Parameter estimation and rate model simulation of partial breakthrough of bovine serum albumin on a column packed with large Q Sepharose anion-exchange particles

This work presents a systematic procedure for using the general rate model to predict experimental chromatograms. The model considered axial dispersion, interfacial film mass transfer and intraparticle diffusion with parameters that have been intensively investigated in classical chemical engineering mass-transfer research. Theoretical equations, mass-transfer correlations and experimental procedures for obtaining bed voidage, particle porosity, mass-transfer parameters and Langmuir isotherm parameters are described. Three simple experiments were used to obtain system delay volume, bed voidage and particle porosity, respectively. Mass-transfer parameters were estimated using existing correlations in the literature without the need for additional experiments. A complete example was used to illustrate the approach. The model satisfactorily predicted the partial breakthrough curve of bovine serum albumin on a chromatography column packed with large anion-exchange particles with a nominal diameter of 90 μm. A parameter sensitivity analysis indicated the importance of accurate intraparticle diffusion modeling and demonstrated that lumped-particle models would be inadequate for understanding chromatographic behavior of large particles.