Photo-Reversible Polymers for the Opto-Bio Interface

最终目标是设计、制备和测试可层叠在软光纤末端的含染料聚合物，这些聚合物可以在近距离进行微观定位，甚至与活的神经细胞接触，以便在与它们进行双向通信时感知和发出信号。为了实现这一目标，三管齐下的方法将平等地结合三个领域的独立项目：合成有机染料化学、聚合物和界面材料化学以及物理光纤光谱学。所有三个并行的组成部分项目都在每个领域提出了重大进展，以实现联合方案目标，但每个进展都可能是独立有价值的。设计的聚合物将是真实生物组织的软、湿模拟，并将包含少量敏感的偶氮染料，在突触事件期间释放的特定神经递质存在时，这些染料会发生明显变化。最终，这将允许在活的神经细胞和发送和接收的光纤之间制造和优化有源双向接口-使用类似的光可逆染料来释放可能刺激动作电位的化学信号。 在活体脑组织和读出技术之间建立工作接口的历史尝试总是使用植入的金属微电极。然而，这些表面基本上是侵入性的，在开始排斥之前只持续几个小时-神经细胞不可避免地会对植入的金属电极作为异物做出反应，将它们包裹在星形胶质疤痕中，最终在电极和神经通讯机制之间建立障碍。相反，这里概述的方法是新颖的，因为在界面自组装的软湿聚合物具有固有的稳定的生物相容性，并且使用光来感知和信号而不是电流。指导这一方法的将是生物模仿和自组装原理，其中表面生物膜主体聚合物以其柔软、潮湿、顺应性的可调谐能力模仿真实的生物组织，而光响应型形状变化的偶氮染料模仿我们的视紫红质/视网膜系统，从而实现视觉和直接的光-神经信息接口。 更具体地说，这项建议寻求将当前偶氮生物膜的可逆光开关能力扩展到双向可逆通信(传感和信号)，使用具有pH敏感性的新型多功能染料，以及可结合和检测多巴胺类二醇神经递质的悬挂硼酸基团。既然细胞反应已被证明能够由偶氮表面触发，这里的开发挑战和风险也代表着值得实现的目标：a)整个细胞生长到仅仅是神经突触，b)不可逆到可逆，c)1路到2路通信，d)长时间预照射到实时通信，e)静态切换到动态，f)体外到体内检测，以及g)大表面到小纤维。 从实用的角度来看，这些新材料由于结合了软光化学功能和其固有的生物兼容性，被认为是用于传感、发送信号和控制邻近生物活动的智能表面。从基础科学的角度来看，这些新材料及其研究将使我们能够从化学和材料的角度对活细胞和人工介质之间的界面上的生物功能以及它们之间的交流做出基本的了解。结合在一起，这一提议代表了一个令人兴奋的新方向，以实现以自然为灵感的脑机接口，以软有机材料为灵感，并以光为通信媒介。

The eventual goal is to design, prepare, and test dye-containing polymers that can be layered onto soft optical fiber ends, that can be micro-positioned in close proximity or even contact with live neural cells to both sense and signal in 2-way communication with them. A 3-pronged approach towards this goal will combine separate projects equally in 3 fields working together of: synthetic organic dye chemistry, polymer and interfacial materials chemistry, and physical fiber optic spectroscopy. All 3 component projects in parallel propose significant advances in each field order for the combined program goals to be realized, yet advances realized in each can be independently valuable. The polymers designed will be soft, wet mimics of real biological tissue and will contain small amounts of sensitive azo dyes that change visibly in the presence of specific neurotransmitters released during synaptic events. Ultimately, this will allow for the fabrication and optimization of an active 2-way interface between live neural cells and optical fibers that sends as well as receives—using similar photo-reversible dyes to release chemical signals back that could stimulate an action potential. Historic attempts towards a working interface between live brain tissue and readout technology invariably used implanted metal micro-electrodes. These are fundamentally invasive surfaces however, and last only hours before rejection is initiated—the neural cells inevitably eventually respond to implanted metal electrodes as foreign objects by enclosing them in astroglial scars that ultimately create a barrier between the electrode and the neural communication mechanisms. The approach outlined here instead is novel in the inherent stable biocompatibility of the soft wet polymers self-assembled at the interface, and in the use of light to sense and signal instead of electrical current. Guiding the approach will be principals of bio-mimicry and self-assembly, where the surface bio-film host polymers mimic real biological tissue in their soft, wet, compliant tune-ability, and the light-responsive shape-changing azo dyes mimic our rhodopsin/retinal systems that enable vision and a direct opto-neural information interface. More specifically, this proposal seeks to extend the reversible photo-switching capability of current azo bio-films into 2-way reversible communication (sensing and signaling), using new multi-functional dyes with pH sensitivities, and pendant boronic acid groups tuned to bind and detect the dopamine class of diol neurotransmitters. Now that cell response has been shown to be able to be triggered by an azo surface, the development challenges and risks here also represent worthwhile goals to achieve: a) entire cell growth to just neural synapse, b) irreversible to reversible, c) 1-way to 2-way communication, d) long pre-irradiation to real-time communiction, e) static switching to dynamic, f) in vitro to in vivo detection, and g) large surface to small fiber. From a practical standpoint these new materials are of interest as ‘smart’ surfaces for sensing, signaling, and controlling adjacent biological activity, due to the combination of soft photochemical functionalities, and their inherent biocompatibility. From the standpoint of fundamental science, these new materials and their study will enable us to contribute to a basic understanding of biological function at the interface between living cells and artificial media, and communication between them, from a chemical and materials perspective. Combined together, this proposal represents an exciting new direction towards achieving a brain-machine interface using nature as the inspiration for both the soft organic materials, and for light as the communication medium.