Infineon of Munich is not the first company to make a DNA microarray on a silicon substrate. And it is not the first semiconductor company to set foot in the microarray ring. But the 1999 spinoff of Siemens — formerly known as Siemens Semiconductors — does enjoy the distinction of being the first company to combine silicon-based microarrays with an integrated electronic detection platform.
To develop these arrays, the company has solicited a little help from its friends, namely Siemens, as well as German partners Eppendorf, November and the Fraunhofer Institute for Silicon Technology. The team plans to target these arrays toward applications in diagnostics and pharmacogenomics, said Roland Thewes, a senior director for corporate research at Infineon.
In the prototype, Infineon researchers have combined standard semiconductor technology, called CMOS for complementary metal oxide semiconductors, and gold, which is an unusual material in that area but works well for immobilizing biological material like DNA. “We had to marry these two different worlds, and that was one of the challenges,” said Thewes. The other one, he added, was to amplify very small signals.
Each position on the silicon chip is about 100-250 microns in diameter and consists of a set of one micron-wide gold finger electrodes arranged in a comb-like grid. DNA probes are spotted onto these electrodes.
After the sample has been added, its DNA being labeled with an enzyme — for example beta-galactosidase —, hybridization takes place. Detection occurs when the enzyme breaks down a substrate, a para-aminophenol derivate, into charged subparticles. These are attracted to the electrodes and circle between anode and cathode in a process called redox-cycling, which creates an electric current.
Beneath the sensor electrodes are amplifiers and decoders. Currently the chip has 128 positions on approximately 30 square millimeters, but that is "definitely not the limit," said Thewes, noting that the number could be increased tenfold.
What is special about this chip is not so much the electrochemical detection — Motorola''s eSensor, for example, also applies reversible redox reactions — but the fact that it uses semiconductor-based electronic circuits rather than a passive chip. Thus it allows for a comparatively large number of small positions but is more expensive, Thewes noted.
Infineon and its partners, who started their collaboration with funding from the German Federal Ministry of Education and Research in 2000, want to validate the technology in clinics a year from now order to see what happens "when this is operated by doctors, nurses, but not by people who are specifically educated in electronics or biochemistry," said Thewes.
The company is also planning to launch an optical chip, which it has been developing with Gene Logic spinoff MetriGenix, in the third quarter of this year. These arrays, which will have about 400 spots each, are constructed with pores that allow fluid to be pumped through, which speeds up hybridization. Infineon is delivering the silicon substrate while MetriGenix is adding the DNA probes and providing the readout system. One of the first applications will be cancer, most probably breast cancer, said Hans-Christian Hanke, director for biochips marketing and sales at Infineon. The chip will be first marketed to pharmaceutical companies for research purposes but might find other applications later, he noted. While Infineon will distribute the chips in Germany, Switzerland, Austria, and Scandinavian countries, MetriGenix will deliver them in the U.S. and other parts of the world.