Electromagnetic stirring in a microbioreactor with non-conventional chamber morphology and implementation of multiplexed mixing

Abstract

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 4.5s, 2.9s, and 2.5s 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.