Model-based scale-up methodology for aerobic fed-batch bioprocesses: application to polyhydroxybutyrate (PHB)...

Area of Science:

• Bioprocess Engineering
• Chemical Engineering
• Biotechnology

Background:

• Fed-batch bioprocesses are crucial for producing valuable compounds.
• Scaling up these processes from lab to industrial scale presents significant challenges.
• Current empirical scale-up methods often fail to maintain optimal process dynamics.

Purpose of the Study:

• To develop a general model-based methodology for scaling up fed-batch bioprocesses.
• To establish a dynamics hierarchy for determining optimal scale-up factors and timing.
• To provide theoretical support for existing empirical rules and compare the proposed method against them.

Main Methods:

• Utilizing linear control theory concepts, including singular value decomposition of the Hankel matrix.
• Developing a process model to establish a dynamics hierarchy.
• Applying the methodology to a polyhydroxybutyrate (PHB) fed-batch bioreactor.
• Comparing the model-based approach with three traditional empirical criteria.

Main Results:

• The proposed methodology successfully predicts similar process dynamic behavior and PHB production at a larger scale.
• It provides theoretical validation for the empirical rule of scaling aerobic bioreactors at a constant volumetric oxygen transfer coefficient.
• Empirical scale-up criteria were found to rarely reproduce similar bioreactor dynamic behavior.

Conclusions:

• The model-based methodology offers a robust and theoretically sound approach to fed-batch bioprocess scale-up.
• This method ensures better predictability of process performance at industrial scales compared to empirical methods.
• It enhances the design and optimization of bioprocesses for consistent product yield and quality.