Integrated Microfluidic Device for Drug Studies of Early C. Elegans Embryogenesis

Small molecules inhibitors are powerful tools for studying multiple aspects of cell biology and stand at the forefront of drug discovery pipelines. However, in the early Caenorhabditis elegans (C. elegans) embryo, which is a powerful model system for cell and developmental biology, the use of small molecule inhibitors has been limited by the impermeability of the embryonic eggshell, the low-throughput manual embryo isolation methods, and the lack of well-controlled drug delivery protocols. This work reports a fully integrated microfluidic approach for studies of C. elegans early embryogenesis, including the possibility of testing small molecule inhibitors with increased throughput and versatility. The setup enables robust on-chip extraction of embryos from gravid adult worms in a dedicated pillar array chamber by mechanical compression, followed by rapid fluidic transfer of embryos into an adjacent microtrap array. Parallel analysis of ≈100 embryos by high-resolution time-lapse imaging from the one-cell stage zygote until hatching can be performed with this device. The implementation of versatile microfluidic protocols, in particular time-controlled and reversible drug delivery to on-chip immobilized embryos, demonstrates the potential of the device for biochemical and pharmacological assays.