Bioreactor Design for Chemical Engineers

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Back to Basics, 12 cient at making ethanol whereas others are better at produc. Log Viable Cell Count mL, Stationary ing CO2 to make bread rise The common bacterium E coli. Growth can be modified to make a wide variety of different products. Lag Living organisms can die or go into shock Dead organ. 6 isms will not react and organisms in shock may have a. 4 different productivity or create different products For exam. ple if an aerobic organism is briefly exposed to an anaerobic. region in the reactor it might slow down its metabolism as. 0 20 40 60 a means of protection and it might not return to its normal. Time h metabolic activity for minutes or even hours after return. ing to an aerobic region Thus small regions of suboptimal. p Figure 2 A generic growth curve illustrates the exponential growth of. cells after they are acclimated to the environment After they reach their conditions can have a drastic effect on the productivity of the. maximum density the cells begin to die entire bioreactor This is sometimes called cycling. Nutrient feed and aeration strategies affect not only. inoculum tank are optimized for the production of more rate but also yield and product distribution in a bioreactor. bugs The conditions in the production fermenter may be Unlike chemical reactors different reaction paths or meta. different depending on the product There are sometimes bolic pathways may be used by the organism depending. fewer than three steps from shaker flask to production and on conditions. sometimes there are more depending on the scale of the Although microbiologists normally control issues and. production fermenter strategies related to the organisms chemical engineers. The organisms in most production fermenters follow the complement their knowledge with expertise in mass trans. generic growth curve in Figure 2 After inoculation they fer mixing heat transfer reaction engineering and process. require some time to adjust to the new environment before optimization. they begin growing and the cell density remains almost con. stant for a while This is called the lag phase After acclima Mass transfer. tizing the bugs enter a period of rapid exponential growth Although not a major factor in anaerobic fermentation. called the growth phase mass transfer is crucial in aerobic fermentation Without. When competition for nutrients or oxygen becomes sufficient transfer of oxygen from the air to the liquid organ. limiting growth stops and the organisms enter the station isms may die go into shock or make the wrong product. ary phase During this phase they may continue to make Aerobic processes demand a certain oxygen uptake rate. the desired product If the end product is the organism OUR Under quasi steady state conditions this equals the. itself as in the production of yeast or single cell proteins oxygen transfer rate OTR Although OUR varies through. the process is normally stopped after the growth phase out the process engineers must design for the peak rate. ends as it would be a waste of nutrients and oxygen to Traditional processes have rates ranging from about 100. continue Finally organisms begin to die off this is the mmol L h easy through about 150 200 mmol L h aver. decline or death phase age to more than 300 mmol L h difficult Some newer. After fermentation the broth is sent to a harvest tank to processes occur at microaerobic conditions typically less. await downstream processing The downstream processing than 5 mmol L h Some modified E coli fermentations may. may involve separating cells from the broth and purifying consume up to 500 mmol L h which may require oxygen. the product concentrating the cells if they are the product or enriched air as a feed gas. rupturing the cells if the product is inside them The basic mass transfer equation is. Bioreactor vs chemical reactor OTR k L a C sat C h 1ah. Bioreactors and chemical reactors differ in several Z C C C C. sat hout sat hin b,important respects OTR k L a 1bh. satC C hout, Chemicals react the same way each time and the reac ln. C sat C hin b, tion depends only on composition and temperature No past a.
history of chemicals will affect their reactions There are no The term in parentheses is the driving force It can be. different strains of the same chemical expressed in a simple form Eq 1a or in a log mean form. Different strains of the same organism may have differ Eq 1b In small vessels 1 m tall where both liquid. ent metabolic pathways productivities yields and product concentration and saturation are almost constant the simple. distributions For example some yeast strains are more effi form is adequate In tall vessels the log mean driving force. 22 www aiche org cep August 2011 CEP Copyright 2011 American Institute of Chemical Engineers AIChE. distributed productivity yield and,product distribution can be affected. Some processes and organisms are,more sensitive than others Unfortu. nately there is presently no good way,to model the actual concentration distri. bution in a fermenter Various research,Axial Turbine. ers are attempting to use numerical,Rushton Turbine methods to combine mixing mass.
