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Mass Transfer

5.1

Mass Transfer in Biological Reactors

Multiphase reaction systems usually involve the transport of material between two or more phases. Usually one of the reactants is transferred from one phase into a second phase, in which the reaction takes place. The following cases are examples of biological systems.

5.1.1 Gas Absorption with Bioreaction in the Liquid Phase


The gas phase is dispersed as gas bubbles within the liquid phase. Mass transfer occurs across the gas-liquid interface, out of the gas into the liquid, where the reaction occurs. The typical example is aeration of the bioreactor broth and the supply of oxygen to the cells as shown in Fig. 5.1.

Figure 5.1. Absorption of oxygen from an air bubble to the liquid medium.

Biological Reaction Engineering, Second Edition, I. J. Dunn, E. Heinzle, J. Ingham, J. E. Pfenosil Copyright 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30759-1

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5 Mass Transfer

5.1.2

Liquid-Liquid Extraction with Bioreaction in One Phase

An immiscible liquid phase is dispersed in a continuous liquid phase. Mass transfer of a reactant takes place across the liquid-liquid interface, shown here (Fig. 5.2) from the continuous phase into the dispersed phase, where reaction occurs. An example might be the transfer of a substrate in an oil phase to an enzyme in the droplet aqueous phase.

Figure 5.2. Liquid-liquid extraction plus reaction.

5.1.3

Surface Biocatalysis

In this case, a liquid phase is in contact with solid biocatalyst. Substrates A and B diffuse from the liquid to the reaction sites on the surface of the solid, where reaction occurs. The product C must similarly be transferred away from the solid reaction surface, as shown in Fig. 5.3. Examples are found with immobilized enzyme and cell systems. In Sec. 6.1 the modelling aspects of this type of system are considered in detail.

5.2 Interface Gas-Liquid Mass Transfer

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Figure 5.3. Reaction of two substrates on a solid biocatalyst surface.

5.1.4

Diffusion and Reaction in Porous Biocatalyst

Here a porous biocatalyst sphere is suspended in a liquid medium. Substrates diffuse into the porous internal structure of the biocatalyst support and react. Similarly, the products must diffuse away from the reaction sites within the solid to the outer surface, where they are then transported into the liquid. Detailed modelling of this process is treated in Ch. 6.

Figure 5.4. Reaction within a solid biocatalyst.

5.2

Interphase Gas-Liquid Mass Transfer

Concentration gradients are the driving forces for mass transfer. Actual concentration gradients (Fig. 5.5) in the very near vicinity of the gas-liquid

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5 Mass Transfer

interface, under mass transfer conditions, are very complex. They result from an interaction between the mass transfer process and the local fluid hydrodynamics, which change gradually from stagnant flow, close to the interface, to perhaps fully-developed turbulence within each of the bulk phases. According to the Two-Film Theory, the actual concentration profiles, as represented in Fig. 5.5 can be approximated by linear gradients, as shown in Fig. 5.6. A thin film of fluid is assumed to exist at either side of the interface. Away from these films, each fluid is assumed to be in fully developed turbulent flow. There is therefore no resistance to mass transfer within the bulk phases, and the concentrations, CG and CL, are uniform throughout each relevant phase. At the phase interface itself, it is assumed there is no resistance to mass transfer, and the interfacial concentrations, CGI and CLI, are therefore in local equilibrium with each other. All the resistance to mass transfer must, therefore, occur within the films. In each film, the flow of fluid is assumed to be stagnant, and mass transfer is assumed to occur only by molecular diffusion and therefore to be
Interface
Gas

Figure 5.5. Concentration gradients at a gas-liquid interface.

described by Pick's law, which says that the flux JA (mol/s m2) for the molecular diffusion of some component A is given by,

dZ

5.2 Interface Gas-Liquid Mass Transfer

121
Interface

Gas

Liquid

Figure 5.6. Concentration gradients according to the Two-Film Theory.

where D is the molecular diffusion coefficient (m2/s) and dC/dZ is the steady state concentration gradient (mol/m3). Thus applying the same concept to mass transfer across the two films,

