FERMENTER DESIGN

BY:

NIKHIL.K.POTDUKHE M.PHARM

INTRODUCTION
Fermenter y Guidelines for fermenter design y Requirements of a fermenter y Parameters for fermenter design y Gas transfer y Heat transfer y Nutrient transfer y Aeration & agitation y References
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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

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3 to 0.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: 0.4 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 .

-Agitation and aeration -Cell suspension -Enhance the aeration (oxygen limitation problem) -Mixing -Problem with shear-sensitive cells -Heating and cooling -Sensors -pH Control .Cont«««.

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 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 .

turnovers-perminute.MIXING RELATED DESIGN ISSUES ‡ Agitator selection. ‡ Heat removal. ‡ Power draw and torque calculations. . cloud height). blend time. ‡ Blending performance (scale of agitation. ‡ Scale-up. settled solids fraction. possible heat damage. ‡ Mechanical design. homogeneity). temperature field. ‡ Solid-liquid mixing (just-suspended speed.

solids and gas drawdown. ‡ pH control. gas holdup. ‡ Surface motion. ‡ Shear rates and impact velocities. ‡ Reaction performance (productivity. ‡ Oxygen starvation or poisoning (local or global). possible shear damage.Cont«««. . ‡ Substrate concentration field. selectivity). ‡ Gas-liquid mixing (mass transfer. power factors). nutrient starvation. ‡ Optimum feed locations. ‡ CO2 or other product poisoning (local or global)..

PARAMETERS FOR THE FERMENTER DESIGN y Physical Parameters Chemical Parameters Biochemical Parameters Biological Parameters y y y .

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

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

BIOCHEMICAL PARAMETERS y y y y y y y Amino acids ATP/ADP/AMP Carbohydrates Cell mass composition Enzyme NAD/NADH Vitamins & nucleic acid .

BIOLOGICAL PARAMETERS y y y y y y y Age distribution Aggregation & contamination Genetic instability Mutation Total cell count Degeneration Doubling time .

GAS TRANSFER y 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.

Rate of utilization of DO by microbial biomass .y The availability of the oxygen to the biological system depends upon: 1.Mass transfer rate of oxygen in the fermentation broth 3.Solubility 2.

a = overall mass transfer coefficient y y . the saturation level increases as the total pressure of the system increases. a(m²) ‡ The thickness of the liquid fi lm. the saturation level of dissolved oxygen is lower in warmwater than coldwater systems. Cs ± C ‡ The area of the gas-liquid interface. D dC/dt = KL . Gas solubility increases as the total pressure (sum of atmospheric and hydrostatic pressure) or mole fraction increases. (Cs ± C) Where: dC/dt = rate of gas transfer KL . In other words. a . The rate of dissolution of a gas into water is proportional to: ‡ The difference between actual and saturation concentrations of the gas in solution. d ‡ The diffusion coefficient. For example.y Solubility decreases as temperature or salinity increases.

) y Sodium sulfite oxidation method Dynamic method Direct method Oxygen yield coefficient method y y y .DETERMINATION OF OXYGEN TRANSFER COEFFICIENTS KLa =no2/(C* ± CL )-------1.

KLa = no /C* 2 Where. Of 10¯ M & mechanical agitation. in solution .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.   no2 =rate of oxygen transfer C*=saturation dissolved oxygen conc. Of dissolved oxygen in the liquid is nearly zero since the oxidation reaction is extremely fast. Therefore. NaSO3 + ½ O2  Na2SO4 To find KLa by this method. ³  The conc. air is sparged through a 1 N Na2SO3 solution in the presence of copper ions at a conc.

which has the following form y dCL/dt = KL . (C* ± CL)-Qo2X Where y Qo2X=rate of oxygen consumption per unit mass of cell .DYNAMIC METHOD y This method is the simplest one since it requires only the dynamic oxygen balance in a batch culture. a .

This method contains three versions: y y y y Addition of lethal agent The gassing out method Dynamic oxygen balance Frequency response technique Therefore. KLa can be calculated as: KLa = Qo2X/ C* ± CL .

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..i no2. CL & C*.T = 1/VL(no2.T = rate of oxygen transfer VL=volume of fermentation broth The dissolved & saturated oxygen conc. oxygen balance for the sparged air yields no2.DIRECT METHOD y This method based upon oxygen balance in inlet & outlet gas streams around a fermenter. .o) Where no2.

between the inlet & outlet of the fermenter should be used in the following equation determining KLa. mean of the driving force i.mean. y But in large scale fermenter.mean .e. the assumption of a perfectly mixed gas stream may not be valid.Cont««.T/ (C* ± CL)log. the log. So..(C* ± CL)log. KLa = no2.

Yo2 = yield coefficient of oxygen no2. .T = oxygen transfer rate Once no2. no2.T = uX/Yo2 y Where U = specific growth rate of microorganism X = cell conc.) can be used to calculate the KLa provided that the dissolved oxygen conc. is measured.T is determined by this equation then equation 1.OXYGEN YIELD COEFFICIENT METHOD y The rate of oxygen transfer can be related to the growth rate of microorganism using the Oxygen yield coefficient according to the following eq.

HEAT TRANSFER y y y y 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 .

y .TRANSPORT OF NUTRIENT y 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.

Baffles -.Spargers -. The structural components are: -.Impellers -.Stirrer gland y y .AERATION AND AGITATION y 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.

. heat transfer. mixed flow. of mixing objectives ex.bulk fluid & gas phase mixing. in general more vanes are more efficient. axial and peripheral and are selected on the basis of the pump design and the application. air dispersion & maintaining a uniform environment through out the vessel contents. The agitator is required to achieve a no. oxygen transfer. y y . The number of vanes will affect the efficiency.IMPELLERS y Impeller types can be radial..

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SPARGER y y What is a Sparger? Sparger is a technical term for injecting gas into a liquid or for spraying a liquid onto a solid. . 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.. Porous Stones and Diffusers. Spargers are porous disc or tube assemblies that are also referred to as Bubblers. Aerators. Carbonators. Porous Metal Spargers are widely used in Gas-Liquid contacting applications that affect everyday living.

Cont««.agitator Typical sparger installation . Types of spargers: Porous sparger Orifice Nozzle Combined sparger.

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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 GLAND y 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: Stuffing box Simple bush seal Mechanical seal Magnetic drive y y y y y .

WHITAKER Bioprocess engineering.L.F.STANBURY & A.REFERENCES y Principles of fermentation technology.google. basic concepts.SHULER & F.com y y y .com www. 2nd edition by P. 2nd edition by M.KARGI ebook.

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