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Proteomics on a chip

June 18, 2002

'Golden approach' human proteine classification
Proteomics on a chip

Knowledge of the human proteome may provide us with even more insight than knowledge of DNA. This 'protein blueprint' of a human contains valuable information about cell properties and disease causes. A single cell, however, already consists of several thousands of proteines. To be able to classify them, dr. Richard Schasfoort of the University of Twente is developing a special chip, able to make hundreds or thousands proteine analyses at the same time. For his 'out-of-the-ordinary' ideas, he got the Dutch Innovation impulse last year. Important steps have been made already, in the development of a chip for patient monitoring of prostate cancer, using the same proteine analysis technique. In his new Biochip research group at UT, starting July 1st, Schasfoort is extending this concept towards use in proteomics.

The blueprint of an organism can be found in the proteome, the total 'package' of proteins being expressed within this organism. Not all proteins are in a direct way linked to DNA, they interact themselves. Finding the protein pattern -each cell has about 10000 proteins, of which several thousands are unknown- is a new race, providing more information than the DNA-map. The Human Proteome Organisation (HUPO) faces the challenge of identifying over 300.000 proteines.

Gold
There are techniques for this, Schasfoort admits. But for these amounts of data, they are very time-consuming: they are in fact based on visual recognition of proteines and selecting the interesting ones with a kind of chemical 'pair of tweezers'. Schasfoort is convinced of the need for a new approach: he proposes a combination of 'microfluidics' and a detection technique called Surface Plasmon Resonance imaging (SPR). In this way, he wants to build a complete lab on a chip, for imaging of hundreds or thousands of proteines at the same time. On the chip, a separation technique splits the proteome in individual proteins. They 'land' on tiny gold surfaces, specially prepared for capturing the proteines: one proteine on every gold. Caused by the interaction, a change in refractive index is induced: in this way optical detection is possible. A laser scans all the golden rectangles with proteines on them, and a camera makes an image of the proteine pattern.

Schasfoort's new Biochip group is part of the chair of Biophysical Techniques, faculty of Applied Physics, University of Twente. In this group, Schasfoort wants to develop a complete integrated system. For this idea, NWO the Dutch organisation for scientific research, granted him with the 'Vernieuwingsimpuls', about 700 thousand euro for a period of five years. Schasfoort doesn't start 'from scratch': he already developed the basic components, for a prostate cancer monitoring system using the same technique SPR. This is done in a EU-project to be finished in approx half a year. In the project, directed by IMEC in Belgium, detection of the cancer-specific proteine in blood is possible, in quantities of less than a tenth of a nanogram per millilitre. All handling and separation of fluids is done on the same chip. The laser and the camera can be made very small as well.

Dr. Richard Schasfoort (43), chemical engineer, developed large-scale industrial SPR systems before, in a company called Ibis Technologies. After getting acquainted with microfluidics in the group of Albert van den Berg (MESA+), he decided to combine best of both worlds. The power of the 'lab-on-a-chip' concept was already seen in the human genome project, when analysis chips became commercially available. Schasfoort starts with a group of six scientists and technicians.

Twente, University of