Intracortical neural probes are a key enabling technology for acquiring high fidelity neural signals within the cortex. They are viewed as a crucial component of brain–computer interfaces (BCIs) in order to record electrical activities from neurons within the brain. Smaller, more flexible, polymer-based probes have been investigated for their potential to limit the acute and chronic neural tissue response. Conventional methods of patterning electrodes and connecting traces on a single supporting layer can limit the number of recording sites which can be defined, particularly when designing narrower probes. We present a novel strategy of increasing the number of recording sites without proportionally increasing the size of the probe by using a multilayer fabrication process to vertically layer recording traces on multiple Parylene support layers, allowing more recording traces to be defined on a smaller probe width. Using this approach, we are able to define 16 electrodes on 4 supporting layers (4 electrodes per layer), each with a 30 $\mu \text{m}$ diameter recording window and 5 $\mu \text{m}$ wide connecting trace defined by conventional LWUV lithography, on an $80~\mu \text{m}$ wide by 9 $\mu \text{m}$ thick microprobe. Prior to in vitro and in vivo validation, the multilayer probes are electrically characterized via impedance spectroscopy and evaluating crosstalk between adjacent layers. Demonstration of acute in vitro recordings in a cerebral organoid model and in vivo recordings in a murine model indicate the probe’s capability for single unit recordings. This work demonstrates the ability to fabricate smaller, more compliant neural probes without sacrificing electrode density. [2021-0017]

中文翻译：

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多层植入式皮质微电极探针的制造以提高记录电位


皮质内神经探针是获取皮质内高保真神经信号的关键技术。它们被视为脑机接口（BCI）的重要组成部分，用于记录大脑内神经元的电活动。人们已经研究了更小、更灵活的聚合物探针限制急性和慢性神经组织反应的潜力。在单个支撑层上形成电极图案和连接迹线的传统方法会限制可定义的记录位点的数量，特别是在设计较窄的探针时。我们提出了一种新颖的策略，通过使用多层制造工艺在多个聚对二甲苯支撑层上垂直分层记录迹线，在不按比例增加探针尺寸的情况下增加记录位点的数量，从而允许在更小的探针宽度上定义更多记录迹线。使用这种方法，我们能够在 4 个支撑层上定义 16 个电极（每层 4 个电极），每个电极具有 30 $\mu \text{m}$ 直径的记录窗口和 5 $\mu \text{m}$ 宽由传统 LWUV 光刻定义的连接迹线，位于 $80~\mu \text{m}$ 宽、9 $\mu \text{m}$ 厚的微探针上。在体外和体内验证之前，通过阻抗谱对多层探针进行电学表征并评估相邻层之间的串扰。大脑类器官模型中的急性体外记录和小鼠模型中的体内记录的演示表明探针具有单单位记录的能力。这项工作展示了在不牺牲电极密度的情况下制造更小、更顺应的神经探针的能力。 [2021-0017]