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Quantifying process tradeoffs in the operation of chromatographic sequences
Sheau-Huey Ngiam1, Daniel G Bracewell, Yuhong Zhou
1Innovative Manufacturing Research Centre for Bioprocessing, Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, United Kingdom.
Biotechnology Progress
|August 2, 2003
Summary
This study introduces a rapid method using fractionation diagrams to analyze tradeoffs between yield and purity in chromatographic separations. It aids in optimizing sample collection strategies for complex purification sequences.
Area of Science:
- Biochemistry and Analytical Chemistry
- Chromatographic Separation Science
Background:
- Chromatographic sequences require careful balancing of yield and purity.
- Predicting the impact of decisions in early steps on later ones is challenging.
Purpose of the Study:
- To develop a rapid method for analyzing process tradeoffs in chromatographic sequences.
- To extend the fractionation diagram approach to multi-step chromatographic separations.
Main Methods:
- Construction of fractionation and maximum purification factor versus yield diagrams.
- Application of the method to a two-step separation: hydrophobic interaction chromatography (HIC) followed by size exclusion chromatography (SEC).
Main Results:
- The fractionation diagram approach effectively visualizes yield-purity tradeoffs.
- Demonstrated straightforward analysis of performance in a HIC-SEC sequence.
- Highlighted the impact of HIC cut-point decisions on subsequent SEC performance.
Conclusions:
- The proposed methodology provides a fast and precise tool for predicting sample fraction collection strategies.
- Facilitates identification of critical process tradeoffs in multi-step chromatography.
- Informs cut-point decisions to optimize overall purification efficiency.