Polyethersulfone copolymers and articles prepared therefrom

Abstract

Polyethersulfone copolymers and porous polymer articles containing this copolymer are provided. This copolymer is formed from a reaction mixture containing (a) a functional diphenyl-containing macromer having grafted side chains and (b) a functional diphenyl sulfone. Porous polymer articles are typically membranes, often either flat sheets or hollow fibers. Porous polymer articles can be used, for example, to separate mixtures of biomaterials having different average sizes based on the average pore diameter of the porous polymer article. For example, biomaterials such as proteins, viruses, and cells can be separated based on size.

Description

[Technical Field]

[0001] Separators with porous polymer substrates have been used in a wide range of industrial, pharmaceutical, and medical applications. Some of these separators work by separating mixtures of materials based on the average size of the materials in the mixture. These separators typically hold materials of a certain size, such as those with a diameter larger than the pore diameter in the polymer substrate, while allowing other materials with a diameter smaller than the pore diameter in the polymer substrate to pass through.

[0002] Membranes formed from polyether sulfone (PES) have been used to separate biological materials such as proteins, viruses, and cells based on size. The pore size of PES membranes can be adjusted during membrane casting to suit specific filtration needs. Furthermore, hydrophilic homopolymers such as poly(vinyl pyrrolidone) (PVP), poly(oxazoline) (POx), and poly(ethylene glycol) (PEG) can be added to the membrane casting solution to make the membrane hydrophilic and thus somewhat resistant to fouling by biological elements, oils, surfactants, and other fluid components that tend to adhere to the membrane surface. However, membranes cast with these hydrophilic homopolymers are often not uniformly hydrophilic and are still susceptible to fouling when contaminated compositions pass through them. Moreover, since these hydrophilic homopolymers are typically water-soluble, some of them may be extracted from the membrane during use. Therefore, users typically pre-flush the membrane before filtering the composition of interest to reduce the extractable content to a suitable level. [Overview of the Initiative]

[0003] A polyether sulfone copolymer and a porous polymer article containing this copolymer are provided. This copolymer is formed from a reaction mixture containing (a) a functional diphenyl-containing macromer having grafted side chains and (b) a functional diphenyl sulfone. The porous polymer article is typically a membrane, often either a flat sheet or hollow fibers. The porous polymer article can be used, for example, to separate mixtures of biomaterials having different average sizes based on the average pore diameter of the porous polymer article. For example, biomaterials such as proteins, viruses, and cells can be separated based on size.

[0004] In a first aspect, a copolymer is provided that includes a plurality of repeating units linked by -O- groups. The plurality of repeating units includes (a) a repeating unit of formula (I)

Chemical formula

Chemical formula

[0005] In formula (I), the group R 1 is a plurality of repeating groups of the formula -(CH2) y -X- (where X is -O- or -NH, and each y is an integer in the range of 1 to 4). More specifically, R 1 is a group of the formula -[(CH2) y -X] n - (where n is an integer in the range of 3 to 1000). The asterisk (*) is the bonding site to the -O- group that binds two repeating units.

[0006] In a second aspect, a porous polymer article is provided that includes the copolymer described above in the first aspect. In most embodiments, the porous polymer article is a membrane.

[0007] A third embodiment provides a method for separating biomaterials based on size. The method comprises providing a porous polymer article as described above in a second embodiment, and passing an aqueous mixture of biomaterials through the porous polymer article such that the mixture of biomaterials comprises a plurality of biomaterials having different average sizes. The method further comprises separating the mixture of biomaterials based on their average size such that the first biomaterials, which are smaller than the second biomaterials, permeate the porous polymer article at a faster rate.

[0008] As used herein, the terms "a," "an," "the," and "at least one" are interchangeable.

[0009] The term "and / or" means either one or both. For example, "A and / or B" means A alone, B alone, or both A and B.

[0010] The term "alkylene" refers to the divalent group, which is the radical of an alkane. An 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. Alkylenes may be linear, branched, cyclic, or a combination thereof. Linear alkylenes have at least one carbon atom, while cyclic or branched alkylenes have at least three carbon atoms.

[0011] The term "leaving group" refers to a group that can detach from a compound containing an electron pair, such as -F, -Cl, -Br, -I, CF3SO3-, and -SO2-C6H4-CH3.

[0012] The term "nucleophile" refers to a group having an electron-rich atom that can donate an electron pair to form a covalent bond. As used herein, nucleophiles are often hydroxy(-OH) or -O-Si(R c )3(wherein, R c (It is alkyl or aryl.)

[0013] The term "macromer" is used herein to refer to a reactive compound having grafted polymer groups. More specifically, as used herein, the term macromer refers to a functional diphenyl-containing compound having (1) at least two functional groups that are leaving or nucleophilic groups, and (2) a covalently bonded (grafted) polymer side chain. The number of functional groups is usually equal to 2. Macromers are sometimes called polymers.

[0014] The term "monomer" is used herein to refer to reactive compounds that do not have polymer groups. A monomer is typically a compound having at least two functional groups, which are either leaving groups or nucleophiles. The number of functional groups is usually equal to 2.

[0015] The terms “polymer” and “polymer material” are used interchangeably and refer to materials formed by reacting one or more monomers and / or macromers. These terms include homopolymers, copolymers, terpolymers, and so on. Similarly, the terms “polymerize” and “polymerizing” refer to the process of producing polymer materials, which may include homopolymers, copolymers, terpolymers, and so on. The term “copolymer” is used herein to refer to polymers and polymer materials derived from two or more types of monomers and / or macromers.

[0016] The terms "casting solution" and "polymer dope" are used interchangeably to refer to compositions used to form porous membranes.

[0017] The term "membrane" refers to a porous article formed from a polymer composition. A membrane may be in the form of a flat sheet or hollow fibers. The membranes described herein are typically prepared using a phase separation process.

[0018] For any given range, the end values ​​are considered part of the range. [Brief explanation of the drawing]

[0019] [Figure 1] This is a perspective view of a partial cross-section of an exemplary hollow fiber membrane. [Figure 2] This is a cross-sectional view of an exemplary hollow fiber membrane. [Figure 3] This is a scanning electron microscope image of a cross-section of the hollow fiber membrane of Example HFM1 at 200x magnification. [Figure 4] This is a scanning electron microscope image of a cross-section of the hollow fiber membrane of Example HFM1 at a magnification of 1,000x. [Figure 5] This is a scanning electron microscope image of the tubular wall of the hollow fiber membrane of Example HFM1 at a magnification of 5,000x. [Figure 6] This is a scanning electron microscope image of the outer wall of the hollow fiber membrane of Example HFM1 at a magnification of 5,000x. [Figure 7] This is a scanning electron microscope image of a cross-section of the comparative hollow fiber membrane CHFM1 at a magnification of 200x. [Figure 8] This is a scanning electron microscope image of a cross-section of the comparative hollow fiber film CHFM1 at a magnification of 1,000x. [Figure 9] This is a scanning electron microscope image of the lumen wall of the comparative hollow fiber membrane CHFM1 at a magnification of 5,000x. [Figure 10] This is a scanning electron microscope image of the outer wall of the comparative hollow fiber membrane CHFM1 at a magnification of 5,000x. [Figure 11] This plot shows the volumetric measurement throughput of membrane modules containing hollow fiber membranes in Example HFM1 and Comparative Example CFM1, obtained by dividing the flux of a 0.1 wt percent TWEEN®-80 solution by the flux of a buffer solution without TWEEN®-80. [Modes for carrying out the invention]

[0020] Copolymers and porous polymer articles containing these copolymers are provided. The copolymer is formed from a reaction mixture containing (a) a functional diphenyl-containing macromer having grafted polymer side chains and (b) a functional diphenyl sulfone. Porous polymer articles containing copolymers are typically membranes, often either flat sheets or hollow fibers. Porous polymer articles can be used, for example, to separate mixtures of biomaterials having different average sizes based on the average pore diameter of the porous polymer article. For example, biomaterials such as proteins, viruses, and cells can be separated based on size.

[0021] Advantageously, copolymers contain macromer units with hydrophilic covalent polymer side chains, substantially reducing the amount of pre-flushing required to remove extractable hydrophilic polymers from porous polymer articles prepared from these copolymers. Furthermore, the grafted polymer side chains of the copolymers result in the formation of films with a uniform hydrophilic surface. As a result, these films tend to have greater resistance to fouling than those formed using hydrophilic homopolymers. Moreover, copolymers with grafted polymer side chains are typically amphiphilic but not water-soluble. Because these copolymers are typically not water-soluble, they are usually less extractable than previously used hydrophilic homopolymers.

[0022] Functional diphenyl-containing macromers having grafted polymer side chains Functional diphenyl-containing macromers having grafted polymer side chains are provided. These macromers having grafted polymer side chains typically have at least two functional groups that can react with other monomers to form copolymers. The functional groups may be either leaving groups or nucleophiles.

[0023] The functional diphenyl-containing macromer is of formula (III). [ka] Group R 1 is -(CH2) y -X-(where X is -O- or -NH-), and contains a plurality of repeating groups. More specifically, R 1 is a group of the formula -[(CH2) y -X] n -(where n is an integer in the range of 3 to 1000). Each y is an integer in the range of 1 to 4, for example, in the range of 1 to 3, in the range of 2 to 3, or equal to 2. Each R 2 is independently a functional group that is a leaving group or a nucleophilic group. The compound of formula (III) is usually of formula (III-A). [Chemical formula]

[0024] In many embodiments, the group R 1 is of the formula -R 3 -C(=O)-Z-[(CH2) y -X] n -R 4 (where R 3 is alkylene, Z is -O or -NH-, X is -O- or -NH-, and R 4 is a terminal group). The variable y is an integer in the range of 1 to 4, and the variable n is an integer in the range of 3 to 1000. The group X is often -O-, and Z is either -O- or -NH-. That is, the compound of formula (III) is of formula (III-1) [Chemical formula] and the compound of formula (III-A) is of formula (III-A-1). [Chemical formula] In many embodiments of the compounds of formula (III-1) and (III-A-1), X is -O-, and the group -[(CH2)-X] n- is a poly(alkylene oxide) such as poly(butylene oxide), poly(propylene oxide), poly(ethylene oxide), or poly(methylene oxide) group.

[0025] The base n in equations (III-1) and (III-A-1) is an integer equal to at least 3, and is often in the range of 3 to 1000. That is, n is at least 3, at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, at least 100, at least 200, at least 300, at least 400, or at least 500, and at most 1000, at most 900, at most 800, at most 700, at most 600, at most 500, at most 400, at most 300, at most 200, at most 100, at most 90, at most 80, at most 70, at most 60, at most 50, at most 40, at most 30, or at most 20. For example, the variable n may be in the range of 3 to 500, 3 to 100, 5 to 100, or 5 to 50.

