A 3-D Microfluidic/Electronic Neural-Interfacing System

描述(由申请人提供)：来自佐治亚理工学院/埃默里大学医学院、伊利诺伊大学厄巴纳香槟分校和南伊利诺伊大学医学院的多个部门的研究人员提出了一个多学科项目，旨在开发一种用于在体外高级对接三维神经组织的微型制造神经元接口系统(UNIS)，并将该技术应用于神经元网络的可塑性和损伤的研究。该项目的具体目标是围绕开发和整合一系列促进三维细胞培养和切片研究的技术进步而制定的：(1)带有连接交叉桥的垂直塔，为形成结构化网络以及电子连接提供基础设施；(2)在这些塔中包括微流体通道，以选择性地注入营养物质和营养因子，并对组织的局部区域应用化学刺激；以及(3)设计集成电路，放大、多路传输和处理在统一信息系统中产生的大量(&gt；1000)信号，并促进同时记录和刺激。这项技术将直接应用于三维体外神经组织的研究，重点是解决神经元功能网络的发展、可塑性在这些网络中的作用以及损伤及其对网络行为的影响的研究。在拨款的第一年，将开发微塔、微流体结构和电子设备的原型，并将其与神经组织整合。这笔为期五年的赠款的其余部分将专注于该技术的改进和测试，以及一系列验证该方法和测试拟议假说的生物实验。该项目的成功完成将导致建立一个技术框架，用于研究各种各样的细胞(神经和非神经)以及实验数据，如果没有这种三维技术，这些数据是无法获取的。

DESCRIPTION (provided by applicant): Investigators from multiple departments at the Georgia Institute of Technology / Emory University School of Medicine, from the University of Illinois at Urbana Champaign, and from the Southern Illinois University School of Medicine propose a multidisciplinary project to develop a microfabricated neuronal interfacing system (uNIS) for advanced interfacing to three-dimensional neural tissue in vitro, and to apply this technology to the study of plasticity and injury in neuronal networks. The specific aims of the project are formulated around the development and integration of a set of technological advances that facilitate the study of three-dimensional cell cultures and slices: (1) vertical towers with connecting crossbridges that provide infrastructure for the formation of structured networks as well as for the electrical connectivity; (2) the inclusion of microfluidic channels into these towers to selectively inject nutrients and trophic factors and to apply chemical stimulation to localized regions of the tissue; and (3) the design of integrated circuits that amplify, multiplex, and process the large number (>1000) of signals generated in the uNIS and that facilitate simultaneous recording and stimulation. This technology will be applied directly to the study of three-dimensional, in vitro neural tissue with a particular focus on hypotheses addressing the development of functional networks of neurons, the role of plasticity in these networks, and the study of injury and its effects on network behavior. During the first year of the grant, prototypes of the microtowers, microfluidic structures, and electronics will be developed and integrated with neural tissue. The remainder of the five-year grant will focus on the refinement and testing of the technology and on a set of biological experiments that validate the approach and test the proposed hypotheses. The successful completion of this project will result in the creation of a technological framework for studying a wide variety of cells (neural and non-neural) as well as experimental data that would be inaccessible without this three-dimensional technology.