(148e) Multicolumn Countercurrent Solvent Gradient Purification

Authors: 
Aumann, L., ETH Zurich
Stroehlein, G., ETH Zurich
Morbidelli, M., Institute of Chemical and Bioengineering, ETH Zurich
Mueller-Spaeth, T., ETH-Zuerich


A countercurrent multicolumn chromatographic separation process (MCSGP-Process) has been developed, which can continuously purify large molecules e.g. peptides and proteins. The process transfers an arbitrary solvent gradient from a single column batch device to a multicolumn arrangement and enables the simultaneous use of solvent gradient chromatography and countercurrent simulated solid movement in one chromatographic device.

A continuous 6-column configuration has been applied to the purification of a polypeptide mixture and a semi-continuous 3-column setup to the separation of polypeptides and to a mixture of monoclonal antibody variants.

To increase the productivity and to decrease the investment- as well as maintenance costs of the multicolumn equipment, the process has been transferred from a continuous 6-column configuration to a semi-continuous 3-column setup.

Simulations and experiments of both configurations are discussed in detail and the experimental performance for a highly nonlinear adsorption isotherm is discussed with a simulation model.