# US 9,434,829 B2 · Ligand grafted substrates

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- Number: US 9,434,829 B2
- Document ID: US9434829B2
- Status: Granted
- Kind: B2
- Application number: 14/415,862
- Filed: 2013-09-23
- Published: 2015-07-23
- Granted: 2016-09-06
- Earliest claimed: 2012-09-27
- Assignees: 3M Innovative Properties Company
- Applicants: 3M Innovative Properties Company
- Inventors: Jerald K. Rasmussen; Catherine A. Bothof
- Web page: https://patentgrep.com/patent/US9434829B2

## CPC

- B01J 20/267: {Cross-linked polymers}
- B01J 20/289: bonded via a spacer
- B01J 20/3212: {consisting of a polymer obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds}
- B01J 20/3219: {involving a particular spacer or linking group, e.g. for attaching an active group}
- B01J 20/327: {Polymers obtained by reactions involving only carbon to carbon unsaturated bonds}
- B01J 20/3272: {Polymers obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds}
- B01J 20/3276: {Copolymers}
- B01J 20/3278: {Polymers being grafted on the carrier}
- B01J 20/3282: {Crosslinked polymers}
- C07K 1/22: Affinity chromatography or related techniques based upon selective absorption processes
- C07K 14/765: Serum albumin, e.g. HSA
- C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- C08G 73/02: Polyamines
- C08J 7/0427: {with only one layer of a composition containing a polymer binder (with more layers C08J7/042)}
- C08J 7/043: Improving the adhesiveness of the coatings per se, e.g. forming primers (adhesives in the form of films or foils characterised by the primer layers between the polymer carriers and the adhesives C09J7/50)
- C08J 7/056: Forming hydrophilic coatings
- C08J 7/18: using wave energy or particle radiation
- C09D 4/00: Coating compositions, e.g. paints, varnishes or lacquers, based on organic non-macromolecular compounds having at least one polymerisable carbon-to-carbon unsaturated bond {; Coating compositions, based on monomers of macromolecular compounds of groups C09D183/00 - C09D183/16}
- C09D 5/002: {Priming paints (C09D5/08 takes precedence)}
- C09D 133/24: Homopolymers or copolymers of amides or imides
- C09D 179/02: Polyamines
- G01N 33/54393: {Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding}
- C08J 2333/24: Homopolymers or copolymers of amides or imides
- C08J 2377/06: Polyamides derived from polyamines and polycarboxylic acids (C08J2377/10 takes precedence)
- C08J 2433/14: of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen
- C08J 2433/24: Homopolymers or copolymers of amides or imides
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08J: WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H (working, e.g. shaping, of plastics B29)
- C09D: COATING COMPOSITIONS, e.g. PAINTS, VARNISHES OR LACQUERS; FILLING PASTES; CHEMICAL PAINT OR INK REMOVERS; INKS; CORRECTING FLUIDS; WOODSTAINS; PASTES OR SOLIDS FOR COLOURING OR PRINTING; USE OF MATERIALS THEREFOR (cosmetics A61K; processes for applying liquids or other fluent materials to surfaces, in general, B05D; staining wood B27K5/02; glazes or vitreous enamels C03C; natural resins, French polish, drying-oils, driers, turpentine, per se, C09F; polishing compositions other than French polish, ski waxes C09G; adhesives or use of materials as adhesives C09J; materials for sealing or packing joints or covers C09K3/10; materials for stopping leaks C09K3/12; processes for the electrolytic or electrophoretic production of coatings C25D)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Ligand-functionalized substrates are describe that are useful in selectively binding and removing biological materials from biological samples, and methods for preparing the same.

## Claims

### Claim 1

A method for preparing a ligand-functionalized substrate comprising:
a) providing a base substrate;
b) providing a coating solution comprising a copolymer of one or more monomer units having a photoinitiator group, one or more monomer units having a crosslinkable functional group, one or more hydrophilic monomer units, and optionally one or more “other” monomer units;
c) coating the base substrate with the coating solution;
d) crosslinking the coating to produce a crosslinked copolymer;
e) imbibing the substrate bearing the crosslinked copolymer with a solution or suspension comprising (a) one or more ligand functional monomers, (b) optionally one or more hydrophilic monomers; and optionally c) one or more “other” monomers;
f) exposing the imbibed base substrate to UV radiation so as to generate free radicals from the photoinitiator groups of the copolymer, and
g) graft-polymerizing the monomers of step e) onto the surface of the base substrate.

### Claim 2 (depends on 1)

The method of claim 1, wherein the hydrophilic monomer units of the copolymer comprise one or more of poly(oxyalkylene) (meth)acryloyl monomer units, (meth)acrylamide monomer units, vinyl amide monomer units, and hydroxyalkyl(meth)acryloyl monomer units.

