Significance Statement
Model organisms play an important role in the cycle of drug discovery. Drosophila melanogaster is one of the invertebrate model organisms that has been extensively used to study human diseases and disorders. However, the widespread use of this organism has been impeded by the lack of automated and high throughput technologies for screening. In this article, we have developed a microfluidic device (shown schematically) consisting of porous agar with integrated networks of microchannels used to selectively infuse chemicals at desired concentrations to favorable locations in the device. We have used this technology to study the effect of zinc and acetic acid on oviposition or egg laying behavior of adult fruit flies. Our findings show that fruit flies are capable of sensing the concentration of chemicals in single-chemical assays and use this functionality to explore and select desirable oviposition sites in multi-chemical platforms. This technology can be used for screening drugs, studying learning and memory functions, and investigating biological pathways of oviposition in agricultural, drug discovery, biological, and medical applications.
About the author
Jacob C.K. Leung received his Bachelor of Engineering degree with honors distinction in Biomedical Engineering from Ryerson University, Toronto, ON, Canada. He obtained his Master of Science degree in Mechanical Engineering at York University under the supervision of Professor Pouya Rezai. His research focused on developing efficient microfluidic devices to perform toxicological assays on Drosophila melanogaster. He also gained expertise in developing sacrificial layer based microfabrication techniques to produce PDMS and composite PDMS micropillars and microbridges for sensor applications. In addition to his engineering background, Jacob is also pursuing higher education in Occupational Therapy at the University of Toronto. Integrating his engineering skills with rehabilitation medicine, Jacob’s research interests include developing person-centered assistive devices and automated, low-cost, and high-throughput biomedical diagnostic technologies for developmental biology, toxicology, and drug discovery.
About the author
Professor Arthur Hilliker completed his PhD at the University of British Columbia (1975) and pursued postdoctoral work at the University of Connecticut before joining CSIRO in Australia as a research scientist (1978) in the Division of Plant Industry. His first academic appointment was at University of Guelph in 1982 as an Assistant Professor, advancing through the ranks to Professor in 1993. Dr. Hilliker moved to York University to be the Chair of the Department of Biology in 2000. Dr. Hilliker has had a long standing record of service to the scientific community. He was the first person awarded the Young Scientist Award from the Genetics Society of Canada (1987). In 2005, he was again recognized by the Genetics Society of Canada with the Award of Excellence for lifetime scientific contributions to genetics. He was Co-Editor in Chief of the National Research Council of Canada Press journal Genome from 2007 until 2014. Since 2010 he has served on the Executive of the Canadian Society of Biochemistry and Molecular and Cell Biology (now renamed the Canadian Society of Molecular Biosciences) and is currently a Past President and Treasurer. His research is primarily although not entirely focused on using Drosophila as a model organism. His research covers a wide breadth of subject areas relating to genetics.
About the author
Professor Pouya Rezai is an emerging researcher in the area of microfluidics and Lab-on-a-Chip (LoC) devices. He is an Assistant Professor and the Graduate Program Director at the Department of Mechanical Engineering at York University. He received his Master of Science in Electrical Engineering from Chalmers University of Technology in 2008 and his PhD in Mechanical Engineering from McMaster University in 2012. Dr. Rezai was an NSERC Visiting Fellow at Public Health Agency of Canada before joining York University in July 2013. His research interest includes advancing micromachining and microfabrication techniques to develop LoC devices to study interactions between micro-particles, small biological substances and fluids in microenvironments. He has developed (i) LoC devices for quantitative investigation of neurobehavioral responses of bio-organisms (e.g., D. melanogaster, C. elegans, D. rerio) to electric, acoustic, or chemical cues; (ii) microfluidic platforms for multiplexed sorting of pathogens and microparticles in fluidic samples; and (iii) micro-electro-mechanical sensors for measuring properties of polymers and carbon nano-structures.
Journal Reference
Lab Chip. 2016 Feb 21;16(4):709-19.
Leung JC, Hilliker AJ, Rezai P.
Department of Mechanical Engineering, York University, BCEE 433B, 4700 Keele St, Toronto, ON M3J 1P3, Canada. [email protected].
Abstract
Chemical screening using Drosophila melanogaster (the fruit fly) is vital in drug discovery, agricultural, and toxicological applications. Oviposition (egg laying) on chemically-doped agar plates is an important read-out metric used to quantitatively assess the biological fitness and behavioral responses of Drosophila. Current oviposition-based chemical screening studies are inaccurate, labor-intensive, time-consuming, and inflexible due to the manual chemical doping of agar. In this paper, we have developed a novel hybrid agar-polydimethylsiloxane (PDMS) microfluidic device for single- and multi-concentration chemical dosing and on-chip oviposition screening of free-flying adult stage Drosophila. To achieve this, we have devised a novel technique to integrate agar with PDMS channels using ice as a sacrificial layer. Subsequently, we have conducted single-chemical toxicity and multiple choice chemical preference assays on adult Drosophila melanogaster using zinc and acetic acid at various concentrations. Our device has enabled us to 1) demonstrate that Drosophila is capable of sensing the concentration of different chemicals on a PDMS-agar microfluidic device, which plays significant roles in determining oviposition site selection and 2) investigate whether oviposition preference differs between single- and multi-concentration chemical environments. This device may be used to study fundamental and applied biological questions in Drosophila and other egg laying insects. It can also be extended in design to develop sophisticated and dynamic chemical dosing and high-throughput screening platforms in the future that are not easily achievable with the existing oviposition screening techniques.
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