More often, reaction takes place inside the particle so that internal mass transfer must also occur through the solid. The temperatures used during secondary drying are higher and the pressures lower than for primary drying. The atomic weight of an element is its mass relative to carbon-12 having a mass of exactly 12; atomic weight is also dimensionless. In our example, Sc is a square 4 3 4 matrix: this is a consequence of the system being determined so that the number of unknown rates is equal to the number of equations available to solve for them. AMSTERDAM BOSTON HEIDELBERG LONDON NEW YORK O, Views 8,194

The mole fraction of component A in a mixture is defined as: mole fraction A 5 number of moles of A total number of moles 2:23 Mole percent is mole fraction 3 100. Because the dried solid near the surface is generally a poor conductor of heat, the rate of heat transfer declines progressively. MATERIAL AND ENERGY BALANCES 170 5. For example, metabolite D in Figure 12.27 is a diverging pathway branch point, producing metabolites F and H that then proceed along different reaction routes. If the specific activity of the cells is independent of cell loading, what is the maximum particle size for aerobic conditions? Accordingly, a stoichiometric coefficient is not required for the consumption term in the balance for I2. Syst. (iii) System boundary The system boundary indicated in Figure 5.5 separates the gluconic acid solution from the cooling water. (iv) What is the observed overall yield of biomass from substrate? Flow sheet and system boundary These are shown in Figure 6.4. Let A be the unknown mass of air added. The cumulative undersize fraction in Table 11.9 is the fraction of the crystal population with size less than L. Another property that can be derived from the population balance is the dominant size LD (see Section 11.12.1, Size Distribution subsection), which is the crystal size corresponding to the maximum value of the mass density m: LD 5 3 VG F 11:154 TABLE 11.9 Properties of MSMPR Crystallisers Derived from Population Balance Analysis Property Number of crystals Mass of crystals * The dimensionless quantity 5 Total per Unit Volume in an MSMPR Crystalliser Cumulative Undersize Fraction in an MSMPR Crystalliser* V G n0 F VG 4 6 kv n0 F 1 2 e2 2 3 1 1 2 e2 1 1 1 2 6 FL : VG E X A M P L E 1 1 . (d) For the conditions described in (c), what minimum volume of air at 20 C and 1 atm pressure must be provided to the bioreactor during growth. ), Comprehensive Biotechnology, vol. The result is an equation for the observed reaction rate rA,obs in a single particle: h p p i 13:21 rA;obs 5 4RDAe CAs R k1 =DAe coth R k1 =DAe 2 1 where coth is the abbreviation for hyperbolic cotangent defined as: coth x 5 ex 1 e2x ex 2 e2x 13:22 Note that, because the observed reaction rate was found by integrating the local reaction rate over the volume of a single particle, rA,obs in Eq. (11.153): 1m 5 2:00 3 109 m23 h21 B 5 n0 G 5 6:76 3 1013 m24 29:6 m h21 6 10 m The crystal nucleation rate is 2.0 3 109 m23 h21. It is often disappointing for the biology-trained scientist that engineers seem to ignore the wonder, intricacy, and complexity of life to focus only on those aspects that have a significant quantitative effect on the final outcome of the process. Valves D, C, H, and I are then closed to isolate both the fermenter and the empty inoculum tank that can now be disconnected at A and B.

