A 3-D Microfluidic/Electronic Neural-Interfacing System

描述（由申请人提供）：来自乔治亚理工学院/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，旨在开发一种微制造神经元接口系统（uNIS），用于体外三维神经组织的高级接口，并将该技术应用于神经网络的可塑性和损伤研究。该项目的具体目标是围绕促进三维细胞培养和切片研究的一系列技术进步的发展和整合而制定的：(1)具有连接交叉桥的垂直塔，为结构化网络的形成以及电气连接提供基础设施；(2)在这些塔中包含微流体通道，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施加化学刺激；以及(3)集成电路的设计，该集成电路放大、复用和处理uNIS中产生的大量（bbb1000）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，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的影响的研究。在拨款的第一年，将开发微型塔、微流体结构和电子设备的原型，并将其与神经组织集成。五年拨款的剩余时间将集中在技术的改进和测试，以及一组验证方法和测试提出的假设的生物实验上。这个项目的成功完成将创造一个技术框架，用于研究各种各样的细胞（神经细胞和非神经细胞），以及没有这种三维技术就无法获得的实验数据。

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.