Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberUS20100059443 A1
Publication typeApplication
Application numberUS 12/551,762
Publication date11 Mar 2010
Filing date1 Sep 2009
Priority date2 Sep 2008
Also published asCA2736814A1, CA2736814C, EP2334413A2, EP2334413A4, US20170145053, WO2010027955A2, WO2010027955A3
Publication number12551762, 551762, US 2010/0059443 A1, US 2010/059443 A1, US 20100059443 A1, US 20100059443A1, US 2010059443 A1, US 2010059443A1, US-A1-20100059443, US-A1-2010059443, US2010/0059443A1, US2010/059443A1, US20100059443 A1, US20100059443A1, US2010059443 A1, US2010059443A1
InventorsDamian Brellisford, Donna L. Crossley, Greg Mclntosh, Robert Ruman, John Rydall, Christopher S. Shields
Original AssigneeNatrix Separations Inc.
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Chromatography Membranes, Devices Containing Them, and Methods of Use Thereof
US 20100059443 A1
Abstract
Described herein are fluid treatment devices for use in tangential flow filtration, comprising a housing unit and a composite material, wherein the composite material comprises: a support member comprising a plurality of pores extending through the support member; and a non-self-supporting macroporous cross-linked gel comprising macropores having an average size of 10 nm to 3000 nm, said macroporous gel being located in the pores of the support member. The invention also relates to a method of separating a substance from a fluid, comprising the step of placing the fluid in contact with an inventive device, thereby adsorbing or absorbing the substance to the composite material contained therein.
Images(31)
Previous page
Next page
Claims(44)
1. A fluid treatment device comprising
a housing unit, wherein the housing unit comprises
(a) an inlet and an outlet;
(b) a fluid flow path between the inlet and the outlet; and
(c) a composite material within the housing unit, wherein the composite material comprises
a support member comprising a plurality of pores extending through the support member; and
a non-self-supporting macroporous cross-linked gel comprising macropores having an average size of 10 nm to 3000 nm, said macroporous gel being located in the pores of the support member;
wherein said macropores of said macroporous cross-linked gel are smaller than said pores of said support member; and
wherein the pores of the support member are substantially perpendicular to the fluid flow path.
2. The fluid treatment device of claim 1, wherein the composite material is arranged in a substantially coplanar stack of substantially coextensive sheets, a substantially tubular configuration, or a substantially spiral wound configuration.
3. The fluid treatment device of claim 1, wherein
the support member is in the form of hollow porous fibers;
each hollow porous fiber defines a lumen;
the lumen is from about 20 μm to about 100 μm in diameter; and
the lumen is substantially perpendicular to the pores in the hollow porous fiber support member.
4. The fluid treatment device of claim 3, wherein a plurality of hollow porous fibers are arranged in a bundle.
5. The fluid treatment device of claim 1, wherein the housing unit is substantially cylindrical.
6. The fluid treatment device of claim 1, wherein the housing unit is disposable or reusable.
7. The fluid treatment device of claim 1, wherein the housing unit is plastic or stainless steel.
8. The fluid treatment device of claim 1, wherein the inlet or the outlet is a press fit attachment point, a luer lock attachment point, or a hose barb attachment point.
9. The fluid treatment device of claim 1, wherein the macroporous cross-linked gel is a hydrogel, a polyelectrolyte gel, a hydrophobic gel, a neutral gel, or a gel comprising functional groups.
10. The fluid treatment device of claim 9, wherein the macroporous cross-linked gel is a gel comprising functional groups; and said functional groups are selected from the group consisting of amino acid ligands, antigen and antibody ligands, dye ligands, biological molecules, biological ions, and metal affinity ligands.
11. The fluid treatment device of claim 10, wherein said functional groups are metal affinity ligands.
12. The fluid treatment device of claim 11, further comprising a plurality of metal ions complexed to a plurality of said metal affinity ligands.
13. The fluid treatment device of claim 11, wherein said metal affinity ligands are octadentate, hexadentate, tetradentate, tridentate or bidentate ligands.
14. The fluid treatment device of claim 11, wherein said metal affinity ligands are iminodicarboxylic acid ligands.
15. The fluid treatment device of claim 11, wherein said metal affinity ligands are iminodiacetic acid ligands.
16. The fluid treatment device of claim 12, wherein said metal ions are transition metal ions, lanthanide ions, poor metal ions or alkaline earth metal ions.
17. The fluid treatment device of claim 12, wherein said metal ions are selected from the group consisting of nickel, zirconium, lanthanum, cerium, manganese, titanium, cobalt, iron, copper, zinc, silver, gallium, platinum, palladium, lead, mercury, cadmium and gold.
18. The fluid treatment device of claim 12, wherein said metal affinity ligands are iminodicarboxylic acid ligands; and said metal ions are nickel.
19. The fluid treatment device of claim 10, wherein said functional groups are biological molecules or biological ions.
20. The fluid treatment device of claim 19, wherein said functional groups are selected from the group consisting of albumins, lysozyme, viruses, cells, γ-globulins of human and animal origins, immunoglobulins of both human and animal origins, proteins of recombinant or natural origin including, polypeptides of synthetic or natural origin, interleukin-2 and its receptor, enzymes, monoclonal antibodies, antigens, lectins, bacterial immunoglobulin-binding proteins, trypsin and its inhibitor, cytochrome C, myoglobulin, recombinant human interleukin, recombinant fusion protein, Protein A, Protein G, Protein L, Peptide H, nucleic acid derived products, DNA of either synthetic or natural origin, and RNA of either synthetic or natural origin.
21. The fluid treatment device of claim 19, wherein said functional groups are Protein A.
22. The fluid treatment device of claim 1, wherein the macroporous crosslinked gel is cross-linked by N,N′-methylenebisacrylamide or a polyfunctional macromonomer.
23. The fluid treatment device of claim 1, wherein the support member consists essentially of polymeric material in the form of a membrane that has a thickness of from about 10 μm to about 500 μm and comprises pores of average size between about 0.1 to about 25 μm.
24. The fluid treatment device of claim 1, wherein the support member consists essentially of a polyolefin.
25. A method comprising the step of:
contacting a first fluid comprising a substance with a composite material in a fluid treatment device of claim 1, thereby adsorbing or absorbing the substance onto the composite material.
26. The method of claim 25, further comprising the step of
placing the first fluid in an inlet of the fluid treatment device.
27. The method of claim 26, wherein the first fluid is passed along a fluid flow path substantially perpendicular to the pores of the support member.
28. The method of claim 27, further comprising the step of
contacting a second fluid with the substance adsorbed or absorbed onto the composite material, thereby releasing the substance from the composite material.
29. The method of claim 28, wherein the second fluid is passed through the macropores of the composite material, thereby releasing the substance from the composite material.
30. The method of claim 28, wherein the second fluid is passed along the fluid flow path substantially perpendicular to the pores of the support member, thereby releasing the substance from the composite material.
31. The method of claim 25, wherein the macroporous gel displays a specific interaction for the substance; and the specific interactions are electrostatic interactions, affinity interactions, or hydrophobic interactions.
32. The method of claim 31, wherein the specific interactions are electrostatic interactions, the composite material bears charges on the macroporous gel; the substance is charged; and the substance is separated based on Donnan exclusion.
33. The method of claim 27, wherein the first fluid is a suspension of cells or a suspension of aggregates.
34. The method of claim 27, wherein the substance is a biological molecule or biological ion.
35. The method of claim 34, wherein the biological molecule or biological ion is selected from the group consisting of albumins, lysozyme, viruses, cells, γ-globulins of human and animal origins, immunoglobulins of both human and animal origins, proteins of recombinant or natural origin including, polypeptides of synthetic or natural origin, interleukin-2 and its receptor, enzymes, monoclonal antibodies, trypsin and its inhibitor, cytochrome C, myoglobulin, recombinant human interleukin, recombinant fusion protein, nucleic acid derived products, DNA of either synthetic or natural origin, and RNA of either synthetic or natural origin.
36. The method of claim 34, wherein the biological molecule or biological ion is a protein; and the protein comprises exposed amino acid residues selected from the group consisting of Glu, Asp, Try, Arg, Lys, Met, and His.
37. The method of claim 34, wherein the biological molecule or biological ion is a protein; and the protein comprises exposed His amino acid residues.
38. The method of claim 34, wherein the biological molecule or biological ion is a monoclonal antibody.
39. The method of claim 27, wherein the substance is a metal-containing particle, or a metal-containing ion.
40. The method of claim 39, wherein the metal-containing particle or metal-containing ion comprises a transition metal, a lanthanide, a poor metal, or an alkaline earth metal.
41. The method of claim 39, wherein the metal-containing particle or metal-containing ion comprises a metal selected from the group consisting of nickel, zirconium, lanthanum, cerium, manganese, titanium, cobalt, iron, copper, zinc, silver, gallium, platinum, palladium, lead, mercury, cadmium and gold.
42. The method of claim 27, wherein the first fluid is waste water.
43. The method of claim 27, wherein the first fluid comprises egg white.
44. The method of claim 27, wherein the first fluid comprises egg white; and the substance is lysozyme.
Description
    RELATED APPLICATIONS
  • [0001]
    This application claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 61/093,600, filed Sep. 2, 2008; and U.S. Provisional Patent Application Ser. No. 61/102,797, filed Oct. 3, 2008; both of which are hereby incorporated by reference in their entirety.
  • BACKGROUND OF THE INVENTION
  • [0002]
    Membrane-based water treatment processes were first introduced in the 1970s. Since then, membrane-based separation technologies have been utilized in a number of other industries. In the pharmaceutical and biotechnology industries, the use of preparative chromatography, direct flow filtration (DFF) and tangential flow filtration (TFF), including micro-, ultra-, nano-filtration and diafiltration are well-established methods for the separation of dissolved molecules or suspended particulates. Ultrafiltration (UF) and microfiltration (MF) membranes have become essential to separation and purification in the manufacture of biomolecules. Biomolecular manufacturing, regardless of its scale, generally employs one or more steps using filtration. The attractiveness of these membrane separations rests on several features including, for example, high separation power, and simplicity, requiring only the application of pressure differentials between the feed stream and the permeate. This simple and reliable one-stage filtering of the sample into two fractions makes membrane separation a valuable approach to separation and purification.
  • [0003]
    Notably, the separation and recovery of biomolecules, such as enzymes and glycoproteins, are critical cost-determining steps in most of the down-stream processes in the biotechnology industry. For example, separation of lysozyme from crude sources, such as egg white, has been achieved by salt precipitation (U.S. Pat. No. 4,504,583), or ion exchange techniques (U.S. Pat. Nos. 4,705,755; 4,966,851; 4,518,695; and 4,104,125). Due to the viscous, highly concentrated nature of egg white, and the nature of the other protein constituents, recovering high-purity lysozyme in good yield is extremely laborious and costly.
  • [0004]
    In one class of membrane separations, the species of interest is that which is retained by the membrane, in which case the objective of the separation is typically to remove smaller contaminants, to concentrate the solution, or to affect a buffer exchange using diafiltration. In another class of membrane separations, the species of interest is that which permeates through the filter, and the objective is typically to remove larger contaminants. In MF, the retained species are generally particulates, organelles, bacteria or other microorganisms, while those that permeate are proteins, colloids, peptides, small molecules and ions. In UF the retained species are typically proteins and, in general, macromolecules, while those that permeate are peptides, ions and, in general, small molecules.
  • [0005]
    In “dead-end,” “normal flow,” or “direct flow” filtration (DFF), a filtration device is used that has one inlet and one outlet. The total (100%) solution volume is forced through a porous filter. DFF devices are commonly single-use devices. Such membrane filters or depth filters are commercially available in different filter area sizes as well as different pore sizes. Depending upon the selected pore size, molecules or particulates smaller than the average membrane pore size will pass (together with solvent) through the filter. Thus, direct flow filtration (DFF) devices allow for the selective removal of particulates, bacteria, viruses, cell debris, and large macromolecules.