(ix) At the end of the growth phase, what is the observed yield of biomass from substrate based on the initial concentrations of biomass and substrate? The kinetic expression is: rA 5 k0 12:25 where rA is the volumetric rate of reaction with respect to component A and k0 is the zeroorder rate constant. Therefore: YPX 1 mP Y0PS 5 1 mS YXS 12:114 In many anaerobic fermentations such as ethanol production, the yield of product from substrate is a critical factor affecting process economics. 2. A similar expression can be obtained for the second term of Eq. (12.122), r2 is the number of moles of I1 reacted per unit time, from the stoichiometry of conversion of I1 to I2, the number of moles of I2 formed per unit time must be 2r2. Consider the formation of an extracellular product CjHkOlNm during growth. If k 5 420 kJ C21 h21, estimate the heat capacity of the laboratory, that is, the energy required to raise the temperature of the room by 1 C. References [1] [2] [3] [4] J.C. Arya, R.W. In a continuous fermenter operated at 33 C, 20 g h21 water is evaporated in this way. Solution (a) To assess the effect of internal mass transfer on the reaction rate, we need to calculate the observable Thiele modulus. (6.5): dV 5 Fi i 2 Fo o dt 6:6 Equation (6.6) is a differential equation representing an unsteady-state mass balance on total mass. Most users of linear regression choose this technique because they believe it will automatically give them an objective and unbiased analysis of their data. (iii) Is 24 hours an appropriate batch culture duration for nisin production? Maintenance requirements and the difference between observed and true yields are discussed further in Chapter 12. The mass of cells in the reactor, M, is equal to the cell concentration x multiplied by the liquid volume V. The mass rate of cell growth RG is equal to rXV where rX is the volumetric rate of growth. Control and elasticity coefficients are subject to certain constraints and relationships that can be expressed mathematically. (11.42) is difficult. To overcome these difficulties, enzyme quantity is often expressed as units of activity measured under specified conditions. INTRODUCTION 2:21 2.4 MEASUREMENT CONVENTIONS lb-moles 5 mass in lb molar mass in lb 25 2:22 Molar mass is the mass of one mole of substance, and has dimensions MN21. The kinetic parameters for the immobilised enzyme can be assumed to be equal to those for the free enzyme: Km is 8.8 mM and the turnover number is 2.4 3 1023 gmol of sucrose (g enzyme)21 s21. (b) The product mixture contains 13% sucrose. (14.57) gives an expression for D: D5 max s 0:3 h21 1:5 g l21 5 0:26 h21 5 KS 1 s 0:2 g l21 1 1:5 g l21 From the definition of dilution rate in Eq. Erickson, Estimation of heats of combustion of biomass from elemental analysis using available electron concepts, Biotechnol. Similarly, the latent heat evolved in freezing or solidification of liquid to solid is 2hf. MATERIAL AND ENERGY BALANCES 118 4. About 135 kg of water is lost by evaporation during the culture. The context and meaning of many of the equations introduced as problems and examples are explained in more detail in later sections of this book; the emphasis in this chapter is on the use of basic mathematical principles irrespective of the particular application. At a nitrate concentration of 3 g m23, the conversion rate is 0.011 g s21 m23 of catalyst. If you have ever attempted this you will know that, although correct in principle, it can be an extremely difficult exercise. Bioprocess Engineering Principles, Second Edition 139 2013 Elsevier Ltd. All rights reserved. Freezing takes place at roughly atmospheric pressure as the temperature is progressively reduced. An adequate background in biology is assumed. As a result, the reduction in cell numbers outside of the holding period is significant. Two types of membrane module are being considered for this separation: a hollow fibre unit operated to give a mass transfer coefficient of 10 l m22 h21 and a plateand-frame device with a mass transfer coefficient of 6.5 l m22 h21. The rate of consumption RC is equal to RA, and RG 5 0. (14.59), we can divide through by V, substitute the definition of dilution rate from Eq. (4.4) causes some problems in practical application. 12.14.2 Biomass Yield from Substrate Equations for the true biomass yield can be determined for systems without extracellular product formation or when product synthesis is directly coupled to energy metabolism. When you make assumptions about a problem, it is vitally important that you state them exactly. Small cracks or gaps in joints and fine fissures in welds are a haven for microbial contaminants and are avoided in fermenter construction whenever possible. Because the volumetric rate of a catalytic reaction depends on the amount of catalyst present, when Eq. 21 (1979) 21752201. c If the first-order Thiele modulus is known, we can use Figure 13.11 to find the internal effectiveness factor. 3.3.3 Goodness of Fit: Least-Squares Analysis Determining how well data conform to a particular model requires numerical procedures. (12.84) is strictly valid only if is unchanging, a plot of ln x versus t is often used to assess whether the specific growth rate is constant. PHYSICAL PROCESSES 558 3. To reduce the cost of any bioprocess, it is first necessary to identify which aspects of it are cost-determining. MATERIAL BALANCES fermenter, or settler and fermenter, together. 140 No. The crystalliser is operated with a solution feed rate of 1.8 m3 h21. (12.140) gives the following equation 32 2 6 27 76 5 0 4 1 0 0 21 0 3 0 0 7 7 0:05 mol g21 h21 0 5 0:08 21 Using the associative multiplication rule Eq. You can verify answers quickly using this method, often without needing a calculator. In addition, many physical property data collected before 1960 are published in lists and tables using nonstandard units.

