is when we heard about the Nano-Tera

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NutriChip: an electronic intestine for a healthy diet

LAB-ON-CHIP NutriChip has be developed to test the nutritionalquel of dairy products

The fruit of a collaboration between a nurnber of Swiss institutes and universities, the project labelled Na.no-Tera is proving that the line between in sitico and in vivo ceEl biology can be very thin.

BY PIERRE-YVES FREI

At

first glance, there seems to be little likeness between a human being and a very small pile of electronics measuring four cen- timetres by two. And yet, to the designers of this miniature machine, it is a sort of functional reproduction of our gas - trointestinal tract. And its code name is Nu- triChip. The point of such a minute concen- tration of technology lies in its capacity to test the nutritional quality of dairy products or, more specifically, in its ability to select products winch will prove to be particularly

efficient in down regulating -reducing - the human body' s inflammatory response.

AN OUTCOME OF THE NANO-TERA FEDERAL RESEARCH PROGRAMME Developed within the Nano-Tera federal research programme, the NutriChip project brings together various laboratories from the Swiss Federal Institutes of Technology in Lausanne and Zurich, the University of Basel and the Agroscope Liebefeld-Posieux Research Station, along with a collaboration with the Bern University Hospital. The collaboration's broad base is designed to take in talents from different horizons in an ef- fort to carry through a project that borrows as much from engineering as it does from nutrition studies and medical sciences.

The Agroscope Liebefeld-Posieux Re- search Station is at the heart of tins asto- nishing project. For a number of years its researchers have been seeldng a greater understanding of the effects of dairy products on human health. "Various studies have already stressed the fact that the regu-

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lar consumption of dairy products seems to decrease certain inflarnmatory reactions,"

explains Guy Vergères, head of the Nu- tritional and Functional Biology research group at the research station. "Others daim that this is flot the case. We wanted to make our contribution to this scientific issue."

But why sa much interest in dairy products? Guy Vergères explains that milk is the only substance that marnais both produce and consume. So milk must be stashed full of ail sorts of goodness. What needs to be done now is ta identify the nature of this goodness and any biological activities it may have.

The Agroscope team is already carrying out research on human beings. A number of volunteers were asked ta swallow various dairy products, and were then observed ta see how their metabolism reacted ta them.

Screening was done by way of microarrays, which is a technology that is able ta take a "snapshot" of the expression profile of thousands of genes at any given time. Mi-

croarrays are very useful for identifying genes whose expression is modified when an organism is faced with a particular stress or assimilates a given product.

FROM IN VITRO TO IN SILICO

"These studies on human beings were very rewarding but they have their constraints, namely when it cames ta human and fi- nancial resources," continues Guy Ver - gères. "Accordingly, we sought for a way ta continue our experiments by transferring them into the realm of in vitro. And that

is when we heard about the Nano-Tera

programme and the prospects of research across disciplines that it offered."

A few encounters and sessions later, the project saw the light of day in March 2010 and is fundedby the Swiss National Science Foundation. NutriChip is still in its infancy.

It will take another two years before it is possible ta estimate whether it cari contri- bute significantly ta the evaluation of nu-

' tritional benefits in dairy products. But the team's optimism is undaunted: in fact, the feeling of uncertainty that induces greater optimism, as uncertainty always accompa- nies innovative projects.

"Taken separately, the technologies inte - grated in the NutriChip are far from revolu- tionary," remarks Qasem Alramadan from the Laboratory of Microsystems at the Swiss Federal Institute of Technology in Lausanne, which is directed by NutriChip project su- pervisor Martin Gijs. "On the other hand, they have never been associated in tins way, and even less so on such a miniature scale.

The amount of liquid found in a NutriChip is measured in microlitres. jUst imagine."

It's no surprise that the engineer cites tins example, since he is in charge of the microfluidics in tins experiment. Micro- fluidics is the technology that contrais the dynamics within the miniature digestive

tract, winch makes the chip sa special.

Qasem Alramadan explains why: "As it is necessary to imitate one functional part of the digestive tract, our NutriChip includes two cell cultures. One is made up of epithelial cells, winch represent the first cell layer and hence the first intestinal barrier.

The second is made up of macrophages, in other words one of the main classes of de - fence cens in the immune system."

More often than not, an inflamma -

tory reaction is expressed by the making of macrophages. In the presence of a pa- thogen, macrophages release molecules known as cytokines, winch are frequently responsible for inflammatory reactions.

Ta find out whether certain dairy products are really capable of inhibiting an inflammatory reaction in vitro, they must first be digested by enzymes that have been extracted from the digestive system it - self. The resulting molecules have then ta be "filtered" through a substitute for the epithelial tissue of the digestive tract. In fact, only the molecules capable of cros - sing tins natural barrier have any effect on the macrophages or - more precisely - on

the inflarnmatory reactions the macro-

phages are able ta induce (and winch must therefore be prompted artificially by or on the NutriChip). In sa doing, these digested molecules end up in an extracellular me- dium in winch circulate chemical messages that shuttle between epithelial cens and

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macrophages. Microfluidics technology thus allow two cell cultures to communi-

cate with one another, much in the way it would happen in real life.

Though tins work on microfluidics is

essential to the NutriChip's success, so is its miniaturisation, as such a tiny la-

boratory can detect biomarkers using as few reagents as possible. And that is not ail: Sandro Carrara from the Integrated Systems Laboratory at the Swiss Federal Institute of Technology in Lausanne also intends to install an optical system on the NutriChip that will be able to detect biomarkers by way of fluorescence.

At a time when the link between nutrition and health issues is becoming increasingly

significant besides the economic oppor- tunities it represents firms are beginning to show an interest in the NutriChip. Guy Vergères from the Agroscope confirms that the food giant Nestlé is already aware of their research and showing interest. But he also adds that it is still too early to gua- rantee any applied development out of tins innovative research. "We still have to carry out ail sorts of experiments in order to validate the NutriChip's efficiency. That said, we have just begun to work with Dr. Kurt Laederach of the Bern University Hospital, with whom we willbe developing a protocol that will enable us to validate our conclu- sions with respect to human beings." And that should be around 2013.

EN FRANÇAIS DANS LE TEXTE

Nutri'Chip : un intestin électronique

NutriChip est une sorte de reproduction fonctionnelle de notre tube digestif. Ce minuscule concentré de technologies sera capable de tester les qualités nutritives des produits laitiers. Et ce, notamment, afin de sélectionner ceux qui se révéleront particulièrement efficaces à moduler à la baisse les réponses inflammatoires du corps humain.

Développé au sein du programme fédéral de recherche Nano-Tera, il réunit plusieurs laboratoires de l'EPFL, de l'ETHZ, de l'Université de Bâle, et de l'Agroscope Liebefeld-Posieux (ALP); mais également une collaboration avec 'Hôpital universitaire de l'île, à Berne. Il intéresse des industriels comme Nestlé.

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