Bodla, Vijaya Krishna

Processer baseret på biokatalyse kan i mange tilfælde være et attraktivt alternativ til traditionel kemisksyntese til produktion af mange industrielt relevante produkter. I de fleste tilfælde er det dog meget udfordrende at implementere nye biokatalytiske processer. Det er for eksempel meget tidskrævende at screene mange biokatalysatorer og forskellige proceskonfigurationer, samt karakterisere processen for at vurdere den økonomiske suverænintet, inden opskalering af processen foretages. Brugen af mikro-strukturerede moduler som et screeningværktøj, vil potentielt give et paradigmeskift i hvordan processer udvikles ved at forkorte udviklingstiden gennem brugen af standard moduler til procesudviklingen og procesintensivering. Ydermere, er det relativt nemt at lave brugerdefinerede mikro-strukturerede reaktor moduler og proceskonfigurationer til specielle applikationer. Alle disse features vil muliggøre effektiv screening og hurtig procesudvikling af biokatalytiske processer, der i sidste ende vil opfylde økonomiske restriktioner og derved forkorte tiden til markedet. Arbejdet præsenteret i denne afhandling er baseret på brugen af mikrostrukturerede moduler til screening og karakterisering af procesmuligheder i biokatalytiske processer. Med specielt fokus på to interessante casestudies. Første casestudy er asymmetrisksyntese af chirale aminer ved brug af ω-transaminaser og det andet casestudy omhandler syntese af industrielt relevante iminer ved brug af monoaminoxidase. Den første del af denne afhandling fokuserer på udvikling af nye reaktorkonfigurationer til at styre de biokatalytiske processer der er i fokus. Kombineret brug af mikro-reaktorer og Computational Fluid Dynamics (CFD) har vist sig at bidrage væsentligt til forståelsen af diffusionsmæssige egenskaber af substrater og produkter. Denne viden kan efterfølgende anvendes til at designe optimale reaktorkonfigurationer. Det er blevet påvist, at denne viden kan være afgørende for valg og design af reaktorer. Anden del fokuserer på at udvikle mikro-skala moduler til hurtig screening og integrering af enheds operationer til at intensivere processer, forbedringer vurderes ved at analysere procesproduktiviteten. Et eksempel demonstrerer anvendeligheden mikro-systemer, ved at anvende en mikro-packed bed – kolonne til at screene resiner for deres anvendelighed til in-situ produkt fjernelse. CFD simuleringer blev benyttet til at designe et effektivt kolonne design. Yderligere eksempler fokuserede på at demonstrere udviklingen og optimering af modul baserede forsøgsopstillinger med integreret separations processer i microskala for at overkomme procesbegrænsninger, som tidligere er blevet identificeret i laboratoriet. Fra et akademisk synspunkt er det ønsket at opnå en generel procesudviklingsmetode. Der er derfor foreslået en systematisk screenings metode for brugen af micro-systemer i denne afhandling. Den foreslåede metode er generelt anvendelig, med få undtagelser.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

Online Research Database In Technology

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

http://orbit.dtu.dk/ws/files/104237429/thesis_Vijaya_Bodla.pdf

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

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Online Research Database In Technology