The following is a small selection. McCabe, J.C. Smith, P. Harriott, Unit Operations of Chemical Engineering, seventh ed., McGraw-Hill, 2005 (Chapter 24). However, because we are interested primarily in the distribution of carbon within pathways, flux is sometimes reported in terms of moles of C rather than moles of chemical compounds. Bailey, Structurefunction relationships in immobilized chymotrypsin catalysis, Biotechnol. For a set of experimental data, the standard deviation is calculated from the residuals of all the datum points as follows: v uX s u n x1 2 x2 1 x2 2 x2 1 x3 2 x2 1 . 200 No. Chem., 240, 863869. (b) 14 kg h21 water must be used to dilute the ethanol in the feed stream. 2.

Let us consider the situation for spherical particles and first-order, zero-order, and MichaelisMenten kinetics. (14.34) to Eq. EXAMPLE 4.8 PRODUCT YIELD AND OXYGEN DEMAND The chemical reaction equation for respiration of glucose is: C6 H12 O6 1 6 O2 !

In Sections 12.10 and 12.11, we employed the notion that the rates of different processes, such as substrate consumption and product formation, could be related using appropriate yield coefficients. Parts I and II, Chem. However, equations similar to Eq. The term CSTF is also sometimes used to denote continuous stirred tank fermenter. MATERIAL AND ENERGY BALANCES 4.6 STOICHIOMETRY OF CELL GROWTH AND PRODUCT FORMATION 117 TABLE 4.10 Elemental Composition of Escherichia coli Bacteria Element % Dry weight C 50 O 20 N 14 H 8 P 3 S 1 K 1 Na 1 Ca 0.5 Mg 0.5 Cl 0.5 Fe 0.2 All others 0.3 From R.Y. There are up to five steps that can pose significant resistance to adsorption as indicated in Figure 11.21. INTRODUCTION 3.4 GRAPH PAPER WITH LOGARITHMIC COORDINATES 65 more readily available on hand-held calculators and in graphics software packages than nonlinear routines, which are generally less easy to use and require more information about the distribution of errors in the data. Linearisation of data for the Langmuir plot minimises distortions in experimental error. For multiplication and division the rule is: add relative errors. PRESENTATION AND ANALYSIS OF DATA 50 50 Rate of heat production (kJ l1 h1) Rate of oxygen production (kJ l1 h1) 58 40 30 20 10 0 0 20 40 60 80 100 40 30 20 10 0 0 20 40 60 80 100 Rate of oxygen consumption (mmol l1 h1) Rate of oxygen consumption (mmol l1 h1) (a) (b) FIGURE 3.4 Experimental data for the rates of heat production and oxygen consumption in two different microbial cultures: (x) Escherichia coli, and () Schizosaccharomyces pombe. (The triple point is an invariant condition of pressure and temperature at which ice, liquid water, and water vapour are in equilibrium with each other.) It is usual to run continuous processes as close to steady state as possible; however, unsteady-state conditions will exist during start-up and for some time after any change in operating conditions. Certain information is available about a process; the task is to calculate unknown quantities. However, metabolic flux analysis is generally carried out using fluxes expressed as molar rates. 4.5 MATERIAL BALANCES WITH RECYCLE, BYPASS, AND PURGE STREAMS So far, we have performed mass balances on simple single-unit processes. Calculate Ws 5 0; Mv 5 0. The occurrence of reactions in biological systems is of particular importance; terminology involved in stoichiometric analysis is considered in this chapter. Mass-balancing techniques are another approach to state estimation. Larson, Theory of Particulate Processes, second ed., Academic Press, 1988. Barker, M.J. DeBergalis, S.E. REACTIONS AND REACTORS 686 12. ENERGY BALANCES EXAMPLE 5.2 ENTHALPY OF CONDENSATION Fifty grams of benzaldehyde vapour is condensed at 179 C. What is the enthalpy of the liquid relative to the vapour?

7.4 MOMENTUM TRANSFER Viscous drag forces responsible for the velocity gradient in Figure 7.6 are the instrument of momentum transfer in fluids.

