Head of Bioassay development Nagi Bioscience SAINT-SULPICE, Switzerland
Abstract: Pharmaceutical, chemical, and biomedical research heavily depend on traditional in vivo experiments involving vertebrate models. Although animal testing is becoming more resource-intensive and facing ethical and legal concerns, alternative in vitro models fall short in providing comprehensive phenotypic data at the organism level. This limitation is particularly crucial for investigating intricate human processes or diseases, including neurodegeneration and age-related diseases, as well as developmental and reproductive toxicity effects.
In response, we present a robotic device based on the patented Organism-on-Chip technology as an alternative high-content screening method that bridges the gap between in vitro data and vertebrate testing in early pipeline stages. The robotic platform SydLab™ One can autonomously test 64 independent conditions on 1000 organisms (C. elegans nematodes) in one run. The nematode Caenorhabditis elegans constitutes a valuable alternative model for multiple applications and gained popularity for its ideal small size, short 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 and humans, the current experimentation methods lack automation and standardization, limiting their wider use in screenings.
Hence, the aim of SydLab™ One is to standardize and automatize the whole C. elegans experimentation process to enable the use of this powerful 3Rs model in safety and efficacy screenings. The platform combines advanced microfluidic technology, robotics, biology, and AI-based algorithms to automate the entire process of C. elegans culture, treatment administration, high-content imaging, data extraction, and phenotypic analysis. SydLab™ One is able to execute multiple toxicity and aging assays, including the possibility of using the existing wide collection of reporter strains thanks to the fluorescent imaging capability.
As an illustration, we present here one of the multiple validated assays on SydLab™ One in the scope of early toxicology. We blindly assessed the reproductive and developmental effects of twenty benchmark chemicals using the proposed platform. SydLab™ One handled the worms’ culture, treatment administration (five doses of each compound), hourly data extraction, and analysis of time-resolved phenotypic readouts, including growth dynamics, sexual maturity, fertility, embryonic viability, progeny accumulation and survival rate. After unblinding, a balanced accuracy of 87.5% was reached (sensitivity: 75%, specificity: 100%) according to ECHA database.
Overall, SydLab™ One proposes an innovative solution for rapid identification of toxic compounds and their mechanism of toxicity, effectively bridging the gap between in vitro and in vivo assays thanks to automation. The platform allows not only endpoint measurements’ collection, but also the monitoring of biological responses’ dynamics. All in all, enabling the automated generation of whole-organism readouts in high-throughput, without the barrier of in vivo studies (feasibility, scaling, ethics).
