Tech-Transfer: worms in high-tech housing replace laboratory mice
The worms are placed individually into 128 tiny compartments on a tray© 2018 Alain Herzog
In an effort to improve drug, cosmetic and other chemical product tests, a device has been created at EPFL to automatically grow, feed, house and analyze laboratory worms. This invention will save researchers both time and money and sharply reduce the number of tests that require laboratory rondents. A prototype has already been tested and approved by several laboratories.
There is nothing new about the idea of using worms instead of mice in a wide array of pharmaceutical and toxicological tests. But the tedious task of growing these tiny nematodes and the time-consuming process of analyzing them have made this an unlikely alternative for systematic use on an industrial scale – until now. EPFL researchers have developed a device that automatically feeds, houses and tests these invertebrates. They launched a spin-off project called Nagi Bioscience. The Laboratory of microsystems (School of Engineering) created microfluidic chips and integrated them in an automated platform, in close collaboration with the Laboratory of Integrative Systems Physiology (School of Life Sciences). Several experiments have now demonstrated the promising aspects of the technology.
The prototype was assessed and validated by pharmaceutical companies at EPFL Innovation Park. The project has also won over a number of other experts, since it is among five candidates in the running for the PERL (Prix Entreprendre Région Lausanne) award,.
The adult worms are not much more than a millimeter long. In order to observe them, they are placed individually into 128 tiny compartments on a tray. A defined concentration of nutrients or molecules to be tested is delivered to each compartment through microfluidic channels. The device comes with a software program for the researcher to plan out the experiment. “By automating this process, we have reduced the time it takes to grow worms from several hours per day throughout the experiment to around 30 minutes on the first day,” says Laurent Mouchiroud, the startup’s project co-founder and a life sciences researcher.
The C. elegans nematode is not new to the lab. Around 60% of human genes have a counterpart in the worm, which has been used for over 60 years in a range of tests that require complete organisms in order to observe interactions between the various organs.
Proving its mettle in industrial laboratories
But these worms could enjoy a resurgence in labs thanks to Nagi Bioscience’s device, which automates the process of growing and testing them. “This case makes it possible to sift very quickly a larger number of potentially usable molecules for a treatment, and this directly in a whole organism,” says Pénélope Andreux, Senior Principal Scientist at Amazentis.
The little nematode housing unit measures a number of parameters – such as growth, fertility and mobility – constantly and simultaneously. “This could allow us to identify specific toxicity mechanisms in the early stages of development by comparing the changes caused by test compounds with those of compounds with known toxicity,” adds Robert Mader, in charge of toxicological studies at Debiopharm. The objective is to select the molecule with the fewest side effects on humans for clinical testing. In addition to ethics, this device can also save researchers money, since just a very small amounts of a substance are required in order to be tested on a worm. “When we are looking for new molecules, sometimes only a couple of milligrams of a substance are available,” says Mader.
By improving the test process and providing a way to grow a large quantity of worms – which are not subject to the same legal constraints as rodents – Nagi Bioscience’s device has pushed laboratory mice to the tail end of traditional protocols governing pharmaceutical, cosmetic and toxicological testing, right before clinical trials on humans.