C. H. Keck, N. Rommelfanger, Zihao Ou, Guosong Hong
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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. 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引用次数: 2
摘要
高灵敏度的视蛋白可以减少对光纤的依赖,并通过完整的头皮和颅骨实现脑深部光遗传刺激,同时最大限度地减少脑组织加热和相关的神经活动偏倚。虽然优化的视蛋白工程已经产生了适合经颅光遗传刺激的超灵敏和红移视蛋白,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104的近场强度增强,但到目前为止,纳米材料还没有应用于光遗传学应用中放大局部光强度。在本文中,我们建议使用领结纳米天线对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470nm处提供的近场强度增强。接下来,我们调整了铝领结纳米天线的几何参数,以最大限度地提高470 nm处的强度。我们通过构建受生物学模式启发的领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,仅50 mW mm - 2的经颅470 nm照明能够刺激小鼠脑深部(~ 5 mm)的领结致敏ChR2,从而实现传统光遗传学工具箱中发现的视蛋白的微创脑深部刺激。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,可以提高光遗传神经调节、光学神经活动成像和大脑高度局部电微刺激的效率。
Bioinspired nanoantennas for opsin sensitization in optogenetic applications: a theoretical investigation
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.