Development and characterization of a microfluidic magnetic oscillation reactor for enzymes

Process development poses one of the main bottlenecks during development of biocatalytic processes for fine and bulk chemicals. Therefore novel tools to decrease the cost of process development have come into the focus of interest. While modelling and small scale liquid handling in multi well based platforms are already employed, there is still a lack of continuous microfluidic reaction systems for enzyme process development. In this thesis the magnetic oscillation reactor for enzymes (µMORE), a novel continuous microfluidic reactor concept for process optimization has been developed. The system is mixed by magnetic beads, on which the enzyme is immobilized, by utilization of an oscillating magnetic field. The concept has been designed to allow for simple parallelization of multiple reactors. A six-fold enzyme microreactor system was constructed. The novel reactor system was developed, characterized and finally tested with benzoylformate decarboxylase from Pseudomonas putida. This enzyme catalyzes the carboligation of benzaldehyde and acetaldehyde to (S)-2-hydroxypropiophenone. The results indicate that the system provides a useful tool for enzyme process optimization, generating process parameters that are useful for scale up of the process from micro- to bench scale.