436 Fermentation and Biochemical Engineering Handbook Ladisch/78] has worked with a variety of column sizes ranging from 2 to 16 mm in diameter and 10 to 600 cm in length. His experience is that published semi-empirical scaleup correlations are useful in obtaining a first estimate on large scale column performance When scaling-up a chromatographic process, it may be necessary to change the order of certain steps from that used in the laboratory. Gel filtration, though a frequent first step at the laboratory scale, is not suitable for handling large scale feedstream volumes. 179) When gel filtration is used to separate molecules of similar molecular weights, sample sizes may range from 1%to 5% of the total gel volume. Thus, a 100 liter feedstream would require a gel filtration column of 2, 000 to 10,000 liters. When one is separating a large molecule from small molecules, as in desalting operations, the applied volume may be up to 30% of the gel volume On the other hand, ion exchange chromatography is a very good first step because its capacity is approximately 30 mg of protein per ml of resin This capacity is relatively independent of feed volume. For the same 100 liter feedstream, only a 20 liter ion exchange column would be required 5.6 Pressure Dro The pressure drop across an ion exchange bed has been represented by an equation [80 which depends on the average particle diameter, the void fraction in the bed, an exponent and a friction factor dependent on the Reynolds number, a shape factor, the density of the fluid, the viscosity of the fluid and the flow rate While that equation has internally consistent units(English system) the variables are not normally measured in those units. Another disadvantage is that one must check graphs of the exponent and friction factor versus the Reynolds number to use the equation ar flow with spherical particl fied to 007384(c)V0(l/min)(1-)3 Eq(28) ar cm)= For most ion exchange resins, the void volume is about 0. 38, so that(1-6) 8=4.34 and
436 Fermentation and Biochemical Engineering Handbook Ladisch['*I has worked with a variety of column sizes ranging from 2 to 16 mm in diameter and 10 to 600 cm in length. His experience is that published semiempirical scaleup correlations are usefbl in obtaining a first estimate on large scale column performance. When scaling-up a chromatographic process, it may be necessary to change the order of certain steps from that used in the laboratory. Gel filtration, though a frequent first step at the laboratory scale, is not suitable for handling large scale feedstream volumes.[79] When gel filtration is used to separate molecules of similar molecular weights, sample sizes may range from 1% to 5% of the total gel volume. Thus, a 100 liter feedstream would require a gel filtration column of 2,000 to 10,000 liters. When one is separating a large molecule from small molecules, as in desalting operations, the applied volume may be up to 30% of the gel volume. On the other hand, ion exchange chromatography is a very good first step because its capacity is approximately 30 mg of protein per ml of resin. This capacity is relatively independent of feed volume. For the same 100 liter feedstream, only a 20 liter ion exchange column would be required. 5.6 Pressure Drop The pressure drop across an ion exchange bed has been represented by an equation[80] which depends on the average particle diameter, the void fraction in the bed, an exponent and a friction factor dependent on the Reynolds number, a shape factor, the density of the fluid, the viscosity of the fluid and the flow rate. While that equation has internally consistent units (English system), the variables are not normally measured in those units. Another disadvantage is that one must check graphs of the exponent and friction factor versus the Reynolds number to use the equation. For laminar flow with spherical particles, the equation can be simplified to: AP O.0738p(cp)V0 (Ilmin) (1- E)~ -(bar/cm)= Eq. (28) L Dp2 (mm2) E3 For most ion exchange resins, the void volume is about 0.38, so that (1- 2)l 2 = 4.34 and:
lon Exchange 437 0.32u(cp)Vo(/ mir Eq(29) (bar/cm)= D2( Table 16 shows the agreement between results from experiments and those calculated with this n for several ion exchange resins Table 16. Pressure Drop for Commercial Ion Exchange Resins Flow Rate Mean Bead Pressure Drop(bar/cm) Resin (/min) Diameter(mm) Calculated Measured Dowex SBR-P 151.4 0.750 Dowex WGR-2 2.7 0.675 Dowex MWA-1 15.1 0.675 0.67 0.77 Dowex MSA-I 0.650 2.13 DowexMSC-1 0.740 1.22 Figure 25 shows the use of a size factor for resins which is used to develop a pressure factor. This pressure factor can then be used to calculate the pressure drop under conditions of different solution viscosities, flow rates or particle size distributions once the pressure drop is known at one viscosity flow rate and particle size distribution
Ion Exchange 437 AP - (bar / cm) = Eq. (29) L D; (mm2) 0.32~ (cp) V, (I / min) Table 16 shows the agreement between results from experiments and those calculated with this equation for several ion exchange resins. Table 16. Pressure Drop for Commercial Ion Exchange Resins Resin Flow Rate Mean Bead Pressure Drop (barkm) (L/min) Diameter (mm) Calculated Measured Dowex SBR-P 15 1.4 0.750 5.28 5.08 Dowex WGR-2 22.7 0.675 1 .oo 1.06 Dowex MWA-1 15.1 0.675 0.67 0.77 DowexMSA- 1 37.8 0.650 1.79 2.13 DowexMSC- 1 30.3 0.740 1 .os 1.22 Figure 25 shows the use of a size factor for resins which is used to develop a pressure factor. This pressure factor can then be used to calculate the pressure drop under conditions of different solution viscosities, flow rates or particle size distributions once the pressure drop is known at one viscosity, flow rate and particle size distribution
