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Andreas Manz. (Img: European Patent Office)

Andreas Manz. (Img: European Patent Office)

05.10.2016

“This is the century of biology and biology for medicine”

Andreas Manz is considered one of the pioneers in the field of microfluidics and at present is a researcher at the Korea Institute of Science and Technology in Saarbrücken (KIST Europe) and professor at Saarland University.

In our interview, the successful scientist explains the motivation that drives him to research and what it means to receive a lifetime achievement award from the European Patent Office.

You are known as a pioneer of microfluidics. How did you come to start researching in a completely new field?
Andreas Manz*:
Even as a child I was really fascinated by small things. They were mostly stones, insects or bugs that I took home with me. This interest in small things stayed with me, and eventually I went on to study chemistry at the ETH Zurich. In my PhD thesis I examined the natural law of molecular diffusion. If you entrap two molecules in a very small volume – rather like two birds in a cage – they cannot get away and become faster. I was instantly fascinated by this acceleration. My professor Willy Simon, an expert in chemical sensors and chromatography, talked in his lectures about processes can also get very fast when they are reduced in size. And that instantly fascinated me.

But so far you have been talking about pure chemistry – when did you get the idea of using chips?
I started working for a company in Japan in 1987. That’s where I first came into contact with chip technology. I was part of the research department myself, but I kept seeing colleagues disappearing into cleanrooms and coming back with tiny chips. That inspired me and got me wondering whether you could not also pack chemistry onto these chips instead of electronics. After all, even the inner workings of the tiniest insect involves the transportation of fluid, so it should also work on a small chip. At Hitachi I was eventually able to get my first microfluidic chip produced for test purposes.

From Japan your journey then took you to Ciba-Geigy in Basel. What prompted that move?
Michael Widmer was then Head of Analytical Chemistry Research at Ciba-Geigy in Basel. This brilliant fascinated me from the word go: he had the vision that you should also integrate crazy things in research and not only look for short-term financial success. Industry should allow itself to invest in quality and also develop or promote new methods in the research activities of a company if it could be of benefit to the company. So Professor Widmer brought me to Basel, where it was my mission to pack “the whole of chemistry”, as he put it, on a single chip. While Michael Widmer did not yet know what to expect, he had a feeling that it could be worthwhile.

How did you go about it?
At that time, chips were very new and not entirely appropriate for the world of pharmaceuticals. Ciba-Geigy, too, was not enthusiastic about the new application initially. There was no great interest in making changes to existing technologies and processes that worked. But in my research I was able to try out what might be possible. I found, for example, that electrophoresis – a method for separating molecules – could work. It would be relatively easy to miniaturize this method and test it to see whether it also speeds up the process. And the results were very good: We were able to show that a tenfold miniaturization of electrophoresis makes the process 100 times faster without compromising the quality of the information. This realization was really useful for clinical diagnosis and the search for effective molecules in drug discovery. At the same time, we were also testing different types of chips that we sourced from a wide variety of producers.

When did the time come to go public with the new technology?
At the ILMAC in Basel in 1996, Michael Widmer organized a conference in the field of microfluidics – which proved to be a bombshell. We had planned for this effect to a large extent, because in the run-up to the meeting we had already invited selective researchers and shown them our work. This hyped things up a little, and at the conference we were eventually able to mobilize researchers from Canada, the USA, the Netherlands, Japan and other countries to present the new technology of microfluidics.

Although the attention was there, Ciba-Geigy nevertheless later brought research in this field to an end. Why was that?
Basically we lacked lobby groups within the company and a concrete link to a product. Our research was somewhat too technical and far ahead of its time, and within Ciba-Geigy they were simply not yet able to assess the potential of the technology. Added to which, we had not given any concrete consideration to applications; we were more interested in the technology and experiments than in its commercial use. When a large picture of me then appeared in a magazine with a report on microfluidics, and the journal pointed out on its own initiative that Ciba-Geigy was not adequately implementing the technology, the research was stopped. I was quite fortunate under the circumstances: Since the company had terminated the project, I found that – despite a non-compete clause – I was able to follow the call to Imperial College in London within a short time, where I could continue research in microfluidics with students. In addition, I joined a company in Silicon Valley as consultant.

