(582t) Droplet-Based Microfluidic Device for Small Animal Drug Screening

The millimeter-scale nematode Caenorhabditis elegans (C. elegans) is a model organism for research in biology and medicine. These nematodes have a simple nervous system, short lifespan and are genetically tractable. These attributes have made C. elegans an attractive animal model for drug discovery and testing. Multiwell plates aided by automated pipetting represent the prevailing paradigm for performing drug-screening assays with C. elegans. In addition to requiring large volumes of reagents, automated image-based detection of the response of the worm to drugs in well plates is difficult due to the presence of multiple animals per well, non-uniform illumination conditions particularly at the well edges where the worms tend to reside, and three-dimensional swimming motion of worms in the unconfined environment of the well.

We report the development of a microfludic device that captures C. elegans in arrays of static droplets surrounded by an oil phase. The device consists of an array of trap chambers (3000x150 μm), optimized to trap mostly single animals. The shallow depth of the trap chambers and their small size maintains the nematode in the field of view and the device transparency reduces non-uniform illumination. An automated microscope stage acquires movies of each trap continuously or after a set time interval. In this work, assays were performed in the microfluidic device using the drug levamisol HCl that causes paralysis due to prolonged activation of nicotinic acetylcholine (nACh) receptors on body wall muscle. We also assess the effect of surrounding oil phase on the efficacy of drug action on C. elegans.  

Thus, the developed microfluidic device solves many of the issues commonly encountered with drug screening in well plates. Our device is simple, as worms can be trapped using a single pressure source or hand pipetting. We will also discuss the potential of the device to perform on-chip dilution and obtain the full kinetics of drug action at single animal resolution with sophisticated image-based readouts.