FERMENTER DESIGN

BY:

NIKHIL.K.POTDUKHE
M.PHARM
INTRODUCTION
Fermenter
Guidelines for fermenter design
Requirements of a fermenter
Parameters for fermenter design
Gas transfer
Heat transfer
Nutrient transfer
Aeration & agitation
References
FERMENTER
 Fermenter provide a suitable environment in which an
organism can efficiently produce a target product, that might
be:
1.Cell biomass
2.Metabolite
3.Bioconversion product

 The sizes of bioreactor can vary over several orders of

magnitudes.
1.The microbial cell (few mm³)
2.Shake flask (100-1000ml)
3.Laboratory fermenter (1-50 L)
4.Pilot scale (0.3-10 m³)
5.Plant scale (2-500 m³)
PARTS OF FERMENTER

.
1 Vessel
2.Impellers
3.Baffle
4.Sparger
5.Drain point
6.Shaft
7.Aseptic inoculation pipe
8.Sampling point
GUIDELINES FOR FERMENTER
DESIGN AND OPERATION
 Material: Stainless steel
 Height to diameter ratio of the vessel: 2 to 1
or 3 to 1
 Impeller
 Two or three disk turbine impellers
 Diameter: 0.3 to 0.4 of tank diameter
 Agitation speed: 50 – 200 rpm
 Impeller shaft enters either from the top or
bottom.
 Baffle
 Four equally spaced to prevent vortex
formation
 Width: one tenth of the tank diameter
 Sparger
 Ring sparger (Single orifice for a small
Fermenter)
 Heating or cooling coil
 For sterilization or to control the temperature
Cont……….

-Agitation and aeration

-Cell suspension
-Enhance the aeration (oxygen limitation problem)
-Mixing
-Problem with shear-sensitive cells
-Heating and cooling
-Sensors
-pH Control
DESIGN OF A FERMENTER

Factors to consider when designing a fermenter

 Aseptic and regulator capability, long-term

reliability
 Adequate aeration and agitation
 Low power consumption
 Temperature and pH controls
 Sampling facilities
Cont………..

 Large volume & low value products

 High value & low volume products

 Productivity & yield

 Product purification

 Water management

 Energy requirements

 Waste treatment
REQUIREMENTS OF A
FERMENTOR

 The vessel must be strong enough to withstand

pressure

 The vessel should not corrupt the fermentation

product

 Preventionof growth of contaminating

microorganism must be provided

 Efficient O2 Supply if fermentation is aerobic

 Cont……..

 Addition of anti-foaming agent as demanded by the

foaming state of the medium

 Fermenter should posses temperature Control

 Fermenter should posses a mechanism for detecting

pH values of culture media

 There must be drain in the bottom of the fermenter

MIXING RELATED DESIGN
ISSUES

• Agitator selection.
• Power draw and torque calculations.
• Scale-up.
• Mechanical design.
• Blending performance (scale of agitation, turnovers-per-
minute, blend
time, homogeneity).
• Heat removal, temperature field, possible heat damage.
• Solid-liquid mixing (just-suspended speed, settled solids
fraction, cloud
height).
Cont………..

• Reaction performance (productivity, selectivity).

• Surface motion, solids and gas drawdown.
• Shear rates and impact velocities, possible shear
damage.
• Optimum feed locations.
• Substrate concentration field, nutrient starvation.
• Oxygen starvation or poisoning (local or global).
• CO2 or other product poisoning (local or global).
• pH control.
• Gas-liquid mixing (mass transfer, gas holdup,
power factors).
PARAMETERS FOR THE
FERMENTER DESIGN
Physical Parameters

Chemical Parameters

Biochemical Parameters

Biological Parameters
 PHYSICAL PARAMETERS
1. Agitation power & speed
2. Broth volume
3. Color
4. Density
5. Foaming
6. Gas flow rate & humidity
7. Heat generation rate & transfer rate
8. Liquid flow rate
9. Temperature
10. Osmotic pressure
CHEMICAL PARAMETERS

1. Amino acid
2. CO2
3. Cat ion level
4. Conductivity
5. Ionic strength
6. Malliard reaction products
7. Nitrogen
8. Nutrient composition
9. O2
10. Phosphorous
BIOCHEMICAL PARAMETERS

Amino acids
ATP/ADP/AMP
Carbohydrates
Cell mass composition
Enzyme
NAD/NADH
Vitamins & nucleic acid
BIOLOGICAL PARAMETERS

Age distribution
Aggregation & contamination
Genetic instability
Mutation
Total cell count
Degeneration
Doubling time
GAS TRANSFER
The theory of gas transfer refers to a process where
the gaseous form of a compound is eventually
dissolved into or driven out of the water .The rate at
which the gas is transferred from air to water or
vice versa is proportional to the area of the gas-
liquid interface and the difference between
saturation concentration and the actual concentration
in the water. These dictate both the direction and
rate of gas transfer at the gas-water interface.
The availability of the oxygen to the
biological system depends upon:

1.Solubility

2.Mass transfer rate of oxygen in the

fermentation broth

3.Rate of utilization of DO by microbial biomass

 Solubility decreases as temperature or salinity increases. For
example, the saturation level of dissolved oxygen is lower in warm-
water than coldwater systems.

 Gas solubility increases as the total pressure (sum of atmospheric

and hydrostatic pressure) or mole fraction increases. In other words,
the saturation level increases as the total pressure of the system
increases.

