ISBN 9783843907330

978-3-8439-0733-0, Reihe Verfahrenstechnik

Peter van Beijeren
Membrane Adsorption for the Capturing of Proteins

193 Seiten, Dissertation Technische Universität Dortmund (2012), Softcover, A5

Zusammenfassung / Abstract

The low initial product purity of biopharmaceuticals, in comparison with products obtained from chemical sources, and the complex nature of mixtures, like fermentation broths and cell culture supernatants, requires the use of highly selective separation processes. The high resolving power and robustness of chromatographic columns has made chromatography the unit operation of choice for the purification of biopharmaceuticals.

In this thesis the use of membrane adsorbers for the capturing of proteins as an alternative to chromatographic columns is investigated. For this purpose a detailed dynamic model for membrane adsorption was developed, which allows for simulation of complete purification cycles under the consideration of process scale. The model was validated with experimental data on affinity and ion exchange membrane adsorption. A good match between experimental and simulated breakthrough, washing and elution curves was obtained over wide ranges of operating conditions. The validated model for membrane adsorption was used to investigate the advantages and disadvantages of four different scale-up strategies of membrane adsorber unit operations. The high flexibility of membrane adsorbers, with respect to adjustment of the adsorber volume to production capacity and adsorber lifetime, was demonstrated in a case study on the purification of antibodies.

A comparison of the performance of membrane adsorption and chromatography showed that the potential of membrane adsorption as a direct replacement of chromatography is decreasing with the currently increasing product titres. Therefore, a novel application of membrane adsorption (CHROM2), which is feasible at low and high product concentrations, has been developed, using the detailed membrane adsorber model. CHROM2 allows for the debottlenecking of a chromatographic column by forming a serial connection of the column with a membrane adsorber. Experiments on the adsorption of BSA on strong anion exchange adsorbents showed that a disproportional large increase in the productivity or the dynamic binding capacity of a chromatographic column can be achieved by forming a serial connection with a small membrane adsorber module. The effect was most pronounced at high linear velocities.