See companion article on page 1029.
A continuous multicolumn countercurrent solvent gradient purification (MCSGP) process†
Article first published online: 14 JUN 2007
Copyright © 2007 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 98, Issue 5, pages 1043–1055, 1 December 2007
How to Cite
Aumann, L. and Morbidelli, M. (2007), A continuous multicolumn countercurrent solvent gradient purification (MCSGP) process. Biotechnol. Bioeng., 98: 1043–1055. doi: 10.1002/bit.21527
- Issue published online: 17 OCT 2007
- Article first published online: 14 JUN 2007
- Manuscript Accepted: 23 MAY 2007
- Manuscript Revised: 19 MAY 2007
- Manuscript Received: 20 FEB 2007
- three-fraction separation;
- continuous countercurrent solvent gradient purification;
- peptide purification;
Biomolecules are often purified via solvent gradient batch chromatography. Typically suitable smooth linear solvent gradients are applied to obtain the separation between the desired component and hundreds of impurities. The desired product is usually intermediate between weakly and strongly adsorbing impurities, and therefore a central cut is required to get the desired pure product. The stationary phases used for preparative and industrial separations have a low efficiency due to strong axial dispersion and strong mass transfer resistances. Therefore a satisfactory purification often cannot be achieved in a single chromatographic step. For large scale productions and for very valuable molecules, countercurrent operation such as the well known SMB process, is needed in order to increase separation efficiency, yield and productivity. In this work a novel multicolumn solvent gradient purification process (MCSGP-process) is introduced, which combines two chromatographic separation techniques, which are solvent gradient batch and continuous countercurrent SMB. The process consists of several chromatographic columns, which are switched in position opposite to the flow direction. Most of the columns are equipped with a gradient pump to adjust the modifier concentration at the column inlet. Some columns are interconnected, so that non pure product streams are internally, countercurrently recycled. Other columns are short circuited and operate in batch mode. As a working example the purification of an industrial stream containing 46% of the hormone Calcitonin is considered. It is found that for the required purity the MCSGP unit achieves a yield close to 100% compared to a maximum value of a single column batch chromatography of 66%. Biotechnol. Bioeng. 2007;98: 1043–1055. © 2007 Wiley Periodicals, Inc.