CHIME: CMOS-hosted in-vivo microelectrodes for massively scalable neuronal recordings
CHIME: CMOS-hosted in-vivo microelectrodes for massively scalable neuronal recordings
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CHIME：CMOS 托管体内微电极，用于大规模可扩展的神经元记录
DOI：
10.1101/570069
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Kollo M
中科院分区：
文献类型：
--
作者：
Kollo M
哺乳动物的大脑由几千万到几千亿个以毫秒为时间尺度运作的神经元组成，目前的记录技术只能捕捉到其中的一小部分。能够在高时空分辨率下采样神经活动的记录技术很难扩展。最深入研究的哺乳动物神经网络，如新皮层，显示出一种分层结构，其中最佳的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主要的二维微制造技术之间的不匹配，深刻地限制了神经生理学研究和神经假肢。在这里，我们讨论了一种可扩展神经元记录的新策略，该策略将玻璃包覆微线束与来自高密度CMOSin体外mea系统或高速红外摄像机的大型放大器阵列相结合。高信噪比（<25 μV RMS噪声底，信噪比高达25）是由于玻璃包覆微线芯金属的高导电性，允许超薄金属芯（低至<1 μm）和可忽略的杂散电容。尖端的多步电化学修饰可以在最小的几何面积下实现超低的访问阻抗，这在很大程度上与芯直径无关。我们的研究表明，微线的尺寸可以减小，从而在插入时几乎消除对血脑屏障的损害，并且我们证明了微线阵列可以稳定地记录单个单元的活动。结合微线束和CMOS阵列允许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。该系统的模块化设计允许自定义安排的记录地点。我们采用微创、高度绝缘和功能化微线束的方法，将二维CMOS架构扩展到三维，可以转化为其他CMOS阵列，如电刺激设备。
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 CMOSin vitroMEA 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.