Best Practices for Microbial Fermenter Equipment Characterization - - BioPharm International


Best Practices for Microbial Fermenter Equipment Characterization

BioPharm International Supplements

Oxygen Supply Characterization

The fermenter must have sufficient oxygen transfer to supply enough oxygen to the culture to support cell respiration. Oxygen transfer rates (OTR) are lower as the scale increases because of potentially lower power per volume input, which causes a common scale-up problem. Process modifications can be explored to decrease growth rate and oxygen demand; however, sufficient oxygen supply may be achieved with modifications such as manipulating aeration (air supplemented with oxygen, gas flow rate), agitation (impeller design, number, and location; agitator speed), headspace pressure, and baffles.

The above equipment settings can influence the OTR in a fermenter. These settings can be optimized to increase the oxygen driving force or the mass transfer coefficient (k L a) of the reactor. The OTR can be calculated using the following equation:

in which k L is the mass transfer coefficient (cm/h), a is the gas/liquid interface area per liquid volume (cm2 /cm3), C* is the saturated dissolved oxygen concentration (mmoles/dm3), and C L is the concentration of dissolved oxygen in the fermenter (mmoles/dm3).

For process transfer and scale-up, k L a is a useful parameter because it helps determine whether a reactor can supply oxygen at a nonlimiting rate. Several methods can be used to estimate k L a. During fermentation, a steady state mass balance calculation can be used to equate the oxygen uptake rate of the culture, as measured by a mass spectrometer, to the OTR. Additionally, chemicals such as sodium sulphite can be used to estimate k L a based on the rate of sodium sulphite oxidation, which is equivalent to the oxygen transfer rate.2

Dynamic pressure and gassing methods also can be used to estimate k L a. A dynamic pressure method can be used by measuring the change in dissolved oxygen (DO) concentration after a small change in system pressure. The dynamic gassing method measures the change in DO concentration versus time for predetermined step changes in the sparge gas oxygen concentration. These dynamic methods can be problematic in microbial systems with high k L a values because the oxygen concentration changes so rapidly that the DO sensor response becomes limiting. However, more accurate k L a can be estimated by accounting for the DO sensor kinetics.2,3

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