I-Corps: Implantable Brain-Computer Interface with Integrated Optics and Electrodes

缺乏系统的神经活动理论由于人脑的规模而变得复杂，人脑估计有850亿个神经元，100万亿个突触和100种化学神经递质。了解是什么使任何一个神经元放电或不放电是神经科学的一个核心问题，因此，如果我们要了解特定的“细胞类型”如何吸收信息，理想的传感工具必须从单个神经元跨越到它的连接网络。通过光遗传学的最新进展，特定的细胞类型可以通过使用特定波长的光控制来激活和/或沉默，从而实现对细胞活性的高精度操纵。结合电记录系统，光遗传探针可以同时刺激和记录目标神经群，具有高时空分辨率。尽管最近光遗传学取得了快速进展，但可靠地将光传递到大脑深部结构并记录电信号的支持技术还不容易获得。早期涉及体内光遗传学的工作依赖于人工组装市售组件，如微线和光纤，这些组件不仅体积庞大，而且由于人为错误还可能出现很大的错位。I-Corps团队开发了支持光遗传学应用的技术解决方案，使用先进的微制造技术将光学和电子元件单片集成到紧凑的MEMS探针中。该技术允许多个微型led或波导与记录电极精确对齐在同一探头杆上，从而避免了将组件组装到探头杆上的混合工艺。这反过来又增加了每个探针杆的光源数量的可扩展性，最小化了杆的尺寸，并提供了在蜂窝分辨率和多个位置限制发射的光源单独控制。该团队设计的探针在批量生产晶圆工艺中具有很高的产量，并且需要最少的组装工作。通过与几个世界级神经科学实验室的合作，在急性和慢性行为动物模型中证明了卓越的性能。这项技术的影响可以根据其在研究或临床应用中的效用进行分类：支持光遗传学研究，神经科学家通过光控制细胞来研究大脑功能；更好地了解和治疗神经系统疾病（帕金森氏症、癫痫等），恢复失去的身体功能（耳聋、失明、假肢等）。

The lack of a systematic theory of neural activity is complicated by the scale of the human brain, with an estimated 85 billion neurons, 100 trillion synapses, and 100 chemical neurotransmitters. Understanding what makes any one neuron fire or not is a central question in neuroscience and so the ideal sensing tool must span from the single neuron to its network of connections if we are to understand how that particular "cell type" assimilates information. Through recent advance in optogenetics, specific cell types can be activated and/or silenced by optical control using specific wavelengths to achieve high precision manipulation of cellular activity. Combined with an electrical recording system, an optogenetic probe can simultaneously stimulate and record from targeted neural population with high spatiotemporal resolution. In spite of recent rapid advances in optogenetics, supporting technologies to reliably deliver light to and record electrical signals from deep brain structures are not readily available. Early work involving in vivo optogenetics relied on the manual assembly of commercially available components such as microwires and optical fibers, which are not only bulky but can also experience large misalignments due to human error.This I-Corps team has developed the technical solutions to support optogenetic applications using advanced micro-fabrication techniques to monolithically integrate optical and electrical components into a compact MEMS probe. The technology allows for multiple micro-LEDs or waveguides to be precisely aligned on the same probe shank with the recording electrodes, obviating the need for hybrid processes to assemble components onto the probe shank. This, in turn, leads to increased scalability of the number of light sources per probe shank, minimized shank dimensions, and provides individual control of light sources for confined emission at cellular resolution and multiple locations. The probes the team has designed are practical to fabricate in bulk wafer processes with high yield and require minimal assembly effort. Excellent performance has been demonstrated in acute and chronic, behaving animal models through collaborations with several world-class neuroscience labs. The impact of this technology can be categorized by its utility in either research or clinical applications: to support optogenetic research where neuroscientists control cells through light to study brain functions; to better understand and to treat neurological diseases (Parkinson's, epilepsy, etc.), and to restore lost body functions (deafness, blindness, artificial limbs, etc.).