CSEM prepares an electronic alternative to animal testing
Researchers at the Swiss Centre for Electronics and Microtechnology (CSEM) in Neuchâtel are in the middle of a massive development to design an electronic chip and microporous membranes as part of a replacement for the laboratory rat. The development is part of the InLiveTox project which aims to demonstrate that the toxicity of nanoparticles can be tested via a fluidics device incorporating microelectromechanical systems (MEMS) – instead of a rodent – with the aim of reducing animal experimentation.
In charge of coordinating the project with the other partner research centres, the CSEM is dealing with some of the technical aspects of InLiveTox. “As engineers, we are working on the development and the integration of a system which is able to take electrical measurements of cell layers,” explains Martha Liley, the project coordinator, who has a PhD in theoretical physics. Toxicologists in the partnership will study how the system can be used to test the presence of nanoparticles, many of which are thought to be toxic once inhaled or ingested.
A team of eight scientists at the CSEM is currently developing membranes for two different cell cultures that model the intestinal wall and the blood system (veins and arteries), respectively. These cultures are linked to one another by way of a fluidics system. “A toxicologist usually works with static cultures in which there is no flow of any kind,” explains Martha Liley, head of the biological microelectromechanical systems (BioMEMS) section at the CSEM. “The fluidics system we are designing is much closer to the environment we have in our bodies.”
By way of illustration, the model of the intestine involves a silicon membrane covered with living cells. On either side of the membrane is a fluidic circuit; one represents the inside of the intestine, the other the blood. “Our aim is to find out whether nanoparticles are actually able to cross the intestine and reach the blood,” continues Martha Liley. “If they do, then we will be able to observe how the blood vessels react.” Consequently, the support on which the cells rest has to be microporous to allow researchers to determine whether the ultrafine particles can make their way across the intestinal wall. The scientists are using electrodes to measure membrane permeability on the models they have already designed. A further illustration of organ simulation is the scientists’ model of the liver, which is essential for filtering the blood.
Currently, the InLiveTox team is examining how its liver model copes with the presence of nanoparticles. “We are also looking into how organs communicate with one another,” says Martha Liley, “because even if no nanoparticles cross into the blood, for example, they may still cause inflammatory reactions of the intestine that will be sensed by other organs.”
The analysis of such minute elements and their possible toxicity is a major challenge for InLiveTox: “The hazard posed by a nanoparticle depends on a range of factors, one being its shape, for instance,” says Martha Liley. “Urgent measures have to be taken in order to understand these factors and the influence they may have on toxicity – especially as nanoparticles are found in all kinds of materials, from air to food.” The world of organ simulation
The InLiveTox system has been designed to differentiate the different types of nanoparticle, from the least harmful to the most toxic. “Only a small palette of nanoparticles will be studied in the project,” says Martha Liley. “All we want to do is test enough of them so that we can compare the data with that gathered from in vivo tests. This will enable us to check whether the model is reliable.” In the long term, if a given nanoparticle has no effect whatsoever in vitro, then in vivo testing should not be necessary. However, if the effects are not insignificant, animal testing would be carried out to confirm the in vitro tests. Whatever the outcome, the need for rats in laboratories would be less.
The design of a device which could simulate a rat in its entirety is still the stuff of scientists’ dreams. But the CSEM is confident that it can make its models even more complex by adding more tissues and organs, in the hope of approaching the reality of a living organism. “It will be possible in the future,” says Martha Liley. “We cannot say whether our method is better than all the others, but we have no doubt that we are heading in the right direction.”
An ambitious programme
“It’s a European project which so far is progressing well,” says a thrilled Martha Liley, Doctor of Physics at the CSEM. InLiveTox was launched in May 2009 for a period of three years. The project, whose total cost is some 3.4 million euros, is funded chiefly by the European Commission. The CSEM coordinates InLiveTox in partnership with a number of European universities. All are working towards an alternative to laboratory experiments on rats.
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Une alternative aux souris de labo
Lancé en mai 2009 pour une durée de trois ans, le projet de recherche européen InLiveTox (3,4 millions d’euros) est coordonné par le CSEM. Son objectif est de créer une alternative à l’expérimentation sur les rats de laboratoire en développant des systèmes fluidiques et microélectromécaniques pour y tester des cultures de cellules. Martha Liley, responsable de la section BioMEMS, qui supervise le projet, et les ingénieurs du CSEM développent en particulier les membranes de silicium couvertes de cellules de chaque sous-système et les intègrent dans un dispositif simulant l’intestin et le circuit sanguin. A terme, les toxicologistes utiliseront ces biopuces pour tester diverses nanoparticules, nombre d’entre elles étant considérées comme potentiellement dangereuses pour la santé. La nouvelle réglementation REACH a par ailleurs relancé le débat sur les alternatives à l’expérimentation animale.