Spatially-controlled modified porous membrane

Generally, the present invention relates to a porous membrane having a massive matrix of a first substance having a layer of porous structure coated with a free radical polymerization coating, particularly a massive matrix of the first substance, and from one outer surface to the membrane. With respect to a porous membrane with a surface coating of a second substance that extends deep into the controlled local area of.

Porous membranes are used in a variety of applications. The porous membrane has a first porous surface, a second porous surface, and a continuous porous structure extending from the first surface to the second surface in the membrane. This continuous porous structure includes a massive material matrix and a network of pores. The interface that separates the massive matrix from the pore volume portion (ie, the surface of the network of internal pores) is known as the pore surface. The distance from the first surface to the second surface defines the thickness of the film. Depth is used herein to mean the vertical distance from one surface to another.

As used herein, the term "outer surface" shall mean one or both of the first and second surfaces. When discussing surface modifications, "one surface" or "plurality of surfaces" shall mean the outer surface and the interstitial surface.

Porous membranes can be classified as pore membranes or ultrafiltration membranes based on the size of the pores in the membrane. Generally, the pore size range of the pore membrane is considered to be about 0.05 microns to about 10.0 microns, while the pore size range of the ultrafiltration membrane is about 0.002 microns to about 0.05. It is considered to be micron. The size of these holes refers to the hole diameter of circular or nearly circular holes, or the characteristic dimensions of non-circular holes.

The size of the pores of the membrane can be named by the size of the smallest species (particle or molecule) that cannot pass through the membrane over a particular fragment passage. A common ratio is less than 10% pass, which corresponds to a 90% cutoff or retention. Other methods are known to those of skill in the art and include scanning electron microscopy image analysis to characterize the pore size distribution. Pore membranes are commonly used to remove particles from liquids and gases. An important application of pore membranes is in sterile filtration of drug solutions to remove any bacteria that may be present in the solution. The pore membrane is also used as a vent for sterilized gas, which allows the gas to flow, but does not prevent airborne bacteria from passing through the filter. Ultrafiltration membranes are commonly used in applications where retention of small species is desirable. Ultrafiltration membranes, for example, are used in the biotechnology industry to concentrate proteins and in filtration dialysis applications to remove salts and low molecular weight species from protein solutions. Ultrafiltration membranes and pore membranes can be manufactured in several forms, including sheets, tubes and hollow fibers.

Porous membranes are made from a variety of materials, with polymers being the most common. Many commercially available films are made of engineered plastics such as polyethersulfone, polysulfone, polyvinylidene fluoride, polyethylene, polytetrafluoroethylene and other perfluorinated thermoplastic polymers such as poly (tetrafluoroethylene-co-perfluoro). Made from (alkyl vinyl ether)) (POLY- (PTFE-CO-PFVAE)), or poly (tetrafluoroethylene-co-hexafluoropropylene) (FEP), polypropylene, etc., these robust, thermal, mechanical And take advantage of chemical resistance properties.

Porous membranes can be classified as symmetric or asymmetric membranes, which refer to the uniformity of pore size in the thickness of the membrane. In the case of hollow fibers, this is the porous wall of the fibers. The symmetric membrane has a substantially uniform pore size in the membrane cross section. The asymmetric membrane has a structure in which the size of the pores is a function of the position in the cross section. Another way to clarify the asymmetry is the ratio of the size of the holes on one surface to that of the opposite surface.

Membrane manufacturers generally modify the membrane surface of a massive matrix material made of porous membranes (ie, the first and second surfaces, and the interstitial surface) to improve membrane performance. For example, US Pat. No. 4,618,533, issued to Michael J. Steuck on October 21, 1986, is a porous body formed of the first polymer with an average pore size between about 0.001 and 10 microns. A second polymer in which the entire surface is crosslinked, which is a composite porous thermoplastic membrane containing a membrane support layer, wherein the support layer is formed from a monomer polymerized in situ by a free radical polymerization initiator on the support layer. The composite porous membrane is directly coated with, and has a porous shape almost the same as that of the membrane support layer. The membrane is disclosed and patented. Such methods are used to deform membranes with hydrophobic surfaces that allow large amounts of protein during use to bind to membranes with hydrophilic surfaces that have low protein binding properties.

