FERMENTER DESIGN FERMENTER DESIGN

BY:

NIKHIL.K.POTDUKHE M.PHARM

INTRODUCTIONINTRODUCTIONFermenterGuidelines for fermenter designRequirements of a fermenterParameters for fermenter designGas transferHeat transferNutrient transferAeration & agitationReferences

FERMENTERFERMENTER 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 PARTS OF FERMENTER

11..VesselVessel2.Impellers2.Impellers3.Baffle3.Baffle4.Sparger4.Sparger5.Drain point5.Drain point6.Shaft 6.Shaft 7.Aseptic inoculation pipe7.Aseptic inoculation pipe8.Sampling point8.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 REQUIREMENTS OF A FERMENTORFERMENTOR

The vessel must be strong enough to withstand pressure

The vessel should not corrupt the fermentation product

Prevention of 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 MIXING RELATED DESIGN ISSUESISSUES

• 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 PARAMETERS FOR THE FERMENTER DESIGNFERMENTER DESIGN

Physical Parameters

Chemical Parameters

Biochemical Parameters

Biological Parameters

PHYSICAL PARAMETERSPHYSICAL 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 PARAMETERSCHEMICAL 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 PARAMETERSBIOCHEMICAL PARAMETERS

Amino acidsATP/ADP/AMPCarbohydrates Cell mass compositionEnzyme NAD/NADHVitamins & nucleic acid

BIOLOGICAL PARAMETERSBIOLOGICAL PARAMETERS

Age distributionAggregation & contaminationGenetic instability MutationTotal cell countDegeneration Doubling time

GAS TRANSFERGAS 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 transferKL . a = overall mass transfer coefficient

DETERMINATION OF OXYGEN DETERMINATION OF OXYGEN TRANSFER COEFFICIENTSTRANSFER COEFFICIENTS

KLa =no2/(C* – CL )-------1.)

Sodium sulfite oxidation method

Dynamic method

Direct method

Oxygen yield coefficient method

SODIUM SULFITE OXIDATION SODIUM SULFITE OXIDATION METHODMETHOD

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 in the presence of copper ions at a conc. Of 10¯³ M & mechanical agitation.

The conc. Of dissolved oxygen in the liquid is nearly zero since the oxidation reaction is extremely fast. Therefore,

KLa = no2/C*

Where,

no2 =rate of oxygen transfer

C*=saturation dissolved oxygen conc. in solution

DYNAMIC METHODDYNAMIC 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 agentThe gassing out methodDynamic oxygen balanceFrequency response technique

Therefore, KLa can be calculated as:

KLa = Qo2X/ C* – CL

DIRECT METHODDIRECT 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…….

But in 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 OXYGEN YIELD COEFFICIENT METHODMETHOD

The rate 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 TRANSFERHEAT TRANSFER

Efficient heat 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 NUTRIENTTRANSPORT 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 AGITATIONThe 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

IMPELLERSIMPELLERS

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.

SPARGERSPARGERWhat 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 BAFFLES Four baffles are normally incorporated into vessel of all

sizes to prevent a vortex & to improve aeration efficiency.

The agitation increased with wider baffles but drops sharply with narrow baffles.

STIRRER GLANDSTIRRER GLANDThe 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:

Stuffing boxSimple bush sealMechanical sealMagnetic drive

REFERENCESREFERENCES 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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