《发酵与生物工程手册》（英文版）7 Cross-Flow Filtration

Cross-Flow Filtration Ramesh. bhave 1.0 INTRODUCTION Cross-flow filtration( CFF)also known as tangential flow filtration is not of recent origin. It began with the development of reverse osmosis(Ro) more than three decades ago. Industrial ro processes include desalting ofsea water and brackish water, and recovery and purification of some fermentation products. The cross-flow membrane filtration technique was next applied to the concentration and fractionation ofmacromolecules commonly recognized as ultrafiltration (UF) in the late 1960s. Major UF applications include electrocoat paint recovery, enzyme and protein recovery and pyrogen re moval(1-(31 In the past ten to fifteen years or so, the applications sphere of cross flow filtration has been extended to include microfiltration(MF) which primarily deals with the filtration of colloidal or particulate suspensions with size ranging from 0.02 to about 10 microns. Microfiltration applications are rapidly developing and range from sterile water production to clarification of beverages and fermentation products and concentration of cell mass, yeast E-coli and other media in biotechnology related applications. 01-14) Table I shows the types of separations achievable with MF, UF and RO membranes when operated in cross-flow configuration. For MF or UF application, the choice of membrane materials includes ceramics, metals or polymers, whereas for RO at the present only polymer membranes are predominantly used. Although cross-flow filtration is practiced in all the above three types of membrane applications, the description of membrane

7 Cross-Flow Filtration Ramesh R. Bhave 1.0 INTRODUCTION Cross-flow filtration (CFF) also known as tangential flow filtration is not of recent origin. It began with the development of reverse osmosis (RO) more than three decades ago. Industrial RO processes include desalting of sea water and brackish water, and recovery and purification of some fermentation products. The cross-flow membrane filtration technique was next applied to the concentration and fractionation ofmacromolecules commonly recognized as ultrafiltration (UF) in the late 1960's. Major UF applications include electrocoat paint recovery, enzyme and protein recovery and pyrogen re￾moval. [11-r31 In the past ten to fifteen years or so, the applications sphere of cross￾flow filtration has been extended to include microfiltration (MF) which primarily deals with the filtration of colloidal or particulate suspensions with size ranging from 0.02 to about 10 microns. Microfiltration applications are rapidly developing and range from sterile water production to clarification of beverages and fermentation products and concentration of cell mass, yeast, E-coli and other media in biotechnology related applications .[11-[41 Table 1 shows the types of separations achievable with MF, UF and RO membranes when operated in cross-flow configuration. For MF or UF application, the choice of membrane materials includes ceramics, metals or polymers, whereas for RO at the present only polymer membranes are predominantly used. Although cross-flow filtration is practiced in all the above three types of membrane applications, the description of membrane 2 71

Table 1. Separation Spectrum Nominal Size of Examples of Spccics Scparated Process Remarks Spccies 100500 Organic acld acetic acld Dalton itric acld, aImino acids Product recovered in permeate 2002.000 MF/UF Product recovered In permeate peniclllln, cephalosporin 10.000-200000 Proteins/poly saccharides retained by the membrane Is trated in retentate. Some losses 00103 Viruses. Inter concentrated in retentate colloidal silica MF/UF Product In concentrate phase o.1-10t E-coll. Pseudonomus dimInuta Species retained by the membrane mIcroorganisms from af Permeate sterile air ME Oils retained by the membrane are 1-100μ Bacteria cells, yeasts, molds Specles retained by the membrane is concentrated In retentate

