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Printed biochips

Microchips with biological functions now have a permanent place in biochemical analytics. These microchips are powerful tools for the rapid and reliable identification of bacteria, antibodies and new medical substances. However, the microtechnical production of microchips is very sophisticated and quite expensive. In a collaborative project, scientists at the Fraunhofer Institute for Manufacturing Engineering and Automation IPA in Stuttgart and the German Cancer Research Centre (DKFZ) in Heidelberg succeeded in cutting the production costs for highly complex peptide arrays by a factor of 100 at the same time as being able to increase the number of functional peptides by a factor of 20.

Peptides are protein fragments consisting of up to 50 amino acids. Peptides 15 to 20 amino acids long arranged in arrays are sufficient for the identification of pathogenic proteins and for drug research. Unfortunately, the capacities of such arrays are limited: At the present time, a maximum of 10,000 peptides fit on a glass side, but biochips with 100,000 peptides in the form of 100 overlapping peptides are needed in order to represent each of the approximately thousand proteins in a bacterium. As many as 500,000 peptides are required for a malaria pathogen. Another drawback is the price: an individual peptide spot costs around 5 euros, amounting to almost 50,000 euros for a full array. Scientists from the German Cancer Research Centre (DKFZ) in Heidelberg and their colleagues from the Fraunhofer Institute for Manufacturing Engineering and Automation IPA in Stuttgart have now found a cheap way to mass produce peptide arrays: printed biochips.

Quantum leap in terms of price and performance

“At present, peptide arrays are manufactured using a spotting technique that employs a robot to dab the individual amino acids onto a paper-like membrane,” explains Dr. Stefan Güttler of the IPA. “Trying to do the same thing with a laser printer is something completely new.” The project requirements were clear and stringent, requiring printing on glass rather than on a flexible medium. In addition, 20 different toners had to be used because the peptides consist of 20 different amino acids that have to be linked to form specific chains. The DKFZ scientists provided a bio-toner: encapsulated amino acids. During printing, the amino acid particles are first processed in a dry state. They need to be dissolved for a chemical reaction to occur. “We dissolve the amino acids by heating the carrier,” said Dr. F. Ralf Bischoff of the DKFZ explaining that the toner particles melt, enabling the amino acids to couple with the carrier.
The prize winners: F. Ralf Bischoff, Stefan Güttler (1st row, from left to right) Frank Breitling, Martin Gröning, Peter Willems (2nd row, from left to right), Thomas Felgenhauer, Klaus Leibe, Simon Fernandez (3rd row, from left to right) (Photo: Fraunhof
The prize winners: F. Ralf Bischoff, Stefan Güttler (1st row, from left to right) Frank Breitling, Martin Gröning, Peter Willems (2nd row, from left to right), Thomas Felgenhauer, Klaus Leibe, Simon Fernandez (3rd row, from left to right) (Photo: Fraunhofer/Kai-Uwe Nielsen)

The amino acid particles are printed layer by layer on the glass slide, one precisely on top of another, and they are subsequently linked. Compared to state-of-the-art biochips, printed peptide arrays are much more complex. They contain over 155,000 microspots on a carrier measuring 20 cm by 20 cm, and can be manufactured much faster at a price that is at least 100 times lower than that of conventionally manufactured peptide arrays. The arrays can now be offered for a few cents per peptide.

This quantum leap in terms of price and performance opens up new perspectives in analytics. For example, peptide arrays can be used for the complete analysis of the antibody and T-cell specificities of an individual patient or for the effective screening of new medical substances, vaccines and catalytic functions in the field of chemistry. In addition, the inexpensive production of the microchips considerably simplifies all other applications of this technology, for example, the individual diagnosis of patients through their doctor. Experts expect that the new method for the production of highly complex biochips will become a key technology and make considerable contributions to the resolution of immanent questions in the life sciences field.

The research teams were awarded the Stifterverband Science Prize 2008 for the development of this manufacturing process. The work was funded with own resources and through grants from the German Federal Ministry of Education and Research (BMBF) and the VW Foundation.

Website address: https://www.gesundheitsindustrie-bw.de/en/article/press-release/printed-biochips