(466d) Mini Continuous Stirred Tank Reactors (mini-CSTR) for Cell and Tissue Culture Applications

Authors: 
Gallegos Martínez, S., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Mendoza Buenrostro, C. C., Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias
Rellstab-Sanchez, P. I., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Hernández Medina, R., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Anaya Morales, I., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Samandari, M., College of Engineering, University of Tehran
Gonzalez Gonzalez, E., EverDo S.A. de C.V., Calle Sexta 816, Col. La herradura, CP. 67140, Guadalupe, Nuevo León, México.
García Rubio, A., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Rodríguez-González, C. A., Departamento de Mecatrónica y Eléctrica, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Trujillo-de Santiago, G., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
Alvarez, M. M., Centro de Biotecnología-FEMSA, Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias
An ideal cell culture system will provide a well-controlled, homogeneous, and steady environment for cells and tissues. For instance, well-controlled steady states would greatly benefit organ-on-chip experiments, stem cell culture, and tissue propagation (among other relevant biomedical applications). However, at present, no continuously stirred mini-reactors are commercially available for lab-scale culture applications.

We are developing simple, low-cost, and user-friendly miniaturized continuously stirred tank reactors (CSTRs) for biomedical and biotechnological agitations. These well-mixed mini-CSTRs will enable cost-efficient continuous culture at small scales. We use high resolution 3D-printing to fabricate these CSTRs and an Arduino platform to measure and control key parameters, such as temperature and pressure, in small portable incubators. Nutrients are fed by syringe pumps, and well-controlled low-speed (benign) agitation is provided by a custom-made magnetic system. Since the reactor behaves as a well-mixed reservoir, all bulk-liquid concentrations can be measured at the outlet stream, thereby greatly reducing the need for intrusive instrumentation. Here we present an exhaustive validation of the mixing performance of this system, including results from computational fluid dynamic experiments (CFD) at different agitation speeds. In addition, we present preliminary results of the use of this culture platform in two model applications: (a) the extended culture of breast cancer spheroids, and (b) the culture of Chinese Hamster Ovary Cells (the warhorse for biopharmaceutical production) for continuous production of biopharmaceutical compounds.