JA = DG

where DG and DL are the effective diffusivities of each film, and ZG and ZL are the respective thicknesses of the two films. The above equations can be expressed in terms of mass transfer coefficients kc and kL (m2/s) for the gas and liquid films, JA = k G (C G -C G i) = k L (C Li -C L ) The total rate of mass transfer, Q (mol/s), is given by, Q = JAA = jA(aV) where "A" is the total interfacial area available for mass transfer, and "a" is defined as the specific area for mass transfer or interfacial area per unit liquid volume (m2/m3). Thus for the total rate of mass transfer: In terms of the total interfacial area A, Q = k G A(C G -C G i ) = k L A(C L i -C L ) In terms of a and VL, Q = ko a (Co - CGi) VL = k L a(C L i -C L )V L

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5 Mass Transfer

Since the mass transfer coefficient, k, and the specific interfacial area, a, depend on the same hydrodynamic conditions and system physical properties, they are frequently combined and referred to as a "ka value" or more properly a mass transfer capacity coefficient. In the above theory, the interfacial concentrations CGI and CLI cannot be measured, and are therefore of relatively little use, even if the values of the film coefficients are known. For this reason, by analogy to the film equations, overall mass transfer rate equations are defined, based on overall coefficients of mass transfer, KG and KL, and overall concentration driving force terms, where: Q = K G A(C G -C G *) = K L A(C L *-C L ) Here, CG* and CL* are the respective equilibrium concentrations, corresponding to the bulk phase concentrations, CL and CG, respectively, as shown in Fig. 5.6. Equilibrium relationships for gas-liquid systems, at low concentrations of component A usually obey Henry's law, which is a linear relation between gas partial pressure, PA, and equilibrium liquid phase concentration, CLA*:

PA=
where HA (bar m3/kg) is the Henry's law constant for component A in the medium. Henry's law is generally accurate for gases with low solubility, such as the solubility of oxygen in water or in fermentation media. Thus from this relation, as shown in Fig. 5.7, the corresponding equilibrium concentrations can be easily established.

CLC* Figure 5.7. Equilibrium concentrations based on Henry's law.

For gases of low solubility, e.g., oxygen and carbon dioxide in water, the concentration gradient through the gas film is very small, as compared to that within the liquid film, as illustrated in Fig. 5.6. This results from the relatively

5.3 General Oxygen Balances for Gas-Liquid Transfer

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low resistance to mass transfer in the gas film, as compared to the much greater resistance to mass transfer in the liquid film. The main resistance to mass transfer is predominantly within the liquid film. This causes a large change in concentration (Cy - CL), since the resistance is almost entirely on the liquid side of the interface. At the interface, the liquid concentration, Cy, is in equilibrium with that of the gas, CGI, and since CGI is very close in magnitude to the bulk gas concentration, CLI must then be very nearly in equilibrium with the bulk gas phase concentration, CG- This is known as liquid film control and corresponds to the situation where the overall resistance to mass transfer resides almost entirely within the liquid phase. The overall mass transfer capacity coefficient is KLa. Hence the overall mass transfer rate equation used for slightly soluble gases in terms of the specific area is Q = KLa (C L *-C L )V L where CL* is in equilibrium with CG, as given by Henry's law, C G = HCL*, Mass transfer coefficients in fermentation are therefore generally spoken of as KL values or K^a values for the case of mass transfer capacity coefficients.

5.3

General Oxygen Balances for Gas-Liquid Transfer

In order to characterize aeration efficiency, to predict dissolved oxygen concentration, or to follow the biological activity it is necessary to develop models, which include expressions for the rate of oxygen transfer and the rate of oxygen uptake by the cells. Well-mixed phase regions, in which the oxygen concentration can be assumed uniform, can be described by simple balancing methods. Situations in which spatial variations occur require more complex models, as described in Sec. 5.4. The following generalized oxygen balance equations are derived for well-mixed phases, using the well-mixed tank concept. In the situation in Fig. 5.8, both the liquid and gas phases are defined by distinct well-mixed regions and by the total volumes of each phase, VL and

VG.

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5 Mass Transfer

Gas

CQO GO

Figure 5.8. The balance regions for well-mixed gas and liquid phases in a continuous reactor.

