In batch chromatography of peptides and oligos, impure side fractions often have to be discarded to reach a certain product purity. With YMC’s patented MCSGP approach, impure product-containing side fractions are internally (automatically) recycled in a periodic closed-loop process while pure product is continuously extracted. Thereby, little product is lost, and the yield of pure product is maximized without any accumulation of impurities while retaining target purity.
Multicolumn Countercurrent Solvent Gradient Purification process (MCSGP) is a continuous process operated by Contichrom 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 by the achievement of significantly 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.
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 are required. MCSGP (red) operates at an optimum in 3D space, with high yield and purity at increased productivity.
High performance liquid chromatography employing MCSGP provides a novel purification technology for peptides or oligos 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 a significantly higher yield without compromising target purity. The process allows an up to tenfold higher productivity with potentially 75% lower solvent consumption, providing an overall attractive economical production scenario and allowing to push the boundary of economic synthesis of long peptides.
MCSGP can purify complex biological mixtures, such as omega-3 eicosapentaenoic acid ethyl ester (EPA-EE) to a high target purity in a single purification step. Generic fish oil feed with a feed purity of 74% EPA-EE was subjected to an MCSGP process design to achieve a target purity of >97% EPA-EE. MCSGP was operated under high pressures in countercurrent mode with internal recycling of impurity-containing side fractions with docosahexaenoic acid ethyl ester (DHA-EE) as the main impurity, extracting continuously pure EPA-EE and discarding impurities without significant product loss. Five cycles of MCSGP achieved significantly improved yield at target purity (+ 250%), productivity throughput (+ 590%), and reduced solvent consumption by 75% compared to batch HPLC.
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.
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, straightforward, 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.
YMC / 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.
The challenges in the purification of oligonucleotides (including RNA/DNA) and peptides of time, cost, yield, and purity can be overcome with a technique called MCSGP.
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Contichrom CUBE bench top instrument
YMC Contichrom® TWIN HPLC with MCSGP
TWIN 500 LPLC Tour
Technology and Economics for the Purification of Oligonucleotides (and Peptides) by Twin-Column Continuous Chromatography
Process Intensification for the Purification of Peptidomimetics: The Case of Icatibant through Multi-column Countercurrent Solvent Gradient Purification (MCSGP)
Comparison of Multicolumn Capture Processes
Process Control and Optimization by AutomAb
Dynamic Process Control (MControl®) for Countercurrent Polish Processes (MCSGP)
Hybrid Approach to Continuous Downstream Biomanufacturing
Scale-Up of Twin-Column Periodic Counter-Current Chromatography for MAb Purification
Affinity Capture of F(ab’)2 Fragments: Using Twin-Column Countercurrent Chromatography
Purifying Common Light-Chain Bispecific Antibodies
Oligonucleotides: Current Trends and Innovative Applications in the Synthesis, Characterization, and Purification
Model assisted process characterization and validation for a continuous two column protein A capture process
Continued insights into virus clearance validation across continuous capture chromatography, Journal of Chromatography A
Comparison of batch and continuous multi-column protein A capture processes by optimal design
Model-assisted process characterization and validation for a continuous two-column protein A capture process
Virus Clearance Validation across Continuous Capture Chromatography
Increasing Capacity Utilization in Protein A Chromatography
AutomAb®: UV-based Dynamic Process Control for CaptureSMB
Twin-column CaptureSMB: a novel cyclic process for protein A affinity chromatography
Enabling High Purities and Yields in Therapeutic Peptide Purification Using Multicolumn Countercurrent Solvent Gradient Purification
Comparison of batch and MCSGP chromatography for the purification of oligonucleotides and peptides showing improvements in yield/purity through MCSGP
Contichrom CUBE bench-top FPLC – a chromatographic new tool for drug discovery and purification
Mini Webinar Library : Peptide, Oligo, DNA, and RNA Continuous Purification by HPLC MCSGP
Mini Webinar Library on mABs and rProteins by YMC TWIN Column CaptureSMB
Mini Webinar Library on mAbs and rProteins by YMC TWIN Column CaptureSMB
Multi-Column Chromatography Modeling Tool
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