Closed loop control of the multi-column solvent gradient purification process

A PID controller able to support the operator in the operation of the Multi-column Countercurrent Solvent Gradient Purification (MCSGP) process which is a continuous, countercurrent chromatographic process has been developed. As measurement, only the online UV signals at each column outlet are used. This guarantees a simple and cheap control implementation and a fast control action. Accordingly, the controller does not guarantee any purity or yield value, but simply that the withdrawn window of the product is centered in a specific region of the UV chromatogram where the purity specifications are expected to be satisfied. This can be determined by the operator based on the batch chromatogram selected for designing the MCSGP operating conditions. Thus the controller provides a reliable and efficient tool for the operator to run properly a MCSGP unit in combination with suitable offline analytics for the quantification of purity and yield. The applications are discussed involving the purification of a model protein and a peptide. It is shown that the developed controller is effective in driving the unit to steady state during start up and in keeping a stable steady state while rejecting external disturbances.

► We developed a controller for the MCSGP process based on the online UV signal.
► The controller was applied in the field of protein and peptide purification.
► The controller is able to hold a defined operation point.
► Startup of the continuous process is guided by the controller.
► External disturbances can be rejected and product purity is restored.