The production of recombinant monoclonal antibodies (mAbs) for therapeutic use is an expanding area of the biopharmaceutical industry. However, the traditional production in bioreactors faces challenges related to the quality of product, glycosylation and reproducibility. One approach to control the quality of product is to reduce the scale of the production through microfluidic devices. In this work is presented a PDMS/glass microfluidic device with sequential cisterns in four microchannels for culture of mAb expressing cells. First, we evaluated the
conditions for seeding CHO-K1 (Chinese Hamster Ovary) cells in the microfluidic device. After seeding 2x105 cells/mL in the device, we observed a homogeneous distribution, achieving cell monolayer of 620 cells/mm2 at day 7 of culture. The Comsol 5.2a software package was used to simulate flow velocity and shear stress in the microchannels. The computational 3D simulation showed that the configuration of the microchannels provided an optimally distribution of the fluid across the cell culture surface. A maximum velocity of 2 m/s was observed the
center of the microchannels, but in the cisterns it was at 0.25 m/s. The calculated shear stress shows values of 0.1 to 0.6 Pa for the cisterns and the microchannels respectively. These values are within the observed in the physiological environment, suitable to sustain successive cycles of cell culture without the need for a new inoculation. The productivity in the microfluidic device was evaluated in two cell lines CHO-K1 and HEK293 (Human Embryonic Kidney) that express the mAb anti-IFN- α2b. This mAb is a scFv-Fc minibody developed for the treatment of Systemic Lupus Erythematosus. Cells were able to grow, reaching confluence and covering the total area of the device. The culture for mAbs production in the devices was extended for 18 days. The overall productivity of anti hIFN α2b per cell in cell culture supernatant was evaluated by indirect ELISA. Interestingly, the productivity in the devices using both cell lines was up to 7.5 fold higher compared to that obtained in T flasks run in parallel. Moreover, the mAbs produced in the devices showed no significant differences in the neutralizing antiproliferative activity of the hIFN α2b or the cytokine cell signaling compared to the mAbs produced by standard methods. These results show that cell lines can be cultured in microfluidic devices in monolayer, with low shear stress, with significantly higher productivity compared to standard culture conditions, without affecting quality attributes of the product. These observations suggest that microfluidic devices could be an interesting option for development of mAbs and other recombinant proteins with potential for therapeutic use.