Bioreactor Engineering Outline of Lecture 1. Bioreactor configurations 2. Bioreactor operation modes 3.
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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 Waste Nutrients tank Bioreactor Recycle Product 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
Bioreactor Configurations - 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.
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 downcomer.
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 reactant, and the pH of the reactant is maintained by employing either buffer solution or a pH controller Change of Cs with time, t
r
dC s dt
K r
max
m C S C S
Batch operation with stirring
K m
ln
C s
0
C s
C s
0
C s
r
max
t
Bioreactor Operation Modes -2. Plug-flow mode In a plug-flow reactor, the substrate enters one end of a cylindrical tube with is packed with immobilized enzyme and the product steam leaves at the other end.
F, Cs0 V An ideal plug-flow reactor can approximate the long tube, packed-bed and hollow fiber or multistaged reactor t = 0
V F
Continuous operation without stirring
F, Cs
Residence time
K m
ln
C s
0
C s
C s
0
C s
r
max
t
Bioreactor Operation Modes -3. Continuous stirred-tank A continuous stirred-tank reactor (CSTR) is an ideal reactor which is based on the assumption that the reactants are well mixed.
F, Cs0 V F, Cs
Continuous operation with stirring
Bioreactor Operation Modes -3. Continuous stirred-tank reactor-Con.
F, Cs0
Mass balance of substrate:
Input Output Consumptio n Accumulati on V F, Cs
FC s
0
FC s
r s V
V dC s dt
Steady state:
dC s dt
0
Michaelis Menten rate:
r
K r
max
m C S C S FC s
0
FC s
V K r
max
m C s C s
0
Bioreactor Operation Modes -3. Continuous stirred-tank reactor-Con.
F, Cs0 F, Cs
Mass balance of substrate:
FC s
0
FC s
V K r
max
m C s C s
0 V
V F
C s
0
r
max
C s
C
K s m
C s
F V
1
C s
K m
r
max
C s
0
C s
C s
Practical Issues for Bioreactors
Temperature Control (Heat Load)
Heat load: Heat load is determined by energy balances
Heat production rate: q
V
C
1
Y kcal q
: heat production rate,
kcal/l
s
Popular method V: reactor liquid volume,
l
: specific growth rate,
s -1
C: biomass concentration
(g/l)
Y kcal : 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 oxygen
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.
J
C
*
A g P A g
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