Mammalian brains consist of 10s of millions to 100s of billions of neurons operating at millisecond time scales, of which current recording techniques only capture a tiny fraction. Recording techniques capable of sampling neural activity at high spatiotemporal resolution have been difficult to scale. The most intensively studied mammalian neuronal networks, such as the neocortex, show a layered architecture, where the optimal recording technology samples densely over large areas. However, the need for application-specific designs as well as the mismatch between the three-dimensional architecture of the brain and largely two-dimensional microfabrication techniques profoundly limits both neurophysiological research and neural prosthetics. Here, we discuss a novel strategy for scalable neuronal recording by combining bundles of glass-ensheathed microwires with large-scale amplifier arrays derived from high-density CMOS in vitro MEA systems or high-speed infrared cameras. High signal-to-noise ratio (<25 μV RMS noise floor, SNR up to 25) is achieved due to the high conductivity of core metals in glass-ensheathed microwires allowing for ultrathin metal cores (down to <1 μm) and negligible stray capacitance. Multi-step electrochemical modification of the tip enables ultra-low access impedance with minimal geometric area, which is largely independent of the core diameter. We show that the microwire size can be reduced to virtually eliminate damage to the blood-brain-barrier upon insertion and we demonstrate that microwire arrays can stably record single-unit activity. Combining microwire bundles and CMOS arrays allows for a highly scalable neuronal recording approach, linking the progress in electrical neuronal recordings to the rapid progress in silicon microfabrication. The modular design of the system allows for custom arrangement of recording sites. Our approach of employing bundles of minimally invasive, highly insulated and functionalized microwires to extend a two-dimensional CMOS architecture into the 3rd dimension can be translated to other CMOS arrays, such as electrical stimulation devices.

中文翻译：

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CHIME：CMOS 托管的体内微电极，用于大规模可扩展的神经元记录


哺乳动物的大脑由数十亿到数十亿个神经元组成，这些神经元在毫秒时间尺度上运行，而当前的记录技术只能捕获其中的一小部分。能够以高时空分辨率对神经活动进行采样的记录技术很难规模化。研究最深入的哺乳动物神经元网络（例如新皮质）显示出分层结构，其中最佳记录技术在大面积上密集采样。然而，对特定应用设计的需求以及大脑的三维结构与二维微加工技术之间的不匹配极大地限制了神经生理学研究和神经修复术。在这里，我们讨论了一种可扩展神经元记录的新策略，通过将玻璃鞘微线束与源自高密度 CMOS 体外 MEA 系统或高速红外相机的大规模放大器阵列相结合。由于玻璃护套微线中芯金属的高导电性，允许超薄金属芯（低至 <1 μm）和可忽略的杂散，因此实现了高信噪比（<25 μV RMS 本底噪声，SNR 高达 25）电容。对尖端进行多步电化学修饰，以最小的几何面积实现超低接入阻抗，这在很大程度上与芯直径无关。我们证明，微丝尺寸可以减小，以几乎消除插入时对血脑屏障的损害，并且我们证明微丝阵列可以稳定地记录单个单元的活动。将微线束和 CMOS 阵列相结合，可实现高度可扩展的神经元记录方法，将电神经元记录的进展与硅微加工的快速进展联系起来。 系统的模块化设计允许自定义布置记录站点。我们采用微创、高度绝缘和功能化的微线束将二维 CMOS 架构扩展到第三维的方法可以转化为其他 CMOS 阵列，例如电刺激设备。