title: A microfluidic device for whole-animal drug screening using electrophysiological measures in the nematode C. elegans.
abstract: This paper describes the fabrication and use of a microfluidic device for performing whole-animal chemical screens using non-invasive electrophysiological readouts of neuromuscular function in the nematode worm, C. elegans. The device consists of an array of microchannels to which electrodes are attached to form recording modules capable of detecting the electrical activity of the pharynx, a heart-like neuromuscular organ involved in feeding. The array is coupled to a tree-like arrangement of distribution channels that automatically delivers one nematode to each recording module. The same channels are then used to perfuse the recording modules with test solutions while recording the electropharyngeogram (EPG) from each worm with sufficient sensitivity to detect each pharyngeal contraction. The device accurately reported the acute effects of known anthelmintics (anti-nematode drugs) and also correctly distinguished a specific drug-resistant mutant strain of C. elegans from wild type. The approach described here is readily adaptable to parasitic species for the identification of novel anthelmintics. It is also applicable in toxicology and drug discovery programs for human metabolic and degenerative diseases for which C. elegans is used as a model.
authors.affiliation: Institute of Neuroscience, University of Oregon, Eugene, OR 97403-1254, USA. shawn@uoregon.edu
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Lockery
authors.forename: S Elizabeth
authors.initials: SE
authors.lastname: Hulme
authors.forename: William M
authors.initials: WM
authors.lastname: Roberts
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Robinson
authors.forename: Anna
authors.initials: A
authors.lastname: Laromaine
authors.forename: Theodore H
authors.initials: TH
authors.lastname: Lindsay
authors.forename: George M
authors.initials: GM
authors.lastname: Whitesides
authors.forename: Janis C
authors.initials: JC
authors.lastname: Weeks
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000871:Anthelmintics / Q000633:toxicity; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D055724:Electrophysiological Phenomena; D007559:Ivermectin / Q000633:toxicity; D007978:Levamisole / Q000633:toxicity; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D051598:Whole Body Imaging
chemical_list: D000871:Anthelmintics; D007978:Levamisole; D007559:Ivermectin