Fermentation and Biochemical Engineering Handbook

Cross- Flow Filtration 275 characteristics, operational aspects and applications will be limited to MF and UF, where the cross-flow mode shows the greatest impact on filtration performance compared with dead end filtration. Figure I shows the sche matic of cross-flow filtration including the critical issues and operational modes for clarification or concentration using a semipermeable polymeric or Despite the growing use in a broad range of applications, cross-flow filtration still largely remains a semi-empirical science. Mathematical models and correlations are generally unavailable or applicable under very specific and well-defined conditions, owing to the complex combination of hydrodynamic, electrostatic and thermodynamic forces that affect flux and/ or retention. Membrane fouling is not yet fully understood and is perhaps the biggest obstacle to more widespread use of CFF in solid-liquid separations Membrane cleaning is also not well understood. The success of a membrane- based filtration process depends on its ability to obtain a reproducible performance in conformance with the design specifications over a long period of time with periodic(typically once a day) membrane cleaning 2.0 CROSS-FLOW yS. DEAD END FILTRATION The distinction between cross-flow and dead end (also known as through-flow) filtration can be better understood if we first analyze the mechanism of retention. The efficiency of cross-flow filtration is largely dependent on the ability of the membrane to perform an effective surface Table 2 shows the advantages and versatility of cross-flow filtration in meeting a broad range of filtration objectives. 1-316 Figure 2 illustrates the differences in separation mechanisms of CFF versus dead end filtration High recirculation rates ensure higher cross-flow velocities(and hence Reynold,'s number) past the membrane surface which promotes turbulence and increases the rate of redispersion of retained solids in the bulk feed. This is helpful in controlling the concentration polarization layer. It may be of interest to note that polarization is controlled essentially by cross-flow velocity and not very much by the average transmembrane pressure(ATP) It should also be noted that higher particle or molecular diffusivity under the influence of high shear can enhance the filtration rates. Since diffusivity values of rigid particles(MF)under turbulent conditions are typically much higher than those for colloidal particles or dissolved macromolecules (UF microfiltration rates tend to be much higher than ultrafiltration rates under otherwise similar conditions [5

Cross-Flow Filtration 273 characteristics, operational aspects and applications will be limited to MF and UF, where the cross-flow mode shows the greatest impact on filtration performance compared with dead end filtration. Figure 1 shows the sche￾matic of cross-flow filtration including the critical issues and operational modes for clarification or concentration using a semipermeable polymeric or inorganic membrane. Despite the growing use in a broad range of applications, cross-flow filtration still largely remains a semi-empirical science. Mathematical models and correlations are generally unavailable or applicable under very specific and well-defined conditions, owing to the complex combination of hydrodynamic, electrostatic and thermodynamic forces that affect flux and or retention. Membranefouling is not yet fully understood and is perhaps the biggest obstacle to more widespread use of CFF in solid-liquid separations. Membrane cleaning is also not well understood. The success of a membrane￾based filtration process depends on its ability to obtain a reproducible performance in conformance with the design specifications over a long period of time with periodic (typically once a day) membrane cleaning. 2.0 CROSS-FLOW VS. DEAD END FILTRATION The distinction between cross-flow and dead end (also known as through-flow) filtration can be better understood if we first analyze the mechanism of retention. The efficiency of cross-flow filtration is largely dependent on the ability of the membrane to perform an effective surface filtration, especially where suspended or colloidal particles are involved. Table 2 shows the advantages and versatility of cross-flow filtration in meeting a broad range of filtration 0bjectives.[']-[~1[~] Figure 2 illustrates the differences in separation mechanisms of CFF versus dead end filtration. High recirculation rates ensure higher cross-flow velocities (and hence Reynold's number) past the membrane surface which promotes turbulence and increases the rate of redispersion of retained solids in the bulk feed. This is helpful in controlling the concentration polarization layer. It may be of interest to note that polarization is controlled essentially by cross-flow velocity and not very much by the average transmembrane pressure (ATP). It should also be noted that higher particle or molecular difisivity under the influence of high shear can enhance the filtration rates. Since difisivity values of rigid particles (MF) under turbulent conditions are typically much higher than those for colloidal particles or dissolved macromolecules (UF) microfiltration rates tend to be much higher than ultrafiltration rates under otherwise similar condition^.[^]

Clean Product (e.g. antibiotics, bacteria-free or pyrogen-free water) Cross-flow Filtration Feed (polymeric, inorganic) Concentrated Product (clarification/ (e.g. cells, yeast, concentration) Critical Issues (fouling, polarization and cleaning) essss Batch, feed bleed, continuous, diafiltration, multistage Figure 1. Schematic of cross-flow filtration

