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Bioreactor Design
Bioreactors have requirements that add complexity
compared to simpler chemical reactors
Usually three-phase (cells, water, air)
Need sterile operation
Often need heat removal at ambient conditions
Bioreactor Design
Enzyme catalysis
Cell growth and metabolism
Cleaning and sterilization
Stirred tank fermenter design
Other bioreactors
Enzyme catalysis
Enzymes are biocatalysts and can sometimes be isolated
from host cells
Low cost enzymes are used once through: amylase, ligninase
High cost enzymes are immobilized for re-use
C
R=
+C
R = reaction rate
C = substrate concentration
, = constants
Chemical Engineering Design
Feed
Reactor
Filter
M
Product
Bioreactor Design
Enzyme catalysis
Cell growth and metabolism
Cleaning and sterilization
Stirred tank fermenter design
Other bioreactors
Cell Growth
Cell growth rate can be limited by many factors
Availability of primary substrate
Typically glucose, fructose, sucrose or other carbohydrate
Availability of oxygen
Hence mass transfer properties of reaction system
III
IV
Intracellular product
concentration
Batch time
III
IV
Intracellular product
accumulation is slow at
first (not many cells)
Intracellular product
concentration
Product accumulation
continues even after
live cell count falls
(dead cells still contain
product)
Batch time
Ks + s
s
max
-1
III
IV
Intracellular product,
batch process
Intracellular product
concentration
III
IV
Intracellular product,
continuous process
Intracellular product
concentration
Batch time
III
IV
Extracellular product,
continuous process
Intracellular product
concentration
Batch time
Bioreactor Design
Enzyme catalysis
Cell growth and metabolism
Cleaning and sterilization
Stirred tank fermenter design
Other bioreactors
Cleaning Policy
Typically multiple steps to cleaning cycle:
Sterilization Policy
Sterilization is also a reaction process: cell death is typically
a 0th or 1st order process, but since we require a high
likelihood that all cells are killed, it is usually treated
probabilistically
Typical treatments: 15 min at 120C or 3 min at 135C
SIP is usually carried out by feeding LP steam and holding
for prescribed time. During cool-down only sterile air should
be admitted
Feed sterilization can be challenging for thermally sensitive
feeds such as vitamins need to provide some additional
feed to allow for degradation
Chemical Engineering Design
Holding coil
Feed
To vacuum
Expansion
valve
Flash cooler
Sterile product
Feed
Holding coil
Sterile product
Condensate
Steam
Bioreactor Design
Enzyme catalysis
Cell growth and metabolism
Cleaning and sterilization
Stirred tank fermenter design
Other bioreactors
1.0
300
1.5
400
3
800
5
7.5
1500 2000
15
4000
25
7000
30
8000
Air
Coolant out
Coolant in
Foam breaker
Baffle
Agitator blade
Sparger
Condensate out
Product out
2.
Even in continuous mode, several reactors may be needed to allow for periodic cleaning and reinnoculation
Establish cell concentration, substrate feed rate, product formation rate per unit volume per unit
time
Hence determine number of standard reactors to achieve desired production rate: assume vessel
is 2/3 full
3.
4.
Determine mass transfer rate and confirm adequate aeration (see Ch15 for correlations)
5.
Determine heat transfer rate and confirm adequate cooling (see Ch19 for correlations)
6.
7.
Recalculate productivity allowing for non-operational time (CIP, SIP, etc.): revisit step 2 if
necessary.
Bioreactor Design
Enzyme catalysis
Cell growth and metabolism
Cleaning and sterilization
Stirred tank fermenter design
Other bioreactors
Shaftless Bioreactors
Use gas flow to provide agitation of liquid
Eliminates pump shaft seal as potential source of
contamination
Design requires careful attention to hydraulics
Off gas to
vapor recovery
Gas feed
Liquid feed
Off gas to
vapor recovery
Liquid feed
Gas feed
Draft tube
Sparger
Liquid product
Liquid product
Questions ?