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U. of Twente s Richard Schasfoort Discusses Microfluidic Protein Chips

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AT A GLANCE

Richard Schasfoort, senior scientist, miniaturized biochemical analysis systems, MESA+ (Micro Engineering and Sensors and Actuators) Research Institute, University of Twente, Enschede, The Netherlands.

PhD, applied physics and electrical engineering, University of Twente, 1989.

Developed technology for TNO, Dutch applied research organization, from 1990 to1994.

Founded Ibis Technology in 1994. Company produced instrument for biomolecular interaction sensing, to do protein interaction work.

Returned to University of Twente, 1998 to work with Albert van den Berg on Lab-on-a-chip microfluidics technology.

Received Ý700,000 five-year grant in June 2002 to set up a protein biochip working group.

You have an interesting career track. As I understand it, you went from the University of Twente, where you did your PhD, to start a private company, then back to the University.

I started my company, Ibis technology, in 1994, to market new equipment as a competitor of Biacore instruments. Ibis is the Greek bird, but it also stands for “instrument for biomolecular interaction sensing.” This equipment was based on surface plasmon resonance (a process wherein lasers bounce light off of a surface and detect molecular binding to the surface through measuring the angle of diffraction). This technology had success, and I was really involved in the technological things. But with the personal [interactions] with banks and related [business], you have to be an entrepreneur. I was more [interested] in the scientific and research level, so I decided to sell the company.

 

I am reminded of Michael Heller, who recently left his position as chief technical officer at Nanogen to go back primarily into academic research because he was more interested in developing new technology than in marketing existing products.

Yes, for me it is not pulling the company, but rather pushing the [technology]. I can do this better with students and postdocs, and also try out new things, than you can do with a company. Companies are really focused on products. For me personally it is better that others do this part and I can concentrate on research and scientific things.

 

Can you tell me about your project to put together the biochip research group at the University of Twente? What factors led you to start this group?

What we want to develop is a combination of new technologies based on microfluidics with SPR imaging. The first goal we have is to combine microfluidics and SPR, and address with microfluidics different areas on the SPR image.

 

Now, you received a large grant from the Dutch organization for scientific research to set up this group. How are you going about this?

Now I am [working] in the perfect combination of a biomedical and technical [environment]. In the University of Twente’s Institute for Micro Engineering and Sensors and Actuators, or MESA, you can make your chips, microfluidics, silicon, and glass technology, all sorts of micromachining, and microparts. In the biophysical engineering department, I can combine the technologies with the biological parts — the antibodies, proteins, and [work] with blood too, that belongs also to the Biomedical Technological Institute of the University of Twente. Again, the best of both worlds.

 

Under the grant, you can hire six scientists and technicians. Have you hired them all?

I was here for four years before I received this grant. I also run the Pamela project, (www.imec.be/PAMELA), a research project with ten European partners, which involves the Ibis technology, and another biochip project dedicated to a detection biochip system for prostate cancer. This [new grant] gives me the finances to install a base of people. At the moment there are three postdocs, there is a student, a technician [who] will start in August, and an analyst in the laboratory. She will work on a new item on rheumatoid arthritis, on a system testing parameters [for that disease]. Our focus is to measure many [parameters] at the same time.

 

Can you explain how you are employing microfluidics?

We want to [commercially] launch this technology a bit later, so we cannot explain exactly how. But with address flow microfluidics, we can address a sample over a specific interaction field. Our devices have an area of several millimeters, and [include] hundreds or thousands of [interaction] fields. We can flow our sample over specific areas, and that’s a very elegant trick to work with microfluidics in a liquid rather than only spotting the sample.

 

So it’s a combination of a protein spotted microarray and a microfluidics chip. What sort of substrates do you use?

We work with glass and later we [will] start with plastics. You can also work with silicon, but it becomes quite expensive; because of the interactions on the surfaces you have to throw away the chip. And if you have monocrystaline silicon, that is quite expensive.

 

Isn’t it hard to get big and sticky proteins molecules to flow through fluidics channels? What is your approach to solving this problem?

The company, Ibis, is in the background [of the project], and Ibis has experience with biomolecular coatings. With biochips, you can apply different coating materials that will not affect the performance of the chip negatively. With our new spotting technology — we will use TopSpot from HSG-IMIT [a non-profit institute in Villingen-Schwenningen Germany that makes non-contact microarrayers with microfluidics-based print heads] — we can adapt the print head of the arrayers. The non-contact spotting is very important for proteins. Besides in this spotting machine you have the same challenges with protein transport through small channels. Also, we combine this with SPR.

 

What kinds of detection devices do you use?

We are building the instruments ourselves. We’re at an applied physics and optical group, so SPR is standard. We take a laser and camera, and with the user, the more [difficult] point is the software. You have to invest in software. You have to [process] the data with a nice elegant piece of software to find the right interactions, the proteins that are more of interest to the company [than others].

 

Recently we were both at the IBC EuroBiochips meeting in Berlin. What did you think of the different technologies presented there?

The acoustic wave technology presented by Advalytix [of Munich] was very exciting for me. The surface acoustic waves [achieved] a nice transportation of droplets over the surface [of the chip]. Like a surfer over the waves of the sea. In combinatorial chemistry, where you have a drug-type substance and another drug,[with this technology] they can meet each other using the surface acoustic waves. There are also other possibilities: You can split droplets up — I saw this phenomenon with electrowetting technology — and react them with each other. If you do it several times, you can do your combinatorial chemistry [on the chip]. You can put a drop on a certain sensing area, you wait and see the interactions, and then this drop is transported to another interaction sensing area. You are free to think how to organize this technology.