Laboratory for Biomedical Microtechnology, Department of Microsystems Engineering, University of Freiburg, Freiburg, Germany.
Neurophysics, Natural and Medical Sciences Institute, University of Tübingen, Reutlingen, Germany.
Biosens Bioelectron. 2022 Jun 1;205:114090. doi: 10.1016/j.bios.2022.114090. Epub 2022 Feb 15.
Optical stimulation of genetically modified nerve cells has become one of the state-of-the-art methods in neuroscience. This so-called optogenetic approach allows cell-type specific activation in comparison to more generalized electrical stimulation. Combinations of both stimulation modalities would be desirable to investigate effects in detail and specify differences. This work presents the design of a miniaturized optoelectronic device that allows optical and electrical activation at the same spot. Indium tin oxide (ITO), which is transparent to visible light, has been chosen as electrode material. Light emitting diodes were assembled on a polyimide substrate with integrated interconnection lines, directly behind the electrodes to compare optical with electrical stimulation. The optical transparency of the ITO-polyimide layer stack was investigated and showed sufficient transmission in the required wavelength range. ITO electrodes with diameters up to 1000 μm were electrochemically characterized using electrical impedance spectroscopy (EIS). Several diameters did show comparable results to platinum, a commonly used electrode material. Fully assembled devices were used in combination an ex vivo setting with genetically modified retina to demonstrate the functionality of this approach. Retinal ganglion cells were excited by both, optical and electrical stimulation at the same spot and signals were recorded via standard microelectrode arrays (MEA) as reference. The simultaneous stimulation and recording of directly evoked action potentials indicates a similar mode of action of the two stimulation modalities. Further engineering work is needed to transfer the presented and proven concept into devices for chronic implantation, might it be in animal or first-in-human studies.
光刺激遗传修饰的神经细胞已经成为神经科学的最先进方法之一。与更广泛的电刺激相比，这种所谓的光遗传学方法允许细胞类型特异性激活。将这两种刺激模式结合起来，将有利于详细研究效果并明确差异。这项工作提出了一种小型化光电设备的设计，该设备允许在同一位置进行光和电激活。透明可见光的氧化铟锡（ITO）已被选为电极材料。发光二极管被组装在聚酰亚胺基板上，带有集成的互连线，直接位于电极后面，以比较光刺激和电刺激。研究了 ITO-聚酰亚胺层叠的光学透明度，并显示出在所需波长范围内有足够的传输。使用电化学阻抗谱（EIS）对直径达 1000μm 的 ITO 电极进行了电化学表征。几种直径与常用的电极材料铂表现出可比的结果。在体外环境中，使用完全组装的设备与遗传修饰的视网膜相结合，以证明这种方法的功能。通过标准微电极阵列（MEA）作为参考，同时在同一位置用光和电刺激来激发视网膜神经节细胞，并记录信号。直接诱发动作电位的同时刺激和记录表明两种刺激模式的作用方式相似。需要进一步的工程工作将提出和验证的概念转化为用于慢性植入的设备，无论是在动物还是首次人体研究中。
