Continuous Monoclonal Antibody Production On a Chip

An important number of experimental reports are now available on the use of micro-devices in cell culture applications,  including a few examples of continuous flow micro-devices for cell culture. However, reports on the use of micro-devices for the production of recombinant proteins are still scarce. To our knowledge, no previous study has documented the production of biopharmaceuticals in continuous micro-devices.

We report a proof-of-principle for the use of micro-devices as continuous bioreactors for the production of a glycosylated pharmaceutical product (a monoclonal antibody). We culture CHO cells on the surface of PMMA/PDMS micro-channels textured with semi-spherical cavities and coated with fibronectin. Three different micro-channel geometries were tested in a continuous flow regime in the range of  0.1 to 6.0 microL/min. Both, the geometry of the micro-device and the flow rate had a significant effect on cell adhesion, cell proliferation, and monoclonal antibody production. In the most proficient configuration, we observe a steady-state productivity above 7,000 mg L^-1 day^-1, at least 100 times higher than that observed in commercial scale fed-batch systems.

Immediate applications of these micro-devices are the optimization of process conditions for CHO cell production, the comparison of CHO cell clones, or the precise evaluation of productivity of a cell line.