A high-throughput microplate toxicity screening platform based on Caenorhabditis elegans

Abstract

Caenorhabditis elegans (C. elegans), an established model organism, has been widely used in environmental toxicology research. However, most of the current toxicity testing methods based on worms are time-consuming. In this study we aimed to develop an automated and highly-integrated platform for high-throughput and in situ toxicity testing. Considering the superiority of C. elegans as a neurotoxicological model, this platform mainly evaluates general toxicology and neurotoxicology endpoints, which are usually induced by metals and pesticides, the major environmental contaminants. Microplates were used as a worm culturing system, which have good compatibility with any commercial microplate applicable instruments. We developed a microfluidic-based module for worm dispensing, and an image acquisition/analysis module for monitoring worms and detecting toxicity endpoints in bright filed. These were collectively incorporated with a commercial pipetting workstation for automated food/drug delivery and a high-content analysis system for fluorescence detection. The integrated platform achieved an efficient on-demand worm dispensing, long-term maintenance, regular monitoring and imaging, survival assay and behavioral analyses, and visualized gene reporter assay. Moreover, “Lab on Web” was achieved by connecting the platform to the web for remote operation, worm monitoring, and phenotype calculation. To demonstrate the ability of the platform for automated toxicity testing assays; worms were treated with cadmium and longevity, neurotoxicity, developmental toxicity and gst-4 expression were evaluated. We determined its feasibility and proposed the potential application in high-throughput toxicity screening for environmental risk assessment in the nearest future.

Keywords

• Caenorhabditis elegans
• Toxicity testing
• High-throughput
• Environmental risk assessment
• Worm dispensing
• Microfluidics