For the gas phase the oxygen balance can be developed as follows: Rate of accumulation of oxygen in gas ( Rate of ^ > Flow of f Flow of \ transfer oxygen in _ oxygen out _ of oxygen Vin exit stream/ ; inlet gas streamy v from gas ,

Thus, for the gas phase, dCGi K L a(C L i*- C L i)V L

where VQ represents the volume of gas in the dispersed phase, or the gas holdup. For the liquid phase, Rate of ^ accumulation of oxygen ^ in liquid /Flow of ( Flow of oxygen oxygen in inlet out in liquid exit V stream J ' Rate of consumption of oxygen in liquid Rate of transfer of oxygen ^ from gas

Rate of oxygen consumption = -rO2 = -qo2

5.3 General Oxygen Balances for Gas-Liquid Transfer

125

Thus for the liquid phase, dCLi - LiC L i + K L a(C L 1 *-C L i)V L -

The above equations include accumulation, convective flow, interphase transfer and biological oxygen uptake terms. Here CLI* is the equilibrium solubility of oxygen corresponding to the gas phase concentration, CGI , and is calculated by Henry's law, according to the relationship:

Typical units are as follows: CG and CL (kg/m3); G and L (m3/s); K^a (1/s); VG and VL (m3); qO2 (kg/kg s); X (kg/m3). In the next sections, the general equations, given above, will be applied to important special situations.

5.3.1

Application of Oxygen Balances

5.3.1.1

Case A. Steady-State Gas Balance to Determine the Biological Uptake Rate

The convective terms in the generalized liquid balance equation can usually be neglected, owing to the low solubilities of oxygen in water (about 8 g/m3). This gives the steady state liquid balance, dCL/dt=0, relation as: K L a(C L i*- CLI) = qo2Xi Thus at steady-state, the oxygen transfer rate is effectively equal to the oxygen uptake rate. Even during batch fermentations this is approximately true. Substituting this relationship into the steady state gas balance gives,

0 = GO CGO - GI CGI - qo2 X VL


The above equation can also be derived from a steady state balance around the entire two-phase system. It shows that the biological oxygen uptake rate can be calculated from knowledge of the gas flow rates and the gas concentrations.

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5 Mass Transfer

This application is very important in fermentation technology, since it permits the on-line monitoring of the rate of fermentation, by gas balancing methods (Heinzle and Dunn, 1991, Ingham and Dunn, 1991).

5.3.1.2

Case B. Determination of Ki,a Using the Sulfite Oxidation Reaction

If a chemical reaction, classically the oxidation of sodium sulfite, is used to take up the oxygen from solution, then the term qo2 X VL in the liquid phase balance may be replaced by the chemical reaction term, ro2 VL- At steadystate, K L a(C L i*-C L i) = r02 Usually ro2 is obtained by taking samples and titrating for the fractional conversion of sulfite, which can be related by stoichiometry to the oxygen consumption. Since the chemical reaction causes the liquid dissolved concentration CLI to fall essentially to zero and with CLI* calculated from the oxygen concentration in the exit gas, the value of the overall mass transfer capacity coefficient, K^a, can be estimated. An improved method uses the gas balance instead of titration to obtain ro2 in the manner outlined above for qO2 X and also provides a check on the sulfite measurements. The sulfite method is useful for comparing aeration systems, but the values are difficult to relate to actual fermentation conditions owing to the very different physical conditions (coalescence, aeration rates) (Ruchti et al., 1985).

5.3.1.3

Case C. Determination of Ki,a by a Dynamic Method

If water is initially deoxygenated and is then re-aerated, the concentration of the dissolved oxygen will increase with time, from zero to effectively 100% air saturation at the end of the experiment. The exact form of the response curve obtained depends on the values of KLa, the driving force, (CLI* - CLI), and the measurement dynamics of the dissolved oxygen electrode. The liquid balance, for the unsteady state batch aeration condition, gives:
=

K L a(CLi*-C L i)V L

5.3 General Oxygen Balances for Gas-Liquid Transfer

127

The classical dynamic KLa method assumes that K^a and CLI* are constant. Under these conditions, the differential equation can be integrated analytically to give the relationship: CL* ^ = K L at r * CL - r CL\}

