MESA+ University of Twente
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Wim de Malsche (promotion date: 30 May 2008)

Solving advanced micromachining problems for ultra-rapid and ultra-high resolution on-chip liquid chromatography

Promotion date: 30 May 2008

Thesis advisor: Prof. Han Gardeniers, Mesoscale Chemical Systems

Assistant thesis advisor: Prof. Gert Desmet (Vrije Universiteit Brussel)

Micromachining technologies have been employed to solve a number of stringent issues in liquid chromatography. An automatic injection system was developed for shear-driven chromatography (SDC). Also the development of a pillar array prototype has been studied, using non-porous pillars of diameters near to four micrometers, coated with a C8 phase.

To meet common characteristics of high-performance liquid chromatography (HPLC), also porous shells were created on highly doped p-type silicon pillars, having a diameter of ten micrometers. This closed channel configuration was tested up to seventy bar, without observing leakages or losses in consistency. Coating this layers with a C8 phase, an enormous increase in retention behaviour was observed.

It seems like using lab-on-a-chip concepts for liquid chromatography is very attractive. What is the main cause for this?

It has been proven that injecting, separating and detection on one chip is possible. We use pillar arrays which are very orderly packed. The future of the pillar array column concept seems very bright indeed. A reduction of analysis time by a factor of ten is only a very cautious estimatie, in my opinion. Theoretical ideas, stemming from the university of Brussels, predictions and computer simulations came together in my promotion research.

I worked half of the time in Brussels and half of the time at MESA+. A lot has changed in four years time. When I started I was working on my own on this concept, at this moment in Brussels three people are working, and here in Twente two other researchers are involved.

The hope now is that in my post-doc project at the Vrije Universiteit Brussel, where I will still be closely cooperating with MESA+ and also Imec, Belgium, a real commercial product will be further developed. Industry still has a lot of rethinking to do: proven detection systems must be developed and changed, to this new way of analyses. Also there remain some principle questions, like the high-pressure connection between the pump and the chip.

Was there a major break-through moment?

The pillar arrays could be made porous, adding more reaction surface and interaction capacity to the whole concept. It is a creative combination of etching techniques in silicon, doping in HF, and adding an external electrical field. Also anodic bonding techniques are involved to “glue” the lid in a way pressure differences up to a hundred bar are possible, in principle.

So ... you used a lot of different cleanroom techniques?

Originally being a bio-enigineer, I was wondered by the almost futuristic possibilities of micromachining. I learned to work with them very quickly, using the great facilities and technical support from MESA+. The different techniques seemed to be very accessible. In the cleanroom at MESA+ you are allowed to use a lot of apparatus, in a very free kind of way. If you succeed in explaining the need for using special equipment and the costs involved, a lot of things are possible here.

Does this reflect your personal way of researching?

Yes, I believe so. It is fair to characterize my way of working in the first stage as a team-player. But as work develops I like to work things out on my own. In my case it proves to work out faster, most of the times.

On the other hand, now a lot of people are working on this concept. Only by working as a team it is possible that in future a real spin-off product will see daylight.

Will you miss Enschede?

In an ideal world MESA+ would be located in Brussels. The facilities and organization here, are top of the world. I choose to move over because of the topic of study, of course, but in these two years I actually learned to appreciate Enschede. But going back to Belgium is great for me, being close to my girlfriend, family and friends.