可植入光遗传学神经刺激光极研究  

Development of An Implantable Optrode for Optogenetic Stimulation

作　　者：岳森[1,2,3] 袁明军[1,2,3] 张云鹏[1] 王玺渊 王守岩[1] 

机构地区：[1]中国科学院苏州生物医学工程技术研究所,苏州215163 [2]中国科学院长春光学精密机械与物理研究所,长春130033 [3]中国科学院大学,北京100049 [4]山东农业大学,泰安271018

出　　处：《生物医学工程学杂志》2016年第2期337-342,367,共7页Journal of Biomedical Engineering

基　　金：国家自然科学基金面上资助项目(81471745);苏州市神经工程技术重点实验室资助项目(SZS01414);苏州市医疗器械与新医药专项重点资助项目(ZXY201425)

摘　　要：本文为实现多点神经环路、核团功能的在体调控,研发了可植入光遗传学神经刺激光极。首先,使用了柔性电路板工艺制作光极的基底,将微型发光二极管焊接于基底之上后使用真空气相镀膜技术制作光极的覆盖膜。然后使用光功率计等设备对光极进行性能测试,结合动物实验实现光极的验证。最终制作完成的光极尺寸为500μm×150μm(宽度×基底厚度);将其置于生理盐水14d后仍可正常发光;最大发光功率为9.31mW,有效光照面积达到3.03mm2;在体实验中检测到了光刺激诱发的小鼠皮层响应,并成功调控了小鼠的次级运动皮层。本文研制的光极具有光照面积大、植入方便、可长期植入等特点,为核团功能调控等研究提供了新的光遗传学工具。In this study,an implantable optrode was developed for optogenetics stimulation of neural population in nuclei or multi-sites in neural circuits.The optrode was composed of base layer,micro-light emitting diode（LED）and coating layer.The base layer was a 150μm thick polyimide substrate on which copper wires and contacts were fabricated by flexible printed circuit board processes.The micro-LED was soldered on the contacts using SnBi.ParyleneC was deposited over the optrode as the coating layer using a vacuum vapor deposition system.The optical output power was tested by optical power meter and the insulating property was tested using saline in the experiment.The stimulation function of the optrode was demonstrated through animal experiment.The width of the optrode was500μm and the maximum thickness of the optrode was 310μm at the LED position.The thickness of the parylene coating layer was about 1μm.The maximum optical output power of optrode was 9.31 mW and the effective illumination area was a 3.03mm2 spherical cap at 650μm deep in brain tissue.The optrode was still functional after 14 days in physiological saline.Conventional copper electrodes were used to verify the efficacy of the optrode for stimulation and robust spiking activities of the expressing Channelrhodopsin-2neurons in the entire cortex of a mouce were recorded.Obvious behavior change happened when light stimulation was applied to the expressing Channelrhodopsin-2neurons in the secondary motor cortex of the mice.The optrode has the characteristics of large effective illumination range,flexible in implantation and long-term implantable,which provide neural population in nuclei research a new tool.

关 键 词：光遗传学 神经刺激 光极 

分 类 号：TN312.8[电子电信—物理电子学] Q42[生物学—神经生物学]