Optimization of ion-exchange displacement separations. I. Validation of an iterative scheme and its use as a methods development tool

J Chromatogr A. 2000 Apr 21;876(1-2):51-62. doi: 10.1016/s0021-9673(00)00138-2.

Abstract

Displacement chromatography has been demonstrated to be a powerful, high-resolution preparative tool. The performance of displacement systems can be affected by a variety of factors such as the feed load, flow-rate, initial salt concentration and the displacer partition ratio. Thus, the optimization of displacement separations is a uniquely challenging problem. In this manuscript, an iterative optimization scheme has been presented whereby one can identify the optimum operating conditions for displacement separations at a given level of loading on a given resin material. The solid film linear driving force model has been employed in concert with the Steric Mass Action formalism of ion-exchange chromatography to describe the chromatographic behavior in these systems. Simple pulse techniques have been employed to estimate the transport parameters. The iterative scheme has been validated using a rigorous Feasible Sequential Quadratic Programming algorithm. Finally, the utility of the iterative optimization scheme as a methods development tool for displacement separations has been demonstrated for a difficult separation. The results indicate that the use of the optimization scheme leads to significantly better performance than standard rules of thumb.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Chromatography, Ion Exchange / methods*
  • Proteins / analysis
  • Quality Control
  • Reproducibility of Results
  • Salts / chemistry

Substances

  • Proteins
  • Salts