Optimization of azeotropic protein separations in gradient and isocratic ion-exchange simulated moving bed chromatography

The separation of dilute binary mixtures of proteins by salt aided ion-exchange simulated moving bed (SMB) chromatography is optimized with respect to throughput, desorbent consumption and salt consumption. The optimal flow-rate ratios are analytically determined via an adopted “triangle theory”. Azeotropic phenomena are included in this procedure. The salt concentrations in the feed and recycled liquid are subsequently determined by numerical optimization. The azeotropic separation of bovine serum albumin and a yeast protein is used to illustrate the procedure. Gradient operation of the SMB is generally preferred over isocratic operation. A feed of azeotropic salt concentration can only be separated in a gradient SMB. Desorbent and salt consumption are always lower in gradient than in isocratic SMB chromatography.