Other modified membranes are made to increase the hydrophobicity of the membrane surface. U.S. Pat. Nos. 5,217,802 and 5,554,414 describe a method of forming a crosslinked polymerized coating of a second polymer that does not get wet with a solvent having a surface tension greater than about 21 mN / m. U.S. Patent Application Publication No. 2002/0139095 describes a lipophilic film made by forming a polydimethylsiloxane coating on the surface of a filtration support layer. U.S. Patent Application Publication No. 2002/00144595 describes lipophilic and hydrophobic filter media made by forming a fluorosulfone coating on the surface of the filter support layer. Such membranes are useful for vents.

Membrane modification methods using coatings copolymerized with free radical polymerization initiators have proven to be industrially successful. These methods, exemplified by the teachings of US Pat. No. 4,618,533, have been successfully used to manufacture a variety of products. These methods do not significantly change the size of the pores in the basement membrane, and they can be used to create a variety of surface properties such as hydrophilicity, hydrophobicity, ionic chargeability and the like.

The above examples are common to many methods by which the membrane manufacturer modifies the membrane. In such cases, these methods have in common that they modify the entire surface of the membrane. There are not many ways to modify a membrane to a controlled depth from one surface.

Membranes modified to a controlled depth are useful, for example, in 96-well equipment for protease assays. The MultiScreen DP assay system from Millipore Corporation (Bedford, MA) incorporates a hydrophilic pore membrane with a single outer surface treated to be hydrophobic. DP membrane plates are recommended for small total volumes (<50 μl) and protease assays, especially for optical detection of filtrate after long-term (72 hours) incubation. Studies of enzyme activity by precipitation assays in which reagents are incubated, precipitated, washed and counted are widely accepted. The precipitation technique stops the enzymatic reaction at the same time and precipitates (insolubilizes) the enzyme.

For example, when using a 96-well plate device, the general procedure for such an assay involves the following steps: 1. Add the liquid containing the enzyme sample and reagents to the wells of the plate. 2. Incubate (for enzymatic reaction). 3. Add a precipitating substance (usually trichloroacetic acid [TCA], usually a final concentration of 5%) to stop the reaction and precipitate the protein. Incubate at 4.4 ° C or on ice. 5. Wash and remove unreacted or free components. (If it is necessary to quantify the free material, collect it.) 6. Precipitate (bonded to filter) and / or filter (free) To count.

Membranes with a hydrophilic layer and a hydrophobic layer are very useful for performing small volume assays. During the incubation, the liquid sample is applied to the hydrophilic (upper) layer and retained. The bottom hydrophobic layer prevents leakage until a vacuum or pressure force is applied to overwhelm the hydrophobic force, thereby preventing penetration or leakage.

Methods for modifying the outer surface are known.

US Pat. No. 5,468,390, issued by Crivello et al. On November 21, 1995, provides an arylpolysulfone membrane in the presence of a hydrophilic vinyl monomer dissolved in a solvent without the addition of a sensitizer or free radical polymerization initiator. Chemically grafting and binding the monomer to the membrane surface by covalent bonding without a sensitizer or free radical polymerization initiator by placing and exposing the membrane to non-iononizing ultraviolet light for a period of time to modify the membrane. Describes a method of modifying an arylpolysulfone membrane according to the above. According to a related paper (J. Membrane Sci. 105 (1995) 237-247), changing the depth from the outer surface exposed to ultraviolet light is an excessively long processing time for industrial methods. The author shows. In addition, UV light may damage the aryl sulfone polymer membrane, and such a long time may cause excessive damage to the porous structure of the membrane.

U.S. Patent Application Publication No. 2002/0155311, filed by Mayes et al. On December 5, 2001, is a branched component compounded with a compatible matrix component and has a desired functional group. A film having a (outer surface) surface with the desired chemical functional groups, made by surface coagulation of the components, is disclosed. This patent application covers articles having a hydrophobic core material with a hydrophilic surface. No discussion has been given or intended for controlling changes in depth. Furthermore, this technique is limited to formulations of compatible polymers in which one polymer can move to the surface by entropy change.

U.S. Pat. No. 5,369,012, issued by Koontz et al. Disclosed are some of the organic polymeric articles in which the membrane is hydrophilic by forming a hydrophilic homogeneous surface layer of hydrophilic hydroxyl groups when exposed at temperatures below 40 ° C. This seems to cover the modification of the outer surface of the non-porous membrane, referred to in this patent as the "outer". The very shallow modified depth indicates this. This is because the vacuum-based plasma technology used is expected to penetrate the porous membrane immediately. In addition, this method does not produce a free radical polymer coating, but reacts with the basic polymer of the membrane. Generally, such a reaction deteriorates the physical properties of the polymer.

