Block copolymers grafted to porous polymer substrates

Abstract

A separation article is provided that can be used to separate complex samples containing materials having different sizes and optionally with different ionic groups. The separation article comprises a plurality of block copolymers grafted to a solid polymeric substrate using a reversible inactivating radical polymerization process. The block copolymer extends away from the surface of the solid porous polymeric substrate. The block has an outer block (i.e., a second polymer block) providing dimensional or steric exclusion and an inner block (i.e., a first block) having an acidic group or salt thereof, a basic group or salt thereof, or a combination thereof, the internal block may be bound to a compound having a complementary group and being sufficiently small to exclude the second polymer block by size or space. The separation article can be used, for example, for separating biological material in a sample.

Description

Summary of the invention

[0001] Provided are a separation article, a method for making the separation article, and a method for separating various materials (e.g., biomaterials). The separation article includes a block copolymer grafted to a solid porous polymer substrate. The block copolymer has a second polymer block that provides size exclusion and a first polymer block that can bind to an acidic or basic group on a biomaterial that is not excluded by the second polymer block.

[0002] In a first aspect, a separation article is provided, the separation article comprising (1) a porous polymer substrate, the porous polymer substrate being solid and (2) a plurality of block copolymer chains grafted to the solid porous polymer substrate and extending away from the surface of the solid porous polymer substrate. The block copolymer chain comprises (a) a first polymer block covalently attached to the porous polymer substrate and (b) a second polymer block covalently bonded to the first polymer block, wherein the first polymer block is located between the second polymer block and the porous polymer substrate. The first polymer block comprises a first monomer unit, the first monomer unit being an acidic monomer unit comprising an acidic group or a salt thereof, a basic monomer unit comprising a basic group or a salt thereof, or a combination thereof. The second polymer block comprises a monomer unit containing a polyether.

[0003] In a second aspect, a method for making a separation product is provided. The separation product includes a porous polymer substrate that is solid and a plurality of block copolymers grafted to the porous polymer substrate and extending away from the surface of the porous polymer substrate. The method includes providing the porous polymer substrate and using a reversible deactivation free radical polymerization method to graft the plurality of first polymer blocks to the porous polymer substrate, wherein the first polymer block is covalently bonded to the porous polymer substrate. The first polymer block is the reaction product of a first polymerizable composition, and the first polymerizable composition includes 1) an acidic monomer comprising an ethylenically unsaturated group and an acid group or a salt thereof, 2) a basic monomer comprising an ethylenically unsaturated group and a basic group or a salt thereof, or 3) a combination thereof. The method also includes forming a plurality of second polymer blocks using a reversible deactivation free radical polymerization method, wherein the second polymer block is covalently bonded to the first polymer block, and wherein the first polymer block is located between the porous polymer substrate and the second polymer block. The second polymer block is the reaction product of a second polymerizable composition comprising a polyether-containing monomer comprising at least one ethylenically unsaturated group and a polyether group.

[0004] In a third aspect, a method for separating a mixture of materials having different sizes and optionally different ionic charges is provided. The method includes preparing or providing a separation article, the separation article comprising a solid porous polymer substrate and a plurality of block copolymers grafted to the porous polymer substrate using a reversible deactivation free radical polymerization method, wherein the block copolymer extends away from the surface of the porous polymer substrate. The block copolymer comprises 1) a first polymer block covalently attached to a solid porous polymer substrate and 2) a second polymer block covalently bonded to the first polymer block, wherein the first polymer block is located between the second polymer block and the porous polymer substrate. The first polymer block comprises a first monomer unit having a binding group, the binding group being an acid group or its salt, a basic group or its salt, or a combination thereof for interacting with a material having a complementary group. The second polymer block comprises a monomer unit containing a polyether. The method also includes passing a mixture of materials through the separation article, wherein the second polymer block separates a mixture of materials based on size or steric exclusion and allows only a portion of the material to contact with the acid group, the basic group, or their salt of the first polymer block. DETAILED DESCRIPTION

[0005] A separation product is provided, which can be used to separate complex samples containing a mixture of materials with different sizes and optionally different ionic charges. The separation product comprises a plurality of block copolymers grafted onto a solid porous polymer substrate using a reversible inactivation free radical polymerization method. The block copolymer extends away from the surface of the porous polymer substrate. The block copolymer has an external polymer block (i.e., a second polymer block) providing size or spatial exclusion and an internal polymer block (i.e., a first polymer block) having an acidic group or its salt, a basic group or its salt, or a combination thereof, which can be combined with a material having a complementary group and being small enough to exclude the second polymer block by size or space. The separation product can be used, for example, for separating biological materials in a sample.

[0006] As used herein, the terms "a," "an," "the," and "at least one" are used interchangeably.

[0007] The term "and / or" means either or both. For example, "A and / or B" means A alone, B alone, or both A and B.

[0008] The term "alkyl" refers to a monovalent group that is a free radical of an alkane. The alkyl group may have 1 to 32 carbon atoms, 1 to 20 carbon atoms, 1 to 12 carbon atoms, 1 to 10 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms. The alkyl group may be straight chain, branched, cyclic, or a combination thereof. A straight chain alkyl group has at least one carbon atom, while a cyclic alkyl group has at least 3 carbon atoms, and a branched chain alkyl group has at least 2 carbon atoms.

[0009] The term "alkylene" refers to a divalent group that is a free radical of an alkane. The alkylene group may have 1 to 32 carbon atoms, 1 to 20 carbon atoms, 1 to 12 carbon atoms, 1 to 10 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms. The alkylene group may be straight chain, branched, cyclic, or a combination thereof. A straight chain alkylene group has at least one carbon atom, while a cyclic alkylene group has at least 3 carbon atoms, and a branched chain alkylene group has at least 2 carbon atoms.

[0010] The term "alkoxy" refers to a radical of the formula -OR a A monovalent group, where R a is an alkyl group as defined above.

[0011] The term "alkenyl" refers to a monovalent group as a free radical of an alkene, which is a hydrocarbon compound with at least one carbon-carbon double bond. In some embodiments, the alkenyl has a single carbon-carbon double bond. In some more specific embodiments, the alkenyl has an olefinically unsaturated group (carbon-carbon double bond between the last two carbon atoms in the chain). The alkenyl can be straight chain, branched or cyclic. The alkenyl typically has at least 2, at least 3, at least 4 or at least 5 carbon atoms, and can have up to 32 carbon atoms, up to 24 carbon atoms, up to 20 carbon atoms, up to 12 carbon atoms, up to 10 carbon atoms or up to 5 carbon atoms.

[0012] The term "alkenyloxy" refers to a radical of the formula -OR b A monovalent group, where R b is alkenyl as defined above.

[0013] The term "aryl" refers to a monovalent group that is a free radical of an aromatic carbocyclic compound. The aryl group has at least one aromatic carbocyclic ring and can have 1 to 3 optional rings that are connected to or fused to the aromatic carbocyclic ring. The additional rings can be aromatic, aliphatic or a combination thereof. The aryl group typically has 5 to 20 carbon atoms or 6 to 10 carbon atoms.

[0014] The term "arylene" refers to a divalent group that is a free radical of an aromatic carbocyclic compound. The arylene group has at least one aromatic carbocyclic ring and can have 1 to 3 optional rings that are connected to or fused to the aromatic carbocyclic ring. The additional rings can be aromatic, aliphatic or a combination thereof. The arylene group typically has 5 to 20 carbon atoms or 6 to 10 carbon atoms.

[0015] The term "aralkyl" refers to an alkyl group substituted with at least one aryl group. That is, the aralkyl group has the formula -R d -Ar, where R d Ar is an alkylene group and Ar is an aryl group as defined above. The aralkyl group contains 6 to 40 carbon atoms. The aralkyl group usually contains an alkylene group with 1 to 20 carbon atoms or 1 to 10 carbon atoms and an aryl group with 5 to 20 carbon atoms or 6 to 10 carbon atoms.

[0016] The term "aralkylene" refers to an alkylene group substituted with at least one aryl group.

[0017] The term "aralkyloxy" refers to a radical having the formula -OR d -Ar monovalent group, where R d and Ar are the same as defined above for the aralkyl group.

[0018] The term "alkaryl" refers to an aryl group substituted with at least one alkyl group. That is, the alkaryl group has the formula -Ar 1 -R a , where Ar 1 R is an arylene group and R is an alkyl group. The alkaryl group contains 6 to 40 carbon atoms. The alkaryl group usually contains an arylene group having 5 to 20 carbon atoms or 6 to 10 carbon atoms and an alkyl group having 1 to 20 carbon atoms or 1 to 10 carbon atoms.

[0019] The terms "boronic acid group" and "boronato" are used interchangeably to refer to a group of formula -B(OH)2. The boronic acid group may be present in the form of a salt with a cationic counterion.

[0020] The terms "carboxylic acid group" and "carboxy" are used interchangeably to refer to a group of formula -C(=O)-OH. The carboxylic acid group may be present in the form of a salt with a cationic counterion.

[0021] The term "iniferter" is used to refer to a group that can act as a free radical initiator, chain transfer agent, or free radical chain terminator under appropriate conditions. Iniferters activated by UV radiation may be referred to as "photoiniferters." The iniferters described herein are generally suitable for use in reversible addition-fragmentation chain transfer (RAFT) polymerization processes and may be referred to as RAFT agents.

[0022] The term "hydrocarbyl" refers to a monovalent group of a hydrocarbon. The hydrocarbyl group may be saturated, partially unsaturated or unsaturated and may have up to 20 carbon atoms, up to 10 carbon atoms, up to 6 carbon atoms or up to 4 carbon atoms. It typically has at least 1 carbon atom or at least 2 carbon atoms. The hydrocarbyl group is typically an alkyl, aryl, aralkyl or alkaryl group.

[0023] The term "alkylene" refers to a divalent radical of a hydrocarbon. The alkylene group may be saturated, partially unsaturated or unsaturated and may have up to 40 carbon atoms, up to 20 carbon atoms, up to 10 carbon atoms, up to 6 carbon atoms or up to 4 carbon atoms. It typically has at least 1 carbon atom or at least 2 carbon atoms. The alkyl group is typically an alkylene, arylene, aralkylene or alkarylene.

[0024] The term "linking atom" refers to an atom in a chain (rather than an atom of a chain substituent).

[0025] The term "linked heteroatom" refers to a heteroatom that replaces one or more carbon atoms in a carbon chain. The heteroatom is typically oxygen, sulfur or nitrogen.

[0026] The term "fluid" refers to liquids and / or gases.

[0027] The term "grafting density" refers to the number of millimoles of monomer units grafted to a substrate per gram. The number of millimoles is calculated by dividing the mass gain by the molecular weight of the monomer and multiplying by 1000. The value is then normalized by dividing by the initial mass of the substrate in grams. The grafting density is expressed as the number of millimoles of monomer units grafted per gram of substrate (mmol / g). For clarity, the grafted material is typically a polymeric material containing multiple monomer units.

[0028] The term "heteroatom" means an atom other than carbon or hydrogen. The heteroatom is typically sulfur, nitrogen or oxygen.

[0029] The term "heteroalkyl" refers to an alkyl group in which at least one, but not all, of the linked carbon atoms are replaced with a heteroatom selected from oxygen (-O-), sulfur (-S-), and nitrogen (eg, -NH-).

[0030] The term "(hetero)hydrocarbyl" refers to hydrocarbyl, heterohydrocarbyl, or both.

[0031] The term "heteroalkylene" refers to an alkylene group in which at least one, but not all, of the linking carbon atoms are replaced with a heteroatom selected from oxygen (-O-), sulfur (-S-), and nitrogen (eg, -NH-).

[0032] The term "(hetero)alkylene" refers to alkylene, heteroalkylene, or both.

[0033] The term "heteroaralkylene" refers to an aralkylene group having a heteroatom in the aryl group. In other words, it is an alkylene group bonded to a heteroaryl group, wherein the heteroaryl group is an aryl group in which one of the ring carbon atoms is replaced by a heteroatom selected from oxygen (-O-), sulfur (-S-) and nitrogen (e.g., -NH-).

[0034] The term "hydrogen bond acceptor" refers to a heteroatom selected from oxygen, nitrogen and sulfur having a lone electron pair. The hydrogen bond acceptor is typically a carbonyl, carbonyloxy or ether oxygen.

[0035] The term "hydrogen bond donor" refers to a moiety consisting of a hydrogen atom covalently bonded to a heteroatom selected from oxygen, nitrogen and sulfur. The hydrogen bond donor is typically an imino, thio or hydroxyl group.

[0036] The term "hydrogen bonding moiety" means a moiety that includes at least one hydrogen bond donor and at least one hydrogen bond acceptor.

[0037] The term "iminocarbonylimino" refers to a divalent group or moiety of the formula -N(R e )-C(=O)-N(R e )-, where each R e R is independently hydrogen, alkyl (e.g., selected from alkyl groups having one to four carbon atoms), or aryl. Typically one or two R e The radical is hydrogen.

[0038] The term "imidothiocarbonylimido" refers to a divalent group or moiety of the formula -N(R e )-C(=S)-N(R e )-, where each R e R is independently hydrogen, alkyl (e.g., selected from alkyl groups having one to four carbon atoms), or aryl. Typically one or two R e The radical is hydrogen.

[0039] The term "isocyanato" refers to a group of the formula -N=C=O.

[0040] The term "modified substrate" refers to a polymer substrate (eg, a porous polymer substrate) having a plurality of covalently attached thiocarbonylthio-containing groups or semi-pinacol-containing groups.

[0041] The term "oxycarbonylimino" refers to a divalent group or moiety of the formula -OC(=O)-N(R e )-, where R e is hydrogen, alkyl (e.g., selected from alkyl groups having one to four carbon atoms), or aryl. e The radical is hydrogen.

[0042] The term "oxythiocarbonylimino" refers to a divalent radical or moiety of the formula -OC(=S)-N(R e )-, where R e is hydrogen, alkyl (e.g., selected from alkyl groups having one to four carbon atoms), or aryl. e The radical is hydrogen.

[0043] The term "ethylenically unsaturated" refers to a group of the formula -CY=CH2, where Y is hydrogen or a hydrocarbyl group (eg, alkyl or aryl).

[0044] The terms "phosphonic acid group" and "phosphono" interchangeably refer to a group of formula -PO3H2, where the group is not attached to an oxygen atom (it is usually attached to a carbon atom). The phosphonic acid group may exist as a salt with a cationic counterion.

[0045] The terms "phosphate group" and "phosphato" refer interchangeably to a group of formula -OPO3H2. A phosphate group may exist as a salt with a cationic counterion.

[0046] The terms "polymer" and "polymer material" are used interchangeably and refer to a material formed by reacting one or more monomers. The term includes homopolymers, copolymers, terpolymers, and the like. Likewise, the terms "polymerization" and "polymerizing" refer to the process of making a polymer material, which may be a homopolymer, copolymer, terpolymer, and the like.

[0047] The term "reversible deactivation radical polymerization" or "RDRP" refers to a polymerization process in which there is rapid and reversible activation and deactivation of a growth chain. Although a variety of RDRP techniques are available, the most common of these techniques are: a) stable radical-mediated polymerization (e.g., nitroxide-mediated polymerization or NMP), b) atom transfer radical polymerization (or ATRP), and c) reversible addition-fragmentation chain transfer polymerization (or RAFT). For a review of the industrial utilization of these methods, see M. Destarac, Polymer Chemistry, 2018, Vol. 9, No. 40, pp. 4947-4967. As used herein, a method mediated by a group containing semipinacol is considered to be a RDRP polymerization method.

[0048] The term "semipinacol" refers to a monovalent group covalently attached to a substrate. A semipinacol group typically has two aromatic rings connected by a carbon atom that is also bonded to the substrate and a hydroxyl group. A semipinacol group typically has formula (A) or formula (B).

[0049]

[0050] Each R x and R y The group X is hydrogen, alkyl (such as those having 1 to 4 carbon atoms), hydroxyl, alkoxy (such as those having 1 to 4 carbon atoms), halo, sulfo or sulfoalkyleneoxy (such as those having 1 to 4 carbon atoms). The group X is a single bond, an alkylene group having 1 to 3 carbon atoms, or a heteroatom (such as -O- or -S-). The asterisk (*) shows the attachment site of the semi-pinacol group to the substrate. The semi-pinacol group is typically formed by UV excitation of a Type II photoinitiator, which forms a semi-pinacol radical by abstracting hydrogen from the substrate to form a treated substrate radical. The two radicals then combine to covalently attach the semi-pinacol group to the substrate.

[0051] The terms "sulfonic acid group" and "sulfono" interchangeably refer to a group of formula -SO3H, where the group is not attached to an oxygen atom (it is usually attached to a carbon atom). The sulfonic acid group may exist as a salt with a cationic counterion.

[0052] The terms "sulfate group" and "sulfato" refer interchangeably to a group of formula -OSO3H. The sulfate group may exist as a salt with a cationic counterion.

[0053] The term "thiocarbonylimido" refers to a radical of the formula -C(=S)NR e - a divalent group or moiety, wherein R e is hydrogen, alkyl (eg, selected from alkyl groups having one to four carbon atoms) or aryl. The group R e Typically hydrogen.

[0054] The term "thiocarbonylthio" refers to the divalent group -SC(=S)-.

[0055] The term "treated substrate" refers to a polymeric substrate having a plurality of free radicals available to react with another compound, such as a thiocarbonylthio-containing compound or a semi-pinacol radical.

[0056] The terms "in a range of or in the range of" are used interchangeably to refer to all values ​​within the range plus the end value of the range.

[0057] The separation product includes a porous polymer that is solid and a plurality of block copolymers grafted to the porous polymer substrate and extending away from the surface of the porous polymer substrate. The block copolymer generally comprises a first polymer block covalently attached to the porous polymer substrate and a second polymer block covalently attached to the first polymer block, wherein the first polymer block is located between the porous polymer substrate and the second polymer block. The first polymer block has a plurality of acidic monomer units or salts thereof, basic monomer units or salts thereof, or combinations thereof, and the second polymer block has a plurality of monomer units containing polyethers that may be optionally cross-linked.

[0058] Separation products can be prepared by grafting multiple first polymer blocks to a solid porous polymer substrate using a reversible deactivation free radical polymerization method, wherein the first polymer block is covalently bonded to the porous polymer substrate. In most embodiments, the first polymer block is directly bonded to the carbon atoms in the main chain of the polymer material of the porous polymer substrate. The first polymer block is the reaction product of the first polymerizable composition, and the first polymerizable composition includes 1) an acidic monomer containing an ethylenically unsaturated group and an acid group or its salt, 2) a basic monomer containing an ethylenically unsaturated group and a basic group or its salt, or 3) a combination thereof. Multiple second polymer blocks are covalently bonded to the first polymer block using a reversible deactivation free radical polymerization method. The second polymer block is the reaction product of a second polymerizable composition containing a polyether monomer, and the polyether monomer contains at least one ethylenically unsaturated group and a polyether group. The first polymer block is located between the second polymer block and the solid porous polymer substrate. Although the additional polymer block can be covalently attached to the second polymer block, the separation product generally has a plurality of attached diblock copolymers.