Plotting the natural logarithmic concentration function on the left side of the equation versus time, should, in principle, give a straight-line relationship, with ^a as the slope. Usually deoxygenation is accomplished with nitrogen, so that initially the gas phase consists of nitrogen, which is gradually displaced and mixed with air. Under these conditions, CLI* is nt constant, and a gas balance must be employed to calculate the variation in CGI versus t. Since the liquid phase concentration, CLI, is measured by means of a membrane covered oxygen electrode, the dynamics of measurement method usually cannot be neglected. The dynamics of the measurement electrode can be described, approximately, by a first-order lag equation,
dCE

where TE represents the electrode time constant, and CE is the measurement signal. The fractional response of the electrode for a step change in CL would appear as shown in Fig. 5.9.

time Figure 5.9. Response of electrode for a step change in CE from zero to 100 % saturation according to a first-order lag model.

Note that TE corresponds to the time for the electrode to reach 63 % of the final response. The overall process dynamics involves thus the gas phase, the liquid

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5 Mass Transfer

phase and the electrode response. The three responses might appear as shown below:

time Figure 5.10. Response of the gas, the liquid and the electrode measurement during a dynamic KLa experiment.

The values of three individual time constants determine the process response. These are TG = VG/G, (representing the dynamics of the gas phase), 1/KLa (representing the dynamics of the liquid phase mass transfer process), and IE (representing the measurement dynamics). This is illustrated in the simulation example KLADYN, Sec. 8.5.5.

5.3.1.4

Case D. Determination of Oxygen Uptake Rates by a Dynamic Method

Low oxygen uptake rates, as exist in slow growing systems (plant and animal cell cultures, aerobic sewage treatment processes, etc.), cannot easily be measured by a gas balance method, since the measured difference between inlet and outlet oxygen gas phase concentrations is usually very small. Due to the low solubility of oxygen in the liquid media, quite small oxygen uptake rates will cause measurably large changes in the dissolved oxygen concentration. Thus it is possible to measure qo2 X either by taking a sample and placing it in a small chamber or by turning off the reactor air supply, according to the liquid balance equation dCLi

5.3 General Oxygen Balances for Gas-Liquid Transfer

129

Dissolved oxygen concentration decreases linearly and is equal to qo2 X as shown in Fig. 5.11.

Figure 5.11. Oxygen uptake rate determined by a dynamic method.

When the time required for an appreciable decrease in dissolved oxygen is large, as compared to the electrode time constant, the method is quite accurate and no correction for the electrode measurement dynamics is required (Mona et al., 1979). If the response is too fast the sample can be diluted. This method is illustrated by the simulation example OXDYN, Sec. 8.5.4. A similar simulation example, ANAMEAS, Sec. 8.8.7, illustrates dynamic measurements in anaerobic systems.

5.3.1.5

Case E. Steady-State Liquid Balancing to Determine Oxygen Uptake Rate

If the biomass is immobilized or retained by membranes within the reactor, oxygen can be supplied to the cells by means of a circulating liquid supply, which is aerated in a separate unit, external to the reactor.

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5 Mass Transfer

CL1

CLO
Figure 5.12 Oxygen uptake rate determined by a steady-state liquid balance.

It then becomes possible to determine the oxygen uptake rate, simply by measuring the liquid flow rate and the difference in dissolved oxygen in the liquid inlet and outlet flow streams, according to the following steady-state liquid phase balance equation: 0 = L(CLo - CLI) - qo2 Xi VL Thus the rate of oxygen supply via the liquid is equal to the rate of oxygen uptake by the cells. This method provides a very sensitive way of measuring low oxygen uptake rates (Keller et al., 1992, Tanaka et al., 1982). The casestudy H in Sec. 5.3.1.8 is an example of this use for an experimental reactor. The simulation example FBR, Sec. 8.4.9, also demonstrates this method.

