Background and Objectives
Nematode Caenorhabditis elegans constitutes a valuable NAMs model for multiple applications, including predictive toxicology. This microscopic worm gained popularity for its ideal short size and life cycle, ease of cultivation and propagation, and powerful genetic toolkit. While C. elegans has the potential to complement in vitro models to better predict toxic outcomes in mammals, the current experimentation methods lack automation and standardization, limiting their wider use in screenings.
Material and Methods
In response, we developed SydLab™ One, a microfluidic-based robotic platform that automates the entire process of C. elegans culture, treatment, high-content imag-ing, and phenotypic analysis. The platform is able to execute multiple toxicity assays, including the possibility of using the existing ample collection of reporter strains thanks to the fluorescent imaging capability.
As an illustration, we evaluated the reproductive and developmental effects of twenty benchmark chemicals on C. elegans using the proposed platform. Synchronized populations of worms were chronically exposed to five doses of test compounds starting f rom the last larval stage (L4). Time-resolved phenotypic readouts were automatically extracted f rom the hour-ly-collected images of the worms, including growth dynamics, sexual maturity, fertility, embryonic viability, progeny accumulation and survival rate. Out of the tested compounds, methotrex-ate showed the most pronounced embryonic viability adverse effects, while bisphenol A strongly impacted the mothers’ development.
Discussion and Conclusion
Overall, we propose an innovative solution for rapid identification of toxic compounds and their mechanism of toxicity, bridging the gap between in vitro and in vivoassays. Our technology allows not only endpoint measurements’ collection, but also the moni-toring of biological responses’ dynamics.