 The rate of dissolution of a gas into water is proportional to:

• The difference between actual and saturation concentrations of
the gas in solution, Cs – C
• The area of the gas-liquid interface, a(m²)
• The thickness of the liquid fi lm, d
• The diffusion coefficient, D

dC/dt = KL . a . (Cs – C)
Where:
dC/dt = rate of gas transfer
KL . a = overall mass transfer coefficient
DETERMINATION OF OXYGEN
TRANSFER COEFFICIENTS
KLa =no2/(C* – CL )-------1.)

Sodium sulfite oxidation method

Dynamic method

Direct method

Oxygen yield coefficient method

SODIUM SULFITE OXIDATION
METHOD
 This method employs the oxidation of sodium sulfite by oxygen in the
presence of copper or cobalt which act as catalyst.

NaSO3 + ½ O2 → Na2SO4

 To find KLa by this method, air is sparged through a 1 N Na2SO3 solution

³
in the presence of copper ions at a conc. Of 10¯ M & mechanical agitation.
 The conc. Of dissolved oxygen in the liquid is nearly zero since the oxidation
reaction is extremely fast. Therefore,

KLa = no /C* 2

Where,

 no2 =rate of oxygen transfer

 C*=saturation dissolved oxygen conc. in solution

DYNAMIC METHOD
 This method is the simplest one since it requires only
the dynamic oxygen balance in a batch culture, which
has the following form

 dCL/dt = KL . a . (C* – CL)-Qo2X

Where
Qo2X=rate of oxygen consumption per unit mass of
cell
This method contains three versions:

Addition of lethal agent

The gassing out method
Dynamic oxygen balance
Frequency response technique

Therefore, KLa can be calculated as:

KLa = Qo2X/ C* – CL
DIRECT METHOD

 This method based upon oxygen balance in inlet & outlet gas
streams around a fermenter. oxygen balance for the sparged air
yields
no2.T = 1/VL(no2.i ‒no2.o)
Where

no2.T = rate of oxygen transfer

VL=volume of fermentation broth
The dissolved & saturated oxygen conc., CL & C*, need to be
measured experimentally in order to determine KLa
C* can be calculated from the partial pressure of oxygen in
the exit gas stream in small scale fermenter.
Cont…….

 Butin large scale fermenter, the assumption of a

perfectly mixed gas stream may not be valid. So, the
log. mean of the driving force i.e.,(C* –
CL)log.mean, between the inlet & outlet of the
fermenter should be used in the following equation
determining KLa,

KLa = no2.T/ (C* – CL)log.mean

OXYGEN YIELD COEFFICIENT
METHOD
 Therate of oxygen transfer can be related to the growth rate
of microorganism using the Oxygen yield coefficient
according to the following eq.
no2.T = uX/Yo2
 Where

U= specific growth rate of microorganism

X = cell conc.

Yo2 = yield coefficient of oxygen

no2.T = oxygen transfer rate
Once no2.T is determined by this equation then equation 1.)
can be used to calculate the KLa provided that the
dissolved oxygen conc. is measured.
HEAT TRANSFER
Efficientheat transfer is important in controlling
the temperature during sterilization operations
Heat generated in the fermentor needs to be
dissipated by cooling
Optimum temp. should be maintain in the
fermentor
This can be achieved by:

◦ External jackets
◦ Internal coils
◦ External surface heat exchanger
TRANSPORT OF NUTRIENT
Transport of reactants to & from phase to
the biological component has a significant
impact on the performance of the reactor.

It is affected if the rate of the transport of

the limiting nutrients is slower than the
rate of utilization by the cells.
AERATION AND AGITATION
 The primary purpose of aeration is to provide
microorganism in submerged culture with sufficient
oxygen for metabolic requirements.

 Agitation should ensure that a uniform suspension of

microbial cells is achieved in a homogenous nutrient
medium.

 The structural components are:

-- Impellers
-- Baffles
-- Spargers
-- Stirrer gland
IMPELLERS
 Impeller types can be radial, mixed flow, axial and
peripheral and are selected on the basis of the pump
design and the application.
 
 The number of vanes will affect the efficiency, in
general more vanes are more efficient..

 The agitator is required to achieve a no. of mixing

objectives ex..bulk fluid & gas phase mixing, oxygen
transfer, heat transfer, air dispersion & maintaining a
uniform environment through out the vessel contents.
SPARGER
 What is a Sparger?
 Sparger is a technical term for injecting gas into a liquid
or for spraying a liquid onto a solid. Spargers are porous
disc or tube assemblies that are also referred to as
Bubblers, Carbonators, Aerators, Porous Stones and
Diffusers. Porous Metal Spargers are widely used in
Gas-Liquid contacting applications that affect everyday
living. A common example of sparging can be seen in
an aquarium where air is bubbled into the tank through a
fine porous “stone” in order to maintain the level of the
dissolved oxygen in the water..
Cont…….

Types of spargers:

 Porous sparger
 Orifice
 Nozzle
 Combined sparger- agitator

Typical sparger installation

BAFFLES
 Four baffles are normally incorporated into vessel of all
sizes to prevent a vortex & to improve aeration
efficiency.

 Theagitation increased with wider baffles but drops

sharply with narrow baffles.
STIRRER GLAND
 The satisfactory sealing of the stirrer shaft assembly has
been one of the most difficult problems to overcome in
the construction of fermentation equipment which can
be operated aseptically for long periods.

 Types of stirrer glands:

 Stuffingbox
 Simple bush seal
 Mechanical seal
 Magnetic drive
REFERENCES
Principles of fermentation technology, 2nd
edition by P.F.STANBURY & A.WHITAKER

Bioprocess engineering, basic concepts, 2nd

edition by M.L.SHULER & F.KARGI

ebook.com

www.google.com
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