438 Fermentation and Biochemical Engineering Handbook 8 HLd3dq日d0划da 9R9888 c冯导8R
438 Fermentation and Biochemical Engineering Handbook .d B x LDoooooooo O~N+Wod~d$ !I %I 2 I: n a
Ton Exchange 439 5.7 Ion Exchange Resin Limitations When ion exchange resins are used for an extended period of time, the exchange capacities are gradually decreased. Possible causes for these decreases include organic contamination due to the irreversible adsorption of organics dissolved in the feedstream, the oxidative decomposition due to the cleaving of the polymer cross- links by their contact with oxidants, the thermal decomposition of functional groups due to the use of the resin at high temperature and the inorganic contaminations due to the adsorption of InorganIc ions When a resin bed has been contaminated with organic foulants procedure is available that can help to restore the resin. tB Three bed volumes of 10% NaCI-2% NaOH solution are passed through the resin bed at 50oC The first bed volume is passed through at the same flow rate, followed by a through rinsing and two regenerations with the standard regenerate If the fouling is due to microbial contamination, the same authors recommend backwashing the bed and then filling theentire vessel with a dilute lution (<0.05%)of organic chlorine. This solution should be circulated through the bed for 8 hours at a warm(50 C)temperature. After this treatment, the resin should be backwashed, regenerated and rinsed before returning it to service. This procedure may cause some oxidation of the polymeric resin, thereby reducing its effective cross-linking and strength Therefore, treating the resin in this fashion should not be a part of the normal resin maintenance program Physical stability of a properly made cation or anion exchange resin more than adequate for any of the typical conditions of operation. These resins can be made to have a physical crush strength in excess of 300 grams per bead Perhaps more important are the limitations inherent in the structure of certain polymers or functional groups due to thermal and chemical degrada tion. Thermally, styrene-based cation exchange resins can maintain their chemical and physical characteristics at temperatures in excess of 125C.At temperatures higher than this, the rate of degradation increases. Operating temperatures as high as 150oC might be used depending on the required life for a particular operation to be economically attractive Strong base anion exchange resins, on the other hand, are thermally degraded at the amine functional group. Operating in the chloride form, this is not a severe limitation, with temperatures quite similar to those for cation exchange resins being tolerable. However, most strong base anion exchange sins used involve either the hydroxide form, the carbonate or bicarbonate form. In these ionic forms, the amine functionality degrades to form lower
Ion Exchange 439 5.7 Ion Exchange Resin Limitations When ion exchange resins are used for an extended period of time, the exchange capacities are gradually decreased. Possible causes for these decreases include organic contamination due to the irreversible adsorption of organics dissolved in the feedstream, the oxidative decomposition due to the cleaving ofthe polymer cross-links by their contact with oxidants, the thermal decomposition of functional groups due to the use of the resin at high temperature and the inorganic contaminations due to the adsorption of inorganic ions. When a resin bed has been contaminated with organic foulants, a procedure is available that can help to restore the resin.[*l] Three bed volumes of 10% NaCl - 2%NaOH solution are passed through the resin bed at 50°C. The first bed volume is passed through at the same flow rate, followed by a through rinsing and two regenerations with the standard regenerate. If the fouling is due to microbial contamination, the same authors recommend backwashing the bed and then filling the entire vessel with a dilute solution (< 0.05%) of organic chlorine. This solution should be circulated through the bed for 8 hours at a warm (50°C) temperature. After this treatment, the resin should be backwashed, regenerated and rinsed before returning it to service. This procedure may cause some oxidation of the polymeric resin, thereby reducing its effective cross-linking and strength. Therefore, treating the resin in this fashion should not be a part of the normal resin maintenance program. Physical stability of a properly made cation or anion exchange resin is more than adequate for any of the typical conditions of operation. These resins can be made to have a physical crush strength in excess of 300 grams per bead. Perhaps more important are the limitations inherent in the structure of certain polymers or functional groups due to thermal and chemical degradation. Thermally, styrene-based cation exchange resins can maintain their chemical and physical characteristics at temperatures in excess of 125°C. At temperatures higher than this, the rate of degradation increases. Operating temperatures as high as 150°C might be used, depending on the required life for a particular operation to be economically attractive. Strong base anion exchange resins, on the other hand, are thermally degraded at the amine functional group. Operating in the chloride form, this is not a severe limitation, with temperatures quite similar to those for cation exchange resins being tolerable. However, most strong base anion exchange resins used involve either the hydroxide form, the carbonate or bicarbonate form. In these ionic forms, the amine functionality degrades to form lower
