Bioreactor Design and Operation - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 956

It is desirable to sterilize process fluid continuously as it is more reliable and requires less
steam. In this case, CSTR or stirred-tank sterilization is not recommended, whereas tubular
sterilizers are highly desirable. For continuous sterilization in laminar flow regime, the prob-
ability of microorganisms surviving the thermal sterilization is given by

exp

4ðk d s þ2Þ
k d s ðk d s þ8Þ

k d s
2

pð s Þ z (18.47)

where is the space time of the sterilizing fluid in the sterilization zone. The probability of the

entire population in one reactor-full process fluid not vanishing from the laminar flow heat
treatment is

s

exp

4 ðk d s þ2Þ
k d s ðk d s þ8Þ

1
2 k d s

C X 0 V

exp

P 1 ð s Þ z (18.48)

2 ðC X 0 V 1 Þðk d s þ 2 Þ
k d s ðk d s þ8Þ

1
2 k d s

1þ

which corresponds to the characteristic sterilization time of

1
2 k d s ln

4 ðk d s þ2Þ
k d s ðk d s þ8Þ lnðC X 0 VÞ

t S ¼ (18.49)

where C X0 is the estimated cell concentration in the sterilizing fluid and V is the volume of
fluid of basis for sterilization. The sterility can be measured by the probability of unsuccessful
fermentations or contamination in a certain time period of fermentation (1 day of operation,
1 week of operation, or 1 month of operation). Thus, the volume V depends on the basis of
sterility. If one fermentor volume full of medium is considered as the basis and then V is the
volume of the fermentor.
For continuous sterilization with a tube of length L and diameter D R in the turbulent flow
regime, the probability of microorganisms surviving the thermal sterilization is given by

1 !

p

1þ4a d D R L 1

k d s

pð s Þ¼exp L (18.57)

2a d D R

where the dispersion constant a d is given by,

a d ¼ 310 7 Re 2:1 þ1:35Re 0:125 (18.56)

The probability of the entire population in one reactor-full process fluid not vanishing
from the heat treatment is

1 !

p

1þ4a d D R L 1

k d s

C X 0 Vexp L

2a d D R

1 !

P 1 ð s Þ z (18.58)

p

1þ4a d D R L 1

1þ C X 0 V 1
2

k d s

exp L

2a d D R