AN INNOVATIVE COILED FLOW INVERTER REACTOR FOR CONTINUOUS REFOLDING OF DENATURED RECOMBINANT PROTEINS AND OTHER MIXING OPERATIONS

摘要

The present invention provides an innovative reactor design based on coiled flow inverter geometry for carrying out continuous protein refolding reactions in-vitro by dilution method. The reactor consists of an inline mixer followed by a design to provide cross sectional mixing of diluted denatured proteins through flow inversion thereby changing the. direction of centrifugal force in helically- coiled tube. The unique feature of Coiled Flow Inverter Reactor � (CFIR) is that it improves contact amongst the various entities such �as chaotropes, stabilizers, buffer ions, reducing and oxidizing agents and the protein molecules, within the cross section in a low shear environment, thus providing a sharp residence time distribution and stabilizing the refolding reaction by reducing the side reactions that otherwise result in formation of aggregates and oxidized impurities and result in reduced refolding yield. The reactor is also exemplified for its versatility of being applicable to other biotech unit operations by demonstration of continuous precipitation of impurities from cell culture harvest of a monoclonal antibody therapeutic. The proposed invention can be used for achieving homogeneity in concentrations of protein and other reactants throughout the process so as to achieve the desirable outcome of the resulting reaction for protein refolding, precipitation, viral inactivation etc.