[0026] The base R in equations (III-1) and (III-A-1) 3 It is usually alkylene. Alkylene can have any preferred number of carbon atoms, but R 3 In many cases, it is ethylene. That is, the group R 1 In many cases, the formula is -CH2CH2-C(=O)-Z-[(CH2) y -X] n -R 4 That is the case.

[0027] Base R in equation (III-A-1) 4 is a terminal group. Any suitable terminal group can be used, but R 4 In many cases, they are alkyl groups. Alkyl groups often have 1 to 4 carbon atoms, 1 to 3 carbon atoms, or 1 to 2 carbon atoms. In many cases, R 4 It is methyl.

[0028] Each base R in equations (III), (III-A), and (III-A-1) 2These are independently leaving groups or nucleophiles. Suitable leaving groups include, for example, -F, -Cl, -Br, -I, CF3SO3-, and -SO2-C6H4-CH3. Suitable nucleophiles include, for example, -OH or -O-Si(R 6 )3(in the formula, each R 6 Examples of groups include alkyl groups having 1 to 4 carbon atoms.Optionally, a nucleophilic group -O-Si(R 6 )3 can be converted to an -OH group after the formation of a compound of formula (III) having grafted polymer side chains. When a polymer material (i.e., copolymer) containing repeating units derived from the macromer of formula (III) is formed, the group R 2 This is reactivity (i.e., sensory appeal).

[0029] The compound of formula (III-A) can be formed using any suitable method. An example of such a method is shown in reaction scheme A.

[0030] Reaction scheme A [ka] Compound (1) often has Z equal to -O-, and R 3 It is ethylene, and each R 2 It is a diphenolic acid in which is hydroxyl. Compound (2) is often a polyethylene glycol monoamine (where X is equal to -O- and Z is -NH-) or a polyethylene glycol monoalcohol (where X is -O- and Z is -O-), where R 4 It is usually methyl. Compound (3) is the compound of formula (III-A-1).

[0031] Functional diphenyl-containing macromers of formula (III) (e.g., those of formula (III-1), (III-A), and (III-A-1)) typically have a weight-average molecular weight (Mw) in the range of 350 daltons to 50,000 daltons. Mw is often at least 350, at least 400, at least 500, at least 1000, at least 1500, at least 2000, at least 2500, at least 3000, at least 4000, at least 5000, at least 10,000, at least 15,000, or at least 20,000 Daltons, and at most 50,000, at most 45,000, at most 40,000, at most 30,000, at most 25,000, at most 20,000, at most 15,000, at most 10,000, at most 5,000 Daltons, at most 2,000 Daltons, or at most 1,000 Daltons. For example, this range could be 380-20,000, 500-10,000, 500-5000, 500-2000, 500-1000, 1000-10,000, 2500-10,000, 2000-10,000, 2000-5000, or 2500-5000 Daltons. The weight-average molecular weight of the compound of formula (I) can be determined by nuclear magnetic resonance (NMR) spectroscopy, as described in the following examples.

[0032] Copolymer having repeating units derived from functional diphenyl-containing macromers having grafted polymer side chains. formula R 1 A functional diphenyl-containing macromer of formula (III) having a grafted polymer side chain can be used to form a copolymer. For ease of discussion, this copolymer will be referred to herein as "POLY-1". POLY-1 is an amphiphilic graft copolymer. POLY-1 typically has two functional groups R 2 The first macromer of formula (III) having [ka] Two functional groups R, which are either nucleophilic or leaving groups. 5The second monomer of formula (IV) [ka] It is formed by reacting with [another compound]. In many embodiments, the first macromer of formula (III) is of formula (III-A), and the second monomer of formula (IV) is of formula (IV-A). [ka] [ka]

[0033] The reaction product is typically a copolymer (POLY-1) having multiple repeating units linked via -O- groups. The multiple repeating units are (a) repeating units of formula (I) derived from the macromer of formula (III). [ka] and repeating units of formula (II) derived from monomers of formula (IV) [ka] This includes the following. Each asterisk (*) is a binding site to an -O- group that connects the repeating units. In many embodiments, the multiple repeating units of formula (I) are those of formula (IA), and the multiple repeating units of formula (II) are those of formula (II-A). [ka] [ka]

[0034] The repeating unit of formula (IA) is derived from the macromer of formula (III-A), and the repeating unit of formula (II-A) is derived from the monomer of formula (IV-A).

[0035] R in the first macromer of equation (III) 2 However, if it is a leaving group (L) as shown in formula (III-B), [ka] At least a portion of the second monomer of formula (IV) is either two hydroxynucleophiles as shown in formula (IV-1), or -O-Si(R) as shown in formula (IV-2). c )3(in the formula, each R c It has two groups (which are alkyl or aryl). [ka] In most embodiments, the second monomer having a nucleophile is of formula (IV-1). Often, the first macromer is of formula (III-B-1). [ka] (wherein L is -F, -Cl, -Br, -I, CF3SO3-, or -SO2-C6H4-CH3), and the second monomer is of formula (IV-A-1). [ka]

[0036] However, equation (III-C) [ka] As shown, R in the first macromer of equation (III) 2 If is a nucleophile such as hydroxyl, then at least a portion of the second monomer of formula (IV) has two leaving groups as shown in formula (IV-3). [ka] In most embodiments, the first macromer is given by formula (III-C-1) [ka] The second monomer is of formula (IV-A-2) [ka] (wherein L is typically -F, -Cl, -Br, -I, CF3SO3-, or -SO2-C6H4-CH3)

[0037] In many embodiments, the molar ratio of the first macromer of formula (III) to the second monomer of formula (IV) is less than 1. To provide copolymers with a molar ratio of less than 1, a mixture of the second monomer of formula (IV) is R 5 A portion of the second monomer having a nucleophilic group, and R 5 It is used in conjunction with another second monomer having a leaving group. Therefore, the second monomer is often a mixture of monomers of formula (IV-1) and / or formula (IV-2) and monomer of formula (IV-3). In many embodiments, the second monomer is a mixture of monomers of formula (IV-1) and formula (IV-3). The first macromer and the second monomer are combined such that the total moles of nucleophiles are equal to or approximately equal to the moles of leaving groups.

[0038] In many embodiments, the second monomer is of formula (IV-A-1), formula (IV-A-2), or a mixture thereof. [ka] The monomer of formula (IV-A-1) is within the range of formulas (IV-A) and (IV-1) above, while the monomer of formula (IV-A-2) is within the range of formulas (IV-A) and (IV-3) above. In many embodiments, L is -Cl or -F.

[0039] POLY-1 may include additional optional repeating units in addition to those given in formulas (I) and (II) above. These optional repeating units are formulas (VA), (VB), (VC), (VD), (VE), and (VF). [ka] [ka] [ka] [ka] [ka] [ka] The following third repeating units, or combinations thereof, are included in the formula (wherein an asterisk (*) is a binding site to an -O- group that binds the repeating unit). In many embodiments, these repeating units are derived from monomers such as those of formulas (VI-A) to (VI-F) or their isomers, respectively. The monomer unit of formula (VI-F) may, for example, arise from the hydrolysis of a portion of the monomer of formula (III). In these formulas, the group R 8 R is either a nucleophile or a leaving group as described above. In many embodiments, R 8 It is hydroxyl. [ka] [ka] [ka] [ka] [ka] [ka]

[0040] While POLY-1 can be formed using any amount of the first macromer of formula (III), this amount often needs to be controlled when preparing membranes, such as those described below, using the resulting copolymer POLY-1. For example, when a membrane is prepared using a phase separation process, the amount of the first macromer of formula (III) typically needs to be controlled so that POLY-1 is amphiphilic but not water-soluble. If the amount of the first macromer of formula (III) is too small, the membrane formed from the copolymer tends to lack sufficient antifouling properties, and biomaterials such as proteins may adhere undesirably to its surface. Increasing the amount of the first macromer of formula (III) used to form the graft copolymer POLY-1 tends to increase the amount of POLY-1 on the membrane surface during solvent-induced phase separation (SIPS) casting, and tends to provide desired membrane surface properties (e.g., water wettability and fouling resistance) at lower concentrations of POLY-1 in the casting solution. However, if the content of the first macromer of formula (III) is too high, POLY-1 may become water-soluble. Water solubility of POLY-1 is generally undesirable because it can lead to the loss of copolymer into the precipitation bath during membrane casting and / or higher water extractability of the graft copolymer from the finished membrane. Therefore, in many cases, it is desirable to prepare POLY-1 using the maximum amount of macromer of formula (III) that can be incorporated without making POLY-1 water-soluble. This maximum amount depends on the hydrophilicity of the grafted polymer side chains, which in turn depends on the composition of the grafted polymer side chains.

[0041] The amphiphilic graft copolymer POLY-1 is often prepared from a polymerizable composition containing 10% to 60% by weight of the first macromer of formula (III), based on the total weight of the polymerizable material (i.e., macromer and monomer). The amount of the first macromer is often at least 10, at least 15, at least 20, at least 25, or at least 30% by weight, and up to 60, up to 55, up to 50, up to 45, up to 40, up to 35, or up to 30% by weight, relative to the total weight of the polymerizable composition. In some embodiments, the amount of the first macromer of formula (III) is in the range of 10-55, 10-50, 10-45, 10-40, 10-30, 15-60, 15-55, 15-50, 15-45, 15-40, 20-60, 20-55, 20-50, 20-45, 20-40, 20-35, or 20% to 30% by weight, based on the total weight of the polymerizable composition.

[0042] In addition to the macromer of formula (III), the polymerizable composition used to form POLY-1 may contain 40 to 90 weight percent of a second monomer of formula (IV). The amount of monomer of formula (IV) may be at least 40, at least 45, at least 50, at least 55, at least 60, at least 65, or at least 70, and at most 90, at most 85, at most 80, at most 75, at most 70, at most 65, or at most 60 weight percent, based on the total weight of the polymerizable composition. In some embodiments, the amount of the second monomer of formula (IV) is in the range of 45-90, 50-90, 55-90, 60-90, 70-90, 40-85, 45-85, 50-85, 55-85, 60-85, 40-80, 45-80, 50-80, 55-80, 60-80, 65-80, or 70-80% by weight, based on the total weight of the polymerizable composition.

[0043] In addition to the macromer of formula (III) and the monomer of formula (IV), the polymerizable composition used to form POLY-1 may optionally contain 0 to 50 weight percent of a third monomer of formulas (VA), (VB), (VC), (VD), (VE), (VF), or a mixture thereof. If present, the amount of the third monomer may be at least 1, at least 2, at least 5, at least 10, or at least 15, and up to 50, up to 40, up to 30, up to 25, up to 20, up to 15, up to 10, or up to 5 weight percent, based on the total weight of the polymerizable composition.

