In terms of protein purification, the biopharmaceutical industry is increasingly reaching its technical and economic limits. The currently used chromatography procedures are expensive, time-consuming and associated with high product losses due to the large number of individual processing steps involved. Special magnetic microparticles, such as those developed by the chemist Dr. Jochen F. Peter with his recently established company SensScreen Technologies in Esslingen, now offer a promising alternative.
This company is in the described form no longer active in the market.
The first time Jochen F. Peter discovered the small magnetic beads was during his doctorate at the Technical University in Munich in 1997. In cooperation with the pharmaceutical company Roche Diagnostics, the chemist focused on the development of a test for the identification of biomarkers.
However, the prostate-specific antigen (PSA), which is a marker for the early detection of prostate cancer, was not an easy nut to crack because the protein, which is produced in the prostate, is only present in very small concentrations in the blood and can only be isolated with great difficulty.
In order to increase the PSA yield, Jochen Peter coupled the antibody used for the identification of PSA to the surface of magnetic microparticles, which he mixed with sample material, rather than coupling it to a two-dimensional matrix used in solid-phase ELISA. The goal of the procedure was to increase the reactive surface - and the success that he achieved was groundbreaking. Peter managed to isolate sufficient quantities of PSA in order to analyse its protein structure. "This was a decisive step towards a more sensitive measurement procedure," said the chemist recalling the experiments which led to the determination of the molecular structure of this highly complex glycoprotein.
The method of magnetic separation is now firmly established in laboratory analytics, not only for the isolation of proteins or nucleic acids, but also for cell sorting and typing. "Commercially available magnetic microparticles for such applications are nowadays two a penny," says Peter, "but they differ considerably in their composition."
"While many particles were developed on polystyrene, which is a plastic, Peter coated the magnetic crystals contained in his particles with a special silica composite material. This material has the advantage that no unspecific binding of proteins occurs which might hamper diagnostics. "But a great deal of innovation is also found in the special systems which are used to couple the antibodies to the surface of the particles," said the chemist who, until recently, was project leader in the Heinz Nixdorf Department for Medical Electronics at the Technical University of Munich.
Peter is firmly convinced of the technical and economic potential of his magnetic particles for which he has filed a patent. "For example, our reverse phase (RP) SensBeads have a ten times greater sensitivity on the peptide level than our competitors' products." However, Peter's company SensScreen Technologies founded in Esslingen in March 2009, not only aims to produce particles for use in analytics: "The modification of the method for use in large-scale production - for example for the purification of recombinant antibodies or proteins - will be the next big challenge."
The modification also requires the development of suitable marketable magnetic separators. “We are therefore working in close cooperation with a company that specialises in the development of permanent ring magnets,” said Peter. “With these permanent ring magnets we are also able to selectively retain the magnetic particles loaded with the target protein in the sample container using larger amounts of liquid and separate them from the rest of the solution. Subsequent elution, i.e. the extraction of the bound substance – then yields the sought-after product in purified form. “Magnetic separation does not require the filtration of the fermentation broth, which is usually necessary in classical chromatography,” explains Peter. “This not only saves time, but also a huge amount of material costs.” These are two important aspects that mean that Peter is fairly confident that magnetic separation will become established in biotechnological fields of application.
At present, magnetic isolation can only be used for small volumes and this is still a limiting factor. "The currently available methods are only suitable for no more than around 100 litres," explains Peter. However, current developments in the production of biopharmaceutical products are quite positive for Peter. While in 2006 the yield of recombinant antibodies produced with cell cultures was as low as 50 micrograms per millilitre, nowadays concentrations of 5 milligrams per millilitre can be achieved. "This increase in efficiency considerably reduces the starting volume in the bioreactor," said Peter. "Nowadays we only need 10 litres rather than 1000." And Jochen F. Peter considers his SensScreen products to be well equipped to deal with this kind of volume.
The young businessman received support from the state of Baden-Württemberg and the city of Esslingen where Peter recently relocated to rooms in the Life Sciences Centre. Peter also hopes to get another financial injection from the High-Tech Gründerfonds: “At present things are looking up,” said the 44-year-old who, although he seems to have inherited his family’s tinkerer and entrepreneur gene (his great-grandfather invented a packaging machine and established the company Hesser AG in the city of Cannstadt in 1861 (now Robert Bosch GmbH), and his father ran a successful engineering office in Stuttgart), Jochen F. Peter still a scientist at heart: “I still hope that our method will one day enable us to develop an effective method for breast cancer diagnosis.”Over the last few years, Peter has optimised his method in order to enable the highly sensitive analysis of the secretion of tumour cells. “Our analytical method now enables us to analyse any cell and any cell state,” said the chemist who has received two renowned international prizes for his analytical methods. He succeeded in identifying numerous peptides in invasive breast tumour cells, which cannot be found in non-invasive cells. He would like to be able to focus more on these peptides because he is sure that “they are potential biomarkers that would considerably improve the early detection of breast cancer.”