Abstract:
An improved cross-flow filtration unit utilizing at least one two-ply membrane is disclosed that has a particular pore size relationship in the two membrane layers.

Description:
[0001]     This is a Section 371 application of PCT/EP 00/13073 that claims priority of DE 100 00 196.3 filed Jan. 5, 2000.  
       BACKGROUND OF THE INVENTION  
       [0002]     In cross-flow filtration, a liquid feed flows tangentially over the surface of a filter material and is thereby split into a concentrate (retentate) stream and a filtrate (permeate) stream. Generally, microporous membranes are used which fall into the ultrafiltration and microfiltration classifications. Ultrafiltration membranes have average pores sizes that are capable of retaining macromolecules having a molecular weight between 500 and 1,000,000 Daltons, known in the filtration art as having a molecular weight cutoff (MWCO) of 500 to 1,000,000 Daltons. Microfiltration membranes exhibit average pore sizes of between 0.01 and 10 microns. See generally Chapter 4.3.3 in Gasper,  Handbook of Industrial Solids/Fluids Filtration  (1990).  
         [0003]     Retentate flowing over the surface of the separation membrane is typically recycled to flow over the membrane&#39;s surface repeatedly. The permeate which penetrates the membrane generally perpendicular to its surface is removed from the back side of the membrane. The target substances can be in either the permeate and/or the retentate. Cross-flow filtration units are often used in the form of filter cassettes, as described, for example in U.S. Pat. No. 4,715,955 and in DE PS 34 41 249. Cassettes are comprised of a multiplicity of adjacent filter arrays, each array generally consisting of flat custom-cut sections of retentate spacers which form feed flow channels, a first single membrane layer, a spacer for the formation of a filtrate collection opening, and a second single membrane layer. Each feed flow channel is in fluid communication with a liquid feed inlet and with a retentate outlet, and each permeate channel is in fluid communication with a permeate outlet. UK Patent Application 2,236,693 discloses a similar cross-flow filter, but with either self-supporting porous filter plates or porous polymeric membranes supported by and bonded to a porous ceramic layer having larger pores.  
         [0004]     As the feed flows over the membrane surface, the retentate substance, because of its size, is blocked from passage through the pores of the membrane and is rinsed away from the membrane surface, so that it will not plug the membrane pores, thus preventing its permeation through the membrane. In spite of this, for various reasons, build-up of non-filtered residue is formed on the surface of the feed side of the membrane, which generally impairs the filtering capacity, the yield of targeted substances and the service life of the cross-flow filtration unit.  
         [0005]     Thus a primary object of the invention is to provide an improved cross-flow filtration unit, which is characterized by an improved filtration capacity, a longer service life and a high product yield.  
         [0006]     The foregoing and other objectives, features, and advantages of the invention will be more readily understood upon consideration of the following detailed description of the invention, taken in conjunction with the accompanying drawing.  
       BRIEF SUMMARY OF THE INVENTION  
       [0007]     The present invention provides an improved cross-flow filtration unit that separates 
        the contents in a feed liquid;     the permeate content in a permeate; and     the retentate content in a retentate.        
 
         [0011]     The essence of the invention comprises sizing the pores in the two layers of a two-ply microporous membrane such that the pores of the layer facing the feed channel of the cross-flow filtration unit are on average 1.3 to 5 times the pores of the layer facing the permeate channel.  
         [0012]     With the inventive cross-flow filtration units, fluids can be filtered which include liquids, emulsions, suspensions, potable fluids such as beer, beer flavorants, wine, juice, water, milk and whey; laboratory grade water; wastewater; fluids in the fields of pharmaceuticals, medicine, cosmetics, chemistry, biotechnology, gene technology, environmental protection and in laboratory work. The inventive cross-flow filtration units can be employed for recovery of valuable material, for separation of substances such as macromolecules and biomolecules, for depyrogenation and sterilization of solutions, for the separation of corrosive substances from fluids, for the filtration and concentration of biological solutions, for the separation of microorganisms such as bacteria, yeasts, virus and cell components and for the desalination of protein solutions and other biological media. 
