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A continuous multicolumn countercurrent solvent gradient purification (MCSGP) process.

Lars Aumann1, Massimo Morbidelli

  • 1ETH Zurich, Institute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, Hoenggerberg, HCI, 8093 Zurich, Switzerland.

Biotechnology and Bioengineering
|June 16, 2007
PubMed
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A novel multicolumn solvent gradient purification process (MCSGP) enhances biomolecule purification. This method combines batch and continuous countercurrent chromatography, achieving near 100% yield for Calcitonin, significantly outperforming single-step batch methods.

Area of Science:

  • Biochemistry
  • Chemical Engineering
  • Chromatography

Background:

  • Biomolecule purification commonly uses solvent gradient batch chromatography.
  • Industrial chromatography faces challenges with low efficiency, axial dispersion, and mass transfer resistances, often requiring multiple steps.
  • High-value biomolecules necessitate efficient, high-yield purification methods like countercurrent chromatography (e.g., simulated moving bed - SMB).

Purpose of the Study:

  • To introduce a novel multicolumn solvent gradient purification process (MCSGP).
  • To combine the advantages of solvent gradient batch chromatography and continuous countercurrent SMB.
  • To improve separation efficiency, yield, and productivity in large-scale biomolecule purification.

Main Methods:

  • The MCSGP process utilizes multiple chromatographic columns with position switching opposite to flow direction.

Related Experiment Videos

  • Columns are equipped with gradient pumps for precise modifier concentration control.
  • Internal countercurrent recycling of non-pure streams and batch operation of some columns are incorporated.
  • Main Results:

    • The MCSGP process was successfully applied to purify an industrial stream containing 46% Calcitonin.
    • The MCSGP unit achieved a yield close to 100% for the desired purity.
    • Single-column batch chromatography yielded a maximum of 66% for the same purification task.

    Conclusions:

    • The MCSGP process offers a significant advancement in biomolecule purification efficiency and yield.
    • This hybrid approach effectively addresses limitations of traditional batch chromatography for industrial applications.
    • MCSGP demonstrates superior performance, particularly for valuable and complex biomolecules like Calcitonin.