(320e) Flow-through Chromatography of Proteins As a Continuous and Integrated Separation Method
AIChE Annual Meeting
Tuesday, November 12, 2019 - 1:50pm to 2:10pm
An operation method known as flow-through chromatography (FTC) is considered to be an efficient method for separating a target protein as the flow is continuous. In FTC, a target protein is eluted from the chromatography column without adsorption whereas contaminants are strongly bound. Since at least two different modes of chromatography are needed in order to remove contaminants, two FTC columns have to be connected in order to build the continuous process. This is not an easy task since the mobile phase properties (pH, salt, buffer ions) are different for the two columns.
In this paper, we investigated how FTC can be designed based on linear gradient elution (LGE) data based on our LGE model. As a model separation system removal of dimer from BSA monomer was chosen. Model calculation showed that FTC is very sensitive to a small change in salt concentration and/or pH of the mobile phase. We also examined the efficiency of FTC processes in terms of impurity removal efficiency from the cell culture broth containing monoclonal antibody. It was found that two FTC (anion exchange chromatography - cation exchange chromatography) can remove impurities efficiently when the mobile phase pH and conductivity were properly chosen. It was also shown that the two columns can be connected for a pseudo continuous FTC operation.