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Techniques & Tools Liquid Chromatography, Technology

Realizing Great Vision – in a Material World

What’s the “origins” story from your perspective?

I joined Gert Desmet as a PhD student after he had been looking at the influence of order on dispersion, using computational fluid simulations in pillar arrays – relatively easy to simulate in 2D. During those simulations, Gert realized that the performance gains could be exploited in better chromatographic columns. He considered many aspects that I could use; the sidewall effect and the shape of the pillars, for example. During my PhD, I explored several different directions, developing even better solutions in some cases, but I have to say that Gert had already considered many theoretical aspects at that point.

And then you decided to make the leap from theory to practice?

Correct. But it’s a whole different world stepping from simulations to reality. Of course, everyone who proves something in theory would like to see it demonstrated – it’s an intellectual reward. If you’ve thought of a system with millions of theoretical plates, you eventually want to do separations that need those plates. But different practical engineering challenges arise that you cannot predict with simulations.

The time had come then for “someone” (me) to actually fabricate those structures and to consider more practical aspects, such as the need for porous materials, the need to avoid sidewall effects, and so on. Increasing volume loadability was another important aspect, because it’s one of the major “bottlenecks” in miniaturized devices. People are often impressed with miniaturization because you can use less sample, but it’s a double-edged sword when it comes to performance – you have to optimize all aspects to find the right balance. If you try to increase the volume and flow rate – by increasing pillar height, for example – uncontrolled taper may quickly lead to substantial loss in performance. The same happens with sidewall effects; minor offsets from the “ideal” sidewall distance based on computer simulations may increase peak dispersion. Making the microfluidic U-turns to “fold” 2 m columns onto the footprint of a 150 mm wafer is yet another art we needed to master.

Optimization takes time – and I was the guy who spent time in the clean rooms, where I started fabricating the first chips myself, learning many of the lithographic process steps directly from the experts. More generally, it was very fortunate that many of the microfabrication techniques I needed to employ had already been developed for use in other fields, such as microelectronics – and that allowed me to move very rapidly.

And at some point you saw commercial potential?

Towards the end of my PhD I said, “Gert, I want to start a spin-off company, I want to bring this to the market!” Several communities were crying out for high peak capacities – omics, for example – so the need was clearly there. For the next two years or so, during my postdoc, that became my goal. In 2009, I became a part-time professor and that meant I could write my own grant proposals. With such a grant for extra postdoc support, we were able to further develop the technology. We already had columns that we could couple to commercial instrumentation – but there were many further challenges to tackle before it was truly user-friendly technology.

Of course, everyone who proves something in theory would like to see it demonstrated – it’s an intellectual reward.
And then you founded PharmaFluidics?

Yes. The grant had to be used to start a spin-off company, so we founded PharmaFluidics at the very end of 2010, and started tackling the product development issues with even greater zeal.

Could you sum up the biggest challenges during development?

At first, when interfacing with a commercial instrument, we had issues with dead volumes wiping out any intrinsic gains delivered by the columns. So we focused on developing new kinds of interfaces, which proved to be a huge step in the right direction. The second major challenge was developing the surface porosity and the bonded phase chemistry of the backbone – as we improved the anodization protocols, we also improved our silanization protocols; both the uniformity of the layers and the stability of silanization were essential features to master. Solving those two challenges really put on us on the right path towards full commercialization. 

Now, our first generation of products is market-ready and actually being sold. And we are busy working on developing new generations. We are initially aiming at complex separations, which require several hundred thousand theoretical plates, but we are also moving towards faster separations.

What have you enjoyed most about the whole project?

It’s relatively simple to demonstrate a new principle in microfluidics – and to publish good papers – but to make it into something that people can really use and then, a step further, successfully commercialize that technology? Well, that is very much underestimated! From a scientific point of view, the journey has been (and still is) challenging – but also very rewarding.

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About the Author
Wim De Malsche

Wim De Malsche, co-founder, CTO and Director at PharmaFluidics, and Associate Professor at VUB, Belgium.

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