Opsins with high sensitivity are desired to reduce dependence on optical fibers and enable deep-brain optogenetic stimulation through the intact scalp and skull, while minimizing brain tissue heating and the associated biasing of neural activity. While optimized opsin engineering has produced ultrasensitive and red-shifted opsins suitable for transcranial optogenetic stimulation, further improvements in sensitivity are throttled by biological limitations. Nanostructures are capable of generating near-field intensity enhancements of over 10⁴, but thus far nanomaterials have not been applied to amplify local light intensity for optogenetic applications. In this manuscript, we propose the use of bowtie nanoantennas for local enhancement of 470 nm light to sensitize channelrhodopsin (ChR2) to low light intensities. We begin with a comparison of the near-field intensity enhancement offered by different metals at 470 nm, before selecting aluminum as the optimal material. Next, we tune the geometric parameters of aluminum bowtie nanoantennas to maximize the intensity enhancement at 470 nm. We further optimize enhancement by constructing bowtie nanoantenna arrays inspired by patterns occurring in biology, obtaining intensity enhancements up to a factor of 5000. Monte Carlo simulations suggest that transcranial 470 nm illumination of only 50 mW mm⁻² is capable of stimulating bowtie-sensitized ChR2 in the deep brain (∼5 mm) in mice, enabling minimally invasive deep-brain stimulation with opsins found in the traditional optogenetic toolbox. This computation-guided optical antenna engineering approach opens opportunities for designing multifunctional materials for enhancing the efficiency of optogenetic neuromodulation, optical neural activity imaging, and highly localized electrical microstimulation in the brain.

需要具有高灵敏度的视蛋白来减少对光纤的依赖，并通过完整的头皮和颅骨实现深部脑光遗传学刺激，同时最大限度地减少脑组织加热和相关的神经活动偏差。虽然优化的视蛋白工程已经产生了适合经颅光遗传学刺激的超敏感和红移视蛋白，但灵敏度的进一步提高受到生物学限制的限制。纳米结构能够产生超过 10 ^{4 的}近场强度增强，但迄今为止，纳米材料尚未用于放大局部光强度以用于光遗传学应用。在这份手稿中，我们建议使用蝴蝶结纳米天线对 470 nm 光进行局部增强，以使通道视紫红质 (ChR2) 对低光强度敏感。在选择铝作为最佳材料之前，我们首先比较了不同金属在 470 nm 处提供的近场强度增强。接下来，我们调整铝领结纳米天线的几何参数，以最大限度地提高 470 nm 的强度。我们通过构建受生物学中发生的模式启发的蝴蝶结纳米天线阵列进一步优化增强，获得高达 5000 倍的强度增强。蒙特卡罗模拟表明经颅 470 nm 照明仅为 50 mW mm ^-2能够刺激小鼠大脑深部（约 5 毫米）中蝴蝶结致敏的 ChR2，从而使用传统光遗传学工具箱中的视蛋白进行微创深部大脑刺激。这种计算引导的光学天线工程方法为设计多功能材料提供了机会，以提高光遗传学神经调节、光学神经活动成像和大脑中高度局部电微刺激的效率。