PhD Offer - Digitalization tools for up-scaling bioprocesses: A modeling approach coupling metabolism and hydrodynamics

The implementation of bioeconomy requires digitalization tools allowing to assess the feasibility of the proposed technology before being implemented at industrial level. Although available, fast and reliable digitalization tools need to be developed to address properly the scale-up of bioprocesses at industrial scale and test their impacts into an integrated bioeconomy. Nowadays, many bioprocesses show promising results at lab-scale, while their transfer to industrial scale remain uncertain due to the difficulty of predicting the effects of scale-up especially in the bioreactor (e.g. reduced titer, lower yields and productivity, and by-product formation). These effects are mainly due to mixing, heat and mass transfer limitations since the repeated exposure to concentration changes lead to the drift from the expected biosynthesis route. The number of existing works coupling hydrodynamics and biokinetics in a rigorous way, through a combination of chemical engineering, heterogeneous catalysis and multiphase flow principles, is limited [1], [2], [3]. An effort is necessary to develop a generic bioreactor model for industrial scale applications. While considering cell functioning with fluid dynamics, it should provide fast and reliable results to better predict the process performance across scales with minimal losses.

Besides bioreactors, digitalization tools are also needed to conceive a complete production chain including upstreaming and down-streaming processes which must be evaluated in a whole to guarantee that the emerging bioprocesses meet the environmental criteria and generates less impacts than the chemical production. The scientific core of the PhD relates to chemical, biochemical process modeling and simulation with special emphasis on the multiphase reaction step.

The objective of this PhD is to develop digitalization tools considering an integrated modeling framework to predict the variability on process performances through scale-up and the inclusion of the bioreactor into an environmentally friendly production chain. Starting from our understanding of the interplay between bioreaction and hydrodynamics we aim at representing the consequences of scale-up effects on bioprocess performances in the reactor and in the downstream process. The coupled full-scale model will allow the evaluation of technical and environmental performances of a case study value chain.

The outcome of the PhD project consists in producing a case study for the scale-up a bioproduction including model, code and documentation to be published in an open-access platform.

The scientific questions that will be addressed are:

• How to couple biokinetics with hydrodynamics?

• How to manage the gas/liquid transfer and the mixing in the bioreactor?

• How to integrate the bioreactor model with the production chain?

The PhD thesis will follow three parts: 1) coupling hydrodynamic models with reduced metabolic models, 2) application to a well-known case study, 3) integration of the bioreactor in the production chain and evaluation of technical and environmental performances.