Photo-Reversible Polymers for the Opto-Bio Interface

最终的目标是设计、制备和测试含有染料的聚合物，这种聚合物可以分层到柔软的光纤末端，可以被微定位在靠近甚至接触活的神经细胞的地方，以与它们进行双向通信，既能感知又能发出信号。为了实现这一目标，三管齐下的方法将在三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以及物理光纤光谱学。所有三个并行的组成部分项目在每个领域都提出了重要的进展，以实现合并的计划目标，但每个领域的进展都可以独立地有价值。设计的聚合物将是柔软的，湿的模拟真实的生物组织，并包含少量敏感的偶氮染料，在突触事件中释放的特定神经递质存在时，偶氮染料会发生明显的变化。最终，这将允许制造和优化活的神经细胞和光纤之间的主动双向界面，发送和接收-使用类似的光可逆染料释放化学信号，可以刺激动作电位。

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.