Multi-modal ion-exchange membranes for rapid separations
Ion exchange membranes (e.g., anion exchange membranes) and methods of using the membranes are described. The ion exchange membranes are multi-modal ion exchange membranes containing a plurality of multi-modal exchange ligands. The membranes can achieve high dynamic and equilibrium binding capacities at solution conductivities typical for production of biologics (e.g., greater than about 10 mS/cm) and can provide excellent binding at high flow rates. Systems incorporating the membranes can dramatically increase isolation and purification speeds. Membranes are disclosed for use in production of biologics.
1 . A multi-modal ion exchange membrane comprising:
a porous membrane substrate;
a plurality of polymers grafted at a surface of the porous membrane substrate; and
a plurality of ligands bonded to and pendant from each of the grafted polymers, each of the ligands that is bonded to and pendant from each grafted polymer providing first and second modes of sorptive functionality, the first mode of sorptive functionality being an ionic fixed charge at a binding site linking the ligand with the grafted polymer to which it is bonded to and pendant from, the second mode of sorptive functionality being a component of the ligand that is bonded to and pendant from the grafted polymer.
2 . The multi-modal ion exchange membrane of claim 1 , wherein the first mode of sorptive functionality is cationic.
3 . The multi-modal ion exchange membrane of claim 1 , wherein the second mode of sorptive functionality comprises hydrophobic functionality, hydrophilic functionality, thiophilic functionality, hydrogen bond donating functionality, hydrogen bond accepting functionality, pi-pi bond donating functionality, pi-pi bond accepting functionality, metal chelating functionality, or a combination thereof.
4 . The multi-modal ion exchange membrane of claim 1 , wherein the porous membrane substrate comprises interconnected pores, the pores having an absolute pore size of about 0.1 micrometers or greater.
5 . The multi-modal ion exchange membrane of claim 1 , the polymer comprising polymerized dimethylaminoethyl methacrylate monomer, (diethylamino) ethyl methacrylate monomer, (dimethylamino) ethyl acrylate monomer, (diisopropylamino) ethyl methacrylate monomer, hydroxyethyl acrylate monomer, hydroxyethyl methacrylate monomer, poly (ethylene glycol) methacrylate monomer, or combinations thereof.
6 . The multi-modal ion exchange membrane of claim 1 , wherein prior to bonding with the grafted polymer and thereby becoming bonded to and pendant from the grafted polymer, each of the ligands have the following structure:
in which
R 1 is selected from halogen, hydroxyl, amine, C1 to C6 alkyl, alkyl halide, alkoxy, alcohol, carboxylic acid, sulfonic acid, phosphonic acid, amine, or combinations thereof; and
R 2 through R 6 are independently selected from hydrogen, halogen, hydroxyl, amine, C1 to C6 alkyl, alkyl halide, alkoxy, alcohol, carboxylic acid, sulfonic acid, phosphonic acid, amine, or combinations thereof; and
wherein one or more of R 2 through R 6 are optionally substituted with a conjugated and/or non-conjugated ring.
7 . The multi-modal ion exchange membrane of claim 1 , the membrane incorporating the ligands at a ligand density of from about 50 μM/ml to about 1000 μM/ml.
8 . The multi-modal ion exchange membrane of claim 1 , further comprising one or more additional modes of sorptive functionality.
9 . The multi-modal ion exchange membrane of claim 6 , wherein the conjugated and/or non-conjugated ring comprises a heterocyclic ring or a fused ring system.
10 . The multi-modal ion exchange membrane of claim 6 , wherein the conjugated and/or non-conjugated ring is derivatized with one or more of hydrogen, halogen, or alkoxy.
11 . A method for forming the multi-modal ion exchange membrane of claim 1 , the method comprising:
grafting the plurality of polymers at the surface of the porous membrane substrate, and
covalently binding the plurality of ligands to each of the polymers such that each of the plurality of ligands is bonded to and pendant from a polymer.
12 . The method of claim 11 , wherein the plurality of polymers is grafted at the surface of the porous membrane substrate according to a grafting from process, the grafting from process comprising anchoring an initiator molecule to the surface of the porous membrane substrate and activating the initiator molecule in the presence of a monomer.
13 . The method of claim 12 , wherein the grafting from process comprises an atom transfer radical polymerization process.
14 . A method for separating a targeted species from a solution, the method comprising contacting the multi-modal ion exchange membrane of claim 1 with a solution, the solution comprising one or more targeted species, the solution having a solution conductivity of from about 0.5 millisiemans per centimeter to about 50 millisiemans per centimeter.
15 . The method of claim 14 , wherein the targeted species is a proteinaceous species, the multi-modal membrane exhibiting a dynamic binding capacity for the proteinaceous species of from about 10 milligrams per milliliter to about 250 milligrams per milliliter.
16 . The method of claim 14 , wherein the targeted species is a polynucleotide, the multi-modal ion exchange membrane exhibiting a dynamic binding capacity for the polynucleotide of from about 1 milligram per milliliter to about 50 milligrams per milliliter.
17 . The method of claim 14 , wherein the solution passes through a column at a rate of about 10 column volumes per minute or greater.
18 . The method of claim 14 , wherein the solution has a solution conductivity of from about 8 millisiemans per centimeter to about 30 millisiemans per centimeter.
19 . The method of claim 14 , the targeted species comprising proteinaceous targets, polynucleotide targets, endotoxins, virus particles, virus-like particles, aggregates, isoforms of biological compounds, or a combination thereof.