Is it not typical that a large company fails to transform a pearl in its portfolio into a new era?
You should not see it so negatively, because microfluidics was a pearl not for the pharmaceutical industry, but rather for environmental analysis, research or clinical diagnosis. The pharmaceutical industry dances to a different tune. It prefers to buy in the finished microscope at a higher price than get it constructed itself for relatively little money. Michael Widmer and his team in research and analytical chemistry at Ciba-Geigy developed many things in a wide variety of fields – with which were far ahead of their time.

Microfluidics is an established field today. What are the driving forces now?
To my mind there are two driving forces: firstly the application and the users and secondly academic curiosity as regards the technology and also training. The first of these is the stronger driving force: there are cases in which the application of a microfluidic solution is not absolutely necessary to do justice to the application. Take “point of care”, for example. The objective is to analyse a patient directly at the place where he or she is treated – for example, in intensive care. The patient is evaluated, blood and respiratory values are analysed, and it is possible to assess immediately whether the measures taken are having an effect in the patient. Another possibility is to integrate the widest variety of analytical options in smartphones – similar to the Tricoder in Star Trek. I’m pretty sure that something like that is feasible. But at the moment the hottest topic in the commercial sector is clinical diagnostics. This came as a surprise to me, because you cannot reuse a chip that has come into contact with a patient’s blood. You need a lot of consumable material, which is also reflected in the price. But perhaps new funding models can be found in which, for example, the device is provided, but the consumable material – i.e. the chips – are paid for separately, rather like a razor and razor blades.

Where do you see opportunities for Switzerland in this field?
The education of qualified people is important. Here the ETH and EPFL play a particularly important role for Switzerland, because they attract students from all over the world. They hopefully leave Switzerland with good memories and could possibly campaign later for the commercialization of technologies. That could be a huge opportunity. Of course there are also generous people within Switzerland, but there is a tendency here to economize and think twice before deciding whether and, if so, where to invest one’s money. It’s a question of mentality and not necessarily typically Swiss. It’s also not a bad thing, because in precision mechanics, for example, reliability and precision are essential – and this technology fits with our mentality. “Quick and dirty” works better in Silicon Valley and Korea – but the products then often fail to ensure up to the quality standards here. As a high-price island, Switzerland offers little, opportunity for cheap production, which is why the focus is on education and existing technologies. This too is very important and has a good future.

Will microfluidics one day become as big as microelectronics is today?
I don’t think so, because it is limited to chemical and cytobiological applications and is also not as flexible as microelectronics. At most, I see the new technology being used on existing equipment or processes.

But most of the systems on the market today are very much closed, so it is difficult to integrate new technologies here.
Yes, but that’s only partly true, because existing devices also have to be upgraded. Take a mass spectrometer, for example. You can buy one of these, and there are certainly many companies that sell this equipment. But if ten companies offer something equivalent, you have to stand out from the mass. So if a “Lab on a Chip” is added on, then this mass spectrometer enjoys a clear advantage. While the company makes money from the sale of the equipment, it is the microfluidic chip that gives the incentive to buy – and there is certainly a lot of money to be made from this. You see, we are living in the century of biology and medicine and are only just beginning to takes cells from the body to regenerate them and then perhaps re-implanting them as a complete organ. When you see what has been achieved in physics and electrical engineering in the last century, and translate that into biology and medicine, then we have an awful lot ahead of us. Technology is needed to underpin these radical changes. SMEs in particular are very good at selling their products to research; that’s a niche. In most cases, small companies use old technology and modify it – such as a chip in a syringe that then analyses directly what the constituents of a fluid are when it is drawn up into the syringe. This opens up many opportunities.

