Droplet array for screening acute behaviour response to chemicals in Caenorhabditis elegans

Abstract

Caenorhabditis elegans is an excellent model organism for studying chemosensation as a significant part of its nervous system and genome are devoted to the detection of chemical cues. Studies of decision-making, learning, mating behaviour, and intraspecies communication require measuring the acute behavioural response to chemical stimulation. Such assays require precise and repeatable chemical delivery and are often arduous when performed manually. Microfluidic platforms have been developed for chemosensation studies in C. elegans. However, these platforms lack temporal resolution in chemical delivery necessary for screening acute behaviour and cannot selectively recover animals, a necessary feature for genetic screens. Here we present a droplet array for screening acute behavioural responses of C. elegans to chemical stimulation. Using droplets enables isolating the worms and controlling the chemical environment. The chamber design of the static array allows continuous monitoring of animal behaviour. By combining a gradient of confinement and flow restriction features, we demonstrate selective and sequential trapping of multiple droplets as well as their release on demand. These functions enable repeated capture of animals, monitoring of their behaviour upon chemical stimulation and subsequent release. To demonstrate the ability to screen multiple conditions, we measured worm thrashing activity in response to different concentrations of tetramisole. To illustrate the ability to capture acute behavioural responses, we monitored the behavioural response of male to pheromone stimulation. Due to the versatility of the chamber operation and its ultra-low volume uses of reagents, we envision this platform to be highly suited to combinatorial screening and drug discovery.