Control strategy for multi-column continuous periodic counter current chromatography subject to fluctuating inlet stream concentration

• Published in: Journal of Chromatography A Vol. 1667; p. 462884
• Main Authors: Gerstweiler, Lukas, Billakanti, Jagan, Bi, Jingxiu, Middelberg, Anton P.J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 29.03.2022
• Subjects: Bays; Chromatography; Computer Simulation; Continuous downstream processing; control methods; Controlling; countercurrent chromatography; Diffusion; dispersions; feeds; Fluctuating concentration; Periodic counter current chromatography; Process integration; streams; Continuous downstream processing; Controlling; Fluctuating concentration; Process integration; Periodic counter current chromatography
• ISSN: 0021-9673; 1873-3778
• DOI: 10.1016/j.chroma.2022.462884

•Control strategy for periodic counter current chromatography with changing inlet feed concentration.•Proposed method enabled constant column loading while using a standard method resulted in inconsistent column loading.•Easily adaptable for commercially available PCC systems.•In-silico modeling unveiled that product column breakthrough is accurately calculated. Fluctuations of the inlet feed stream concentration are a challenge in controlling continuous multi-column counter current chromatography systems with standard methods. We propose a new control strategy based on calculated product column breakthrough from UV sensor signals by neglecting an impurity baseline and instead using the impurity to product ratio. This calculation is independent of the inlet feed concentration. In-silico simulation showed that the proposed method can calculate the product column breakthrough perfectly even with fluctuating and highly unstable inlet feed concentration during a loading cycle. Applying the proposed method to control a three column periodic counter current chromatography process with fluctuating inlet feed concentration resulted in constant column loading in each cycle, while using the standard method failed to do so. Unavoidable band broadening caused by diffusion and dispersion has been identified as an inherent limiting factor for accurate calculation of column breakthrough comparing inlet and outlet UV signals. The proposed advanced calculations increase the robustness of periodic counter current chromatography and extend the capability to process unstable inlet streams.