了材料科学家、神经工程师、 电子工程师和神经学家将透明纳米网格技术转化为大规模大脑- 测绘工具和可植入设备。

Abstract There is a growing interest to effectively combine optical approaches with electrophysiology at large scale and with great precision to fully leverage the complementary spatial and temporal resolution advantages of both techniques. It is also widely recognized that device softness and compliance are important attributes to dramatically lower tissue injury and irritation and maintain signal quality over time. Our long-term goals are (i) to converge electrophysiology with optical brain recording/stimulation seamlessly at the large scale to achieve high-spatiotemporal-resolution brain activity mapping which captures both the finest spatial intricacies of the neuronal circuit and fastest temporal dynamics of neuronal communication and (ii) to integrate electrode arrays seamlessly with the brain tissue. The objective of this R01 application, which is the first step in achieving these goals, is to develop and validate a novel neuroelectronic tool which provides state-of-the-art electrophysiological capabilities while allowing at the same time, optical and chronic-bio- compatibilities, realized critically through the optical transparency and mechanical ultra-softness of the entire MEA, along with other engineering efforts. We are very ambitious about tackling both of these two big challenges because of a unified technical concept, nanomeshing conventional electrode materials. In our prior work, we have proposed this novel electrode concept, which has led to the demonstration of transparent, flexible electrodes with high performance of sizes down to 15×15µm2, and with the ability to record single-unit spikes. In this application, we aim to prove: this nanomeshing concept can lead to 100s-electrode- scale, high-density, transparent and ultra-soft electrode arrays that simultaneously allow both the capability of (i) effectively integrating electrical recordings/stimulation with optical imaging in vivo, and (ii) chronic stability of single-unit recordings. The proof of this concept will readily enable stable, concurrent electrical/optical investigations of the brain at the mm-to-cm scale with further scalability, while also providing unique opportunities for next-generation therapeutic interventions via sustainable neural prosthetics. In three inter- related aims, we will develop and validate proof-of-concept, nanomesh-microelectrode-based, transparent, ultra-soft, high-density (NANOMESH) array with at least 256 high-performance nanomesh microelectrodes and artifact rejecting wireless data link through an interdisciplinary 3-year plan integrating innovative technological developments with basic neuroscience testing. We will benchmark our devices to industry standards in vivo, and integrate neural engineering feedback throughout the design, testing and validation phases of the project. This project leverages a vibrant and successful collaboration between material scientists, neuro-engineers, electrical engineers, and neuroscientists to translate transparent nanomesh technology into large-scale brain- mapping tools and implantable devices.