     
    
     BRIEF DESCRIPTION OF THE DRAWING  
       [0013]      FIG. 1  is a schematic cross-sectional view of the operative parts of an exemplary cross-flow filtration unit of the present invention. 
     
    
     DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS  
       [0014]     The present invention comprises an improvement in cross-flow filtration unit that enhances its efficiency and extends its service life and provides greater yield of target substances.  
         [0015]     Referring to  FIG. 1 , there is depicted in schematic form the operative parts of a cross-flow filtration unit of the invention, consisting of a series of liquid feed inlets  10 , feed flow channels  12 , permeate flow channels  20 , permeate outlets  22 , retentate outlets  30  and two-ply microporous polymeric membranes  40 , each membrane consisting of a front side layer or ply  41  facing feed flow channel  12 , and a back side layer or ply  42  facing permeate flow channel  20 , with the two plys  41  and  42  being joined together by small spacers  43  in their peripheries. The two plys  41  and  42  physically lie one on top of the other, but are not bonded together in the area  44  between them. The feed and permeate collection channels are advantageously held open by spacers (not shown in  FIG. 1 ) which are conventional.  
         [0016]     The flow of fluid through the filtration unit is as depicted by the arrows in  FIG. 1 , with the liquid feed initially entering the unit through feed inlet  10 , flowing through feed flow channel  12 , where the stream is split into a retentate-containing fluid flowing out through retentate outlet  30  and a permeate-containing fluid that permeates membrane  40  substantially perpendicularly from its front side  41  to its back side  42  into permeate flow channel  20  and permeate flow outlet  22 .  
         [0017]     In the case of single ply or supported microporous membranes suitable for using in microfiltration and ultrafiltration wherein the pore sizes of the filtration membrane are in the range of a MWCO of 1000 Daltons to 1.2 microns there is often build-up on the feed side of the membrane. Rather surprisingly, it has been discovered that demonstrably greater permeate flow and greater yields are achieved when the filter material consists of two microporous polymeric membrane layers situated one on top of the other but slightly spaced apart and wherein the membrane layer  41  facing the feed flow channel  12  has an average pore size greater by a factor of from about 1.3 to about 5 than the average pore size of the membrane layer  42  facing the permeate flow channel  20 . The slight spacing apart in the area  44  of the two polymeric membrane plys  41  and  42 , which are inherently flexible, permits the two membrane plys to flex during filtration, which tends to retard blinding of the membrane layers and consequently accelerate filtration.  
         [0018]     If the pore sizes of the membrane layers differ by a factor of less than 1.3, then, from a commercial operation standpoint, either insignificant or no effects on filtration efficiency are observed. On the other hand if the pore sizes in the membrane layers differ by a factor of greater than 5, then blinding of the membrane layer with the greater average pore size occurs very quickly, especially in the case of particulate-laden feed liquids, causing a halt to filtration.  
         [0019]     In a preferred embodiment, the cross-flow filtration unit is constructed as a filter cassette, the membrane layers of which consist of microfiltration membranes. Particularly preferred is a filter cassette, in which the membrane layers facing the permeate collection channels have an average pore diameter in the range of 0.1 to 1.2 μm.  
         [0020]     In an additional advantageous embodiment the filtration unit has a single two-ply membrane, a single feed inlet and channel, a single retentate outlet and a single permeate channel and outlet wherein the two layers of the microporous membrane are oriented as noted above, and the average pore sizes of the two layers comply with the above-noted restriction.  
