Printed biochips

Peptides are protein fragments consisting of up to 50 amino acids. However, peptides with a length of 15 to 20 amino acids arranged in arrays are sufficient for drug research and for identifying pathogenic proteins. Unfortunately, the capacity of such arrays is limited.

A maximum of 10,000 peptides will fit onto a glass slide at present, but biochips with 100,000 peptides are needed in order to represent each of the approximately thousand proteins in a bacterium – in the form of 100 overlapping peptides – and a staggering 500,000 are required for a malaria pathogen. Another drawback is the price: An individual peptide spot costs around 5 euros, adding up to almost 50,000 euros for a full array.

In cooperation with developers from the Fraunhofer Institute for Manufacturing Engineering and Automation IPA in Stuttgart, scientists at the German Cancer Research Center (DKFZ) in Heidelberg have found a cheap way of mass-producing peptide arrays: printed biochips. “At present, peptide arrays are manufactured by a spotting technique that uses a robot to dab the individual amino acids onto a paper-like membrane,” explains Dr. Stefan Güttler of the IPA. “Trying to do this with a laser printer is something completely new.”

The project requirements were stringent, calling for printing on glass, rather than a flexible medium, and involving the use of 20 different toners – because peptides consist of 20 different amino acids which must be linked to form specific chains. The DKFZ scientists provided the bio-toner: encapsulated amino acids. During printing, the amino acid particles are first processed in a dry state. For a chemical reaction, however, they need to be dissolved. “We dissolve the amino acids by heating the carrier,” explains Dr. F. Ralf Bischoff of the DKFZ.

The toner particles melt, enabling the amino acids to couple with the carrier. The amino acid particles are printed layer by layer on the glass slide, exactly on top of one other, and subsequently linked. Compared to the state of art, printed peptide arrays are much more complex. They contain over 155,000 micro spots on a carrier measuring 20 by 20 cm, and can be manufactured much faster at a price that is at least 100 times lower than that of conventionally produced peptide arrays. The arrays can now be offered for a few cents per peptide.

The research teams were awarded the Stifterverband Science Prize 2008 for developing this manufacturing process for highly complex biochips. The work was funded internally and by the Federal Ministry of Education and Research (BMBF) and the VW Foundation.