μ-structured devices as tools for screening process intensification in biocatalysis

Biocatalytic processes have been emerging as potential replacements of traditional chemical synthesis in many industrial relevant production processes. However the implementation of new biocatalytic processes can be a very challenging procedure which requires both biocatalyst and process screening and characterization for economic evaluation before scale-up.

Microstructured devices have been used as screening tools that allow paradigm changes in process development by shortening process development times through modularity and intensification. Customized reactor designs and process configurations by integrating different modules can be developed at microscale.

Such configurations enable effective screening and rapid process development of biocatalytic reactions assuring economic viability and shorter time to market for pharmaceutical products. Thus the work presented in this thesis is based on the application of microstructured devices for screening and characterization of process options in biocatalytic processes.The thesis focuses on interesting case studies like the asymmetric synthesis of chiral amines using ω-transaminases and synthesis of an industrially relevant imine product using monoamine oxidase.

The first part of the thesis is focused on the development of novel reactor configurations for biocatalysis. A combination of micro reactors and computational fluid dynamics (CFD) has been found to contribute significantly towards the understanding of diffusional properties of the substrate and the product.

Such knowledge is subsequently applied to design customized reactor configurations. It has been demonstrated that this knowledge can be crucial for the choice and design of reactors. The second part focuses on developing μ-scale modules for rapid screening and integrating process units. The increase in productivity is evaluated through process metrics.

A case study demonstrates the applicability of using a micro-scale packed bed column for screening synthetic resins for in-situ product removal. CFD simulations were performed to guide the design of a packed column for efficient operation. Further case studies demonstrate the development of modular set-ups with integrated processes at microscale to address process limitations which were determined by initial experiments at lab scale.

The degree of integration of functionalities requires process optimization. Thus optimization studies were also performed by varying operational parameters. From an academic point of view, a general methodology is desired and thus a systematic screening methodology is proposed that relies on microstructured devices during process development.

The methodology can be applied to other biocatalytic reactions with some limitations.