Chromatography Membranes, Devices Containing Them, and Methods of Use Thereof

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.

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.