1. Immobilized Cell System
Provide high cell concentration
Reuse cell
Elimination of washout problem at high dilution rate and cell recovery
May provide favorable microenvironmental conditions
May prove genetic stability
Protect against shear damage
Can perform multi-step biosynthesis reactions that are not practical purified immobilized enzyme preparation.
Disadvantages:
Diffusional limitation are important.
Growth and gas evalution may lead to significant mechanical disruption of the immobilizing matrix.

2. Immobilized Cell System
Immobilized methods:
- Active immobilization of cells
Entrapment and Binding
similar to immobilized enzyme except covalently binding (toxic agents, e.g. glutaraldehyde)
- Passive immobilization of cells: biological film.
Multi-layer growth of cells on solid surface.
e.g. common in biological waste water treatment and mold fermentation
thick biofilm: high concentration but diffusion problem
Bioreactor consideration:
- low hydrodynamic shear: packed-column, fluidized-bed or airlift reactors.

3. Bioreactor Operation Consideration
Mixing - Agitation and Aeration
To provide adequate mixing of its contents is one the most factors to consider in design a fermenter.
- to disperse the air bubbles
- to suspend the organism cells
- to enhance heat and mass transfer in the medium
Agitation: providing mixing
Aeration: providing oxygen and mixing in aerobic systems

4. Scale-up stirred-tank reactor bubble column jet loop reactor
airlift loop reactor
propeller loop reactor

5. Bioreactor Operation Consideration
Some basic bioreactor types for aerobic cultivation of suspended cells:
Reactors with Internal mechanical agitation.
high KLa, flexible, medium with high viscosity
Bubble column relying on gas sparging for agitation
must avoid plugging of spargers
Loop reactors: mixing and liquid circulation are induced by the motion of an injected gas, by a mechanical pump, or by a combination of the two.
similar to the above.

6. Bioreactor Operation Consideration
- Internal mechanical Agitation
Rushton impeller: impeller diameter 30-40% of the tank diameter, 1980s
Axial flow system hydrofoil impellers:
increasingly popular
Baffle: to augment mixing and gas dispersion

7. Bioreactor Operation Consideration
Volumetric oxygen mass transfer coefficient determination
Unsteady state method:
An examined reactor filled with pure water or a medium, no organism cells.

8. Bioreactor Operation Consideration
- Heat removal: internal coil and jacketed vessel
Foam: increases pressure drop, decreases gas flow and provide a pathway for contaminated cells’ entry
- mechanical foam breaker
- surfactant (toxic)
The working volume is 75% of the total fermenter volume.
Sterility: pressurized steam for in-place sterilization of reactors, seals, probes and valves.
limited openings.
- Clean: spray balls for clean-in-place

9. Instrumentation and control
Parameters: to be monitored and controlled
Temperature
Pressure
Agitator shaft power
Flowrate
Liquid level
Viscosity
Turbidity pH
Redox potential
Ion concentration DO
Read pages in the text book.