5.3.1.6

Case F. KLa

Steady-State Deoxygenated Feed Method for

Feeding a deoxygenated liquid continuously to an aerated tank (Fig. 5.11) allows the oxygen transfer rate to be determined by difference measurement. Thus the liquid phase balance becomes 0 = L (CLO - CLI) + KLa (CLi* - C L i)V L Knowing the flow rate L, the oxygen liquid concentrations CLO and CLI and the outlet oxygen in the gas phase (to determine CLI*) permits the calculation of

5.3 General Oxygen Balances for Gas-Liquid Transfer

131

KLa. Another variation of this would be to gas with oxygen-enriched air or with nitrogen, which would avoid the difficulty of producing a continuous source of deoxygenated liquid. A similar steady state method has been employed to obtain steady oxygen concentration profiles in column (Meister et al., 1980), and tubular bioreactors (Ziegler et al., 1977). A suitable steady state model for the tubular reactor then allows calculating the unknown K^a by parameter estimation (Shioya et al., 1978).
Deoxygenated C liquid LO

/"VX

"N^

-^^^

r-^^-~\_/~\^^x

nM&^/m^M:WM.

Xiiiiiiiiiiji ^^^SRSSSS

^^^iO^wiBii O

Wiiiiilmiiiiiii
Air
Figure 5.12. Steady-state dissolved oxygen difference measurement for Kj^a.

5.3.1.7

Case G. Biological Oxidation in an Aerated Tank

A batch reactor liquid is aerated with a continuous flow of air to support a biological reaction, as shown in Fig. 5.13.
air

air
Figure 5.13. A batch bioreactor with continuous aeration.

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5 Mass Transfer

The biological reaction in the liquid phase is first-order in oxygen concentration. Since oxygen is relatively insoluble (approximately 8 g/m3 saturation for air-water) the transfer rate is important to maintain a high dissolved oxygen concentration CL. The batch oxygen balance for the liquid phase is then: f Rate of \ accumulation of V 02 in liquid )
dCL

,^ f f N (Transfer rate o f \ l02 mto the hqmdj

/ Uptake rate of ^ by the cells

= K L a(CL*-C L )VL - k C L V L

A steady-state can be reached for which the mass transfer rate is equal to the oxygen uptake rate by reaction:
0 = KLa (CL* - CL) - k CL

giving for CL

CL = K L a

KLaCL*

Using this equation, the reaction rate constant, k, can be determined if CL is measured and K^a is known or measured. The equilibrium value, CL*, can be calculated from the gas phase concentration, and if there is little oxygen depletion it can be calculated from the inlet gas conditions. If the oxygen depletion in the gas phase is appreciable, then the mole fraction of oxygen in the exit may not be the same as in the inlet, and a gas phase balance must be applied to determine CL*:

Figure 5.14. Inlet and outlet oxygen mole fractions and total gas molar flow rates.

5.3 General Oxygen Balances for Gas-Liquid Transfer

133

From the ideal gas law as shown before, assuming a well-mixed gas phase in steady state, N = (p / RT) F, where NO is the molar flow rate of air and F is the air volumetric flow rate.
0 =

/ Rate of O2 \ / Rate of O2 \ / Transfer rate of \ V in by flow ) ~ Vout byflow) ~ \ C>2 to the liquid )

Using the nomenclature in Fig 5.13,

where

0 = yoN0-yiNi-KLa(CL*-CL)VL

Assuming NO = NI, these equations can be solved to obtain yi and CLSolving for CL gives,

CL =
or for the apparent reaction rate,
k re = -

k~" CL*
,

k~ CL

Thus it is possible to distinguish between two different regimes for this system, transfer control and reaction control: 1) 2) 3) Reaction rate control applies for low values of k/KLa, when re approaches k CL*, and CL approaches CL* Diffusion control applies for high values of k/KLa, when re approaches KL& CL* and CL approaches 0. If KLa = k, then rc = - (k/2) CL*, and CL approaches (1/2) CL*.

5.3.1.8

Case H. Modelling Nitrification in a Fluidized Bed Biofilm Reactor

Nitrification is a two-step microbiological process, in which the ammonium ion is oxidized to nitrite ion and further to nitrate ion as shown: NH4+ - NO2- - NO3-

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5 Mass Transfer

This reaction is important in waste water treatment because of the toxicity of ammonia and its large oxygen demand. Several known organisms can gain energy from either of the two oxidation steps, but most commonly Nitrosomonas and Nitrobacter are responsible for steps (1) and (2), respectively. These organisms grow very slowly, obtaining their carbon from dissolved carbonate. Due to the very slow grow rates, it is of interest to retain the biomass within the reactor. One possibility considered here is to immobilize the biomass as a natural biofilm on a fluidized bed of sand (Tanaka and Dunn, 1982). The stoichiometric relations for the reaction steps (1) and (2) are:
, 3 , NH4+ + j O2 -> NO2" + H2O + 2 H+ O2 -> NO3"