274 Fermentation and Biochemical Engineering Handbook 1 Y v) Od m m W i - .- - s m iE - Y E Y .- 0 K - I= f 3 0 3 v) a W 75- ou Y .- a 0, W 75 rn m Y V i L 0

Table 2. Cross-Flow Filtration: Key Advantages Process Go Cross-low Fltration Deadend FIltration Ability to handle wide Excellent Generally poor variations in particle size Ability to handle wide Exccllent Poor or unacceptable variations in solids concentration Continuous concentration Excellent Poor or unacceptable witll recycle Waste minimization Superior Can minimize waste If handling low solids feed where cartridge disposal Is infrequent Iligh product purity or yield Excellent: Performance Is generally but may require diafiltration acceptable except in situations to ovcrcome excessive nux involving high solids or loss at higher recovery adsorptive fouling

Cross-Flow Filtration 275 w :: 0 - W c d a 0 0 L 2 3 C m V V 4 5 4 e, 0 C v, 3 a e, L - 0 L 3 r: v) .d 0 E .- I

276 Fermentation and Biochemical engineering handbook DEADEND FILTRATION CROSS-FLOW FILTRATION FEED CAKE 单o MEMBRANE FILTRATE PERMEATE Figure 2. Cross-flow versus dead end filtration On the other hand, in dead end filtration the retention is achieved by particle or gel layer buildup on the membrane and in the pores of the medium such as when a depth type filter is used. This condition is analogous to that encountered in packed-bed geometries In dead end filtration, the applied pressure drives the entire feed through the membrane filter producing a filtrate which is typically particle- free while the separated particles form a filter cake. The feed and filtrate travel concurrently along the length ofthe filter generating oneproduct stream forevery feed. In CFF, one feed generates two product streams, retentate and permeate. Per pass recovery in through-flow mode is almost 100%(sinc only the solids are removed) whereas in the cross- flow mode the per pass recovery typically does not exceed 20% and is often in the l to 5%range Recirculation of retentate is thus necessary to increase the total recovery at the expense of higher energy costs

276 Fermentation and Biochemical Engineering Handbook DEADEND FlLTnATlON CROSS-FLOW FILTRATION FlLl r J I IT nhTE Figure 2. Cross-flow versus dead end filtration. On the other hand, in dead end filtration the retention is achieved by particle or gel layer buildup on the membrane and in the pores of the medium such as when a depth type filter is used. This condition is analogous to that encountered in packed-bed geometries. In dead end filtration, the applied pressure drives the entire feed through the membrane filter producing a filtrate which is typically particle￾free while the separated particles form a filter cake. The feed and filtrate travel concurrently along the length ofthe filter generating one product stream for every feed. In CFF, one feed generates two product streams, retentate and permeate. Per pass recovery in through-flow mode is almost 100% (since only the solids are removed) whereas in the cross-flow mode the per pass recovery typically does not exceed 20% and is often in the 1 to 5% range. Recirculation of retentate is thus necessary to increase the total recovery at the expense of higher energy costs. PERMEAT E

