Martin Bufajer, Jose Mauricio; (2021) Design of Counter-current Tangential Chromatography to Improve Resin Lifetime and Operational Simplicity. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis aims to understand current counter-current tangential chromatography (CCTC) design in bioprocessing. It assesses the structural and performance changes that occur in agarose- and synthetic-based chromatography resins as they are exposed to different equipment designs in order to improve resin lifetime and operational simplicity. The mixing and tangential flow filtration modules were characterized to provide a minimum residence time of 120 seconds and an operational flux of 70 LMH. The chromatography resin was used in different equipment designs for 36 hours to assess the performance and structural properties. The results indicate that the shear caused by peristaltic pumps and hollow fibres caused an average size reduction of 5% in both synthetic and agarose resins. However, the agarose-based resin had significantly deformed. Both resins exhibited a deviation of 5% from their original dynamic binding capacity. The system’s separation performance was tested using a two-component separation (BSA and myoglobin) and a salt step gradient separation of ovalbumin variants. The two-component separation was a success with a purity and a yield of 99.9% and 93.2%, respectively. In contrast when attempting the more challenging separation of closely related ovalbumin variants using a step-gradient separation the inline mixing in the CCTC system prevented successfully separation. Different coiled flow inverter reactor (CFIR) designs were explored as viable mixing modules for their operational flexibility, system simplification and cost-effectiveness. The best performing CFIR (λ 13.8) showed inferior results to the set of static mixers showing a normalised batch binding capacity of 0.9 and 1.0, respectively. However, this CFIR showed to be a more cost-effective reactor by being 17x cheaper while operating at 90% binding capacity efficiency. The project established critical considerations for adsorbent use and CFIRs as a simplified and cost-effective mixing option, which aids the adoption of this technology for biopharmaceutical manufacturing.

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