Chromacon

MCSGP for Peptide Purification

MCSGP economic benefits

Multi-column Counter-current Solvent Gradient Purification process (MCSGP) is a continuous process operated on the lab-scale Contichrom CUBE and Contichrom Twin pilot / process scale equipment. It provides significant economic benefits compared to single column batch chromatography operated at low, medium and high pressure. The economic benefits are derived from the achievement of significant higher yield at target purity, lower buffer/solvent consumption and higher productivity. Economic benefits are always obtained, not depending on products or applications, yet, the more complex the separation task, the higher the benefits obtained through the MCSGP process.

Application of MCSGP for peptide purification

High pressure liquid chromatography employing MCSGP provides a novel purification technology for peptides produced by chemical synthesis. MCSGP offers a step change in efficiency compared to batch HPLC processing. With MCSGP, two identical reverse-phase columns are operated under high pressures in countercurrent mode with internal recycling of impurity-containing side fractions, extracting continuously pure product and discarding impurities without significant product loss. Peptides can be purified at preparative / production scale with significantly higher yield without compromising target purity. The process allows an up to 10-fold higher productivity with typically 75% lower solvent consumption providing an overall economical attractive production scenario and allowing to push the boundary of economic synthesis of long peptides.

MCSGP process principle and design

The MCSGP process is the only known ternary continuous separation process that can unlock the yield-purity trade-off dilemma by providing high yield at target purity, thereby enhancing productivity.

Selected publications:

  • Process Intensification for the Purification of Peptidomimetics: The Case of Icatibant through Multicolumn Countercurrent Solvent Gradient Purification (MCSGP). De Luca, C., Felletti, S., Bozza, D., Lievore, G., Morbidelli, M., Sponchioni, M., Cavazzini, A. 2021. Ind  . Closely. Chem. Res. 2021, 60, 18, 6826-6834
  • Experimental design of a twin-column countercurrent gradient purification process. Steinebach F, Ulmer N, Decker L, Aumann L, Morbidelli M Journal of Chromatography A 2017, 1492, 26
  • Enabling high purities and yields in therapeutic peptide purification using multicolumn countercurrent solvent gradient
    T. Müller-Späth, G. Ströhlein, O. Lyngberg, D. Maclean,   Chimica Oggi-Chemistry Today 2013, 31 (5), 56-61 . open access.

The MCSGP process can provide maximum yield and purity, even in cases where conventional batch processes require to compromise on either one..

Figure: Yield-purity-productivity relationship of MCSGP versus conventional batch chromatography. Single column batch processes (blue) operate on a low productivity level without the potential for productivity gains, when high yield and purity is required. MCSGP (red) operates at optimum in 3D space with high yield and purity at increased productivity.

The process eliminates the need for re-chromatography and the associated time and resources for sampling and testing. The MCSGP technology is patented by ChromaCon, and its process principle is intuitive, straight forward and allows a high degree of automation. This is visualized in an animation of the two-column MCSGP design. A dedicated software wizard in the accompanying ChromIQ software allows for easy batch-to-continuous process design, transfer and optimization.

ChromaCon offers customized services and expertise to companies and academics who wish to quickly advance their projects or test MCSGP capabilities before investing in a system.