Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates.
Scanning electron microscopy of chronically implanted intracortical microelectrode arrays in non-human primates.
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DOI：
10.1088/1741-2560/13/2/026003
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发表时间：
2016-04
影响因子：
4
通讯作者：
Donoghue JP
中科院分区：
文献类型：
--
作者：
Barrese JC;Aceros J;Donoghue JP
信号衰减是皮层内传感器在慢性神经假体应用中面临的主要问题。许多研究表明，失效是由于电极尖端周围的胶质化，然而，失效的机械和材料原因往往被忽视。本研究的目的是通过扫描电子显微镜(SEM)观察慢性种植阵列的结构变化，并通过组织学检查相应植入部位的组织反应，来研究导致进行性信号下降的因素。我们研究了8个长期植入的皮质内微电极阵列(MEA)，这些微电极阵列从植入后37天到1051天从非人灵长类动物移植而来。我们使用扫描电子显微镜、活体神经记录和组织学方法(GFAP、Iba-1、Neun)。三个从未植入的MEA也被成像为对照组。扫描电子显微镜显示铂电极尖端的渐进性腐蚀和下层硅的变化。聚对二甲苯绝缘容易破裂和分层，在某些情况下，有机硅弹性体也会从MEA的边缘剥离。可观察到大量的组织包裹，常见于铂金和对二甲苯的缺陷中。随着体内时间的增加，这些材料缺陷变得更加常见。植入后37天和1051天的组织学显示胶质增生，正常皮质结构破坏，神经元丢失最少，Iba-1活性高，尤其是在蛛网膜和硬脑膜内。1051d时，大脑皮质中没有电极束或几乎看不到电极束，但在纤维包裹材料中可以看到电极束，这表明MEA被从大脑中取出。神经记录显示，随着时间的推移，阻抗、信号幅度和可行的通道逐渐下降。这些结果提供了证据，证明MEAS中的信号损失确实是多因素的。神经胶质增生症发生在植入后的头几个月，但并不妨碍在几年内进行有用的记录。进行性脑膜纤维化将MEAs包裹并抬出皮质，而持续的异物反应会导致材料的进行性降解。长期阻抗下降是由于铂的腐蚀、对二甲苯的破裂和分层以及有机硅弹性体的分层造成的。免疫系统细胞释放的氧自由基可能会调节这些物质的降解。未来的MEA设计必须通过更耐用的绝缘材料、更多的惰性电极合金以及对成纤维细胞和白细胞的药物抑制来解决这些问题。
Signal attenuation is a major problem facing intracortical sensors for chronic neuroprosthetic applications. Many studies suggest that failure is due to gliosis around the electrode tips, however, mechanical and material causes of failure are often overlooked. The purpose of this study was to investigate the factors contributing to progressive signal decline by using scanning electron microscopy (SEM) to visualize structural changes in chronically implanted arrays and histology to examine the tissue response at corresponding implant sites. We examined eight chronically implanted intracortical microelectrode arrays (MEAs) explanted from non-human primates at times ranging from 37 to 1051 days post-implant. We used SEM, in vivo neural recordings, and histology (GFAP, Iba-1, NeuN). Three MEAs that were never implanted were also imaged as controls. SEM revealed progressive corrosion of the platinum electrode tips and changes to the underlying silicon. The parylene insulation was prone to cracking and delamination, and in some instances the silicone elastomer also delaminated from the edges of the MEA. Substantial tissue encapsulation was observed and was often seen growing into defects in the platinum and parylene. These material defects became more common as the time in vivo increased. Histology at 37 and 1051 days post-implant showed gliosis, disruption of normal cortical architecture with minimal neuronal loss, and high Iba-1 reactivity, especially within the arachnoid and dura. Electrode tracts were either absent or barely visible in the cortex at 1051 days, but were seen in the fibrotic encapsulation material suggesting that the MEAs were lifted out of the brain. Neural recordings showed a progressive drop in impedance, signal amplitude, and viable channels over time. These results provide evidence that signal loss in MEAs is truly multifactorial. Gliosis occurs in the first few months after implantation but does not prevent useful recordings for several years. Progressive meningeal fibrosis encapsulates and lifts MEAs out of the cortex while ongoing foreign body reactions lead to progressive degradation of the materials. Long-term impedance drops are due to the corrosion of platinum, cracking and delamination of parylene, and delamination of silicone elastomer. Oxygen radicals released by cells of the immune system likely mediate the degradation of these materials. Future MEA designs must address these problems through more durable insulation materials, more inert electrode alloys, and pharmacologic suppression of fibroblasts and leukocytes.