Programmable, Soft Optical Waveguide for Optogenetics

项目摘要 拟议项目旨在开发一种可编程的软光波导， 精确和均匀的光传输，提供大的侧向通路，并最大限度地减少大脑中的炎症反应 组织.为了最大限度地发挥这些功能的潜力， 光遗传学在研究脑功能和治疗人类神经系统疾病方面有着重要的应用价值，但目前尚不成熟 在当前的光遗传学探针及其集成光电器件中。所提出的波导将被制成 其核心是由藻酸盐包覆的生物相容性形状记忆聚合物（SMP） 在另一个实施方案中，SMP包含水凝胶层，其具有比SMP更低的折射率（RI）。这种RI不匹配将有助于实现 SMP和水凝胶层的界面中的光的全内反射。在相变之上 温度（< 37 ℃）下，SMP将变得高度透明，并显示软机器人驱动。该致动 力将驱动高度紧凑的光波导-以便于插入脑组织-以形成 预编程的三维（3D）波浪形和扩展形状。具有限定的光学孔径沿着 通过单独的柄部，光可以均匀且精确地传递到脑组织。继承的 SMP和水凝胶的生物相容性和柔软性将导致很少或没有炎症反应。 脑组织据我们所知，这将是开发这种类型的光波导的第一次尝试。 为了实现所提出的目标，将首先设计波导的光学和机械结构。 然后将开发数值模型来优化静态和动态致动过程， 作为实验的精密设计原则。将制造光波导， 程序化的。它的光传输和形状驱动性能将被评估。得到的SMP和 藻酸盐水凝胶将具有最佳的折射率和机械性能。他们的界面将是 坚固且光滑，以使光散射最小化。预期波导显示出令人满意的形状 在模拟脑组织的粘弹性环境的0.6%琼脂糖水凝胶中， 如果成功，这项技术将是变革性的。首先，它将为知识分子和 为具有新功能的可植入设备提供新平台的技术方法， 普通设备无法提供的，如真正的3D界面，精确和均匀的光传输，最小化的损伤， 到大脑。所有这些都将有助于加深对大脑功能的理解。此外， 可以与波导一起进行信号记录的微电极将使设备具有以下功能： 刺激和记录。它们可以进一步发展为基于光遗传学的神经调节疗法 用于治疗人类神经系统疾病，如帕金森氏病和癫痫，这些疾病是高度相关的 公共卫生。最后，这里介绍的这种3D神经接口的概念和技术可能会导致生物- 电子光电系统，将显示响应和自适应功能的未来。

Project Summary The proposed project aims at developing a programmable and soft optical waveguide which will enable precise and uniform light delivery, provide large lateral access, and minimize inflammatory response in the brain tissue. Combination of these functions in one device is highly demanded for maximizing potentials of optogenetics in studying brain functions and treating human’s neurological diseases, but it is still not accessible in current optogenetic probes and their integrated optoelectronic devices. The proposed waveguide will be made of interconnected shanks whose core is a biocompatible shape memory polymer (SMP) cladded by alginate hydrogel layers, which has a lower refractive index (RI) than that of the SMP. This RI mismatch will help to realize total internal reflection of light in the interface of the SMP and the hydrogel layers. Above the phase transition temperature (< 37 ℃), the SMP will become highly transparent and show soft-robotic actuation. This actuation force will drive the highly compact optical waveguide—for easy insertion to the brain tissue—to form a preprogrammed three-dimensional (3D) wavy and expanding shape. With defined optical apertures along the individual shank, the light can be uniformly and precisely delivered to the brain tissue. The inherited biocompatibility and softness of the SMP and the hydrogel will cause little or no inflammatory response to the brain tissue. To our knowledge, it will be the first attempt of developing such a type of optical waveguide. To accomplish the proposed goal optical and mechanical structures of the waveguide will be first designed. Then numerical models will be developed to optimize the static and dynamic actuation processes, which will serve as the sophisticated design principles for the experiments. The optical waveguide will be fabricated, programmed. Its light transport and shape actuation performance will be evaluated. The resulting SMP and alginate hydrogel will have the optimum refractive indices and mechanical properties. Their interface will be strong and smooth for minimizing the light scattering. The waveguide is expected to show satisfactory shape actuation and little light loss in 0.6% agarose hydrogel that mimics the viscoelastic environment of brain tissue. If success, this proposed technology will be transformative. First of all, it will pave the intellectual and technological way to provide a novel platform for implantable devices with new functionalities which other ordinary devices cannot offer, such as truly 3D interfaces, precise and uniform light delivery, minimized damage to the brain. All of them will help to deepen the understanding of brain functions. Moreover, integration of the microelectrodes that can do signal recording with the waveguide will empower the devices the functions of stimulation and recording. They can be further developed into optogenetics-based neuromodulation therapies for treating human’s neurological diseases such as Parkinson’s disease and epilepsy, which are highly relevant to public health. Finally, concepts and technologies of this 3D neural interface introduced here may result in bio- electronic-optoelectronic systems that will show responsive and adaptive features in future.