Drug Trips for Worms: Smart Droplet Microfluidics for Real-time, High-throughput Drug Screening of Single Organisms

目的：该计划的目的是开发一个集成的液滴为基础的微流控系统，用于平行筛选不同化学成分的液滴微环境内蠕虫的表型变化。这项工作的目的是从现有的低通量蠕虫活力测定彻底转变为真正的高通量、全生物体测定，用于测试针对线虫的多药物化合物。智力优势：其智力价值是提供了一个强大的芯片实验室分析系统，用于全动物模型的生物学研究，具有前所未有的高通量。该系统将独特地结合联合收割机自动生成和调节药物编码的药理学液滴库、引导运动刺激、运动测定和液滴内单个生物体的电生理记录。这项研究是变革性的，因为该系统可以提供药物暴露下线虫神经生理学变化的独特细节，促进目前技术不可能完成的实验。拟议的技术是通用的，因为该系统可以适用于测试广泛的重要线虫和药物化合物。更广泛的影响：拟议的研究将有助于回答诊断，控制和预测线虫寄生虫耐药性的基本问题，从而揭示宿主-寄生虫相互作用的复杂机制。这项研究将产生广泛的教育机会，为本科生和研究生，并有利于课程开发的一个新的本科生物工程未成年人计划的爱荷华州。妇女和少数民族学生，以及中学生将通过开放实验室图尔斯参观和课堂演示被吸引到科学和工程领域。高中科学教师将合作开发K-12教学材料在微/纳米技术和生物工程的主题。

Objective: The objective of the program is to develop an integrated droplet-based microfluidic system for parallel screening of phenotypic changes in nematode worms within droplet microenvironments of varying chemical compositions. This work aims to provide a radical translation from existing low-throughput worm motility assays to a truly high-throughput, whole-organism assay for testing multi-drug compounds against nematodes. Intellectual Merit: The intellectual merit is to provide a powerful lab-on-a-chip assay system for biological studies on whole-animal models with unprecedented high throughput. The system will uniquely combine automated generation and modulation of drug-coded pharmacological droplet libraries, guided movement stimulation, locomotion assay, and electrophysiological recording for single organisms inside droplets. This research is transformative because the system can provide unique details of neurophysiological changes in nematodes with drug exposures, facilitating experiments that are impossible by current techniques. The proposed technology is generic because the system can be adapted to test a wide range of important nematodes and drug compounds. Broader Impacts: The proposed research will help answer fundamental questions in diagnosing, controlling and predicting drug resistance in nematode parasites, thereby unraveling complex mechanisms of host-parasite interactions. This research will generate broad educational opportunities for both undergraduate and graduate students, and benefit curriculum development for a new Undergraduate Bioengineering Minor Program of the Iowa State. Women and minority students, and middle school students will be attracted into science and engineering through open-lab tours, and in-class presentations. High school science teachers will be collaborated to develop K-12 instructional materials in the topics of micro/nanotechnology and bioengineering.