Electromagnetic Stirring in a Microbioreactor with Non-conventional Chamber Morphology and Implementation of Multiplexed Mixing

Abstract

Background: Microbioreactors have recently emerged as novel tools for early bioprocess development. Mixing lies at the heart of bioreactor operation (at all scales), and 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: We developed a microbioreactor 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 we demonstrate mixing in cylindrical, diamond and triangular shaped reactor chambers. Mixing times between the cylindrical and diamond-shaped chamber compared well, with the shortest mixing times in both being 3.4 s. Ease of micro-bubble free priming, a typical challenge of cylindrical microbioreactor chambers, was obtained with diamond shaped chamber. Consistent mixing behaviour was observed between the constituent reactors in a duplex system, and batch and continuous culture fermentation of Staphylococcus carnosus successfully performed. Conclusion: A novel stirring method using electromagnetic actuation offering rapid mixing and easy integration with microbioreactors was characterized. The gained design flexibility 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 parallelized systems for both batch and chemostat bioreactor operation.