Use of MiniColumns for linear isotherm parameter estimation and prediction of benchtop column performance

• Published in: Journal of Chromatography A Vol. 1418; pp. 94 - 102
• Main Authors: Keller, William R., Evans, Steven T., Ferreira, Gisela, Robbins, David, Cramer, Steven M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.10.2015
• Subjects: Cation Exchange Resins; Chromatography, Ion Exchange - instrumentation; Column modeling; High throughput screening; MiniColumns; Parameter estimation; Scale-down models; High throughput screening; Scale-down models; Parameter estimation; MiniColumns; Column modeling
• ISSN: 0021-9673; 1873-3778
• DOI: 10.1016/j.chroma.2015.09.038

•Provides transformations to compare data between MiniColumn and benchtop systems.•Provides experimental protocol for parameter estimation using only MiniColumn data.•Provides a simple model describing column performance requiring only 3 parameters.•Demonstrates predictive use of SMA model from parameters estimated with MiniColumns. 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.