[0059] Porous polymer substrates

[0060] The separation article has a porous polymer substrate that is solid. The term "solid" with respect to the porous polymer substrate means that the substrate is not liquid and does not dissolve in solution. The pores of the porous polymer substrate may have any desired average size. In some embodiments, the pores are macropores, mesopores, micropores, or mixtures thereof. As used herein, the term "macroporous" refers to a polymer substrate having pores greater than 50 nanometers in diameter, the term "mesoporous" refers to a polymer substrate having pores in the range of 2 nanometers to 50 nanometers in diameter, and the term "microporous" refers to a material having pores less than 2 nanometers in diameter.

[0061] The terms "solid porous polymeric substrate," "porous polymeric substrate," "polymeric substrate," "substrate" and similar variations are used interchangeably herein.

[0062] The porous polymer substrate can have any desired size, shape and form. For example, the porous polymer substrate can be in the form of particles, fibers, films, nonwoven webs, woven webs, membranes, sponges or sheets. In some examples, the polymer substrate is a porous membrane or a porous nonwoven web. In order to prepare large separation products or many separation products and for ease of manufacture, the polymer substrate can be in the form of a roll or formed by a roll, such as the roll of a film, nonwoven webs, woven webs, membranes, sponges or sheets. This allows the use of roll-to-roll processing to prepare separation products. The porous polymer substrate can include a monolayer or multilayer identical or different polymeric material.

[0063] The porous polymer substrate is typically formed from a thermoplastic material. Suitable thermoplastics include, but are not limited to, polyolefins, poly(isoprene), poly(butadiene), fluorinated polymers, chlorinated polymers, polyamides, polyimides, polyethers, poly(ethersulfones), poly(sulfones), poly(vinyl acetate) and copolymers thereof such as poly(ethylene)-co-poly(vinyl acetate), polyesters such as poly(lactic acid), poly(vinyl alcohol) and copolymers thereof such as poly(ethylene)-co-poly(vinyl alcohol), poly(vinyl esters), poly(vinyl ethers), poly(carbonates), polyurethanes, poly((meth)acrylates) and copolymers thereof, and combinations thereof.

[0064] Suitable polyolefins for use in the porous polymer substrate include poly(ethylene), poly(propylene), poly(1-butene), copolymers of ethylene and propylene, alpha-olefin copolymers (such as copolymers of ethylene or propylene with 1-butene, 1-hexene, 1-octene and 1-decene), poly(ethylene-co-1-butene), poly(ethylene-co-1-butene-co-1-hexene), poly(butadiene) and copolymers thereof, and combinations thereof.

[0065] Suitable fluorinated polymers for the porous polymer substrate include poly(vinyl fluoride), poly(vinylidene fluoride), vinylidene fluoride copolymers such as poly(vinylidene fluoride-co-hexafluoropropylene), chlorotrifluoroethylene copolymers such as poly(ethylene-co-chlorotrifluoroethylene), and combinations thereof.

[0066] Suitable polyamides for the porous polymer substrate include various nylon compositions such as, for example, poly(imidoadipimidohexamethylene), poly(imidoadipimidodecamethylene), polycaprolactam, and combinations thereof. Suitable polyimides include poly(pyromellitimide) and combinations thereof.

[0067] Suitable poly(ethersulfones) for use in the porous polymer substrate include poly(diphenyl ether sulfone), poly(diphenyl sulfone-co-diphenyl ether sulfone), and combinations thereof.

[0068] Suitable vinyl acetate copolymers for use in the porous polymeric substrate include copolymers of ethylene and vinyl acetate and terpolymers of vinyl acetate, vinyl alcohol and ethylene.

[0069] In some embodiments, the porous polymer substrate is a porous membrane having an average pore size (average longest diameter of the pores) generally greater than 0.1 microns to minimize size exclusion separation, minimize diffusion constraints and maximize surface area and separation. Typically, the average pore size can be in the range of 0.1 microns to 10 microns. For example, the average pore size is at least 0.2 microns, at least 0.4 microns, at least 0.6 microns, or at least 0.8 microns, and up to 8 microns, up to 6 microns, up to 4 microns, or up to 2 microns.

[0070] The porous polymer substrate can be a macroporous membrane, such as a thermally induced phase separation (TIPS) membrane. TIPS membranes are generally prepared by forming a solution of a thermoplastic material and a second material having a melting point higher than the thermoplastic material. After cooling, the thermoplastic material crystallizes and separates from the second material. The crystallized material is generally stretched. The second material is optionally removed before or after stretching. Macroporous membranes are further described in U.S. Patents No. 4,539,256 (Shipman), No. 4726989 (Mrozinski), No. 4867881 (Kinzer), No. 5120594 (Mrozinski), No. 5260360 (Mrozinski) and No. 5962544 (Waller, Jr.). Some exemplary TIPS membranes include poly(vinylidene fluoride) (PVDF), polyolefins such as poly(ethylene) or poly(propylene), vinyl-containing polymers or copolymers such as ethylene-vinyl alcohol copolymers and butadiene-containing polymers or copolymers, and (meth)acrylate-containing polymers or copolymers. TIPS membranes including PVDF are further described in U.S. Pat. No. 7,338,692 (Smith et al.).

[0071] In some embodiments, the porous polymer substrate may include a nylon macroporous film or sheet (e.g., a macroporous membrane), such as those described in U.S. Pat. Nos. 6,056,529 (Meyering et al.), 6,267,916 (Meyering et al.), 6,413,070 (Meyering et al.), 6,776,940 (Meyering et al.), 3,876,738 (Marinaccio et al.), 3,928,517 (Knight et al.), 4,707,265 (Barnes, Jr. et al.), and 5,458,782 (Hou et al.).

[0072] In other embodiments, the porous polymer substrate can be a nonwoven web, which can include a nonwoven web made by any known method for producing a nonwoven web. As used herein, the term "nonwoven web" refers to a fabric having a structure of individual fibers or filaments that are randomly and / or unidirectionally interlaced in a mat-like manner.

[0073] For example, fiber nonwoven webs can be made by wet-laid, carded, air-laid, jet-spun, spunbond or melt-blown technology or their combination. Spunbond fibers are usually small diameter fibers, which are formed by extruding a plurality of tiny, usually circular capillaries of a spinneret as filaments from a molten thermoplastic polymer, wherein the diameter of the extruded fibers is rapidly reduced. Meltblown fibers are usually formed as follows: molten thermoplastic material is extruded into a high speed, usually heated gas (e.g., air) stream in the form of a melt line or filament by a plurality of tiny, usually circular die capillaries, and the gas stream thins the filaments of the molten thermoplastic material to reduce their diameter. Then, meltblown fibers are carried by a high-speed gas stream and deposited on a collecting surface to form a web of randomly dispersed meltblown fibers. Any nonwoven web can be made of a single type of fiber or of two or more fibers having different types and / or thicknesses of thermoplastic polymers.

[0074] Further details of methods of making useful nonwoven webs are described in Wente, "Superfine Thermoplastic Fibers," Indus. Eng. Chem., 48, 1342 (1956) and Wente et al., "Manufacture of Superfine Organic Fibers," Naval Research Laboratories Report No. 4364 (1954).

[0075] The nonwoven web substrate may also optionally include one or more layers of scrim. For example, any one or two major surfaces of the nonwoven web may also optionally include a scrim layer. Scrim (usually a woven or nonwoven reinforcement layer made of fiber) is included to provide strength for the nonwoven web. Suitable scrim materials include but are not limited to nylon, polyester, fiberglass, polyethylene, polypropylene, etc. The average thickness of the scrim can be variable, but the scope is typically about 25 microns to about 100 microns, preferably about 25 microns to about 50 microns. The scrim layer may optionally be bonded to the nonwoven article. A variety of adhesive materials can be used for bonding scrim to nonwoven material. Alternatively, scrim can be thermally bonded to the nonwoven web.

[0076] The porosity of nonwoven substrates is usually characterized by properties such as fiber diameter, or basis weight, or solidity, rather than by pore size. The fibers of nonwoven substrates are usually microfibers having an effective fiber diameter of at least 0.5 micron, 1 micron, 2 microns, or even 4 microns and at most 15 microns, 10 microns, 8 microns, or even 6 microns, as calculated according to the method listed in the following document: Davies, CN, "The Separation of Airborne Dust and Particles," Institution of Mechanical Engineers, London, Proceedings 1B, 1952. Nonwoven substrates preferably have a porosity of at least 5 g / m 2 , 10g / m 2 , 20g / m 2 Or even 50g / m 2 ; and up to 800g / m 2 , 600g / m 2 , 400g / m 2 , 200g / m 2 Or even 100g / m 2 The minimum tensile strength of a nonwoven web is about 4.0 Newtons. It is generally believed that the tensile strength of a nonwoven substrate is lower in the machine direction than in the cross-web direction due to better fiber bonding and entanglement in the latter.

[0077] Nonwoven web bulk is measured by Solidity, a parameter that defines the solid fraction in the web volume. Lower Solidity values ​​indicate greater web bulk. Solidity (α) is a unitless fraction, usually expressed as: α = m f ÷ρ f ×L 非织造物 , where m f is the fiber mass per sample surface area, ρ f is the fiber density, and L 非织造物 L is the thickness of the nonwoven. The density used herein refers to the nonwoven substrate itself rather than the functionalized nonwoven substrate. When the nonwoven substrate contains a mixture of two or more fibers, the same L is used. 非织造物 The individual stiffness of each fiber is determined and these individual stiffnesses are added together to obtain the stiffness of the web, a.

[0078] Grafting the first polymer block to the porous polymer substrate

[0079] Multiple block copolymers are grafted onto the surface of a porous polymer substrate using reversible deactivation radical polymerization (RDRP), which is sometimes referred to as controlled radical polymerization. Using this polymerization method, free radical polymerization can occur under conditions that simulate a living polymerization method, with the significance of minimizing termination reactions, such as, for example, described in N. Corrigan et al. in the article Progress in Polymer Science, 2020, 111, 101311. Using RDRP, the polymer structure, microstructure, molecular weight, and molecular weight distribution of solution polymerization reactions can generally be controlled.

[0080] The RDRP method can be used to covalently modify porous substrates. Attachment of the RDRP initiator to the substrate allows for surface-initiated RDRP (SI-RDRP), or graft polymerization from the surface of the substrate (see the above-mentioned Progress in PolymerScience article). Attaching RDRP initiators to porous polymer substrates is generally quite difficult, involves multiple synthesis steps, and can be very dependent on the substrate. The porous polymer substrate generally must have functional groups to which the RDRP initiator can be covalently attached, typically by a condensation reaction. For example, carboxylic acid-containing -RDRP reagents can be covalently attached to cellulose membranes or fibers by esterification to cellulose hydroxyl groups. If the appropriate functional group is not available, the substrate must first be chemically modified to introduce the functional group.

[0081] A simple, industrially feasible method for attaching RDRP reagents directly to solid polymer substrates without chemical modification is described in U.S. Patent Application Publication 2021 / 0095088 (Rasmussen et al.). More specifically, multiple thiocarbonylthio-containing groups can be directly and covalently bonded to a solid porous polymer substrate. The thiocarbonylthio-containing groups are generally directly and covalently attached to carbon atoms in the main chain of the polymer material in the polymer substrate. These modified substrates with directly attached RDRP reagents (e.g., thiocarbonylthio-containing groups) can be used as RDRP initiators or photoinitiators-transfer-terminators. As shown in U.S. Patent Application Publication 2020 / 0368694 (Rasmussen et al.), this method allows a variety of free radical polymerizable monomers to be grafted to a substrate. The method is referred to herein as "grafting method 1" and is further described below.

[0082] In another simple, industrially feasible method, the RDRP reagent is combined with the monomer in solution. Unlike grafting method 1, there is no separate step of forming a modified substrate with multiple directly and covalently attached thiocarbonylsulfide-containing groups before the monomer polymerization. Instead, the thiocarbonylsulfide-containing compound and the type II photoinitiator are combined with the monomer in solution. The solution is coated on the substrate, and the coated substrate is then subjected to actinic radiation (e.g., UV irradiation). If a photosensitive substrate is used, the type II photoinitiator is optional. This method is referred to as "grafting method 2" in this article and is further described below.

[0083] In a modification of "Grafting Method 2", the substrate is converted to a treated substrate via electron beam irradiation, and the treated substrate is subsequently mixed with a solution comprising monomers and a RDRP agent.

[0084] The thiocarbonylthio-containing compounds and thiocarbonylthio-containing groups can be any of those compounds and agents known to be useful as RAFT agents, such as those described in Moad et al., Aust. J. Chem, 2005, 58, 279-410. Suitable RAFT agents are described in this reference as those of the formula RSC(=S)-Z. Wherein Z is selected to activate or deactivate the thiocarbonyl double bond to alter the stability of the intermediate free radical, and R is a free radical leaving group. The reference states that the RAFT agent should have a reactive C=S double bond, the SR bond should be easily broken (i.e., the bond should be weak) and not produce side reactions, and the expelled free radical (R*) should effectively reinitiate polymerization.

[0085] While any known RAFT agent may be used herein, including all those described in the Moad et al. reference above, particularly grafting method 2, it may be advantageous to select a RAFT agent having the formula -SC(=S)-R 1 The group R in the thiocarbonylthio group is 1 Typically, they are selected to be alkoxy, aralkyloxy, alkenyloxy or –N(R 4 )2. Each R 4 is an alkyl group, or two adjacent R 4The group combines with the nitrogen to which they are both attached to form a first heterocyclic ring having 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, the first heterocyclic ring being saturated or unsaturated and optionally fused to one or more second rings, the second ring being a carbocyclic or heterocyclic ring. Although such thiocarbonylthio-containing compounds may be advantageous when using either grafting method 1 or grafting method 2, these compounds are particularly advantageous when using grafting method 1. The thiocarbonyl-containing groups selected for grafting method 1 are generally not those groups that are typical reagents for reversible addition-fragmentation chain transfer (RAFT) polymerization reactions.

[0086] For R 1 Suitable alkoxy groups typically have at least 1 carbon atom, at least 2 carbon atoms, at least 3 carbon atoms, or at least 4 carbon atoms, and can have up to 20 carbon atoms, up to 18 carbon atoms, up to 16 carbon atoms, up to 12 carbon atoms, or up to 10 carbon atoms. Some exemplary alkoxy groups have 1 to 20 carbon atoms, 1 to 10 carbon atoms, 2 to 10 carbon atoms, 1 to 6 carbon atoms, 2 to 6 carbon atoms, or 1 to 4 carbon atoms.

[0087] For R 1 Suitable alkenyloxy groups typically have at least 2 carbon atoms, at least 3 carbon atoms, or at least 4 carbon atoms, and may have up to 20 carbon atoms, up to 18 carbon atoms, up to 16 carbon atoms, up to 12 carbon atoms, or up to 10 carbon atoms. Some exemplary alkenyloxy groups have 2 to 20 carbon atoms, 2 to 10 carbon atoms, 2 to 6 carbon atoms, or 2 to 4 carbon atoms.

[0088] For R 1 Suitable aralkyloxy groups typically contain an alkylene group having 1 to 10 carbon atoms, 1 to 6 carbon atoms or 1 to 4 carbon atoms and an aryl group having 5 to 12 carbon atoms, 6 to 12 carbon atoms or 6 to 10 carbon atoms. The aryl group in the aralkyloxy group is typically phenyl.

[0089] In some embodiments of thiocarbonylthio-containing groups, R 1 With the formula –N(R 4 )2, where each R 4 is an alkyl group or two adjacent R 4 The group combines with the nitrogen to which they are both attached to form a first heterocyclic ring having 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur and 2 to 5 carbon atoms, which first heterocyclic ring is saturated or unsaturated (e.g., partially or fully unsaturated) and is optionally fused to one or more second rings, which are carbocyclic or heterocyclic.

[0090] Suitable alkyl groups R 4Typically has at least 1 carbon atom, at least 2 carbon atoms, at least 3 carbon atoms, or at least 4 carbon atoms, and can have up to 20 carbon atoms, up to 18 carbon atoms, up to 16 carbon atoms, up to 12 carbon atoms, or up to 10 carbon atoms. Some exemplary alkyl groups have 1 to 20 carbon atoms, 1 to 10 carbon atoms, 2 to 10 carbon atoms, 1 to 6 carbon atoms, 2 to 6 carbon atoms, or 1 to 4 carbon atoms.

[0091] When the formula –N(R 4 )2When forming the first heterocyclic ring, the heterocyclic ring generally has a first ring structure containing 5 to 7 ring members or 5 to 6 ring members and containing 1 to 3 heteroatoms or 1 to 2 heteroatoms in the ring. The ring members that are not heteroatoms are carbon. If there is one heteroatom in the first ring structure, the heteroatom is nitrogen. If there are two or three heteroatoms in the first ring structure, one heteroatom is nitrogen and any additional heteroatoms are selected from nitrogen, oxygen and sulfur. The first ring can be optionally fused with one or more second ring structures, which are heterocyclic or carbocyclic and are saturated or unsaturated (e.g., partially or completely unsaturated). If the second ring structure is heterocyclic, it generally has 5 to 7 or 5 to 6 ring members and 1, 2 or 3 heteroatoms selected from nitrogen, oxygen and sulfur. If the second ring structure is carbocyclic, it is generally benzene or a saturated ring with 5 or 6 ring members. In many embodiments, the heterocycle has a monocyclic structure having 5 or 6 ring members and 1 or 2 heteroatoms in the ring. Examples of heterocycles include, but are not limited to, morpholino, thiomorpholino, pyrrolidinyl, piperidinyl, homopiperidinyl, indolyl, carbazolyl, imidazolyl, and pyrazolyl.

[0092] Thiocarbonylsulfide-containing compounds generally have the general formula QSC(=S)-R 1 , wherein Q is the remainder of the compound. If the thiocarbonylthio-containing compound contains more than one such group, the group Q may include the formula -SC(=S)-R 1 The second group (or even the third group) of the group R 1 Same as defined above. These thiocarbonylthio-containing compounds are interchangeably referred to as RAFT agents or as iniferters (eg, photoiniferters).

[0093] General formula QSC(=S)-R 1 Some exemplary thiocarbonylthio-containing compounds are symmetrical compounds of formula (I).

[0094] R 1 -C(=S)-SSC(=S)-R 1

[0095] (I)

[0096] The group R in the thiocarbonylthio-containing group 1 Typically, alkoxy, aralkyloxy, alkenyloxy or –N(R 4 )2. Each R 4 is an alkyl group, or two adjacent R 4 The groups combine with the nitrogen to which they are both attached to form a first heterocyclic ring having 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, which is saturated or unsaturated and optionally fused to one or more second rings, which are carbocyclic or heterocyclic.

[0097] Examples of thiocarbonylsulfide-containing compounds of formula (I) include, but are not limited to, dixanthogen (wherein R 1 is ethoxy) and tetraethylthiuram disulfide (where R 1 With the formula –N(R 4 )2, where each R 4 is ethyl).

[0098] General formula QSC(=S)-R 1 Other exemplary thiocarbonylthio-containing compounds have formula (II).