Adopted by the 14th General Conference on Weights and Measures (1971, Resolution 3). Proper adjustment of PID controllers usually provides excellent regulation of measured variables. (4.2): mass in 1 mass generated 5 mass out 1 mass consumed For total mass and N2, the appropriate mass balance equation is Eq. 4.3 PROCEDURE FOR MATERIAL BALANCE CALCULATIONS The first step in material balance calculations is to understand the problem. Depending on the process, changes in variables such as pH and temperature at critical times can improve the production rate and yield. (6.5), the mass balance equation for product is: dpV 5 qP xV dt 14:29 If cell death is negligible and is equal to max, x is given by Eq. As a result, greater changes in enzyme activity can occur over a narrower range of substrate concentration. (Ed. Because cells are the catalysts in fermentation processes, it is often advantageous to recycle them from spent fermentation broth. means DAe dr After substituting these terms into Eq. Substrates with a high degree of reduction S (see Table C.2 in Appendix C) contain large amounts of energy that, in reaction, cannot all be transferred to the biomass and other products, and must therefore be dissipated as heat. Delaney, R. A. M. (1980). Process characteristics are then learnt or incorporated into the model structure as information becomes available from on- and offline measurements. At the air humidity used, the temperature at the wet crystal surface is 24 C and the crystal equilibrium moisture content is 7.5%, dry basis. The controller produces a signal that is transmitted to the actuator, which executes the control action.

When YXS is constant throughout growth, its experimentally determined value can be used to evaluate the stoichiometric coefficient c in Eq. (12.39), the value of vmax for enzyme reaction depends on the concentration of active enzyme present. 3. 8 . (14.97) completes the holding time calculation. The most common nonlinear methods, such as the GaussNewton procedure, available as computer software, are based on gradient, search, or linearisation algorithms and use iterative solution techniques. PHYSICAL PROCESSES 11.13 DRYING 569 As drying commences, the water content of the solid is high. In general, the rate of reaction depends on reactant concentration; therefore, the rate of 4. The number 2. glucose 1 2 ADP 1 2 NAD-2 pyruvate 1 2 ATP 1 2 NADH 1 2 H2 O pyruvate 1 NADH-lactate 1 NAD pyruvate 1 CoA 1 NAD-acetyl CoA 1 CO2 1 NADH pyruvate 1 CoA-formate 1 acetyl CoA acetyl CoA 1 ADP-acetate 1 CoA 1 ATP acetyl CoA 1 2 NADH-ethanol 1 CoA 1 2 NAD ATP-ADP The overall stoichiometry and cofactor requirements for glycolytic conversion of glucose to pyruvate are well known.

(c) What operating pressure is required to release 90% of the protein contained in the cells from continuous culture in five passes? These variables are called state properties or functions of state; examples include temperature, pressure, density, and composition. 61, 239245. (i) Does the culture undergo a lag phase? Chem. At steady state, the cell concentration is 4.5 g l21, the rate of consumption of succinic acid is 395 g h21, and the outlet water temperature is 27.5 C. (a) What is the enthalpy change of the cooling water in the jacket? (12.22) is applicable is quite limited.

Exponential growth of the host cells is assumed. (12.34), if a reaction follows first-order kinetics, a plot of CA versus time on semi-logarithmic coordinates gives a straight line with slope 2k1 and intercept CA0. Biotechnol. [7] A. Mizrahi, M. Sullivan, Mathematics: An Applied Approach, seventh ed., Wiley, 2000. [13] N.S. Wang, C.L. Interaction of the substrate with other concentration gradients, and phenomena affecting the transport of charged species, are ignored. Substituting these results into Eq. Although we can never be certain this would occur, uncertainties may still be represented using probable errors rather than maximum possible errors. From Table 13.6 for spherical geometry: 5 R rA;obs 3 3 1023 m 0:011 g s21 m23 5 5 0:37 25 3 kS CAb 3 10 m s21 3 g m23 As this value of is relatively large, external mass transfer effects are significant. In such a particle, substrate is depleted just at the centre point. Only the Thiele modulus for first-order reaction does not depend on the substrate concentration. Values of G are available in handbooks such as those listed in Section 2.6. In contrast, for zeroorder reactions, i0 5 1 does not imply that gradients are absent because, as long as CA .