You have also co-founded companies, but describe yourself mainly as a researcher. How do the two go together?
Actually I was never an entrepreneur, but always just a scientific advisor. I preferred to experience the academic world instead of becoming fully engaged in a company. Deep down, I’m an adventurer who comes to a company with wild ideas. Money is also never a priority for me; I always wanted to improve the quality of life or give something to humanity. It is curiosity that drives me. When I see a bug that flies, that drives me to find out how it works. There are ingenious sensors in the tiniest of creatures, and as long as we cannot replicate these as engineers, we still have work to do. This inspires me much more than quarterly sales revenue and profits.

But money is also an important driver for research.
Yes, it’s all about money, right down to university research. Research groups are commissioned by companies because of the profit they hope to gain. Even publicly funded research always has to show evidence of a commercial application. Curiosity or the goal of achieving something of ethical value is hardly a topic in the engineering sciences. Of course it’s important that our students can also enter industry; after all, most of the tax revenue comes from industry. But if I personally had the freedom to choose, then I would prefer to pursue work as a form of play – which can by all means result in something to be taken seriously. Take electrophoresis on a chip: That was also quite an absurd idea to begin with, and it led to something really exciting! A lot of my work therefore has a playful, non-serious aspect to it – for me that is exactly right. You see, I can produce a chip which deep inside it is as hot as the surface of the sun, but which you can nevertheless hold in your hand. It’s crazy, but it works, because only the electrons have a temperature of 20,000 Kelvin. The glass outside does not heat up very much as a result, and the chip does not melt. And suddenly you have plasma emission spectroscopy on a chip as the result of a crazy idea. I feel research calls for a certain sense of wit, and I often like to say that, with microfluidics research, we take big problems and make them so small that you can “no longer see them”.

You have covered so many areas of microfluidics yourself – are other researchers still able to surprise you with their work?
Admittedly, I am rather spoiled today by all the microfluidic examples that I have already seen. Sometimes I feel bored when I go to a microfluidics conference and see what “new” things have emerged – I somehow get the feeling I’ve seen it all before. The pioneering days, when there was also a degree of uncertainty at play, are probably definitely over. Today you can liken microfluidics to a workshop where you get the tools you need at any given time. This means of course that the know-how has also become more widespread: Initially I possessed perhaps a third of all knowledge about microfluidics worldwide; today it is much less. So I now enjoy casting my research net further afield.

You received a lifetime achievement award from the European Patent Office last year. What does this award mean to you?
You cannot plan for an award – at most you can perhaps hope for one. When you then get it, it brings a great sense of joy. The award process itself was also exciting: as with the Oscars, there were three nominees: a Dutchman who developed the coding standard for CD, DVD and Blu-ray discs, which is still used to this day, and a researcher from Latvia who is one of the most successful scientists and inventors in medical biochemistry with more than 900 patents and patent applications. Faced with this competition, I reckoned I did not have much chance of the award and was absolutely astonished when I was chosen. The jury explained that its decision was down to the snowball effect: citations almost always refer to my patents at the time with Ciba-Geigy.

Interview: Fabian Käser and Nadine Nikulski, BaselArea.swiss

*Andreas Manz is a researcher at the Korea Institute of Science and Technology in Saarbrücken (KIST Europe) and professor at the Saarland University. He is regarded today as one of the pioneers in microchip technology for chemical applications.

After positions in the research labs of Hitachi in Japan and at Ciba-Geigy in Basel, he took up a professorship at Imperial College in London, where he headed the Zeneca-SmithKline Beecham Centre for Analytical Chemistry. In the meantime he was also a scientific advisor for three companies in the field of chip laboratory technology, one of which he founded himself. In 2003, Manz moved to Germany and headed the Leibniz Institute of Analytical Sciences (ISAS) in Dortmund until 2008.

Around 40 patents can essentially be attributed to him, and he has published more than 250 scientific publications, which have been cited more than 20,000 times to date.

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