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

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 downflowing 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 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
A foam breaker may be installed to disperse foam

dCs rm axCS r dt K m CS
Batch operation with stirring

Cs 0 K m ln C s 0 C s rm axt Cs

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.
An ideal plug-flow reactor can approximate the long tube, packed-bed and hollow fiber or multistaged reactor F, Cs0 V F, Cs

t=0

V F

Residence time

Continuous operation without stirring

Cs 0 K m ln C s 0 C s rm axt Cs

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

F, Cs V

Continuous operation with stirring

Bioreactor Operation Modes -3. Continuous stirred-tank reactor-Con.

F, Cs0

Mass balance of substrate:

Input - Output Consumption Accumulation
F, Cs V

dCs FCs 0 FCs rsV V dt

dCs 0 Steady state: dt

Michaelisrm axC S Menten rate: r K C m S

rm axC s FC s 0 FC s V 0 K m Cs

Bioreactor Operation Modes -3. Continuous stirred-tank reactor-Con.

F, Cs0

Mass balance of substrate:

F, Cs V

rm axC s FC s 0 FC s V 0 K m Cs rm axCs F V Cs 0 Cs K m Cs

F 1 V

rm axCs 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:
V C q 1 Ykcal

Popular method

: heat production rate, kcal/ls q

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

-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

Practical Issues for Bioreactors

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 Kl C C Ag
* A

* CA 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 corrosionresistant 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