A High-Throughput Open-Well System for Engineering Neurovascular Units

项目摘要 工程技术的进步为控制细胞的组织方式提供了前所未有的机会 并在文化中互动。小型化的流体系统，包含组织合理的各种单元 已经被用来建立各种人体器官的基本单位的模型，包括肝脏， 肺、肾、骨等。在神经系统中，这些类型的系统被用来模拟 血脑屏障、神经血管单位和脑实质。这些系统前景看好。 促进对人类基本生物学的了解，开发疾病的治疗方法，以及 用于神经系统疾病的个性化治疗。此外，他们还有可能 减少在生物和医学研究中使用啮齿动物和其他非人类动物。一 重要的技术挑战是，这些系统操作起来可能很复杂， 重复性和健壮性，以及有限的吞吐量。拟议的研究旨在开发一种 一种易于使用的系统，增强了健壮性和再现性，同时 保持高吞吐量并保持重要特征--如血液供应-- 对这些生物模型的生物和医学用途很重要。我们提出了一口露天井 这种结构允许轻松接触电池，并消除了容易出现故障的油管连接。然后我们 建议使用该系统来研究神经元和脑血液之间的耦合 它们与之相连的容器。这种耦合对大脑的正常运作很重要，而且 不恰当的偶联被认为与神经退行性疾病有关。通过创建一个简单易用的 系统，我们可以开始更容易、更健壮、更可重复地研究这种耦合。

Project Summary Advances in engineering have provided unprecedented opportunities to control how cells are organized and interact in culture. Miniaturized fluidic systems containing a variety of cells in proper organization have been used to establish models of the essential units of a variety of human organs, including liver, lung, kidney, bone, etc. In the nervous system, these types of systems have been used to model the blood brain barrier, the neurovascular unit, and brain parenchyma. These systems hold great promise for advancing the understanding of fundamental human biology, for developing cures for disease, and for personalizing therapy for nervous system disorders. Additionally, they have the potential to decrease usage of rodents and other non-human animals in biological and medical research. One important technical challenge is that these systems can be complicated to operate, have limited reproducibility and robustness, and limited throughput. The proposed research aims to develop a system that results in an easy-to-use system, which enhances robustness and reproducibility, while maintaining high throughput and maintaining the important features—like a blood supply—that are important for the biological and medical utility of these biological models. We propose an open-well structure that allows easy access to cells and removes failure-prone tubing connections. We then propose to use this system to perform studies of the coupling between neurons and the brain blood vessels that they couple with. This coupling is important for proper functioning of the brain, and improper coupling has been implicated in neurodegenerative disease. By creating a simple-to-use system, we can begin to study this coupling much more easily, robustly, and reproducibly.