Department of Biomedical Engineering, University of Southern California, 1042 Downey Way, DRB-140, Los Angeles, CA 90089-1111, USA.
J Neural Eng. 2013 Aug;10(4):045002. doi: 10.1088/1741-2560/10/4/045002. Epub 2013 May 31.
Reliable chronic recordings from implanted neural probes remain a significant challenge; current silicon-based and microwire technologies experience a wide range of biotic and abiotic failure modes contributing to loss of signal quality.
A multi-prong alternative strategy with potential to overcome these hurdles is introduced that combines a novel three dimensional (3D), polymer-based probe structure with coatings. Specifically, the Parylene C sheath-based neural probe is coated with neurotrophic and anti-inflammatory factors loaded onto a Matrigel carrier to encourage the ingrowth of neuronal processes for improved recording quality, reduce the immune response, and promote improved probe integration into brain tissue for reliable, long-term implementation compared to its rigid counterparts.
The 3D sheath structure of the probe was formed by thermal molding of a surface micromachined Parylene C microchannel, with electrode sites lining the interior and exterior regions of the lumen. Electrochemical characterization of the probes via cyclic voltammetry and electrochemical impedance spectroscopy was performed and indicated suitable electrode properties for neural recordings (1 kHz electrical impedance of ∼200 kΩ in vitro). A novel introducer tool for the insertion of the compliant polymer probe into neural tissue was developed and validated both in vitro using agarose gel and in vivo in the rat cerebral cortex. In vivo electrical functionality of the Parylene C-based 3D probes and their suitability for recording the neuronal activity over a 28-day period was demonstrated by maintaining the 1 kHz electrical impedance within a functional range (<400 kΩ) and achieving a reasonably high signal-to-noise ratio for detection of resolvable multi-unit neuronal activity on most recording sites in the probe. Immunohistochemical analysis of the implant site indicated strong correlations between the quality of recorded activity and the neuronal/astrocytic density around the probe.
The provided electrophysiological and immunohistochemical data provide strong support to the viability of the developed probe technology. Furthermore, the obtained data provide insights into further optimization of the probe design, including tip geometry, use of neurotrophic and anti-inflammatory drugs in the Matrigel coating, and placement of the recording sites.
可靠的植入式神经探针的慢性记录仍然是一个重大挑战；目前的硅基和微丝技术经历了广泛的生物和非生物失效模式，导致信号质量下降。
引入了一种多管齐下的替代策略，具有克服这些障碍的潜力，该策略结合了新型的三维（3D）聚合物探针结构和涂层。具体来说，基于派莱克斯 C 鞘的神经探针用负载在基质胶载体上的神经营养和抗炎因子进行涂层，以促进神经元突起的生长，从而提高记录质量，减少免疫反应，并促进探针与脑组织的更好整合，以实现可靠的长期植入，与刚性探针相比具有更好的性能。
通过表面微加工的聚对二甲苯 C 微通道的热成型形成了探针的 3D 鞘结构，电极位点位于内腔的内部和外部区域。通过循环伏安法和电化学阻抗谱对探针进行了电化学表征，结果表明其具有适合神经记录的电极特性（体外 1 kHz 电阻抗约为 200 kΩ）。开发了一种用于将顺应性聚合物探针插入神经组织的新型导入工具，并在体外使用琼脂糖凝胶和体内大鼠大脑皮层进行了验证。通过将 1 kHz 电阻抗保持在功能范围内（<400 kΩ），并在探针的大多数记录位点上实现了可分辨的多单位神经元活动的合理高信噪比，证明了基于派莱克斯 C 的 3D 探针的体内电功能及其在 28 天内记录神经元活动的适用性。植入部位的免疫组织化学分析表明，记录活动的质量与探针周围的神经元/星形胶质细胞密度之间存在很强的相关性。
提供的电生理和免疫组织化学数据为所开发的探针技术的可行性提供了强有力的支持。此外，获得的数据为进一步优化探针设计提供了深入的见解，包括尖端几何形状、在基质胶涂层中使用神经营养和抗炎药物以及记录位点的放置。
