CN116919410A - 一种微创植入式高密度脑电电极的制备 - Google Patents
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Abstract
一种微创植入式高密度脑电电极的制备，通过对薄膜电极的导电图案、基底形状进行设计，之后将其卷曲，实现了在一根直径为微米级纤维器件上集成超过100个脑电监测通道，通道在纤维上的分布及方向可调。该电极可以以微创的方式植入脑部。与现有技术相比，本方法采用平面微纳制造技术实现三维脑电监测电极制备，操作简单，设备简单。所制备高密度脑电监测电极尺寸小，生物相容性好，精密度高，使用寿命长，其可在神经细胞尺度上实现脑电信号的监测，可用于脑研究、脑机接口、神经调控等领域。
Description
技术领域
本发明涉及植入电极领域，尤其涉及一种微创植入式高密度脑电电极的制备。
背景技术
目前商业化的植入式脑电电极主要以金属、金属氧化物和合金这类刚性材料为主，这类材料具有优越的导电性能，但其硬度远高于生物组织，并且在植入和使用过程中也容易对生物组织造成损害。近年来，基于聚合物、水凝胶、碳材料等柔性材料的脑电电极被开发，以解决接口与生物组织模量不匹配的问题。植入脑电电极需要具备良好的生物相容性以及较小尺寸，以减小其在植入过程中对生物组织的创伤。同时，柔性脑电电极还面临着导电性差的问题。此外，提高电极的通道数量也是实现脑电电极在脑机接口、脑研究等领域应用的关键因素。针对这些问题，开发微创植入式高密度脑电监测电极是实现高效神经电生理信号监测的有效策略。
发明内容
本发明的目的在于解决现有技术中的上述问题，提供一种微创植入式高密度脑电电极的制备，通过薄膜基底制备、导电图案设计、基底图形裁剪、卷曲折叠等方法来制备微创植入式高密度脑电监测电极。该方法能兼容平面微纳制造技术，操作简单，过程设备简单。脑电监测电极是集成了高密度通道的微米级纤维器件，通道分布可调，其可以以微创的方式植入体内。这种高密度脑电监测电极尺寸小，既柔软又坚韧，生物相容性好，使用寿命长，其不仅限用于脑机接口，该方法还可以延伸应用至其它领域如癫痫的预警与治疗、神经调节、肿瘤的监测与治疗等。
为达到上述目的，本发明采用如下技术方案：
一种微创植入式高密度脑电电极的制备，对薄膜电极的导电图案及基底图形进行设计，制备后将其反向卷曲或折叠，由此实现高密度脑电电极的制备；所述的导电图案为多个“L”形依次嵌套排列，所有“L”形图案的一端沿平行于“L”形另一条线的基底的一边直线排布，另一端通过调控相应边的长度形成斜线、弯折线或者曲线中的至少一种线条；将基底沿多个“L”形图案另一端所形成的线条进行剪裁，对电极的暴露长度进行调控。
通过对所述基底图形的底角进行调节，可对电极在纤维上的分布调节，优选的底角范围10°～85°。
所述基底的材料包括聚氨酯、聚酰亚胺、聚乙烯醇、聚酯、聚萘二甲酯乙二醇酯、聚二甲基硅氧烷、聚苯乙烯丁二烯嵌段共聚物、氢化聚苯乙烯丁二烯嵌段共聚物、聚酰亚胺、胶原蛋白、蚕丝蛋白的一种或多种。
所述基底的制备方法包括旋涂、刮涂、物理/化学气相沉积、卷对卷的一种或多种。
所述基底的厚度不低于200nm，优选厚度为500～2000nm。
导电图案的原材料包括金属材料(金、银、铜、铂)、合金材料(液态合金)、金属盐、碳材料(炭黑、石墨、碳纤维、碳纳米管)、导电有机化合物(聚乙炔、聚吡咯、聚噻吩)的一种或几种。
导电图案的制备方法包括磁控溅射、热蒸镀、电子束沉积、电化学沉积、化学气相沉积、光刻、喷涂、3D打印、喷墨打印、丝网印刷、点胶。
导电路径的线宽不低于2μm，优选的线宽为20μm～500μm；导电路径的间距不低于2μm，优选的间距为20μm～500μm。
将薄膜电极反向卷曲或折叠制备得高密度纤维脑电电极，其尺寸由薄膜电极尺寸决定，直径不小于25μm，优选直径为50μm～1000μm，长度不小于2cm，优选长度为5～10cm。
本发明所述电极可用于微创植入脑内，实现神经细胞尺度上的高密度脑电的定向精准监测、多点及多种定向刺激，也可用于微创植入人体，癫痫的预警与治疗、神经调节、肿瘤的监测与治疗等领域。
相对于现有技术，本发明技术方案取得的有益效果是：
1、本发明提供一种微创植入式高密度脑电监测电极，其在一根微米级的纤维器件上可以集成100个以上通道，可以实现神经细胞尺度上的定向高密度的脑电监测。
2、本发明所提供的制备策略可以兼容平面维纳制造技术，不仅能扩展制备方法及其适用材料，还能显著降低制备脑机接口的成本及其操作难度。
3、本发明所制备的微创植入式高密度脑电监测电极尺寸小、通道密度高，柔性好，生物相容性好，其可以通过微创植入人体且不容易引起机体的排异反应。
4、本发明所制备的微创植入式高密度脑电监测电极不仅限于脑机接口的应用，还可以为延伸应用于癫痫的预警与治疗、神经调节、肿瘤的监测与治疗等领域。
附图说明
图1为实施例1制备高密度脑电监测电极的示意图。
