(316c) Characterization of Kla Using Definitive Screening Designs for Fermentation Development and Scale-Up

Characterization of k_La using Definitive Screening Designs for Fermentation Development and Scale-Up

Fermentation development and optimization are typically performed at small scale to reduce their cost and time requirement.  High cell density aerobic fermentation is scaled-up often based on keeping volumetric mass transfer coefficient (k_La) constant. To facilitate a successful transfer of an optimized small-scale fermentation process to lab, pilot, and industrial scale, the k_La profiles for these fermentors should be determined. Although a number of correlations and predictive models for k_La are available, they do not have universal applicability.  

 The purpose of this study was to use a statistical Design of Experiments (DoE) approach to characterize k_La in 1.3L DASGIP, 10L Biostat B, 40L Biostat CDCU and 200L ABEC microbial fermentors, and hence to use this information for fermentation scale-up. Polarographic dissolved oxygen sensors were used to measure dissolved oxygen concentrations in the fermentors. k_La was determined in de-ionized water by using the dynamic re-oxygenation method. Definitive Screening Designs, a new efficient statistical Design of Experiment, were used to characterize k_La in the fermentors. Four experimental factors, temperature, agitation, air flow rate, and volume, were included in the experimental design as input parameters, and k_La was the output parameter. Definitive Screening Designs showed that agitation, air rate and volume were statistically significant for all the fermentors. Air and volume had strong positive correlations with k_La, and agitation had strong quadratic effects on k_La. Results showed that four fermentors have comparable k_La profiles. The correlations determined here will be used as an effective tool for fermentation development, scale up and tech transfer.