[0044] POLY-1 typically has a weight-average molecular weight (Mw) in the range of 10,000 daltons to 250,000 daltons. The weight-average molecular weight is typically at least 10,000, at least 15,000, at least 20,000, at least 25,000, at least 30,000, at least 35,000, at least 40,000, at least 45,000, at least 50,000, at least 75,000, or at least 100,000 Daltons, and at most 250,000, at most 225,000, at most 200,000, at most 175,000, at most 150,000, at most 125,000, at most 100,000, at most 80,000, at most 60,000, at most 50,000, at most 40,000, at most 35,000, or at most 30,000 Daltons. In some embodiments, the range is 20,000 to 200,000, 25,000 to 100,000, 25,000 to 80,000, 25,000 to 60,000, 25,000 to 50,000, or 25,000 to 40,000 Daltons. The weight-average molecular weight can be determined by gel permeation chromatography (GPC), as described in the following examples.

[0045] Porous Articles A porous polymer article is provided containing an amphiphilic grafted copolymer POLY-1 having repeating units derived from a functional diphenyl-containing macromer having grafted polymer side chains as described above. The porous polymer article may be in any form, but is typically a membrane. The membrane may be, for example, a flat sheet or a hollow fiber. The membrane is typically formed by a phase separation process.

[0046] In many embodiments, the phase separation process used to form the film is a solvent-induced phase separation (SIPS) process, and the resulting film can be called a “SIPS film.” SIPS films may also be referred to by other names, such as “DIPS films” formed by diffusion-induced phase separation, “NIPS films” formed by non-solvent-induced phase separation, or “phase-conversion films.” All of these processes are referred to herein as SIPS processes, and the products are referred to as SIPS films.

[0047] In the SIPS process, the polymer material is combined with other solution components, such as a solvent suitable for the polymer material, to prepare a substantially homogeneous solution interchangeably called a “casting solution” or “polymer dope.” The casting solution is formed into a flat sheet using a coating process or into a hollow tube using a spinning process. The flat sheet or hollow fiber is then immersed in a “quench solution” containing the non-solvent of the polymer material. Phase separation of the polymer solution occurs due to the exchange of the solvent in the casting solution with the non-solvent in the quench solution, resulting in a solid, flat, porous sheet or hollow fiber. In some embodiments, the flat sheet or hollow fiber can be exposed to a humid atmosphere or vapor before immersion in the quench solution to initiate the phase separation process.

[0048] The casting solution used to form the SIPS film typically comprises a mixture of polymer material and a water-miscible organic solvent. The mixture of polymer material includes POLY-1 described above, which has grafted polymer side chains; POLY-2, a second polymer which is typically an aromatic polyethersulfone lacking grafted polymer side chains; and an optional third polymer which is typically a hydrophilic pore-forming agent. In addition to the polymer material, the casting solution also contains a water-miscible solvent capable of dissolving POLY-1, POLY-2, and the optional POLY-3. Furthermore, the casting solution may optionally contain water.

[0049] The casting solution is (1) grafted polymer side chain R 1 Formula (I) is derived from a bifunctional diphenyl-containing macromer having [ka] Repeating unit and (2) Formula (II) derived from a bifunctional diphenyl sulfone without grafted polymer side chains [ka] Repeating unit The casting solution contains POLY-1, which is the copolymer described above. The casting solution typically contains 1% to 20% by weight of POLY-1 based on the total weight of the casting solution. This amount may be at least 1, at least 1.5, at least 2, at least 2.5, at least 3, at least 4, or at least 5% by weight, and up to 20, up to 18, up to 15, up to 12, up to 10, up to 8, or up to 5% by weight, based on the total weight of the casting solution. For example, the amount of POLY-1 may range from 1.5 to 20, 1.5 to 15, 2 to 20, 2 to 15, 2 to 10, or 2% to 5% by weight, based on the total weight of the casting solution. Various repeating units are linked by -O-bonds.

[0050] In addition to POLY-1, the casting solution contains a second polymer which can be called POLY-2. POLY-2 is given by formula (II) [ka] It is an aromatic polyethersulfone having repeating units of formula (I) (wherein the formula, the asterisk (*) is a binding site to an -O- group that connects two repeating units). This second polymer may be a homopolymer or a copolymer. If POLY-2 is a copolymer, it is made from a polymerizable mixture that does not contain the repeating units of formula (I) and does not contain the macromer of formula (III). POLY-2 lacks the grafted polymer side chains present in POLY-1.

[0051] In some embodiments of POLY-2, the repeating unit of formula (II) is combined with one or more optional repeating units of formulas (VA), (VB), (VC), (VD), (VE), (VF), or combinations thereof, as listed above, which may be included in POLY-1. Adjacent repeating units are typically linked by an -O- group. These optional repeating units are typically no more than 50 mole percent of all repeating units in POLY-2. That is, they can be present in amounts from 0 mole percent to 50 mole percent based on all repeating units in POLY-2. For example, these optional repeating units may be up to 50, up to 45, up to 40, up to 35, up to 30, up to 25, up to 20, up to 15, up to 10, or up to 5 mole percent of all repeating units in POLY-2.

[0052] POLY-2 typically has a weight-average molecular weight (Mw) in the range of 30,000 daltons to 150,000 daltons (30 kDa to 150 kDa). For example, Mw is often at least 30, at least 40, at least 50, at least 60, or at least 70, and at most 150, at most 140, at most 130, at most 120, at most 100, at most 90, at most 80, at most 70, at most 60, or at most 50 kDa. This range may be, for example, 30 to 120, 50 to 120, or 60 kDa to 100 kDa. The weight-average molecular weight can be determined by gel permeation chromatography (GPC), as described in the following examples.

[0053] The amount of POLY-2 in the casting solution is typically in the range of 10 to 40 weight percent based on the total weight of the casting solution. This amount can be at least 10, at least 12, at least 15, or at least 20 weight percent, and up to 40, up to 35, up to 30, up to 25, up to 20, or up to 15 weight percent based on the total weight of the casting solution. For example, the amount of POLY-2 can be in the range of 10-35, 10-30, 10-25, 12-40, 12-35, 12-30, 12-25, 15-40, 15-35, 15-30, 15-25, 20-40, 20-35, or 20-30 weight percent based on the total weight of the casting solution. The amount of POLY-2 in the casting solution can affect the pore size of the resulting membrane formed from the casting solution. For example, increasing the amount of POLY-2 tends to decrease the average pore size of the membrane. Varying the amount of POLY-2 can be used to change the size of the material that can permeate the membrane and / or the rate at which it permeates the membrane.

[0054] In addition to POLY-1 and POLY-2, an optional third polymer material, often called POLY-3, is included in the casting solution. This third polymer is typically selected to be a hydrophilic polymer having higher water solubility than either POLY-1 or POLY-2. If phase separation occurs during the film manufacturing process, the third polymer (POLY-3) typically does not undergo phase separation. That is, POLY-3 remains in the solution, unlike either POLY-1 or POLY-2. Suitable hydrophilic polymers for POLY-3 include, for example, poly(2-vinylpyrrolidone), polyethylene glycol, polyoxazoline, polyvinyl alcohol, polyglycol monoesters, polysorbates such as carboxymethylcellulose and polyoxyethylene sorbitan monooleate, carboxymethylcellulose polyacrylic acid, polyacrylamide, copolymers thereof, or blends thereof. In many embodiments, POLY-3 is polyethylene glycol or a polymer mixture containing polyethylene glycol.

[0055] POLY-3 can have any desired molecular weight and may contain a mixture of polymers of multiple molecular weights. In some embodiments, the amount of one or more components of POLY-3 in the membrane is desirable to be low in order to reduce its extractability. In such cases, the weight-average molecular weight of that component of POLY-3 is often less than 1000 daltons. For example, the weight-average molecular weight may be up to 750 daltons, such as in the range of 100-750, 100-500, 100-400, 200-750, 200-500, or 200-400 daltons. In other embodiments, the molecular weight of one or more components of POLY-3 in the membrane is selected to be higher in order to impart higher fouling resistance or to adjust the porosity of the membrane. In such cases, the weight-average molecular weight of that component of POLY-3 is often greater than 1000 daltons. For example, the weight-average molecular weight of the component of POLY-3 can range from a maximum of 750,000 daltons, for example, from 1,100 daltons to 750,000 daltons, 1,100 daltons to 500,000 daltons, 1,100 daltons to 400,000 daltons, 2,000 daltons to 500,000 daltons, or 20,000 daltons to 50,000 daltons. The weight-average molecular weight can be determined by gel permeation chromatography (GPC), as described in the following examples.

[0056] The amount of POLY-3 in the casting solution is typically in the range of 0 to 65 weight percent based on the total weight of the casting solution. This amount may be at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 35, or at least 40 weight percent, and at most 65, at most 60, at most 55, at most 50, at most 45, at most 40, or at most 35 weight percent, based on the total weight of the casting solution. For example, this amount may be in the range of 1 to 65, 1 to 60, 5 to 60, 10 to 60, 10 to 50, 10 to 40, 10 to 30, 20 to 60, 20 to 50, 20 to 40, 30 to 30 to 60, 30 to 50, or 30 to 40 weight percent, based on the total weight of the casting solution.

[0057] In addition to POLY-1, POLY-2, and POLY-3, the casting solution may contain a water-miscible organic solvent. Examples of usable water-miscible organic solvents include glycols, glycerols, butyrolactones, ε-caprolactams, N-methylpyrrolidones, dimethyl sulfoxides, dimethylacetamides, dimethylformamides, and combinations thereof. In some embodiments, the water-miscible organic solvent contains N-methylpyrrolidone, as N-methylpyrrolidone is typically a good solvent for both POLY-1 and POLY-2.

[0058] Any suitable amount of a water-miscible organic solvent may be included in the casting solution. This amount may range from 20 to 70 weight percent based on the total weight of the casting solution. This amount may be at least 20, at least 25, at least 30, at least 35, at least 40, or at least 45 weight percent, and up to 70, up to 65, up to 60, up to 55, up to 50, up to 45, or up to 40 weight percent based on the total weight of the casting solution. For example, this amount may range from 20 to 65, 20 to 60, 20 to 55, 20 to 50, 20 to 45, 20 to 40, 25 to 65, 25 to 60, 25 to 55, 25 to 50, 25 to 45, 25 to 40, 30 to 60, 30 to 55, 30 to 50, 30 to 45, or 30 to 40 weight percent based on the total weight of the casting solution.