图2为实施例1的含有导电路径图案薄膜基底的照片。
图3为实施例1的导电路径图案的显微镜照片。
图4为实施例1所得的微创植入式高密度脑电监测电极照片。
图5为实施例2的高密度脑电监测电极的示意图。
图6为实施例3的高密度脑电监测电极的示意图。
具体实施方式
为了使本发明所要解决的技术问题、技术方案及有益效果更加清楚、明白，以下结合附图和实施例，对本发明做进一步详细说明。
实施例1
如图1～4所示，以厚度为1μm的聚苯乙烯丁二烯嵌段共聚物为基底，利用掩模版覆盖薄膜并通过磁控溅射制备嵌套排列100nm厚的“L”形的金作为导电通路。具有导电通路的聚苯乙烯丁二烯嵌段共聚物基底如图2所示，其中金导电通路的个数为40，输入端线宽为250μm，间距为150μm，输出端线宽为580μm，间距为878μm(如图3所示)。通过手术刀将薄膜切割成斜边为直线，底角为45°的直角梯形再进行反向卷曲，制备得到纤维状的高密度脑电监测电极，如图4所示。所制备的脑机接口直径为300μm，长度为9cm。通过穿刺装置将电极安放置大脑内，对脑电进行精准且稳定的监测。
实施例2
以厚度为500nm的聚氨酯薄膜为基底，通过光刻制备掩模版以及通过热蒸镀30nm厚的“L”形的金作为导电通路，其中金导电通路的个数为120，输入端线宽为20μm，间距为80μm，输出端线宽为150μm，间距为350μm。参见图5，通过手术刀将薄膜切割成斜边为曲线，底角为15°的类梯形，再将其卷曲，制备得到具有高密度通道的纤维器件。所制备的纤维直径为350μm，长度为9cm，其在拉伸150％时，依旧能实现对生理电信号的稳定监测。通过穿刺装置将纤维器件安放置脊髓组织中，其可以实现对神经信号精准采集。
实施例3
以厚度为800nm的聚氨酯薄膜为基底，通过光刻制备掩模版以及通过电子束蒸发30nm厚的“L”形的金作为导电通路，其中金导电通路的个数为100，输入端线宽为25μm，间距为85μm，输出端线宽为120μm，间距为300μm。参见图6，本实施例中，斜边为两段直线组成的弯折线和底角分别为75°和30°的梯形基底，再将其卷曲，制备得到具有高密度通道的纤维器件。所制备的脑机接口直径为380μm，长度为11cm。通过穿刺装置将电极安放置大脑内，对脑电进行精准且稳定的监测。
Claims (10)
1.一种微创植入式高密度脑电电极的制备，其特征在于：对薄膜电极的导电图案及基底图形进行设计，制备后将其反向卷曲或折叠，由此实现高密度脑电电极的制备；所述的导电图案为多个“L”形依次嵌套排列，所有“L”形图案的一端沿平行于“L”形另一条线的基底的一边直线排布，另一端通过调控相应边的长度形成斜线、弯折线或者曲线中的至少一种线条；将基底沿多个“L”形图案另一端所形成的线条进行剪裁，对电极的暴露长度进行调控。
2.如权利要求1所述的一种微创植入式高密度脑电电极的制备，其特征在于：所述基底图形的底角范围10°～85°。
3.如权利要求1所述的一种微创植入式高密度脑电电极的制备，其特征在于：所述基底的材料包括聚氨酯、聚酰亚胺、聚乙烯醇、聚酯、聚萘二甲酯乙二醇酯、聚二甲基硅氧烷、聚苯乙烯丁二烯嵌段共聚物、氢化聚苯乙烯丁二烯嵌段共聚物、聚酰亚胺、胶原蛋白、蚕丝蛋白的一种或多种。
4.如权利要求1所述的一种微创植入式高密度脑电电极的制备，其特征在于：所述基底的制备方法包括旋涂、刮涂、物理/化学气相沉积、卷对卷的一种或多种。
5.如权利要求1所述的一种微创植入式高密度脑电电极的制备，其特征在于：所述基底的厚度不低于200nm，优选厚度为500～2000nm。
6.如权利要求1所述的一种微创植入式高密度脑电电极的制备，其特征在于：导电图案的原材料包括金属材料、合金材料、金属盐、碳材料、导电有机化合物的一种或几种；导电图案的制备方法包括磁控溅射、热蒸镀、电子束沉积、电化学沉积、化学气相沉积、光刻、喷涂、3D打印、喷墨打印、丝网印刷、点胶。
7.如权利要求1所述的一种微创植入式高密度脑电电极的制备，其特征在于：导电路径的线宽不低于2μm，优选的线宽为20μm～500μm；导电路径的间距不低于2μm，优选的间距为20μm～500μm。
8.如权利要求1所述的一种微创植入式高密度脑电电极的制备，其特征在于：将薄膜电极反向卷曲或折叠制备得高密度纤维脑电电极，其尺寸由薄膜电极尺寸决定，直径不小于25μm，优选直径为50μm～1000μm，长度不小于2cm，优选长度为5～10cm。
9.权利要求1～8任一项制备的一种微创植入式高密度脑电电极的应用，其特征在于：用于微创植入脑内，实现神经细胞尺度上的高密度脑电的定向精准监测、多点及多种定向刺激。
10.权利要求1～8任一项制备的一种微创植入式高密度脑电电极的应用，其特征在于：用于微创植入人体，癫痫的预警与治疗、神经调节、肿瘤的监测与治疗领域。
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