Somewhat relevant technology is described in US Pat. No. 5,141,806, issued to SLKoontz on August 25, 1992. In this patent, a micropore structure with a layered intervening surface treated is continuously subjected to atomic oxygen treatment on a homogeneously surface-treated structure to remove the outer layer of the surface treatment agent and become almost uniform. It is made to a depth and then the exposed layer is surface treated with another surface treatment agent.

As described in US Pat. No. 5,141,806, the entire surface of the porous particles is treated homogeneously with the first material. The homogeneously treated particles are then oxidized with atomic oxygen and / or hydroxyl groups to remove the surface treatment agent from the outer layer of the intervening (and outer surface) region and modified with the inner region or first treatment agent. Leave the layer that was made.

The disclosures and examples of this reference are directed to inorganic silica particles. It is unlikely that the polymer membrane can withstand the oxidative conditions used to remove the treatment without damaging its structure. Moreover, such methods would not appear to be usable for asymmetric membranes. This is because any damage to the micropore retention region, which is characteristic of asymmetric membranes and has a gradient in pore size, would impair the usefulness of the membrane.

U.S. Patent Application Publication No. 2,002 / 0189455, filed by Lamon et al. On May 1, 2001, describes a lipophilic coating. The disclosure relates to lipophilic filtration media, including polymeric membranes and other support layers coated with polymerization-substituted or unsubstituted para-xylene. The coating material of the preferred embodiment is derived from one or more para-xylene dimers. The powdered dimer is converted to a gaseous monomer, which condenses and polymerizes on the support layer at room temperature to form a parylene coating.

Poly-para-xylene is generally applied to the support layer using a vacuum application system. The para-xylene dimer powder is usually placed in a vacuum steam chamber and heated to temperatures above 150 ° C to convert the powder into a vapor form. The vaporized dimer can then be converted to reactive para-xylene vapor by pyrolysis at 650 ° C in a pyrolysis chamber. The reactive vapor can then be transferred to a polymerization chamber containing the coated membrane. The polymerization chamber can be kept at ambient temperature. The reactive vapor usually polymerizes on the surface of the support layer to form a homogeneous parylene coating.

In a preferred embodiment, the attachment of the parylene layer is controlled so that only a portion covers the support layer. For example, the parylene coating can be applied to the membrane on one surface in only one layer without completely spreading to the pores throughout the thickness portion of the membrane. The parylene layer can also be attached to the support layer in the form of "polka dots". A "polka dot" shape is a general regularity of regions that have a circular or other shaped contour and is separated from each other by regions of uncoated support layers that contain adhered parylene and do not contain adhered parylene. Defined as an array.

This method is limited to para-xylene polymers and cannot be adapted to free radical polymerized polymers. Furthermore, since this method relies on the condensation of volatile monomers on the surface that occurs from the outer surface to the intervening regions, the outer and outer regions are always more densely coated, especially for membranes with small pores. It results in blockage and reduces permeability.

The single film bipolar membrane, disclosed in US Pat. No. 4,140,815 issued to Dege et al. On February 20, 1979, is a relatively large amount of aromatic polymers, such as bi- or polyfunctional compounds. Contains a matrix of polymer films in which the polymer that crosslinks properly is in a densely dispersed state. The highly dissociative cation exchange group chemically bonds to the aromatic nucleus on one side of the film, while the highly dissociative anion exchange group later chemically bonds to the remaining aromatic nucleus on the other side. The membrane thus constructed functions as a durable water-decomposable membrane to produce acids and bases from salts dissolved by electrodialysis. Such single film bipolar films are made from pre-expanded films containing relatively large amounts, i.e. at least 15% of insoluble crosslinked aromatic polymers. Under controlled conditions, the highly dissociative cation exchange group chemically bonds to the aromatic nucleus at the desired depth on only one side of the film, after which the highly dissociative anion exchange group is the opposite of the film. Chemically binds to the unreacted aromatic nucleus on the side. Bipolar membranes are essentially non-porous.