Summing the above steps (1) and (2) gives NH4+ + 2O 2 The reactor of volume, Vr, consisted of a conical sand bed column, which was fluidized by the liquid recycle stream flowing up through the bed. The recycle stream was oxygenated in a separate, baffled, tank contactor of volume VT, with turbine impeller and air or oxygen sparging. The reactor and oxygenator were thus separate parts of a recycle loop configuration. This could be operated batchwise or with a continuous feed and effluent stream flow to and from the system. When operating at high recycle rates, the whole system acted effectively as one well-mixed tank system. The reactor-oxygenator recycle loop can be analyzed as a total system or broken down into its individual components as shown in Fig. 5.14. These include liquid phase balance over the reactor and combined phase, liquid phase and gas phase balances over the oxygenator and over the total system.

5.3 General Oxygen Balances for Gas-Liquid Transfer

135

Figure 5.15. Mass balancing regions for the fluidized bed reactor nitrification system.

The mass balances to be considered are those for oxygen and the nitrogencontaining reactants and products. The oxygen balance taken over the total system can be simplified by neglecting the accumulation terms and the liquid flow terms, that will be small compared to the gas rates and the consumption by reaction, owing to the relatively low solubility of oxygen in the liquid medium. Thus the oxygen balance becomes,
0 =

Here Vr is the volume of the reactor column. The nitrogen (N) components, NH4+, NCV, and NOs', in the liquid phase can be balanced around the total system by considering the accumulation, flow, and reaction terms for each of the N-containing components. For the total system each component equation has the form, VdCp = F(C N i-C N 2 ) dt When the reactor is operated as a batch system, F = 0, and when used as a continuous steady state reactor, dCN2/dt = 0. This equation can be used in column systems for very low single-pass conversion, when the differences in local reaction rate at the reactor inlet and outlet are not large. Although the reactions actually occur in the solid phase, because of the high solid-liquid interfacial area, the system is treated here as being quasi-homogeneous. The gas-liquid interfacial mass transfer area will often be small enough to be important for the overall process, and it is therefore useful to consider the gas

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5 Mass Transfer

and liquid phases as separate balance regions. The absorption tank can be described by the oxygen balances for the liquid phase: 0 = F R (C L4 -C L3 ) + K L a(C L *-C L3 )V T and for the gas phase: 0 = G(CGi - CG2) - KLa (CL* - CL3) VT The liquid phase oxygen balance for the total system is
0 = KL

where ro2 is the oxygen uptake rate by the reaction. These equations, which assume ideally mixed phases, are useful in designing the gas absorber according to the required oxygen transfer coefficient. Balancing the oxygen around the reactor gives
0 =

Since CL4 at the reactor outlet is usually very low, then,


FR CL3 = - ro2 Vr

which says that the oxygen uptake rate by reaction must be equal to the supply rate from the oxygenation tank. This is the condition of reaction-rate limitation by the oxygen transfer in the absorber. From the stoichiometry, the relationships between the molar reaction rates (rNH4> rO2 rH* r2,NO2 an^ fNO3) can be found. Thus, for example, the first nitrification step gives
TNH4 =
2 T r l , O 2 = ~ri,NO2

and the total rate for 02 is given by the sum of the rates for steps (1) and (2).
r

O2 = r l,O2 + r2,O2

From the measured concentration dependency of these rates, the reaction kinetics of the individual steps can be determined. The dependency of these rates on the individual concentrations can then be used to establish the reaction kinetic model. This model is the basis of the simulation example NITRIF, Sec. 8.5.3. A similar type of recycle, fluidized-bed reactor is the theme of simulation examples FBR, Sec. 8.4.9 and DCMDEG, Sec. 8.4.6.

