Magnetic Separation of Immobilized Biocatalyst Enables Continuous Manufacturing with a Solids-Forming Reaction

End-to-end continuous manufacturing often provides improvements to product quality control and process economics over traditional batch processes. Design of new continuous unit operations for product isolation and catalyst recovery is necessary for realization of fully continuous processes involving difficult or coupled chemistries and separations. In this work, a magnetic separation technique is designed and applied to separate biofunctionalized catalyst particles from crystalline product in a continuous process to yield a high-purity product stream and continuously recycle catalyst to a reactor. A separator was created to recover and recycle >99.9% of catalyst in a continuous reactive crystallizer. The separator is demonstrated for enzymatic synthesis of amoxicillin, yielding pure amoxicillin trihydrate with a volumetric productivity of >250 g L-1 per day. Magnetic separation systems are envisioned to enable other continuous, heterogeneously catalyzed, solids-forming reactions.