### Claim 3 (depends on 1)

The method of claim 1, wherein the monomer units having a crosslinkable functional groups are derived from monomers of the formula:
wherein
X1 is —O— or —NR1—,
R1 is H or C1-C4 alkyl;
R2 is a single bond or a (hetero)hydrocarbyl linking group,
A is an reactive functional group that is reactive with a crosslinking compound or is self-crosslinking; and
x is 0 or 1.

### Claim 4 (depends on 3)

The method of claim 3 wherein A is an amine reactive functional group and is selected from carboxyl, oxazolinyl, azlactone, acetyl, acetonyl, acetoacetyl, ester, isocyanato, epoxy, aziridinyl, acyl halide, and cyclic anhydride groups.

### Claim 5 (depends on 1)

The method of claim 1, wherein the monomer units having a crosslinkable functional groups are self crosslinkable and are derived from monomers selected from alkenyl or (meth)acryloyl silanes, hydroxymethyl(meth)acrylamides and alkoxymethyl(meth)acrylamides.

### Claim 6 (depends on 4)

The method of claim 4, wherein the coating solution further comprises an amine functional crosslinking compound.

### Claim 7 (depends on 6)

The method of claim 6 wherein the amine functional crosslinking compound is of the formula
(HNR1)r—R4-(FG)q,
where R1 is H or C1-C4 alkyl,
R4 is a (hetero)hydrocarbyl group;
FG is a functional group that is a) reactive toward the functional group of the copolymer, or b) self-crosslinking, and subscripts r and q are at least one.

### Claim 8 (depends on 7)

The method of claim 7 wherein FG is —NHR1, where R1 is H or C1-C4 alkyl.

### Claim 9 (depends on 8)

The method of claim 8 wherein the crosslinking compound is a polyamine of the formula
R4(NHR1)m, wherein
R4 is a (hetero)alkylene group;
R1 is H or C1-C4 alkyl, and at least one R1 is H, and m is at least two.

### Claim 10 (depends on 1)

The method of claim 1 wherein the ligand functional monomers are of the formula:
Z1—Y2—X1—CO—CR1═CH2, or
Z1—Y2—CR1═CH2
wherein X1 is —O— or —NR1—,
R1 is H or C1-C4 alkyl,
Y2 is a linking group selected from a single bond or a (hetero)hydrocarbyl divalent group;
Z1 is a ligand functional group that binds biological species by ionic, covalent, hydrophobic, and biological affinity interactions.

### Claim 11 (depends on 1)

The method of claim 1, wherein the ligand-functional monomer units are derived from monomers of the formulas:
wherein
R1 is H or C1-C4 alkyl;
R2 is a (hetero)hydrocarbyl group;
each R3 is independently H or C1-C4 alkyl;
R4 is H, C1-C12 alkyl or —N(R3)2;
R7 is H or hydrocarbyl, preferably C1-C12 alkyl or aryl;
X1 is —O— or —NR3—,
e is 0 or 1, and
d is 1 or 2.

### Claim 12 (depends on 1)

The method of claim 1 wherein the monomers of the imbibing step e) comprises hydrophilic monomers.

### Claim 13 (depends on 1)

The method of claim 1 wherein the monomers of the imbibing step e) comprises crosslinking monomers.

### Claim 14 (depends on 1)

The method of claim 1 wherein the copolymer, prior to crosslinking, is of the formula:
-(MPI)k-(MHydrophil)l-(MFG)m-(Mother)i-, where
(MPI)k are photoinitiator functional monomer units having “k” polymerized monomer units, where k is at least one
(MHydrophil)l are hydrophilic monomer units having “l” polymerized monomer units,
(MFG)m are monomer units having crosslinkable functional groups and having “m” polymerized monomer units,
(Mother)i are other monomer units, having “i” polymerized monomer units, where “i” may be zero.

### Claim 15 (depends on 6)

The method of claim 6 wherein stoichiometry between the amine groups of the crosslinker and the reactive functional groups of the copolymer is 0.1:1 to 1:1.

### Claim 16

A ligand-functionalized substrate represented by the formula:
where
MPI* represents the residue of the MPI monomer units having “f” polymerized monomer units, where f is at least one,
Mcrosslink represent the monomer units derived from the MFG monomer units, having been subsequently crosslinked, and having “g” polymerized monomer units, where g is at least one and (MFG)m are crosslinkable monomer units;
MHydrophil represents hydrophilic monomer units having “h” polymerized monomer units, where h may be zero;
MLigand represents ligand monomer units having “j” polymerized monomer units, where “j” is at least 1
Mother represents other (meth)acryloyl monomer units, where “i” may be zero.