Cross- Flow Filtration 277 As the filtration progresses, the filter cake becomes increasingly thicker which results in a reduced filtration rate(at a constant transmembrane pressure). When the flow or transmembrane pressure( depending on the control strategy)approaches a limiting value, the filtration must be inter rupted in order to clean or replace the membrane filter. This discontinuous mode of operation can be a major disadvantage when handling process streams with a relatively high solid content Cross-flow filtration can overcome this handicap by efficient fluid management to control the thickness of the concentration-polarization layer Thus, feed streams with solid loading higher than 1 wt % may be better suited for CFF whereas feed streams containing less than 0.5 wt. solids may be adequately served by dead end filtration. However, if the retained solids constitute the product to be recovered or when the nature of solids is the cause of increased fouling, cross-flow filtration should be considered. CFF is also the preferred mode when particle size or molecular weight distribution is an important consideration, such as in the separation of enzymes, antibiotics, proteins and polysaccharides from microbial cell mass, colloidal matter and oily emulsions. Tubular cross-flow filters are being used to continuously concentrate relatively rigid solids up to 70 wt. and up to 20 wt. with 3.0 COMPARISON OF CROSS-FLOW WITH OTHER COMPETING TECHNOLOGIES Cross-flow filtration as a processing alternative for separation and concentration of soluble or dissolved components competes with traditional equipment such as dead end cartridge filtration, pre-coat filtration and centrifugation. The specific merits and weaknesses of each of these filtration alternatives are summarized in Table 3. In addition to the ability to handle wide variations in processing conditions, other considerations may need to be addressed for economical viability of cross-flow filtration. These are briefly discussed below. A more detailed discussion on process design aspects capital and operating cost considerations is presented in Sec. 6.7 I. Energy Requirements. Centrifugal devices typically re- quire high maintenance. In contrast, cross-flow filtration requires minimal maintenance with low operating costs in most situations except for large bore(6 mm) tubular membrane products operating under high recirculation rates. The energy requirements in dead end filtration ar typically low

Cross-Flow Filtration 277 As the filtration progresses, the filter cake becomes increasingly thicker which results in a reduced filtration rate (at a constant transmembrane pressure). When the flow or transmembrane pressure (depending on the control strategy) approaches a limiting value, the filtration must be inter￾rupted in order to clean or replace the membrane filter. This discontinuous mode of operation can be a major disadvantage when handling process streams with a relatively high solid content. Cross-flow filtration can overcome this handicap by efficient fluid management to control the thickness of the concentration-polarization layer. Thus, feed streams with solid loading higher than 1 wt.% may be better suited for CFF whereas feed streams containing less than 0.5 wt.% solids may be adequately served by dead end filtration. However, if the retained solids constitute the product to be recovered or when the nature of solids is the cause of increased fouling, cross-flow filtration should be considered. CFF is also the preferred mode when particle size or molecular weight distribution is an important consideration, such as in the separation of enzymes, antibiotics, proteins and polysaccharides from microbial cell mass, colloidal matter and oily emulsions. Tubular cross-flow filters are being used to continuously concentrate relatively rigid solids up to 70 wt.% and up to 20 wt.% with gelatinous materials. 3.0 COMPARISON OF CROSS-FLOW WITH OTHER COMPETING TECHNOLOGIES Cross-flow filtration as a processing alternative for separation and concentration of soluble or dissolved components competes with traditional equipment such as dead end cartridge filtration, pre-coat filtration and centrifugation. The specific merits and weaknesses of each ofthese filtration alternatives are summarized in Table 3. In addition to the ability to handle wide variations in processing conditions, other considerations may need to be addressed for economical viability of cross-flow filtration. These are briefly discussed below. A more detailed discussion on process design aspects, capital and operating cost considerations is presented in Sec. 6.7. 1. Energy Requirements. Centrifugal devices typically re￾quire high maintenance. In contrast, cross-flow filtration requires minimal maintenance with low operating costs in most situations except for large bore (>6 mm) tubular membrane products operating under high recirculation rates. The energy requirements in dead end filtration are typically low

Table 3. Comparison of Cross-Flow Filtration vs Competitive Technologies Pocess Conditlons Cross-[ow FUlrallon Deadend Filtraton PeroaL Filtration centrifugation ww solids Can handle cmdlently bu an handle clleculvely: Can handle effectively: Can handle but eeds hlgh nux lo be cost by volume economics depends Can handle adequately Can handle adequately gh solids (10 to 70 by at>25 st hlgh capltal and maintenance Emulsifed Can handle eliclently Not well sulled Not well sullen suited due to wide Can landle Cannot handle cfnclently UP/ME Can handle Not well sulled Not feasible cost elective allenatlv low throughput solvents and/or Can handle adequately ol well sulted Not well sulted In May be dificult to handle resistant mcmbrancs Not well sulted Can handle adequately