[0099]

[0100] In formula (II), each R 1 is alkoxy, aralkyloxy, alkenyloxy or –N(R 4 )2. For R 1 Suitable alkoxy, aralkyloxy, alkenyloxy and -N(R 4 )2 groups are the same as those described above for the thiocarbonylthio-containing groups. 2 With the formula –(OR 5 ) q -OR 6 or having the formula -C(=O)-XR 7 . Group R 3 is hydrogen, alkyl, aryl, substituted aryl (i.e., aryl substituted with at least one alkyl, alkoxy, or halo), alkaryl, a radical of the formula -C(=O)-OR 8 A group or a group of the formula -C(=O)-N(R 9 )2. Group R 5 is an alkylene group, the group R 6 is an alkyl group, and q is an integer equal to at least 0. The group R 7 is hydrogen, alkyl, aryl, aralkyl or substituted aryl (i.e. aryl substituted by at least one alkyl, alkoxy or halo). 8 and R 9Each is independently an alkyl, aryl, aralkyl or alkaryl group. Group X is a single bond, an oxy group or -NR 10 . Group R 10 is hydrogen, alkyl, aryl, aralkyl, or alkaryl. The compound of formula (II) can be formed using any suitable method, such as those described in U.S. Patent Application Publication No. 2021 / 0095088 (Rasmussen et al.).

[0101] Examples of the thiocarbonylthio-containing compound of formula (II) include, but are not limited to, 1,1-bis(10-undecenyloxythiocarbonylthio)methyl ether, 2,2-bis(isopropoxythiocarbonylthio)-2-methoxy-acetic acid methyl ester, 1,1-bis(isopropoxythiocarbonylthio)methyl methyl ether, 1,1-bis(isopropoxythiocarbonylthio)methyl butyl ether, 1,1-bis(ethoxythiocarbonylthio)methyl butyl ether, 2,2-bis(isopropoxythiocarbonylthio)acetic acid 2-ethylhexyl ester, 2,2-bis(isopropoxythiocarbonylthio)acetic acid methyl ester, 2,2-bis(isopropoxythiocarbonylthio)acetic acid tert-butyl ester, 1,1-bis(isopropoxythiocarbonylthio)acetic acid 2,2-bis(isopropoxythiocarbonylthio)-1-acetophenone and 2,2-bis(isopropoxythiocarbonylthio)-1-(4-bromophenyl)ethanone, 2,2-bis(isopropoxythiocarbonylthio)phenyl acetate, N,N-dibutyl-2,2-bis(isopropoxythiocarbonylthio)acetamide, 1,1-bis(diethylthiocarbamoylthio)methyl butyl ether, 1,1-bis(diethylthiocarbamoylthio)methyl methyl ether, 2-ethylhexyl 2,2-bis(diethylthiocarbamoylthio)acetate, methyl 2,2-bis(diethylthiocarbamoylthio)acetate and octyl 2,2-bis(diethylthiocarbamoylthio)acetate.

[0102] General formula QSC(=S)-R 1 Other exemplary thiocarbonylthio-containing compounds have formula (III).

[0103] R 1 -C(=S)-S-CH2-R 12

[0104] (III)

[0105] Group R 1 The same as defined above for the thiocarbonylthio-containing group. 12 The formula is –C(=O)-OR 13 A group in which each R 13 is hydrogen, alkyl, aryl, aralkyl or alkaryl; formula -C(=O)-R 14 A group in which each R 14are independently alkyl, aryl, aralkyl or alkaryl; formula -OR 15 A group in which R 15 is an alkyl, aryl, aralkyl or alkaryl group; or a group of the formula -C(=O)-N(R 16 )2, wherein R 16 are independently hydrogen or alkyl. 13 When it is hydrogen, R 12 The group may be neutralized so that it is of the formula -C(=O)-O - M + A group wherein M+ is an alkali metal ion, a tetraalkylammonium ion, a trialkylammonium ion or a dialkylammonium ion.

[0106] Specific examples of thiocarbonylthio-containing compounds of formula (III) include, but are not limited to, 2-ethoxythiocarbonylthioacetic acid methyl ester, O-ethyl-(2-amino-2-oxo-ethyl)thiomethylthioate, (isopropoxythiocarbonylthio) methyl octyl ether 2-ethoxythiocarbonylthioacetate, sodium salt. The preparation of these compounds is described in U.S. Patent Application Publication 2021 / 0095088 (Rasmussen et al.).

[0107] Using grafting method 1, thiocarbonylthio-containing groups are grafted onto the surface of a porous polymer substrate to form a modified substrate. The polymer substrate itself generally does not contain thiocarbonylthio-containing groups. That is, the polymer substrate does not include a polymer material having thiocarbonylthio-containing groups (e.g., a (meth)acrylate polymer having pendant thiocarbonylthio-containing groups) and / or does not include a coating containing a polymer material having thiocarbonylthio-containing groups. Alternatively, additional thiocarbonyl-containing groups may be grafted onto the polymer substrate or onto a coating containing thiocarbonylthio-containing groups. Grafting can significantly increase the density of thiocarbonylthio-containing groups on the surface of the polymer substrate.

[0108] The modified substrate has a plurality of thiocarbonylthio-containing groups directly and covalently attached to the surface of the porous polymer substrate. The thiocarbonylthio-containing groups are typically covalently attached to carbon atoms on the polymer backbone of the porous polymer substrate. The thiocarbonylthio-containing groups are covalently attached by reacting with free radicals on the surface of the porous polymer substrate. Various methods can be used to generate free radicals on the surface. A polymer substrate having free radicals available for further reaction is referred to as a "treated substrate".

[0109] In a first method of forming a treated substrate, an absorption solution is prepared. The absorption solution contains a Type II photoinitiator dissolved in a solvent. The solvent may include water and / or an organic solvent. The absorption solution is applied to the surface of a porous polymer substrate as a coating. The coating is then exposed to actinic radiation, which is typically in the ultraviolet region of the electromagnetic spectrum. Upon exposure to actinic radiation, the Type II photoinitiator extracts hydrogen from the porous polymer substrate, resulting in the generation of free radicals on its surface and forming a treated substrate.

[0110] The type II photoinitiator contained in the absorption solution is generally an aromatic ketone compound. Examples include, but are not limited to, benzophenone, carboxybenzophenone (e.g., 3-carboxybenzophenone), 4-(3-sulfopropoxy)benzophenone sodium salt, Michler's ketone, benzil, anthraquinone, 5,12-tetraacenoquinone, acetanthracenequinone, benzo(A)anthraquinone-7,12-dione, 1,4-chrysenequinone, 6,13-pentaacenoquinone, 5,7,12,14-pentacenetetraone, 9-fluorenone, anthrone, xanthone, thioxanthone, 2-(3-sulfopropoxy)thioxanthene-9-one, acridone, dibenzosuberone, acetophenone, and chromone.

[0111] The absorption solution may contain any suitable amount of Type II photoinitiator. The concentration is typically in the range of 0.1 wt % to 20 wt %, based on the total weight of the Type II photoinitiator and the solvent. For example, the concentration may be at least 0.2 wt %, at least 0.5 wt %, at least 1 wt %, at least 2 wt %, or at least 5 wt %, and depending on its solubility in the solvent, may be up to 20 wt %, up to 16 wt %, up to 12 wt %, up to 10 wt %, up to 8 wt %, up to 6 wt %, or up to 5 wt %.

[0112] Suitable solvents for absorption solutions are generally organic solvents, but can be water (when the II type photoinitiator is water-soluble) or a mixture of water and an organic solvent. Suitable aprotic polar organic solvents include esters (e.g., ethyl acetate, propyl acetate), acetic acid alkoxyalkyl esters (e.g., methoxyethyl acetate, ethoxyethyl acetate, propoxyethyl acetate and butoxyethyl acetate), trialkyl phosphates (such as triethyl phosphate), ketones (e.g., acetone, methyl ethyl ketone, methyl propyl ketone and methyl isobutyl ketone), sulfoxides (e.g., dimethyl sulfoxide) and mixtures thereof. Suitable protic polar organic solvents include alcohols (e.g., methanol, ethanol, propanol, isopropanol, n-butanol and tert-butanol), glycols (e.g., ethylene glycol and propylene glycol), glycol ethers (e.g., methoxyethanol, ethoxyethanol, propoxyethanol, butoxyethanol, methyl carbitol and ethyl carbitol) and mixtures thereof. If desired, the solvent can be water (e.g., when the II type photoinitiator is soluble in water) or can be an organic solvent mixed with water. Suitable non-polar organic solvents include alkanes (e.g., pentane, hexane, heptane, isooctane, and decane), aromatic solvents (e.g., benzene, toluene, and xylene), and ethers (e.g., diethyl ether, tetrahydrofuran, dioxane). Although they are useful in some cases, most alcohols and ethers are not preferred as solvents because they tend to undergo interfering hydrogen abstraction reactions.

[0113] Any method of applying the absorbing solution may be used. In many methods, the absorbing solution is applied as a coating to the polymeric substrate. Pressure may optionally be applied to remove air bubbles and excess absorbing solution prior to exposing the treated substrate to actinic radiation. For example, a cover film that is transparent to actinic radiation may be applied such that the absorbing coating is between the polymeric substrate and the cover film. Pressure may be applied to the surface of the cover film opposite the absorbing coating.

[0114] The source of actinic radiation is typically an ultraviolet (UV) light source. The UV light can be provided by a variety of light sources, such as light emitting diodes (LEDs), black lights, medium pressure mercury lamps, or the like, or combinations thereof. Actinic radiation can also be provided by higher intensity light sources, such as those available from Fusion UV Systems Inc. The UV light source can be a relatively low light intensity source, such as a black light, which provides typically 10 mW / cm 2 or less (as measured according to a procedure approved by the National Institute of Standards and Technology, such as with a UVIMAP manufactured by Electronic Instrumentation & Technology, Inc. in Sterling, VA TM UM 365L-S radiometer). Alternatively, a relatively high light intensity source may be used, such as a medium pressure mercury lamp, which provides typically greater than 10 mW / cm2 , preferably at 15mW / cm 2 With 450mW / cm 2 The exposure time can be up to about 30 minutes or even longer.

[0115] In some embodiments, it is preferred to use light that emits a narrow spectrum in the ultraviolet region of the electromagnetic spectrum. These light sources (including LEDs and lasers) can increase the rate of free radical generation, or can increase the polymerization rate while maintaining the reactivity of the polymer material in the subsequent monomer grafting step.

[0116] The thiocarbonylthio-containing compound may be present when the free radicals are generated on the surface of the solid polymer substrate, or may be introduced after the free radicals are generated. If the thiocarbonylthio-containing compound is present during the free radical generation, it is typically dissolved in the absorption solution along with the Type II photoinitiator. If the thiocarbonylthio-containing compound is not present during the free radical generation, the intermediate semi-pinacol radical derived from the Type II photoinitiator via hydrogen abstraction typically couples with the free radicals on the surface of the substrate to form semi-pinacol groups. The thiocarbonylthio-containing compound may be applied as a second coating to the solid polymer substrate containing semi-pinacol groups. The coated substrate is again exposed to actinic radiation to regenerate the substrate free radicals and transfer the thiocarbonylthio-containing groups to the surface of the substrate.

[0117] In another method that can be used to generate free radicals on the surface of a polymer substrate, the substrate itself is photoactive and a Type II photoinitiator is not required. An absorption solution containing a thiocarbonylsulfide-containing compound dissolved in a solvent is prepared. The absorption solution is applied to the surface of the polymer substrate as a coating. The coating is then exposed to actinic radiation, which is generally in the ultraviolet region of the electromagnetic spectrum. Upon exposure to actinic radiation, the polymer substrate absorbs sufficient energy to break some of its covalent bonds, resulting in the generation of free radicals on its surface and forming a treated substrate. The thiocarbonylsulfide-containing groups are then transferred to the substrate. Examples of photoactive polymer substrates include polysulfones and poly(ethersulfones). Other photoactive polymer substrates typically contain aromatic groups, such as, for example, homopolymers and block copolymers of poly(methylphenylsilane) and various polyimides based on benzophenonetetracarboxylic dianhydride.

[0118] In other methods for generating free radicals on the surface of a polymer substrate, ionizing radiation is used instead of a Type II photoinitiator. As used herein, the term "ionizing radiation" refers to radiation having sufficient dose and energy to form free radical reaction sites on the surface and / or in the body of a polymer substrate. If the radiation is absorbed by the polymer substrate and causes the cleavage of chemical bonds in the substrate and the formation of free radicals, the radiation has sufficient energy. The ionizing radiation is typically beta radiation, gamma radiation, electron beam radiation, x-ray radiation, plasma radiation, or other suitable types of electromagnetic radiation. Preferably, the ionizing radiation is carried out in an inert environment to prevent oxygen from reacting with the free radicals.

[0119] In many embodiments of the method, the ionizing radiation is electron beam radiation, gamma ray radiation, x-ray radiation or plasma radiation, because suitable generators are readily available. Electron beam generators are commercially available, such as, for example, the ESI ELECTROCURE EB SYSTEM from Energy Sciences, Inc. (Wilmington, MA, USA) and the BROADBEAM EB PROCESSOR from E-beam Technologies (Davenport, IA, USA). Gamma ray radiation generators using a cobalt-60 high energy source are commercially available from MDS Nordion.

[0120] For any given type of ionizing radiation, the delivered dose can be measured according to ISO / ASTM 52628-13, “Standard Practice for Dosimetry in Radiation Processing,” by ASTM International (West Conshohocken, PA.) A variety of dose rates can be obtained by varying the extractor grid voltage, beam diameter, exposure time, and distance from the irradiation source.

[0121] When ionizing radiation is used, free radicals are generally formed on the surface of the polymer substrate prior to contact with the thiocarbonylthio-containing compound. That is, there is a first step of generating free radicals on the surface of the solid polymer substrate to form a treated substrate and a second step of applying a coating of the thiocarbonylthio-containing compound to the treated substrate. The thiocarbonylthio-containing compound and the polymer substrate having free radicals (i.e., the treated substrate) react to covalently attach the thiocarbonylthio-containing group to the polymer substrate, thereby forming a modified substrate.

[0122] The thiocarbonylthio-containing group is typically attached to (e.g., grafted to) the polymer substrate in the modified substrate. In most cases, the thiocarbonylthio-containing group is directly attached to a carbon atom in the backbone of the polymer material used to form the porous polymer substrate. There is typically no intermediate linking group, such as an ester bond, an amide bond, a carbamate bond, an ether bond, a siloxane bond, etc., between the polymer substrate and the thiocarbonyl-containing group.

[0123] When grafting method 1 is used, the thiocarbonylsulfide-containing compound reacts with the porous polymer substrate (PPS) as shown in reaction scheme A.

[0124] Reaction Scheme A

[0125]

[0126] In reaction scheme A, free radical sites are first generated on a porous polymer substrate (PPS) in reaction I to form PPS*, which represents a porous polymer substrate (i.e., treated substrate) (1) having free radicals. When the thiocarbonylsulfide-containing compound (2) is contacted with the porous polymer substrate (1) having free radicals in reaction II, the group -SC(=S)-R 1 Transfer to the porous polymer substrate via the intermediate sulfur-stabilized free radical (3), which then expels a free radical Q* (5). This results in the transfer of the free radical from the surface of the substrate to the radical Q of the thiocarbonylthio-containing compound. Reaction (II) is indicated to be reversible; however, the reaction is not necessarily reversible provided that a forward reaction can occur. The modified substrate is PPS-SC(=S)-R 1 (4) Although for simplicity, reaction scheme A shows only one -SC(=S)-R attached to the porous polymer substrate. 1 group, but there may be multiple such attachment groups on the modified substrate.

[0127] The group Q in the thiocarbonylthio-containing compound becomes a free radical during the transfer process shown in Reaction Scheme A. The group can be selected so that the SQ bond is weak enough to allow homolysis without any side reactions. In contrast to typical RAFT polymerization reactions, there is no need to select the expelled free radical (Q*) so that it can initiate free radical polymerization reactions because no monomer is present when the thiocarbonylthio-containing group is covalently attached to the porous polymer substrate using grafting method 1. This allows the use of thiocarbonylthio-containing compounds that are not usually used in typical RAFT-controlled free radical polymerization reactions.

[0128] Thus, the expelled radical (Q*) may be a primary radical, as opposed to a secondary or tertiary radical used in typical RAFT polymerizations. The expelled radical may cause a reversal of the transfer reaction (i.e., if the reaction shown in the second step of Reaction Scheme A is reversible, the covalently attached group -SC(=S)-R 1 Can combine with the expelled free radical (Q*) to reform QSC(=S)-R 1 , resulting in the reformation of free radicals on the surface of the substrate). Alternatively, the expelled free radical (Q*) may be deactivated in a variety of free radical termination processes well known in the art, such as by coupling to form QQ.

[0129] The amount of thiocarbonylthio-containing groups attached to the polymer substrate is typically 0.1 micromoles to 100 micromoles per gram of modified substrate (i.e., micromoles per gram of modified substrate). The amount is typically at least 0.2 micromoles per gram, at least 0.5 micromoles per gram, at least 1 micromoles per gram, at least 2 micromoles per gram, at least 4 micromoles per gram, at least 5 micromoles per gram, or at least 10 micromoles per gram, and typically up to 100 micromoles per gram, up to 80 micromoles per gram, up to 60 micromoles per gram, up to 40 micromoles per gram, up to 30 micromoles per gram, or up to 20 micromoles per gram.

[0130] In grafting method 1, the modified substrate PPS-SC(=S)-R was prepared as described above. 1 . A surface of a polymer substrate having multiple covalently attached molecules of the formula -SC(=S)-R 1 The modified substrate containing thiocarbonylthio groups is placed in contact with the first polymerizable composition to form a first reaction mixture. When the first reaction mixture is exposed to actinic radiation such as ultraviolet radiation, RDRP polymerization of the monomers in the first polymerizable composition can occur with the thiocarbonylthio-containing groups acting as RAFT agents (e.g., initiators-transfer terminators or photoinitiators-transfer terminators). This polymerization method is schematically shown in Reaction Scheme B.

[0131] Reaction Scheme B

[0132]

[0133] In reaction scheme B, exposure of the first reaction mixture to actinic radiation (e.g., ultraviolet radiation) results in the formation of free radicals (11) and free radicals (12) containing thiocarbonylthio groups on the surface of the porous polymer substrate, as shown in reaction I. The first monomer (shown as CH2=CR2 in reaction scheme B for simplicity) x R y(13)) reacts with free radicals (11) on the surface of the substrate, resulting in the generation of a second free radical that can react with another monomer. The polymerization of (n+1) moles of the first monomer is shown as free radical (14) in reaction II. At any point in the process, the growing free radical (14) can recombine with the thiocarbonylthio radical (12) to form a terminated chain as shown by the product (15) in reaction III. Upon continued exposure to actinic radiation, free radical (14) and thiocarbonylthio radical (12) can be formed again from product (15). If more monomers are present, the regenerated free radical (14) can undergo further polymerization. Ultimately, the free radical will combine with the thiocarbonylthio radical (12). When exposure to actinic radiation is stopped or monomers are no longer present, the polymerization reaction stops. The product contains multiple first polymer blocks grafted to the polymer substrate. At least some of the first polymer blocks are terminated with thiocarbonylthio-containing groups. Typically, the thiocarbonylthio-containing group has the formula -SC(=S)-R 1 , as shown in the product (15) of reaction III. To ensure that the majority of the first polymer blocks are terminated with thiocarbonylthio-containing groups, the thiocarbonylthio-containing compound is typically added to the first reaction mixture even if the substrate already has thiocarbonylthio-containing groups attached.

