A 3-D Microfluidic/Electronic Neural-Interfacing System

描述（申请人提供）：来自格鲁吉亚理工学院/埃默里大学医学院多个部门、伊利诺伊大学厄巴纳分校尚潘分校和南伊利诺伊大学医学院的研究人员提出了一个多学科项目，以开发一种用于体外三维神经组织高级接口的微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一系列技术进步的发展和整合而制定的，这些技术进步促进了三维细胞培养和切片的研究：（1）具有连接横桥的垂直塔，为结构化网络的形成以及电气连接提供基础设施;（2）在这些塔中包括微流体通道，以选择性地注入营养物和营养因子，并向组织的局部区域施加化学刺激;和（3）设计集成电路，其放大、多路复用和处理在uNIS中产生的大量（>1000）信号，并且便于同时记录和刺激。该技术将直接应用于三维体外神经组织的研究，特别关注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影响的研究。在资助的第一年，微塔，微流体结构和电子器件的原型将被开发并与神经组织集成。五年赠款的剩余部分将集中在技术的改进和测试以及一系列生物实验上，以验证该方法并测试所提出的假设。该项目的成功完成将导致创建一个技术框架，用于研究各种细胞（神经和非神经）以及实验数据，如果没有这种三维技术，这些数据将无法访问。

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.