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by Susanna Maria Lladó Maldonado (Author)
The miniaturisation of bioreactors to the microliter-scale and the integration of online sensors for monitoring the most important process variables during the cultivations is a promising approach for the screening and optimization of cultivation and biocatalysis processes, enabling information-rich, parallelised and cost-effective experiments under well-controlled environmental conditions. The main advantages of microbioreactors (MBRs) are minimization of space and reagents, their easy manipulation, and their high-throughput screening potential, which make them very interesting tools to develop bioprocesses. This thesis is focused on the development of MBRs and the sensor integration for monitoring optical density (OD), dissolved oxygen (DO), pH and glucose as well as their validation for different biotechnological applications. On the basis of a developed PDMS-based MBR, a borosilicate glass-based microbubble column-biroeactor (gμBC) (working volume of 60 μL, aeration occurs through a nozzle with =26 μm) was designed and manufactured by wet etching and powder blasting technology. The g BC proved to have good oxygen transfer capacity, reaching kLa values up to 320 1/h and fast mixing times θ95 down to 5.5 s when working at a gas superficial velocity uG of 2.25∙10-3 m/s. The mixing performance was simulated using a simplified CFD model, and the tracer profile yielded a good qualitative prediction that was comparable to the experimental results, presenting a tolerable deviation of the mixing times. The g BC was validated as a suitable cultivation screening tool with a batch cultivation of Saccharomyces cerevisiae with the real-time online monitoring of OD and DO. Furthermore, a cuvette-based microbubble column-bioreactor (cμBC) made of polystyrene (working volume of 550 μL, aeration occurs through a nozzle with