[0134] When the thiocarbonylthio-containing compound is reacted with the treated substrate using grafting method 1, there is no monomer having a free radical polymerizable group (such as an ethylenically unsaturated group). This tends to increase the likelihood of the thiocarbonylthio group being transferred to the treated substrate, and thus can increase the density of thiocarbonylthio-containing groups at the surface of the polymeric substrate. This also allows the preparation and isolation of modified substrates having covalently attached thiocarbonylthio-containing groups in the absence of any competing polymerization or grafting reactions, and can allow for better control of subsequent intended grafting (polymerization) reactions. No polymer material is formed in the solution simultaneously with the formation of the modified substrate.

[0135] The product of reaction scheme B is an intermediate product with a covalently attached first polymer block. The first polymer block is attached to (e.g., grafted to) a porous polymer substrate. In most cases, the first polymer block is directly and covalently attached to carbon atoms of the porous polymer substrate. There is generally no intermediate linking group between the polymer substrate and the first polymer block, such as an ester bond, an amide bond, a carbamate bond, an ether bond, a siloxane bond, etc. At least some of the first polymer blocks are terminated with a thiocarbonylthio-containing group.

[0136] Alternatively, grafting method 2 can be used. Grafting method 2 differs from grafting method 1 in that there is no separate step for forming a modified substrate having a thiocarbonylthio-containing group covalently attached to the porous polymer substrate. Instead, the first reaction mixture includes monomers for forming the first polymer block, a thiocarbonylthio-containing compound, and an optional Type II photoinitiator. Type II photoinitiators are not required in the case where the polymer substrate is photoactive, but are used for non-photoactive polymer substrates. The advantage of using grafting method 2 is that fewer steps are required to graft the first polymer block to the porous polymer substrate.

[0137] In grafting method 2, the first reaction mixture is exposed to actinic radiation (e.g., UV radiation) to form free radicals on the porous polymer substrate surface (PPS*). The free radicals can react with the thiocarbonylsulfide-containing compound QSC(=S)-R 1 or monomer (CH2=CR x R y ) reaction. Because the monomer is generally present in a higher concentration than the thiocarbonylthio-containing compound, the product is generally similar to the product of the free radical (14) shown in Reaction Scheme B. As in Reaction Scheme B, if additional monomer is present, the free radical (14) can continue to grow. Ultimately, the free radical will form a polymer product (15) by combining with the free radical (12) of the thiocarbonylthio-containing compound. Upon continued exposure to actinic radiation, the free radical (14) and the thiocarbonylthio radical (12) can be formed again from the product (15). If more monomer is present, the regenerated free radical (14) can undergo further polymerization. Ultimately, the free radical will combine with the thiocarbonylthio radical (12). When exposure to actinic radiation is stopped or monomer is no longer present, the polymerization reaction stops. The product contains a plurality of first polymer blocks grafted to the polymer substrate. At least some of the first polymer blocks are terminated with a thiocarbonylthio-containing group, as shown in the product (15) of Reaction III of Reaction Scheme B.

[0138] Although the use of grafting method 1 or grafting method 2 with thiocarbonylthio-containing compounds (such as those of formula (I), (II) or (III)) is advantageous to form a separation article, other methods of forming the separation article can be used. For example, the separation article can be prepared using an alternative reversible deactivation radical polymerization (RDRP) initiator, or can be prepared using an alternative method with a RDRP initiator.

[0139] In an alternative method that does not include a thiocarbonylsulfide-containing compound, an absorption solution containing a Type II photoinitiator is coated on the surface of a porous polymer substrate and subsequently exposed to actinic radiation. Upon exposure to actinic radiation, the Type II photoinitiator extracts hydrogen from the porous polymer substrate, resulting in the generation of free radicals on its surface and forming a treated substrate. The intermediate semi-pinacol radical derived from the Type II photoinitiator via hydrogen abstraction is typically coupled with a free radical on the surface of the substrate to form a semi-pinacol group. Such a substrate with attached semi-pinacol groups can be used as a RDRP initiator, as described, for example, in the article Macromolecules, 2000, 33, 331 by H. Ma et al. Therefore, the substrate with attached semi-pinacol groups can be coated with a first monomer solution and subsequently exposed to actinic radiation to graft polymerize the first monomer to the substrate to obtain a covalently grafted polymer chain terminated with semi-pinacol groups. This method of adding the first monomer solution after the formation of semi-pinacol groups on the substrate surface is referred to as grafting method 3.

[0140] In another alternative method that does not include a thiocarbonylsulfide-containing compound, an absorption solution containing a first monomer and a Type II photoinitiator is coated on the surface of a porous polymer substrate and subsequently exposed to actinic radiation. Upon exposure to actinic radiation, the Type II photoinitiator extracts hydrogen from the porous polymer substrate, resulting in the generation of free radicals on its surface and forming a treated substrate. The treated substrate then interacts with the first monomer to form a grafted polymer chain covalently attached to the substrate. Finally, the semi-pinacol free radical derived from the Type II photoinitiator via hydrogen abstraction couples with the free radicals on the polymer chain end to form a grafted polymer chain with a semi-pinacol chain end, as described in the article Macromolecules by Yang and Ranby, 1996, 29, 3308. The grafted substrate can be used to initiate the polymerization of the second block. This method in which the first monomer and the Type II photoinitiator are present simultaneously is called grafting method 4.

[0141] In other alternative methods, a porous polymer substrate having hydroxyl or amino groups on its surface can be reacted with a RDRP initiator containing a carboxylic acid or acyl halide group to covalently attach the RDRP initiator through an ester or amide bond. Such a reaction is shown in Reaction Scheme C below for attaching an atom transfer radical polymerization (ATRP) initiator.

[0142] Reaction Scheme C

[0143] PPS-X 3 H+Br-(C=O)-C(CH3)2-Br→PPS-X 3 -(C=O)-C(CH3)2-Br In this reaction scheme, X 3is -O- or -NH-, and PPS refers to a porous substrate. 3 -(C=OC(CH3)2-Br has been used to graft ion exchange functional groups onto cellulose membranes (Bhut et al., J. Membr. Sci., 325 (2008), 176-183). Similarly, RAFT and NMP initiators have been attached to porous polymer substrates. A review (Peng Liu, e-Polymers, 2007, No. 062) describes a variety of methods for attaching RDRP initiators to surfaces. Since these methods generally involve batch chemical processes for attaching RDRP control agents to substrates, they are not preferred methods for use in current methods for forming separation articles. However, RDRP modified substrates can be used as starting materials for generating separation articles having attached block copolymers as described herein.

[0144] Regardless of the method of attaching the first block of the block copolymer to the porous polymer substrate, the first polymerizable composition contains at least one first monomer that is an acidic monomer, a basic monomer, or a salt thereof. The first monomer may be in a neutral state, but may be negatively charged (if acidic) or positively charged (if basic) under certain pH conditions. The first monomer may be permanently charged (for example, when the ligand functional group is in the form of a quaternary ammonium salt). The acidic group and the basic group are not polypeptides or proteins. As used herein, the term "polypeptide" refers to a compound containing more than four amino acid units.

[0145] The first monomer may comprise a single ethylenically unsaturated group or a plurality of ethylenically unsaturated groups (eg two or three or up to six), which may be the same or different in nature (preferably the same). The first monomer typically has only one ethylenically unsaturated group.

[0146] Suitable acidic groups of the first monomer include those that exhibit at least a certain degree of acidity (which can be in the range of relatively weak to relatively strong) and salts thereof. Such acidic groups or their salts include those that are commonly used as ion exchange or metal chelate ligands. Acidic groups are generally selected from carboxylic acid groups, phosphonic acid groups, phosphoric acid groups, sulfonic acid groups, sulfuric acid groups, boric acid groups and their salts. If the acidic group is a salt, the counterion is generally selected from alkali metals (e.g., sodium or potassium), alkaline earth metals (e.g., magnesium or calcium), ammonium and tetraalkylammonium, etc. and combinations thereof.

[0147] Suitable acidic monomers include, for example, various sulfonic acids such as N-acrylamidomethanesulfonic acid, 2-acrylamidoethanesulfonic acid, 2-acrylamido-2-methyl-1-propanesulfonic acid, 2-methacrylamido-2-methyl-1-propanesulfonic acid, vinylsulfonic acid, and 4-styrenesulfonic acid; (meth)acrylamidophosphonic acids such as (meth)acrylamidoalkylphosphonic acids such as 2-(meth)acrylamidoethylphosphonic acid and 3-(meth)acrylamidopropylphosphonic acid; (meth)acrylic acid; and (meth)acrylic acid carboxylalkyl esters such as (meth)acrylic acid 2-carboxyethyl ester, (meth)acrylic acid 3-carboxypropyl ester. Other suitable acidic monomers include (meth)acryloylamino acids such as those described in U.S. Pat. No. 4,157,418 (Heilmann). Exemplary (meth)acryloylamino acids include, but are not limited to, N-acryloylglycine, N-acryloylaspartic acid, N-acryloyl-β-alanine, and 2-acrylamidoglycolic acid. Salts of any of these acidic monomers may also be used.

[0148] Suitable basic groups of the first monomer include those that exhibit at least a certain degree of basicity (which can be in the range of relatively weak to relatively strong) and salts thereof. Such basic groups or their salts include those that are commonly used as ion exchange or metal chelate ligands. Basic groups are typically primary amino groups, secondary amino groups, tertiary amino groups, quaternary amino groups, guanidine groups, biguanidine groups or their salts. If the basic group is a salt, the counterion is typically selected from halides (e.g., chlorine or bromine), carboxylates (e.g., acetate), nitrates, phosphates, hydrogen sulfates, methyl sulfates, hydroxide ions, etc. and combinations thereof.

[0149] Suitable basic monomers include, for example, aminoacrylates, amino(meth)acrylamides, and various monomers with quaternary ammonium groups. Exemplary aminoacrylates include N,N-dialkylaminoalkyl acrylates, such as, for example, N,N-dimethylaminoethyl acrylate, N,N-dimethylaminoethyl methacrylate, N,N-diethylaminoethyl acrylate, N,N-diethylaminoethyl methacrylate, N,N-diethylaminoethyl methacrylate, N,N-diethylaminoethyl methacrylate, N,N-dimethylaminopropyl acrylate, N,N-dimethylaminopropyl methacrylate, N-tert-butylaminopropyl methacrylate, N-tert-butylaminopropyl acrylate, etc. Exemplary amino(meth)acrylamides include, for example, N-(3-aminopropyl)methacrylamide, N-(3-aminopropyl)acrylamide, N-[3-(dimethylamino)propyl]methacrylamide, N-(3-imidazolylpropyl)methacrylamide, N-(3-imidazolylpropyl)acrylamide, N-(2-imidazolylethyl)methacrylamide, N-(1,1-dimethyl-3-imidazolylpropyl)methacrylamide, N-(1,1-dimethyl-3-imidazolylpropyl)acrylamide, N-(3-benzimidazolylpropyl)acrylamide, and N-(3-benzimidazolylpropyl)methacrylamide.

[0150] Exemplary monomers having a quaternary ammonium group include, but are not limited to, (meth)acrylamidoalkyltrimethylammonium salts (e.g., 3-methacrylamidopropyltrimethylammonium chloride and 3-acrylamidopropyltrimethylammonium chloride) and (meth)acryloyloxyalkyltrimethylammonium salts (e.g., 2-acryloyloxyethyltrimethylammonium chloride, 2-methacryloyloxyethyltrimethylammonium chloride, 3-methacryloyloxy-2-hydroxypropyltrimethylammonium chloride, 3-acryloyloxy-2-hydroxypropyltrimethylammonium chloride, and 2-acryloyloxyethyltrimethylammonium methylsulfate).

[0151] In some embodiments, it is advantageous to use an acidic or basic monomer with a longer chain length between the ethylenically unsaturated group and the acidic or basic group. The acidic or basic group may be referred to as a "functional group", and the intermediate group between the ethylenically unsaturated group and the acidic or basic group may be referred to as a "spacer group". In some embodiments, the number of linking atoms is at least 6, at least 8, at least 10, at least 12, at least 14, at least 16, at least 18, or at least 20, and up to 30, up to 28, up to 26, up to 24, up to 22, up to 20, up to 18, up to 16, up to 14, or up to 12. If the monomer has a (meth)acryloyl group, the carbonyl group of the group is counted as part of the spacer group.

[0152] Although not wishing to be bound by theory, the length of the spacer can contribute to the polymer backbone (formed by monomer polymerization) adopting a spiral or partially spiral conformation. When the spacer is relatively short (e.g., less than 6 linking atoms), the ionic repulsion between the acidic groups or between the basic groups can force the polymer backbone to form a random coil conformation. When the spacer length increases, the adoption of the spiral conformation may become possible and can be maximized when the spacer length is about 8 to about 14 linking atoms. The spiral conformation of the substrate grafted polymer can promote the presentation of acidic groups, basic groups or their salts for use in interacting with target biomaterials, such as viruses and other microorganisms, proteins, cells, endotoxins, acidic carbohydrates, nucleic acids, etc.

[0153] In certain embodiments, the spacer group includes at least one hydrogen bonding portion, which is defined above as a portion including at least one hydrogen bond donor and at least one hydrogen bond acceptor (both of which are heteroatom-containing). Exemplary hydrogen donors are imino, thio and hydroxyl. Exemplary hydrogen acceptors are carbonyl, carbonyloxy or ether oxygen. Preferred spacers include at least two hydrogen bonding portions or include at least one hydrogen bonding portion and at least one hydrogen bond acceptor that is different from the hydrogen bonding portion (not a part thereof).

[0154] In certain embodiments, hydrogen bonding moieties include those comprising at least two hydrogen bond donors (e.g., donors such as imino, thio, or hydroxy), at least two hydrogen bond acceptors (e.g., acceptors in the form of carbonyl, carbonyloxy, or ether oxygen), or both. For example, an iminocarbonylimino moiety (having two NH donors and at least two acceptors in the form of two lone electron pairs on the carbonyl) can sometimes be preferred to a single iminocarbonyl moiety. In certain embodiments, spacer groups include those comprising at least one iminocarbonylimino moiety (more preferably, in combination with at least one acceptor such as a carbonyloxy group), at least two iminocarbonyl moieties, or combinations thereof.

[0155] The hydrogen bond donor and hydrogen bond acceptor of the hydrogen bonding moiety may be adjacent to each other (directly bonded) or may not be adjacent (preferably, adjacent or separated by a chain of no more than 4 linking atoms; more preferably, adjacent). The heteroatom of the hydrogen bond donor and / or hydrogen bond acceptor may be located within the chain of linking atoms of the spacer group, or alternatively, may be located within a chain substituent.

[0156] Although hydrogen bond donors can also serve as hydrogen bond acceptors (via lone electron pairs of heteroatoms of the donor), the hydrogen bonding moieties preferably include different donor and acceptor moieties. This can promote the formation of intramolecular (inter-monomer) hydrogen bonds. Although not wishing to be bound by theory, such intramolecular hydrogen bonds between adjacent monomers or adjacent repeating units in the polymer molecule can contribute to at least some degree of spacer group hardening, which can facilitate the presentation of acidic groups, basic groups, or salts thereof for interaction with the target biomaterial.

[0157] In certain embodiments, hydrogen bonding moieties include carbonyl imino, thiocarbonyl imino, iminocarbonyl imino, iminothiocarbonyl imino, oxycarbonyl imino, oxythiocarbonyl imino, and the like and combinations thereof. In certain embodiments, hydrogen bonding moieties include carbonyl imino, iminocarbonyl imino, oxycarbonyl imino, and combinations thereof (more preferably, carbonyl imino, iminocarbonyl imino, and combinations thereof). In certain embodiments, spacer groups include those that are divalent, trivalent, or tetravalent (more preferably, divalent or trivalent; even more preferably, divalent).

[0158] One useful class of first monomers containing a spacer group having at least 6 linking atoms are those of formula (IV).

[0159] CH2=CR 21 -C(=O)-X 1 -R 22 -[Z 1 -R 22 ] n -L

[0160] (IV)

[0161] In formula (IV), the group R 21 is selected from hydrogen or methyl. Each group R 22 is independently a (hetero)alkylene group. 1 Is -O- or -NR 23 -, where R 23 is selected from hydrogen or hydrocarbon. 1 It is a heteroalkylene group having at least one hydrogen bond donor, at least one hydrogen bond acceptor or a combination thereof. The variable n is an integer of 0 or 1. The group L is a ligand functional group as an acidic group, a basic group or their salt. If desired, different compounds of formula (IV) can be used in combination. Different compounds can all be acidic monomers or their salts, can all be basic monomers or their salts, or can be a combination of acidic monomers and basic monomers or their salts. In addition, the monomer of formula (IV) can be used in combination with other acidic and / or basic monomers of non-formula (IV).

[0162] The monomer of formula (IV) has the formula CH2=CR21 - an ethylenically unsaturated group, wherein R 21 is hydrogen or methyl.

[0163] Each R 22 is independently a (hetero)alkylene group. Exemplary alkylene groups include alkylene groups, arylene groups, aralkylene groups, and alkarylene groups. Exemplary heteroalkylene groups include heteroaralkylene groups, hydroxy-substituted alkylene groups, and hydroxy-substituted aralkylene groups. In certain embodiments, each R 22 are independently alkylene groups. For example, each R 22 are independently alkylene.

[0164] Group X 1 is -O-(oxy) or -NR 23 -. Group R 23 is hydrogen or a hydrocarbon group. The hydrocarbon group can be an alkyl group or an aryl group. In many examples, R 23 It's hydrogen.

[0165] Group Z 1 is a heteroalkylene group including at least one hydrogen bond donor, at least one hydrogen bond acceptor, or a combination thereof. The hydrogen donor is typically a donor such as an imino, thio, or hydroxyl group. The hydrogen acceptor is typically a carbonyl, carbonyloxy, or ether oxygen group. Thus, the group Z 1 Typically, the hydrogen bonding moiety is a carbonyl imino group, a thiocarbonyl imino group, an iminocarbonyl imino group, an iminothiocarbonyl imino group, an oxycarbonyl imino group, an oxythiocarbonyl imino group, and the like, and combinations thereof. In certain embodiments, the hydrogen bonding moiety comprises a carbonyl imino group, an iminocarbonyl imino group, an oxycarbonyl imino group, and combinations thereof (more preferably, a carbonyl imino group, an iminocarbonyl imino group, and combinations thereof).

[0166] In the monomers of formula (IV), the variable n is generally an integer of 1.

[0167] The group L is a ligand functional group including at least one acidic group or its salt, and the acidic group or its salt is selected from carboxyl, phosphonyl, phosphoric acid, sulfonic acid, sulfate radical, boric acid and their combination (more preferably, selected from carboxyl, phosphonyl, sulfonic acid and their combination). In other embodiments, L is a functional group including at least one basic group or its salt. Basic group is typically tertiary amine, quaternary amine, guanidine or biguanide. In some embodiments, L is carboxyl, guanidine or their salt.

