Department of Chemical and Biomolecular Engineering, Rice University , Houston, Texas 77005, United States.
Applied Physics Program, Rice University , Houston, Texas 77005, United States.
Nano Lett. 2018 Jan 10;18(1):326-335. doi: 10.1021/acs.nanolett.7b04184. Epub 2017 Dec 15.
Soft and conductive nanomaterials like carbon nanotubes, graphene, and nanowire scaffolds have expanded the family of ultraflexible microelectrodes that can bend and flex with the natural movement of the brain, reduce the inflammatory response, and improve the stability of long-term neural recordings. However, current methods to implant these highly flexible electrodes rely on temporary stiffening agents that temporarily increase the electrode size and stiffness thus aggravating neural damage during implantation, which can lead to cell loss and glial activation that persists even after the stiffening agents are removed or dissolve. A method to deliver thin, ultraflexible electrodes deep into neural tissue without increasing the stiffness or size of the electrodes will enable minimally invasive electrical recordings from within the brain. Here we show that specially designed microfluidic devices can apply a tension force to ultraflexible electrodes that prevents buckling without increasing the thickness or stiffness of the electrode during implantation. Additionally, these "fluidic microdrives" allow us to precisely actuate the electrode position with micron-scale accuracy. To demonstrate the efficacy of our fluidic microdrives, we used them to actuate highly flexible carbon nanotube fiber (CNTf) microelectrodes for electrophysiology. We used this approach in three proof-of-concept experiments. First, we recorded compound action potentials in a soft model organism, the small cnidarian Hydra. Second, we targeted electrodes precisely to the thalamic reticular nucleus in brain slices and recorded spontaneous and optogenetically evoked extracellular action potentials. Finally, we inserted electrodes more than 4 mm deep into the brain of rats and detected spontaneous individual unit activity in both cortical and subcortical regions. Compared to syringe injection, fluidic microdrives do not penetrate the brain and prevent changes in intracranial pressure by diverting fluid away from the implantation site during insertion and actuation. Overall, the fluidic microdrive technology provides a robust new method to implant and actuate ultraflexible neural electrodes.
软质且导电的纳米材料，如碳纳米管、石墨烯和纳米线支架，扩展了超柔韧微电极的家族，这些电极可以随大脑的自然运动弯曲和变形，减少炎症反应，并提高长期神经记录的稳定性。然而，目前植入这些高柔韧性电极的方法依赖于临时的硬化剂，这些硬化剂会暂时增加电极的尺寸和硬度，从而在植入过程中加重神经损伤，导致细胞丢失和神经胶质细胞激活，即使在硬化剂被去除或溶解后仍然存在。一种将薄而超柔韧的电极递送到神经组织深处而不增加电极的刚度或尺寸的方法，将能够实现对大脑内部的微创电记录。在这里，我们展示了专门设计的微流控装置可以向超柔韧的电极施加张力，防止在植入过程中电极弯曲，而不会增加电极的厚度或硬度。此外，这些“流体微驱动器”使我们能够以微米级的精度精确地驱动电极位置。为了证明我们的流体微驱动器的有效性，我们使用它们来驱动高度灵活的碳纳米管纤维（CNTf）微电极进行电生理学研究。我们在三个概念验证实验中使用了这种方法。首先，我们在柔软的模式生物水螅中记录了复合动作电位。其次，我们精确地将电极靶向到脑切片中的丘脑网状核，并记录了自发和光遗传学诱发的细胞外动作电位。最后，我们将电极插入大鼠大脑超过 4 毫米深的地方，并在皮质和皮质下区域检测到自发的单个单元活动。与注射器注射相比，流体微驱动器不会穿透大脑，并通过在插入和驱动过程中使流体从植入部位分流来防止颅内压的变化。总的来说，流体微驱动器技术为植入和驱动超柔韧神经电极提供了一种强大的新方法。
