Bioreactor Engineering

Outline of Lecture

1. Bioreactor configurations
2. Bioreactor operation modes
3. Practical considerations for
bioreactor design
 What is a bioreactor?
Bioreactor: device, usually a vessel, used to direct the activity of a
biological catalyst to achieve a desired chemical transformation.

Fermenter: type of bioreactor

in which the biocatalyst is a
living cell.

Pre-filtration

Input

Nutrients tank
Waste

Recycle

Product
Bioreactor
Product
separation & purification
 Challenges in Bioreactor Design

1. Aerobic bioreactor: Need

adequate mixing and
aeration
2. Anaerobic bioreactor: no
need for sparging or
agitation
Bioreactor Configurations
- 1. Stirred tank
Mixing method: Mechanical
agitation
• Baffles are usually used to
reduce vortexing
• Applications: free and
immobilized enzyme reactions
• High shear forces may
damage cells
• Require high energy input
• Effective O2transfer and
bubble break
 Bioreactor Configuration
Two class of bubble dirver
- 2. Bubble column
Mixing method: Gas
sparging
• Simple design
• Good heat and mass
transfer
• Low energy input

Gas-liquid mass transfer

coefficients depend largely
on bubble diameter and gas
hold-up without
mechanical agitation
Bioreactor Configurations
- 3. Airlift reactor

Mixing method: airlift

• Compared to bubble
column reactors, in
an airlift reactors,
there are two liquid
steams: up-flowing
and down-flowing
steams. Liquid
circulates in an airlift
reactor as a resutl of
density difference
between riser and
 Airlift bioreactor
Air-riser and down-comer
• An air-lift reactor is divided into three regions:

- the air-riser
- down-comer
- disengagement zone.
 Airlift bioreactors -
Disengagement zone

• The roles of the disengagement zone are to

· add volume to the reactor,

· reduce foaming and

· minimise recirculation of bubbles through the

down comer.
 Airlift bioreactors

• The major disadvantages of air-lift fermenters are

- high energy requirements

- excessive foaming

- cell damage due to bubble bursting;

particularly with animal cell culture
 Airlift bioreactors
• An airlift fermenter differs from bubble column bioreactors
by the presence of a draft tube.
• The main functions of the draft tube are to:
· Increase mixing through the reactor
The presence of the draft tube enhances axial
mixing throughout the whole reactor
· Reduce bubble coalescence.
This presumably occurs due to circulatory effect
that the draft tube induces in the reactor. The
circulation occurs in one direction and hence the
bubbles also travel in one direction.
Bioreactor Configurations
- 4. Packed-bed reactor

Packed-bed
reactors are used
with immobilized
or particulate
biocatalysts.

Medium can be
fed either at the
top or bottom and
forms a
continuous liquid
phase.
Bioreactor Configurations
- 5. Trickle-bed reactor

The trickle-bed
reactor is another
variation of the
packed bed
reactors.

Liquid is sprayed
onto the top of the
packing and
trickles down
through the bed in
small rivulets.
Bioreactor Configurations
- 6. Fluidized bed reactor

When the packed beds

are operated in upflow
mode, the bed expands
at high liquid flow rates
due to upward motion
of the particles.
 Bioreactor Operation Modes
-1. Batch Operation
• A foam breaker may be installed to disperse foam
A batch bioreactor
is normally
equipped with an
agitator to mix the dCs rmax CS
reactant, and the
r 
dt K m  CS
pH of the reactant
is maintained by
employing either
buffer solution or a Batch
operation with
pH controller stirring
Cs 0
Change of
K m ln   C s 0  Cs   rmax t
Cs with time,
Cs
t
 Bioreactor Operation Modes
-2. Plug-flow mode
An ideal plug-flow reactor can
approximate the long tube,
In a plug-flow packed-bed and hollow fiber or
reactor, the multistaged reactor
substrate enters
one end of a F, Cs0 V F, Cs
cylindrical tube
with is packed with V Residence
immobilized t=0  time
enzyme and the
F
Continuous
product steam operation without
leaves at the other stirring
end.
Cs 0
K m ln   C s 0  C s   rmax t
Cs
 Bioreactor Operation Modes
-3. Continuous stirred-tank
A continuous
F, Cs0
stirred-tank reactor
(CSTR) is an ideal
reactor which is
F, Cs
based on the V
assumption that
the reactants are
well mixed. Continuous
operation with
stirring
 Bioreactor Operation Modes
-3. Continuous stirred-tank reactor-Con.
F, Cs0
Mass balance of substrate:
Input - Output  Consumptio n  Accumulation

F, Cs
dCs
V
FCs 0  FCs  rsV  V
dt
dC s
Steady state: 0
dt
Michaelis- rmax CS
Menten rate: r  K  C
m S

rmax C s
FCs 0  FCs  V 0
K m  Cs
 Bioreactor Operation Modes
-3. Continuous stirred-tank reactor-Con.
F, Cs0
Mass balance of substrate:

rmax Cs
FCs 0  FCs  V 0
F, Cs K m  Cs
V

F rmax Cs


V  Cs 0  Cs  K m  Cs 
F 1

V 
rmax Cs
Cs   K m 
Cs 0  Cs
 Practical Issues for Bioreactors
- Temperature Control (Heat Load)
Heat load: Heat load is determined by energy balances

Heat production rate:

1 Popular
q  V    C 
Ykcal method

q : heat production rate, kcal/ls

V: reactor liquid volume, l

: specific growth rate, s-1
C: biomass concentration (g/l)
Ykcal: a yield coefficient given as
grams of cells formed per kcal
energy released, g cells/kcal
 Practical Issues for Bioreactors
-Temperature control (heat transfer)
Heat transfer surface area:
1. Low in (a) external jacket and (b) external coil for small reactors
2. High in (c) internal helical coil and (d) internal baffle coil for large reactors
3. Easily adjustable in (e) a separate external heat exchange unit

Difficult to clean
Easily fouled by cell
growth on the
surface

No cleaning problem

• Sterility
requirement
• Shear forces
imposed on cells
• Depletion of
 Practical Issues for Bioreactors
-Agitation (gas transfer)
1. Biological reactions almost invariably are three-phase reactions
(gas-liquid-solid). Effective mass transfer between phases is often
crucial. For example, for aerobic fermentation, the supply of
oxygen is critical.
The equation governing the oxygen transfer rate is:


J A  K l C  C Ag
*
A  C A*  PAg H

Agitation:
• Mechanical stirring (for small reactors, and/or viscous liquids,
low reaction heat)
• Air-driven agitation (for large reactors and/or high reaction
heat)
Practical Issues for Bioreactors
- Foaming removal

1. Mechanical foam
breaker (a
supplementary
impeller)
2. Chemical antifoam
agents (may
reduce the rate of
oxygen transfer)
 Practical Issues for Bioreactors
- Other issues
1. Aseptic operation (3-5% of fermentations in
an industrial plant are lost due to failure of
sterilization.
2. Construction materials (glass for small
bioreactors, e.g., < 30 liters and corrosion-
resistant stainless steel for large reactors)
3. Sparage design (three designs: porous, orifice
and nozzle)
4. Evaporation control due to dry air input
 Summary of Lecture

1. Bioreactor configurations
2. Bioreactor operation modes
3. Practical considerations for
bioreactor design
 .

THE END

COMING NEXT CLASS DO YOU HAVE

TEST EXAM including part
 enzyme kinetics
 cell kinetics