Chorion-less zebrafish embryos may hold key to improving toxicity bioassays

Phenotype-based in situ screening is commonly used to identify the effects of chemicals and drugs on physiological processes. New lab-on-a-chip systems applied zebrafish models for phenotypical analysis, using chip-based devices for embryos protected by a chorion structure. While the use of chorion-less zebrafish held promise for improving toxicity bioassays, their fragility proved challenging. An Australian research team has demonstrated a chip-enabled automated approach that immobilizes the embryos hydrodynamically, transports and docks them inside elastomeric chips without jeopardizing their normal development. Their findings are presented in Biomicrofluidics.

The chorion membrane forms a molecular barrier that slows or prevents chemicals from reaching the embryo, so dechorionation of zebrafish embryos could be valuable in improving toxicity bioassays critical for experimental and predictive toxicology. According to lead author Donald Wlodkowic, their approach is a proof of principle. Zebrafish with enzymatically stripped chorions were placed in PDMS-on-glass living embryo arrays fabricated using a high definition SLA process that allowed devices to be prototyped in approximately 90 minutes. The embryo array incorporated integrated modules with a serpentine channel for specimen loading and drug delivery, twenty miniaturized cages with cage geometry to address challenges presented by the developing embryo, and interconnecting channels. Using microperfusion, 100% of the trapped specimens maintained their position over the 48-hour experimental period at acceptable mortality rates.

According to Wldokowic, this work proves that culture and phenotypic analysis of dechorionated zebrafish embryos using millifluidic chip-based devices can be accomplished by “caging” them with a combination of elastomeric substratum, gentle hydrodynamic trapping and micromechanical caging, yielding toxicity assay results that are well correlated with conventional approaches, and providing a new and powerful tool for phenotype in situ bioassays.

Source: “Development of chorion-less zebrafish embryos in millifluidic living embryo arrays,” by Nurul Mohd Fuad, Jan Kaslin, and Donald Wlodkowic, Biomicrofluidics (2017). The article can be accessed at https://doi.org/10.1063/1.5001848 .