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). At present, no continu- ously 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 cast Polydimethylsiloxane (PDMS) casting on poly(methyl-methacrylate) molds, or directly use high resolution 3-D-printing, to fabricate these CSTRs and an Arduino platform to measure and control key parameters, such as agitation, 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. We are currently validating 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.