Chronic implantation of intracortical microelectrode arrays (MEAs) capable of recording from individual neurons can be used for the development of brain-machine interfaces. However, these devices show reduced recording capabilities under chronic conditions due, at least in part, to the brain's foreign body response (FBR). This creates a need for MEAs that can minimize the FBR to possibly enable long-term recording. A potential approach to reduce the FBR is the use of MEAs with reduced cross-sectional geometries. Here, we fabricated 4-shank amorphous silicon carbide (a-SiC) MEAs and implanted them into the motor cortex of seven female Sprague-Dawley rats. Each a-SiC MEA shank was 8 μm thick by 20 μm wide and had sixteen sputtered iridium oxide film (SIROF) electrodes (4 per shank). A-SiC was chosen as the fabrication base for its high chemical stability, good electrical insulation properties, and amenability to thin film fabrication. Electrochemical analysis and neural recordings were performed weekly for 4 months. MEAs were characterized pre-implantation in buffered saline and using electrochemical impedance spectroscopy and cyclic voltammetry at 50 mV/s and 50,000 mV/s. Neural recordings were analyzed for single unit activity. At the end of the study, animals were sacrificed for immunohistochemical analysis. We observed statistically significant, but small, increases in 1 and 30 kHz impedance values and 50,000 mV/s charge storage capacity over the 16-week implantation period. Slow sweep 50 mV/s CV and 1 Hz impedance did not significantly change over time. Impedance values increased from 11.6 MΩ to 13.5 MΩ at 1 Hz, 1.2 MΩ–2.9 MΩ at 1 kHz, and 0.11 MΩ–0.13 MΩ at 30 kHz over 16 weeks. The median charge storage capacity of the implanted electrodes at 50 mV/s was 58.1 mC/cm on week 1 and 55.9 mC/cm on week 16, and at 50,000 mV/s, 4.27 mC/cm on week 1 and 5.93 mC/cm on week 16. Devices were able to record neural activity from 92% of all active channels at the beginning of the study, At the study endpoint, a-SiC devices were still recording single-unit activity on 51% of electrochemically active electrode channels. In addition, we observed that the signal-to-noise ratio experienced a small decline of −0.19 per week. We also classified observed units as fast and slow repolarizing based on the trough-to-peak time. Although the overall presence of single units declined, fast and slow repolarizing units declined at a similar rate. At recording electrode depth, immunohistochemistry showed minimal tissue response to the a-SiC devices, as indicated by statistically insignificant differences in activated glial cell response between implanted brains slices and contralateral sham slices at 150 μm away from the implant location, as evidenced by GFAP staining. NeuN staining revealed the presence of neuronal cell bodies close to the implantation site, again statistically not different from a contralateral sham slice. These results warrant further investigation of a-SiC MEAs for future long-term implantation neural recording studies.

中文翻译：

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用于大鼠运动皮层慢性记录的平面非晶碳化硅微电极阵列

能够记录单个神经元的皮质内微电极阵列（MEA）的长期植入可用于脑机接口的开发。然而，这些设备在慢性条件下表现出记录能力下降，至少部分原因是大脑的异物反应（FBR）。这就需要 MEA 能够最大限度地减少 FBR，从而可能实现长期记录。降低 FBR 的一种潜在方法是使用横截面几何形状减小的 MEA。在这里，我们制造了 4 柄非晶碳化硅 (a-SiC) MEA，并将其植入七只雌性 Sprague-Dawley 大鼠的运动皮层中。每个 a-SiC MEA 柄厚 8 μm，宽 20 μm，并具有 16 个溅射氧化铱薄膜 (SIROF) 电极（每个柄 4 个）。 A-SiC 因其高化学稳定性、良好的电绝缘性能和适合薄膜制造而被选为制造基础。为期 4 个月，每周进行一次电化学分析和神经记录。 MEA 在缓冲盐水中进行植入前表征，并使用电化学阻抗谱和循环伏安法在 50 mV/s 和 50,000 mV/s 下进行表征。分析神经记录的单个单元活动。研究结束时，处死动物进行免疫组织化学分析。我们观察到在 16 周的植入期间，1 kHz 和 30 kHz 阻抗值以及 50,000 mV/s 电荷存储容量有统计学上显着但较小的增加。慢速扫描 50 mV/s CV 和 1 Hz 阻抗不会随时间发生显着变化。 16 周内，阻抗值在 1 Hz 时从 11.6 MΩ 增加到 13.5 MΩ，在 1 kHz 时从 1.2 MΩ–2.9 MΩ，在 30 kHz 时从 0.11 MΩ–0.13 MΩ。植入电极的中位电荷存储容量在 50 mV/s 时，第 1 周为 58.1 mC/cm，第 16 周为 55.9 mC/cm；在 50,000 mV/s 时，第 1 周为 4.27 mC/cm，第 16 周为 5.93 mC/cm第 16 周。在研究开始时，设备能够记录 92% 的所有活性通道的神经活动。在研究终点，a-SiC 设备仍在 51% 的电化学活性电极通道上记录单个单元的活动。此外，我们观察到信噪比每周小幅下降 -0.19。我们还根据波谷到波峰的时间将观察到的单元分为快速和慢速复极化。尽管单个单元的总体存在量下降，但快速和慢速复极化单元以相似的速度下降。在记录电极深度时，免疫组织化学显示对 a-SiC 装置的组织反应最小，如 GFAP 染色所证明的那样，植入的大脑切片和距植入位置 150 μm 的对侧假切片之间的激活神经胶质细胞反应在统计上无显着差异。 。 NeuN 染色显示植入位点附近存在神经元细胞体，这与对侧假切片在统计学上再次没有差异。这些结果值得对 a-SiC MEA 进行进一步研究，以用于未来的长期植入神经记录研究。