title: Use of MiniColumns for linear isotherm parameter estimation and prediction of benchtop column performance.
abstract: In this paper, a comparison between experimental chromatography data and column simulations is carried out to determine the efficacy of using miniaturized chromatography columns (MiniColumns) for both column modeling parameter estimation and process development. Normalization of the data with respect to column volumes along with appropriate translations to account for system differences is shown to result in comparability of the experimental data for the MiniColumn and benchtop systems. A parameter estimation protocol is then employed to determine the linear steric mass-action (SMA) isotherm and lumped mass transport parameters for two cation exchange resins. The models are then validated and simulations using different parameter sets from the MiniColumn and benchtop systems are shown to result in similar predicted chromatography profiles and calculated retention volumes. The parameters generated from the MiniColumn system are demonstrated to be well suited for predicting experimental data from the benchtop system. These simulation results, the ability to operate MiniColumns in parallel, and the significantly lower material requirements per experiment support an industry trend toward increased usage of miniaturized chromatography columns as a scale-down model for process development.
authors.affiliation: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180, United States.
authors.forename: William R
authors.initials: WR
authors.lastname: Keller
authors.affiliation: Purification Process Sciences, MedImmune LLC, Gaithersburg, MD 20878, United States.
authors.forename: Steven T
authors.initials: ST
authors.lastname: Evans
authors.affiliation: Purification Process Sciences, MedImmune LLC, Gaithersburg, MD 20878, United States.
authors.forename: Gisela
authors.initials: G
authors.lastname: Ferreira
authors.affiliation: Purification Process Sciences, MedImmune LLC, Gaithersburg, MD 20878, United States.
authors.forename: David
authors.initials: D
authors.lastname: Robbins
authors.affiliation: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180, United States. Electronic address: crames@rpi.edu.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Cramer
mesh_terms: D002411:Cation Exchange Resins; D002852:Chromatography, Ion Exchange / Q000295:instrumentation*
chemical_list: D002411:Cation Exchange Resins
keywords: Column modeling; High throughput screening; MiniColumns; Parameter estimation; Scale-down models