5.4 Models for Oxygen Transfer in Large Scale Bioreactors

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5.4

Models for Oxygen Transfer in Large Scale Bioreactors

Large-scale industrial fermenters can generally be expected to exhibit deviations from the two idealized flow conditions of perfect mixing or perfect plug flow. Thus the assumption of completely mixed gas or liquid phases may not be valid. Little experimental information is available on concentration inhomogeneities or concentration gradients within large bioreactors. Residence time distribution information, from which a physical and mathematical model could be established, is also generally not available. Convection currents within the liquid phase of a bioreactor are usually caused by the mechanical energy inputs of agitation and aeration. It is often reasonable to assume that slowly changing quantities, such as biomass concentration, substrate concentration, pH and temperature are uniform within the whole mass of bioreactor liquid. Oxygen must be considered, however, as a rapidly changing substrate, owing to its low solubility in fermentation media. It is therefore necessary to consider that differences in oxygen transfer and uptake rates will create oxygen concentration gradients throughout the reactor. Buoyancy forces carry the gas from the lower gas inlet point up to the top liquid surface. In the absence of mechanical agitation, the gas phase might move from the bottom to the top of the reactor in an approximate plug flow manner, with very little backmixing. If the stirring power supplied to the fermenter, however, is sufficient to create liquid velocities, that are greater than the free rise velocity of a bubble (about 26 cm/sec) then the bubbles will circulate around the fermenter, before eventually escaping. Very high power inputs can cause the smaller bubbles to circulate many times within the vessel and spend an appreciable time before reaching the surface. Under such conditions, if no bubble coalescence occurs, the gas phase would contain a fraction of small bubbles, depleted of oxygen but with a large surface area. Obviously any well-mixed phase assumption becomes difficult to justify. The gas phase flow conditions in large scale industrial fermenters usually lie somewhere between the extreme cases of idealized plug flow and perfect mixing. Experimental residence-time distribution information, obtained by helium tracer techniques under actual operating conditions, are then necessary to characterize the gas phase flow. Unfortunately very little experimentation on industrial scale equipment has been reported. Hydrostatic pressure gradients in tall fermenters will cause large differences in the oxygen solubility, CL*, with regard to the depth position in the tank. In a 10m tall reactor, the oxygen solubility for a given gas composition will be twice that at the bottom of the tank as compared to the top surface, since the total pressure is effectively doubled. This is seen by Henry's law which can be written as:

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5 Mass Transfer

2p d* = yH
where yo2 is the mole fraction of oxygen in the air and p is the total pressure at some point in the tank. The possibility that oxygen gas compositions, dissolved oxygen concentrations, oxygen solubilities, gas holdup volumes, bubble sizes and other transfer parameters can vary with depth in a tall fermenter introduces a much greater degree of complexity to the problem of modelling the reactor. This makes it difficult to obtain data on oxygen mass transfer coefficients. Although it is impossible to give specific recommendations that apply to any particular situation, a further discussion of possible models and their underlying assumptions may help to define the problem. Incorporated into the more complex models, discussed below, are such factors as gas and liquid phase flow pattern, gas composition gradients and the effects of hydrostatic pressure. Great caution and wisdom must be exercised to avoid creating a model that is too complex to verify by experimentation. Experienced engineers will say "Keep it simple!" and "Avoid too much model!". All large scale reactors, whether multi-impeller tanks or column fermenters, will display some axial dissolved oxygen concentration gradients. The most general method for modelling is to represent the reactor using balances in a series of sections or stages. Mass balances in multi-stage process are easy to formulate, since both the liquid and gas phases may be assumed to be wellmixed, for any given stage of the cascade.

Figure 5.16. A single gas-liquid stage with backmixing of the liquid phase.

The formulation of the mass balances for a single stage, as shown in Fig. 5.16, follows closely that described previously, except that now the reactor is made up of many stages which are interconnected by the flows of gas and liquid between stages and by diffusive mass transfer mechanisms.

5.4 Models for Oxygen Transfer in Large Scale Bioreactors

139

5.4.1.

Case Studies

5.4.1.1

Case A. Model for Oxygen Gradients in a Bubble Column Bioreactor

The application of the stagewise modelling approach is shown below, where a bubble column reactor is modelled as a five-stage reactor system. The reactor will be assumed to operate cocurrently, as would be also the case for the riser of an airlift bioreactor.
Exit Gas Exit Liquid

A CQB A CLS
Gas

i l l

Gas Feed

Liquid Feed
GO L' LO

Figure 5.17. Stagewise model of a bubble column bioreactor.

