472722 High-Throughput Combinatorial Drug Screening of Caenorhabditis Elegans Using Droplet-on-Demand Technology
Here we present a platform to enable high-throughput combinatorial screening of drugs for C. elegans. Animals are encapsulated in individual droplets and ordered in an array for imaging. The chambers are designed to have a trapping capacity over a wide range of volume, enabling sequential loading of droplets containing worms and stimuli, and to release the droplets on demand. We optimized structured wall design to obtain 100% trapping efficiency. Chemical reagents are mixed on chip to create combinatorial stimuli in an automated way via the actuation of valves and then delivered to the worms. Upon merging of droplets, worm responses are recorded, then the array is flushed, freeing space for the next batch. Videos are subsequently analyzed, screening for specific behaviors. To demonstrate screening capability, we studied worm responses to an anesthetics (tetramisole). Thrashing frequency as a function of drug concentration was analyzed over time to quantify paralysis, using a custom MATLAB program. We demonstrate strong increase of paralysis efficiency with increased drug concentration.
This platform provides a robust method to perform high-throughput combinatorial screening of chemicals in C. elegans, using droplets on demand to create mixtures while minimizing reagent consumption. We envision this platform to be determinant in discovering drugs or deciphering genetic basis of neurodegenerative disorders.
See more of this Group/Topical: Food, Pharmaceutical & Bioengineering Division