Effects of protein aggregation in isocratic nonlinear chromatography

Roger D. Whitley, Kevin E. Van Cott, James A. Berninger, N. ‐H Linda Wang

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


A versatile reaction‐separation (VERSE) model was developed to quantitatively simulate the behavior of chromatographic separations coupled with reactions. Detailed mass transfer and reaction mechanisms are considered. Aggregation data of myoglobin and β‐lactoglobulin A verified the model. The effects of concentration, equilibrium distribution, reaction rate, convection rate, particle radius, and relative affinity are shown for a dimerizing system. When the aggregation rate is relatively slow compared with convection and mass transfer rates, the individual forms behave as separate species in frontal, elution, and displacement chromatography. For rapid aggregation rates, the individual forms behave as a single component with an average affinity. The wave asymmetry and increased spreading due to aggregation depend on relative affinity differences. Serious error may result if aggregation is overlooked in parameter estimation using frontal or pulse analysis. The dimensionless group principles developed here are useful in scaling and predicting when peak or wave splitting or merging will occur in reaction chromatography systems.

Original languageEnglish (US)
Pages (from-to)555-568
Number of pages14
JournalAIChE Journal
Issue number4
StatePublished - Apr 1991
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Environmental Engineering
  • Chemical Engineering(all)


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