[0168] Such monomers can be prepared by known synthesis methods or by methods analogous to known synthesis methods. For example, carboxylic acids, sulfonic acids or phosphonic acids containing amino groups can be reacted with ethylenically unsaturated compounds containing at least one group reactive with amino groups. Similarly, acidic group-containing compounds which also contain hydroxyl groups can be reacted with ethylenically unsaturated compounds comprising at least one group reactive with hydroxyl groups, optionally in the presence of a catalyst.

[0169] Preferred monomers are (meth)acryloyl-containing monomers, which refer to acryloyl-containing monomers and / or methacryloyl-containing monomers. Similarly, the term "(meth)acrylate" refers to acrylate and / or methacrylate monomers. In such monomers, the carbonyl group is part of the spacer group.

[0170] Representative examples of useful monomers of formula (IV) can be prepared by reacting an alkenyl azlactone of formula (V)

[0171]

[0172] It is prepared by reacting with a compound of formula (VI) (or its salt).

[0173] HX 2 -R 22 -L

[0174] (VI)

[0175] Group R 21 , R 22 and L are as defined in formula (IV). Group X 2 is oxy or -NR 23 -, where R 23 is hydrogen or a hydrocarbon group (eg, an alkyl group or an aryl group). The resulting compound has the formula (IV-1).

[0176] CH2=CR 21 -C(=O)-NH-R 22 -C(=O)-X 2 -R 22 -L

[0177] (IV-1)

[0178] These compounds have the formula (IV) wherein X 1 is -NH-, variable n is equal to 1, and Z 1 Equal to –C(=O)-X 2 -.

[0179] Representative examples of useful alkenyl azlactones of formula (V) include 4,4-dimethyl-2-vinyl-4H-oxazol-5-one (vinyl dimethyl azlactone, VDM), 2-isopropenyl-4H-oxazol-5-one, 4,4-dimethyl-2-isopropenyl-4H-oxazol-5-one, 2-vinyl-4,5-dihydro-[1,3]oxazin-6-one, 4,4-dimethyl-2-vinyl-4,5-dihydro-[1,3]oxazin-6-one, 4,5-dimethyl-2-vinyl-4,5-dihydro-[1,3]oxazin-6-one, and the like, and combinations thereof.

[0180] Other representative examples of usable monomers of formula (IV) can be obtained by using (meth)acryloyl isocyanate monomers of formula (VII)

[0181] CH2=CR 21 -C(=O)-X 1 -R 22 -N=C=O

[0182] (VII)

[0183] It is prepared by reacting with the compound of formula (VI) (or its salt) as described above. The resulting monomer has the formula (IV-2).

[0184] CH2=CR 21 -C(=O)-X 1 -R 22 -NH-C(=O)-X 2 -R 22 -L

[0185] (IV-2)

[0186] These monomers have the formula (IV) wherein the variable n is equal to 1 and Z 1 Equal to –NH-C(=O)-X 2 -. Group R 21 , R 22 , X 1 , X 2 and L are the same as defined above.

[0187] Representative examples of the ethylenically unsaturated isocyanate of formula (VII) include 2-isocyanatoethyl (meth)acrylate (IEM or IEA), 3-isocyanatopropyl (meth)acrylate, 4-isocyanatocyclohexyl (meth)acrylate, and the like, and combinations thereof.

[0188] Representative examples of available compounds of formula (VI) that can provide an acidic L group (or its salt) include amino-containing carboxylic acids, sulfonic acids, boric acid and phosphonic acids and combinations thereof and / or salts thereof. Available aminocarboxylic acids include α-amino acids (L-, D- or DL-α-amino acids), such as glycine, alanine, valine, proline, serine, phenylalanine, histidine, tryptophan, asparagine, glutamine, N-benzylglycine, N-phenylglycine, sarcosine, etc.; β-amino acids, such as β-alanine, homoleucine, homoglutamine, homophenylalanine, etc.; other α, ω-amino acids, such as γ-aminobutyric acid, 6-aminocaproic acid, 11-aminoundecanoic acid, etc.; and combinations thereof. Available aminosulfonic acids include aminomethanesulfonic acid, 2-aminoethanesulfonic acid (taurine), 3-amino-1-propanesulfonic acid, 6-amino-1-hexanesulfonic acid, etc. and combinations thereof. Available aminoboric acids include m-aminophenylboric acid, p-aminophenylboric acid, etc. and combinations thereof. Useful aminophosphonic acids include 1-aminomethylphosphonic acid, 2-aminoethylphosphonic acid, 3-aminopropylphosphonic acid, and the like, and combinations and / or salts thereof.

[0189] Representative examples of other useful compounds of formula (VI) having an acidic L group (or a salt thereof) include compounds comprising a hydroxyl group and an acidic group. Specific examples include glycolic acid, lactic acid, 6-hydroxycaproic acid, citric acid, 2-hydroxyethylsulfonic acid, 2-hydroxyethylphosphonic acid, and the like, and combinations and / or salts thereof.

[0190] Other representative compounds of formula (VI) having an acidic L group (or a salt thereof) are those containing more than one acidic group, including aspartic acid, glutamic acid, α-aminoadipic acid, iminodiacetic acid, N α ,N α - bis(carboxymethyl)lysine, cysteic acid, N-phosphonomethylglycine, and the like, and combinations and / or salts thereof.

[0191] Many compounds of the above formula (VI) with acidic L groups (or salts thereof) are commercially available. Other available acidic group-containing compounds can be prepared by conventional synthesis processes. For example, various diamines or amino alcohols can be reacted with an equivalent of a cyclic anhydride to produce an intermediate compound containing an acidic group including a carboxyl group and an amino or hydroxyl group.

[0192] In addition, useful monomers having an acidic group may be prepared by reacting a hydroxyl- or amine-containing (meth)acrylate or (meth)acrylamide monomer with a cyclic anhydride to produce a carboxyl-containing monomer.

[0193] In certain embodiments, useful monomers of formula (IV) having an L group as an acidic group (or a salt thereof) may be prepared from the reaction of an alkenyl azlactone with an aminocarboxylic acid, a monomer prepared from the reaction of an alkenyl azlactone with an aminosulfonic acid, a monomer prepared from the reaction of an ethylenically unsaturated isocyanate with an aminocarboxylic acid, a monomer prepared from the reaction of an ethylenically unsaturated isocyanate with an aminosulfonic acid, or a combination thereof.

[0194] Some exemplary monomers having group L in formula (IV) that is an acidic group or a salt thereof are further described in U.S. Pat. No. 10,352,835 (Rasmussen et al.) and may include the following (many of which are shown as acids, but salts of such acids may also be used):

[0195] VDM-4-aminomethyl-cyclohexanecarboxylic acid

[0196]

[0197] VDM-2-Hydroxy-4-aminobutyric acid

[0198]

[0199] VDM-2-amino-3-hydroxypropionic acid (VDM-serine)

[0200]

[0201] VDM-2-amino-3-(4-hydroxyphenyl)propionic acid (VDM-tyrosine)

[0202]

[0203] VDM-(2S)-2-amino-3-(1H-indol-3-yl)propionic acid (VDM-Tryptophan)

[0204]

[0205] VDM-7-aminoheptanoic acid

[0206]

[0207] VDM-2-amino-3-(1H-imidazol-4-yl)propionic acid (VDM-histidine)

[0208]

[0209] IEM-3-aminopropionic acid

[0210]

[0211] IEM-Taurine

[0212]

[0213] VDM-Taurine

[0214]

[0215] VDM-2-(Hydroxyethyl)phosphonic acid

[0216]

[0217] VDM-3-aminopropionic acid

[0218]

[0219] VDM-4-aminobutyric acid

[0220]

[0221] VDM-5-aminovaleric acid

[0222]

[0223] VDM-6-aminocaproic acid

[0224]

[0225] VDM-Phenylalanine

[0226]

[0227] IEM-Phenylalanine

[0228]

[0229] IEM-Glycine

[0230]

[0231] IEM-4-aminobutyric acid (IEM-GABA)

[0232]

[0233] IEM-aminomethylphosphonic acid

[0234]

[0235] Representative examples of useful compounds of formula (VI) that can provide a basic L group generally contain at least one amino or hydroxyl group and at least one basic group (such as a tertiary amino or quaternary amino group). Specific examples include 2-(dimethylamino)ethylamine, 3-(diethylamino)propylamine, 6-(dimethylamino)hexylamine, 2-aminoethyltrimethylammonium chloride, 3-aminopropyltrimethylammonium chloride, 2-(dimethylamino)ethanol, 3-(dimethylamino)-1-propanol, 6-(dimethylamino)-1-hexanol, 1-(2-aminoethyl)pyrrolidine, 2-[2-(dimethylamino)ethoxy]ethanol, histamine, 2-aminomethylpyridine, 4-aminomethylpyridine, 4-aminoethylpyridine, and the like, and combinations thereof.

[0236] Some exemplary monomers having a group L as a basic group (such as a tertiary amino group or a quaternary amino group) in formula (IV) are as follows:

[0237] VDM-2-aminoethyltrimethylammonium chloride

[0238]

[0239] IEM-Diethylaminoethylamine

[0240]

[0241] IEM-Diisopropylaminoethylamine

[0242]

[0243] IEM-2-aminoethyltrimethylammonium chloride

[0244]

[0245] VDM adducts of dimethylaminoalkanol

[0246]

[0247] Some monomers of formula (IV) have an L group that is a guanidino or biguanidino group. That is, L has the formula -NR 24 -[C(=NR 24 )-NR 24 ] m R 25 , wherein m is 1 or 2. When m is equal to 1, the group L is a guanidino group, and when m is equal to 2, the group L is a biguanidino group. The group R 24 is hydrogen or a hydrocarbon group, the group R 25 is hydrogen, hydrocarbon or -N(R 24 )2. For R 24 and R 25Suitable hydrocarbon groups are typically aryl or alkyl groups. 24 and / or R 25 Such monomers can be prepared as described in PCT patent applications WO 2014 / 204763 (Rasmussen et al.) and WO 2013 / 184366 (Bothof et al.).

[0248] The monomer having a guanidine group or a biguanidine group can be prepared, for example, by reacting a (meth)acryloyl halide (e.g., (meth)acryloyl chloride), (meth)acryloyl isocyanate (as in the above formula (VI)) or an alkenyl azlactone (as in the above formula (V)) with a compound of formula (VIII).

[0249] HNR 23 -R 22 -NR 24 -[C(=NR 24 )-NR 24 ] m R 25

[0250] (VIII)

[0251] The compound of formula (VIII) corresponds to the compound wherein X 2 Yes - NR 23 - and L is -NR 24 -[C(=NR 24 )-NR 24 ] m R 25 Compounds of formula (VI) are obtained. These compounds can be formed by reacting a diamine with a guanylating agent as described in PCT patent application WO 2014 / 204763 (Rasmussen et al.). The group R 22 , R 23 , R 24 and R 25 Same as above except for the variable m. Some compounds of formula (VIII) are commercially available, for example 4-aminobutylguanidine (agmatine).

[0252] When the compound of formula (VIII) is reacted with an alkenyl azlactone, a monomer of formula (IV-3) is formed.

[0253] CH2=CR 21 -C(=O)-NH-R 22 -C(=O)-NR 23 -R 22 -NR 24 -[C(=NR 24 )-NR 24 ] mR 25

[0254] (IV-3)

[0255] The monomer has the formula (IV), wherein n is equal to 1, Z 1 is -C(=O)-NR 23 -, and X 1 is -NH-. The group R 21 , R 22 , R 23 , R 24 and R 25 Same as above except for the variable m.

[0256] When the compound of formula (VIII) reacts with (meth)acryloyl isocyanate, a monomer of formula (IV-4) is formed.

[0257] CH2=CR 21 -C(=O)-X 1 -R 22 -NH-C(=O)-NR 23 -R 22 -NR 24 -[C(=NR 24 )-NR 24 ] m R 25

[0258] (IV-4)

[0259] The monomer has the formula (IV), wherein n is equal to 1, Z 1 It is -NH-C(=O)-NR 23 -, L has the formula -NR 24 -[C(=NR 24 )-NR 24 ] m R 25 . Group R 21 , R 22 , R 23 , R 24 and R 25 Same as above except for the variable m.

[0260] Some specific examples of first monomers having a guanidine group for L are shown below. For simplicity, the structure is shown as a neutral compound, but may exist as various salts, such as, for example, a chloride salt or a sulfate salt:

[0261] 2-({[(4-[amino(imino)methyl]aminobutyl)amino]carbonyl}-amino)ethyl methacrylate

[0262]

[0263] N 2 -Acryloyl-N 1 -(4-{[amino(imino)methyl]amino}butyl)-2-methylalaninamide

[0264]

[0265] N 2 -Acryloyl-N 1 -(6-{[amino(imino)methyl]amino}hexyl)-2-methylalaninamide

[0266]

[0267] 2-({[N-(2-[amino(imino)methyl]aminoethyl)-N-benzylamino]carbonyl}-amino)ethyl methacrylate

[0268]

[0269] The first monomers described above can be homopolymerized to provide the first polymer block. In other embodiments, various first monomers can be combined and copolymerized. In other embodiments, other types of monomers can be combined and copolymerized with the first monomers.

[0270] The first polymer block is usually a homopolymer of an acidic monomer or a basic monomer to prepare a block copolymer with a high binding capacity for the material desired to be captured. That is, the first polymer block can be up to 100% by weight of an acidic monomer unit or its salt, a basic monomer unit or its salt or a combination (mixture) thereof. In some embodiments, other monomers (the second monomer) are copolymerized with the first monomer to regulate the binding capacity and / or to achieve other desired characteristics of the first polymer block. Any suitable second monomer can be used.

[0271] Based on the gross weight of monomeric units in the first polymer block, the amount of the first monomer with acidic or basic groups can be in the range of, for example, 50% by weight to 100% by weight of acidic or basic monomeric units. Based on the gross weight of monomeric units in the first polymer block, the amount can be at least 50% by weight, at least 60% by weight, at least 70% by weight, at least 75% by weight, at least 80% by weight, at least 85% by weight, at least 90% by weight or at least 95% by weight, and up to 100% by weight, up to 99% by weight, up to 98% by weight, up to 97% by weight, up to 95% by weight, up to 90% by weight, up to 85% by weight, up to 80% by weight or up to 75% by weight. The first monomer of higher amount tends to increase the binding capacity to various target compounds (such as biomaterials). In many embodiments, the amount of the first monomer that is an acidic group, a basic group, or a salt thereof is in the range of 80 wt % to 100 wt %, 85 wt % to 100 wt %, 90 wt % to 100 wt %, or 95 wt % to 100 wt %, based on the total weight of the monomer units.

[0272] The second monomer in the first polymer block can be, for example, a hydrophilic monomer to adjust the degree of hydrophilicity imparted to the substrate. The hydrophilic monomer has an ethylenically unsaturated group and a hydrophilic group, such as, for example, a hydroxyl group or an amide group. Suitable hydrophilic monomers include acrylamide, dimethylacrylamide, hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, ethoxyethyl methacrylate, diethylene glycol methyl ether methacrylate, 2-hydroxyethyl acrylamide, N-vinyl pyrrolidone, and the like, and combinations thereof.

[0273] Other second monomers in the first polymer block include those with more than one ethylenically unsaturated group. This type of second monomer is usually used only in a relatively small amount to give the resulting copolymer a certain degree of branching and / or relatively light crosslinking. For example, based on the gross weight of monomers in the first polymerizable composition, the amount of these multifunctional monomers with more than two ethylenically unsaturated groups can be present in an amount ranging from 0.1 wt % to 5 wt %. The amount can be at least 0.1 wt %, at least 0.2 wt %, at least 0.5 wt % or at least 1.0 wt % wt %, and up to 5 wt %, up to 4 wt %, up to 3 wt %, up to 2 wt % or up to 1 wt %. Higher amounts can be used for some applications, but higher amounts may reduce the binding capacity to various biomaterials.

[0274] The total amount of the second monomer can be up to 50% by weight of the monomers used to form the first polymer block. Lower amounts of the second monomer generally enhance the binding ability to various target compounds (such as biomaterials). Based on the total weight of the monomers in the first polymerizable composition, this amount, if present, is generally equal to 100 minus the weight percent of the first monomer.

[0275] The first polymer block typically has a grafting density of about 0.02 mmol / g to about 3 mmol / g or even higher. The grafting density can be at least 0.02 mmol / g, at least 0.05 mmol / g, at least 0.1 mmol / g, at least 0.2 mmol / g, at least 0.5 mmol / g, or at least 1 mmol / g, and up to 3 mmol / g, up to 2.5 mmol / g, up to 2 mmol / g, up to 1.5 mmol / g, up to 1 mmol / g, up to 0.8 mmol / g, up to 0.7 mmol / g, or up to 0.5 mmol / g. This corresponds to a weight gain of 1% to 85% or more. The weight gain is calculated by the formula [100 (weight 2–weight 1) ÷ weight 1], where weight 1 is the weight of the substrate and weight 2 is the weight of the substrate to which the grafted polymer is attached. The weight gain can range from 1 wt % to 85 wt % or even higher. The amount can be, for example, at least 1 wt%, at least 2 wt%, at least 5 wt%, at least 10 wt%, at least 15 wt%, at least 20 wt%, at least 25 wt%, at least 30 wt%, at least 35 wt%, at least 40 wt%, at least 45 wt%, or at least 50 wt%, and up to 85 wt%, up to 80 wt%, up to 75 wt%, up to 70 wt%, up to 65 wt%, up to 60 wt%, up to 55 wt%, up to 50 wt%, up to 45 wt%, up to 40 wt%, up to 35 wt%, or up to 30 wt%.

[0276] Whether grafting method 1 or grafting method 2 is used to form the first polymer block, a thiocarbonylthio-containing compound is generally added to the first reaction mixture. Although its addition is optional, the presence of the thiocarbonylthio-containing compound can increase the likelihood that the terminal group of the first polymer block is a thiocarbonylthio-containing group. The presence of this group is required to initiate the formation of the second polymer block. The amount of the thiocarbonylthio-containing compound can be in the range of 0 wt % to 20 wt % for grafting method 1, and can be in the range of 0.5 wt % to 20 wt % for grafting method 2. The amount used for grafting method 1 is typically at least 0 wt%, at least 0.1 wt%, at least 0.2 wt%, at least 0.3 wt%, at least 0.5 wt%, at least 1 wt%, at least 2 wt%, at least 3 wt%, at least 4 wt%, or at least 5 wt%, and up to 20 wt%, up to 15 wt%, up to 10 wt%, up to 8 wt%, up to 6 wt%, up to 5 wt%, up to 4 wt%, up to 3 wt%, or up to 2 wt%. The amount used for grafting method 2 is typically at least 0.5 wt%, at least 1 wt%, at least 2 wt%, at least 3 wt%, at least 4 wt%, or at least 5 wt%, and up to 20 wt%, up to 15 wt%, up to 10 wt%, up to 8 wt%, up to 6 wt%, up to 5 wt%, up to 4 wt%, up to 3 wt%, or up to 2 wt%. If the thiocarbonylthio compound is added using grafting method 1, it may be the same as or different from the thiocarbonylthio-containing compound that is bonded to the surface of the polymeric substrate to form the modified substrate.