  • [0006]
    Conventional filters in which all of the fluid entering the filter housing passes through the filter element (DFF) typically operate at low shear near the surface of the filter medium. Thus, when a highly flocculating dispersion is delivered into a conventional filter device by a conventional delivery system, flocs ordinarily tend to form near the surface of the filter medium. The flow field moves the flocs onto the surface and into the bulk of the filter medium, ultimately resulting in plugging of the filter. In practice, a plugged filter may cause a significant amount of downtime for a filter change.
  • [0007]
    A raw or semi-conditioned process stream that contains high-value materials is often highly viscous or highly contaminated. As such, DFF separation approaches are difficult or challenging due to blinding of the membrane with the solute present in the feed stream. Additionally, these processes often require high pressure to maintain a reasonable flux of permeate.
  • [0008]
    In contrast, tangential flow filtration (TFF) devices, also known as cross-flow filtration devices, have one inlet, one retentate outlet and at least one permeate outlet. Tangential flow denotes a filtration configuration in which a flowing fluid is directed along the surface of a filter medium, substantially parallel (tangential) to the surface of the filter medium. In this configuration, the solute adsorbs or absorbs to the surface or the pores of the membrane as the eluent flows over the surface. The purified portion of fluid that passes through such filter medium has a velocity component which is “cross-wise”, i.e., perpendicular to the direction of the fluid flowing along the surface of such filter medium. In TFF, the retentate (or decantate) can be repeatedly re-circulated with the objective of improving filtration efficiency and enhancing the permeate yield. The re-circulated retentate solution pathway runs parallel to the membrane surface and is pumped past the membrane with sufficient velocity to ensure a surface cleaning action. However, only a relatively small amount of permeate is collected during each retentate volume-pass, and thus a significant processing time is typically associated with TFF procedures. If an appropriate membrane is selected for a specific separation, a second liquid can be used to elute the material adsorbed or absorbed to the membrane for harvesting.
  • [0009]
    Crossflow filtration or tangential filtration is a well known filtration process. Reference may be had e.g., to U.S. Pat. Nos. 5,681,464, 6,461,513; 6,331,253, 6,475,071, 5,783,085, 4,790,942, the disclosures of which are incorporated herein by reference. Reference may also be had to “Filter and Filtration Handbook”, 4th Ed., T. Christopher Dickenson, Elsevier Advanced Technology, 1997, the disclosure of which is incorporated herein by reference.
  • [0010]
    In TFF careful attention must be paid in the device design, as flow dynamics play an important role in the efficiency of the system. Turbulent flow must be minimized in these systems, so as to not physically disassociate a desired substance from the membrane surface. Turbulence is flow dominated by recirculation, eddies, and apparent randomness. Flow in which turbulence is not exhibited is called laminar. A steady, laminar flow is desired.
  • [0011]
    For optimal results, both DFF and TFF demand careful attention to filter porosity and filter area, as well as required differential pressures and selected pump rates. However, filtration devices tend to clog when used over an extended period of time and must be timely replaced. Clogging of a filtration device occurs: (1) when the membrane pores become obstructed, typically with trapped cells, particulate matter, cell debris or the like, or (2) when the feed channel (into a TFF device) becomes obstructed by solids or colloidal material and/or cell debris. This clogging of the feed channel or membrane pores results in a decreased liquid flow across the porous filter membrane. The result is a change in system pressure which, if not properly addressed, runs the risk of serious detriment to the operation which incorporates the filtration procedure.
  • [0012]
    As such, the choice of membrane in each of the filtration techniques is critical to the efficiency and success of the separation. Composite membranes with high specificity and high binding capacity have been described in U.S. Pat. No. 7,316,919, and US Patent Application Publication Nos. 2008/0314831 and 2008/0312416, which are hereby incorporated by reference in their entirety. These materials are highly versatile and can be designed for specific separation situations.
  • [0013]
    A wide variety of devices are available for these applications. Typically, devices are categorized by configuration into categories including the following: flat plate (for example, cassette or plate and frame), spiral (or spiral wound), tubular, or hollow fiber. The choice of device configuration is driven by reliability, performance, and cost for each specific application.
  • [0014]
    Flat plate or cassette devices consist of membranes cast on plates; the plates are then reliably stacked. The devices may or may not have flexible screens in the feed channels to support the membranes. An appealing advantage of a configuration such as this is its very compact design. However, channel height control, defined by plate-to-plate interaction and distance, must be very carefully considered
  • [0015]
    Tubular devices consist of a membrane cast on the inside surface or outside diameter of a porous support tube. Typically, a feed solution is pumped through the center of the tube at velocities as high as 20 ft/s. These cross-flow velocities minimize the formation of a concentration polarization layer on the membrane surface, promoting high and stable flux and easy cleaning. The permeate is driven through the membrane. Despite the apparent advantages of using a system such as this, the cost tends to be high.
  • [0016]
    Spiral-wound devices consist of multiple layers of folded membrane, feed screen, and permeate screen wound around a center permeate collection tube (FIG. 23). Typically found in water purification applications, these devices are also compact and can operate at low pressure to save energy, but are suitable for high pressure applications as well. The cost per membrane area is typically low.
  • [0017]
    Typical spiral wound filters consist of about 1 to about 6 spiral wound elements coupled in a serial flow mode and placed in a cylindrical pressure vessel. Between two membranes in the roll is placed a permeable porous medium for conduction of fluid, the concentrate spacer, to ensure that the concentrate can flow over the membrane in order to be distributed all over the surface and to continuously rinse the membrane from accumulating solids. The filter elements are kept tightly wound by a hard, impermeable shell. In this configuration flow in and out of the filter element will be through the ends in an axial direction.
  • [0018]
    An unmet need exists in many applications where high contaminate feed streams will immediately plug or blind the membrane media in a typical DFF mode or, when the membranes employed are incapable of any appreciable substrate capture, in cross-flow modes. Utilizing versatile, high performance, high throughput membranes capable of high binding capacities in filtration devices would provide separation systems with performances far exceeding any known technology in a variety of art areas.
  • SUMMARY OF THE INVENTION
  • [0019]
    In certain embodiments, the invention relates to a fluid treatment device comprising
      • a housing unit, wherein the housing unit comprises
      • (a) an inlet and an outlet;
      • (b) a fluid flow path between the inlet and the outlet; and
      • (c) a composite material within the housing unit, wherein the composite material comprises
        • a support member comprising a plurality of pores extending through the support member; and
        • a non-self-supporting macroporous cross-linked gel comprising macropores having an average size of 10 nm to 3000 nm, said macroporous gel being located in the pores of the support member;
        • wherein said macropores of said macroporous cross-linked gel are smaller than said pores of said support member;
          wherein the pores of the support member are substantially perpendicular to the fluid flow path.
  • [0027]
    In certain embodiments, the invention relates to a fluid treatment device comprising
      • a plurality of housing units, wherein each housing unit comprises
      • (a) an inlet and an outlet;
      • (b) a fluid flow path between the inlet and the outlet; and
      • (c) a composite material within the housing unit, wherein the composite material comprises
        • a support member comprising a plurality of pores extending through the support member; and
        • a non-self-supporting macroporous cross-linked gel comprising macropores having an average size of 10 nm to 3000 nm, said macroporous gel being located in the pores of the support member;
        • wherein said macropores of said macroporous cross-linked gel are smaller than said pores of said support member; and
          wherein the pores of the support member are substantially perpendicular to the fluid flow path.
  • [0035]
    In certain embodiments, the invention relates to any one of the aforementioned fluid treatment devices, wherein the composite material is arranged in a substantially coplanar stack of substantially coextensive sheets, a substantially tubular configuration, or a substantially spiral wound configuration.
  • [0036]
    In certain embodiments, the invention relates to any one of the aforementioned fluid treatment devices, wherein the macroporous cross-linked gel is a neutral or charged hydrogel, a polyelectrolyte gel, a hydrophobic gel, a neutral gel, or a gel comprising functional groups.
  • [0037]
    In certain embodiments, the invention relates to any one of the aforementioned fluid treatment devices, wherein said functional groups are selected from the group consisting of amino acid ligands, antigen and antibody ligands, dye ligands, biological molecules, biological ions, and metal affinity ligands.
  • [0038]
    In certain embodiments, the invention relates to any one of the aforementioned fluid treatment devices, wherein said functional groups are metal affinity ligands. In certain embodiments, the invention relates to any one of the aforementioned fluid treatment devices, further comprising a plurality of metal ions complexed to a plurality of said metal affinity ligands. In certain embodiments, the invention relates to any one of the aforementioned fluid treatment devices, wherein said metal affinity ligands are iminodicarboxylic acid ligands; and said metal ions are nickel.
  • [0039]
    In certain embodiments, the invention relates to any one of the aforementioned fluid treatment devices, wherein said functional groups are biological molecules or biological ions. In certain embodiments, the invention relates to any one of the aforementioned fluid treatment devices, wherein said functional groups are Protein A.
  • [0040]
    In certain embodiments, the invention relates to a method comprising the step of:
      • contacting a first fluid comprising a substance with a composite material in any one of the aforementioned fluid treatment devices, thereby adsorbing or absorbing the substance onto the composite material.
  • [0042]
    In certain embodiments, the invention relates to any one of the aforementioned methods, further comprising the step of
      • placing the first fluid in an inlet of the fluid treatment device.
  • [0044]
    In certain embodiments, the invention relates to any one of the aforementioned methods, wherein the first fluid is passed along a fluid flow path substantially perpendicular to the pores of the support member.
  • [0045]
    In certain embodiments, the invention relates to any one of the aforementioned methods, further comprising the step of
      • contacting a second fluid with the substance adsorbed or absorbed onto the composite material, thereby releasing the substance from the composite material.
  • [0047]
    In certain embodiments, the invention relates to any one of the aforementioned methods, wherein the first fluid is a suspension of cells or a suspension of aggregates.
  • [0048]
    In certain embodiments, the invention relates to any one of the aforementioned methods, wherein the substance is a biological molecule or biological ion. In certain embodiments, the invention relates to any one of the aforementioned methods, wherein the biological molecule or biological ion is a protein; and the protein comprises exposed His amino acid residues. In certain embodiments, the invention relates to any one of the aforementioned methods, wherein the biological molecule or biological ion is a monoclonal antibody.
  • [0049]
    In certain embodiments, the invention relates to any one of the aforementioned methods, wherein the substance is a metal-containing particle, or a metal-containing ion.
  • [0050]
    In certain embodiments, the invention relates to any one of the aforementioned methods, wherein the first fluid is waste water.
  • [0051]
    In certain embodiments, the invention relates to any one of the aforementioned methods, wherein the first fluid comprises egg white; and the substance is lysozyme.
  • BRIEF DESCRIPTION OF THE FIGURES
  • [0052]
    FIG. 1 depicts the results of dead-end compared to cross-flow modes for viral capture using an ion-exchange membrane. In both cases, the lower value obtained with dead-end flow was due to fouling of the membrane during the experiment.
  • [0053]
    FIG. 2 depicts a chromatogram from the elution of a mixture proteins (ovalbumin and lysozyme) captured directly from unprocessed egg whites using ion-exchange membranes in cross-flow mode. The results demonstrate that proteins can be selectively removed from an unprocessed, highly viscous feed stream.
  • [0054]
    FIG. 3 depicts chromatograms of eluent fluids from egg white-loaded ion-exchange membranes. Curves show selectivity of elution, based on buffer (saline solution) selection. This series of curves demonstrates the ability selectively to separate (i.e., chromatographically) captured target materials in high purity, or as mixtures essentially free from other constituents.
  • [0055]
    FIG. 4 depicts a schematic of the cross-flow and capture steps (top and middle), and a trans-membrane collection step (bottom).
  • [0056]
    FIG. 5 depicts the effects of wrap design on device performance showing that coarse mesh spacers lead to improved performance in separating lysozyme from egg white using ion-exchange membrane.
  • [0057]
    FIG. 6 depicts a wrapped column device inserted into a housing. Inlet cap not shown for clarity.
