A generalized approach to thermodynamic properties of biomolecules for use in bioseparation process design

Tangir Ahamed, Marcel Ottens, Beckley K. Nfor, Gijs W.K. Van Dedem, Luuk A.M. Van Der Wielen

Research output: Contribution to journalArticlepeer-review

Abstract

Bioseparation techniques exploit the differences of physicochemical or thermodynamic properties between the product and the contaminants. Rapid development of a downstream process, therefore, requires physicochemical and thermodynamic characterization of the components to be separated. In this paper, we investigate whether a generalized thermodynamic interrelation exists among different parameters. For instance activity coefficients, osmotic virial coefficients and the solubility of macromolecules are interrelated to each other. Experimental determination of any one of these parameters can be translated across the boundaries of different separation techniques. A number of downstream separation processes, including size-exclusion chromatography, hydrophobic-interaction chromatography, reversed-phase chromatography, aqueous two-phase separation, crystallization and precipitation, are found to be explained and designed using this generalized thermodynamics. This generalization of thermodynamic properties together with high-throughput experimentation provides a systematic and high-speed approach to bioseparation process development and optimization. The applicability of this approach for bioseparation process design was investigated by a case study on nystatin, a medium-sized biomolecule. The distribution coefficients of nystatin in reversed-phase chromatography showed straightforward relationship with the solubilities at various solvent compositions and the experimental data supported the trend of the relationship.

Original languageEnglish
Pages (from-to)268-282
Number of pages15
JournalFluid Phase Equilibria
Volume241
Issue number1-2
DOIs
Publication statusPublished - 15 Mar 2006
Externally publishedYes

Keywords

  • Activity coefficient
  • Biomolecule
  • Bioprocess design
  • Bioseparation
  • Nystatin
  • Osmotic virial coefficient

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