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An improved dynamic method to measure kL a in bioreactors
Andrew L Damiani1, Min Hea Kim, Jin Wang
1Auburn University, 212 Ross Hall, Auburn, Alabama, 36849.
Biotechnology and Bioengineering
|May 20, 2014
Summary
This study introduces an improved dynamic method for accurately measuring the volumetric mass transfer coefficient (kL a) in bioreactors, especially for high cell densities. The new method enhances precision and enables measurements previously impossible with classical techniques.
Area of Science:
- Biotechnology and Biochemical Engineering
- Chemical Engineering
- Bioreactor Design and Operation
Background:
- Accurate estimation of the volumetric mass transfer coefficient (kL a) is vital for bioreactor design, operation, and scale-up.
- The classical dynamic method is widely used but has limitations, particularly with high cell densities and moderate agitation, hindering kL a estimation.
- Existing improvements to the dynamic method do not fully address these limitations under specific bioreactor conditions.
Purpose of the Study:
- To develop and validate an improved dynamic method for estimating the volumetric mass transfer coefficient (kL a) in bioreactors.
- To overcome the limitations of the classical dynamic method, especially in scenarios with high cell density and reduced agitation.
- To enable more accurate and efficient measurement of kL a across a wider range of bioreactor operating conditions.
Main Methods:
- An improved dynamic method incorporating a refined model that accounts for headspace-broth mass transfer.
- Implementation of a procedure involving nitrogen sparging during air shut-off to enhance dissolved oxygen changes.
- Utilizing Scheffersomyces stipitis as a model organism to demonstrate the method's effectiveness and investigate the impact of cell density and agitation.
Main Results:
- The improved dynamic method provides faster and more accurate estimations of kL a compared to the classical method.
- Successfully enabled kL a measurement for high cell densities with medium/low agitation, a condition where the classical method fails.
- Experimental data confirmed the influence of cell density and agitation speed on the volumetric mass transfer coefficient.
Conclusions:
- The presented improved dynamic method significantly enhances the accuracy and applicability of kL a estimation in bioreactors.
- This method is particularly valuable for optimizing processes involving high cell densities and varying agitation rates.
- The findings contribute to more robust bioreactor design, operation, and scale-up strategies.
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