       EXAMPLE  
       [0021]     The invention is better understood with the aid of the following filtration example whereby a cross-flow filtration unit having the pores of the two-ply membranes sized as noted above is used to filter a yeast cell suspension (pichia) with a cell concentration of 6×10 6  yeast cells (retentate content) per mL, which contains a targeted protein having a molecular weight of 70,000 Daltons (permeate content) in a concentration of 127 mL. The filtration takes place in a cross-flow mode with recycle of the retentate. During the filtration, the filtration unit is operated at a constant transmembrane pressure of 0.64 bar (the transmembrane pressure is equal to [input pressure+outlet pressure]/2 minus permeate pressure). The pressure was at 0.9 bar at the feed inlet, 0.4 bar at the retentate outlet and 0.1 bar at the permeate outlet.  
         [0022]     In order to be able to compare the results and relate these back to the mode of construction, the cell suspension feed was held constant for both the Example and the Comparative Example.  
         [0023]     A cross-flow filtration unit fabricated in the form of a filter cassette was employed with two-ply membranes exposed to the liquid feed and having a total membrane surface area of 0.4 m 2 , and which had 13 feed flow channels and 12 permeate flow channels. The membrane layers facing the permeate flow channels were of cellulose acetate with an average pore size of 0.2 μm and the membrane layers facing the feed flow channels were also of cellulose acetate, but having an average pore size of 0.45 μm, larger by a factor of 2.25. A volume of 7.3 L of the cell suspension was concentrated to a final volume of 1 L. The average permeate flow rate was 0.875 L/min·m 2 . Filtration was conducted for 18 minutes. The concentration of the target protein in the permeate and the retentate was 107 and 238 mg/L, respectively. The yield of targeted protein was 72%.  
       Comparative Example 1  
       [0024]     The Example of the invention was repeated with the following exceptions: both plys of the two-ply membrane had an average pore size of 0.2 μm, so that the ratio of pore sizes was less than 1.3, i.e., 1; the average permeate flow rate was 0.29 L/min·m 2 ; filtration was conducted for 54 minutes; the concentration of the target protein in the permeate and in the retentate was 86 and 387 g/L, respectively; and the yield was 58%, or 14% less than with the inventive filtration device.  
       Comparative Example 2  
       [0025]     The Example of the invention was repeated with the following exceptions: the average pore size of the ply facing the feed flow channel was 1.2 μm, while that of the ply facing the permeate channel was 0.2 μm, so that the ratio of pore sizes was greater than 5, i.e., 6; the average permeate flow rate was 0.49 L/min·m 2 ; filtration was conducted for 37 minutes; the concentration of the target protein in the permeate and in the retentate was 89 and 365 g/L, respectively; and the yield was 61%, or 11% less than with the inventive filtration device.  
       Comparative Example 3  
       [0026]     A cross-flow filtration cassette of conventional design (Sartocon® from Sartorius AG of Goettingen, Germany) was employed having a membrane surface exposed to the same feed of 0.7 m 2 , which had 17 feed flow channels and 16 permeate flow channels. The membrane layers facing the permeate flow channels consisted of a single-ply cellulose acetate membrane with an average pore size of 0.2 μm. A volume of 12.7 L of the cell suspension were concentrated to a final volume of 1 L. The average permeate flow was 0.328 L/min·m 2 . The filtration was terminated after 51 minutes. The concentration of targeted protein in the permeate and retentate was found to be 81.3 and 621 mg/L, respectively. The yield of targeted protein in the filtrate was thus 59%, or 13% less than with the inventive filtration device. The permeate flow was increased by a factor of 2.7.  
         [0027]     A further advantage apparent from use of the inventive cross-flow filtration unit was that a single filtration simultaneously encompassed both pre-filtration and final filtration; by way of contrast, in conventional practice two filtration steps must be carried out to achieve pre- and final filtration. Thus, use of the cross-flow filtration unit of the invention clearly results in a reduction of the costs of filtration.  
         [0028]     The terms and expressions which have been employed in the foregoing specification are used therein as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding equivalents of the features shown and described or portions thereof, it being recognized that the scope of the invention is defined and limited only by the claims which follow.