Photo-Reversible Polymers for the Opto-Bio Interface

用于光生物界面的光可逆聚合物

• 批准号: RGPIN-2014-06655
• 负责人: Barrett, Christopher
• 金额: $ 3.93万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632549
• 关键词: Photo; Reversible; Polymers; Opto; Bio

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.

最终的目标是设计、制备和测试含染料的聚合物，这些聚合物可以层叠在柔软的光纤末端上，可以被微定位在离活神经细胞很近的地方，甚至与活神经细胞接触，以与它们进行双向通信。实现这一目标的三管齐下的方法将联合收割机在3个领域平等地结合单独的项目：合成有机染料化学，聚合物和界面材料化学，物理光纤光谱学。所有3个平行的组成项目在每个领域都提出了重大的进展，以实现联合计划的目标，但每个领域实现的进展都是有价值的。所设计的聚合物将是真实的生物组织的柔软、潮湿的模拟物，并将含有少量敏感的偶氮染料，这些染料在突触事件期间释放的特定神经递质存在时发生明显变化。最终，这将允许在活神经细胞和光纤之间制造和优化一个主动的双向接口，该接口可以发送和接收使用类似的光可逆染料释放化学信号，从而刺激动作电位。在活体脑组织和读出技术之间建立工作界面的历史尝试总是使用植入的金属微电极。然而，这些基本上是侵入性的表面，并且在排斥反应开始之前仅持续几个小时神经细胞最终不可避免地对植入的金属电极作为异物做出反应，将它们包围在星形胶质细胞疤痕中，最终在电极和神经通信机制之间形成屏障。相反，这里概述的方法在界面处自组装的软湿聚合物的固有稳定生物相容性方面是新颖的，并且使用光来感测和发送信号而不是电流。指导该方法的将是生物模仿和自组装的原理，其中表面生物膜主体聚合物模仿真实的生物组织的柔软，湿润，顺应性的可调能力，以及光响应的形状变化偶氮染料模仿我们的视紫红质/视网膜系统，使视觉和直接的光神经信息接口。更具体地说，该提议试图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（感测和信号传导），使用具有pH敏感性的新的多功能染料，以及被调谐为结合和检测多巴胺类二醇神经递质的侧基硼酸基团。既然细胞反应已被证明能够由偶氮表面触发，那么这里的开发挑战和风险也代表了值得实现的目标：a）整个细胞生长到神经突触，B）不可逆到可逆，c）单向到双向通信，d）长时间预照射到实时通信，e）静态转换到动态，f）体外到体内检测，和g）大表面到小纤维。从实用的观点来看，由于软光化学功能性的组合及其固有的生物相容性，这些新材料作为用于感测、发信号和控制邻近生物活性的“智能”表面是令人感兴趣的。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界面的生物功能以及它们之间的通信进行基本了解。结合在一起，这一提议代表了一个令人兴奋的新方向，即利用自然作为软有机材料和光作为通信介质的灵感，实现脑机接口。