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一种基于硅的神经探针,具有高密度低阻抗氮化钛微电极,可实现超高分辨率的活体记录。

A silicon-based neural probe with densely-packed low-impedance titanium nitride microelectrodes for ultrahigh-resolution in vivo recordings.

机构信息

Institute of Cognitive Neuroscience and Psychology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, H-1117 Budapest, Hungary; Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Práter utca 50/A, H-1083 Budapest, Hungary.

Interuniversity Microelectronics Center (IMEC), Kapeldreef 75, B-3001 Heverlee, Belgium; Electrical Engineering Department (ESAT), KU Leuven, Kasteelpark Arenberg 10, B-3001 Leuven, Belgium.

出版信息

Biosens Bioelectron. 2018 May 30;106:86-92. doi: 10.1016/j.bios.2018.01.060. Epub 2018 Jan 31.

DOI:10.1016/j.bios.2018.01.060
PMID:29414094
Abstract

In this study, we developed and validated a single-shank silicon-based neural probe with 128 closely-packed microelectrodes suitable for high-resolution extracellular recordings. The 8-mm-long, 100-µm-wide and 50-µm-thick implantable shank of the probe fabricated using a 0.13-µm complementary metal-oxide-semiconductor (CMOS) metallization technology contains square-shaped (20 × 20 µm), low-impedance (~ 50 kΩ at 1 kHz) recording sites made of rough and porous titanium nitride which are arranged in a 32 × 4 dense array with an inter-electrode pitch of 22.5 µm. The electrophysiological performance of the probe was tested in in vivo experiments by implanting it acutely into neocortical areas of anesthetized animals (rats, mice and cats). We recorded local field potentials, single- and multi-unit activity with superior quality from all layers of the neocortex of the three animal models, even after reusing the probe in multiple (> 10) experiments. The low-impedance electrodes monitored spiking activity with high signal-to-noise ratio; the peak-to-peak amplitude of extracellularly recorded action potentials of well-separable neurons ranged from 0.1 mV up to 1.1 mV. The high spatial sampling of neuronal activity made it possible to detect action potentials of the same neuron on multiple, adjacent recording sites, allowing a more reliable single unit isolation and the investigation of the spatiotemporal dynamics of extracellular action potential waveforms in greater detail. Moreover, the probe was developed with the specific goal to use it as a tool for the validation of electrophysiological data recorded with high-channel-count, high-density neural probes comprising integrated CMOS circuitry.

摘要

在这项研究中,我们开发并验证了一种带有 128 个紧密排列的微电极的单通道硅基神经探针,适用于高分辨率的细胞外记录。该探针的 8mm 长、100µm 宽和 50µm 厚的植入式探臂采用 0.13µm 互补金属氧化物半导体(CMOS)金属化技术制造,包含由粗糙多孔氮化钛制成的方形(20×20µm)、低阻抗(~50kΩ,在 1kHz 时)记录位点,这些记录位点以 32×4 密集排列的方式排列,电极之间的间距为 22.5µm。该探针的电生理性能通过将其急性植入麻醉动物(大鼠、小鼠和猫)的新皮层区域进行体内实验进行了测试。我们从三个动物模型的新皮层所有层记录到了具有优异质量的局部场电位、单个和多个单元活动,即使在多次(>10 次)实验中重复使用该探针后也是如此。低阻抗电极以高信噪比监测尖峰活动;可分离神经元的细胞外记录动作电位的峰峰值幅度范围从 0.1mV 到 1.1mV。神经元活动的高空间采样使得有可能在多个相邻记录位点上检测到同一神经元的动作电位,从而能够更可靠地分离单个单元,并更详细地研究细胞外动作电位波形的时空动力学。此外,该探针是专门为验证包含集成 CMOS 电路的高通道计数、高密度神经探针记录的电生理数据而开发的。

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