Application: Impurity Removal from Clarified Cell Culture
Initial experiments sought to test the hypothesis that QSD could be used in flow-through mode following cell culture clarification to remove impurities during one quick in-line step.
A 0.5 g/L model IgG cell culture solution at a pH of 7.5 and conductivity of 9.8 ms/cm was filtered through QSD and three other anion-exchange membranes to test this notion. After the cell mass was removed using a 0.45 μm polysulfone hollow fiber microfilter in tangential flow mode 100 membrane volumes (MV) of clarified cell culture solution was applied to each membrane at a flow rate of 5 MV/min.
Host cell protein (HCP) and DNA concentrations in the flow through material of each membrane were measured using ELISA (HCP) and the Quant-iT™ dsDNA BR assay kit (DNA) from Invitrogen.
As Figure 1 illustrates, QSD successfully removed contaminants from clarified cell culture. The pH (7.5) and conductivity (9.8 ms/cm) of the cell culture solution proved to be in the optimal range for QSD.
Excellent removal of contaminants coupled with flexible flow rates intrinsic to membrane adsorbers suggests that QSD is a robust tool for use post-clarification. The efficiency at which impurities are eliminated reduces the load on purification steps downstream of QSD while the flow rate independent binding and salt tolerance support in-line compatibility of QSD with a microfilter or other clarification steps without the need for solution adjustment.