Wireless, implantable optofluidic systems for programmed pharmacology and optogenetics

项目摘要/摘要 在过去的十年里，神经科学研究因许多技术进步而发生了革命性的变化。 药理学和光遗传学代表着两种截然不同、有时相辅相成的工具 神经科学研究在大脑主动性的背景下研究中枢和外周神经系统的科学。 然而，对潜在神经回路和生物学的高级审讯经常受到技术的阻碍 限制使用这些方法来研究不受束缚的、自由移动的自然行为 动物。用于光遗传学的传统光缆和与外部连接的笨重的金属套管 用于药理的机械泵对脆弱的神经组织造成重大损害，限制自然行为 在复杂、自然的3D环境中，影响社会互动和运动，以及 由于机械失配和微运动，导致生物/非生物界面的持续刺激。这些 缺点，再加上当前技术的昂贵设置，推动了创新技术的发展 工程设计，以提高保真度、易操作性、多功能性和高级大脑研究的范围 用活体动物模型进行研究。 我们在第一阶段的工作中开发了一个集成的无线平台，它结合了可编程 通过软μ-流体通道的药理学和通过植入式μ规模的无机发光的光遗传学 二极管(μ-ILED)。第二阶段的拟议工作侧重于翻译工程研究，以完善 设备设计，并开发低成本的大规模制造工艺。具体地说，拟议的工作将(1) 为低成本、外包生产建立设备设计和制造流程；(2)扩展 与周围神经和脊髓直接对接的功能，以及(3)开发高级功能 在能量获取、调制和控制方面，并扩大了对神经科学研究的影响。这项工作将 为各种领域的可编程药理学和光遗传学提供广泛有用、低成本的无线平台 与大脑主动性密切相关的环境。

Project Summary/Abstract Neuroscience research over the last decade has been revolutionized by many technological advancements. Pharmacology and optogenetics represent two distinct, and sometimes complementary tools used in neuroscience research to study the central and peripheral nervous systems in the context of the BRAIN initiative. Advanced interrogations of underlying neural circuits and biology are often frustrated, however, by technological limitations that prevent the use of these approaches to study natural behaviors of untethered, freely moving animals. Traditional fiber-optic cable for optogenetics and bulky metal cannulas connected with external mechanical pumps for pharmacology impart significant damage to fragile neural tissue, limit the natural behavior of freely moving animals, affect social interactions and movements in complex, naturalistic 3D environment, and lead to persistent irritation at the biotic/abiotic interface due to mechanical mismatch and micromotions. These drawbacks, together with the costly setup, of current technologies motivate the development of innovative engineering designs to improve fidelity, operational ease, versatility and range of advanced brain research studies with live animal models. Our work during Phase I developed an integrated, wireless platform that combines capabilities in programmable pharmacology via soft μ-fluidic channels and optogenetics through an implantable μ-scale inorganic light emitting diodes (μ-ILEDs). The proposed work for Phase II focuses on translational engineering research to refine the device designs and to develop a low-cost, mass-manufacturing process. Specifically, the proposed work will (1) establish device designs, and manufacturing process for low-cost, outsourced production, (2) expand the functionality for directly interfacing with peripheral nerve and spinal cord, and (3) develop advanced capabilities in power harvesting, modulation, and control, and broaden the impact on neuroscience research. This work will yield a broadly useful, low-cost, wireless platforms for programmable pharmacology and optogenetics in various contexts of essential relevance to the BRAIN initiative.