Chapter 10

Selection, scale up, operation

and control of bioreactors
1. Baffles, Material and surfaces
2. Impellers
3. Heating and Cooling system
(Coil vs. Jacket)
4. Sterility
5. Energy efficiency
1. Reactors with internal
mechanical agitation
2. Bubble column
reactors
3. Loop reactors
 1. Disc(Rushton type) and Turbine type
impeller: common
D 2. Marine and paddle impellers
d 3. Axial flow hydrofoil impellers: axial
flow system

d/D= 0.3-0.4

d/D= 0.5
Pg: power
requirement
Vs: superficial gas
exit speed.
N: rotational speed
of agitator
Pu: power requirement in the
ungassed fermenter
Di : impeller diameter
Q: aeration rate(volume of
gas/min/liquid volume in the
reactor)
1) Unsteady state method
2) Sulfite method: over estimation of kLa
Cu2+
SO3-2 + ½ O2
SO4-2

3) Steady state method: mass balance on O2 in the gas using Mass

spectrometry(measure O2 uptake rate)

C* value is proportional to pO2, which is dependent

on total pressure.
At sparget point, pO2 is significantly high.
Log mean value is some times used.
4) Dynamic method: profiling of DO level,
Air supply is shut off for a short period of time(< 5 min.) = kLa becomes zero.

Ascending period is used to

measure OTR
dCL/dt + qO2X = kLa(C*-CL)
10.2.4 Scale up: highly empirical, make no change in controlling regime
during scale up

i) Const P0/V (α N3Di2 )= const OTR=

const kLa
1) P0 α N3Di5
ii) Const N=const mixing time
2) V α Di3
iii) Cost N*Di= const tip speed= const
3) Q α N*Di3
shear
4) Nre = ρvD/μ
iv) Const Nre= similar flow pattern
Characteristic time constant= predicting possible reactor
limitation
1) Sterilizable
2) Preventing probe fouling
3) Response time
4) Prevent Potential contamination source
1) Primary
measurement : data
Logging

2) Secondary
Parameters:
X, RQ, kLa

RQ= mole of CO2

formed/moles of O2
consumed
 10.4 Sterilization of Process Fluids

10.4.1 Introduction and the Kinetics of Death

Definition of Death: failure of cell, spore, or virus to

reproduce or germinate

Probability of extinction:

N0: initial number of cells

P(t): Probability that individual cell is viable at time t
 E[N(t)]: expected value of the number of the cells
at time t

D: decimal reduction
time(time for the
number of viable cells
to decrease 10X)

N(t)/N0= survival
curve
10.4.2 Sterilization of Liquids

Chemicals:
i) Ethylene oxide
ii) 70% EtOH/ water (pH 2
with HCl)
iii) Formaldehyde
iv) Sodium hypochlorite(3%)
v) Ozone
vi) Thermal sterilization
 Main factors in Sterilization:
i) Temp
ii) Time of exposure
iii) N0

Ex) For spores, kd= 0.5-5.0

min-1

Dependence of specific death rate on Temp follows

Arrhenius Eqn:
Probability of
unsuccessful
sterilization: 1-P0(t)

n0= concentration of
cell in the reactor
Sterilization Chart:

Ex) for 1-P=10-3 and N0=108,

kdt=ca. 26, which means that
if kd=1 min-1 at 121˚C, then
t=26 min at 121˚C is required
to ensure 999/1000 successful
sterilizations
: dilution of medium is disadvantage
c. Filter sterilization: Viruses and mycoplasma can pass the filter.