CN106308754A - 一种可植入式微型led神经探针 - Google Patents
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Abstract
本发明涉及一种可植入式微型LED神经探针，包括探针体，探针体前端为探针头，探针体后端为连接端，探针体包括微型LED阵列、驱动电路和探针插脚；微型LED阵列含x*y个的LED元件，各LED元件分别对应一个驱动单元，x*y个的驱动单元构成驱动电路；各LED元件与驱动单元电连接，位于探针体前端的探针头处；驱动单元的电极与探针插脚连接，各驱动单元分别对应一个探针插脚，x*y个探针插脚并行排列位于探针体后端的连接端。本发明可实现神经探针的超高分辨率和大脑神经细胞的多区域多角度刺激和监测，本发明还通过电气互连的方法实现微型LED阵列与ParyleneC柔性聚合物的互连，增强了探针对人体的亲和力，避免了刚性物体对脑组织施加太多的压力而造成伤害。
Description
技术领域
本发明涉及一种神经科诊疗设备，更具体的说是提供一种用于监测大脑神经活动的可植入式微型LED神经探针，是一种有助于医学人员寻找治愈神经系统疾病的工具。
背景技术
神经探针通过揭示生物神经元网络的运作，让我们对大脑的理解产生了显著的效果。神经探针目前在医学领域主要用于脑疾病，如癫痫，偏头痛，阿尔茨海默氏症，痴呆等神经疾病。近年来，在微电子技术和光遗传学不断发展完善的背景下，神经探针的研究也取得了快速的进步和发展。通过将神经探针植入大脑的不同区域，以记录和刺激大脑中特定的位点，从而能够进行细胞级的检测、处理以及解释神经数据，从而帮助医学人员深入了解神经疾病并做出合理对策。
然而，现有的神经探针，其光源在大脑组织中的传播以及成像方面还缺乏一个高分辨率辨识，并且由于找不到可用于慢性实验研究的可用光源，目前的使用仅仅局限于急性研究。虽然在一些研究中，可以通过利用光学纤维和微型内窥镜使光传输到大脑中，但是这些方案对于大脑来说是有很大危害的，因为它们使得刚性物体对脑组织施加太多的牵引力，因此限制了它们在急性实验中的使用，所以神经探针的研究在很大程度上还需要不断地改进和提高。
发明内容
本发明所要解决的技术问题是克服现有技术中的不足，提供一种能够存在于多个脑区域多角度记录和刺激神经元活动的可植入式微型LED神经探针。
为解决现有技术问题，本发明采用的技术方案是：
一种可植入式微型LED神经探针，包括探针体，探针体前端为探针头，探针体后端为连接端，所述探针体包括微型LED阵列、驱动电路和探针插脚；所述微型LED阵列是由x*y个的LED元件构成，每个LED元件分别对应一个驱动单元，x*y个的驱动单元构成驱动电路；各LED元件与驱动单元通过超薄（微米级）柔性电缆电连接并集成，位于探针体前端的探针头处；驱动单元的电极与探针插脚连接，各驱动单元分别对应一个探针插脚，x*y个探针插脚并行排列位于探针体后端的连接端。LED元件就由所述驱动电路中的驱动单元独立支配控制发光效果，从而可以实现照射单个或多个神经元，所述LED元件也可以通过生成任意形态的光对大脑神经组织进行照射以查看神经组织的三维视图；微型LED阵列发出的光能直接射入大脑组织，所述微型LED阵列上的LED元件直径大约有5，能够发射波长范围为420-450nm的可见光，可应用于大脑组织的光遗传学刺激。
其中探针体的连接端和所述探针头的尺寸大小可以通过光学光刻技术任意界定，本微型LED神经探针结合光遗传学技术能够对大脑神经组织进行刺激并记录神经活动。
优选的，所述神经探针还包括Parylene C柔性衬底，所述探针体中的驱动电路、微型LED阵列均与所述Parylene C柔性衬底电连接。Parylene C柔性衬底的外形与探针体保持一致。
优选的，所述LED元件、驱动电路和Parylene C柔性衬底从上到下依次排列，使得可植入式微型LED神经探针的厚度只有10μm。
优选的，所述Parylene C柔性衬底是一个具有生物相容性的超薄聚合物体。
优选的，所述探针体上表面均匀涂敷有柔性生物材料包覆层，并裸露LED元件；仅探针头的LED元件暴露在外，从而使探针体具有较高的生物相容性和较强的亲和力，在诊疗过程中不易发生排异反应，减少外来物体对大脑组织造成的伤害。
优选的，所述LED元件是通过激光剥离技术去除蓝宝石衬底的发光元件，具体是在蓝宝石衬底上通过分子束外延技术生成一层由氮化镓和量子结构组成的异质结构，在异质结构上完成电极的制作之后通过激光剥离技术除去微型LED阵列的蓝宝石衬底，进而可以使得微型LED阵列发出的光能直接射入大脑组织而避免蓝宝石衬底对光源的吸收。
与现有技术相比，本发明的有益效果为：可植入式微型LED神经探针的厚度只有10， LED元件的直径大约有5μm，在微型LED阵列上可以集成更多的LED发光元件，可以实现神经探针的超高分辨率， LED元件可以发射波长范围为420-450nm的可见光，光电转化效率大于5%，这意味着在脑组织中最小加热光功率为0.5-1mW，利用光遗传学技术使微型LED神经探针插入转基因老鼠的大脑组织，结合Parylene C超薄柔性聚合物涂层的超高生物相容性的特点，使微型LED神经探针能够深入大脑组织内部进行高分辨率的监测活动并且能够在大脑中保持自由浮动而不造成很大伤害，通过采用全细胞膜片钳记录来监测所述微型LED神经探针的驱动效果，由于所述LED发光管由所述驱动电路独立支配控制发光效果，从而可以记录单个或多个神经元活动，也可以查看神经组织的三维视图效果。