278 Fermentation and Biochemical Engineering Handbook

Cross-Flow Filtration 279 2. Waste Minimization and Disposal. CFF systems mir mize disposal costs(e.g, when ceramic filters are used) DE stantial waste disposal costs may beincurred, particularl if the DE is contaminated with toxic organics. Currently in many applications, DE is disposed of in landfills. In future, however, this option may become less available forcing the industry to use cross-flow microfiltration technology or adopt other waste minimization measures 3. Capital Cost. Many dead end and de based filtrate systems can have a relatively low capital cost basis. 2JOn the other hand, CFF systems may require relatively higher capital cost. Centrifuges can also be capital intensiv especially where large-scale continuous filtration is 4.0 GENERAL CHARACTERISTICS OF CROSS-FLOw FILTERS The performance of a cross-flow filter is primarily defined by its efficiency in permeating or retaining desired species and the rate of transport of desired species across the membrane barrier. Microscopic features of the membranes greatly influence the filtration and separation performance. 031 The nature of the membrane material Pore dimensions Surface properties such as zeta potential Hydrophobic/hydrophilic cha aracter Membrane thickness From an operational standpoint, the mechanical, thermal and chemical stability ofthe membrane structure is important to ensure long service life and liability table 4 summarizes the influence and significance of these features on the overall performance of a cross-flow filter The discussion on the general characteristics of polymeric and inorganic membranes is treated separately partly due to their differences in productio methods and also due to important differences in their operating characteristics

Cross-Flow Filtration 279 2. Waste Minimization and Disposal. CFF systems mini￾mize disposal costs (e.g., when ceramic filters are used) whereas in diatomaceous (DE) pre-coat filtration sub￾stantial waste disposal costs may be incurred, particularly if the DE is contaminated with toxic organics. Currently, in many applications, DE is disposed of in landfills. In future, however, this option may become less available forcing the industry to use cross-flow microfiltration technology or adopt other waste minimization measures. 3. Capital Cost. Many dead end and DE based filtration systems can have a relatively low capital cost basis.[2] On the other hand, CFF systems may require relatively higher capital cost. Centrifuges can also be capital intensive especially where large-scale continuous filtration is required. 4.0 GENERAL CHARACTERISTICS OF CROSS-FLOW FILTERS The performance of a cross-flow filter is primarily defined by its efficiency in permeating or retaining desired species and the rate of transport of desired species across the membrane barrier. Microscopic features of the membranes greatly influence the filtration and separation The nature of the membrane material Pore dimensions Pore size distributions Porosity Surface properties such as zeta potential Hydrophobichydrophilic character Membrane thickness From an operational standpoint, the mechanical, thermal and chemical stability ofthe membrane structure is important to ensure long service life and reliability. Table 4 summarizes the influence and significance of these features on the overall performance of a cross-flow filter. The discussion on the general characteristics of polymeric and inorganic membranes is treated separately partly due to their differences in production methods and also due to important differences in their operating characteristics

Table 4. Influence of Membrane Characteristics on Filtration or Separation Performance Fogarty Influence or Significance symmetric high marginal Flux is hlgher compared with symmetric membranes ymmetric Particle retention In porous structure provides higher surface area per unlt volume. Thls also makes them susceptible to irreversible fouling Bubble point marginal Critical factor for membrane integrity. Porc dimensions marginal Must be carefully optimized to provide high flux combined Pore size marginal substantial Narrow pore size distribution often provides better separation efficienc Porosity hi marginal or none HIgher poroslty typically results In hlgher permeabilIty Zeta potential marginal to Relates to charge effects and can influence fouling due to adsorption/preclpl Hydrophobic margInal can be significant Rejection of water may be Important for sterility purposes Hydrophilic marginal can be significant Provides good wetting of membranes: can Increase transport lutlons; can minimize fouling due to organ substances

Fermentation and Biochemical Engineering Handbook i i j I i U ! I 6 i 2 i I i G P i: 5 0 e 0 C J e 0 L 0 E m - J R C 3 c 0 V CI ffi I