Continuous Production of Monoclonal Antibodies in Attached CHO CELL Culture MINI-Reactors: Use of Zein Foams As a Matrix for CELL Adhesion

We present proof-of-principle results of the use of continuous mini-reactors (1mL scale) for the production of monoclonal antibodies in adherent CHO cell cultures using zein-foams as the scaffold for cell adhesion.  Zein foams were produced from thermo-plasticized zein exposed to supercritical CO₂ foaming.

CHO cells were able to colonize and proliferate on the surface of the zein foams achieving confluence under continuous flow. Monoclonal antibody concentrations of 60 mg/L were achieved under steady state conditions at residence times of 1 hr. The maximum cell density of Chinese hamster ovary (CHO) cell cultures grown in the foam mini-bioreactors exceed 10 fold that observed in their stirred tank counterparts. Remarkably, their productivity is 100 fold higher with respect to the one observed in optimized fed-batch cultures in instrumented bioreactors (using the same cell line). Our results demonstrate that cell anchorage growth using plant-derived foamy surfaces is an attractive strategy for the production of biopharmaceutical compounds for screening and inclusively pilot plant scenarios.