用于体外细胞级微磁激活神经元的平面微线圈阵列

Renata Saha, O. J. Benally, S. Faramarzi, Robert P. Bloom, Kai Wu, Denis Tonini, Maple L Shiao, Susan A. Keirstead, Walter C Low, T. Netoff, Jian‐Ping Wang
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摘要

在治疗神经退行性疾病方面,目前仍缺乏单个神经元细胞分辨率的潜在治疗方法。微磁神经刺激技术虽然处于起步阶段,但却是最有前途的技术之一,它通过微米级线圈或微线圈(μ线圈)对神经元进行空间选择性激活。时变电流驱动这些微线圈,产生时变磁场,进而诱导电场激活神经组织。在这项工作中,我们报告了用于激活单个神经元的平面微线圈阵列(称为磁贴(MagPatch))的设计和制造。通过在 ANSYS-Maxwell 和 NEURON 上进行数值计算,我们报告了一种优化的 MagPatch 阵列设计,它利用了微线圈感应电场的方向性来增强空间选择性。每个微线圈的外尺寸为 190 × 190 μm2,一个 MagPatch 阵列包含 8 个微线圈。为了验证概念设计和开发,MagPatch 阵列是在硅基底上使用钛、金和 Si3N4 制作的,以确保初步的生物相容性。然后将它们封装在防水、抗漏电流涂层 Parylene-C 中,从而确保了基本的表面生物相容性。直接在表面封装的 MagPatch 上培养人类神经母细胞瘤细胞,并使用钙荧光成像评估细胞功能。此外,还讨论了 MagPatch 阵列中的μ线圈尺寸缩放对电气特性、Q 因子和这些μ线圈对神经组织的热效应的影响。
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Planar microcoil arrays for in vitro cellular-level micromagnetic activation of neurons
In the treatment of neurodegenerative disorders, a potential cure at a single neuron cell resolution is still lacking. Micromagnetic neurostimulation, although in its infancy, is one of the most promising techniques that offer spatially selective activation of neurons through micrometer-sized coils or microcoils (μcoils). Time-varying current drives these μcoils and generates a time-varying magnetic field which in turn induces an electric field to activate the neural tissues. In this work, we report the design and fabrication of planar μcoil arrays, termed Magnetic Patch (MagPatch), for activating single neurons. Using numerical calculations on ANSYS-Maxwell and NEURON, we report an optimized MagPatch array design that exploits the directionality of the induced electric field from the μcoils to enhance spatial selectivity. Each μcoil has an outer dimension of 190 × 190 μm2 and one MagPatch array contains 8 μcoils. For proof-of-concept design and development, the MagPatch array has been fabricated on Si-substrates using Ti, Au, and Si3N4 to ensure preliminary biocompatibility. They were then encapsulated in Parylene-C, a waterproof, anti-leakage current coating, thereby ensuring basic surface biocompatibility. Human neuroblastoma cells were cultured directly on the surface encapsulated MagPatch, and calcium fluorescence imaging was used to assess cell functionality. The impact of scaling the dimensions of the μcoil in the MagPatch array on electrical characteristics, Q-factor, and thermal effects on neural tissues from these μcoils have also been discussed.
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