Abstract
Accurate determination of the mixing time in orbitally shaken bioreactors (OSRs) is essential for the optimization of mixing processes and minimization of concentration gradients that can be deleterious to cell cultures. The Dual Indicator System for Mixing Time (DISMT) was employed to measure mixing times in cylindrical and Erlenmeyer flask bioreactors. Various aspects of importance for the acquisition of accurate data from the measurement methodology are discussed, utilizing also comparisons of DISMT and pH probe results obtained in two stirred reactors. The OSR results are juxtaposed with data previously reported in the literature for both cylindrical reactors and Erlenmeyer flasks. The employment of a critical Froude number shows promise for the establishment of a scaling law for mixing time across the various types and sizes of shaken bioreactors.
Highlights
Mammalian cell cultures have been widely used for the production of therapeutic proteins and vaccines
In the present study the methodology of the Dual Indicator System for Mixing Time (DISMT) technique for the measurement of mixing times in orbital shaken reactor (OSR) was assessed in detail
Various aspects of the data acquisition and processing procedures were considered and it was shown that utilization of the standard deviation G of the green colour values recorded during an experiment can help provide more reliable data that provide information on the final mixing time and on the development of mixing during the process
Summary
Mammalian cell cultures have been widely used for the production of therapeutic proteins and vaccines. Monoclonal antibodies, in particular, represent a class of therapeutics that has shifted the treatment paradigm in the fields of oncology and immunology by improving the quality of life for the patient during cancer treatment [1,2] Commercial production of these antibodies relies on the development of cost-effective large-scale cultivation methods of genetically engineered mammalian cells. Recent studies in STRs have shown that shear stresses do not significantly affect cell growth of animal cells [13,14], there is a growing interest in understanding the effect of shear stress on stem cells and cells for therapy, and the low shear levels present in OSRs could potentially make this device a suitable option for scaling up cell expansion using suspension cultures [15] From this point of view operating conditions should be carefully selected by comparing the Kolgomorov length scale to
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