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.
Leung JC, Hilliker AJ, Rezai P.
Department of Mechanical Engineering, York University, BCEE 433B, 4700 Keele St, Toronto, ON M3J 1P3, Canada. [email protected]
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.Go To Lab Chip