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Scale-up means increasing the scale of a fermentation, for example from the laboratory scale to the pilot plant scale or from the pilot plant scale to the production scale. Increase in scale means an increase in volume and the problems of process scale-up are due to the different ways in which process parameters are affected by the size of the unit. It is the task of the fermentation technologist to increase the scale of a fermentation without a decrease in yield or, if a yield reduction occurs, to identify the factor which gives rise to the decrease and to rectify it.
When the scale of a process is increased the sterilization regime must be adjusted accordingly, which may result in a change in the quality of the medium after sterilization.
(3) Environmental parameters. The increase in scale may result in a changed environment for the organism. These environmental parameters may be summarized as follows: (a) Nutrient availability, (b) pH, (c) Temperature, (d) Dissolved oxygen concentration, (e) Shear conditions, (f) Dissolved carbon dioxide concentration, (g) Foam production. All the above parameters are affected by agitation and aeration, either in terms of bulk mixing or the provision of oxygen. Thus, agitation and aeration tends to dominate the scale-up literature.
This represents an extremely large increase in power, much greater than is economically or technically feasible with most equipment used for stirring. Because The criterion of constant mixing time can hardly ever be applied for scale-up, it is inevitable that mixing times increase with scale. If instead of mixing time, P/V is kept constant during scale-up, mixing time can be expected to increase in proportion to vessel diameter raised to the power 0.67
if dissolved oxygen concentration is the over-riding environmental condition then power consumption per unit volume and volumetric air flow rate per unit volume should be maintained constant on scale-up.
Power consumption per unit volume is kept constant then impeller tip speed increases and flow per minute per volume decreases. If impeller tip speed is kept constant then power consumption (hence KLa) and mixing decrease
The widely used scale-up criteria are the maintenance of a constant KLa or constant shear conditions. Constant shear be achieved by scaling up on the basis of constant impeller tip speed. Constant KLa may be on the basis of constant power consumption per unit volume and constant volumetric air-flow rate.
The constant power per unit volume, for a mechanical agitated vessel is given by
From power consumptions in a bench-scale bioreactor, the necessary agitation rate is calculated for the scale up ratio, using Equation
that is true for the rotational speed of large tank, which is related to a small tank with the ratio of impeller diameter of large and small tanks to the power of 2/3.
The mass transfer coefficient KLa is constant; the general correlation is considered by many as proportional to the power per unit volume with constant exponent, and gas superficial velocity to another constant power as shown below:
Scale-up Based on Shear Forces Scale-up calculation is based on constant shear forces, where shear is directly related to impeller tip velocity.
where, t is the shear stress, du/dx is the shear rate, and m is the fluid viscosity.
Since the shear is defined as S, which is proportional to NDi, the concept of constant impeller tip velocity and constant power per unit volume were applied.
Now introduce variable S for impeller tip velocity NDi into aboveEquation, then multiply both sides and divide by impeller diameter, so that the power equation is reduced to shear forces related to impeller diameter:
Scale-up for Constant Mixing Time The function of mixing, f(t) is defined as constant mixing time:
where, tm is the mixing time, g is gravity, Dt is the tank diameter, and Y the depth of the liquid. The mixing time:equation is
where tmS and tmL represent the mixing time for small and large fermentation vessels.
That is proportional to impeller diameter to the power of 0.65. Then, solving for mixing time
The major difference will be the height of the vessels resulting in increased pressure at the base of the larger vessel. This would result in higher oxygen and carbon dioxide solubility which would give a higher KLa but might result in carbon dioxide inhibition. .
Scale up of sterilization
Deindoerfer and Humphrey (1959) used the term InNo/Nt as a design criterion for sterilization, which has been variously called the Del factor, Nabla factor and sterilization criterion. The Del factor is a measure of the fractional reduction in viable organism count produced by a certain heat and time regime.
The Del factor does not include a volume term, i.e. absolute numbers of contaminants and survivors are considered, not their concentration. Thus, if the size of a fermenter is increased the initial number of spores in the medium will also be increased, but if the same probability of achieving sterility is required the final spore number should remain the same, resulting in an increase in the Del factor.
For example, if a pilot sterilization were carried out in a 1000-dm3 vessel with a medium containing 106 organisms cm-3 requiring a probability of contamination of 1 in 1000, the Del factor would be:
The Del factor to be achieved in a continuous sterilization process has to be increased with an increase in scale. Thus, if the volume to be sterilized is increased from 1000 dm3 to 10,000 dm3 and the risk of failure is to remain at 1 in 1000 then the Del factor must be increased from 34.5 to 36.8. When a fermentation is scaled up it is important to appreciate that the inoculum development process is also increased in scale and a larger.
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