Therefore, there is a need for a method of modifying the porous membrane to a predetermined depth from one outer surface with a free radical polymerized polymer coating. In addition, there is a need for a complete membrane product in which the intervening volume of a given controlled area of the surface, including one outer surface, is functionally modified. The complete membrane has a unified structure, such as a single layer sheet or a hollow fiber membrane. This includes composite membranes such as those described in US Patent Application No. 4,824,568 and membranes such as those described in PCT Patent Application Publication No. WO 0189673.

For ease of description, the intervening volume of a predetermined controlled region, usually including one outer surface, is referred to herein as a "layer".

A modified film is also needed that has the desired surface pattern, the modification is hindered by molding, and this prevention provides a controlled depth of film.

<p> An object of the present invention is to provide a general method for modifying a porous membrane having a free radical polymerized polymer coating from a first outer surface to a predetermined controlled depth. Another object of the present invention is to provide a general method for modifying a porous membrane having a free radical polymerized polymer coating to a predetermined controlled depth from each outer surface in the layer. Is. Another object of the present invention is to modify a porous membrane having a free radical polymerized polymer coating into a pattern of one surface, the shape of which is maintained at a controlled depth of the membrane. , To provide a general method. Another object of the present invention is to make porous membranes with a free radical polymerized polymer coating a pattern on both surfaces that are the same or different, from the surface on which they are formed to a controlled depth of membrane. It is to provide a general method for modifying a pattern in which its shape is maintained.</p>

<p> An object of the present invention is to provide a modified membrane resulting from these common methods.</p><p> A common method for producing a free radical polymerized polymer coating from the first outer surface to a predetermined controlled depth is to optionally wet the porous membrane with a wetting solution. The completely wet film is then replaced, optionally with a solvent that undertakes the desired film reforming reaction. The membrane then replaces a solution containing at least one free radical polymerizable monomer, an optional polymerization initiator, and a cross-linking agent in the solvent with respect to these three components. The film is then diffused from one outer surface to a controlled desired depth from the outer surface and is contacted with a substance that can prevent polymerization from occurring, namely a polymerization inhibitor (PPA). One preferred PPA is oxygen. It is preferable that the PPA works to prevent the initiation of polymerization from occurring. PPA can also work by limiting the polymerization to low molecular weight oligomeric species that are easily removed in subsequent washes. The membrane is exposed to heat, ultraviolet light, electron beams, gamma radiation, etc., to these energy sources after or during PPA diffusion, which causes PPA diffusion. In the absent volume and the intervening volume where polymerization was initiated in the second outer surface and was not diffused by PPA, and in the second surface, a crosslinked polymer coating was formed on the membrane surface and occupied by PPA. It was not formed on the outer surface in contact with the volume or PPA. 2 so that the PPA diffuses sufficiently from each outer surface to a certain depth to form a layer from each outer surface to a certain depth, leaving a non-diffusing layer in the thick portion of the membrane. One outer surface appears to be well exposed to PPA.</p><p> In another embodiment of the general method, the outer surface of the membrane in contact with the PPA is covered with a pattern mask having an opening region, which allows the PPA to diffuse through the opening region, but the mask. Cannot be diffused where it covers the membrane. This embodiment provides a modified pattern in which the region covered with the free radical polymerized polymer is modified, while the open region provides a non-modified region with a depth controlled by the extent of the diffusion process. .. The mask may be a plastic or metal film cut into the desired pattern. In some embodiments, the mask or mask design can be printed or painted on the surface of the film in contact with the PPA. A pattern can be formed on both sides by using a mask on each outer surface.</p><p> An important feature of this method is that PPA is used to control free radical polymerization to the desired degree. In the prior art, any attempt at control depends on the extent to which the reaction mixture can penetrate the membrane. However, while osmosis moves the reaction mixture deeper into the deeper parts of the membrane, the outer outer surface and adjacent regions are constantly exposed to the reaction mixture. Relatively long reaction times can cause differences in the properties of different regions of depth, making product control difficult. On the contrary, the present invention uses PPA to prevent polymerization when surface modification is not desirable. As a result, the polymerization can be uniformly caused at a depth that does not contain PPA.</p><p> In one embodiment, the hydrophobic membrane is modified to have a layer of functional free radical polymerization crosslinked polymer coating. Such functional coatings include, but are not limited to, hydrophilic, hydrophobic, ionic, and ligand-containing.</p><p> In one embodiment, the uniformly hydrophilically modified porous membrane, eg, described in US Pat. No. 4,618,533, is further modified to have a hydrophobic or functional layer.</p><p> In one embodiment, the uniformly ion-charged modified porous membrane is further modified to have a second ion-charged layer.</p><p> In one embodiment, the hydrophobic layer has a surface that does not get wet with a solvent having a surface tension greater than about 16 mN / m.</p><p> In one embodiment, the uniformly hydrophilically modified porous membrane described, for example, in US Pat. No. 4,618,533, is further modified to have an ion-charged layer.</p><p> In one embodiment, a modified hydrophilic membrane with a hydrophobic layer is suitable for use in a protease assay.</p><p> In other embodiments, one or more layers are formed in one or more patterns.</p>