[0277] The presence of the thiocarbonylthio-containing compound in the reaction mixture can initiate the formation of polymers that are not attached to the substrate. These polymers that are not bonded to the substrate are typically removed after the article is formed so that the only remaining polymers are those that are covalently attached to the porous polymer substrate.

[0278] As noted, in some alternative grafting methods, there is no thiocarbonylthio-containing compound and the covalently attached first polymer block is terminated with a semi-pinacol group. In these alternatives, the terminal semi-pinacol group serves as the RDRP group that initiates the formation of the second polymer block.

[0279] Forming a second polymer block attached to the first polymer block

[0280] A second polymer block is formed that is covalently attached to the first polymer block, wherein the first polymer block is located between the second polymer block and the porous polymer substrate. The resulting block copolymer extends away from the surface of the porous polymer substrate. Although additional polymer blocks may be added, the grafted block copolymer is typically a diblock polymer.

[0281] Regardless of the method used to form the first polymer block, at least some of the chain ends of the block are terminated with a RDRP agent, such as, for example, with a thiocarbonylthio-containing group or a semi-pinacol group. Thus, the chain ends of the first polymer block can be used as initiators for the second polymer block. Typically, the substrate comprising the grafted first polymer block is coated with a second polymerizable composition comprising a polyether monomer having at least one ethylenically unsaturated group and a polyether group. The RDRP agent is then activated, for example, by actinic radiation, to regenerate the free radical chain ends and the free radicals derived from the RDRP agent. The free radical chain ends then initiate polymerization of the second monomer composition, thereby forming a second polymer block. Finally, termination can occur by recombination with free radicals derived from the RDRP agent or by any other well-known free radical termination mechanism.

[0282] The second polymer block is the reaction product of the second polymerizable composition comprising a polyether monomer having at least one ethylenically unsaturated group and a polyether group. The polyether monomer is typically selected to be hydrophilic or water swellable. Regardless of the number of ethylenically unsaturated groups, suitable polyether monomers typically contain a plurality of ethyleneoxy groups, propyleneoxy groups, or mixtures thereof. The number of ethylenically unsaturated groups is typically in the range of 1 to 4, such as 1 to 3 or 1 to 2.

[0283] The second polymer block is formed to provide a porous polymer network that can be used to separate materials in a sample based on size or steric effects. That is, the second polymer block can prevent or reduce the number of larger materials that can interact with the acidic and / or basic groups on the first polymer block. In most embodiments, the second polymer block is cross-linked. However, if the polyether groups are long enough and / or entangled, cross-linking can be optional.

[0284] Any suitable method may be used to crosslink the second polymer block. In some embodiments, crosslinking occurs by using polyether monomers having multiple ethylenically unsaturated groups in the second polymeric composition. Any amount of these polyether monomers may be used to obtain the desired porosity of the second polymer block.

[0285] In some embodiments, all polyether monomers in the second polymerizable composition have at least two ethylenically unsaturated groups. All of these polyether monomers can have the same weight average molecular weight and the same number of ethylenically unsaturated groups, or there can be a mixture of different polyether monomers having different weight average molecular weights and / or different numbers of ethylenically unsaturated groups.

[0286] In other embodiments, the second polymerizable composition comprises a mixture of a polyether monomer having a single ethylenically unsaturated group and a polyether monomer having multiple ethylenically unsaturated groups. The sizes of the polyether monomers in the mixture may be the same or different. The amount of the polyether monomer having multiple ethylenically unsaturated groups may be varied to obtain the desired porosity of the polymer network.

[0287] In other embodiments, the second polymerizable composition further comprises a crosslinking monomer that is not a polyether monomer. The crosslinking monomer is selected to be water-soluble and can be combined with a polyether monomer having a single ethylenically unsaturated group, multiple ethylenically unsaturated groups, or a mixture thereof. The amount of the crosslinking monomer can be varied to obtain the desired porosity of the polymer network.

[0288] The weight average molecular weight of the polyether monomer is generally in the range of 250 to 20,000 Daltons. The weight average molecular weight may be at least 300 Daltons, at least 400 Daltons, at least 500 Daltons, at least 700 Daltons, at least 800 Daltons, at least 1000 Daltons, at least 2000 Daltons, at least 5000 Daltons, and up to 20,000 Daltons, up to 10,000 Daltons, up to 5000 Daltons, up to 2000 Daltons, or up to 1000 Daltons.

[0289] Suitable polyether monomers having one or more ethylenically unsaturated groups are commercially available from Aldrich Chemical, Milwaukee, WI, USA, such as, for example, polyethylene glycol diacrylate (PEGDA) having a number average molecular weight of 302 Daltons, 575 Daltons, 2000 Daltons, 6000 Daltons, and 10,000 Daltons, and poly(ethylene glycol) methyl ether methacrylate (PEGMA) having a number average molecular weight of 200 Daltons, 400 Daltons, and 2000 Daltons. Other suitable polyether monomers are commercially available from Sartomer, Exton, PA, USA, such as, for example, those with the trade names SR415 (ethoxylated (20) trimethylolpropane triacrylate), SR610 (polyethylene glycol diacrylate having an average molecular weight of 600 Da), SR9035 (ethoxylated (15) trimethylolpropane triacrylate), and SR9038 (ethoxylated (30) bisphenol A diacrylate).

[0290] If a crosslinking monomer that is not a polyether monomer is used, the weight average molecular weight is generally in the range of 100 to 500 Daltons. The weight average molecular weight may be at least 100 Daltons, at least 150 Daltons, or at least 200 Daltons, and up to 500 Daltons, up to 450 Daltons, up to 400 Daltons, up to 350 Daltons, or up to 300 Daltons. Examples include, but are not limited to, methylenebisacrylamide, 3-acryloyloxy-2-hydroxypropyl methacrylate, glyceryl dimethacrylate, glyceryl diacrylate, diacryloylpiperazine, and 1,2-ethylenebisacrylamide.

[0291] The second polymer block typically has a grafting density of about 0.01 mmol / g to about 1 mmol / g or even higher. The grafting density can be at least 0.01 mmol / g, at least 0.02 mmol / g, at least 0.05 mmol / g, at least 0.1 mmol / g, at least 0.2 mmol / g, at least 0.3 mmol / g, or at least 0.5 mmoles / gram, and up to 1 mmol / g or even higher, up to 0.8 mmol / g, up to 0.7 mmol / g, up to 0.6 mmol / g, up to 0.5 mmol / g, or up to 0.4 mmol / g. This corresponds to a weight gain of 0.2% to 90% or even higher. The weight gain is calculated by the formula [100 (weight 3–weight 2) ÷ weight 2], where weight 2 is the weight of the substrate plus the attached first polymer block, and weight 3 is the weight of the substrate with the attached block copolymer (both the first polymer block and the second polymer block). The weight can be in the range of 0.2 wt % to 90 wt % or even higher. The amount can be, for example, at least 0.2 wt %, at least 0.5 wt %, at least 1 wt %, at least 2 wt %, at least 5 wt %, at least 10 wt %, at least 15 wt %, at least 20 wt %, at least 25 wt %, at least 30 wt %, at least 35 wt %, at least 40 wt %, at least 45 wt % or at least 50 wt %, and up to 90 wt %, up to 85 wt %, up to 80 wt %, up to 75 wt %, up to 70 wt %, up to 65 wt %, up to 60 wt %, up to 55 wt %, up to 50 wt %, up to 45 wt %, up to 40 wt %, up to 35 wt % or up to 30 wt %.

[0292] Method for separating a mixture of materials

[0293] Separation products can be used to separate mixtures of various materials, such as mixtures of biomaterials. As described above, separation products have block copolymers grafted to porous polymer substrates. Block copolymers contain a first polymer block with acidic monomer units, basic monomer units or a combination thereof, which can be attached to various biomaterials. Depending on pH, these monomer units can be in the form of salts. Block copolymers also contain a second polymer block, which can separate biomaterials based on size or spatial parameters. The separation method includes preparing a separation product as described above, and then passing a mixture of materials through the separation product, wherein the second polymer block only allows a portion of the material in the mixture to contact with an acid group or its salt, a basic group or its salt, or a combination thereof in the first polymer block.

[0294] As used herein, the term "partial" refers to the fact that some components (i.e., materials) of the mixture are restricted from approaching the first block due to the presence of the second block. This restricted access can be observed as a reduction in the binding capacity of the component when the second block is added. Typically, the larger component of the mixture is the most restricted component, and the smaller component can still diffuse through the second block and bind to the first block, thus allowing the selective separation of large and small components. The separation can be 100% selective, for example, the smaller component of the mixture can be completely captured by the first polymer block and removed by the separation device, while the larger component flows through the device (e.g., excluded by the second polymer block and not captured by the first polymer block) and is recovered with 100% purity and yield. Alternatively, the separation can be less than 100% selective and result in only partial removal of one or more components from the mixture. Typical chromatographic manipulations, such as buffer and pH adjustments, flow rates, residence times, etc., can be used to optimize the selectivity of the separation.

[0295] The portion can be any suitable amount. In some embodiments, the portion of the material flowing through the second polymer block to reach the first polymer block is at least 1 wt % based on the gross weight of the separated material. The amount can be at least 2 wt %, at least 5 wt %, at least 10 wt %, at least 20 wt %, at least 30 wt %, at least 40 wt %, at least 60 wt %, at least 70 wt %, at least 80 wt % or at least 90 wt % or even higher based on the gross weight of the separated material.

[0296] While not wishing to be bound by theory, it is believed that the ability of the separation article to provide a selective separation is based on at least one of: (a) manipulation of the pore size of the second polymer block, (b) steric exclusion resulting from the presence of polyether chains in the second polymer block, or (c) a combination of both.

[0297] Engberg et al. Biomed. Mater., 6 (2011), 055006 reported that the diffusion coefficient of proteins in cross-linked polyethylene glycol diacrylate (PEGDA) hydrogels is negatively correlated with the concentration of PEGDA when the cross-linking reaction is initiated. Increased concentrations lead to more tightly cross-linked hydrogels, thereby reducing pore size and slowing protein diffusion. Alternatively, increasing the molecular weight of PEGDA increases the distance between cross-linked portions, thereby increasing the pore size of the hydrogel. Therefore, in the separation product described herein, the material can be optimized to approach the first polymer block by controlling the molecular weight and concentration of the polyether monomer during the formation of the second polymer block.

[0298] It is well known that hydrophilic polymers (such as those derived from polyether monomers) are attached to surfaces to make them antifouling or repel proteins. This phenomenon is at least partly due to steric exclusion, in which the presence of polyether groups causes proteins to preferentially hydrate, resulting in mutual repulsion between the two substances. It is known that this repulsive interaction increases with the increase of the molecular weight of the polyether monomer (see Bhat et al., Protein Science, 1 (1992), pp. 1133-1143). Although the thickness of the hydration shell is protein-dependent to a certain extent, this will affect the effective size of the protein and its ability to penetrate the hydrogel. Therefore, the steric exclusion effect can be adjusted by selecting a polyether monomer for the second polymer block.

[0299] In addition to selecting the polyether monomer and its concentration in the second polymer block, the grafting density of the first polymer block and the second polymer block can also be changed to optimize the separation selectivity of the separation product. Increasing the grafting density of the first polymer block generally increases the binding capacity of the block. Increasing the grafting density of the second polymer block (therefore increasing its thickness) generally improves the selectivity of the block copolymer. Finally, control of the overall grafting density allows control of the flow characteristics of the separation product.

[0300] As noted above, compounds containing thiocarbonylsulfide are advantageously used as RDRP reagents to prepare separation products. In some cases, these reagents can provide better control over selective separation than can be achieved using other RDRP reagents (such as, for example, reagents containing semipinacol). In other words, it has been found that using RDRP reagents containing thiocarbonylsulfide can achieve more refined control over size selectivity. In some embodiments using RDRP reagents containing thiocarbonylsulfide, separation products can be prepared that will capture small biomolecules, such as lysozyme (14.3kD protein), while completely or almost completely excluding larger proteins, such as IgG (150kD protein). This allows small proteins to be separated from large proteins, even if both of them are positively charged at neutral pH. An example where this selectivity may be advantageous is the purification of monoclonal antibodies in a flow-through separation device.

[0301] In other embodiments, such as by using a semipinacol-containing RDRP reagent, the selectivity between large and small proteins may not be very good compared to using a thiocarbonylthio-containing RDRP reagent. However, to separate larger biotherapeutics (such as virus-like particles or viral vectors) from smaller biological materials (such as host cell proteins), it may be advantageous to use a somewhat simpler and less expensive semipinacol-containing RDRP reagent to prepare the separation preparation. An example where such selectivity would be advantageous is in the capture or removal of protein impurities from a production stream of viral vectors or virus-like particles in a flow-through separation device.

[0302] Separation articles can be used to separate mixtures of various materials, such as, for example, mixtures of biological materials. Exemplary separations that can occur using biological materials include, but are not limited to, the following: (1) separation of monoclonal antibodies (mAbs) from host cell protein (HCP) impurities, (2) separation of mAbs from antibody fragments, (3) separation of mAbs from higher molecular weight antibody aggregates, (4) separation of bispecific antibodies (biAbs) from antibody fragments, (5) separation of antibody-drug conjugates (ADCs) from unconjugated drugs, (6) separation of Fc fusion proteins from Fc fusion protein fragments, (7) separation of IVIG antibodies (gamma globulins) from smaller plasma proteins, (8) separation of milk proteins such as lactoferrin, α-lactalbumin, β-lactoglobulin based on size and / or charge, (9) separation of viral vectors, viruses, or virus-like particles from host cell impurities (such as HCP and nucleic acids), and (10) separation of nucleic acids from other nucleic acids or other impurities (e.g., separation of mRNA from its plasmid DNA template, separation of mRNA from DNA fragments, or separation of plasmid DNA from enzymes, DNA fragments, and other impurities).

[0303] As mentioned above, separation products can be used to separate various materials, such as biomaterials, based on size or spatial parameters. For example, the biomaterial trapped by the first polymer block is usually smaller in size than the biomaterial excluded by the second polymer block, and therefore diffuses through the second polymer block to interact and bind with the first polymer block. The biomaterial bound to the first polymer block usually has an ionic charge opposite to the ionic charge of the first polymer block, so that the binding interaction is an interaction of the ion exchange type. The binding interaction can be only of the ion exchange type, or it can be enhanced by other secondary types of interactions (such as hydrogen bonding or hydrophobic or metal affinity types), depending on the structure of the monomer used to form the first polymer block. The bound biomaterial can have a similar net charge or an opposite net charge to the biomaterial from which they are separated by the second polymer block. Obviously, when used to separate materials with similar charge characteristics, the separation method is the most advantageous. The bound biomaterial can be an impurity that is desired to be removed from the mixture. Alternatively, they may be the object of purification, in that once bound, impurities can be washed away and buffer conditions (pH, conductivity, etc.) can subsequently be changed to elute the bound biological material in a purified form.

[0304] Example

[0305] Material

[0306] abbreviation Description and origin

[0307] Nylon membrane Nylon 66 membrane, single-reinforced nylon three-zone membrane, nominal pore size 0.8 μm, #080ZN, obtained from 3M Separation and Purification Sciences, St. Paul, MN

[0308] PEGDA 575 polyethylene glycol diacrylate, average molecular weight 575 Daltons, equivalent weight 288, obtained from Aldrich Chemical, Milwaukee, WI

[0309] PEGDA 302 polyethylene glycol diacrylate, average molecular weight 302 Daltons, equivalent weight 151, obtained from Aldrich Chemical, Milwaukee, WI

[0310] PEGDA 2000 polyethylene glycol diacrylate, average molecular weight 2000 Daltons, obtained from Aldrich Chemical, Milwaukee, WI

[0311] PEGDA 6000 polyethylene glycol diacrylate, average molecular weight 6000 Daltons, obtained from Aldrich Chemical, Milwaukee, WI

[0312] PEGDA 10000 Polyethylene glycol diacrylate, average molecular weight 10000 Daltons, obtained from Aldrich Chemical, Milwaukee, WI

[0313] AMPS 2-acrylamide-2-methylpropane sulfonic acid, available as AMPS 2404 from Lubrizol Corporation, Wickliffe, OH

[0314] PEGDA 600 Polyethylene glycol 600 diacrylate, molecular weight 742 Daltons, available from Sartomer, Exton, PA under the trade name SR610

[0315] SR415 Ethoxylated (20) trimethylolpropane triacrylate, available from Sartomer, Exton, PA

[0316] SR9035 Ethoxylated (15) trimethylolpropane triacrylate, molecular weight 956 Daltons, available from Sartomer, Exton, PA

[0317] SR9038 Ethoxylated (30) bisphenol A diacrylate, molecular weight 1656 Daltons, available from Sartomer, Exton, PA

[0318] HEMA 2-Hydroxyethyl methacrylate, available from Aldrich Chemical, Milwaukee, WI

[0319] MBA Methylenebisacrylamide, obtained from Aldrich Chemical, Milwaukee, WI

[0320] PEGMA 200 Poly(ethylene glycol) methyl ether methacrylate, average molecular weight 280 Daltons, available from Aldrich Chemical, Milwaukee, WI

[0321] PEGMA 400 Poly(ethylene glycol) methyl ether methacrylate, average molecular weight 480 Daltons, available from Aldrich Chemical, Milwaukee, WI

[0322] PEGMA 2000 Poly(ethylene glycol) methyl ether methacrylate, average molecular weight 2000 Daltons, available from Aldrich Chemical, Milwaukee, WI

[0323] AOHPMA 3-Acryloyloxy-2-hydroxypropyl methacrylate, available from Aldrich Chemical, Milwaukee, WI

[0324] MAPTAC Methacrylamidopropyltrimethylammonium chloride, available from Aldrich Chemical, Milwaukee, WI

[0325] IEM / agmatine Monomer prepared from isocyanatoethyl methacrylate and agmatine sulfate as described in U.S. Pat. No. 10,144,760, Example 99

[0326] IEM / GABA Monomer prepared from isocyanatoethyl methacrylate and gamma-aminobutyric acid as described in U.S. Pat. No. 10,352,835, Preparation Example 3

[0327] IEM / Glycine Monomer prepared from isocyanatoethyl methacrylate and glycine as described in U.S. Pat. No. 10,352,835, Preparation Example 12

[0328] VDM / GABA A monomer prepared from vinyl dimethyl azlactone and gamma-aminobutyric acid as described in U.S. Pat. No. 10,352,835, Preparation Example 14

[0329] EXA Ethylxanthoylacetate, sodium salt, also known as 2-ethoxythiocarbonyl-thioacetate, sodium salt, prepared as described in U.S. Pat. No. 2021 / 0095088

[0330] DEX Diethylbisxanthate, also known as dixanthate, prepared as described in U.S. Patent Application 2021 / 0095088

[0331] MEX ethyl xanthoxyacetic acid methyl ester, also known as 2-ethoxythiocarbonylthio-acetic acid methyl ester, prepared as described in U.S. Patent Application 2021 / 0095088

[0332] Sodium 3-carboxybenzophenone Type II photoinitiator, prepared from 3-carboxybenzophenone obtained from Sigma-Aldrich, Milwaukee, WI by dissolving in 1 N NaOH equivalent and diluting with deionized water to a concentration of 0.033 g / mL

[0333] Test Method

[0334] Protein Binding Capacity of Functional Substrates Method

[0335] The protein binding capacity of the first grafted substrate and the second grafted substrate prepared as described in the following examples is analyzed by incubating a substrate disk overnight in a solution of the test analyte (protein dissolved in an appropriate binding buffer). The disk is prepared by punching a disk of 18 mm diameter from a sheet of the grafted substrate. Each disk is placed in a 5 mL centrifuge tube with 4.5 mL of the test analyte solution. The test tube is covered and rolled overnight (usually 14 hours) on a rotating mixer (BARNSTEAD / THERMOLYN LABQUAKE tube shaker, obtained from VWR International, Eagan, MN; Thermo Scientific tube rotator, obtained from ThermoScientific, Waltham, MA). The supernatant is discarded, the tube is filled with binding buffer and rolled for 15 minutes to 30 minutes to wash away the excess protein solution. The supernatant is discarded, and the buffer wash is repeated twice. The bound protein is eluted by adding 4.5 mL of binding buffer containing 1 M NaCl and rolling for 1 hour. The fluorescence images were acquired using a UV-VIS spectrometer (Agilent 8453, Agilent Technologies, Santa Clara, CA) at 280 nm (background correction was applied at 325 nm) or using a NANODROP One C The eluted supernatant was analyzed by a microvolume UV-VIS spectrophotometer (Thermo Scientific, Waltham, MA). The binding capacity of each substrate was determined by UV absorbance and protein extinction coefficient provided by the supplier. Results are reported as the average of three replicates in mg / mL (mg of bound protein / mL of substrate volume).

