Automated droplet-based platform for combinatorial screens on whole animals

项目摘要/摘要 生成化合物组合库的能力对于各种 问题，特别是感觉神经生物学，以及药物筛选和潜力的开发 疾病治疗学。目前，使用小型模式生物如C. 秀丽和斑马鱼实际上是成本抑制和复杂的实施，因为这些动物是 通常在多孔培养皿中培养和筛选。此外，处理复杂的小动物 流畅的机动是具有挑战性的。我们长期的主要利益是开发技术 平台，并研究线虫的感觉生物学，作为人类神经疾病的模型。在这 项目，我们将设计一种液滴-微流控芯片，可以自动生成 化学物质的组合库，然后演示该系统在 研究了几种信息素化合物对线虫的组合作用。这个项目是 意义重大，因为它解决了当前组合屏幕的两个主要瓶颈 模型生物。硬件设计和软件(自动化和量化行为 分析)将可翻译为其他问题和系统。我们设想这项技术将使 使用小型模型生物的各种组合筛选将导致新的生物学 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.