440 Fermentation and Biochemical Engineering Handbook amines and alcohols. Operating temperatures in excess of 50C should be avoided for Type I strong base anion exchange resins in the hydroxide form Type II strong base resins in the hydroxide form are more susceptible to thermal degradation and temperatures in excess of 35"C should be avoided The amine functionality of weak base resins is more stable in the free- base form than that of strong base resins. Styrene-divinylbenzene weak base resins may be used at temperatures up to 100oC with no adverse effects Chemical attack most frequently involves degradation due to oxida tion. This occurs primarily at the cross- linking sites with cation exchange resins and primarily on the amine sites of the anion exchange resins. From an operating standpoint and, more importantly, from a severe oxidizing conditions are to be avoided in ion exchange columns Oxidizing agents, whether peroxide or chlorine, will deg grade ion exchange resins. 182 On cation resins, it is the tertiary hydrogen attached to a carbon involved in a double bond that is most vulnerable to oxidative degradation. In the presence of oxygen, this tertiary hydrogen is transformed first to the hydroperoxide and then to the ketone, resulting in chain scission The small chains become soluble and are leached from the resin. This chain scission may also be positioned such that the cross-linking of the resin is decreased, as evidenced by the gradual increase in water retention values The degradation of anion resins occurs not only by chain scission, but also at the more vulnerable nitrogen on the amine functionality. As an example, the quaternary nitrogen on Type I strong base anion resins is progressively transformed to tertiary, secondary, primary nitrogen and finally to a nonbasic product Oxidative studies on resins with different polymer backbones and functionalities have been performed as accelerated tests. [831 The data is shown in Table 17 for polystyrene and polydiallylamine resins. Although the polydiallylamine resins have a higher initial capacity, they are much more susceptible to oxidative degradation. When the polystyrene resin has a mixture of primary and secondary amino groups or when a hydroxy containing group is attached to the amine of the functional group, the susceptibility to oxidation is enhanced. Thus one can understand the lower ermal limit for Type lI anion resins compared to Type I resins The effect of thermal cycling on strong base anion resins has been studied by Kysela and Brabec. [84) The average drop per cycle in strong base capacity was 2. 1 x 10-mmol(OH)/ml over the 480 cycles between 20oC and 80oC. Figure 26 shows the decrease in total exchange capacity(open circle and in strong base(salt splitting) capacity(solid circles) for each of the ndividual resins included in the study
440 Fermentation and Biochemical Engineering Handbook amines and alcohols. Operating temperatures in excess of 50°C should be avoided for Type I strong base anion exchange resins in the hydroxide form. Type I1 strong base resins in the hydroxide form are more susceptible to thermal degradation and temperatures in excess of 35°C should be avoided. The amine functionality of weak base resins is more stable in the freebase form than that of strong base resins. Styrenedivinylbenzene weak base resins may be used at temperatures up to 100°C with no adverse effects. Chemical attack most frequently involves degradation due to oxidation. This occurs primarily at the cross-linking sites with cation exchange resins and primarily on the amine sites of the anion exchange resins. From an operating standpoint and, more importantly, from a safety standpoint, severe oxidizing conditions are to be avoided in ion exchange columns. Oidizing agents, whether peroxide or chlorine, will degrade ion exchange resins.[82] On cation resins, it is the tertiary hydrogen attached to a carbon involved in a double bond that is most vulnerable to oxidative degradation. In the presence of oxygen, this tertiary hydrogen is transformed first to the hydroperoxide and then to the ketone, resulting in chain scission. The small chains become soluble and are leached from the resin. This chain scission may also be positioned such that the cross-linking of the resin is decreased, as evidenced by the gradual increase in water retention values. The degradation of anion resins occurs not only by chain scission, but also at the more vulnerable nitrogen on the amine functionality. As an example, the quaternary nitrogen on Type I strong base anion resins is progressively transformed to tertiary, secondary, primary nitrogen and finally to a nonbasic product. Oxidative studies on resins with different polymer backbones and hctionalities have been performed as accelerated tests.[83] The data is shown in Table 17 for polystyrene and polydiallylamine resins. Although the polydiallylamine resins have a higher initial capacity, they are much more susceptible to oxidative degradation. When the polystyrene resin has a mixture of primary and secondary amino groups or when a hydroxycontaining group is attached to the amine of the functional group, the susceptibility to oxidation is enhanced. Thus one can understand the lower thermal limit for Type I1 anion resins compared to Type I resins. The effect of thermal cycling on strong base anion resins has been studied by Kysela and bra be^.[*^] The average drop per cycle in strong base capacitywas 2.1 x 10-4mm01 (0H~)/m1overthe480cyc1esbetween20"Cand 80°C. Figure 26 shows the decrease in total exchange capacity (open circles) and in strong base (salt splitting) capacity (solid circles) for each of the individual resins included in the study