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5 Mass Transfer

The oxygen balance equations for the gas and liquid phases of each stage are as follows: if
f\(~^

= FG(C G n-l-C Gn ) - K L a(C Ln *-C Ln )V L

VL-dT = F L(C L n-i-C Ln ) + K L a(C L n*-C L n)VL - rn VL where,


P

r * - 1 r c * C <~Ln H r Gn or CLn
and
rn = Qo2m |

-77rl

02

For simplification only oxygen is assumed limiting and growth is not considered; however the biomass concentration is contained in the maximum oxygen uptake Qo2m- The dynamics of the oxygen transfer and uptake processes are obtained by solving these differential equations simultaneously for each stage. The resulting solution then gives CLH and CGn > for each stage as functions of time and also yields the resulting final steady state values. Note that the biomass concentrations Xn are assumed constant, otherwise biomass balance and growth kinetics equations would have to be added to the model. Using simulation methods, other effects, such as the effect of hydrostatic pressure on CG or on bubble size could be included. The simulation example DCMDEG, Sec. 8.4.6, demonstrates some aspects of the stagewise modelling approach.

5.4.1.2

Case B. Model for a Multiple Impeller Fermenter

Mixing in a tank reactor is complex, and it would be necessary to consider liquid flow in both directions. It is generally assumed, however, that the intensity of mixing is such that no radial variations occur. Fig. 5.16 represents a multiple impeller reactor with well-mixed liquid zones in the region of each impeller. The reactor can be described approximately by means of a threestage model. Mixing of the liquid in a direction which is directly opposite to that of the main flow liquid (here upwards) can be incorporated into the model, by the assumption of a backmixing stream, with flow rate FB- This backmixing stream accounts for a flow interaction between the mixing zones and for deviations from ideal stage mixing. To determine FB, a tracer experiment

5.4 Models for Oxygen Transfer in Large Scale Bioreactors

141

would need to be performed to obtain the necessary information regarding the degree of backmixing actually existing in the reactor.
Exit Gas Exit Liquid
c

G3 A F

A C L3

\_^

Gas
G2 L3 L2

Gas
G1

'LI

FL+FB
Gas

I
Inlet Gas Liquid Feed

G- C GO

\\>cu>

Figure 5.18. Stagewise approximation for stirrer regions in multi-stirrer tank.

To model this system, the liquid-phase impeller zones are assumed to be wellmixed, and the plug-flow gas is described by a series of well-mixed phases, together with an arithmetic-mean, concentration-driving-force approximation. Here the flow rates and mass transfer coefficients are assumed constant.

Stage 1: dCLi VL -ar = FLCLO + FBCL2 - (FL + FB) CLI +


+ K L a(CLi*-C L i)VL + riV L
V

dCGl

"""'

xx-<

-CGI) -KLa(CLi -CLI)VL


f\
\

-rr-

//~1

/"I

\A 7

where the plug flow nature of the gas is partially accounted for by

142

5 Mass Transfer

and
= - Qo2r

CLI

Stage 2:
dCL2 VL -gf = (FL+ FB) CLI + FBCL3 - (FL+ FB) CL2 - FB CL2 K L a(C L 2*-C L 2)V L

= FG (CGI - CG2) - KLa (CL2* - CL2)VL


where

CL2. .
and
CL2 n r2 = -Qo2mK 0 + CL2

Stage 3:
dCL3

K L a(C L 3*-CL3)V L + r 3 V L
V

- CG3) - KLa (CL3*- CL3) VL

where

CL3. .
CL3
= -QO2n K0 + CL3

and

The above equations describe the dynamic oxygen concentrations in the multiimpeller continuous bioreactor. Note that the liquid phase balances for the two end stages 1 and 3 differ from that of the intermediate stage 2, owing to the

5.4 Models for Oxygen Transfer in Large Scale Bioreactors

143

absence of any backmixing flow contribution exterior to the column. A batch reactor would be described by setting the liquid flow, FL, equal to zero. Since the biomass balance and growth kinetics are not included here, the solution would be valid at only one time during the fermentation, corresponding to the assumed value of Qo2m> which is proportional to the value of X existing at that time. Variations in X are, however, easily incorporated into the model by adding cell and substrate balance equations.