transfer and reaction kinetics to plot, p Figure 3 Rushton turbines which have six flat p Figure 4 Axial impellers improve mixing in. blades mounted vertically on a disk were used in fermenters They are often combined with radial dissolved oxygen DO distribution but. early bioreactors impellers on a single shaft which typically has the this is a very complex process and there. axial blades above the radial ones are no models on the market to do this. in a user friendly manner, should be used for more accuracy since both the local There are however several strategies to improve mixing. concentration and the saturation concentration are different in a fermenter at a given OTR. in the top and bottom of a bioreactor The driving force is use a combination of axial and radial impellers with. affected considerably by the value of Csat which depends optimal power distribution for example a 3 impeller. on temperature gas concentration and most importantly system with a radial impeller on the bottom and two upper. absolute pressure Generally Henry s Law can be used axial impellers having a 54 23 23 bottom to top power. distribution, Csat pO2 H 2 when in doubt add an extra axial impeller. specify upper axial impellers to be up pumping which. where H is the Henry s law constant which is a function of seems counter intuitive but such an arrangement has a. temperature Values for Henry s constant may be found in shorter blend time when air is introduced than a down. standard reference handbooks pumping system, It might be tempting to increase the saturation value by use a larger impeller diameter to tank diameter ratio. increasing backpressure However there is a limit to how D T 0 33 if viscosity exceeds about 250 cP. high backpressure can be raised High backpressures impede One might think that in anaerobic bioreactors mix. the release of CO2 which must be kept below reasonable ing would not be an issue since reaction times are always. partial pressures to maintain healthy organisms In practice very long compared to blend times and there seem to be. fermenters usually have a backpressure of less than 1 bar no significant mass transfer issues However agitation in a. The other term in Eq 1 kLa is the overall mass transfer simple ethanol fermenter was found to affect productivity. coefficient It is usually treated as a single variable because it yield and maximum product concentration at specific power. is difficult to separate the interfacial area per unit volume a inputs an order of magnitude or more higher than needed. from the film coefficient kL It is a function primarily of the to mix nutrients or keep solids in suspension 4 Unfortu. broth type superficial gas velocity and agitator power input nately the mechanism responsible for these effects is not. and is often expressed as clear Process engineers may wish to study these effects in. specific fermentations on more than one scale to determine. kLa A P V B US C 3 how to scale up the bioreactor, References 1 3 provide more detailed discussions of agi Heat transfer.
tation airflow mass balances and agitator impeller systems Heat transfer requirements for bioreactors vary. for aerobic fermenters Anaerobic fermenters and cell culture reactors typically. have very low rates of heat production whereas aerobic. Mixing fermenters can have quite high heat production rates The. The first bioreactors used multiple Rushton turbines rate usually correlates well to oxygen consumption A good. Figure 3 which create a staged mixing pattern that does estimate is 460 000 kJ mol of oxygen consumed 5 or. not promote oxygen or nutrient uniformity Almost all new about 110 kcal mol A mid range OUR of 200 mmol L h. fermenters have a combination of axial Figure 4 and radial translates to a heat transfer rate of 22 kcal L h The heat. impellers or all axial impellers to improve mixing of agitation and the air expansion power must be added. When nutrients or dissolved oxygen are not uniformly to this and the heat of water evaporating by airflow is. Copyright 2011 American Institute of Chemical Engineers AIChE CEP August 2011 www aiche org cep 23. Back to Basics,Heat Tranfer Heating Coils Also,Baffles Baffles Helical Coil. Medium Act as Baffles,Heat Tranfer,Second Shell Agitator Agitator. Jacketed Tank Helical Coil Tube Baffles, p Figure 5 Many fermenters remove heat p Figure 6 Helical coils are often installed p Figure 7 Vertical tube bundles which double. using tank jackets in fermenters to remove heat as tank baffles are another type of internal. structure that can remove heat from fermenters, subtracted since it is assumed that the gas enters dry and NNu K NRe 2 3 NPr 1 3 w 0 14 T Z 0 15 5. leaves saturated with water, Even though these heat loads are lower than in many where K 0 74 for Rushton turbines K 0 45 for pitched.
