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what are the three basic types of traditional reactors?
reactors with internal mechanical agitation (stirred tank)
bubble columns
loop reactors
what is a stirred tank mainly known for?
traditional fermenter
how does a stirred bioreactor for biopharmaceutical production differ from a regular stirred tank?
angled impellers
axial flow
less power needed
lower heating/cooling load
what are the advantages of stirred tank reactors?
flexible operation
provide high volumetric mass transfer coefficient values for gas transfer
what are the upper limits on size for stirred tank reactor?
microbial system - 400m3
animal cell culture- 20m3
plant cell culture- 75m3
what is viscosity used commercially in stirred tank reactors?
2000CP or 2 Pas
Stirred tank reactors: Spargers
gas supplied under pressure
influences bubble size, distribution and cell death/damage
placement relative to the impeller is important
stirred tank reactor- impeller, what two types?
rushton (disk) impeller
hydrofoil impellers
features of rushton (disk) impeller
high power number- small size
radial flow pattern
poor axial flow- multiple impellers used
baffles increase mixing
hydrofoil impellers- features
axial flow (up and down mixing)
reduced maximum shear rates
lower energy needed
off center placement instead of baffles
main differences of rushton and hydrofoil impellers
rushton: radial flow
hydrofoil: axial flow (up and down)
what is the working volume for a vessel?
75%
what does CIP stand for?
clean in place
how do bubble column reactors work?
agitation via sparged gas
what are bubble column reactors not suitable for?
highly viscous systems
Features of bubble column reactors
higher energy than stirred tank
low shear environment
simpler design (no mechanical agitation)
limited gas flow rate
How do loop reactors work? (air lift reactors)
agitation via gas
benefits of loop reactors
can handle more viscous fluids than the bubble column
what reactor is targeted for animal cell culture?
single use bioreactors (SUB)
what are advantages of single use bioreactors?
CIP procedures not required
shorter downtime
greater process flexibility
reduce capital and process costs
what are some limitations of single use bioreactors?
upper size limit
mechanical stability of plastic
chemicals that leach out of plastic and inhibit cell growth
plastic acts as insulator
what can scale-up rules effect on cells?
can destroy or injure cells
change their metabolic response or physiological functions
scale up rules: constant power/volume
constant oxygen transfer rate
scale up rules; constant Re
geometrically similiar flow patterns
scale up rules: constant impeller speed
constant mixing times
scale up rules: constant tip speed
constant shear
what are some transport problems during scale up?
degree of heterogeneity in fermenter
change in controlling regime
how do we approach transport problems during scale up?
characteristic time constants
what does pure culture mean?
only the desired organism is detectably present
what is disinfection?
different from sterilization, will greatly reduce the number of viable organisms to a low but non zero value
what does sterility mean?
absence of any detectable viable organisms
what does death mean?
failure of the cell, spore or virus to reproduce or germinate when placed in a favorable environment
what are the types of sterilization agents?
thermal
chemical
radiation
filtration
batch vs continuous sterilization
batch:
longer heat up/cool down time
incomplete mixing
can damage medium
continuous:
shorter time
higher temperature
less damage to the medium
reduced down time in fermenters
Note
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