Flexible probes for brain activity recordings are an attractive emerging approach that reduces mechanical mismatch between probe and neuronal tissue, thus minimizing the risk of brain damage or glial scaring. Although promising, flexible probes still present some technical challenges namely: i) how to overcome probe buckling during brain insertion given its intrinsically low mechanical rigidity; ii) how to fabricate closely spaced electrode configurations for high density recordings by standard lithography techniques in the flexible substrate. Here, we present a new flexible probe based solely on standard and low-cost lithography processes, which has closely spaced 10 μm diameter gold electrode sites on a polyimide substrate with inter-site distances of only 5 μm. By using a double-layer design and fabrication approach we were able to accommodate closely spaced electrode sites at two different depths from probe surface while also providing additional stiffening, just sufficient to prevent probe buckling during brain insertion. Detailed probe characterization through metrology of structural and electrical properties and chemical composition analysis, as well as functional assessment through in vivo high density recordings of neuronal activity in the mouse cortex, confirmed the viability of this new fabrication approach and showed that this probe can be used for obtaining high quality brain recordings with excellent signal to noise ratio (SNR).

中文翻译：

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具有紧密间隔电极的双层柔性神经元探针，用于高密度体内脑记录

用于大脑活动记录的柔性探头是一种有吸引力的新兴方法，它可以减少探头和神经元组织之间的机械失配，从而最大程度地减少脑部损伤或神经胶质细胞惊吓的风险。尽管有前途，但柔性探针仍面临一些技术挑战：i）鉴于其固有的低机械刚度，如何在大脑插入过程中克服探针的弯曲；ii）如何通过标准光刻技术在柔性基板中制造用于高密度记录的紧密间隔的电极构造。在这里，我们提出了一种仅基于标准和低成本光刻工艺的新型柔性探针，该探针在聚酰亚胺衬底上的间距仅为10μm的金电极位置紧密间隔10μm。通过使用双层设计和制造方法，我们能够在距探头表面两个不同深度处容纳间距很近的电极部位，同时还提供了额外的刚性，刚好足以防止在大脑插入过程中探头屈曲。通过结构和电性能的计量学和化学成分分析的详细探针表征，以及通过体内高密度记录小鼠皮质神经元活动的功能评估，证实了这种新制备方法的可行性，并表明该探针可用于用于获得具有出色信噪比（SNR）的高质量大脑记录。足以防止在大脑插入过程中探头弯曲。通过结构和电性能的计量学和化学成分分析的详细探针表征，以及通过体内高密度记录小鼠皮质神经元活动的功能评估，证实了这种新制备方法的可行性，并表明该探针可用于用于获得具有出色信噪比（SNR）的高质量大脑记录。足以防止在大脑插入过程中探头弯曲。通过结构和电性能的计量学和化学成分分析的详细探针表征，以及通过体内高密度记录小鼠皮质神经元活动的功能评估，证实了这种新制备方法的可行性，并表明该探针可用于用于获得具有出色信噪比（SNR）的高质量大脑记录。