School of Biological & Health Systems Engineering, Ira A. Fulton School of Engineering, Arizona State University, Tempe, AZ 85287, United States of America.
Biomed Phys Eng Express. 2020 Feb 17;6(2):025003. doi: 10.1088/2057-1976/ab6fb7.
There is a need for low power, scalable photoelectronic devices and systems for emerging optogenetic needs in neuromodulation. Conventional light emitting diodes (LEDs) are constrained by power and lead-counts necessary for scalability. Organic LEDs (OLEDs) offer an exciting approach to decrease power and lead-counts while achieving high channel counts on thin, flexible substrates that conform to brain surfaces or peripheral neuronal fibers. In this study, we investigate the potential for using OLEDs to modulate neuronal networks cultured in vitro on a transparent microelectrode array (MEA) and subsequently validate neurostimulation in vivo in a transgenic mouse model.
Cultured mouse cortical neurons were transfected with light-sensitive opsins such as blue-light sensitive channel-rhodopsin (ChR2) and green-light sensitive chimeric channel-rhodopsin (C1V1tt) and stimulated using blue and green OLEDs (with 455 and 520 nm peak emission spectra respectively) at a power of ~1 mW mm under pulsed conditions.
We demonstrate neuromodulation and optostimulus-locked, single unit-neuronal activity in neurons expressing stimulating opsins (34 units on n = 4 MEAs, each with 16 recordable channels). We also validated the optostimulus-locked response in preliminary experiments in a channel-rhodopsin expressing transgenic mouse model, where at least three isolatable single neuronal cortical units respond to OLED stimulation.
The above results indicate the feasibility of generating sufficient luminance from OLEDs to perform neuromodulation both in vitro and in vivo. This opens up the possibility of developing thin, flexible OLED films with multiple stimulation sites that can conform to the shape of the neuronal targets in the brain or the peripheral nervous system. However, stability of these OLEDs under chronic conditions still needs to be carefully assessed with appropriate packaging approaches.
新兴光遗传学神经调节对低功耗、可扩展光电设备和系统提出了需求。传统发光二极管 (LED) 受到功率和可扩展性所需的引脚数量的限制。有机发光二极管 (OLED) 提供了一种很有前途的方法，可以在薄而灵活的衬底上实现高通道数，同时减少功率和引脚数量，从而适应大脑表面或周围神经元纤维。在这项研究中，我们研究了使用 OLED 调制体外培养的神经元网络的潜力，然后在转基因小鼠模型中验证体内神经刺激。
培养的小鼠皮质神经元转染光敏感视蛋白，如蓝光敏感通道视蛋白 (ChR2) 和绿光敏感嵌合通道视蛋白 (C1V1tt)，然后使用功率约为 1 mW/mm 的蓝色和绿色 OLED（分别具有 455nm 和 520nm 峰值发射光谱）进行脉冲刺激。
我们在表达刺激视蛋白的神经元中证明了神经调节和光刺激锁定、单细胞神经元活动（在 n=4 个微电极阵列上有 34 个单元，每个单元有 16 个可记录通道）。我们还在表达通道视蛋白的转基因小鼠模型中的初步实验中验证了光刺激锁定反应，其中至少三个可分离的皮质单个神经元单元对 OLED 刺激有反应。
上述结果表明，从 OLED 产生足够的亮度来进行体外和体内神经调节是可行的。这为开发具有多个刺激点的薄而灵活的 OLED 薄膜开辟了可能性，这些薄膜可以适应大脑或外周神经系统中神经元目标的形状。然而，仍需通过适当的封装方法仔细评估这些 OLED 在慢性条件下的稳定性。