  • [0058]
    FIG. 7 depicts a simplified cross-section of a cassette showing trans-membrane flow of target material as indicated by arrows. Harvesting could also be accomplished by cross-flow, if required, using a fluid that selectively eluted the bound target materials.
  • [0059]
    FIG. 8 depicts a schematic illustration of a typical cassette design. Flow is shown with trans-membrane harvesting that is occurring simultaneously with a flowing feed stream.
  • [0060]
    FIG. 9 depicts a cross-section of a disposable or semi-disposable housing for a 25 mm syringe column comprising a disk-shaped filtration membrane for lab-scale use.
  • [0061]
    FIG. 10 depicts top view (top left), side view (right), and actual size views (bottom left) of the outlet half of the syringe tip filters for use in the housing shown in FIG. 9 and FIG. 11. All units in the drawings are in inches.
  • [0062]
    FIG. 11 depicts a cross-section of the disposable or semi-disposable housing for a 25 mm syringe column comprising a disk-shaped filtration membrane for lab-scale use.
  • [0063]
    FIG. 12 depicts a cross-section of the disposable or semi-disposable housing for a 50 mm syringe column comprising a disk-shaped filtration membrane for lab-scale use.
  • [0064]
    FIG. 13 depicts the drainage grid in the housing depicted in FIG. 12 for use with a 50 mm disk-shaped membrane.
  • [0065]
    FIG. 14 depicts an inlet flow deflector in a reusable stainless steel housing for a 50 mm syringe column comprising a disk-shaped filtration membrane for lab-scale use.
  • [0066]
    FIG. 15 depicts a stainless steel holder for use as a reusable housing for a 25 mm disk-shaped membrane for lab-scale use.
  • [0067]
    FIG. 16 depicts a component of a reusable stainless steel housing for lab-scale syringe columns.
  • [0068]
    FIG. 17 depicts two components of a reusable stainless steel housing for lab-scale syringe columns.
  • [0069]
    FIG. 18 depicts a maxi spin column (left), and a device for supporting a cut disk membrane within the column (right).
  • [0070]
    FIG. 19 depicts the dimensions of a maxi spin column.
  • [0071]
    FIG. 20 depicts the dimensions of a maxi spin column with a device for supporting a cut disk membrane within the column.
  • [0072]
    FIG. 21 depicts a mini spin column with a device for supporting a cut disk membrane within the column.
  • [0073]
    FIG. 22 depicts the dimensions of a mini spin column with a device for supporting a cut disk membrane within the column.
  • [0074]
    FIG. 23 depicts an exemplary configuration of a spiral wound device. There are three series of concentric envelopes, wherein each envelope has a spacer material inside and three of the sides are sealed. Each envelope is separated by a feed spacer. Fluid flow is directed such that raw fluid travels on the outside of each envelope and is forced through the membrane. The permeate travels along the permeate spacer to the permeate collection pipe.
  • [0075]
    FIG. 24 depicts an exemplary synthetic scheme for incorporation of a metal affinity ligand into the membrane. In this case, the metal affinity ligand is the sodium salt of iminodiacetic acid (IDA(Na)2).
  • [0076]
    FIG. 25 depicts an exemplary synthetic scheme for incorporation of a metal affinity ligand into the membrane. In this case, the metal affinity ligand is ethylenediamine (EDA).
  • [0077]
    FIG. 26 depicts an exemplary synthetic scheme for incorporation of a metal affinity ligand into the membrane. In this case, the metal affinity ligand is hexamethylenediamine (HMDA).
  • [0078]
    FIG. 27 depicts an exemplary synthetic scheme for incorporation of a metal affinity ligand into the membrane. In this case, the metal affinity ligand is diethanolamine.
  • [0079]
    FIG. 28 depicts an exemplary synthetic scheme for incorporation of a metal affinity ligand into the membrane. In this case, the metal affinity ligand is pentaethylenehexamine (PEHA).
  • [0080]
    FIG. 29 depicts an exemplary synthetic scheme for incorporation of a metal affinity ligand into the membrane. In this case, the metal affinity ligand is triethylenetetramine (TETA).
  • [0081]
    FIG. 30 depicts an exemplary synthetic scheme for incorporation of a metal affinity ligand into the membrane. In this case, the metal affinity ligand is the sodium salt of tris(carboxymethyl)ethylene diamine (TED(Na)3).
  • DETAILED DESCRIPTION OF THE INVENTION Overview
  • [0082]
    Disclosed is a hydrophilic, high binding, high throughput chromatography membrane that is effective for selective capture of target materials, such as bio-molecules, from raw or dirty process streams. This capture process can be accomplished by binding of the target molecules at the surface or near surface of the membrane media (“cross-flow” mode), as opposed to the more typical trans-membrane mode. The captured target species can be collected in a highly purified form in subsequent procedures. These final steps are chromatographic in nature and allow for controlled separation of the target materials. Importantly, the collection step and the separation step can be done in either tangential flow or in trans-membrane flow or combinations thereof. See, e.g., FIG. 1.
  • [0083]
    Exemplary device designs suitable for this process include those in which the membrane is incorporated into a modified cassette, wrap, or spiral-wound cross-flow separation device designed for low-shear fluid-flow, and minimization of uncontrolled or undesired trans-membrane flow. For example, such devices were found to be effective for separating proteins or viruses from highly viscous and or highly contaminated feed streams with a minimum of process fluid flux across the membrane. The cross flow (tangential flow) format allows for greater flexibility in washing and eluting the target molecule(s). The cross flow devices can be run in feed-to-retentate mode and perform a surface ion exchange or affinity separation. Washing can be done in feed-to-retentate mode, feed-to-permeate or permeate-to-feed mode, or in a sequential mode.
  • [0084]
    The incorporation of the hydrophilic, high performance chromatography membrane into a modified cross flow device provides a separation device that purifies target molecules from highly viscous or high particulate feed streams, and completes both clarification and capture of target species with no intervening steps. Moreover, the materials and constructs described here do not preclude the use of the same membrane materials in traditional device designs, such as pleated dead-end capsules. Importantly, these products can produce highly purified proteins, vaccines, or nutraceuticals from feed streams that cannot be processed directly with current commercial technology. Additionally, the devices and methods of the present invention allow for faster processing of large volumes of feed streams than any current technology.
  • [0085]
    For example, due to the viscous, highly concentrated nature of egg white, typical filtration schemes prove to be problematic when trying to collect constituents present in relatively low concentrations. Using the devices and methods of the present invention, lysozyme can be easily separated from egg white with high recovery and high purity.
  • [0086]
    In certain embodiments, the invention relates to a device that displays superior performance in comparison to know devices. In certain embodiments, the devices may tolerate about 10× to about 100× higher throughput than resins. In certain embodiments, the devices may display up to about 25× higher binding capacity than existing chromatographic membranes and resins.
  • [0087]
    In certain embodiments, the invention relates to a device that is scalable and produces predictable results in the transitions from Lab to Pilot to Production, unlike conventional resin products.
  • [0088]
    In certain embodiments, the invention relates to a device that encompasses a robust technology. In certain embodiments, the superior mechanical strength of the devices and the inherent hydrophilicity of the composite membranes lead to longer in-process product lifetimes and more consistent performance.
  • [0089]
    In certain embodiments, the invention relates to a device that may be available as a single use or multi-cycle disposable unit. This flexibility may eliminate costly and time consuming cleaning and storage validation. Furthermore, the devices of the invention enable simple process and may improve regulatory compliance.
  • [0090]
    In certain embodiments, the invention relates to separation processes that may require reduced buffer usage. In certain embodiments, using devices of the present invention may eliminate the need for column cleaning, equilibration, or storage in expensive buffers. In certain embodiments, the devices of the invention may tolerate higher concentration feed stream, so no dilution may be needed.
  • [0091]
    In certain embodiments, using the devices described herein may lower capital expenses and may offer significant operational cost savings for a client. In certain embodiments, the devices of the invention may have a lower initial cost and faster delivery. In certain embodiments, the devices allow for lower staffing requirements and reduced maintenance costs.
  • [0092]
    In certain embodiments, the invention relates to a device with a small footprint. In certain embodiments, the devices of the invention exhibit higher binding capacity and require less floor space than typical resin bed chromatography devices.
  • DEFINITIONS
  • [0093]
    For convenience, before further description of the present invention, certain terms employed in the specification, examples and appended claims are collected here. These definitions should be read in light of the remainder of the disclosure and understood as by a person of skill in the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art.
  • [0094]
    In describing the present invention, a variety of terms are used in the description. Standard terminology is widely used in filtration, fluid delivery, and general fluid processing art.
  • [0095]
    The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.
  • [0096]
    The term “associated with” as used herein in such phrases as, for example, “an inorganic metal oxide associated with an stabilizing compound,” refers to the presence of either weak or strong or both interactions between molecules. For example weak interactions may include, for example, electrostatic, van der Waals, or hydrogen-bonding interactions. Stronger interactions, also referred to as being chemically bonded, refer to, for example, covalent, ionic, or coordinative bonds between two molecules. The term “associated with” also refers to a compound that may be physically intertwined within the foldings of another molecule, even when none of the above types of bonds are present. For example, an inorganic compound may be considered as being in association with a polymer by virtue of it existing within the interstices of the polymer.
  • [0097]
    The terms “comprise” and “comprising” are used in the inclusive, open sense, meaning that additional elements may be included.
  • [0098]
    The term “including” is used to mean “including but not limited to.” “Including” and “including but not limited to” are used interchangeably.
  • [0099]
    The term “polymer” is used to mean a large molecule formed by the union of repeating units (monomers). The term polymer also encompasses copolymers.
  • [0100]
    The term “co-polymer” is used to mean a polymer of at least two or more different monomers. A co-polymer can be comprised of a cross-linker and a monomer, if the cross-linker is a difunctional monomer.
  • [0101]
    The term “two phase fluid” is used to mean a fluid comprising a liquid phase in which either substantially solid particles are dispersed therethrough, or a first liquid phase in which droplets or particles of a second liquid phase immiscible with such first liquid phase are dispersed through such first liquid phase. A “multiphase fluid” is used to mean a fluid comprising a first liquid phase in which at least one additional second solid or liquid phase is dispersed therethrough.
  • [0102]
    The term “particle” is used to mean a discreet liquid droplet or a solid object, with a characteristic dimension such as a diameter or length of between about one nanometer, and about one-tenth of a meter.
  • [0103]
    The term “particle size” is used to mean a number-average or weight-average particle size as measured by conventional particle size measuring techniques well known to those skilled in the art, such as dynamic or static light-scattering, sedimentation field-flow fractionation, photon-correlation spectroscopy, or disk centrifugation. By “an effective average particle size of less than about 1000 nm” it is meant that at least about 90% of the particles have a number-average or weight-average particle size of less than about 1000 nm when measured by at least one of the above-noted techniques. The particular size of particles in a fluid being processed will depend upon the particular application.
  • [0104]
    The term “interstices” is used to mean a space, especially a small or narrow one, between things or parts.
  • [0105]
    The term “dispersion” is used to mean any fluid comprising a liquid phase in which substantially solid particles are suspended, and remain suspended, at least temporarily.
  • [0106]
    The term “slurry” is used to mean any fluid comprising a liquid phase in which substantially solid particles are present. Such particles may or may not be suspended in such fluid.
  • [0107]
    The term “emulsion” is used to mean any fluid comprising a first liquid phase within which droplets or particles of a substantially liquid second phase are suspended, and remain suspended, at least temporarily. In reference to discreet entities of a second liquid phase in a first liquid phase, the terms “droplets” and “particles” are used interchangeably herein.
  • [0108]
    The term “crossflow” in reference to filtration is used to mean a filtration configuration in which a flowing fluid is directed along the surface of a filter medium, and the portion of fluid that passes through such filter medium has a velocity component which is “cross-wise”, i.e., perpendicular to the direction of the fluid flowing along the surface of such filter medium.
  • [0109]
    The term “tangential filtration” is used to mean a filtration process in which a flowing fluid is directed substantially parallel (i.e., tangential) to the surface of a filter medium, and a portion of fluid passes through such filter medium to provide a permeate. The terms “tangential filtration” and “crossflow filtration” are often used interchangeably in the art.