[0059] The casting solution may optionally contain water. For example, the casting solution may contain 0 to 10 weight percent of water. If present, this amount may be at least 1, at least 2, at least 3, at least 4, or at least 5, and at most 10, at most 8, at most 6, at most 5, or at most 4 weight percent, based on the total weight of the casting solution. This amount may range, for example, from 1 to 8, 1 to 6, 1 to 5, 2 to 10, 2 to 8, 2 to 6, 2 to 5, 3 to 10, 3 to 8, 3 to 6, or from 3 to 5 weight percent, based on the total weight of the casting solution.

[0060] In some embodiments, the casting solution contains, based on the total weight of the casting solution, 1% to 20% by weight of POLY-1, 10% to 40% by weight of POLY-2, 0% to 65% by weight of POLY-3, 20% to 70% by weight of a water-miscible organic solvent, and 0% to 10% by weight of water. In some examples, the casting solution contains 1.5% to 15% by weight of POLY-1, 12% to 30% by weight of POLY-2, 20% to 50% by weight of POLY-3, 25% to 55% by weight of a water-miscible organic solvent, and 2% to 6% by weight of water. In other examples, the casting solution contains 2% to 10% by weight of POLY-1, 15% to 25% by weight of POLY-2, 30% to 40% by weight of POLY-3, 30% to 40% by weight of a water-miscible organic solvent, and 3% to 5% by weight of water. In most embodiments, the casting solution is clear and macroscopically homogeneous.

[0061] The membrane formed from the casting solution may be in the form of a sheet or a hollow fiber membrane. Either type of membrane can be formed from the casting solution. After forming either a sheet or hollow fiber, the sheet or hollow fiber is immersed in a quench bath to allow the membrane to precipitate. If desired, the membrane can be optionally transferred to a second bath, such as a water bath, to extract additional material from the membrane.

[0062] In many embodiments, the precipitation bath contains water and may optionally further contain a water-miscible organic solvent, such as those listed above, for use in the casting solution. For example, the precipitation bath often contains 50% to 100% by weight water and 0% to 50% by weight water-miscible organic solvent. In some embodiments, the precipitation bath contains 55% to 100% by weight water and 0% to 45% by weight water-miscible organic solvent, or 60% to 100% by weight water and 0% to 40% by weight water-miscible organic solvent. The water-miscible solvent is often selected to be N-methylpyrrolidone.

[0063] A film sheet can be formed using any preferred method, but the casting solution is often heated to a high temperature, for example, in the range of 40 to 80 degrees Celsius. The casting solution can be coated onto a support that has also been heated in the range of 40 to 80 degrees Celsius. The film can be prepared as a coating using a notch bar having a preferred gap height, for example, in the range of 25.4 to 508 micrometers. The notch bar is often heated in the range of 40 to 80 degrees Celsius before spreading the casting solution onto the surface of the support. Immediately after forming the film of the casting solution on the support, the coated support is typically immersed in a precipitation bath, often heated in the range of 40 to 80 degrees Celsius. If desired, the film can be further extracted in a second bath containing water, optionally. The film can be dried in an oven after formation. The oven temperature may be, for example, in the range of 40 to 80 degrees Celsius.

[0064] In some embodiments, the film is in the form of a sheet. The sheet typically has a thickness ranging from 30 micrometers to 250 micrometers. For example, this thickness may be at least 30, at least 40, at least 50, at least 60, at least 80, or at least 100, and up to 250, up to 225, up to 200, up to 175, up to 150, up to 125, up to 120, up to 110, or up to 100 micrometers. The range may be, for example, 30-200, 30-150, 50-150, 50-125, 50-110, or 50-100 micrometers.

[0065] In many embodiments, the membrane is in the form of hollow fibers. Hollow fibers can be formed by extruding a casting solution through a coaxial spinneret die. This coaxial spinneret die typically has an annular gap and a central internal channel coaxial with the annular gap. The annular gap is separated from the central internal channel by a needle. The casting solution is introduced into the annular gap, while bore fluid is introduced into the internal chamber. The bore fluid stabilizes the lumen of the hollow fiber membrane as it is formed.

[0066] The spinneret die is selected according to the desired dimensions of the hollow fiber membrane. Any suitable spinneret die can be used, but the outer diameter of the ring is often in the range of 300 to 1000 micrometers. The outer diameter of the ring may be, for example, at least 300, at least 400, at least 500, and at most 1000, at most 800, or at most 600 micrometers. The inner diameter of the ring, which is also the outer diameter of the needle, is often in the range of 190 to 980 micrometers. The inner diameter of the ring may be, for example, at least 190, at least 200, at least 300, or at least 500, and at most 980, at most 900, at most 800, at most 600, or at most 500 micrometers. The inner diameter of the needle is often in the range of 40 to 830 micrometers. The inner diameter of the needle may be, for example, at least 40, at least 50, at least 75, at least 100, at least 150, at least 200, at least 250, at least 300, at least 350, at least 400, and up to 830, up to 800, up to 750, up to 700, up to 650, up to 600, up to 550, or up to 500 micrometers.

[0067] One exemplary spinneret die has a ring outer diameter of 1000 micrometers, a needle outer diameter of 980 micrometers, an annular gap of 10 micrometers, a needle inner diameter of 830 micrometers, and a needle thickness of 75 micrometers. Another exemplary spinneret die has a ring outer diameter of 500 micrometers, a needle outer diameter of 300 micrometers, an annular gap of 100 micrometers, a needle inner diameter of 150 micrometers, and a needle thickness of 75 micrometers. Yet another exemplary spinneret die has a ring outer diameter of 410 micrometers, a needle outer diameter of 300 micrometers, an annular gap of 55 micrometers, a needle inner diameter of 150 micrometers, and a needle thickness of 75 micrometers. Yet another exemplary spinneret die has a ring outer diameter of 300 micrometers, a needle outer diameter of 190 micrometers, an annular gap of 55 micrometers, a needle inner diameter of 40 micrometers, and a needle thickness of 75 micrometers.

[0068] The bore fluid composition typically comprises a water-miscible organic solvent, water, and optionally a hydrophilic polymer such as those listed above for POLY-3. Any suitable water-miscible organic solvent, such as those listed above, can be used for casting solutions. In some embodiments, the water-miscible organic solvent used in the bore fluid comprises N-methylpyrrolidone, and any optional hydrophilic polymer used in the bore fluid comprises polyethylene glycol.

[0069] The amount of water-miscible organic solvent in a bore fluid composition is often in the range of 30 to 95 weight percent, based on the total weight of the bore fluid. This amount may be at least 30, at least 35, at least 40, at least 45, or at least 50 weight percent, and at most 95, at most 90, at most 85, at most 80, at most 75, at most 70, at most 65, at most 60, at most 55, or at most 50 weight percent. For example, this amount may be in the range of 30-90, 30-80, 30-75, 30-70, 30-60, 30-50, 40-90, 40-80, 40-75, 40-70, 40-60, or 40 to 50 weight percent.

[0070] The amount of water in the bore fluid composition is often in the range of 1% to 55% by weight, based on the total weight of the bore fluid. This amount can be at least 1.5, at least 2, at least 2.5, at least 3, at least 4, at least 5, at least 10% by weight, and at most 55, at most 50, at most 45, at most 40, at most 35, at most 30, at most 25, at most 20, at most 15, or at most 10% by weight. For example, this amount can be in the range of 1-50, 1-40, 1-30, 1-20, 1-15, 1-10, 2-50, 2-40, 2-30, 2-20, 2-15, 2-10, 5-50, 5-40, 5-30, 5-20, or at least 5% to 15% by weight.

[0071] The amount of an optional hydrophilic polymer in the bore fluid composition is often in the range of 0 to 60 weight percent based on the total weight of the bore fluid. This amount may be 0, at least 1, at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 35, at least 40 weight percent, and up to 60, up to 55, up to 50, up to 45, up to 40, up to 35, or up to 30 weight percent. For example, this amount may be in the range of 0 to 50, 10 to 60, 10 to 55, 10 to 50, 10 to 45, 10 to 40, 20 to 60, 20 to 55, 20 to 50, 20 to 45, 20 to 40, 30 to 60, 30 to 55, 30 to 50, 30 to 45, 40 to 60, or 40 to 50 weight percent.

[0072] Overall, the bore fluid composition contains 30 to 95 weight percent of a water-miscible organic solvent, 1 to 55 weight percent of water, and 0 to 60 weight percent of an optional hydrophilic polymer. In some examples, the bore fluid composition contains 35 to 80 weight percent of a water-miscible organic solvent, 2 to 40 weight percent of water, and 20 to 55 weight percent of a hydrophilic polymer. In other examples, the bore fluid composition contains 35 to 75 weight percent of a water-miscible organic solvent, 2 to 20 weight percent of water, and 30 to 55 weight percent of a hydrophilic polymer. In yet another example, the bore fluid composition contains 40 to 50 weight percent of a water-miscible organic solvent, 5 to 15 weight percent of water, and 40 to 50 weight percent of a hydrophilic polymer. Typically, the bore fluid is clear and macroscopically homogeneous.

[0073] As described above, the bore fluid is introduced into the internal chamber, while the casting solution is introduced into the annular gap of the coaxial spinneret die. In some embodiments, the casting solution and the bore fluid are filtered to remove any particulate material before being introduced into the annular gap and internal chamber, respectively. Both fluid flows are often heated before being introduced into the die. For example, both fluid flows may be heated in the range of 30 to 80 degrees Celsius. The flow rates of the bore fluid and the casting solution can usually be controlled independently.

[0074] After exiting the coaxial spinneret die and before entering the sedimentation bath, the extruded product optionally passes through a climate-controlled zone having specified climatic conditions. The climate-controlled zone is often in the form of a sealed chamber. The extruded product is often held for 10 seconds or less in the climate-controlled zone having a relative humidity of 20 to 95 percent and a temperature of 25 to 75 degrees Celsius. The relative humidity is often at least 40, at least 50, at least 55, at least 60, at least 65, at least 70, or at least 75 percent, and at most 90, at most 85, at most 80, at most 75, or at most 70 percent. The temperature is often at least 25, at least 30, at least 35, at least 40, at least 45, or at least 50 degrees Celsius, and at most 90, at most 85, at most 80, or at most 75 degrees Celsius. For example, a climate control zone may contain air with a relative humidity of 75% to 90% and a temperature of 30°C to 50°C, a relative humidity of 60% to 75% and a temperature of 50°C to 70°C, or a relative humidity of 75% to 90% and a temperature of 50°C to 70°C.

[0075] The retention time within the climate control zone is often at least 0.5, at least 1, at least 2, or at least 3, and at most 10, at most 8, at most 6, or at most 5 seconds. To establish stable conditions within the climate control zone, air often flows through the zone at a speed of less than 0.5 m / s, preferably in the range of 0.15 m / s to 0.35 m / s.

