Team Leader (DSP)

Prof. Dr. Michael Wolff
Prof. Dr. Michael Wolff
Phone: +49 391 67 546 76
Fax: +49 391 6110 588
Room: G25-114

Additional Information

Cooperation:

  • Sartorius Stedim Biotech GmbH
  • Karlsruhe Institute of Technology, Karlsruhe; Biomolecular Separation Engineering (Prof. Dr. Jürgen Hubbuch)
  • IDT Biologika GmbH
  • Tosoh Bioscience GmbH

The project is financed by the industry and the BMBF (0315640C)

Development of Membrane Adsorbers for Virus Purification Processes

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Development of Membrane Adsorbers for Virus Purification Processes

Motivation

Viruses are large bioparticles, which vary in surface structure, size, shape, and composition. For manufacturing of vaccines produced in cell culture or eggs, inhomogeneous mixtures of whole virus particles have to be separated from a complex blend of process- and product-related impurities. Obviously, this task can only be achieved by a combination of different unit operations in downstream processing, whereby chromatographic techniques represent commonly an integral part. Solid phases used for these applications include porous particles, membrane adsorbers and monoliths. The main advantage of the latter two is not only the predominant convective mass transport of the sample but also a comparatively high binding capacity for macromolecules. In particular, the convective mass transport eliminates or reduces diffusion limitations of the solutes allowing high flow rates, which has a positive impact on process productivity.

Aim of the project

Porous beads with pseudo-affinity ligands are commonly used in virus purification processes. However, pseudo-affinity membranes and monolithic materials relying primarily on convective mass transport providing options to design more efficient processes with significant improvements in productivity. In order to take advantage of this technology we develop membrane adsorbers as a platform technology to purify or deplete a variety of viruses, e.g. influenza virus, Vaccinia virus, and baculovirus. 

<strong>Figure:</strong> <em>Chromatographic membrane adsorbers and respective holder.</em> Zoom Image
Figure: Chromatographic membrane adsorbers and respective holder.

References

1.
Opitz, L.; Zimmermann, A.; Lehmann, S.; Genzel, Y.; Lübben, H.; Reichl, U.; Wolff, M. W.: Capture of cell culture-derived influenza virus by lectins: strain independent, but host cell dependent. Journal of Virological Methods 154 (1-2), pp. 61 - 68 (2008)
2.
Wolff, M.; Siewert, C.; Lehmann, S.; Hansen, S.P.; Djurup, R.; Faber, R.; Reichl, U.: Capturing of Cell Culture-Derived Modified Vaccinia Ankara Virus by Ion Exchange and Pseudo-Affinity Membrane Adsorbers. Biotechnology and Bioengineering 105 (4), pp. 761 - 769 (2010)
3.
Wolff, M.; Siewert, C.; Hansen, S. P.; Faber, R.; Reichl, U.: Purification of cell culture-derived modified Vaccinia Ankara virus by pseudo-affinity membrane adsorbers and hydrophobic interaction chromatography. Biotechnology and Bioengineering 107 (2), pp. 312 - 320 (2010)

Patents

4.
Post Hansen, S.; Faber, R.; Reichl, U.; Wolff, M.W.:
Purification Of Vaccinia Viruses Using Hydrophobic Interaction Chromatography.
5.
Wolff, M.W.; Reichl, U.; Opitz, L.:
Method for the preparation of sulfated cellulose membranes and sulfated cellulose membranes.
 
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