Innovation in biomanufacturing using microfluidics

NATALIA BOURGUIGNON; STEVEN DINH; MAXIMILIANO PEREZ; BETIANA LERNER; SHEKHAR BHANSALI

Conferencia; The Bioprocess Summit Virtual Conference; 2020

Rapid innovation in drug discovery for personalized medicine is an important initiative for leading pharmaceutical companies and many startups. To produce innovative biopharmaceuticals in a simplified and personalized way, highly flexible, adaptable, robust, and affordable bioprocess platforms such as bioreactors are essential. The microfluidic-based microbioreactors aim to provide a microenvironment and conditions similar to those produced on a large scale, allowing their application as downscaling models1. They offer advantages such as shorter response times of the process, high surface area/volume ratio, and a homogeneous and controllable microenvironment, which is associated with a significant reduction in development costs and an increase in the quality of the bio-product obtained.In this work, we propose the development of a microfluidic bioreactor and its manufacturing method for the production of monoclonal antibodies.A novel method based on a photopolymer flexographic master mold (Fmold) was used for the microbioreactors fabrication 2. The technique allows obtaining microfluidic devices of higher volume capacity for commercial-scale production, preserving all the advantages of microfluidics in the bioprocess. The microfluidic devices were built with a glass base and polydimethylsiloxane (PDMS) coverWe manufacture two designs that will provide different output, standard size with 32 uL, and medium-size with 766 uL of volume capacity. CHO and HEK-293 cell lines were used to evaluate the cell growth and production of monoclonal antibodies. Values of 1120 pg of monoclonal antibody per cell were reached in the standard size, achieving productivity per day up to 7.3 times higher than that obtained by standard culture methodologies in T-flasks. Moreover, the antibodies produced in the microdevice showed efficient functional activity of neutralization and cellular cytokine signaling 3. The monoclonal antibodies produced in the medium bioreactor showed a 2-fold higher inhibitory activity compared to those produced in a conventional batch process. Also, E. coli producing an intracellular recombinant protein was successfully cultured in this design.These results are preliminary data for the development of the microfluidic bioreactor with a bigger size that will allow us to obtain the commercial productivity needed by biopharma companies. We are working in the scientific advancement and commercial possibilities of this biomanufacturing platform to be sufficiently flexible and adaptable at both ends of the spectrum - small batches for experimental discovery and large-scale commercial production for therapeutics. We believe our technology provides high-quality biomolecules with improved productivity and the possibility of a custom product. The automation, control, and lower stress in the microfluidic bioreactors permit for an automated biomanufacturing process, with reductions in waste, number of operations, and footprint.