Wall‐Immobilized Biocatalyst vs. Packed Bed in Miniaturized Continuous Reactors: Performances and Scale‐Up

Sustainable biocatalysis syntheses have gained considerable popularity over the years. However, further optimizations – notably to reduce costs – are required if the methods are to be successfully deployed in a range of areas. As part of this drive, various enzyme immobilization strategies have been studied, alongside process intensification from batch to continuous production. The flow bioreactor portfolio mainly ranges between packed bed reactors and wall‐immobilized enzyme miniaturized reactors. Because of their simplicity, packed bed reactors are the most frequently encountered at lab‐scale. However, at industrial scale, the growing pressure drop induced by the increase in equipment size hampers their implementation for some applications. Wall‐immobilized miniaturized reactors require less pumping power, but a new problem arises due to their reduced enzyme‐loading capacity. This review starts with a presentation of the current technology portfolio and a reminder of the metrics to be applied with flow bioreactors. Then, a benchmarking of the most recent relevant works is presented. The scale‐up perspectives of the various options are presented in detail, highlighting key features of industrial requirements. One of the main objectives of this review is to clarify the strategies on which future study should center to maximize the performance of wall‐immobilized enzyme reactors. Continuous biocatalysis production is mainly performed using packed bed and wall‐immobilized enzyme reactors. Maximization of the space‐time‐yield, STY, gives highest turnover numbers, TN, which tends to be increased with the use of wall‐enzyme reactor due to improved specific productivities, Psp. This review also clarifies the strategies to be studied in the future to maximize the wall‐enzyme reactor performances and allow its scalability.