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A Swiss sense for “Lab on a chip”

There are more than 30 companies making some form of lab-on-a-chip device

Andreas Manz's vision of a sensor able to detect the presence of chemicals at the molecular level, known as a lab-on-a chip, is still out of reach but it does not stop researchers from trying.

A fire at Sandoz in Basel sparked the concept of a “micro total analysis system” in the late eighties.

The story goes that water used to fight the flames flowed into the Rhein River, taking with it 30 tonnes of the chemicals that pharmaceutical giant was producing at the time, a horrible mixture of pesticides, chemical dyes and fungicides.

The environmental disaster prompted Sandoz’ competitor, Ciba-Geigy, (the two firms have since merged into Novartis), to develop sensors that could in real time sample rain water collected from beneath the complex of buildings and quantify some 200 molecules it was manufacturing, so that if anything leaked, alarms would be set off.

Manz was working with Professor H M Widmer, who came up with the idea for a super sensitive device that would perform a few hundred tests using nanoliters or even picoliters of fluids in real time.

Since then the quest for lab-on-a-chip devices that could be manufactured with the same kind of volume and economy of the computer chip industry has captured the minds of scientists, researchers, semiconductor giants, and more lately venture capitalist investors around the world.

State of the art

Things that are called lab-on-a-chip devices today typically perform only one experiment over and over.

There are more than 30 companies making some form of lab-on-a-chip device. It is a market growing at a rate of 40 per cent, according Yole Developpement, a research and consulting firm based in Lyons. Yole expects the market to grow into a $2bn a year industry by 2005.

They are not as fast or as selective as Manz’s vision requires.

“Only pH glass electrodes, glucose sensors and the lambda sensors in cars have achieved the selectivity [sensitivity] and necessary reliability for such a sensor array,” says Manz, now a professor at Imperial College London.

Manz sees volume business in making miniature analytical tools for oil field exploration, forensics, the military, civil anti-terrorist defence, and chemical production safety systems.

Swiss chips off the old block

Switzerland has more lab-on-a-chip research teams than one would expect, according to Manz. He attributes it to the supply of research funding and says only the Netherlands, Scandinavia, and South Korea have similar research funding per capital flow.

This funding has led to a number of breakthroughs exciting enough for researchers to create spin off companies.

One of the newest is Crystal Vision Microsystems. Another is Gnothis, a Swiss/Swedish startup. Four-year-old DiagnoSwiss is now working with Agilent to take its disposable microfluidic chips for biosensor and proteomic applications to market.

Microsens is manufacturing micro gas and chlorine sensors, while Zeptosens is making a complete system. It recently signed an agreement with Qiagen to market the products.

Tecan, a Zurich-based lab automation equipment vendor based, is emerging as a supplier of reader or instrumentation systems.

Some companies are becoming what might be called “fabs” or foundries. They specialise in materials and mass manufacturing techniques for the glass, polymer or silicon devices designed by the lab-on-a chip companies. An example from the region is Weidmann Plastics. Leister Technologies also has its eye on the field as a potential new market.

Finding the path to profits

New types of chips can “read” the electrical activity in a cell. Such chip manufactures smear cells samples onto a slice of silicon covered with tiny probes that are only visible under a special microscope. Ayanda Biosystems makes such cell chips and it expects them to be used in stem cell research.

The path to profitability is not without hurdles for a Swiss start-up company. “The venture capitalists tend to want to invest at a later stage,” says Salomzi Makohliso, CEO at Ayanda Biosystems in Lausanne.

Government grants have become extremely important because venture capital investors have only recently begun to warm up to investment in the sector and then only at a stage where the risks are relatively small.

This means that strategic partnerships with industrial partners are essential. Swiss start-ups have to find a big name reference customer to complete the “proof of principal” and then go from there into a more traditional venture funding growth model.

True technology

As Switzerland has a number of established sensor firms who are marketing devices internationally made with tried and true technology, the next generation sensor technology firms have a good chance of finding strategic partners close to home.

Older sensor firms have already shown a desire to acquire innovative new products to enhance their existing lines. Disetronic, for example, recently announced it would distribute the cutting edge glucose sensor of TheraSense, a tiny privately owned firm.

Saia Burgess injected capital, in exchange for equity, into MicroChemical Systems, a firm in Neuchatel that makes advanced gas sensors for the automobile industry.

A third example of the trend is Metrohm AG, a maker of pH glass electrode systems, which is participating in technology transfer projects with the universities here.

Zurich-based Zühlke Engineering, a 35-year-old firm with 220 employees, is building a reputation for doing the engineering work required to make lab-on-a-chip devices affordable.

It has taken prototypes from the likes of Zeptosens, Bionas GmbH, and Novartis and made them into mass manufacturable products.

“There is a big difference between a lab experiment and a product you can sell to customers,” says Thomas Fink of Zühlke. He says his firm is working with somewhere between five and ten lab-on-a-chip projects but he would not provide further details due to non-disclosure agreements with clients.

by Valerie Thompson

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