(316d) Scaling Down the Production of Biopharmaceuticals to Continuous Micro-Chips

We report the use of continuous flow micro-devices for the production of a glycosylated pharmaceutical product (a monoclonal antibody). We culture CHO cells on the surface of different PMMA/PDMS micro-channel chips. In particular, three different channel configurations were analyzed: (a) an ondular channel design, (b) a “zigzag” shaped micro-channel, and a (c) series of shallow compartments connected with a chanel. The surfaces of all micro-channels were textured with semi-spherical cavities and coated with fibronectin. Experiments of continuous perfusion at different flow rates were performed in the range of 0.1 to 6.0 microL/min. The velocity field at the different flow rates  and geometries was investigated through CFD.  Significant differences in attached cell density, cell proliferation, and monoclonal antibody production were observed among the different experimental scenarios. In some configurations, we observed sustained monoclonal antibody productions resulting in a steady-state productivity above 6,240 mg L^-1 day^-1, at least 100 times higher than that observed in commercial scale fed-batch systems. We discuss the effect of surface texture, system geometry and flow rate on the performance of these micro-bio-reactors.