(531d) Monoclonal Antibody (mAb) Production in Continuous Microfluidic Systems

Authors: 
Alvarez, M. M., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Trujillo-de Santiago, G., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
González-González, E., Tecnológico de Monterrey
del Toro Runzer, C., Harvard-MIT
Khademhosseini, A., Harvard Medical School
Hernández Medina, R., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
An unfulfilled need exists for cost-effective systems that can screen production conditions for biopharmaceutical compounds. At the lab scale, culture bottles and Erlenmeyer flasks continue to be the first and preferred reactor type for the development and selection of culture conditions (i.e., culture medium, addition protocols, temperatures, additives, among others) used to produce biopharmaceutical compounds (i.e., monoclonal antibodies and other recombinant proteins). These are batch systems that (a) do not provide a tight control of the cell microenvironment, and (b) fail to appropriately mimic commercial production scale conditions.

Here, we illustrate the use of continuous microfluidic systems to perform the operations of selection and screening of high-titer mAb producers. One system consists of a long continuous microfluidic channel (CMC) in which CHO cells remain anchored on the bottom surface while a stream of culture medium is fed continuously through the channel. We show that this simple system can be scaled up (by parallel scaling) to enable production in the order of tens to hundreds of mg day-1.

A second system mimics the operation and dynamic behavior of a continuous stirred tank system (CSTR). We show that this system can achieve different steady state conditions at different flow rates. The low volume of this mini-CSTR (1,500 microliters) allows the use of extremely small quantities of culture medium to characterize the kinetic behavior of CHO cell mAb producers and to provide cost-effective screening of process conditions.

Both the CMC and the mini-CSTR are fully controlled by an Arduino system that regulates temperature and agitation, while monitoring cell concentration.