Substrate S enters a cell and is converted to product P in a linear, unbranched sequence involving two intermediates, I1 and I2, and three reaction steps. Drying is an energy-intensive unit operation; accordingly, drier effectiveness and energy efficiency are of concern for economical processing. Selective precipitation. Chem. 11.38 Drying time for protein crystals Insulin crystals are dried in air in a batch drier under constant drying conditions. HETEROGENEOUS REACTIONS considered constant. (E.9) in Appendix E that (ln CA 2 ln CA0) is the same as ln CA/CA0: ln CA 2F 5 t CA0 V 2. You are already familiar with many units: metre, foot, and mile are units of length, for example, and hour and second are units of time. A batch culture of Atropa belladonna roots is established in an air-driven reactor as shown in Figure 4P11.1. N2 balance 4:424 kg N2 in 5 N2 out N2 out 5 4:424 kg To deduce the other unknowns, we must use stoichiometric analysis as well as mass balances. Bioseparations Engineering: Principles, Practice, and Economics. One way of representing variation in velocity is streamlines, which follow the flow path. (b) When product synthesis is coupled with energy metabolism, as is the case for ethanol, x is evaluated using Eq. (a) Is oxygen uptake affected by external mass transfer? Express your answer in units of mg h21 g21 dry weight. The terms molecular weight and atomic weight are frequently used by engineers and chemists instead of the more correct terms, relative molecular mass and relative atomic mass. 1. (3.4), the specific growth rate is 0.076 h21. In bioprocessing, batch crystallisation is used extensively for purification and final recovery of fermentation products such as antibiotics and amino acids. The mass of wet solids per volume of filtrate is 0.25 g ml21 for the pelleted cells and 0.1 g ml21 for the filamentous culture. Leslie, R.V. A relatively recent development in control engineering is the application of artificial intelligence techniques, especially knowledge-based expert systems. This textbook on bioprocess engineering is designed to prepare you for that challenge. The volume of vegetable oil in the tank at 8 PM is 60 l. (a) If the flow rate of cod liver oil into the tank is 7.5 l h21 and the tank has a maximum capacity of 100 l, will the tank overflow before the factory manager arrives at 9 AM? Normally, cell death at temperatures below about 100 C is minimal. This requires knowledge of growth stoichiometry, which is considered in Example 4.6 and discussed in more detail in Section 4.6. Shuler, F. Kargi, Bioprocess Engineering: Basic Concepts, second ed., Prentice Hall, 2002. A scale for absolute temperature with degree units the same as on the Celsius scale is known as the Kelvin scale; the absolute temperature scale using Fahrenheit degree units is the Rankine scale. Values for heat capacity must be known before enthalpy changes from heating or cooling can be determined. Equation (13.10) is called the symmetry condition. If there are gaps in the reaction network involving unknown sources or sinks of 4. To estimate the flow rate, one of your colleagues starts pumping a 30% NaCl tracer solution into the pipe at a rate of 80 ml s21 while you measure the concentration of NaCl downstream after the solutions are well mixed. 44 (1989) 20312039. Consider again the data of Figures 3.4(a) and 3.4(b). The practical outcome of this chapter is simple criteria for assessing mass transfer limitations in heterogeneous reaction systems. u is specific internal energy, ek is specific kinetic energy, ep is specific potential energy, p is pressure, and v is specific volume. HOMOGENEOUS REACTIONS condition means that control coefficients describe responses to very small changes in system parameters. When this is the case, F remains close to 1 as the plasmid-free population cannot reproduce. However, later in the batch, an inducer may be added to switch on protein synthesis. How much oxygen must be provided for this fermentation to proceed? Here, we extend the macroscopic description of cell metabolism developed in Section 4.6 to include reactions that occur wholly within the cell. The rate of inhibitor binding to the enzyme determines the effectiveness of the inhibition. (5.20). Production of PHB Poly-3-hydroxybutyrate (PHB) is a biodegradable thermoplastic accumulated intracellularly by many microorganisms under unfavourable growth conditions. Molar volumes for an ideal gas at standard conditions are: 1 gmol 5 22:4 litres 2:32 1 kgmol 5 22:4 m3 2:33 1 lbmol 5 359 ft3 2:34 1. Bioeng. Laboratory studies show that the capacity factors for the proteins are 0.85 for the A-chain and 1.05 for the B-chain. 26F, 469496. 115208). Humidity is measured using instruments called hygrometers. We have thus derived a differential equation for the rate of change of M as ^ o , RG, and RC: ^ i, M a function of the system variables, M dM ^ i2M ^ o 1 RG 2 RC 5M dt 6:5 At steady state there can be no change in the mass of the system, so the rate of change dM/dt must be zero. (c) At the flow rate of (a), what concentration of ethanol is produced? The equations and procedures used in this analysis depend on the geometry of the system and the reaction kinetics. Caulcott, A mathematical model for analysing plasmid stability in microorganisms, J. Gen. Microbiol. 3.13 Nonlinear data correlation Saccharomyces cerevisiae cells are homogenised to release recombinant hepatitis B surface antigen for vaccine production. This is illustrated in Figure 3.2, where 13 of 40 datum points lie outside the x 6 range. As enzyme reactions are rarely carried out as fed-batch operations, we will consider fed-batch reactors for cell culture only. The units and dimensions of the mean and standard error are the same as those of x, the variable being measured. Applying Eq. These criteria can be used directly in experimental design and data analysis. Time period of fermentation (h) Measured variable Rate Rate Rate Rate Rate of of of of of uptake of reducing sugars (g l21 h21) biomass production (g l21 h21) lysine production (g l21 h21) oxygen uptake (g l21 h21) heat evolution (kJ l21 h21) 0212 12236 0.42 0.29 0.20 0.40 2.5 2.0 0.21 0.66 0.75 12.1 (a) Use mass and energy balance principles to check whether the data for the 12236-h culture period are consistent (e.g., to within 610%). Other metabolic reactions may also be rationalised. (12.91) with Eq.