  • [0110]
    The term “permeate” is used to mean the portion of the fluid that passes through the filter medium and out through a first outlet port in the filter device that is operatively connected to such filter medium. The term “decantate” is used to mean the portion of the fluid that flows along the surface of the filter medium, but does not pass through such filter medium, and passes out through a second outlet port in the filter device that is operatively connected to such filter medium.
  • [0111]
    Crossflow filtration and tangential filtration are well known filtration processes. Reference may be had to, e.g., U.S. Pat. Nos. 5,681,464, 6,461,513; 6,331,253, 6,475,071, 5,783,085, 4,790,942, the disclosures of which are incorporated herein by reference. Reference may also be had to “Filter and Filtration Handbook”, 4th Ed., T. Christopher Dickenson, Elsevier Advanced Technology, 1997, the disclosure of which is incorporated herein by reference.
  • [0112]
    The term “egg white” refers to the clear, aqueous liquid contained within an egg, as opposed to the yellow egg yolk. Egg white typically comprises about 15% proteins dissolved or suspended in water. Egg white proteins typically include ovalbumin, ovotransferrin, ovomucoid, globulins, lysozyme, ovomucin, and avidin.
  • Exemplary Devices General Device Properties
  • [0113]
    In certain embodiment, the invention relates to a fluid treatment device comprising
      • a housing unit, wherein the housing unit comprises
      • (a) an inlet and an outlet;
      • (b) a fluid flow path between the inlet and the outlet; and
      • (c) a composite material within the housing unit, wherein the composite material comprises
        • a support member comprising a plurality of pores extending through the support member; and
        • a non-self-supporting macroporous cross-linked gel comprising macropores having an average size of 10 nm to 3000 nm, said macroporous gel being located in the pores of the support member;
        • wherein said macropores of said macroporous cross-linked gel are smaller than said pores of said support member; and
          wherein the pores of the support member are substantially perpendicular to the fluid flow path.
  • [0121]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the composite material is arranged in a substantially coplanar stack of substantially coextensive sheets, a substantially tubular configuration, or a substantially spiral wound configuration.
  • [0122]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the composite material has 2 to 10 separate support members.
  • [0123]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein
      • the support member is in the form of hollow porous fibers;
      • each hollow porous fiber defines a lumen;
      • the lumen is from about 20 μm to about 100 μm in diameter; and
      • the lumen is substantially perpendicular to the pores in the hollow porous fiber support member.
  • [0128]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein a plurality of hollow porous fibers are arranged in a bundle.
  • [0129]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the bundle is encased in a shell or a vessel.
  • [0130]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein a plurality of bundles is encased in a shell or a vessel.
  • [0131]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the hollow porous fiber comprises a cap, a plug, or a seal. In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the hollow porous fiber comprises a cap, a plug, or a seal on both ends. In certain embodiments, the end of the hollow porous fiber is “potted” such that the inside of the fiber is isolated from the outside of the fiber. In certain embodiments, this is accomplished through the use of a tubesheet. In certain embodiments, the potting material to form the tubesheet may be comprised of any suitable material. In certain embodiments, the potting material can be in liquid form when preparing the tubesheet and can thereafter be solidified, e.g., by cooling, curing, or the like. In certain embodiments, the solidified potting material should exhibit sufficient structural strength for providing a tubesheet and be relatively inert moieties to which it will be exposed during fluid separation operation. In certain embodiments, the potting material may be organic material (for example, epoxy), inorganic material, or organic material containing inorganic material, and the potting material may be natural or synthetic. In certain embodiments, typical inorganic materials include glasses, ceramics, cermets, metals and the like.
  • [0132]
    In certain embodiments, the hollow porous fiber may be of any convenient configuration. In certain embodiments, the hollow porous fiber is circular, hexagonal, trilobal, or the like in cross-section and may have ridges, grooves, or the like extending inwardly or outwardly from the walls of the hollow porous fibers. In certain embodiments, the hollow porous fiber may have an inner diameter of about 20 microns to about 200 microns. In certain embodiments, the hollow porous fiber may have an inner diameter of about 40 microns. In certain embodiments, the hollow porous fiber may have a hollow ratio (being the area of the fiber bore divided by the area of the total cross-section of the fiber) of about 10% to about 50% percent. In certain embodiments, the hollow porous fiber may have a hollow ratio of about 20%. In certain embodiments, the hollow porous fiber may be fabricated from various polymers such as cellulose, cellulose esters, cellulose ethers, polyamides, silicone resins, polyurethane resins, unsaturated polyester resins or the like, or ceramics.
  • [0133]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the composite material is a pleated membrane.
  • [0134]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the housing unit is substantially cylindrical. In certain embodiments, the housing unit has an inner diameter of from about 5 cm to about 50 cm.
  • [0135]
    In certain embodiments, the thickness of the walls of the housing unit may be adapted to the specific operation conditions.
  • [0136]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the housing unit is disposable or reusable.
  • [0137]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the housing unit is plastic or stainless steel.
  • [0138]
    In certain embodiments, the invention relates to a fluid treatment device comprising a housing unit, wherein the housing unit comprises
  • [0139]
    at least one inlet and at least one outlet; and
  • [0140]
    a fluid flow path between the inlet and the outlet; wherein any one of the above-mentioned fluid treatment elements is across the fluid flow path.
  • [0141]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the composite material comprises:
      • (a) a support member comprising a plurality of pores extending through the support member; and
      • (b) a non-self-supporting macroporous cross-linked gel comprising macropores having an average size of 10 nm to 3000 nm, said macroporous gel being located in the pores of the support member;
      • wherein
        • said macroporous cross-linked gel is present in the pores of the support member in an amount sufficient such that, in use, liquid passing through the composite material passes through said macropores of said macroporous cross-linked gel;
        • said macropores of said macroporous cross-linked gel are smaller than said pores of said support member;
        • the support member is in the form of hollow porous fibers;
        • each hollow porous fiber defines a lumen;
        • the lumen is from about 20 μm to about 100 μm in diameter; and
        • the lumen is substantially perpendicular to the pores in the hollow porous fiber support member.
  • [0151]
    In certain embodiments, the fluid treatment devices comprise the above-mentioned composite material, wherein a plurality of hollow porous fibers is arranged in a bundle. In certain embodiments, the fluid treatment devices comprise the above-mentioned composite material, wherein the bundle is encased in a shell. In certain embodiments, the fluid treatment devices comprise the above-mentioned composite material, wherein the bundle is encased in a vessel. In certain embodiments, the fluid treatment devices comprise the above-mentioned composite material, wherein a plurality of bundles is encased in a shell. In certain embodiments, the fluid treatment devices comprise the above-mentioned composite material, wherein a plurality of bundles is encased in a vessel.
  • [0152]
    In certain embodiments, the invention relates to a fluid treatment device comprising
      • a plurality of housing units, wherein each housing unit comprises
      • (a) an inlet and an outlet;
      • (b) a fluid flow path between the inlet and the outlet; and
      • (c) a composite material within the housing unit, wherein the composite material comprises
        • a support member comprising a plurality of pores extending through the support member; and
        • a non-self-supporting macroporous cross-linked gel comprising macropores having an average size of 10 nm to 3000 nm, said macroporous gel being located in the pores of the support member;
        • wherein said macropores of said macroporous cross-linked gel are smaller than said pores of said support member; and
          wherein the pores of the support member are substantially perpendicular to the fluid flow path.
  • [0160]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the plurality of housing units are arranged in series.
  • [0161]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, comprising from about 2 to about 10 housing units.
  • [0162]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the composite material is arranged in a substantially coextensive stack of substantially coplanar sheets; a substantially tubular configuration; or a substantially spiral wound configuration.
  • [0163]
    In certain embodiments, wherein the inlet or the outlet is a press fit attachment point, a luer lock attachment point, or a hose barb attachment point. In certain embodiments, the inlet is a press fit, luer lock, or hose barb attachment points. In certain embodiments, the outlet is a press fit, luer lock, or hose barb attachment points. In certain embodiments, the inlet and the outlet are different kinds of attachment points from one another. In certain embodiments, the inlet and the outlet are both press fit attachment points. In certain embodiments, the inlet and the outlet are both luer lock attachment points. In certain embodiments, the inlet and the outlet are both hose barb attachment points.
  • Laboratory-Scale
  • [0164]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the composite material is a cut disk membrane. In certain embodiments, the cut disks are intended to be used in re-usable housings. In certain embodiments, the cut disks are intended to be used in disposable housings. In certain embodiments, the cut disk membrane is substantially circular in shape.
  • [0165]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the composite material is a cut disk membrane. In certain embodiments, the cut disk membrane is from about 15 to about 60 mm in diameter. In certain embodiments, the cut disk membrane is from about 20 to about 55 mm in diameter. In certain embodiments, the cut disk membrane is about 25 mm in diameter. In certain embodiments, the cut disk membrane is about 50 mm in diameter. For visualization of certain embodiments, see FIGS. 9-17.
  • [0166]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the housing unit is a syringe tip. The term “syringe column” is used interchangeably with the term “syringe tip.”
  • [0167]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the housing unit is a syringe column; and the composite material is in the form of a cut disk. In certain embodiments, the syringe column housing unit is semi-disposable.
  • [0168]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the housing unit is a spin column. In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the housing unit is a spin column; and the composite material is in the form of a cut disk. A spin column is a tube with an upper and a lower half. The lower half is closed at the bottom. In between the two halves is a cut disk membrane held or suspended in some manner. A user loads the top half with a liquid containing the target (or contaminate) solute and places the spin column into a centrifuge. The centrifuge forces the liquid through the membrane when run at sufficient RPM. Once removed from the centrifuge, the lower half of the device can be removed and the liquid collected (if needed) or the top half can be eluted with additional buffer to remove the retained solute. In certain embodiments, the spin columns can be made in many sizes.
  • [0169]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the housing unit is a spin column; and the spin column has a capacity of from about 0.1 mL to about 60 mL. In certain embodiments, the volume of the spin column refer to the quantity of feed stream that may be processed by an exemplary fluid treatment device. In certain embodiments, the spin column has a capacity of from about 0.3 mL to about 55 mL. In certain embodiments, the spin column has a capacity of about 0.5 mL. In certain embodiments, the spin column has a capacity of about 2 mL. In certain embodiments, the spin column has a capacity of up to about 50 mL. For visualization of certain embodiments, see, e.g., FIGS. 18-22.
  • Process- and Manufacturing-Scale
  • [0170]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the housing unit is a cassette configuration.
  • [0171]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the housing unit is a tubular configuration.
  • [0172]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the housing unit is a spiral wound configuration.
  • [0173]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the housing unit is a plate and frame configuration.
  • [0174]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices, wherein the housing unit comprises a fluid treatment element, wherein the fluid treatment element comprises a hollow porous membrane.
  • Exemplary Fluid Treatment Elements
  • [0175]
    In certain embodiments, the invention relates to fluid treatment elements. In certain embodiments, the fluid treatment element is a cartridge for use in a fluid treatment device of the present invention. In certain embodiments, the invention relates to fluid treatment elements comprising membranes. In certain embodiments, the invention relates to fluid treatment elements comprising composite materials for use as membranes.
  • [0176]
    In certain embodiments, the fluid treatment elements are disposable or reusable.
  • [0177]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment elements, wherein the element comprises a hollow, generally cylindrical form.
  • [0178]
    In certain embodiments, the fluid treatment elements of the present invention accommodate high solid density materials. In certain embodiments, the fluid treatment elements of the present invention are used for their strength. In certain embodiments, the fluid treatment elements of the present invention are used in heavy duty applications. In certain embodiments, the fluid treatment elements of the present invention can tolerate elevated temperatures for sustained periods.
  • [0179]
    In certain embodiments, the fluid treatment elements of the present invention exhibit reduced capture time in chromatography applications. In certain embodiments, the fluid treatment elements of the present invention exhibit high binding capacities.
