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Question 1

Types of bioreactors

Answer 1

1) Stirred tank bioreactor
2) Wave bioreactor
3) Bioreactor Process Control and Monitoring
4) Sterilisation and Cleaning of bioreactor

Question 2

Types of Stirred tank bioreactors

Answer 2

1) Stainless steel
2) Single-use

Question 3

Strategies for operation of bioreactors

Answer 3

1) Discontinuous
- Batch
- Fed-batch
2) Continous

Question 4

Discontinuous bioreactor

Answer 4

• Nothing in,except oxygen for aerobic microbes, antifoam agent, and acid or base to control ph
• Nothing out until process is terminated
• limits cell-density due to accumulation of toxic metabolic products and depletion of substrate
• sometimes, initial substrate may have to be limited due to substrate solubility limits, inhibition and repression.

Question 5

Fed-batch bioreactor

Answer 5

• substrate is added in increments during fermentation
• when a liquid feed stream enters the bioreactor, the culture volume is altered

Question 6

Advantages of fed-batch reactor

Answer 6

1) Control concentration of substrate at desired levels
2) Good when controlling concentrations of a nutrient affect the yield of the desired product
3) Longer growth phase
4) Higher cell and/or product concentrations
5) Mode of choice - High product titers

Question 7

Perfusion

Answer 7

• Cells are separated from the outflow stream and retained inside the bioreactor
• When substrate concentrations reach critical values, fresh medium is added to the culture system at the same flow rate as the exhausted medium is removed.

Question 8

Advantages of perfusion

Answer 8

1) High cell concentrations
2) Culture over longer periods, even months

Question 9

Challenges of perfusion

Answer 9

1) Reliability of cell retention device
2) Cell viability and/or productivity are not affected

Question 10

Aerobic bioreactor

Answer 10

• issue with a bioreactor design lies in the provision of adequate mixing and aeration for large proportion of fermentation requiring oxygen.
• Used for:
  
  • free and immobilised enzyme reactions
  • culture of suspended and immobilised cells
• mixing and bubble dispersion achieved by mechanical agitation

Question 11

Impellers in stirred tank bioreactor

Answer 11

• different shapes and sizes
• different flow patterns

Question 12

Baffles in stirred tank bioreactor

Answer 12

• reduce vortexing

Question 13

Advantages of stirred tank bioreactor

Answer 13

1) suitable for batch or continous
2) adequate mixing and aeration
3) good temperature control

Question 14

Disadvantages of stirred tank bioreactor

Answer 14

1) High shear stresses from the impeller may damage sensitive cells

Question 15

Turndown ratio

Answer 15

refers to width of the operational range of a device, and is defined as the ratio of the maximum capacity to minimum capacity.

Question 16

Why is mixing important?

Answer 16

1) blend soluble components in liquid
2) disperse gases through liquid in the form of small bubbles
3) maintain suspension of solid particles such as cells and cell aggregates
4) promote heat transfer to and from liquid
5) disperse immiscible liquids to form an emulsion

Question 17

Factors affecting liquid flow pattern

Answer 17

• impeller design
• size and geometry of tank
• properties of the fluid (eg. viscosity)

Question 18

Single-use stirred tank bioreactor

Answer 18

Culturing cells in an integral plastic bag that could be mounted within a cylindrical frame to support the bag

Question 19

Wave bioreactor

Answer 19

• used for culture of animal and plant cells, bacteria and viruses.
• rocking platform in motion creates waves in a culture bag
• cell culture media
• cells seeded on micro-carriers as aggregates

Question 20

Principles of wave bioreactor

Answer 20

• Cells and cell culture media contact only a pre-sterile, disposable chamber called the cell bag that rests on a rocking platform
• Rocking motion induces waves in the cell culture media allowing efficient mixing
• Single use, requires no cleaning or sterilisation
• suitable for cultures of up to 500L

Question 21

Biological parameters

Answer 21

1) biomass concentration and composition
2) enzyme concentration
3) viability of cells
4) morphology of cells

Question 22

Cell growth monitoring

Answer 22

• cell growth is monitored by manual or automated counting
• during cell counting, live cells and dead cells can be differentiated by adding a chemical stain
• 2 parameters obtained from cell counting: viable cell density and viability

Question 23

Methods of monitoring

Answer 23

1) On-line monitoring
2) Off-line monitoring

Question 24

On-line monitoring

Answer 24

measures parameter directly from process
(ph,temp,dissolved oxygen,flow rate, stirrer speed)

Question 25

Off-line monitoring

Answer 25

involves the removal of samples and subsequent measurement
(biomass concentration and composition)
also known as atline analyses

Question 26

Challenges in designing bioprocess controller

Answer 26

1) Living organisms are involved
2) Their dynamic behaviour is non-linear and time-varying
3) Complex biological phenomena involving genetic mutation and metabolic variations of cell mass.

Question 27

Proportional controller (P)

Answer 27

-output is proportional to error
- greater the magnitude of error, greater the corrective action
- leads to offset

Question 28

Integral controller (I)

Answer 28

• output is determined by the integral of the error over operation time
• corrective action is slow in the beginning
• no offset

Question 29

Derivative controller (D)

Answer 29

• output is proportional to the rate of change of error
• if error is not changing, there is no corrective action