REACTIONS AND REACTORS 612 12. Natural logarithm of yeast concentration 16 Yeast concentration (g l1) 14 12 10 8 6 4 2 0 0 2 4 6 8 Time (h) (a) 10 12 14 3.0 2.5 2.0 1.5 1.0 0.5 0.0 0.5 1.0 0 2 4 6 8 Time (h) (b) 10 12 14 FIGURE 3.7 Growth curve for Saccharomyces cerevisiae: (a) data plotted directly on linear graph paper; (b) linearisation of growth data by plotting the logarithms of cell concentration versus time.

To solve problems with reaction, stoichiometric relationships must be used in conjunction with mass balance equations. REACTIONS AND REACTORS 12.16 METABOLIC ENGINEERING 681 FIGURE 12.32 Simplified metabolic pathway for mixed acid fermentation showing carbon fluxes in C-mol g21 h21 and the ATP flux in mol g21 h21. Although not the only way to attack these problems, the methods shown will assist your problem-solving efforts by formalising the mathematical approach. REACTIONS AND REACTORS 606 12.

The units of RA are, for example, kg s21. Therefore, even if we do not know the stoichiometry of growth, we can quickly calculate an upper limit for biomass yield from the molecular formulae for the substrate and product. Therefore, if the same mass of cells or enzyme is distributed between more particles, the rate of conversion will increase. Guidance can also be obtained from theoretical considerations. Typical microfiltration membranes have nominal pore diameters of 0.05 to 5 m. This makes application of the observable Thiele modulus difficult for MichaelisMenten kinetics. 6: Chemical Engineering Design (4th ed., Chapters 4 and 5). For example, the rate of reaction of an immobilised enzyme obeying MichaelisMenten kinetics (Section 12.3.3) depends on the values of vmax and Km for the enzyme in its immobilised state. Combining the Monod expression of Eq. Air is sparged into the fermenter; the total amount of off-gas recovered during the entire batch culture is 1250 kg. Applying each substrate separately, the rates of reaction are measured at 60 C using an enzyme concentration of 0.06 mg ml21. In the following discussion of bioreactor configurations, we will assume that aerobic operation is required. As an example, consider the reaction network shown in Figure 12.24. MATERIAL AND ENERGY BALANCES 134 4.20 4.21 4.22 4.23 4.24 4. Therefore, for these products, identification of high-producing strains and optimal environmental conditions is initially more rewarding than improving the bioreactor design and operation. Bioprocess Engineering Principles, Second Edition 45 2013 Elsevier Ltd. All rights reserved. They are: 1. From Eq. The following results were obtained from experiments with 0.15 M NaCl solution. 4. EXAMPLE 14.4 IMMOBILISED ENZYME REACTION IN A CSTR Mushroom tyrosinase is immobilised in spherical beads of diameter 2 mm for conversion of tyrosine to dihydroxyphenylalanine (DOPA) in a continuous, well-mixed bubble column. 11.34 Bench-scale continuous crystalliser A bench-scale mixed suspensionmixed product removal (MSMPR) crystalliser is set up in the laboratory to study the crystallisation of insulin.

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