[0076] As the extrusion product is guided through a climate-controlled zone set to climatic conditions, pre-solidification may occur outside the extrusion product by absorption of water vapor acting as a non-solvent before it enters the precipitation bath.

[0077] After passing through an environmentally controlled zone, the extruded product is led to a precipitation bath in the range of 50°C to 80°C to complete the formation of the hollow fiber membrane structure. The composition of the precipitation bath may be the same as that described above for preparing membranes in sheet form. In the precipitation bath, the membrane structure is formed by precipitation (e.g., coagulation) and then stabilized. Extraction of water-miscible solvents and hydrophilic polymers occurs simultaneously. That is, water, water-miscible organic solvents, and optionally hydrophilic POLY-3 can be extracted. The pores of the membrane are formed in the precipitation bath by the phase separation and extraction processes that take place.

[0078] After formation and extraction in the sedimentation bath, the hollow fiber membrane can be processed using conventional methods. For example, the hollow fiber membrane can optionally be further processed by pouring deionized water through the lumen and extracted in water for several hours at high temperatures, such as 70°C to 100°C.

[0079] After drying at either room temperature or high temperature, the hollow fiber membranes can be wound onto coils or directly formed into bundles having a suitable number and length of fibers. Before manufacturing the bundles, auxiliary threads, for example in the form of multifilament yarn, can be added to the hollow fiber membranes to create spacing between them and to ensure good flow around the individual hollow fiber membranes within the bundle.

[0080] The membrane typically contains 1% to 50% by weight of POLY-1 based on the total weight of the membrane. For example, the membrane may contain at least 1, at least 2, at least 3, at least 5, at least 10, at least 15, at least 20, or at least 25, and up to 50, up to 45, up to 40, up to 35, up to 30, up to 25, or up to 20% by weight of POLY-1. This amount may range from 2 to 50, 2 to 40, 3 to 30, 5 to 30, 5 to 25, or 5% to 20% by weight based on the total weight of the membrane.

[0081] In addition to POLY-1, the membrane typically contains 50 to 99 weight percent of POLY-2, based on the total weight of the membrane. The amount of POLY-2 may be at least 50, at least 55, at least 60, at least 65, at least 70, at least 75, or at least 80, and up to 99, at most 98, at most 97, at most 95, at most 90, at most 85, at most 80, or at most 75 weight percent, based on the total weight of the membrane. The amount of POLY-2 may range from 50 to 98, 60 to 98, 70 to 97, 70 to 95, 75 to 95, or 80 to 95 weight percent, based on the total weight of the membrane.

[0082] The membrane may optionally contain POLY-3, a water-miscible organic solvent, and / or water. The amount of POLY-3 is typically in the range of 0 to 20 weight percent based on the total weight of the membrane. For example, the amount of POLY-3 may be at least 0.1, at least 0.5, at least 1, at least 2, or at least 5, and up to 20, up to 15, up to 10, up to 8, or up to 5 weight percent. The amount of water-miscible organic solvent is typically in the range of 0 to 1 weight percent based on the total weight of the membrane. For example, the amount of water-miscible organic solvent may be at least 0.05, at least 0.1, at least 0.2, at least 0.3, or at least 0.5, and up to 1, up to 0.8, up to 0.6, up to 0.5, up to 0.3, or up to 0.1 weight percent.

[0083] Figure 1 shows a perspective view of a partial cross-section of an exemplary hollow fiber membrane 12. The hollow fiber membrane 12 may have a continuous hollow lumen 16 extending from one end of the fiber to the other. The outer surface 18 facing outward forms the outside of the fiber, and the inner surface 20 facing the hollow lumen 16 defines a fiber portion 26 having a wall thickness 28. The fiber portion 26 is typically porous and contains a polymer blend including a mixture of POLY-1 and POLY-2.

[0084] The resulting hollow fiber membrane is typically a permeable hollow fiber membrane that is asymmetrical overall. As used herein, the term “asymmetrical” means that the average pore diameter varies across the entire wall thickness 28. The term “overall” means that the pore diameter gradually changes in size across the wall thickness 28 of the fiber portion 26.

[0085] The wall thickness 28 of the fiber portion 26 of the hollow fiber membrane 12, measured between the outer surface 18 and the inner surface 20, may be in the range of 10 to 400 micrometers or 20 to 300 micrometers. The fiber portion 26 is formed from a casting solution. The wall thickness may be, for example, at least 10, at least 20, at least 30, at least 40, at least 50, at least 60, at least 80, at least 100 micrometers, and up to 400, up to 350, up to 300, up to 275, up to 250, up to 225, up to 200, up to 175, up to 150, up to 125, up to 100, up to 80, or up to 60, or up to 50 micrometers. In some hollow fiber membranes, the wall thickness is in the range of 30 to 200, 30 to 100, 40 to 150, 40 to 100, 40 to 80, or 40 to 60 micrometers.

[0086] Similarly, to achieve the desired flow and / or pressure drop through the lumen of the hollow fiber membrane, the inner diameter of the hollow fiber membrane, corresponding to the diameter of the inner wall 20 in Figure 1, is often in the range of 50 to 800 micrometers. This diameter may be at least 50, at least 60, at least 80, at least 100, at least 150, at least 200, at least 250, or at least 300 micrometers, and at most 800, at most 700, at most 600, at most 500, at most 400, at most 300, or at most 200 micrometers. In some hollow fiber membranes, the inner diameter is in the range of 50 to 700, 50 to 600, 100 to 500, 100 to 400, 100 to 300, or 100 to 200 micrometers.

[0087] The wall thickness and diameter of the membrane (i.e., inner or lumen diameter, and outer diameter) can also be determined, for example, using scanning electron microscopy or transmission electron microscopy (scanning electron micrograph, SEM, or transmission electron micrograph, TEM) at magnifications up to 20,000x. In some embodiments, the hollow fiber membrane may have a meandering structure extending from the inner surface to the outer surface.

[0088] Figure 2 shows a cross-sectional view of an exemplary hollow fiber membrane 112. The hollow fiber membrane 112 may have a continuous hollow lumen 116 extending from one end of the fiber to the other, an outer surface 118 facing outward that forms the outside of the fiber, and an inner surface 120 facing the hollow lumen 116 that defines the boundary of the continuous hollow lumen 116. The fibrous portion 126 of the membrane has a cross-sectional thickness 128 that starts from the inner surface 120 and extends to the outer surface 118. The pore diameter changes progressively across the cross-sectional thickness 128. The pore diameter may increase or decrease progressively across the cross-sectional zone 128, but in many cases, the pore diameter decreases progressively. Across the cross-sectional zone, for example, pore size (diameter) often varies in the range of 10 nanometers to 100 nanometers, but there may be pores with larger diameters such as up to 500, up to 1000, up to 5000, or even up to 10,000 nanometers.

[0089] Figures 3, 4, 5, and 6 are scanning electron microscope images of exemplary hollow fiber membranes formed in Example HFM1 as described below. Figures 3 and 4 show cross-sections of the hollow fiber membranes at different magnifications, Figure 5 shows the tubular wall of the hollow fiber membrane, and Figure 6 shows the outer wall of the hollow fiber membrane. The hollow fiber membrane is porous in its width direction, but the size and shape of the pores vary in the diameter direction of the membrane.

[0090] The membranes described herein are typically prepared using POLY-1 and POLY-2 and are advantageous compared to membranes known to date. As described above, POLY-1 is often made of the compound R 1 Formula (III) having grafted polymer side chains [ka] The first macromer consists of two functional groups R, which are either nucleophilic or leaving groups. 5 Formula (IV) [ka] It is prepared by reacting it with a second monomer. The reaction product is typically a copolymer having repeating units linked via -O- groups. Thus, the copolymer has multiple R groups that are grafted polymer side chains. 1 It has.

[0091] Unlike previously prepared membranes, the structural characteristics of POLY-1 can be modified and controlled. For example, both the molecular weight and graft density of the polymer side chains can be controlled via stoichiometry during synthesis. Furthermore, the amount of the first macromer used to form POLY-1 can be controlled. This is in contrast to other methods where the graft reaction is performed on a pre-formed polymer material. Thus, the polymer structure of POLY-1 can be systematically modified to impart desired characteristics to the membrane, such as specific porosity, pore size, and / or surface hydrophilicity. For example, with respect to fouling resistance to various biocontaminants (e.g., proteins), detergents, oils, etc., it is advantageous to optimize the graft density and grafted chain length of the copolymer's hydrophilic side chains. Resistance to fouling by some contaminants can be optimized with short, densely spaced hydrophilic side chains, while resistance to other contaminants can be best achieved with longer, more sparsely spaced side chains. Using the methodology described herein, POLY-1 is purified by conventional synthesis techniques and provided as a solid for direct incorporation into membrane casting formulations together with POLY-2 and optionally POLY-3.

[0092] Membranes containing POLY-1 exhibit enhanced fouling resistance compared to membranes without POLY-1. For example, as shown in Figure 2, membranes containing POLY-1 do not show a decrease in flux as throughput increases when the feed flow contains a surfactant such as TWEEN®-80. Surfactants, sometimes also known as detergents, are generally included in solutions containing biomolecules to increase stability during purification and storage. Therefore, membranes containing POLY-1 are suitable for the purification of biomolecules stabilized with surfactants, which can increase the yield and purity of biomolecules purified using membranes containing POLY-1. Membranes containing POLY-1 may also exhibit enhanced resistance to fouling by biomaterials such as proteins, oils, lipids, or other hydrophobic, amphiphilic, or ionic fluid components.

[0093] Methods for using porous materials Porous articles can be used to separate various compositions based on the size of the components in the composition. In many embodiments, porous articles are suitable membranes for separating components of a mixture based on their size. For example, a mixture of biomaterials can be separated based on the size of the various biomaterials in the mixture. Larger biomaterials are typically retained upstream of the membrane and / or pass through the membrane at a slower rate than smaller biomaterials (i.e., permeate). Therefore, the composition exiting the membrane tends to have a concentrated concentration of smaller biomaterials compared to the original mixture of biomaterials.

[0094] Therefore, a method is provided for separating components based on size. This method comprises providing a porous separation article, such as those described above, which is typically a membrane. The method further comprises passing a first composition through a membrane, wherein the first composition of biomaterial comprises a plurality of different biomaterials having different average sizes. The method further comprises separating the plurality of different biomaterials based on their different average sizes. The first biomaterial having a smaller average size than the second biomaterial can typically permeate the membrane more quickly than the second biomaterial. Similarly, the second biomaterial having a larger average size than the first biomaterial is retained by the membrane and / or permeates the membrane more slowly than the first biomaterial. Thus, the second composition exiting the membrane has a higher concentration of the first biomaterial and a lower concentration of the second component compared to the original first composition of biomaterial.

