The most common separation method in biopharmaceutical applications is preparative chromatography with step or gradient elution. In these cases the condition of the mobile phase is changed in steps or linearly in order to achieve separation. In modern, precise and automated chromatographic systems it is possible to generate other types of elution gradients. A natural question is what can be gained if a general elution gradient profile can be generated. A methodology for dynamic optimization of general elution gradient preparative chromatography is presented. The model-based methodology uses nonlinear programming (NLP) using a direct collocation method in the JModelica.org framework. The power of the tool is discussed together with its current limitations.<br/>Two separation case studies are presented and discussed, one ion-exchange and one hydrophobic interaction separation. The base cases are three component separations using linear gradients in salt. The optimal gradients increase the performance in the two cases, both providing higher yields and shorter cycle times.

Optimal elution gradient preparative chromatography

249th National Meeting (2015)

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