  • Exemplary Composite Materials
  • [0180]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements comprising a composite material. In certain embodiments, the invention comprises a composite material for use as a membrane.
  • [0181]
    In certain embodiments, the composite materials used as membranes in the present invention are described in U.S. Pat. No. 7,316,919; and U.S. patent application Ser. Nos. 11/950,562, 12/108,178, 12/244,940, 12/250,861, 12/211,618, and 12/250,869; all of which are hereby incorporated by reference.
  • [0182]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the macroporous crosslinked gel of the composite material has macropores of average size between about 25 nm and about 1500 nm. In certain embodiments, the macroporous crosslinked gel has macropores of average size between about 50 nm and about 1000 nm. In certain embodiments, the macroporous crosslinked gel has macropores of average size of about 700 nm. In certain embodiments, the macroporous crosslinked gel has macropores of average size of about 300 nm.
  • [0183]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the macroporous cross-linked gel of the composite material is a hydrogel, a polyelectrolyte gel, a hydrophobic gel, a neutral gel, or a gel comprising functional groups. In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the macroporous cross-linked gel of the composite material is a neutral or charged hydrogel; and the neutral or charged hydrogel is selected from the group consisting of cross-linked poly(vinyl alcohol), poly(acrylamide), poly(isopropylacrylamide), poly(vinylpyrrolidone), poly(hydroxymethyl acrylate), poly(ethylene oxide), copolymers of acrylic acid or methacrylic acid with acrylamide, isopropylacrylamide, or vinylpyrrolidone, copolymers of acrylamide-2-methyl-1-propanesulfonic acid with acrylamide, isopropylacrylamide, or vinylpyrrolidone, copolymers of (3-acrylamido-propyl)trimethylammonium chloride with acrylamide, isopropylacrylamide, or N-vinyl-pyrrolidone, and copolymers of diallyldimethylammonium chloride with acrylamide, isopropylacrylamide, or vinylpyrrolidone. In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the macroporous cross-linked gel of the composite material is a polyelectrolyte gel; and the polyelectrolyte gel is selected from the group consisting of cross-linked poly(acrylamido-2-methyl-1-propanesulfonic acid) and its salts, poly(acrylic acid) and its salts, poly(methacrylic acid) and its salts, poly(styrenesulfonic acid) and its salts, poly(vinylsulfonic acid) and its salts, poly(alginic acid) and its salts, poly[(3-acrylamidopropyl)trimethylammonium] salts, poly(diallyldimethylammonium) salts, poly(4-vinyl-N-methylpyridinium) salts, poly(vinylbenzyl-N-trimethylammonium) salts, and poly(ethyleneimine) and its salts. In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the macroporous cross-linked gel of the composite material is a hydrophobic gel; and the hydrophobic gel is selected from the group consisting of cross-linked polymers or copolymers of ethyl acrylate, n-butyl acrylate, propyl acrylate, octyl acrylate, dodecyl acrylate, octadecylacrylamide, stearyl acrylate, and styrene. In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the macroporous cross-linked gel of the composite material is a neutral gel; and the neutral gel is selected from the group consisting of cross-linked polymers or copolymers of acrylamide, N,N-dimethylacrylamide, N-methacryloylacrylamide, N-methyl-N-vinylacetamide, and N-vinylpyrrolidone.
  • [0184]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the macroporous cross-linked gel of the composite material is a gel comprising functional groups. In certain embodiments, the macroporous cross-linked gel of the composite material comprises monomers, wherein the monomers comprise functional groups. In certain embodiments, the functional groups are thiols or protected thiols. In certain embodiments, the macroporous cross-linked gel comprises monomers, wherein the monomers are selected from the group consisting of allyl 3-mercaptopropionate thioacetate, (S-benzoyl-3-mercapto-2-hydroxypropyl)-2-methyl-2-propenoate, (S-2,2-dimethylpropanoyl-3-mercapto-2-hydroxypropyl)-2-methyl-2-propenoate, (S-acetyl-3-mercapto-2-acetylpropyl)-2-methyl-2-propenoate, (S-acetyl-3-mercapto-2-hydroxypropyl)-2-methyl-2-propenoate, (S-acetyl-3-mercapto-2-acetoacetylpropyl)-2-methyl-2-propenoate, (S-acetyl-3-mercapto-2-tetrahydropyranyl)-2-methyl-2-propenoate, (S-acetyl-3-mercapto-2-(2-methoxy-2-propoxy))-2-methyl-2-propenoate, (S-acetyl-2-mercapto-3-acetylpropyl)-2-methyl-2-propenoate, S-acetyl-(1-allyloxy-3-mercapto-2-hydroxypropane), S-benzoyl-(1-allyloxy-3-mercapto-2-hydroxypropane) and S-2,2-dimethylpropanoyl-(1-allyloxy-3-mercapto-2-hydroxypropane).
  • [0185]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises functional groups; and the functional groups are selected from the group consisting of amino acid ligands, antigen and antibody ligands, dye ligands, biological molecules, biological ions, and metal affinity ligands.
  • [0186]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises functional groups; and said functional groups are metal affinity ligands. In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises functional groups; said functional groups are metal affinity ligands; and a plurality of metal ions are complexed to a plurality of said metal affinity ligands.
  • [0187]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands are polydentate ligands.
  • [0188]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands are octadentate, hexadentate, tetradentate, tridentate or bidentate ligands.
  • [0189]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands are tetradentate ligands.
  • [0190]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands are tridentate ligands.
  • [0191]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands are bidentate ligands.
  • [0192]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands are iminodicarboxylic acid ligands.
  • [0193]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands are iminodiacetic acid ligands.
  • [0194]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands are salts of iminodiacetic acid ligands.
  • [0195]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands are sodium salts of iminodiacetic acid ligands. See, e.g., FIG. 24.
  • [0196]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands are potassium salts of iminodiacetic acid ligands.
  • [0197]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands comprise ethylenediamine moieties. See, e.g., FIG. 25.
  • [0198]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands comprise hexamethylenediamine moieties. See, e.g., FIG. 26.
  • [0199]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands comprise diethanolamine moieties. See, e.g., FIG. 27.
  • [0200]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands comprise pentaethylenehexamine moieties. See, e.g., FIG. 28.
  • [0201]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands comprise triethylenetetramine moieties. See, e.g., FIG. 29.
  • [0202]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands comprise tris(carboxymethyl)ethylene diamine. See, e.g., FIG. 30.
  • [0203]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands; and said metal affinity ligands comprise conjugate bases of carboxylic acids. In certain embodiments, the conjugate bases are available as salts. In certain embodiments, the conjugate bases are available as sodium salts or potassium salts. In certain embodiments, the conjugate bases are available as sodium salts. In certain embodiments, the conjugate bases are available as potassium salts.
  • [0204]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; and said metal ions are transition metal ions, lanthanide ions, poor metal ions or alkaline earth metal ions.
  • [0205]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; and said metal ions are selected from the group consisting of nickel, zirconium, lanthanum, cerium, manganese, titanium, cobalt, iron, copper, zinc, silver, gallium, platinum, palladium, lead, mercury, cadmium and gold.
  • [0206]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; and said metal ions are nickel or zirconium.
  • [0207]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; and said metal ions are nickel.
  • [0208]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; and said metal ions are zirconium.
  • [0209]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are octadentate, hexadentate, tetradentate, tridentate or bidentate ligands; and said metal ions are transition metal ions, lanthanide ions, poor metal ions or alkaline earth metal ions.
  • [0210]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are octadentate, hexadentate, tetradentate, tridentate or bidentate ligands; and said metal ions are selected from the group consisting of nickel, zirconium, lanthanum, cerium, manganese, titanium, cobalt, iron, copper, zinc, silver, gallium, platinum, palladium, lead, mercury, cadmium and gold.
  • [0211]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are octadentate, hexadentate, tetradentate, tridentate or bidentate ligands; and said metal ions are nickel or zirconium.
  • [0212]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are octadentate, hexadentate, tetradentate, tridentate or bidentate ligands; and said metal ions are nickel.
  • [0213]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are octadentate, hexadentate, tetradentate, tridentate or bidentate ligands; and said metal ions are zirconium.
  • [0214]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are tetradentate ligands; and said metal ions are transition metal ions, lanthanide ions, poor metal ions or alkaline earth metal ions.
  • [0215]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are tetradentate ligands; and said metal ions are selected from the group consisting of nickel, zirconium, lanthanum, cerium, manganese, titanium, cobalt, iron, copper, zinc, silver, gallium, platinum, palladium, lead, mercury, cadmium and gold.
  • [0216]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are tetradentate ligands; and said metal ions are nickel or zirconium.
  • [0217]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are tetradentate ligands; and said metal ions are nickel.
  • [0218]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are tetradentate ligands; and said metal ions are zirconium.
  • [0219]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are tridentate ligands; and said metal ions are transition metal ions, lanthanide ions, poor metal ions or alkaline earth metal ions.
  • [0220]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are tridentate ligands; and said metal ions are selected from the group consisting of nickel, zirconium, lanthanum, cerium, manganese, titanium, cobalt, iron, copper, zinc, silver, gallium, platinum, palladium, lead, mercury, cadmium and gold.
  • [0221]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are tridentate ligands; and said metal ions are nickel or zirconium.
  • [0222]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are tridentate ligands; and said metal ions are nickel.
  • [0223]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are tridentate ligands; and said metal ions are zirconium.
  • [0224]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are bidentate ligands; and said metal ions are transition metal ions, lanthanide ions, poor metal ions or alkaline earth metal ions.
  • [0225]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are bidentate ligands; and said metal ions are selected from the group consisting of nickel, zirconium, lanthanum, cerium, manganese, titanium, cobalt, iron, copper, zinc, silver, gallium, platinum, palladium, lead, mercury, cadmium and gold.
  • [0226]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are bidentate ligands; and said metal ions are nickel or zirconium.
  • [0227]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are bidentate ligands; and said metal ions are nickel.
  • [0228]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are bidentate ligands; and said metal ions are zirconium.
  • [0229]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are iminodicarboxylic acid ligands; and said metal ions are transition metal ions, lanthanide ions, poor metal ions or alkaline earth metal ions.
  • [0230]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are iminodicarboxylic acid ligands; and said metal ions are selected from the group consisting of nickel, zirconium, lanthanum, cerium, manganese, titanium, cobalt, iron, copper, zinc, silver, gallium, platinum, palladium, lead, mercury, cadmium and gold.
  • [0231]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are iminodicarboxylic acid ligands; and said metal ions are nickel or zirconium.
  • [0232]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are iminodicarboxylic acid ligands; and said metal ions are nickel.
  • [0233]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are iminodicarboxylic acid ligands; and said metal ions are zirconium.
  • [0234]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are iminodiacetic acid ligands; and said metal ions are transition metal ions, lanthanide ions, poor metal ions or alkaline earth metal ions.
  • [0235]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are iminodiacetic acid ligands; and said metal ions are selected from the group consisting of nickel, zirconium, lanthanum, cerium, manganese, titanium, cobalt, iron, copper, zinc, silver, gallium, platinum, palladium, lead, mercury, cadmium and gold.
  • [0236]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are iminodiacetic acid ligands; and said metal ions are nickel or zirconium.
  • [0237]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are iminodiacetic acid ligands; and said metal ions are nickel.
  • [0238]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises metal affinity ligands complexed to a plurality of metal ions; said metal affinity ligands are iminodiacetic acid ligands; and said metal ions are zirconium.
  • [0239]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises functional groups; and the functional groups are biological molecules or biological ions. In certain embodiments, the biological molecules or biological ions are selected from the group consisting of albumins, lysozyme, viruses, cells, γ-globulins of human and animal origins, immunoglobulins of both human and animal origins, proteins of recombinant or natural origin including, polypeptides of synthetic or natural origin, interleukin-2 and its receptor, enzymes, monoclonal antibodies, antigens, lectins, bacterial immunoglobulin-binding proteins, trypsin and its inhibitor, cytochrome C, myoglobulin, recombinant human interleukin, recombinant fusion protein, Protein A, Protein G, Protein L, Peptide H, nucleic acid derived products, DNA of either synthetic or natural origin, and RNA of either synthetic or natural origin.