chemical reactions the removal of this heat is made more blade turbines and K 0 31 for common hydrofoils. difficult by the mild operating temperatures typically For a single helical coil with the Nusselt number defined. between 30 C and 40 C for aerobic fermenters As a result as NNu hcdt k. cooling tower water at 30 C is usually inadequate so chilled. water is often used instead NNu K NRe 0 67 NPr 0 37 D T 0 1 dt T 0 5 6. Heat may be removed by an external heat exchange loop. or internal vessel surface The external loop can be made where K 0 17 for pitched blade or radial turbines and. in whatever capacity is needed but may expose organisms K 0 14 for common hydrofoils. to thermal shock and oxygen deprivation Most fermenters For a single bank of vertical tube baffles and the same. therefore use internal surfaces Examples of these include Nusselt number definition NNu hcdt k. tank jackets Figure 5 helical coils Figure 6 and vertical. tube bundles which double as tank baffles Figure 7 Large NNu K NRe 0 65 NPr 0 3 D T 0 33 2 nb 0 2 w 0 14 7. fermenters may require multiple bundles with multiple rows. of tubes per bundle Figure 8 where K 0 09 for pitched blade or radial turbines and. The following equations may be useful for calculating K 0 074 for common hydrofoils. the process side convective heat transfer coefficients h and For multiple banks of helical coils or multiple rows of. hc which are incorporated into the Nusselt number NNu tubes within a bundle the masking effect on the process side. The Nusselt number is used in all standard convective heat coefficient can be estimated by using a factor of 0 8 for each. transfer correlations to relate the convective heat transfer additional row beyond 1. coefficient to physical dimensions thermal conductivity. turbulence and other fluid property and geometry effects K multiple K 0 8 n 1 8. For bottom jackets as in Figure 5,where n is the number of rows in each bundle. NNu K NRe 2 3 NPr 1 3 w 0 14 4 Agitation equipment should be chosen based on mixing. and mass transfer requirements not on heat transfer The. where K 0 5 for Rushton turbines K 1 08 for pitched exponent on agitator power input on the process side coef. blade turbines and K 0 9 for common hydrofoils For ficient is only about 0 22 which can be derived from the. jackets the Nusselt number is NNu hT k above equations and agitator power proportional to N3D5. For jacket sidewalls Figure 5 so little additional heat transfer is gained by increasing. 24 www aiche org cep August 2011 CEP Copyright 2011 American Institute of Chemical Engineers AIChE. power Instead if there is a problem add area or change. t Figure 8 Large, the temperature of the cooling medium fermenters may need. In low viscosity fermentations sometimes the heat multiple bundles with. transfer resistance on the cooling media side of the heat multiple rows of tubes. exchange system is higher than on the agitated side i e the per bundle to remove. the heat produced by, process fluid side In such cases the overall heat transfer the process. coefficient may be improved by using internally finned pipe. or tubing or an annular double pipe arrangement If the ves. sel is jacketed a dimpled jacket or half pipe jacket may be. more effective than a plain jacket,Reaction engineering. As long as conditions are suitable for the microorganisms. inside the bioreactor the bioreactions may be treated as any Vertical Tube Bundles. other chemical reaction although the kinetic expression may. be more complicated than simple first or second order and less total power for a given OTR In addition they are easier. bioreactor design from a chemical engineering viewpoint Details of the biological processes are beyond the scope of this article and are not discussed Kinds of bioreactors Here the terms fermenter and bioreactor are used interchangeably In general there are two main classes of bioreactors anaerobic and aerobic

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