(536g) Microfluidic Chamber Arrays for High-Throughput Combinatorial Screening

Multicellular organisms, such as Caenorhabiditis elegans (C. elegans), have been crucial in elucidating fundamental biological mechanisms and human disease pathogenesis. In particular, the conservation of many genes and biological mechanisms between C. elegans and humans, together with the simplicity and ease of C. elegans maintenance, make it an effective in vivo model for high throughput chemical screens. However, their size makes it difficult for researchers to physically manipulate these microorganisms, which limits the scale on which researchers can run experiments. This makes chemical screening laborious, noisy, and often precludes experiments altogether. We present microfluidic technologies to enable high-throughput combinatorial chemical screening based on whole-organism behavioral responses. The PDMS device includes essential components that allow the rapid loading and monitoring of the phenotypic responses of up to seventy worms in the field of view. Individual worms are loaded in the loading channel connecting the circular chamber to the serpentine channel. The circular chamber isolates worms to avoid crosstalk between individual organisms. Certain design features allow us to load worms at a high success rate with a single worm per chamber and to allow a large number of worms to be observed simultaneously. Worm loading is efficient (in a few minutes), and chemicals can be delivered to the chambers in a quick and fully controllable manner.To demonstrate the capability of this system as a high-throughput chemical screening tool, we observe animals' responses to hermaphrodite-conditioned medium, which contains C. elegans sex pheromones. The quantitative behavior phenotyping yields similar results as reported in the literature while the throughput is 10-100 times faster. We envision this system to enable researchers to perform high throughput chemical screenings for a variety of applications including drug testing.