title: Quantifying process tradeoffs in the operation of chromatographic sequences.
abstract: A method for the rapid representation of key process tradeoffs that need to be made during the analysis of chromatographic sequences has been proposed. It involves the construction of fractionation and maximum purification factor versus yield diagrams, which can be completed easily on the basis of chromatographic data. The output of the framework developed reflects the degree of tradeoff between levels of yield and purity and provides a fast and precise prediction of the sample fraction collection strategy needed to meet a desired process specification. The usefulness of this approach for the purposes of product purification and contaminant removal in a single chromatographic step has been successfully demonstrated in an earlier paper and it is now extended by application to a chromatographic sequence: the separation of a hypothetical three-component protein system by hydrophobic interaction chromatography (HIC) followed by size exclusion chromatography (SEC). The HIC operation has a strong impact upon the subsequent SEC step. The studies show how the analysis of performance in such a chromatographic sequence can be carried out easily and in a straightforward fashion using the fractionation diagram approach. The methodology proposed serves as a useful tool for identifying the process tradeoffs that must be made during operation of a sequence of chromatographic steps and indicates the impact on further processing of the cut-point decisions that are made.
authors.affiliation: Innovative Manufacturing Research Centre for Bioprocessing, Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, United Kingdom.
authors.forename: Sheau-Huey
authors.initials: SH
authors.lastname: Ngiam
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bracewell
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Titchener-Hooker
mesh_terms: D000327:Adsorption; D000465:Algorithms; D005591:Chemical Fractionation / Q000379:methods*; D002845:Chromatography / Q000379:methods*; D002850:Chromatography, Gel / Q000379:methods; D045424:Complex Mixtures / Q000737:chemistry* / Q000302:isolation & purification*; D003198:Computer Simulation; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D011506:Proteins / Q000737:chemistry* / Q000302:isolation & purification*; D011786:Quality Control
chemical_list: D045424:Complex Mixtures; D011506:Proteins