[0095] Examples of biomaterials that can be separated include bacteria, viruses, viral particles, proteins, protein fragments, fusion proteins, cells, cell debris, DNA, and RNA. Biomaterials of different sizes within the same general category, as well as biomaterials within different general categories, can be separated based on their different average sizes. The second composition exiting the membrane has a higher concentration of smaller biomaterials.

[0096] For example, a membrane can selectively retain viruses or viral particles having a larger average size than other biomaterials in a first composition of the biomaterial. Furthermore, viruses and / or viral particles of different sizes can be separated from each other by smaller viruses and / or viral particles passing through the membrane more quickly. In certain examples, adeno-associated viruses or parts of adeno-associated viruses can be separated from larger viruses.

[0097] Similarly, different bacteria can be isolated based on their average size, with smaller bacteria permeating membranes more quickly, or bacteria can be isolated from different types of biological materials based on differences in average size.

[0098] Similarly, proteins or protein fragments can be separated from other biomaterials. In some cases, proteins or protein fragments are smaller than other biomaterials and can permeate membranes more quickly. Proteins or protein fragments may be, for example, monoclonal antibodies, monoclonal antibody fragments, or fusion proteins.

[0099] In some embodiments, the hollow fiber membranes of the present disclosure can be used in a number of extracorporeal blood purification procedures, including dialysis, blood oxygenation, and plasma exchange. [Examples]

[0100] Unless otherwise specified or readily apparent from the context, all parts, percentages, ratios, etc., in the examples and the remainder of this specification are based on weight.

[0101] [Table 1]

[0102] Test method GPC method Gel permeation chromatography data were obtained using an Agilent 1260 Infinity GPC equipped with an isocratic pump, standard degasser, standard autosampler, thermostat-controlled column compartment set to 55°C, and a refractive index detector using two Agilent PLGel 5μm Mixed-D 300×7.5mm gel permeation chromatography columns. Gel permeation chromatography samples were prepared at 5 mg / mL in a solution of 20 mM lithium bromide in N-methylpyrrolidone and then passed over a Pall 0.2 micrometer polypropylene syringe filter. The column was maintained at 55°C with a flow rate of 0.8 mL / min. All molecular weight data are reported against Agilent polystyrene standards (Polystyrene Calibration Kit SM-10, part number PL2010-0100).

[0103] NMR spectroscopy: Characterization of structure Nuclear magnetic resonance spectra were obtained using a Bruker Avance III 300 MHz instrument equipped with a room-temperature broadband probe or a Bruker Avance III 500 MHz instrument equipped with a broadband cryoprobe. Proton ( 1 The H) spectrum was obtained with a pulse angle of 15° and a relaxation delay of 4 seconds.

[0104] Scanning electron microscope (SEM) The pore structure of the film was examined using a scanning electron microscope (obtained from NCI Inc., Brooklyn Park, MN under the trade name "HITACHI TM4000Plus"). Cross-sections were prepared by freeze-rupturing the sample under liquid nitrogen. A thin layer of gold was sputter-coated onto the sample to make it conductive. An accelerating voltage of 15 kV, a current of 51.7 μA, and a working distance of 6 mm to 7 mm were used. Images were obtained using backscattered electrons (BSE mode).

[0105] Examples of polymers (i.e., macromers) Polymer Example 1 (PE1): mPEG 550 diphenolic acid ester (n=10) [ka]

[0106] NMR analysis of poly(ethylene glycol) monomethyl ether 550 used in this experiment revealed that it contained approximately 10 ethylene glycol units.

[0107] A 1 L round-bottom flask was filled with 49.6 g of mPEG 550 dissolved in 400 mL of toluene, followed by the addition of 30.1 g of diphenolic acid and 2 g of pTSA monohydrate. A Dean-Stark trap and reflux condenser were attached to the reaction flask. The mixture was stirred under a nitrogen atmosphere and heated under reflux overnight. The water / toluene mixture in the Dean-Stark trap was drained, and heating was continued. Three more parts of the toluene distillate were then drained. The reaction mixture was cooled and diluted with ethyl acetate. The mixture was washed with saturated NaHCO3 solution. The organic portion was washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting syrup was partitioned between CH2Cl2 and 5% Na2CO3 solution. The layers were separated, and the organic portion was washed sequentially with water and brine. The organic portion was dried with Na2SO4, filtered, and concentrated under reduced pressure to obtain 67.9 g of mPEG 550 diphenolic acid ester as a purple syrup.

[0108] 1 H NMR(500MHz,chloroform-d)δ ppm 7.09-7.25(m,2H)6.98(d,J=8.6Hz,4H)6.72(br d,J=8.4Hz,4H)4.07-4.19(m,2H)3.47-3.70(m,38H)3.35(s,3H)2.29-2.41(m,2H)2.06-2.20(m,2H)1.51(s,3H).

[0109] Polymer Example 2 (PE2): mPEG 2000 diphenolic acid ester (n=48) [ka]

[0110] NMR analysis of poly(ethylene glycol) monomethyl ether 2000 used in this experiment revealed that it contained approximately 48 ethylene glycol units.

[0111] In a 3 L three-necked round-bottom flask equipped with a stirring bar and a Dean-Stark apparatus, 237.33 g of mPEG 2000, 41.73 g of diphenolic acid, and 2.31 g of pTSA monohydrate were added, and the mixture was suspended in 1.05 kg of toluene. The reaction solution was heated under reflux and maintained under reflux for 16 hours. The Dean-Stark apparatus was opened, and toluene was distilled off the reaction mixture to recover 902 g of toluene. The crude concentrate was diluted in 500 mL of acetone and added to 6.2 L of methyl tert-butyl ether. The resulting white precipitate was allowed to settle over 16 hours, and the methyl tert-butyl ether was decanted. The precipitate was collected and dried on a counter in the air for 3 days to obtain 247.86 g of mPEG 2000 diphenolic acid ester as a white solid.

[0112] 1 H NMR(300MHz,DMSO-d6)δ ppm 9.19(br s,2H)6.94(d,J=8.8Hz,4H)6.66(d,J=8.4Hz,4H)4.07(m,2H)3.51(br m,202H)3.25(s,3H)2.26(m,2H)2.03(m,2H)1.47(s,3H).

[0113] Polymer Example 3 (PE3): mPEG 550 diphenolic acid amide (n=12) [ka]

[0114] NMR analysis of poly(ethylene glycol) monomethyl ether 550 (Tokyo Chemical Industries, Ltd. catalog number P2184) used in this experiment revealed that it contained approximately 12 ethylene glycol units.

[0115] A solution of 88.4 g of mPEG 550 dissolved in 500 mL of CH2Cl2 was placed in a 2 L round-bottom flask. Triethylamine (53.7 mL) and DMAP (980 mg) were added to the reaction mixture, and the mixture was cooled to 0°C under an N2 atmosphere. Next, methanesulfonyl chloride (14.9 mL) was added to the stirred mixture over 10 minutes. After stirring overnight, the reaction mixture was quenched by adding 300 mL of saturated NaHCO3 solution. The layers were separated, and the aqueous portion was further extracted with 75 mL of CH2Cl2. The combined organic layers were washed with H2O (200 mL) and brine (100 mL), dried over Na2SO4, and concentrated under reduced pressure to obtain 100 g of mPEG 550 methanesulfonate as an orange oil. 1 H NMR(500MHz,chloroform-d)δ ppm 3.09(s,3H)3.39(s,3H)3.56(m,2H)3.60-3.70(m,42H)3.76(m,2H)4.39(m,2H).

[0116] A solution of 100 g of mPEG 550 methanesulfonate dissolved in 100 mL of anhydrous DMF was placed in a 500 mL round-bottom flask. 12.2 g of sodium azide was added, and the mixture was stirred and heated to 50°C under an N2 atmosphere. After 3 days, the reaction product was concentrated under reduced pressure. The resulting syrup was partitioned between 400 mL of CH2Cl2 and 400 mL of H2O. The layers were separated, and the aqueous portion was further extracted with 200 mL of CH2Cl2. The combined organic layers were washed with H2O (2 × 300 mL), dried over Na2SO4, and concentrated under reduced pressure to obtain 90.4 g of mPEG 550 azide as an amber-colored syrup. 1 ¹H NMR (500 MHz, chloroform-d) δ ppm 3.35-3.37 (m, 5H) 3.54 (m, 2H) 3.60-3.71 (m, 44H).

[0117] A solution of mPEG 550 azide (14.4 g) dissolved in 100 mL of methanol was transferred to a 500 mL Parr bottle. 10% Pd / C (228 mg) was added to the bottle, and the mixture was shaken at 50 PSI under an H2 atmosphere for 2 hours. The reaction mixture was filtered through a Celite pad and concentrated to obtain mPEG 550 amine (13.3 g) as a light-colored oil. 1 ¹H NMR (500 MHz, chloroform-d) δ ppm 2.84 (m, 2H) 3.37 (s, 3H) 3.50 (m, 2H) 3.54 (m, 2H) 3.62 (m, 42H).

[0118] mPEG 550 amine (13.3 g) and 4,4-bis(4-hydroxyphenyl)pentanoate (7.14 g, prepared according to Sane et al. European Polymer Journal 47 (2011) 1621-1629) were combined in a 500 mL round-bottom flask. A 5 M solution of sodium methoxide (11.9 mL) was added to the flask, and the stirred mixture was heated to 70°C under an N2 atmosphere. After stirring for 24 hours, the temperature was raised to 85°C and stirring was continued for 48 hours. The reaction mixture was cooled and treated with 1 N HCl aqueous solution (60 mL) and 110 mL of 10% MeOH / CHCl3. The pH of the aqueous phase was adjusted to pH 7 by adding 1 N NaOH aqueous solution. The layers were separated, the organic portion was dried with Na2SO4, and concentrated under reduced pressure to obtain a syrup-like substance. This was then treated with toluene and concentrated under reduced pressure to obtain 19.8 g of mPEG 550 diphenolic acid amide as a syrup-like substance. 1 H NMR(500MHz,chloroform-d)δ ppm 1.49-1.57(m,3H)1.91-2.01(m,2H)2.35-2.45(m,2H)3.31-3.40(m,5H)3.47-3.51(m,2 H)3.51-3.55(m,2H)3.55-3.66(m,42H)6.03(m,1H)6.64-6.75(m,4H)6.90-7.07(m,4H).