[0336] Test analyte solution (protein in binding buffer unless otherwise stated in the examples below)

[0337]

[0338] Grafting density

[0339] Before grafting, the substrate (film, nonwoven web or first graft substrate) is balanced at a relative humidity (RH) of 20% to 25% in a low humidity chamber (Sanpia dry holder, Sanplatec Corporation, commercially available from VWR International) for at least 18 hours. The substrate is taken out from the low humidity chamber, weighed immediately, and then subjected to a free radical grafting reaction (i.e., grafting process) as described below. After the washing and drying process (as described below), the substrate is again balanced in a low humidity chamber for at least 18 hours, taken out from the chamber, and weighed again immediately to obtain a measured value of mass gain during the grafting reaction. Mass gain is then used to estimate the millimoles of monomer units grafted to the substrate by dividing the mass gain by the molecular weight of the monomer. The grafting density is then normalized by dividing by the initial mass of the substrate and expressed as millimoles (mmol / g) of monomer units grafted per gram of substrate.

[0340] Membrane coating process

[0341] Prepare the coating solution comprising monomer as described below.For each coating solution, the film substrate is placed on a polyester film, and enough coating solutions are pipetted onto the top surface of the substrate to completely wet the film substrate.The coating solution for forming the first graft substrate (i.e. the first polymer block grafted to the substrate) is described in the following process A to E. Make each coating solution immersed in the film substrate for about 1 minute, and then the second polyester film is placed on the top of the substrate.The 2.28kg cylindrical weight is rolled on the top of the obtained three-layer sandwich structure to squeeze out excessive coating solution.The coating solution for forming the second graft substrate is described in each embodiment.

[0342] Nonwoven coating process

[0343] Prepare the coating solution comprising monomer as described below.For each coating solution, nonwoven sheet is placed inside the plastic bag with seal, and enough coating solution is pipetted onto the top surface of nonwoven substrate to completely wet the nonwoven substrate.Cylindrical weight (2.28kg) is rolled on the top of the bag to distribute the fluid over the entire web (i.e., nonwoven substrate).Plastic bag is purged with nitrogen for 10 seconds and the filled plastic bag is closed to ensure that the coated web is in anoxic environment.Slightly open the plastic bag, and immediately roll with cylindrical weight to exhaust gas from the bag, flatten the plastic bag, and squeeze out excessive coating solution.Describe the coating solution for forming the first graft substrate (i.e., the first polymer block grafted to the substrate) in process F and G below.The coating solution for forming the second graft substrate is described in each embodiment.

[0344] Ultraviolet (UV)-Initiated Grafting Process

[0345] Ultraviolet (UV) initiated grafting was performed by irradiating the coated film in a polyester film sandwich or the coated nonwoven in a plastic bag with a seal using a UV station (Classic Manufacturing, Inc., Oakdale, MN) equipped with 18 bulbs (Sylvania RG2 40W F40 / 350BL / ECO, 10 above and 8 below the substrate, 1.17 meters (46 inches) long, spaced 5.1 cm (2 inches) on center) for irradiation times as indicated in Procedures A to G and Examples 1 to 60 below. The film or nonwoven sheet was removed and the resulting first grafted substrate was placed in a polyethylene bottle for washing as described below. After washing and drying, the first grafted substrate was tested for grafting density and protein binding capacity.

[0346] These same conditions were used to form and characterize the second grafted substrate unless otherwise described below.

[0347] Formation of the first grafted substrate (i.e., the first polymer block grafted onto the substrate)

[0348] Process A

[0349] A coating solution containing 0.5M, 0.75M, 1.0M, 1.25M or 1.5M AMPS, sodium salt of 3-carboxybenzophenone (Aldrich Chemical, Milwaukee, WI) (2.0 mL of a 0.033 g / mL aqueous solution) and DEX (140 μL) was prepared in a total volume of 20 mL. This solution was coated onto a nylon membrane sheet (8" x 8") and UV grafted for 15 minutes or 30 minutes by the UV-initiated grafting process above to produce a grafted cation exchange first polymer block derived from AMPS and terminated with ethoxythiocarbonylthio groups. After washing with 0.9% brine, methanol, 0.9% brine, methanol (2 more times, 30 minutes each) and drying the sheet, the mass gain was measured to determine the grafting density (Table 1). Subsequently, segments of each sheet were cut for evaluation or for grafting of the second polymer block.

[0350] Table 1: First grafted substrates A1 to A6

[0351] The first grafted substrate UV irradiation time (minutes) AMPS concentration (M) Grafting density (mmol / g) A1 15 0.5 0.05 A2 15 0.75 0.18 A3 15 1.0 0.28 A4 15 1.25 0.42 A5 15 1.5 0.47 A6 30 1.0 0.42

[0352] Process B

[0353] A coating solution was prepared by mixing AMPS (10.35 grams), a 1% wt / wt solution of benzophenone (Aldrich Chemical, Milwaukee, WI) in methanol (12 mL), DEX (280 μL), methanol (17.65 mL), and deionized water (3 mL). The solution was about 1.16 M in AMPS. It was coated onto two nylon membrane sheets (8" x 8") and UV irradiated for 30 minutes by the UV-initiated grafting process above to produce a membrane grafted with a first polymer block having monomer units derived from AMPS and end-capped with ethoxythiocarbonylthio groups. After washing as described in Process A and drying, membranes B1 and B2 had mass gains of 4.9% and 5.7%, respectively, corresponding to grafting densities of 0.21 mmol / g and 0.25 mmol / g, respectively.

[0354] Process C

[0355] A coating solution identical to that used for membrane A4 in Table 1 was prepared and used to graft two nylon membrane sheets (8" x 8"), UV irradiated for 30 minutes by the UV-initiated grafting process described above, to produce a membrane having a grafted first polymer derived from AMPS and terminated with ethoxythiocarbonylthio groups. The membrane was washed three times with deionized water only and dried to provide membranes C1 and C2 with mass gains of 9.2% and 8.7%, respectively, corresponding to grafting densities of 0.40 mmol / g and 0.38 mmol / g.

[0356] Process D

[0357] Three coating solutions of 20 mL total volume in methanol were prepared containing 1.0 M AMPS, DEX (140 μL) and sodium salt of 3-carboxybenzophenone (1.0 mL for D1, 0.5 mL for D2, and 0.25 mL for D3 of a 0.033 g / mL aqueous solution, respectively). The solutions were coated onto nylon membrane sheets (8" x 8") and UV grafted for 15 minutes by the UV-initiated grafting process above to produce a cation exchange grafted first polymer block terminated with ethoxythiocarbonylthio groups. After washing with 0.9% brine, methanol, 0.9% brine, methanol (2 more times, 30 minutes each) and drying the sheets, the mass gain was measured to determine the grafting density. The grafting densities of D1, D2, and D3 were 0.16 mmol / g, 0.08 mmol / g, and 0.05 mmol / g, respectively.

[0358] Process E

[0359] A coating solution containing 1 wt% benzophenone and 2.5 wt% methyl ethyl xanthoxyacetate (MEX) in acetone was prepared by weighing out 1.125 g MEX and 0.5 g benzophenone and diluting the mixture to a total of 45 g with acetone. The solution was coated onto a nylon membrane sheet (8" x 8") and UV irradiated for 30 minutes via the UV initiated grafting process above to produce a membrane functionalized with ethoxythiocarbonylthio groups. The membrane was washed three times with acetone and dried for subsequent grafting.

[0360] Process F

[0361] A coating solution of 40 mL total volume in methanol was prepared containing 0.25 M AMPS, DEX (560 uL), and sodium salt of 3-carboxybenzophenone (4 mL of a 0.033 g / mL aqueous solution). This solution (approximately 10 mL) was coated onto a sheet (3" x 4") of nylon blown microfiber web (125 grams per square meter, 13.9% solidity, and 5.9 micron effective fiber diameter) inside a plastic bag with a seal. Two sheets were prepared in separate bags. The coated web was UV irradiated for 30 minutes by the UV-initiated grafting process above to produce a nonwoven grafted with a polymer derived from AMPS and terminated by ethoxythiocarbonylthio groups. After washing the grafted substrate three times for 30 minutes with methanol only and drying the web, the mass gain was measured to determine the grafting density. The grafting densities of the first grafted substrates F1 and F2 were 0.70 mmol / g and 0.69 mmol / g, respectively.

[0362] Process G

[0363] A coating solution of 10 mL total volume in water was prepared containing 0.375 M IEM / agmatine, EXA (100 uL of a 17.9% aqueous solution), and 3-carboxybenzophenone sodium salt (0.5 mL of a 0.033 g / mL aqueous solution). The solution was coated onto a sheet (3" x 4") of nylon (nylon 6) blown microfiber web (125 grams per square meter, 13.9% solidity, and 5.9 micron effective fiber diameter) inside a sealed plastic bag. The coated web was UV irradiated for 30 minutes by the UV-initiated grafting process above to produce a nonwoven grafted with a polymer derived from IEM / agmatine and terminated by ethoxythiocarbonylthio groups. After washing the grafted substrate (30 minutes each) with 0.9% saline (once) and water (twice) and drying the web, the mass gain was measured to determine the grafting density. The grafting density of the first grafted substrate G1 was 2.1 mmol / g (85% mass gain).

[0364] Formation of diblock copolymers grafted to substrates

[0365] Examples 1 to 16

[0366] The first grafted substrate containing the grafted first polymer block prepared by the above process A was coated with various concentrations of poly(ethylene glycol) diacrylate (PEGDA) in deionized water, and then grafted by the above UV-induced grafting process UV for 15 minutes or 30 minutes to prepare a film (second grafted substrate) having a grafted diblock copolymer. The grafting density is listed in Table 2. The protein binding ability determined by the above process is listed in Table 3, where the control is the corresponding film having only the grafted first polymer block (i.e., the first grafted substrate).

[0367] Table 2: Preparation and resulting grafting density of Examples 1 to 16

[0368]

[0369] Table 3: Binding of lysozyme and IgG to Examples 1 to 16

[0370]

[0371]

[0372] <LOD – below the detection limit of the NanoDrop instrument

[0373] Evaluation of Example 16: Dynamic Binding Experiment Using a 25-mm Filter Housing

[0374] Buffered protein solutions were used for the dynamic binding capacity test on the membrane medium, using a nominal 25-mm diameter filter acrylic housing, as described below. Functional membrane medium disks with a diameter of 25 mm were die-cut from the above dried medium samples A6 and Example 16. For each test medium, five functional membrane medium disks were placed at the bottom of the acrylic filter housing. Subsequently, the acrylic housing was assembled. The acrylic housing was adapted to provide an edge seal around the perimeter of the medium using an O-ring, defining an effective filtration area (EFA) of 2.84 square centimeters (cm 2 ) such that the impact fluid would flow into the inlet of the housing, then through the five-layer functional membrane medium, and then out of the outlet of the housing. An exhaust valve located near the fluid inlet enabled the air to be discharged from the housing before the test.

[0375] Use AKTA Avant 150 system (Cytiva, Marlborough, MA) to carry out dynamic binding capacity (DBC) according to the manufacturer's instructions.Before each test, first the filter housing is vented and rinsed with 5mL binding buffer, 5mL elution buffer, and subsequently 10mL binding buffer at a flow rate of 1mL / min.Binding buffer and elution buffer are shown in the following table 4.Binding buffer is subsequently replaced with test analyte solution (protein is dissolved in appropriate binding buffer), and the test is started with a flow rate of 1mL / min.During the filtration test, when the membrane load has the protein in the impact fluid, the UV absorbance of the effluent at 280nm increases.The filter is loaded until absorbance reaches 10% of the maximum absorbance of the test analyte solution in the filtrate.After loading, the filter is washed with 10mL binding buffer to wash away any unconjugated protein.Two different elution processes are carried out to elute the protein bound.The first elution process uses 10mL 100% elution buffer. The second elution process used an elution buffer gradient up to 100% elution buffer over 15 mL and a 5 mL hold at the end of the gradient (20 mL total elution volume).After elution, 10 mL of binding buffer was flushed through the filter.

[0376] Cytiva evaluation software (Unicorn) integrates the peak area of ​​the elution peak and calculates the protein concentration based on the extinction coefficient of the protein eluted from the membrane. The dynamic binding capacity is determined by the amount of membrane-bound protein per calculated volume. The filter housing is then washed with 10mL binding buffer, 10mL elution buffer, and rebalanced with 10mL binding buffer for the next test. Test analyte solutions are prepared in each binding buffer, lysozyme is 0.28mg / mL and monoclonal antibody (mAb; IgG1) is 0.25mg / mL. The buffer solutions used are listed in Table 4.

[0377] Table 4: Binding buffer and elution buffer

[0378] Binding buffer Elution buffer (1)50mM HEPES, pH 7, 1.1mS / cm (1)50mM HEPES, 1M NaCl, pH 7 (2)50mM HEPES, pH 7, 3.4mS / cm (2)50mM HEPES, 1M NaCl, pH 7 (3) 20 mM MES, pH 5, 3.4 mS / cm (3) 20 mM MES, 1 M NaCl, pH 5

[0379] DBC testing was performed in each running buffer on membrane A6 and Example 16. The results are listed in Table 5.

[0380] Table 5: DBC test results of Example 16

[0381]

[0382] This example shows that the addition of the PEGDA block in Example 16 did not prevent the binding of lysozyme under flow conditions, but the binding of mAb was reduced and could be adjusted by adjusting the buffer conditions. Therefore, it should be possible to remove small proteins from large proteins even if they have similar charges.

[0383] Examples 17 to 21

[0384] The first grafted substrate prepared by the above procedure B was coated with various concentrations of PEG monomer in deionized water, followed by UV grafting for 15 minutes or 30 minutes by the above UV-initiated grafting process to prepare a second grafted substrate, which is a membrane with grafted diblock copolymer. The grafting density is listed in Table 6. The protein binding capacity determined by the above procedure is listed in Table 7, where the control is the first grafted substrate, which is a membrane with grafted first polymer block.

[0385] Table 6: Preparation and resulting grafting density of Examples 17 to 21

[0386]

[0387] Table 7: Binding of lysozyme and IgG to Examples 17 to 21

[0388]

[0389] These examples demonstrate that a variety of multifunctional PEG monomers provide good protein selectivity.

[0390] Examples 22 to 25

[0391] Segments of the first grafted substrate C1 were coated with various molar ratios of PEG 575 and HEMA monomers (0.1 M total monomer concentration) in deionized water, followed by UV grafting for 30 minutes by the UV-initiated grafting process described above to prepare membranes with grafted diblock copolymers. The mass gain is listed in Table 6. The protein binding capacity determined by the above process is listed in Table 8, where the control is the first grafted substrate.

[0392] Table 8: Binding of lysozyme and IgG to Examples 22 to 24 and Comparative Example 25

[0393]

[0394] These examples demonstrate that selectivity for proteins can be tuned by inclusion of small comonomers and that blocks of 100% small comonomer (CE 25) provide no selectivity.

[0395] Examples 26 to 28

[0396] Segments of the first grafted substrate D1 were coated with various concentrations of PEGMA 2000 or PEGMA 2000 plus MBA in deionized water, grafted by UV irradiation for 15 minutes, washed three times with deionized water, and dried. Although the grafting density was very low, the IgG binding capacity determined by the above process is listed in Table 9, where the control is the first grafted substrate.

[0397] Table 9: Binding of lysozyme and IgG to Examples 26 to 28

[0398]

[0399] These examples demonstrate that monofunctional PEG provides some reduction in binding capacity for large proteins such as IgG, and that inclusion of a cross-linker improves this reduction.

[0400] Examples 29 to 31

[0401] Segments of the first grafted substrate A2 were UV grafted with PEGDA 575 or PEGDA 575 plus additional crosslinker MBA or AOHPMA for 30 minutes. The composition of the coating solutions, mass gain and protein binding are listed in Table 10, where the control is a membrane with only the grafted first polymer block.

[0402] Table 10: Binding of lysozyme and IgG to Examples 29 to 31

[0403]

[0404] These examples demonstrate that the addition of short chain cross-linkers can tune protein selectivity.

[0405] Examples 32 to 34

[0406] Segments of the first grafted substrate C2 were UV grafted with high molecular weight PEGDA monomers of various concentrations in deionized water for 30 minutes. The membranes were washed 3 times with deionized water and dried. Table 11 lists the monomers, concentrations, mass gain, and protein binding capacity.

[0407] Table 11: Binding of lysozyme and IgG to Examples 32 to 34

[0408]

[0409] Examples 35 to 36

[0410] The coating solution was prepared by mixing a MAPTAC solution (50% wt / wt in water) (2.324 mL for Example 35 and 2.905 mL for Example 36) with 0.5 mL of 3-carboxybenzophenone, sodium salt solution (0.033 g / mL aqueous solution) and 35 μL of diethylbisxanthate, and diluting the mixture to a total of 5 mL with methanol. This provided solutions of 1.0 M and 1.25 M in MAPTAC, respectively. These solutions were coated on nylon membranes, UV grafted for 30 minutes, washed three times with methanol, and dried to produce membranes (first grafted substrates) having an anion exchange first polymer block terminated with ethoxythiocarbonylthio groups with grafting densities of 0.25 mmol / g and 0.78 mmol / g, respectively. Subsequently, each membrane was UV grafted with 0.1 M PEGDA 575 in deionized water for 30 minutes, washed and dried to obtain a membrane with a second polymer block (second grafted substrate) with a mass gain of 10.5% and 10.8%.

