Development of a technologically new recycling process for nano- or microscale magnetic particles

(German title: Entwicklung eines technologisch neuen Recyclingverfahrens für nano- oder mikroskalige Magnetpartikel)

Microorganisms such as yeasts, fungi and bacteria or animal cell lines are used to produce pharmacologically relevant proteins. These microorganisms and cell lines are cultivated in industrial bioreactors. This cultivation produces a complex mixture of microorganisms, water, nutrients, the desired biotechnological products, but also many unwanted by-products as impurities. Several purification steps are therefore necessary to isolate the desired biotechnological product. The costs of processing the product can account for up to 95% of the total costs of the process. The current purification process involves at least three steps. Separation of the microorganisms from the biological product (solid-liquid separation), separation from the solvent water (concentration) and separation of the unwanted by-products (contamination).

The use of micro- and nanoscale magnetic particles to combine several separation operations into a single process can reduce production costs. Methods for detecting proteins have already been developed for the field of medical diagnostics. However, only the specificity, but not the product yield, plays the decisive role in this area. The existing laboratory processes for separating magnetic particles and the proteins bound to them cannot therefore be transferred to production scale without solving further scientific and technical challenges. In addition, micro- and nanoscale magnetic particles cannot currently be recycled in these laboratory processes and therefore increase production costs.

The aim of the project is to develop an industrial recycling process for nano- or microscale magnetic particles so that these magnetic particles can be used industrially. With the help of recyclable, coated and functionalized magnetic particles, a model protein is to be separated from impurities. A highly specific recognition molecule will be used to bind the protein. The magnetic particles are separated in a rotor-stator magnetic separator. After separation, the magnetic particles are fed back into the separation process. The focus of the work carried out at the Department of Bioprocess Engineering is on the binding of highly specific recognition molecules on the particle surface of the recyclable magnetic particles. The aim is to realize a chemically and biologically stable coupling of the recognition structures with high density and functional arrangement on recyclable magnetic particles. A further objective is not to negatively influence the stability of the magnetic particle dispersions through functionalization. In order to achieve this, the magnetic particles to be developed must be adapted to the complex fermentation and cleaning media. 

Partner

Prof. Dr.-Ing. Percy Kampeis (Umwelt-Campus Birkenfeld)
Chemagen AG
Vulkan Technic Maschinen-Konstruktions GmbH  
ABBIS bio process automation

StatusCompleted project
Funding organisationBMWi/AiF
Funding period09/2010 - 08/2012
Funding codeKF2031212FRO

Publications and conference papers

  • N. Tippkötter, S. Wollny, P. Kampeis, J. Oster, H. Schneider, R. Ulber; Magnetseparation von Proteinen; GIT Labor-Fachzeitschrift 10 (2011) 666
  • N. Tippkötter, H. Al-Kaidy, S. Wollny, R. Ulber; Functionalized Magnetizable Particles for Downstream Processing in Single-Use-Systems; Chem.-Ing.-Tech. (2012) DOI: 10.1002/cite.201200130
  • N. Tippkötter, R. Stadtmüller, S. Wollny, P. Kampeis, H. Schneider, J. Oster, R. Ulber, Production, application and separation of selective magnetic aptamer particles, Keynote lecture, 32th International Symposium on the Separation of Proteins, Peptides and Polynucleotides, 2012, Istanbul, Turkey

  • S. Wollny, R. Stadtmüller, N. Tippkötter, J. Oster, P. Kampeis, R. Ulber; Optimierung der selektiven Aufarbeitung von Proteinen mit Aptamer-funktionalisierten Magnetpartikeln; 30. DECHEMA-Jahrestagung der Biotechnologen
  • S. Wollny, R. Stadtmüller, N. Tippkötter, H. Schneider, J. Oster, P. Kampeis, R. Ulber, Selektive Aufarbeitung von Proteinen mit Aptamerfunktionalisierten Magnetpartikeln, Vortrags- und Diskussionstagung Biopharmazeutische Produktion, 14.-16.05.2012, Freiburg
  • N. Tippkötter, S. Wollny, R. Stadtmüller, P. Kampeis, H. Schneider, J. Oster, R. Ulber, Hochselektive Aptamere auf magnetisierbaren Mikropartikeln, 7. Deutsches BioSensor Symposium 2011
  • S. Wollny, R. Stadtmüller, N. Tippkötter, H. Schneider, J. Oster, P. Kampeis, R. Ulber; Recyclable aptamer-functionalised magnetic beads for selective single-step protein separation and purification; European Congress of Chemical Engineering and Applied Biotechnology (2011) Berlin
  • S. Wollny, R. Stadtmüller, N. Tippkötter, J. Oster, P. Kampeis, R. Ulber; Optimierung der selektiven Aufarbeitung von Proteinen mit Aptamer-funktionalisierten Magnetpartikeln; DECHEMA-Jahrestagungen (2012) Karlsruhe
  • N. Tippkötter, S. Wiesen, H. Al-Kaidy, S. Wollny, R. Stadtmüller, R. Ulber; Process simplification of bio separations  Application of magnetizable, aptamer and impregnated micro particles in the field of bioprocess engineering; AFS 2012 Fall Conference (2012)
  • S. Wollny, R. Stadtmüller, N. Tippkötter, H. Schneider, J. Oster, P. Kampeis, R. Ulber; Selektive Magnetpartikel: Aptamere als spezifische Proteinfänger; GVC/DECHEMA Vortrags- und Diskussionstagung, Effiziente Verfahren und Anlagen in der Bioverfahrenstechnik und Lebensmittelbiotechnologie (2013) Bad Wildungen