  • [0240]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material comprises Protein A. Protein A is a 40-60 kDa MSCRAMM surface protein originally found in the cell wall of the bacteria Staphylococcus aureus. It is encoded by the spa gene and its regulation is controlled by DNA topology, cellular osmolarity, and a two-component system called ArlS-ArlR. It has found use in biochemical research because of its ability to bind immunoglobulins. It binds proteins from many of mammalian species, most notably IgGs. It binds with the Fc region of immunoglobulins through interaction with the heavy chain. The result of this type of interaction is that, in serum, the bacteria will bind IgG molecules in the wrong orientation (in relation to normal antibody function) on their surface which disrupts opsonization and phagocytosis. It binds with high affinity to human IgG1 and IgG2 as well as mouse IgG2a and IgG2b. Protein A binds with moderate affinity to human IgM, IgA and IgE as well as to mouse IgG3 and IgG1. It does not react with human IgG3 or IgD, nor will it react to mouse IgM, IgA or IgE.
  • [0241]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the macroporous crosslinked gel of the composite material comprises a macromonomer. In certain embodiments, the macromonomer is selected from the group consisting of poly(ethylene glycol) acrylate and poly(ethylene glycol) methacrylate.
  • [0242]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the macroporous cross-linked gel of the composite material is cross-linked by N,N-methylenebisacrylamide or a polyfunctional macromonomer. In certain embodiments, the macroporous cross-linked gel of the composite material is cross-linked by a polyfunctional macromonomer; and the polyfunctional macromonomer is selected from the group consisting of poly(ethylene glycol) diacrylate and poly(ethylene glycol) dimethacrylate. In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the macroporous cross-linked gel of the composite material is cross-linked by N,N-methylenebisacrylamide.
  • [0243]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the macroporous cross-linked gel of the composite material is a positively charged hydrogel comprising a co-polymer of (3-acrylamidopropyl)trimethylammonium chloride (APTAC) and N-(hydroxymethyl)acrylamide cross-linked by N,N′-methylenebisacrylamide.
  • [0244]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material is a membrane; and the macroporous cross-linked gel bears charged moieties.
  • [0245]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite material is a membrane for use as a filter in size exclusion separation.
  • [0246]
    In certain embodiments, the fluid treatment devices or elements of the invention comprise any one of the above-mentioned composite materials, wherein the composite materials comprise negatively-charged moieties. Negatively-charged membranes repel foulants at the membrane surface resulting in higher flux, easier cleanings, and lower system costs.
  • [0247]
    In certain embodiments, the fluid treatment devices or elements of the invention comprise any one of the above-mentioned composite materials, wherein the composite materials are hydrophilic in nature. Foulants are typically hydrophobic species.
  • [0248]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the support member of the composite material consists essentially of polymeric material in the form of a membrane that has a thickness of from about 10 μm to about 500 μm and comprises pores of average size between about 0.1 to about 25 μm.
  • [0249]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the support member of the composite material consists essentially of a polyolefin.
  • [0250]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the support member of the composite material comprises a polymeric material selected from the group consisting of polysulfones, polyethersulfones, polyphenyleneoxides, polycarbonates, polyesters, cellulose and cellulose derivatives.
  • [0251]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the support member of the composite material consists essentially of polymeric material in the form of a fibrous fabric that has a thickness of from about 10 μm to about 2000 μm and comprises pores of average size from about 0.1 to about 25 μm.
  • [0252]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the support member of the composite material comprises a stack of 2 to 10 separate support members.
  • [0253]
    In certain embodiments, the invention relates to any one of the above-mentioned fluid treatment devices or elements, wherein the composite materials are disk-shaped, thereby forming cut disk membranes. In certain embodiments, the cut disk membranes are from about 5 mm in diameter to about 100 mm in diameter. In certain embodiments, the cut disk membranes are from about 10 mm in diameter to about 75 mm in diameter. In certain embodiments, the cut disk membranes are from about 15 mm in diameter to about 55 mm in diameter. In certain embodiments, the cut disk membranes are about 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, or 55 mm in diameter. In certain embodiments, the cut disk membranes are about 18 mm in diameter. In certain embodiments, the cut disk membranes are about 25 mm in diameter. In certain embodiments, the cut disk membranes are about 50 mm in diameter. In certain embodiments, the cut disk membranes are made by simply cutting from sheets of composite material.
  • Exemplary Methods
  • [0254]
    In certain embodiments, the invention relates to a method comprising the step of:
      • contacting a first fluid comprising a substance with a composite material in any one of the above-mentioned fluid treatment devices, thereby adsorbing or absorbing the substance onto the composite material.
  • [0256]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, further comprising the step of
      • placing the first fluid in an inlet of the fluid treatment device.
  • [0258]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the first fluid is passed along a fluid flow path substantially perpendicular to the pores of the support member.
  • [0259]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, further comprising the step of
      • contacting a second fluid with the substance adsorbed or absorbed onto the composite material, thereby releasing the substance from the composite material.
  • [0261]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the second fluid is passed through the macropores of the composite material, thereby releasing the substance from the composite material.
  • [0262]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the second fluid is passed along the fluid flow path substantially perpendicular to the pores of the support member, thereby releasing the substance from the composite material.
  • [0263]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the substance is separated based on size exclusion.
  • [0264]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the macroporous gel displays a specific interaction for the substance.
  • [0265]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the specific interactions are electrostatic interactions, affinity interactions, or hydrophobic interactions.
  • [0266]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the specific interactions are electrostatic interactions, the composite material bears charges on the macroporous gel; the substance is charged; and the substance is separated based on Donnan exclusion.
  • [0267]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the first fluid is a suspension of cells or a suspension of aggregates.
  • [0268]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the substance is a biological molecule or biological ion.
  • [0269]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the biological molecule or biological ion is selected from the group consisting of albumins, lysozyme, viruses, cells, γ-globulins of human and animal origins, immunoglobulins of both human and animal origins, proteins of recombinant or natural origin including, polypeptides of synthetic or natural origin, interleukin-2 and its receptor, enzymes, monoclonal antibodies, trypsin and its inhibitor, cytochrome C, myoglobulin, recombinant human interleukin, recombinant fusion protein, nucleic acid derived products, DNA of either synthetic or natural origin, and RNA of either synthetic or natural origin.
  • [0270]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the biological molecule or biological ion is a protein; and the protein comprises exposed amino acid residues selected from the group consisting of Glu, Asp, Try, Arg, Lys, Met, and His.
  • [0271]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the biological molecule or biological ion is a protein; and the protein comprises exposed His amino acid residues.
  • [0272]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the biological molecule or biological ion is a monoclonal antibody.
  • [0273]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the substance is a metal-containing particle, or a metal-containing ion.
  • [0274]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the metal-containing particle or metal-containing ion comprises a transition metal, a lanthanide, a poor metal, or an alkaline earth metal.
  • [0275]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the metal-containing particle or metal-containing ion comprises a metal selected from the group consisting of nickel, zirconium, lanthanum, cerium, manganese, titanium, cobalt, iron, copper, zinc, silver, gallium, platinum, palladium, lead, mercury, cadmium and gold.
  • [0276]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the first fluid is waste water.
  • [0277]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the first fluid is waste water from ore refining, or seawater.
  • [0278]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the substance is lead or mercury.
  • [0279]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the substance is platinum, palladium, copper, gold, or silver.
  • [0280]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the fluid is waste water; and the metal-containing particle or metal-containing ion comprises lead or mercury.
  • [0281]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the first fluid is waste water from ore refining; and the metal-containing particle or metal-containing ion comprises lead or mercury.
  • [0282]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the first fluid is seawater; and the metal-containing particle or metal-containing ion comprises platinum, palladium, copper, gold, or silver.
  • [0283]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the first fluid comprises egg white.
  • [0284]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the first fluid comprises egg white; and the substance is lysozyme.
  • [0285]
    In certain embodiments, the invention relates to a method in which, in tangential flow separation mode, no pre-processing of the raw reaction mixtures is required due to the high specificity of the composite materials in the devices of the present invention. In certain embodiments, the invention relates to a method in which separations can be carried out on a large scale. In certain embodiments, the invention relates to a method in which separations can be carried out in a shorter amount of time. In certain embodiments, the invention relates to a method in which the devices have a high binding capacity.
  • [0286]
    In certain embodiments, the invention relates to a method that comprises two steps collecting the desired substance onto the composite material and harvesting the desired substance from the composite material. In certain embodiments, the first step is run in tangential separation mode. In certain embodiments, the first step is run in tangential separation mode and the second step is run in direct filtration mode with a second fluid.
  • [0287]
    In certain embodiments, the invention relates to a method of separating a substance from a fluid, comprising the step of:
  • [0000]
    placing the fluid in contact with a composite material in any one of the above-mentioned fluid treatment devices, thereby adsorbing or absorbing the substance to the composite material.
  • [0288]
    In certain embodiments, the invention relates to a method of separating a substance from a fluid, comprising the step of:
  • [0000]
    placing the fluid in an inlet of any one of the above-mentioned fluid treatment devices, thereby adsorbing or absorbing the substance to the composite material and producing a permeate; and collecting the permeate from an outlet of the fluid treatment device.
  • [0289]
    In certain embodiments, the invention relates to the above-mentioned method, wherein the fluid is passed over the surface of the composite material; and the substance is adsorbed or absorbed onto the surface of the composite material.
  • [0290]
    In certain embodiments, the invention relates to the above-mentioned method, wherein the fluid is passed through the macropores of the composite material; and the substance is adsorbed or absorbed within the macropores of the composite material.
  • [0291]
    In certain embodiments, the invention relates to a method of separating a substance from a fluid, comprising the step of:
  • [0000]
    placing the fluid in an inlet of any one of the above-mentioned fluid treatment devices, thereby adsorbing or absorbing the substance to the composite material;
    collecting the permeate from an outlet of the fluid treatment device;
    placing a second fluid in the inlet of the fluid treatment device, thereby releasing the substance from the composite material.
  • [0292]
    In certain embodiments, the invention relates to the above-mentioned method, wherein the fluid is passed over the surface of the composite material; the substance is adsorbed or absorbed onto the surface of the composite material; and the second fluid is passed through the macropores of the composite material, thereby releasing the substance from the composite material.
  • [0293]
    In certain embodiments, the invention relates to the above-mentioned method, wherein the fluid is passed over the surface of the composite material; the substance is adsorbed or absorbed onto the surface of the composite material; and the second fluid is passed over the surface of the composite material, thereby releasing the substance from the surface of the composite material.
  • [0294]
    In certain embodiments, the invention relates to the above-mentioned method, wherein the fluid is passed through the macropores of the composite material; the substance is adsorbed or absorbed within the macropores of the composite material; and the second fluid is passed over the surface of the composite material, thereby releasing the substance from the composite material.
  • [0295]
    In certain embodiments, the invention relates to the above-mentioned method, wherein the fluid is passed through the macropores of the composite material; the substance is adsorbed or absorbed within the macropores of the composite material; and the second fluid is passed through the macropores of the composite material, thereby releasing the substance from the composite material.
  • [0296]
    In certain embodiments, the invention relates to any one of the above-mentioned methods, wherein the substance is radioactive.
  • [0297]
    In certain embodiments, the invention relates to a method of separating a substance from a fluid, comprising the steps of:
  • [0298]
    placing the fluid in an inlet of any one of the above-mentioned fluid treatment devices, thereby adsorbing or absorbing the substance to the composite material and producing a permeate; and
  • [0299]
    collecting the permeate from an outlet of the fluid treatment device,
  • [0300]
    wherein the fluid comprises egg white; and the substance is lysozyme.
  • [0301]
    In certain embodiments, the invention relates to the above-mentioned method, wherein the fluid is passed over the surface of the fluid treatment element; and the substance is adsorbed or absorbed onto the surface of the fluid treatment element.
