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

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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.