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

项目摘要 工程学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。包含适当组织的各种细胞的小型化流体系统 已经被用于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，这些类型的系统已被用于模拟 血脑屏障、神经血管单位和脑实质。这些系统具有很大的潜力 促进对基本人类生物学的理解，开发疾病的治疗方法， 用于神经系统疾病的个性化治疗此外，他们有潜力 减少啮齿动物和其他非人类动物在生物和医学研究中的使用。一 重要技术挑战是这些系统操作起来可能复杂，具有有限的 再现性和鲁棒性以及有限的生产量。这项研究旨在开发一种 系统，导致一个易于使用的系统，这增强了鲁棒性和再现性，同时 维持高通量和维持重要的功能，如血液供应， 这对于这些生物模型的生物学和医学效用是重要的。我们建议开一口井 这种结构允许容易地接近电池并去除容易发生故障的管道连接。然后我们 我建议用这个系统来研究神经元和脑血之间的耦合 与之结合的船只。这种耦合对大脑的正常运作很重要， 不适当的偶联与神经变性疾病有关。通过创建简单易用的 系统，我们可以开始研究这种耦合更容易，鲁棒性和可重复性。

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.