  • [0302]
    In certain embodiments, the invention relates to a method of separating a substance from a first fluid, comprising the steps of:
  • [0303]
    placing the first fluid in an inlet of any one of the above-mentioned fluid treatment devices, thereby adsorbing or absorbing the substance to the composite material;
  • [0304]
    collecting the permeate from an outlet of the fluid treatment device;
  • [0305]
    placing a second fluid in the inlet of the fluid treatment device, thereby releasing the substance from the composite material,
  • [0306]
    wherein the first fluid comprises egg white; and the substance is lysozyme.
  • [0307]
    In certain embodiments, the invention relates to the above-mentioned method, wherein the fluid is passed over the surface of the fluid treatment element; the substance is adsorbed or absorbed onto the surface of the fluid treatment element; and the second fluid is passed through the macropores of the fluid treatment element, thereby releasing the substance from the macropores. In certain embodiments, the invention relates to the above-mentioned method, wherein the fluid is passed over the surface of the fluid treatment element; the substance is adsorbed or absorbed onto the surface of the fluid treatment element; and the second fluid is passed over the surface of the fluid treatment element, thereby releasing the substance from the surface of the fluid treatment element.
  • EXEMPLIFICATION
  • [0308]
    The invention now being generally described, it will be more readily understood by reference to the following examples, which are included merely for purposes of illustration of certain aspects and embodiments of the present invention, and are not intended to limit the invention.
  • Example 1 Dead-End versus Cross-Flow Modes for Viral Capture
  • [0309]
    An example of the improvement of cross-flow technology versus dead-end technology can be realized when the two modes are compared directly to each other. FIG. 1 shows two experiments in which a specific device was run as a dead-end and as cross-flow device. The material of interest is a virus. In both cases, the capture of the cross-flow device exceeded the dead-end version, as indicated by the amount to the pure target material capture after washing and elution.
  • Example 2 Chromatographic Capture and Harvest: Elution of Ovalbumin and Lysozyme
  • [0310]
    The membrane can selectively adsorb two protein materials from the feed stream and then, through the use of an altering buffer fluid, selectively elute the target bio-molecules. FIGS. 2 and 3 illustrate this effect. The initial feed stream of egg white was exposed to a membrane surface in cross-flow mode. Once the feed stream was removed and the membrane washed, both Ovalbumin and lysozyme were found adhered to the membrane (FIG. 2). Under specific buffer conditions, the proteins were selectively eluted (FIG. 3), which demonstrates the chromatographic nature of the membrane in cross-flow mode.
  • Example 3 Orthogonal Two-Step Capture and Harvest
  • [0311]
    See FIG. 4.
  • Example 4 Device Design: Wrap Design Data and Schematics
  • [0312]
    The effect of selecting an optimal spacer material in a simple wrapped design was observed and is depicted in FIG. 5. In this design, a roll was made by layering the necessary membrane sheet between two identical spacer sheets and rolling the multi-layered structure into a column. This column was then placed into a metal tube housing that was fitted with end-caps which have both an inlet(s) and outlet(s) attached (FIG. 6). The larger spacer material and loose-wind structure enabled the ideal cross-flow or tangential-flow adsorption. Importantly, this design eliminated any direct trans-membrane flow, as the process fluid was run on either side of the membrane. Thus, the improvements stemmed, at least partially, from the low shear environment. The purified lysozyme control was run on the device and was used to represent 100% or maximum adsorption of the target species. The remaining data were generated directly from process fluid streams (egg whites). In this embodiment, the spacer layer materials on either side of the membrane were identical but there is no requirement for this symmetry and the “roll” could have differing layers or one layer could be completely absent.
  • Example 5 Device Design: Cassettes
  • [0313]
    The height of the feed channel may impact the ability to maximize the amount of adsorbed target molecule. Smaller feed channel heights may induce greater shear or turbulence at the membrane surface, which either inhibits adsorption or removes target material that does deposit. The channel height needs to be at least 10 mm and more ideally >20 mm, typically 23 mm (FIG. 7).
  • [0314]
    Screen changes have not been identified as a driver for performance in cassette design.
  • Example 6 Device Design: Spiral
  • [0315]
    FIG. 23 depicts a spiral wound device. When membranes of the current invention are incorporated into this device, highly contaminated or very viscous feed streams can be effectively separated into their desired parts.
  • Example 7 Antibody Purification: Membrane Functionalized with Protein A
  • [0316]
    A 0.01 SQM Protein A cassette with an open channel, suspended screen design which enabled a fluid flow tangential to the plane of the membrane was evaluated using an un-clarified feed stream which contained the monoclonal antibody (mAb) target. Traditional resin chromatographic separation processes cannot process un-clarified feed streams. The only method that had been demonstrated able to capture the mAb target on bench scale was an expanded bed column functioning in batch mode with a static soak. This modified expanded bed was uneconomical and impractical at larger scale. On the other hand, the cassettes were effective in capturing the target MAb product when used a simple flow through mode. This mode allowed the process stream to flow across the membrane such that debris in the fluid did not blind the membrane. Binding of the target species in this mode was a surface effect only.
  • [0317]
    Lysis Procedure: 270 g mAb 4420 pellet diluted 1 part pellet, 3 parts 10× phosphate buffer solution (PBS), 1 part 5× Pfenix lysis buffer. Homogenized for 5 minutes, and sonicated for 10 minutes. Loaded onto the membrane as an un-clarified and undiluted feed stream.
  • [0318]
    Membrane Procedure: A membrane cassette with an active surface area of 0.01 m2 and pore size of 0.3 μm was equilibrated in PBS at pH 7.4. This device was then loaded by complete system recirculation with lysed mAb 4420 for one hour. The device was then washed with 1 L of 1×PBS pH 7.4, and eluted using a 10 minute recirculation of 0.1 M Glycine at pH 2.9 followed by 100 mL system flush with 0.1 M Glycine pH 2.9. The feed was run in flow through mode at 100 mL/min with permeate shut off which limited the device to surface binding only from the un-clarified lysate. A gel electrophoresis qualitative analysis indicated that significant amounts of mAb had been captured.
  • [0319]
    Conclusion: The cross-flow product provided a simple, on-off bind-elute capture process that could capture and concentrate intact mAb (observed binding was in the range of 5-10 mg/mL) as well as a lot of contaminants. With development, membrane could serve as a scalable capture method for un-clarified mAb Pseudomonas feed streams.
  • Example 8 His-Tagged Protein Purification: Membrane Functionalized with IMAC Ni
  • [0320]
    A 0.02 SQM IMAC-Ni (iminodiacetic acid complexed to Ni) cassette with an open channel, suspended screen design which enabled a fluid flow tangential to the plane of the membrane was evaluated using a feed stream containing a his-tagged protein target. Traditional resin-based chromatographic separation processes cannot process un-clarified feed streams. In this experiment, the cassettes were effective in capturing the target product in a simple flow through mode. This mode allowed the process stream to flow across the membrane such that debris in the fluid did not blind the membrane. Binding of the target species in this mode was a surface effect only. The product was able to be run with multiple cycles with no loss in binding capacity.
  • [0321]
    Lysis Procedure: 8 L of cell harvest material was diluted with 2 L of 5× Pfenix Lysis Buffer. This mixture was allowed to mix for 2 hours until the material had liquefied.
  • [0322]
    Membrane Procedure: A membrane cassette with an active surface area of 0.02 m2 was equilibrated in 50 mM PBS, 500 mM NaCl, 5% (wt) glycerol and 25 mM Imidazole at pH 8.0. The cassette was then run with the liquefied cell harvest material at a 100 mL/min feed rate with no permeate flow. This was flowed by elution using 500 mL 1×PBS, 500 mM Imidazole at pH 7.4. This process was repeated 3 times in sequence with the follow details:
      • Run 1: 1 L of Lysate was centrifuged and diluted by a factor of 5 in equilibration buffer. The device was then loaded by complete system recirculation for 1 hour time and material was able to permeate through the pores at 20 PSIg inlet pressure. A gel electrophoresis qualitative analysis indicated that significant amounts his-tagged protein had been captured.
      • Run 2: 1 L of Lysate was only centrifuged prior to use. The device was then loaded by complete system recirculation for 1 hour time and material was able to permeate through the pores at 20 PSIg inlet pressure. A gel electrophoresis qualitative analysis indicated that significant amounts his-tagged protein had been captured
      • Run 3: 1 L of Lysate was used without pre-treatment. The device was then loaded by complete system recirculation for 15, 30, 45, 60 minute load times. The device was eluted after each cycle and the membrane not stripped (cleaned) between elutions. When the permeate line was closed, no back pressure increase to system was observed during load indicating that the membrane had not blinded.
  • [0326]
    Conclusion: The IMAC-Ni product yielded excellent purification characteristics (observed binding was in the range of 60-80 mg/mL) without optimization. Despite manufacturers designation as “single-use,” 7× reuse demonstrated for IMAC membrane without the need for EDTA strip and re-charge.
  • INCORPORATION BY REFERENCE
  • [0327]
    All of the U.S. patents and U.S. patent application publications cited herein are hereby incorporated by reference.
  • EQUIVALENTS
  • [0328]
    Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.
Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US3209915 *11 Jun 19625 Oct 1965Aircraft Appliances And EquipmFilter
US3417870 *22 Mar 196524 Dec 1968Gulf General Atomic IncReverse osmosis purification apparatus
US3473668 *23 Mar 196721 Oct 1969Norris Filters LtdStacked filter elements
US3623610 *23 Oct 196930 Nov 1971Danske SukkerfabReverse osmosis apparatus
US3695444 *22 Apr 19703 Oct 1972IonicsMembrane support
US3713921 *1 Apr 197130 Jan 1973Gen ElectricGeometry control of etched nuclear particle tracks
US3875085 *9 Oct 19731 Apr 1975Ici Australia LtdProcess of making amphoteric polymeric compositions from snake-cage resins
US3939105 *18 Jun 197417 Feb 1976Union Carbide CorporationMicroporous polyurethane hydrogels, method and composites with natural and other synthetic fibers or films
US3997482 *8 Jul 197414 Dec 1976Ceskoslovenska Akademie VedHydrophilic polymeric carriers of biologically active compounds and method of preparing the same
US4104125 *13 Jul 19771 Aug 1978The Green Cross CorporationProcess for producing human lysozyme
US4108804 *29 Nov 197622 Aug 1978Toru SeitaProcess for preparation of chromatography solid supports comprising a nucleic acid base-epoxy group containing porous gel
US4133764 *15 Dec 19759 Jan 1979Rhone-Poulenc IndustriesRetaining device for apparatus having semi-permeable membranes
US4170540 *31 Mar 19789 Oct 1979Hooker Chemicals & Plastics Corp.Method for forming microporous membrane materials
US4224415 *18 Jul 195823 Sep 1980Rohm And Haas CompanyPolymerization processes and products therefrom
US4230697 *9 May 197928 Oct 1980Morinaga Milk Industry Co. Ltd.Virus-inactivated HGI-glycoprotein capable of stimulating proliferation and differentiation of human granulocyte, process for preparing same and leukopenia curative containing same
US4275056 *19 Mar 197923 Jun 1981Morinaga Milk Industry Co., Ltd.HGI-Glycoprotein capable of stimulating proliferation and differentiation of human granulocyte, process for preparing same and leukopenia curative containing same
US4397892 *26 Apr 19829 Aug 1983Bor-,Mubor-,es Cipoipari kutato IntezetProcess for the production of chemically bonded non-woven sheet materials containing a binder of microheteroporous structure
US4473474 *23 Oct 198125 Sep 1984Amf Inc.Charge modified microporous membrane, process for charge modifying said membrane and process for filtration of fluid
US4504583 *30 Nov 198212 Mar 1985Kewpie Kabushiki KaishaProcess for crystallizing egg white lysozyme
US4518695 *23 Nov 198221 May 1985Kewpie Kabushiki KaishaProcess for eluting egg white lysozyme
US4525374 *27 Feb 198425 Jun 1985Manresa, Inc.Treating hydrophobic filters to render them hydrophilic
US4525527 *21 Jan 198325 Jun 1985American Colloid CompanyProduction process for highly water absorbable polymer
US4601828 *4 Jan 198522 Jul 1986Yale UniversityTransfer of macromolecules from a chromatographic substrate to an immobilizing matrix
US4678844 *24 Feb 19867 Jul 1987Agency Of Industrial Science & TechnologyChelate, crosslinked polyethyleneimine resin having 2-hydroxy benzoyl group
US4705755 *19 Jul 198510 Nov 1987Kewpie Kabushiki KaishaApparatus for collecting lysozyme from egg white by adsorption
US4836928 *26 Apr 19856 Jun 1989Terumo Kabushiki KaishaSeparation method, separation device and separation apparatus for separating body fluid into respective components
US4923610 *25 Sep 19898 May 1990Ceskoslovenska akademive ved and Akademia Nauk SSSRMacroporous polymeric membranes for the separation of polymers and a method of their application
US4944879 *27 Jul 198931 Jul 1990Millipore CorporationMembrane having hydrophilic surface
US4952349 *23 Jan 199028 Aug 1990Ceskoslovenska Akademie VedMacroporous polymeric membranes for the separation of polymers and a method of their application
US4966851 *19 Nov 198730 Oct 1990The University Of British ColumbiaProcess for isolation of lysozyme and avidin from egg white
US4999171 *2 Aug 198912 Mar 1991Sumitomo Chemical Co. Ltd.Process for recovery of gallium by chelate resin
US5019270 *9 Oct 199028 May 1991Perseptive Biosystems, Inc.Perfusive chromatography
US5059659 *3 Jan 199122 Oct 1991Harry P. GregorSurface treatments to impart hydrophilicity
US5114585 *27 Dec 198919 May 1992Gelman Sciences, Inc.Charged porous filter
US5130343 *13 Mar 199114 Jul 1992Cornell Research Foundation, Inc.Process for producing uniform macroporous polymer beads
US5137633 *26 Jun 199111 Aug 1992Millipore CorporationHydrophobic membrane having hydrophilic and charged surface and process
US5147541 *29 Apr 199115 Sep 1992Koch Membrane Systems, Inc.Spiral filtration module with strengthened membrane leaves and method of constructing same
US5160627 *27 Dec 19913 Nov 1992Hoechst Celanese CorporationProcess for making microporous membranes having gel-filled pores, and separations methods using such membranes
US5176832 *23 Oct 19915 Jan 1993The Dow Chemical CompanyChromatographic separation of sugars using porous gel resins
US5228989 *9 Dec 199220 Jul 1993Perseptive Biosystems, Inc.Perfusive chromatography
US5277915 *27 Mar 199211 Jan 1994Fmc CorporationGel-in-matrix containing a fractured hydrogel
US5282971 *11 May 19931 Feb 1994Pall CorporationPositively charged polyvinylidene fluoride membrane
US5316680 *21 Oct 199231 May 1994Cornell Research Foundation, Inc.Multimodal chromatographic separation media and process for using same
US5334310 *23 Oct 19922 Aug 1994Cornell Research Foundation, Inc.Column with macroporous polymer media
US5384042 *10 May 199324 Jan 1995Perseptive Biosystems, Inc.Perfusive chromatography
US5403482 *12 Oct 19934 Apr 1995Gelman Sciences Inc.Self-supporting, pleated, spirally wound filter and the corresponding process of making
US5422284 *29 Oct 19936 Jun 1995E. I. Du Pont De Nemours And CompanyMethod of performing affinity separation using immobilized flocculating agent on chromatographic support
US5460720 *12 Aug 199324 Oct 1995Schneider; Burnett M.Pleated membrane crossflow fluid separation device
US5470469 *16 Sep 199428 Nov 1995E. I. Du Pont De Nemours And CompanyHollow fiber cartridge
US5593576 *6 Jun 199514 Jan 1997Biosepra, Inc.Passivated porous polymer supports and methods for the preparation and use of same
US5593729 *15 Feb 199514 Jan 1997Cornell Research Foundation, Inc.Pore-size selective modification of porous materials
US5599453 *6 Jun 19954 Feb 1997Biosepra Inc.Passivated porous supports and methods for the preparation and use of same
US5646001 *28 Feb 19958 Jul 1997Immunivest CorporationAffinity-binding separation and release of one or more selected subset of biological entities from a mixed population thereof
US5648390 *4 Aug 199415 Jul 1997The United States Of America As Represented By The Secretary Of AgricultureRepellents for ants
US5672276 *1 Oct 199630 Sep 1997Biosepra Inc.Passivated porous polymer supports and methods for the preparation and use of same
US5681464 *8 Jul 199428 Oct 1997Alfa Laval Brewery Systems AbFilter for cross-flow filtration
US5723601 *16 Mar 19933 Mar 1998Pharmacia Biotech AbSuper porous polysaccharide gels
US5728457 *11 Jun 199617 Mar 1998Cornell Research Foundation, Inc.Porous polymeric material with gradients
US5756717 *24 May 199526 May 1998Perseptive Biosystems, IncProtein imaging
US5780688 *2 Oct 199314 Jul 1998Veba Oel AgSupported-catalyst and use of same
US5783085 *15 May 199621 Jul 1998Estate Of William F. MclaughlinBlood fractionation method
US5906734 *19 May 199725 May 1999Biosepra Inc.Passivated porous polymer supports and methods for the preparation and use of same
US5929214 *25 Feb 199827 Jul 1999Cornell Research Foundation, Inc.Thermally responsive polymer monoliths
US5972634 *19 Oct 199426 Oct 1999The General Hospital CorporationDiagnostic assay for Alzheimer's disease: assessment of Aβ abnormalities
US6033784 *3 Apr 19967 Mar 2000Jacobsen; Mogens HavsteenMethod of photochemical immobilization of ligands using quinones
US6045697 *30 Nov 19984 Apr 2000Life Technologies, Inc.Passivated porous polymer supports and methods for the preparation and use of same
US6086769 *15 Sep 199711 Jul 2000Commodore Separation Technologies, Inc.Supported liquid membrane separation
US6143174 *8 Feb 19997 Nov 2000Sartorius AgFiltration unit with pleated filtering elements
US6258276 *18 Oct 199610 Jul 2001Mcmaster UniversityMicroporous membranes and uses thereof
US6271278 *13 May 19977 Aug 2001Purdue Research FoundationHydrogel composites and superporous hydrogel composites having fast swelling, high mechanical strength, and superabsorbent properties
US6277489 *4 Dec 199821 Aug 2001The Regents Of The University Of CaliforniaSupport for high performance affinity chromatography and other uses
US6461513 *19 May 20008 Oct 2002Filtration Solutions, Inc.Secondary-flow enhanced filtration system
US6475071 *25 Aug 20005 Nov 2002Micron Technology, Inc.Cross flow slurry filtration apparatus and method
US6613234 *22 Mar 19992 Sep 2003Ciphergen Biosystems, Inc.Large pore volume composite mineral oxide beads, their preparation and their applications for adsorption and chromatography
US6635104 *13 Nov 200121 Oct 2003Mcmaster UniversityGas separation device
US6635420 *31 Aug 199821 Oct 2003Roche Diagnostics GmbhPurification of substances from a biological sample
US6766817 *25 Feb 200227 Jul 2004Tubarc Technologies, LlcFluid conduction utilizing a reversible unsaturated siphon with tubarc porosity action
US6780327 *25 Feb 200024 Aug 2004Pall CorporationPositively charged membrane
US6780582 *17 May 200024 Aug 2004Zyomyx, Inc.Arrays of protein-capture agents and methods of use thereof
US6824975 *12 Oct 200130 Nov 2004Dexall Biomedical Labs, IncIncorporation of selective binding substances in a solid phase assay device
US6851561 *15 Jul 20048 Feb 2005Pall CorporationPositively charged membrane
US6911148 *6 Sep 200028 Jun 2005Sartorius AgAdsorptive membrane device for treating particle-laden liquid feeds
US6918404 *13 Apr 200419 Jul 2005Tubarc Technologies, LlcIrrigation and drainage based on hydrodynamic unsaturated fluid flow
US6951880 *15 May 20034 Oct 2005Genelabs Technologies, Inc.Aryl and heteroaryl compounds as antibacterial and antifungal agents
US6984604 *26 Nov 200210 Jan 2006Invista North America S.A.R.L.Supported bis(phosphorus) ligands and their use in the catalysis
US6986847 *12 May 200317 Jan 2006New Jersey Institute Of TechnologyMethod and apparatus for isolation and purification of biomolecules
US7048855 *21 Dec 200123 May 2006Ge Osmonics, Inc.Cross flow filtration materials and cartridges
US7066586 *13 Apr 200427 Jun 2006Tubarc Technologies, LlcInk refill and recharging system
US7094347 *18 Jan 200522 Aug 2006Pall CorporationPositively charged membrane
US7163803 *7 Jun 200216 Jan 2007Electrophoretics LimitedMethod for characterizing polypeptides
US7285255 *10 Dec 200223 Oct 2007Ecolab Inc.Deodorizing and sanitizing employing a wicking device
US7316919 *2 Feb 20048 Jan 2008Nysa Membrane TechnologiesComposite materials comprising supported porous gels
US7507420 *12 Sep 200524 Mar 2009Medarex, Inc.Peptidyl prodrugs and linkers and stabilizers useful therefor
US7598371 *6 Nov 20016 Oct 2009University Of HoustonNucleic acid separation using immobilized metal affinity chromatography
US7824548 *21 Jun 20072 Nov 2010Millipore CorporationPorous adsorptive or chromatographic media
US20020005383 *22 Mar 199917 Jan 2002Nicolas VouteLarge pore volume composite mineral oxide beads, their preparation and their applications for adsorption and chromatography
US20040203149 *2 Feb 200414 Oct 2004Childs Ronald F.Composite materials comprising supported porous gels
US20060175256 *6 Dec 200510 Aug 2006Board Of Trustees Of Michigan State UniversityCeramic membrane water filtration
US20070212281 *9 May 200713 Sep 2007Ecolab, Inc.Deodorizing and sanitizing employing a wicking device
US20080017578 *7 Apr 200524 Jan 2008Childs Ronald FMembrane Stacks
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US941000727 Sep 20139 Aug 2016Rhodia OperationsProcess for making silver nanostructures and copolymer useful in such process
US957505923 May 201321 Feb 20173M Innovative Properties CompanyLanthanum-based concentration agents for microorganisms
US20080242822 *2 Apr 20082 Oct 2008West Richard APolyurethane formulation using protein-based material
US20110117626 *15 Nov 201019 May 2011Komkova Elena NHydrophobic Interaction Chromatography Membranes, and Methods of Use Thereof
US20140231256 *18 Oct 201321 Aug 2014Innovaprep LlcLiquid to Liquid Biological Particle Fractionation and Concentration
CN104884933A *18 Oct 20132 Sep 2015伊诺瓦普瑞普有限公司Liquid to liquid biological particle fractionation and concentration
WO2011058439A1 *12 Nov 201019 May 2011Natrix Separations, Inc.Hydrophobic interaction chromatography membranes, and methods of use thereof
WO2012037101A2 *13 Sep 201122 Mar 2012Natrix Separations Inc.Chromatography membranes for the purification of chiral compounds
WO2012037101A3 *13 Sep 20115 Jul 2012Natrix Separations Inc.Chromatography membranes for the purification of chiral compounds
WO2014063125A1 *18 Oct 201324 Apr 2014Innovaprep LlcLiquid to liquid biological particle fractionation and concentration
WO2014134147A1 *26 Feb 20144 Sep 2014Natrix Separations Inc.Mixed-mode chromatography membranes
Legal Events
DateCodeEventDescription
17 Nov 2009ASAssignment
Owner name: NATRIX SEPARATIONS INC.,CANADA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BRELLISFORD, DAMIAN;CROSSLEY, DONNA LISA;MCINTOSH, GREG;AND OTHERS;SIGNING DATES FROM 20090911 TO 20091103;REEL/FRAME:023528/0619