本发明设计的可植入式微型LED神经探针具有结构简单，使用方便的特点，在神经科患者的诊疗过程中可以进行直接性的刺激和监测活动，并且具有人体排异反应低的特点，为神经科诊疗工作的开展带来了方便。
附图说明
图1是本发明实施例的结构示意图。
图2是本发明实施例的前视图。
图3是本发明实施例的探针头的弯曲示意图。
具体实施方式
以下结合附图对本发明做进一步的解释说明。附图仅用于示例性说明，不能理解为对本发明的限制；为了更好说明本实施例，附图某些部件会有省略、放大或缩小；对于本领域技术人员来说，附图中某些公知结构及其说明可能省略是可以理解的。
如图1所示的一种可植入式微型LED神经探针，包括探针体，探针体前端为探针头，探针体后端为连接端。探针体前端的探针头设有x*y格式的LED元件1和驱动单元2，x*y格式的LED元件1构成微型LED阵列，x*y格式的驱动单元2构成驱动电路；探针体后端的连接端设有探针插脚3。探针头处的LED元件1是基于蓝宝石衬底和氮化物半导体构成，在电极制造完毕通过激光剥离技术除去LED元件1的蓝宝石衬底，使微型LED阵列发出的光能直接射入大脑组织而避免蓝宝石衬底对光源的吸收，就可以使光源强度能够深入到大脑组织内部，各LED元件1的两个电极分别连接到一个驱动单元3的两端， LED元件1位于驱动单元2的正上方，驱动单元2通过焊盘连接与LED元件1集成，这样就可以通过驱动单元2控制对应的LED元件1进行发光。驱动单元2采用有源驱动的方式来控制LED元件1的发光效果，这样可以保证LED元件1在大脑神经组织中持续保持发光并进行有效监测LED元件1形成的x*y阵列，对应的驱动电路的驱动单元2所有电极接线均连接到探针体后端的连接端，在探针体后端的连接端并行的排列形成的探针插脚3，由x*y格式的微型LED阵列、驱动电路和探针插脚3构成的探针体通过电气互连技术连接到Parylene C柔性衬底4上，使探针体位于Parylene C柔性衬底4上方，Parylene C柔性衬底4与探针体的形状大小保持一致，为了进一步增加探针体的生物相容性，在探针体表面均匀涂敷一层柔性生物材料包覆层进行封装，仅x*y个LED元件1暴露在外，这样使探针体具有较高的生物相容性和较强的亲和力，在诊疗过程中不易发生排异反应，探针体还能在大脑组织中进行自由浮动，使探针体可以查看神经组织的三维视图效果。
本实施例，将可植入式微型LED神经探针用于转基因老鼠中进行试验，利用光遗传学技术在转基因老鼠表达的ChR2作为光敏蛋白，使用所述可植入式微型LED神经探针插入转基因老鼠大脑组织中，由于所述探针体具有高生物相容性和强亲和力使所述探针体能够在大脑组织中保持自由的浮动，从而可以对选定的脑区域中特定细胞进行光照刺激，使细胞膜两边的膜电位发生变化，达到对细胞选择性的兴奋或者抑制的目的，还可以通过控制所述LED阵列上不同的LED元件发光，这样能够全面的多角度的观察细胞的反应并进行监测，所述的LED元件可以发射波长范围为420-450nm的可见光，光电转化效率大于5%，这意味着在脑组织中最小加热光功率为0.5-1mW，使所发射的可见光能深入到神经组织内部，克服了现有技术只局限于细胞表面的缺陷。
显然，本发明的上述实施例仅仅是为清楚地说明本发明所作的举例，而并非是对本发明的实施方式的限定。在上述说明的基础上还可以做出其它不同形式的变化或变动，这里无需也无法对所有的实施方式予以穷举。凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等，均应包含在本发明权利要求的保护范围之内。
Claims (6)
1.一种可植入式微型LED神经探针，包括探针体，探针体前端为探针头，探针体后端为连接端，其特征在于，所述探针体包括微型LED阵列、驱动电路和探针插脚；所述微型LED阵列是由x*y个的LED元件构成，每个LED元件分别对应一个驱动单元，x*y个的驱动单元构成驱动电路；各LED元件与驱动单元电连接并集成，位于探针体前端的探针头处；驱动单元的电极与探针插脚连接，各驱动单元分别对应一个探针插脚，x*y个探针插脚并行排列位于探针体后端的连接端。
2.根据权利要求1所述的可植入式微型LED神经探针，其特征在于，所述神经探针还包括Parylene C柔性衬底，所述探针体中的驱动电路、微型LED阵列均与所述Parylene C柔性衬底电连接。
3.根据权利要求2所述的可植入式微型LED神经探针，其特征在于，所述LED元件、驱动电路和Parylene C柔性衬底从上到下依次排列。
4.根据权利要求2所述的可植入式微型LED神经探针，其特征在于，所述Parylene C柔性衬底是一个具有生物相容性的超薄聚合物体。
5.根据权利要求1所述的可植入式微型LED神经探针，其特征在于，所述探针体上表面均匀涂敷有柔性生物材料包覆层，并裸露LED元件。
6.根据权利要求1所述的可植入式微型LED神经探针，其特征在于，所述LED元件是通过激光剥离技术去除蓝宝石衬底的发光元件。
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