Bioprocess Module 9

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