[0119] Examples of graft copolymers Graft copolymer example 1 (GCE1): mPEG 550 diphenolic acid / PES graft copolymer [ka]

[0120] A solution of 67.0 g of mPEG 550 diphenolic acid ester (PE1) dissolved in 400 mL of NMP was added to a 3 L three-necked round-bottom flask. A Dean-Stark trap and reflux condenser were attached to the reaction flask. 22.6 g of 4,4'-sulfonyldiphenol (90.4 mmol) was added to the reaction mixture along with 50 mL of toluene. The mixture was stirred under a nitrogen atmosphere and heated to 150°C. After 2 hours, the toluene collected in the Dean-Stark trap was removed, and another 25 mL of toluene was added to the reaction mixture. Heating was continued, and the toluene collected in the Dean-Stark trap was removed. Bis(4-fluorophenyl)sulfone (46.0 g, 180.8 mmol) and K2CO3 (29.9 g, 217 mmol) were added to the reaction mixture along with 25 mL of toluene. Heating was continued at 150°C for 90 minutes. The temperature was reduced to 110°C, and the mixture was stirred overnight. The reaction mixture was cooled to approximately 80°C and slowly poured into 4 L of ice-cold deionized water while stirring. The precipitated polymer was isolated by filtration through a Buchner funnel and rinsed with water. The recovered polymer was stirred with 2 L of deionized water and isolated again by filtration through a Buchner funnel. Washing with deionized water was repeated two more times. The wet polymer was transferred to a 2 L flask and placed under high vacuum at 50°C until most of the water was removed. The resulting solid was placed in a crystallization dish and dried until it reached a constant weight, yielding 105 g of mPEG 550 diphenolic acid / PES copolymer (GCE1) as a light yellowish-brown solid. GPC analysis showed that Mn was 13,103 g / mol, Mw was 48,570 g / mol, and PDI was 3.71.

[0121] Graft copolymer example 2 (GCE2): mPEG 550 diphenolic acid / PES graft copolymer [ka]

[0122] A 3L plastic kettle was filled with 173.43g of 4,4'-sulfonyldiphenol (693 mmol), 234.93g of bis(4-fluorophenyl)sulfone (924 mmol), 306.49g of K2CO3 (2.22 mol), 200.37g of mPEG 550 diphenolic acid ester (PE1), and 924g of NMP. The plastic kettle was equipped with a heating mantle, a J-KEM temperature control device with a 0.25-inch stainless steel thermocouple, a mechanical stirrer with a stainless steel stirring shaft utilizing a Teflon® stirring blade lined with stainless steel blades and a propeller with four protrusions, and a short-path distillation head with a 0.25-inch stainless steel immersion tube connected to a Schlenkline for N2 sparging, and a 1L receiving flask cooled in a dry ice acetone bath. 346 g of toluene was added to a plastic kettle, and the reaction mixture was heated to 150°C for 2 hours to remove the toluene by distillation. The short-path distillation head was replaced with a glass stopper, the immersion tube was placed over the reaction solution, and the temperature was raised to 165°C. The reaction mixture was maintained at 165°C for 3 hours and 15 minutes, then cooled to room temperature, and the reaction mixture was allowed to stand at room temperature for 18 hours. The reaction mixture was diluted with 300 mL of N,N-dimethylformamide and poured into 12 L of water to precipitate the polymer. The polymer was blended with water in an industrial blender and recovered by filtration. The filtered product was then immersed in 12 L of water at 40°C with mechanical stirring, the water was changed after 3 hours, the polymer was immersed again at 40°C for another 3 hours, the water was changed once more, and the polymer was immersed at 25°C for 16 hours before being collected by filtration. The polymer was dried in a pressurized funnel under a flow of N2 for 6 days to obtain 473.67 g of mPEG 550 diphenolic acid / PES copolymer (GCE2). GPC analysis showed a PDI of 6.38, a Mn of 30,317 g / mol, and a Mw of 193,549 g / mol.

[0123] Graft copolymer example 3 (GCE3): mPEG 2000 diphenolic acid / PES graft copolymer [ka]

[0124] 73.97 g of 4,4'-sulfonyldiphenol (296 mmol), 100.23 g of bis(4-fluorophenyl)sulfone (394 mmol), 108.96 g of K2CO3 (1.58 mol), 240.37 g of mPEG 2000 diphenolic acid ester (PE2), and 700 g of NMP were added to a 3 L plastic kettle. The plastic kettle was equipped with a J-KEM temperature control device with a heating mantle and a 1 / 4” stainless steel thermocouple, a mechanical stirrer with a stainless steel stirring shaft utilizing a Teflon® stirring blade lined with stainless steel blades and a propeller with four protrusions, and a short-path distillation head with a 0.25 inch stainless steel immersion tube connected to a Schlenkline for N2 sparging, and a 1 L receiving flask cooled in a dry ice acetone bath. 262 g of toluene was added to the plastic kettle, and the reaction mixture was incubated at 150°C for 1.5 hours. The toluene was removed by heating and distillation. Once the toluene had been distilled, the short-path distillation head was replaced with a glass stopper, the immersion tube was placed over the reactant solution, and the reactants were maintained at 150°C for 6 hours and 25 minutes. After cooling to room temperature, the reactant solution was allowed to stand at room temperature for 11.5 hours. The reaction mixture was poured into 12 L of water, and the precipitate was cut into small pieces of approximately 1 × 1 cm with scissors. The material was then immersed in 12 L of water at room temperature for 4 hours, the water was changed, and this process was repeated a total of four times. GPC analysis showed a PDI of 2.48, a Mn of 58,572 g / mol, and a Mw of 145,272 g / mol.

[0125] Graft copolymer example 4 (GCE4): mPEG 550 diphenolamide / PES graft copolymer [ka]

[0126] A solution of 19.8 g of mPEG 550 diphenolamide (PE3) dissolved in 100 mL of NMP was added to a 300 mL three-necked round-bottom flask. A Dean-Stark trap and reflux condenser were attached to the reaction flask. The mixture was treated with 20 mL of toluene and heated to 150 °C, sparged with N2 until all toluene was collected in the Dean-Stark trap. The mixture was then cooled to 70 °C, and 4,4'-sulfonyl diphenyl (6.30 g), bis(4-fluorophenyl) sulfone (12.81 g), and K2CO3 (8.41 g) were added to the reactants along with 20 mL of toluene. The temperature was raised to 150 °C until all toluene was collected in the Dean-Stark trap. Another 20 mL of toluene was added to the reaction mixture, and the temperature was raised to 165 °C for 3 hours. The temperature was lowered to 110 °C, and the mixture was stirred overnight. The reaction mixture was cooled to approximately 80°C and slowly poured into 1 L of ice-cold deionized water with stirring. The precipitated polymer was isolated by filtration through a Buchner funnel and rinsed with water. The recovered polymer was stirred with 1 L of deionized water and isolated again by filtration through a Buchner funnel. Washing with deionized water was repeated two more times. The wet polymer was transferred to a 2 L flask and placed under high vacuum at 50°C until most of the water was removed. The resulting solid was placed in a crystallization dish and dried until it reached a constant weight, yielding 33.5 g of mPEG 550 diphenolamide / PES copolymer (GCE4) as a light yellowish-brown solid. GPC analysis showed that Mn was 24,307 g / mol, Mw was 48,335 g / mol, and PDI was 1.99.

[0127] Preparation of polymer dope (i.e., casting solution) and hollow fiber membrane Hollow fiber membrane example 1 (HFM1): Prepared using GCE1 Polymer dopes were prepared with the following composition: 23 wt% PES, 9 wt% PEtOx, 2.6 wt% GCE1, 30.3 wt% PEG200, 33.2 wt% NMP, and 2 wt% deionized water. The polymer dopes were mixed using a centrifugal mixer (available from FlackTek, Landrum, SC as "SPEEDMIXER") at 800 rpm for 15 seconds, followed by 1200 rpm for 9.75 minutes. The polymer dopes were transferred to a hopper, heated to 50°C, and degassed overnight at 200 mbar. The resulting polymer dopes were transparent with a brownish tint and macroscopically homogeneous.

[0128] A gear pump ("Model H-9000," available from Zenith Pumps, Monroe, NC) was used to pump the polymer dope from the hopper to a spinneret die having an internal channel for the bore fluid and an annular gap for the polymer dope, separated by a needle. The flow path was heated to 50°C and included a 15-micrometer inline filter. The spinneret die had an annular gap of 410 micrometers, a needle outer diameter of 300 micrometers, and a needle inner diameter of 150 micrometers. The spinneret die was fixed 20 cm above the aqueous sedimentation bath and heated to 50°C. The bore fluid consisted of 50 wt% PEG200, 45 wt% NMP, and 5 wt% deionized water.

[0129] The extruded polymer dope was dropped through a climate-controlled zone with an air temperature of 45°C and a relative humidity of 96%. Air was blown through the climate-controlled zone to achieve a vapor mass flow rate of 2.8 kg / hour. The extruded polymer dope was then placed in an aqueous precipitation bath heated to 50°C, thereby vitrifying the pore structure of the hollow fiber membrane. The hollow fiber membrane was recovered at a line speed of 150 ft / min and wound onto a drum.

[0130] The resulting hollow fiber membrane bundles were washed to remove the lumen volume with approximately 4 L of deionized water, then extracted in water heated to 90°C for 1 hour, and finally dried overnight at room temperature. The hollow fiber membranes had an inner diameter of 203 micrometers and an average wall thickness of 70 micrometers.

[0131] Scanning electron microscope images of the hollow fiber membrane of Example HFM1 are shown in Figure 3 (cross section at 200x magnification), Figure 4 (cross section at 1,000x magnification), Figure 5 (inner wall at 5,000x magnification), and Figure 6 (outer wall at 5,000x magnification).

[0132] Comparative Hollow Fiber Film Example 1 (CHFM1) Polymer dopes were prepared in the same manner as HFM1, but with the following composition: 25.5 wt% PES, 9 wt% poly(2-ethyl-2-oxazoline), 30.3 wt% poly(ethylene glycol) with a molecular weight of 200 g / mol, 33.2 wt% NMP, and 2 wt% deionized water. The polymer dopes were transferred to a hopper, heated to 50°C, and degassed overnight. The resulting polymer dopes were clear and macroscopically homogeneous.

[0133] A gear pump ("Model H-9000," available from Zenith Pumps, Monroe, NC) was used to pump the polymer dope from the hopper to a spinneret die having an internal channel for the bore fluid and an annular gap for the polymer dope, separated by a needle. The flow path was heated to 50°C and included a 15-micrometer inline filter. The spinneret die had an annular gap of 410 micrometers, a needle outer diameter of 300 micrometers, and a needle inner diameter of 150 micrometers. The spinneret die was fixed 20 cm above the aqueous sedimentation bath and heated to 50°C. The bore fluid consisted of 50 wt% PEG200, 45 wt% NMP, and 5 wt% deionized water.

