BACKGROUND Microbioreactors have emerged as novel tools for early bioprocess development. Mixing lies at the heart of bioreactor operation (at all scales). The successful implementation of micro-stirring methods is thus central to the further advancement of microbioreactor technology. The aim of this study was to develop a micro-stirring method that aids robust microbioreactor operation and facilitates cost-effective parallelization. RESULTS A microbioreactor was developed with a novel micro-stirring method involving the movement of a magnetic bead by sequenced activation of a ring of electromagnets. The micro-stirring method offers flexibility in chamber designs, and mixing is demonstrated in cylindrical, diamond and triangular shaped reactor chambers. Mixing was analyzed for different electromagnet on/off sequences; mixing times of 4.5 s, 2.9 s, and 2.5 s were achieved for cylindrical, diamond and triangular shaped chambers, respectively. Ease of micro-bubble free priming, a typical challenge of cylindrical shaped microbioreactor chambers, was obtained with a diamond-shaped chamber. Consistent mixing behavior was observed between the constituent reactors in a duplex system. CONCLUSION A novel stirring method using electromagnetic actuation offering rapid mixing and easy integration with microbioreactors was characterized. The design flexibility gained enables fabrication of chambers suitable for microfluidic operation, and a duplex demonstrator highlights potential for cost-effective parallelization. Combined with a previously published cassette-like fabrication of microbioreactors, these advances will facilitate the development of robust and parallelized microbioreactors.
Tan, Christabel K. L., Matthew J. Davies, Daniel K. McCluskey, Ian R. Munro, Mauryn C. Nweke, Mark C. Tracey, Nicolas Szita
J. Chem. Technol. Biotechnol.