ScaleUp

The supply of oxygen by aeration-agitation conditions are closely related to the following parameters:

1. Gas/liquid interfacial area

2. Bubble retention time ("hold-up")

3. Thickness of liquid film at the gas/liquid interface

Based on these three parameters, the four scale-up methods have been investigated keeping each parameter constant from laboratory to industrial scale. The parameters for scale-up are the following:

1. Volumetric oxygen transfer coefficient (kta)

2. Power consumption volume

3. Impeller tip velocity

4. Mixing time

Even for the simple stirred, aerated fermenter, there is no one single solution for the scale-up of aeration-agitation which can be applied with high probability of success for all fermentation processes. Scale-up methods based on aeration efficiency (<kta) or power consumption/unit volume have become the standard practice in the fermentation field.

Scale-up based on impeller tip velocity may be applicable to the case where an organism sensitive to mechanical damage was employed with culture broths showing non-Newtonian viscosity. Furthermore, scale-up based on constant mixing time cannot be applied in practice because of the lack of any correlation between mixing time and aeration efficiency. It might be interesting and more useful to obtain information on either mixing time or impeller tip velocity in non-Newtonian viscous systems.

The degree of oxygen saturation Qo2/(Qo2)max an(* oxidation-reduction potential (ORP) have already been found to be very effective for the scale-up of fermentation processes for amino acids, nucleic acids, and coenzyme Q10. The successful scale-up of many aerobic fermentations suggests that the dissolved oxygen concentration level can be regarded as an oxygen. Measurements using conventional dissolved oxygen probes are not always adequate to detect the dissolved oxygen level below 0.01 atm. EvenO.Ol atm is rather high compared to the critical dissolved oxygen level for most bacterial respirations. Due to the lower detection limit of dissolved oxygen probes, oxidation-reduction potential (ORP) was introduced as an oxygen supply index, which is closely connected to the degree of oxygen saturation.

The ORP value Eh in a non-biological system at a constant temperature is given in the following equation:

where

PL = the dissolved oxygen tension = (atm)

Eh = the potential vs hydrogen electrode In microbial culture systems, the ORP value E can be expressed as follows:

Edo - the dissolved oxygen Eph = the pH E, = the temperature Emd = the medium

Ecm = all metabolic activity to the whole ORP E

For most aerobic fermentations at constant pH and temperature, Eq. (2) can be simplified to the following,

As a result, we can generally use the culture ORP to evaluate the dissolved oxygen probe.

An example using the ORP as a scale-up parameter has been reported forthe coenzyme Q10 fermentation using Rhodopseudomonas spheroides. In this case, coenzyme Q10 production occurred under a limited oxygen supply where the dissolved oxygen level in the broth was below a detection limit of conventional dissolved oxygen probes. Therefore, the oxidation-reduction potential (ORP) was used as a scale-up parameter representing the dissolved oxygen level. As a result, the maximum coenzyme Q10 production was attained, being kept the minimum ORP around 200 mV in the last phase of culture (Fig. 10).

In the scale-up of ordinary aerobic processes, oxygen transfer conditions have been adjusted to the maximum oxygen requirement of the fermentation beer during the whole culture period. However, the excess oxygen supply occurs in the early growth due to the lower cell concentration under these conditions. It should be noted that such excess supply of oxygen sometimes has the harmful effect of bioproducts formation. In other words, the oxygen supply should be altered according to the oxygen requirements of microorganisms in various culture phases.

Process t1me(h)

Figure 10. Coenzyme Q10 fermentation under an optimal aeration-agitation condition using 30 liter jar fermenter and the constant rate fed-batch culture. dcw\ dry cell weight, orp: oxidation-reduction potential.

Process t1me(h)

Figure 10. Coenzyme Q10 fermentation under an optimal aeration-agitation condition using 30 liter jar fermenter and the constant rate fed-batch culture. dcw\ dry cell weight, orp: oxidation-reduction potential.

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