[0134] The extruded polymer dope was dropped through a climate-controlled zone with an air temperature of 45°C and a relative humidity of 96%. Air was blown through the climate-controlled zone to achieve a vapor mass flow rate of 2.8 kg / hour. The extruded polymer dope was then placed in an aqueous precipitation bath heated to 50°C, thereby vitrifying the pore structure of the hollow fiber membrane. The hollow fiber membrane was recovered at a line speed of 150 ft / min and wound onto a drum.

[0135] The resulting hollow fiber membrane bundles were extracted in water heated to 90°C for 1 hour, and then dried overnight at room temperature. The hollow fiber membranes had an inner diameter of 194 micrometers and an average wall thickness of 70 micrometers.

[0136] Scanning electron microscope images of the hollow fiber membrane of comparative example CHFM1 are shown in Figure 7 (cross section at 200x magnification), Figure 8 (cross section at 1,000x magnification), Figure 9 (inner wall at 5,000x magnification), and Figure 10 (outer wall at 5,000x magnification).

[0137] Measurement of fouling resistance of hollow fiber membranes HFM1 and CHFM1 Hollow fiber membrane modules containing hollow fiber membranes were fabricated for Example HFM1 and Comparative Example CHFM1. To fabricate each module, two 2.5-inch sections were cut from a 0.25-inch nylon tube (part number 2VDL8, Grainger). The tube sections were inserted into both ends of a polypropylene push-connect T-fitting (part number PP0208W-US, John Guest). Three membrane fibers from either Example HFM1 or Comparative Example CHFM1, each longer than the assembly described above, were threaded from the open end of one section of the nylon tube to the open end of the other section of the resulting assembly. The open ends of each section of the nylon tube were then potted with approximately 0.25-inch plugs of epoxy adhesive (LOCTITE EA608, Henkel). The epoxy adhesive was allowed to cure for approximately 20 minutes, after which the epoxy adhesive plugs at each end of the assembly were cut with a razor blade at approximately their midpoint to expose the open ends of the hollow fibers. Each module had a supply inlet at one potting end, a supply outlet at the opposite potting end, and a permeate outlet at the open connection of the T-fitting. The effective filtration area of ​​each module was calculated as the surface area of ​​three cylinders with diameters equal to the length of the membrane module and the inner diameter of the hollow fiber membrane, approximately 2 cm². 2 It had the value of [value].

[0138] PBS buffer solution was prepared by dissolving one packet of PBS buffer powder per liter of deionized water. 1 g of TWEEN®-80 was added to each liter of the PBS buffer solution to create a 0.1 wt percent TWEEN®-80 solution in the PBS buffer. TWEEN®-80 is a nonionic surfactant present in several biopharmaceutical cell culture fluids and is known to contaminate the surface of many filter membranes. Both solutions were sterile filtered (using NALGENE RAPID-FLOW sterile disposable bottle-top filters with 0.2 micron PES membranes).

[0139] Using a PendoTECH NFF filter screening system (PendoTECH, Princeton, NJ), the flow rate across each type of hollow fiber module was measured as a function of volume throughput at a constant pressure of 2.07 bar (30 psi) while filtering first a PBS solution, followed by 0.1 wt percent TWEEN®-80 in PBS. The supply inlet of each membrane module was fluidly connected to a 700 mL pressure vessel by an assembly consisting of a Luer stopcock (part number EW-12023-27, Cole-Parmer), a locking Luer connector, a 1 / 4-inch tube section, and a polypropylene push-connect union (part number PP0408W-US) connected to the membrane module. The supply outlet of each membrane module was connected to an assembly consisting of a polypropylene push-connect union, a 1 / 4-inch tube section, a locking Luer connector, and a Luer cap that allows the supply outlet to be opened and closed. The permeate outlet of each membrane module was placed on top of the container on the mass balance of the filter screening system. The filter screening system was connected to a computer running software that enabled automatic recording of mass readings on a mass balance every 10 seconds.

[0140] First, the stopcock upstream of each membrane module was closed, and the pressure vessel upstream of each membrane module was filled with PBS solution. Each pressure vessel was closed and pressurized to 2.07 bar (30 psi) using a compressed air supply source and pressure regulator. Next, the lumen of each hollow fiber module was vented by opening the Luer cap at the supply outlet and opening the upstream stopcock until the buffer was observed to exit the supply outlet. Next, the permeate side of each module was vented by closing the Luer cap at the supply outlet and observing the buffer exiting the permeate outlet. Next, the stopcock upstream of each membrane module was closed. Then, automatic collection of mass balance readings was started, and the stopcock upstream of each membrane module was opened to start the flow of PBS buffer solution through both membrane modules. The buffer flow was continued for approximately 10 minutes. Next, the stopcock upstream of each module was closed to stop the buffer flow. The cumulative volume throughput (assuming a buffer density of 1 g / mL) was plotted as a function of time for each membrane module, and a linear relationship was observed in both cases. A regression line was fitted to each dataset, and the slope of the regression line was recorded as the flow rate of pure buffer in each membrane module. The flow velocity of pure buffer in each module was defined as the effective filtration area (2 cm²) of each module. 2 Divide the flux of the pure buffer solution in each membrane module (J) by the upstream pressure (2.07 bar) and the saturation point (J). PBS The pure buffer flux of the membrane modules containing the hollow fiber membranes of Example HFM1 and Comparative Example CHFM1 was 1.51 and 1.85 mL / cm², respectively. 2 It was min·bar.

[0141] Next, each pressure vessel was emptied and refilled with PBS buffer containing 0.1 wt percent TWEEN®-80 as a membrane contaminant. The pressure vessels were closed and repressurized to 2.07 bar (30 psi). Automatic mass recording was restarted, and the stopcock upstream of the membrane module was opened to start the flow of TWEEN®-80 solution, which was continued for 2.9 hours, after which the stopcock was closed. Data analysis was then performed to calculate the membrane flux for each membrane module as a function of volumetric throughput (assuming a fluid density of 1 g / mL). The flow velocity at each time point was calculated as the difference in throughput compared to the previous time point divided by the time difference compared to the previous time point. Then, at each time point, the flux was calculated by dividing the flow velocity by the effective filtration area and the upstream pressure to obtain the membrane flux. The ratio of membrane flux to pure buffer flux (J / J) PBS The following was calculated for each membrane type at each time point: Finally, at each time point, seven J / J values ​​centered on that time point were calculated. PBS The data was smoothed by calculating a moving average of the values.

[0142] Figure 11 shows the smoothed J / J PBS This is plotted as a function of volumetric throughput. The initial flux of each membrane was slightly less than half of the pure buffer flux, likely due to the higher viscosity of the TWEEN®-80 solution. Subsequently, the membrane flux of Comparative Example CHFM1 rapidly decreased during filtration of the TWEEN®-80 solution and then stabilized at a lower value of only about 25% of the pure buffer flux. This decrease in flux is thought to be due to fouling of the membrane pore structure due to the adsorption of TWEEN®-80. The hollow fiber membrane of Example HFM1 maintained its initial flux value in the TWEEN®-80 solution, which is thought to be due to reduced adsorption of TWEEN®-80 on the membrane of Example HFM1, due to the presence of hydrophilic poly(ethylene glycol) chains of GCE1 present on the membrane pore surface. This example demonstrates that improved membrane fouling resistance can be achieved by incorporating the water-insoluble amphiphilic sulfone copolymer of the present invention.

Claims

1. A copolymer comprising a plurality of repeating units linked by an -O- group, wherein the plurality of repeating units are a) Repeating unit of equation (I) 【Chemistry 1】 b) Repeating unit of equation (II) 【Chemistry 2】 (In the formula, R １ This is the formula -X-(CH ２ ) ｙ - (In the formula, X is -O- or -NH-, Each y is an integer in the range of 1 to 4) and includes multiple repeating bases, The asterisk (*) indicates the binding site to the -O- group that connects the two repeating units. A copolymer containing [a certain component].

2. The repeating unit of formula (I) is formula (I-A) 【Transformation 3】 The repeating unit of formula (II) is formula (II-A) 【Chemistry 4】 The copolymer according to claim 1, wherein the copolymer is as described above.

3. R １ is of the formula -R ３ -C(=O)-Z-[(CH ２ ) ｙ -X]] ｎ R ４ (wherein R ３ It is an alkylene, R ４ It is a terminal group, Z is -O- or -NH-, y is an integer in the range of 1 to 4. The copolymer according to claim 1 or 2, wherein n is an integer in the range of 3 to 1000.

4. R １ However, formula -CH ２ CH ２ -C(=O)-O-[(CH ２ CH ２ -O] ｎ R ４ (In the formula, R ４ The copolymer according to claim 3, wherein the group is alkyl.

5. The copolymer according to any one of claims 1 to 4, comprising 10 to 60 weight percent of the first repeating unit of formula (I).

6. The plurality of repeating units further include a third repeating unit different from the first repeating unit and the second repeating unit, wherein the third repeating unit is defined as formula (V-A), formula (V-B), formula (V-C), formula (V-D), formula (V-E), formula (V-F) 【Transformation 5】 【Transformation 6】 【Transformation 7】 【Transformation 8】 【Chemistry 9】 【Chemistry 10】 The copolymer according to any one of claims 1 to 5, wherein the copolymer is one of the following: (wherein the formula, an asterisk (*) is a binding site to an -O- group that binds repeating units) or a combination thereof.

7. The copolymer according to any one of claims 1 to 6, wherein the weight-average molecular weight is in the range of 10,000 grams / mol to 250,000 grams / mol.

8. A porous polymer article comprising a first copolymer which is the copolymer described in any one of claims 1 to 7.

9. The first copolymer in an amount of 1% to 50% by weight, and 50% to 99% by weight, Formula (II) 【Chemistry 11】 A second polymer which is an aromatic polyethersulfone having repeating units of (wherein the formula, an asterisk (*) is a binding site to an -O- group that connects two repeating units) A porous polymer article according to claim 8, which is a film containing the film.

10. The second polymer is a polymer of formula (V-A), formula (V-B), formula (V-C), formula (V-D), formula (V-E), formula (V-F) 【Chemistry 12】 【Chemistry 13】 【Chemistry 14】 【Chemistry 15】 【Chemistry 16】 【Chemistry 17】 The porous polymer article according to claim 9, further comprising repeating units or mixtures thereof.

11. The porous polymer article according to any one of claims 8 to 10, wherein the membrane is a hollow fiber membrane.

12. A method for separating biomaterials based on size differences, To provide a porous polymer article according to any one of claims 8 to 11, The process involves passing an aqueous mixture of biomaterials through a porous polymer material, wherein the mixture of biomaterials includes biomaterials having different average sizes. The separation of the mixture of biomaterials is based on their average size, wherein the first biomaterial, which is smaller than the second biomaterial, permeates the porous polymer article at a faster rate. Methods that include...

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