An EU-funded project has built a 'printer' that can produce protein-type samples to advance healthcare research, particularly diagnostics and drug therapies for virulent diseases such as cancer. The results have already been commercialised, and are being used by scientists.
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Unravelling elusive disease processes and the biochemical interactions involved has dogged the scientific and medical communities for centuries and remains challenging despite major advances in both knowledge and technology. A particularly hot topic that stands to radically advance understanding of key interactions is the analysis of peptides – small chains of amino acids representing the building blocks that create protein.
Peptide arrays – a screening technique involving robotics, data processing and detectors – is expected to lead to major advances. By tracking hundreds to thousands of immobilised peptides, they offer an unparalleled opportunity to identify protein interactions.
Against this backdrop, the EU-funded project PEPLASER conceived a revolutionary way to analyse peptides using laser-printer technology and cartridges.
"We developed a novel particle-based method that allows us to synthesise very high density peptide arrays with a custom laser printer in a uniquely flexible and efficient manner," explains Dr Volker Stadler from PEPperPRINT, the key commercial partner within the project, which ended in December 2011. "We significantly exceeded the state of the art."
In a lab near you
The PEPLASER technology has now been commercialised, and high density peptide microarrays are widely available for the scientific community, representing a cost-effective research tool.
The printer has already led to valuable discoveries. During a spin-off project with the University of Heidelberg, for example, researchers using the printer discovered a prognostic biomarker that enables the differentiation of aggressive glioblastoma (brain tumours) in two different patient groups.
Furthermore, the Heidelberg project recently discovered and optimised a peptide-based drug candidate – the first of its kind – by using peptide microarrays with over 30 000 different peptide variants in a single assay.
PEPperPRINT teamed up with the Karlsruhe Institute of Technology, which was the project’s coordinator, KMS Automation, and the Fraunhofer IPA research institute in Germany to build the peptide laser. To do this they had to generate and adjust suitable amino acid microparticles as toners for the printer.
The team then conducted several biological tests to validate the technology and the functionality of all components. "Without EU funding, none of the partners would have been able to finance the effort required to transfer this new concept and technology up to the level of a robust prototype machine," says Stadler.
Fast and efficient throughput analysis
The project team has likened its success to a recent invention in the field of genetics – gene chip or DNA microarrays gathering tens of thousands of oligonucleotides (short DNA molecules) on a single glass slide.
With PEPLASER, "researchers now have a tool that enables the high throughput analysis of proteins, antibodies and enzymes in a similarly fast, efficient way to that which gene chips have done for the field of genome research", says Stadler.
In the quest for better drug therapies, the new peptide microarray technology advances the fingerprint analysis of antibody responses, vaccination effects and enzyme substrates. "It helps us discover and develop new diagnostic biomarkers that can be correlated with a certain patient group, or even of new peptide-based drugs," explains Stadler.
Many more applications in health research are expected, now that the technology has been developed and validated. Together with a research group at the Karlsruhe Institute of Technology, PEPperPRINT is planning to push peptide microarray technologies to the next level by increasing the numbers of peptides per chip.