Ayub Suleman, Gentet Luc J, Fiáth Richárd, Schwaerzle Michael, Borel Mélodie, David François, Barthó Péter, Ulbert István, Paul Oliver, Ruther Patrick
Department of Microsystems Engineering (IMTEK), University of Freiburg, Freiburg, Germany.
Team Waking, Lyon Neuroscience Research Center (CNRL), INSERM-U1028, CNRS-UMR5292, Bron, France.
Biomed Microdevices. 2017 Sep;19(3):49. doi: 10.1007/s10544-017-0190-3.
This article reports on the development, i.e., the design, fabrication, and validation of an implantable optical neural probes designed for in vivo experiments relying on optogenetics. The probes comprise an array of ten bare light-emitting diode (LED) chips emitting at a wavelength of 460 nm and integrated along a flexible polyimide-based substrate stiffened using a micromachined ladder-like silicon structure. The resulting mechanical stiffness of the slender, 250-μm-wide, 65-μm-thick, and 5- and 8-mm-long probe shank facilitates its implantation into neural tissue. The LEDs are encapsulated by a fluropolymer coating protecting the implant against the physiological conditions in the brain. The electrical interface to the external control unit is provided by 10-μm-thick, highly flexible polyimide cables making the probes suitable for both acute and chronic in vivo experiments. Optical and electrical properties of the probes are reported, as well as their in vivo validation in acute optogenetic studies in transgenic mice. The depth-dependent optical stimulation of both excitatory and inhibitory neurons is demonstrated by altering the brain activity in the cortex and the thalamus. Local network responses elicited by 20-ms-long light pulses of different optical power (20 μW and 1 mW), as well as local modulation of single unit neuronal activity to 1-s-long light pulses with low optical intensity (17 μW) are presented. The ability to modulate neural activity makes these devices suitable for a broad variety of optogenetic experiments.
本文报道了一种用于基于光遗传学的体内实验的可植入光学神经探针的研发情况，即其设计、制造及验证过程。这些探针包含一排十个裸发光二极管（LED）芯片，发射波长为460纳米的光，并沿着使用微机械加工的梯状硅结构加固的柔性聚酰亚胺基衬底集成。由此产生的细长探针杆机械刚度便于将其植入神经组织，该探针杆宽250微米、厚65微米，长5毫米和8毫米。LED由氟聚合物涂层封装，可保护植入物免受大脑生理环境的影响。与外部控制单元的电接口由10微米厚的高柔性聚酰亚胺电缆提供，这使得探针适用于急性和慢性体内实验。报告了探针的光学和电学特性，以及它们在转基因小鼠急性光遗传学研究中的体内验证情况。通过改变皮层和丘脑的大脑活动，证明了对兴奋性和抑制性神经元的深度依赖性光刺激。展示了不同光功率（20微瓦和1毫瓦）的20毫秒长光脉冲引发的局部网络反应，以及低光强度（17微瓦）的1秒长光脉冲对单个神经元活动的局部调制。调节神经活动的能力使这些设备适用于各种各样的光遗传学实验。
