PORTFOLIO

To cure the relentless decline of the drug discovery industry efficiency, a radical change seems today to be needed. Recently, alternative biological models to standard cell cultures and rodents started proving their potential to revolutionize the field. While 3-dimensional cell cultures will likely replace their flat homologous in the near future, small model organisms, such as the tiny roundworm Caenorhabditis elegans, are gaining increasing attention as valid alternatives to mice in various drug screening contexts. A widespread adoption of these models would indeed significantly lower both time and costs of pharmaceutical research and improve its efficiency, by reducing mice testing and optimizing the analysis pipeline in the pre-clinical phase. Unfortunately, however, the protocols for culture and study of these alternative models still mainly rely on the manual techniques currently used in academic biological research, which definitely lack the reproducibility and throughput standards required by the drug discovery industry. To enable such change, a team of scientists at the École Polytechnique Fédérale de Lausanne (EPFL) is working at the interface between microtechnologies and life sciences to develop the first automated platform for roundworm culture, analysis and drug testing. Our technology employs microfluidics -the accurate manipulation of fluids at the sub-millimeter scale- for the precise and automated handling of roundworms and reagents within miniaturized devices. This offers unprecedented control over both worm culture and drug screening conditions, while allowing real-time monitoring of full sets of worm analysis parameters, in a high-throughput format. Overall, we aim to create the first “organism-on-chip” technology for drug screening and pave the way for the widespread use of roundworms -and, possibly, of other small model organisms- for the replacement, reduction and refinement of animal testing within the drug discovery industry.

Our project aims to create a new technology capable of generating complete multi-phenotypic profiles of worms over long-term experiments, without human intervention. From a technological viewpoint, the key element of our innovation consists in the use of passive hydrodynamics for the manipulation and study of roundworms within microfluidic cartridges. In particular, the use of microfluidics ensures: protocol automation, standardization and scalability towards high-throughput applications; (i) fast and accurate regulation of effective drug concentrations within our devices; (ii) more efficient drug intake with respect to currently used culture conditions and minimal consumption of expensive reagents. Our technology is moreover expected to open unprecedented possibilities in terms of spatio-temporal accuracy of the drug tests.

We validated the scientific value of microfluidics as a tool to improve C. elegans research, by demonstrating the first microfluidic chip for high-throughput analysis of C. elegans embryos as well as a semi-automated microfluidic-based device for long-term studies on neurodegenerative disease worm models. We developed a new class of microfluidic devices for the controlled growth and culture of C. elegans throughout their full life-cycle, together with the first version of a laboratory prototype devoted to the automated handling of drug screening experiments on these devices. We pursued biological validation studies to corroborate the value of worm models within different fields of application, with a specific focus on anthelmintic drug discovery. We are currently engaged in a new series of pilot studies with industrial collaborators, aiming to define clear assay formats for their internal research and promote the adoption of our innovative technology within the pharmaceutical domain in the near future.