[0411] The membranes were tested for binding to β-lactoglobulin (3.5 nm diameter protein), bovine serum albumin (BSA, 7.1 nm diameter protein), and phi6 (75 nm to 85 nm diameter phage). The binding buffer for the proteins was 50 mM HEPES, pH 7, while the binding buffer for phi6 was 25 mM Tris, pH 8. The results are listed in Table 12 as the % reduction in binding of the block copolymer membranes relative to the MAPTAC only control. The % reduction was calculated as follows: 100-100 (binding of block copolymer / binding of control).

[0412] Table 12: Evaluation of Examples 35 to 36

[0413]

[0414] These experiments suggest that it should be possible to capture host cell protein impurities present in clarified cell cultures as viruses or virus-like particles flow through and are purified.

[0415] Examples 37 to 39

[0416] A 6" x 8" functionalized membrane prepared by Procedure E above was coated with IEM / agmatine (0.2M in deionized water) and UV grafted for 30 minutes by the UV initiated grafting process described above to produce a membrane with an anion exchange first polymer block terminated with ethoxythiocarbonylthio groups with a ligand density of 0.29 mmol / g. The membrane was cut into 4 pieces, three of which were coated with PEGDA 575 in deionized water, UV for 30 minutes, washed and dried to provide a membrane with a second polymer block. The membrane was tested for protein binding capacity for β-lactoglobulin and BSA. The results are listed in Table 13.

[0417] Table 13: Binding of β-lactoglobulin and BSA to Examples 37 to 39

[0418]

[0419] These experiments show that optimizing the mass gain of the second polymer block can be important. If too little is grafted, no difference is observed; if too much is grafted, smaller proteins begin to be excluded almost as much as larger proteins; when the correct amount is grafted, a decrease in binding of large proteins is observed, with minimal impact on smaller proteins.

[0420] Examples 40 to 42

[0421] A 6" x 8" functionalized membrane prepared by Procedure E above was coated with IEM / GABA (0.5M in deionized water) and UV grafted for 30 minutes by the UV initiated grafting process described above to produce a membrane (first grafted substrate) having a cation exchange first polymer block terminated with ethoxythiocarbonylthio groups with a ligand density of 0.33 mmol / g. The second polymer block was grafted using various concentrations of PEGDA 575 in deionized water and in the presence or absence of added water soluble xanthate EXA, with a UV grafting time of 15 minutes. The results are shown in Table 14.

[0422] Table 14: Evaluation of Examples 40 to 42

[0423] Example PEGDA 575(M) EXA(M) Mass gain (%) 40 0.1 0 0.6 41 0.2 0 1.3 42 0.2 0.004 3.4

[0424] Examples 43 to 45

[0425] A 6" x 8" functionalized membrane prepared by Procedure E above was coated with IEM / GABA (0.7M plus 0.004M EXA in deionized water) and UV grafted for 30 minutes by the UV-initiated grafting process described above to produce a membrane (first grafted substrate) having a cation exchange first polymer block terminated with ethoxythiocarbonylthio groups with a ligand density of 0.61 mmol / g. The second polymer block was grafted using various concentrations of PEGDA 575 in deionized water and in the presence or absence of added water-soluble xanthate EXA, with a UV grafting time of 30 minutes. Protein binding capacity for lysozyme and IgG was measured. The results are shown in Table 15.

[0426] Table 15: Binding of lysozyme and IgG to Examples 43 to 45

[0427]

[0428] These examples demonstrate that IgG binding can be reduced by appropriate tuning of the second polymer block without any effect on lysozyme binding.

[0429] Examples 46 to 47

[0430] Polyethersulfone membrane substrates (MicroPES 8F, nominal pore size 0.8 μm, obtained from 3M Separation and Purification Sciences, St. Paul, MN) were grafted (15 minutes UV) with VDM / GABA at 0.2M and 0.4M monomer concentrations in deionized water. The grafting solution also contained 0.004M and 0.008M EXA, respectively. This produced a first carboxylate functional block (first grafted substrate) terminated with thiocarbonylthio groups. After washing and drying, the second polymer block was added to the membrane by grafting with PEG 575 at a concentration of 0.2M in deionized water, with a 30 minute UV irradiation time to form a second grafted substrate. The first grafted substrate and the second grafted substrate were tested for lysozyme and IgG binding capacity. The results are listed in Table 16 as the % reduction in binding of the block copolymer membrane relative to the VDM / GABA only control.

[0431] Table 16: Binding of lysozyme and IgG to Examples 46 to 47

[0432]

[0433] These examples show that the block copolymers are selective for the smaller protein lysozyme relative to the larger protein IgG. Optimization of the grafting process can improve the selectivity.

[0434] Examples 48 to 50

[0435] A 6" x 8" functionalized membrane prepared by Procedure E above was coated with IEM / Glycine (0.5M plus 0.004M EXA in deionized water) and UV grafted for 30 minutes by the UV initiated grafting process described above to produce a membrane (first grafted substrate) having a cation exchange first polymer block terminated with ethoxythiocarbonylthio groups with a ligand density of 0.41 mmol / g. The second polymer block was grafted using various PEG monomethacrylates PEGMA 200, PEGMA400, and PEGMA 2000 in deionized water, respectively, with a 30 minute UV grafting time. Protein binding capacity for lysozyme and IgG was measured. The results are shown in Table 17.

[0436] Table 17: Binding of lysozyme and IgG to Examples 48 to 50

[0437]

[0438] These examples show that IgG binding can be reduced by a second polymer block of PEG monomethacrylate (presumably by steric exclusion) without any loss in lysozyme binding.

[0439] Embodiment 51

[0440] The first grafted substrate F2 prepared by the above process F was coated inside a plastic bag with a seal with 0.1M PEGDA in deionized water (10 mL) and UV grafted for 30 minutes by the above UV-initiated grafting process. The web was washed once with 0.9% saline, twice with deionized water (30 minutes each), and then dried. The grafting density of the second polymer block was measured as: F3-0.13 mmol / g. The thickness was measured after drying and was determined to be 0.79 mm. The protein binding capacity determined by the above process was determined by the following modification and is listed in Table 18 below: 3 mg / mL lysozyme in 50 mM HEPES buffer (pH 7) was used instead of 3.5 mg / mL lysozyme in 10 mM MOPS buffer (pH 7).

[0441] Table 18: Binding of lysozyme and IgG to Example 51

[0442]

[0443] This example demonstrates that for block copolymers grafted to a nonwoven substrate, there is no reduction in lysozyme binding, but there is some reduction in binding of the larger protein IgG.

[0444] Embodiment 52

[0445] The first grafted substrate G1 prepared by process G above was cut into two halves (2 inches x 3 inches) and one piece was coated with 0.15M PEGDA and EXA (50uL of 17.9% aqueous solution) in deionized water (5mL) inside a plastic bag with a seal. The coated nonwoven sheet was UV grafted for 30 minutes by the UV-initiated grafting process described above. Both nonwoven sheets G1 and G2 were washed once with 0.9% saline, twice with deionized water (30 minutes each), and then dried. The graft density of the second polymer block was measured to be: G2-0.42mmol / g. The thickness was measured after drying and was determined to be 0.79mm.

[0446] Determine protein binding capacity with the modified scheme different from the above scheme.Three disks of each G1 and G2 are prepared by punching out 18-mm diameter disks from the sheet of substrate.Each disk is placed in a 5mL centrifuge tube with a solution of 4.5mL 5mg / mL BSA in 25mMTris-HCl and 100mM NaCl (pH 7.6).Tube is covered and rolled overnight.Discard supernatant, fill tube with 25mM Tris-HCl and 100mM NaCl (pH 7.6) and roll 15 minutes to 30 minutes to wash away excessive protein solution.Discard supernatant, and repeat buffer wash twice again.By adding 3mL 25mMTris-HCl and 1MNaCl (pH 7.6) and rolling 30 minutes to elute the combined BSA.Use NANODROP UV-VIS spectrophotometer to analyze the protein concentration in the eluent. The elution solution was discarded and then back-extracted with another 3mL 25mM Tris-HCl and 1M NaCl (pH 7.6) for 30 minutes while rolling. The back-extraction solution was discarded, and the tube was filled with 25mM Tris-HCl and 100mM NaCl (pH 7.6) and rolled for 15 to 30 minutes to wash and balance the disk. The supernatant was discarded and the buffer wash was repeated twice more. The excess solution in the disk was gently squeezed out and discarded. A solution of 4.5mL 5mg / mL β-lactoglobulin in 25mM Tris-HCl and 100mM NaCl (pH 7.6) was added to each tube in a 5mL tube with washed G1 and G2 disks. The tubes were capped and rolled overnight. The supernatant was discarded, and the tubes were filled with 25mM Tris-HCl and 100mM NaCl (pH 7.6) and rolled for 15 to 30 minutes to wash away the excess protein solution. The supernatant was discarded and the buffer wash was repeated twice. The bound β-lactoglobulin was eluted by adding 3mL 25mMTris-HCl and 1M NaCl (pH 7.6) and rolling for 30 minutes. The protein concentration in the eluate was analyzed using a NANODROP UV-VIS spectrophotometer. The UV absorbance and protein extinction coefficient provided by the supplier determined the binding capacity of each substrate. The results were reported as the mean value of three replicates in mg / mL (mg number of bound protein / mL number of nonwoven volume).

[0447] Table 19: Binding of β-lactoglobulin and BSA to Example 52

[0448]

[0449] This example demonstrates that for block copolymers grafted to a nonwoven substrate, there is no reduction in β-lactoglobulin binding and that the binding of the larger protein BSA is reduced.

[0450] Examples 53 to 54

[0451] A coating solution containing 1.5 M AMPS and the sodium salt of 3-carboxybenzophenone (Aldrich Chemical, Milwaukee, WI) in methanol (2.0 mL of a 0.033 g / mL aqueous solution) was prepared in a total volume of 20 mL. This solution was coated onto a nylon membrane sheet (8" x 8") and UV grafted for 15 minutes via the UV initiated grafting process described above to produce a grafted cation exchange first polymer block derived from AMPS and terminated with semi-pinacol containing groups. After washing with 0.9% brine, methanol, 0.9% brine, methanol (2 more times, 30 minutes each) and drying the sheet, the mass gain was measured to determine a graft density of 1.25 mmol / g. Portions of the first grafted substrate were coated with poly(ethylene glycol) diacrylate (PEGDA 575) at a concentration of 0.1 M (Example 53) or 0.2 M (Example 54) in deionized water, followed by UV grafting for 15 minutes by the UV-initiated grafting process described above to prepare membranes Examples 53 and 54 (second grafted substrates) with grafted diblock copolymers. The grafting densities of these second grafted substrates were 0.22 mmol / g and 0.40 mmol / g, respectively. The protein binding capacity determined by the above process is listed in Table 20, where the control is the corresponding membrane having only the grafted first polymer block (i.e., the first grafted substrate).

[0452] Table 20: Binding of lysozyme and IgG to Examples 53 to 54

[0453]

[0454] Examples 55 to 56

[0455] The first grafted substrate was prepared by a process similar to that described above for Examples 53 to 54, except that the AMPS concentration was 0.75 M, resulting in a grafted nylon membrane having a grafting density of 0.54 mmol / g and at least some of the grafted chains terminated with semi-pinacol groups. Portions of the first grafted substrate were coated with poly(ethylene glycol) diacrylate (PEGDA 575) at a concentration of 0.1 M (Example 55) or 0.2 M (Example 56) in deionized water, followed by UV grafting for 15 minutes by the UV-initiated grafting process described above to prepare membranes Examples 55 and 56 (second grafted substrates) having grafted diblock copolymers. The grafting densities of these second grafted substrates were 0.17 mmol / g and 0.39 mmol / g, respectively. The protein binding capacity determined by the above process is listed in Table 21, where the control is the corresponding membrane having only the grafted first polymer block (i.e., the first grafted substrate).

[0456] Table 21: Binding of lysozyme and IgG to Examples 55 to 56

[0457]

[0458] Examples 57 to 58

[0459] The first grafted substrate was prepared by a process similar to that described above for Examples 53 to 54, except that the AMPS concentration was 0.5 M and the Type II photoinitiator was 1.0 mL of a sodium carboxybenzophenone initiator solution, resulting in a grafted nylon membrane having a grafting density of 0.30 mmol / g and even lower and at least some of the grafted chains terminated with semi-pinacol groups. Portions of the first grafted substrate were coated with poly(ethylene glycol) diacrylate (PEGDA 575) at a concentration of 0.1 M (Example 57) or 0.2 M (Example 58) in deionized water, followed by UV grafting for 15 minutes by the UV initiated grafting process described above to prepare membranes Examples 57 and 58 (second grafted substrates) with grafted diblock copolymers. The grafting densities of these second grafted substrates were 0.09 mmol / g and 0.31 mmol / g, respectively. The protein binding capacity determined by the above procedure is listed in Table 22, where the control is the corresponding membrane having only the grafted first polymer block (ie, the first grafted substrate).

[0460] Table 22: Binding of lysozyme and IgG to Examples 57 to 58

[0461]

[0462] Examples 59 to 60

[0463] A coating solution containing 1 wt% benzophenone in acetone was coated onto a nylon membrane sheet (6" x 8") and UV irradiated for 30 minutes via the UV initiated grafting process described above to produce a membrane functionalized with semi-pinacol containing groups. The membrane was washed three times with acetone and dried for subsequent grafting.

[0464] The membrane was coated with IEM / GABA (0.4 M in deionized water) and UV grafted for 30 minutes by the above-mentioned UV-initiated grafting process to generate a membrane (first grafted substrate) with a cation exchange first polymer block, which was terminated with a semi-pinacol group and had a ligand density of 0.38 mmol / g. The second polymer block was grafted to a portion of the grafted membrane using various concentrations of PEGDA 575 in deionized water and the UV grafting time was 30 minutes. The protein binding capacity for lysozyme and IgG was measured. The results are shown in Table 23.

[0465] Table 23: Binding of lysozyme and IgG to Examples 59 to 60

[0466]

Claims

1. A separation product, comprising: a porous polymer substrate, the porous polymer substrate being a solid material; and A plurality of block copolymer chains grafted to a solid porous polymer substrate and extending away from a surface of the solid porous polymer substrate, wherein the block copolymer chains comprise a) a first polymer block covalently attached to the solid porous polymer substrate, wherein the first polymer block comprises an acidic monomer unit containing an acidic group or a salt thereof, a basic monomer unit containing a basic group or a salt thereof, or a combination thereof; and b) a second polymer block covalently bonded to the first polymer block, wherein the first polymer block is positioned between the second polymer block and the solid porous polymer substrate, wherein the second polymer block comprises a polyether-containing monomer unit. 2 . The separation article of claim 1 , wherein the first polymer block is directly and covalently attached to carbon atoms of the solid porous polymer substrate.

3. The separation product according to claim 1 or 2, wherein the acid monomer and / or the basic monomer has formula (IV) or a salt thereof CH2=CR 21 -C(=O)-X 1 -R 22 -[Z-R 22 ] n -L (IV) in R 21 is hydrogen or methyl; Each R 22 are independently (hetero)alkylene; X 1 Is -O- or -NR 23 -, where R 23 is hydrogen or a hydrocarbon group; Z is a heteroalkylene group comprising at least one hydrogen bond donor, at least one hydrogen bond acceptor, or a combination thereof; n is an integer of 0 or 1; and L is a ligand functional group which is an acidic group, a basic group or a salt thereof.

4. The release article of any one of claims 1 to 3, wherein the porous polymer substrate comprises particles, fibers, films, nonwoven webs, membranes, sponges, or sheets.

5. The release article of claim 4, wherein the porous polymer substrate comprises a nonwoven web or film.

6. The separation article of any one of claims 1 to 5, wherein the second polymer block is hydrophilic or water swellable.

7. A method of making a separation article comprising a solid porous polymer substrate and a plurality of block copolymers grafted to the solid polymer substrate and extending away from a surface of the solid porous polymer substrate, the method comprising: providing the solid porous polymer substrate; as well as Grafting a plurality of first polymer blocks to the solid porous polymer substrate using a reversible deactivation free radical polymerization process, wherein the first polymer blocks are covalently bonded to the solid porous polymer substrate, and wherein the first polymer blocks are the reaction product of a first polymerizable composition comprising 1) an acidic monomer comprising an ethylenically unsaturated group and an acid group or a salt thereof; and / or 2) a basic monomer comprising an ethylenically unsaturated group and a basic group or a salt thereof; and forming a plurality of second polymer blocks, wherein the second polymer blocks are covalently bonded to the first polymer block using the reversible deactivation free radical polymerization method, wherein the first polymer block is located between the solid porous polymer substrate and the second polymer block, and wherein the second polymer block is a reaction product of a second polymerizable composition comprising 1) A polyether monomer comprising at least one ethylenically unsaturated group and a polyether group.

8. The method according to claim 7, wherein the reversible deactivation free radical polymerization method is a reversible addition-fragmentation chain transfer polymerization method.

9. The method according to claim 7 or 8, wherein the reversible deactivation free radical polymerization method comprises using a thiocarbonylsulfide-containing compound as a polymerization control agent.

10. The method according to any one of claims 7 to 9, wherein the thiocarbonylsulfide-containing compound has the formula -SC(=S)-R 1 A thiocarbonylthio-containing group, and wherein R 1 is alkoxy, aralkyloxy, alkenyloxy or –N(R 4 )2; and Each R 4 is an alkyl group, or two adjacent R 4 The groups combine with the nitrogen to which they are both attached to form a first heterocyclic ring having 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, which is saturated or unsaturated and optionally fused to one or more second rings, which are carbocyclic or heterocyclic.

11. The method of any one of claims 7 to 10, wherein the block copolymer is directly and covalently bonded to carbon atoms of the solid porous polymer substrate. 12 . The method according to claim 7 , wherein before forming the second polymer block, the first polymer block has a terminal thiocarbonylthio-containing group or a semi-pinacol group.

13. A method of separating a mixture of materials of different sizes and optionally of different ionic contents, the method comprising: Prepare or provide a separation article comprising a solid porous polymer substrate and a plurality of block copolymers grafted to the solid porous polymer substrate using a reversible deactivation free radical polymerization method, wherein the block copolymers extend away from the surface of the solid porous polymer substrate and comprise a) a first polymer block covalently attached to the porous polymer substrate, the first polymer block comprising a first monomer unit having a binding group, the binding group being an acid group, a basic group or a salt thereof for interacting with a material having a complementary group; as well as b) a second polymer block covalently bonded to the first polymer block, wherein the first polymer block is positioned between the second polymer block and the solid porous polymer substrate, wherein the second polymer block comprises a polyether-containing monomer unit; and The mixture of materials is passed through the separation article, wherein the second polymer block separates the mixture of materials based on size or steric exclusion and allows only a portion of the materials to contact the acid groups, basic groups, or salts thereof of the first polymer block.

14. The method of claim 13, wherein the mixture of materials comprises biological material.

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