title: Droplet Microfluidic System with On-Demand Trapping and Releasing of Droplet for Drug Screening Applications.
abstract: 96-Well plate has been the traditional method used for screening drug compounds libraries for potential bioactivity. Although this method has been proven successful in testing dose-response analysis, the microliter consumption of expensive reagents and hours of reaction and analysis time call for innovative methods for improvements. This work demonstrates a droplet microfluidic platform that has the potential to significantly reduce the reagent consumption and shorten the reaction and analysis time by utilizing nanoliter-sized droplets as a replacement of wells. This platform is evaluated by applying it to screen drug compounds that inhibit the tau-peptide aggregation, a phenomena related to Alzheimer's disease. In this platform, sample reagents are first dispersed into nanolitre-sized droplets by an immiscible carrier oil and then these droplets are trapped on-demand in the downstream of the microfluidic device. The relative decrease in fluorescence through drug inhibition is characterized using an inverted epifluorescence microscope. Finally, the trapped droplets are released on-demand after each test by manipulating the applied pressures to the channel network which allows continuous processing. The testing results agree well with that obtained from 96-well plates with much lower sample consumption (∼200 times lower than 96-well plate) and reduced reaction time due to increased surface volume ratio (2.5 min vs 2 h).
authors.affiliation: Department of Nanotechnology Engineering, University of Waterloo , 200 University Avenue West, Waterloo, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Courtney
authors.affiliation: Department of Mechanical and Mechatronics Engineering, University of Waterloo , 200 University Avenue West, Waterloo, Canada.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Nanotechnology Engineering, University of Waterloo , 200 University Avenue West, Waterloo, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Chan
authors.affiliation: School of Pharmacy, Health Sciences Campus, University of Waterloo , 200 University Avenue West, Waterloo, Canada.
authors.forename: Tarek
authors.initials: T
authors.lastname: Mohamed
authors.affiliation: School of Pharmacy, Health Sciences Campus, University of Waterloo , 200 University Avenue West, Waterloo, Canada.
authors.forename: Praveen P N
authors.identifier: 0000-0001-5703-8251
authors.initials: PP
authors.lastname: Rao
authors.affiliation: Department of Mechanical and Mechatronics Engineering, University of Waterloo , 200 University Avenue West, Waterloo, Canada.
authors.forename: Carolyn L
authors.identifier: 0000-0002-9249-7397
authors.initials: CL
authors.lastname: Ren
mesh_terms: D001391:Azo Compounds / Q000032:analysis* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation; D010316:Particle Size; D066329:Protein Aggregates / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000032:analysis* / Q000494:pharmacology
chemical_list: D001391:Azo Compounds; D066329:Protein Aggregates; D047428:Protein Kinase Inhibitors; C008710:Orange G; D038362:Glycogen Synthase Kinase 3; C080888:tau-protein kinase