Standing-wave Design of Three-Zone, open-loop non-isocratic SMB for purification

Abstract

Chromatography with step changes in modulator properties such as pH, solvent strength, or ionic strength to facilitate desorption is widely used in the purification of proteins and other chemicals. Step changes can be incorporated into non-isocratic simulated moving beds; however, applications of such systems have been limited because one must select numerous operating parameters (zone velocities and port velocities). The operating parameters must be selected correctly to achieve high purity, yield, and productivity and depend on a large number of system parameters (feed, material, and equipment parameters). To address this challenge, the Standing-Wave Design method has been developed for three-zone, open-loop, non-isocratic, and non-ideal systems with both linear and non-linear isotherms. This method directly links the operating parameters to the system parameters. The operating parameters can be solved from a set of algebraic equations. In contrast, for non-ideal systems, previous literature design methods require extensive search using rate model simulations, which involve solving partial differential equations at each grid point. Two examples were tested for the effectiveness of the SWD method using rate model simulations. In both examples, sorbent productivity was pressure limited. Higher pressure sorbents or equipment would lead to higher sorbent productivity. In the first example, a 3-zone open-loop simulated moving bed was designed and compared with an optimal batch step-wise elution system. Compared to batch step-wise elution systems, the simulations showed that the 3-zone open-loop SMB could give an order of magnitude higher productivity in systems with weakly competing impurities and two orders of magnitude higher in systems with strongly adsorbing impurities. In the second example, the simulations showed that an SMB designed using the Standing-Wave method could achieve an order of magnitude higher productivity than a system designed using the Triangle Theory.