Systematic Development of Miniaturized (Bio)Processes using Process Systems Engineering (PSE) Methods and Tools

The focus of this work is on process systems engineering (PSE) methods and tools, and especially on how such PSE methods and tools can be used to accelerate and support systematic bioprocess development at a miniature scale. After a short presentation of the PSE methods and the bioprocess development drivers, three case studies are presented. In the first example it is demonstrated how experimental investigations of the bi-enzymatic production of lactobionic acid can be modeled with help of a new mechanistic mathematical model. The reaction was performed at lab scale and the prediction quality analyzed. In the second example a computational fluid dynamic (CFD) model is used to study mass transfer phenomena in a microreactor. In this example the model is not only used to predict the transient dynamics of the reactor system but also to extract material properties like the diffusion velocities of substrate and product, which is otherwise difficult to access. In the last example, a new approach to the design of microbioreactor layouts using topology optimization is presented and discussed. Finally, the PSE methods are carefully discussed with respect to the complexity of the presented approaches, the applicability with respect to practical considerations and the opportunity to analyze experimental results and transfer the knowledge between different scales.