Model‐Driven Monitoring and Parameter‐Based Development of an Escherichia coli Fed‐Batch Process for Production of a Fab Antibody Fragment Across Scales
Bioprocess modeling study reveals feeding-induced physiological shifts in Escherichia coli, highlighting critical parameters for multi-scale bioreactor scale-down.
Key Points
To evaluate the feasibility and predictive accuracy of mechanistic model-driven scale-down across five bioreactor sizes for an Escherichia coli process producing Fab antibody fragments.
Cultivated an Escherichia coli fed-batch process across five bioreactor scales ranging from 15 mL mini-bioreactors to a 30 L pilot scale.
Extended a macro-kinetic model of aerobic growth and overflow metabolism with equations describing product synthesis and extracellular release to monitor cross-scale physiology.
Compared continuous feeding modes to pulse-based feeding and tested varying IPTG concentrations to maintain a constant IPTG-to-biomass ratio at the milliliter scale.
Batch-phase growth parameters aligned consistently across all five scales, confirming baseline feasibility of scaling down from 30 L to 15 mL vessels.
Pulse-based feeding required in 15 mL and 150 mL vessels prevented complete alignment with continuous-fed reference scales by reducing cell lysis and increasing productivity.
Reducing IPTG concentrations to match biomass ratios at the milliliter scale doubled the specific product yield and prolonged Fab fragment formation.
Cite This Study
Schröder-Kleeberg et al. (2026) studied this question.