Automated droplet-based platform for combinatorial screens on whole animals

项目总结/摘要 生成化合物组合库的能力对于多种化合物来说非常重要 问题，特别是感觉神经生物学，以及药物筛选和潜力开发 疾病治疗学。目前使用小型模式生物（例如C. 线虫和斑马鱼的研究实际上是成本高昂和复杂的，因为这些动物是 通常在多孔板中培养和筛选。此外，处理具有复杂 流体操纵是很有挑战性的我们的长期主要兴趣是开发技术 平台和研究感官生物学在C。线虫作为人类神经系统疾病的模型。在这 项目，我们将设计一个液滴微流控芯片，可以自动生成 化学品的组合库，然后展示该系统在 研究了几种信息素化合物的组合效应。优雅这个项目是 重要的是，它解决了两个目前的主要瓶颈组合屏幕与小 模式生物硬件设计和软件（自动化和定量行为） 分析）将可转化为其他问题和系统。我们设想这项技术将使一个 使用小的模式生物进行各种组合筛选， 发现。

Project Summary/Abstract The ability to generate combinatorial libraries of chemical compounds is important for a variety of problems, particularly sensory neurobiology, and for drug screens and development of potential therapeutics for diseases. Currently combinatorial screens using small model organisms such as C. elegans and zebrafish is virtually cost inhibitive and complex to carry out, because of these animals are cultured and screened usually in multi-well plates. Additionally, handling small animals with complex maneuvers fluidically is challenging. Our main interest in the long-term is to develop technological platforms and study sensory biology in C. elegans as a model for human neurological diseases. In this project, we will design a droplet-microfluidic chip that can be automated for generating combinatorial libraries of chemicals, and then to demonstrate the utility of this system in studying the combinatorial effects of a few pheromone compounds on C. elegans. This project is significant because it addresses two current major bottlenecks for combinatorial screens with small model organisms. Both the hardware design and the software (automation and quantitative behavioral analysis) will be translatable to other problems and systems. We envision the technology will enable a variety of combinatorial screens using small model organisms that will lead to new biological discoveries.