In general, the present invention provides a method that can be used to produce a surface modified porous membrane, the modification being spatially controlled to occur within the desired volume of the membrane, and further if desired. Wake up with the specified pattern.

Membranes made by this method can have a surface modified to a porous structure of the membrane in which the controlled depth from at least one outer surface is less than the total thickness of the membrane. .. This results in a film with a layer of modified surface.

Membranes modified to a controlled depth are useful, for example, in 96-well equipment for protease assays. The MultiScreen DP assay system from Millipore Corporation (Bedford, MA) incorporates a hydrophilic pore membrane with a single outer surface treated to be hydrophobic. DP membrane plates are recommended for small total volumes (&lt;50 μl) and protease assays, especially for optical detection of filtrate after long-term (72 hours) incubation. Studies of enzyme activity by precipitation assays in which reagents are incubated, precipitated, washed and counted are widely accepted. The precipitation technique stops the enzymatic reaction at the same time and precipitates (insolubilizes) the enzyme.

In addition, the membranes produced by this method have a surface in which a controlled depth pattern from at least one outer surface has been modified to a porous structure of the membrane that is less than the entire thickness of the membrane. Can have.

Membranes modified with a controlled depth pattern are useful, for example, in arrays for protein fixation. Arrays are used to give an orderly sequence of samples, especially in matrices that can be determined and identified by mechanical methods. In a protein binding array, each cell in the array has specific binding chemistry. In low pH and low salt containing solutions, proteins can bind to positively charged groups on the array by electrostatic interaction of amino acids such as positively charged lysine, arginine and histidine. In high pH and low salt containing solutions, negatively charged groups on the array bind to proteins by electrostatic interaction of amino acids such as negatively charged aspartic acid and glutamic acid. The antibody is bound to the surface of the array to test its specific interaction with the protein.

A common method for producing a free radical polymerized polymer coating from the first outer surface to a predetermined controlled depth is to moisten the porous membrane with a wet solution in some cases. The completely wet film is then replaced, optionally with a solvent that undertakes the desired film reforming reaction. The membrane then replaces a solution containing at least one free radical polymerizable monomer, an optional polymerization initiator, and a cross-linking agent in the solvent for these three components. The film is then diffused from one outer surface to a controlled desired depth from the outer surface and is contacted with a substance that can prevent polymerization from occurring, namely a polymerization inhibitor (PPA). One preferred PPA is oxygen. It is preferable that the PPA works to prevent the initiation of polymerization from occurring. PPA can also work by limiting the polymerization so that only low molecular weight oligomer species, which are easily removed in subsequent washings, are formed. The membrane is exposed to heat, ultraviolet light, electron beams, gamma radiation, etc., to these energy sources after or during PPA diffusion, which causes PPA diffusion. In the absent volume and the intervening volume where polymerization was initiated in the second outer surface and was not diffused by PPA, and in the second surface, a crosslinked polymer coating was formed on the membrane surface and occupied by PPA. It was not formed on the outer surface in contact with the volume or PPA.

In some embodiments of the invention, both outer surfaces can be contacted with the PPA to form a modified layer at some depth in the membrane.

In other embodiments, the outer surface of the membrane in contact with the PPA is covered with a pattern mask having an opening region, through which the PPA can be diffused, but the mask covers the membrane. Where you are, you cannot spread it. This embodiment provides a modified pattern in which the region covered with the free radical polymerized polymer is modified, while the open region provides a non-modified region with a depth controlled by the extent of the diffusion process. .. The mask may be a plastic or metal film cut into the desired pattern. In some embodiments, the mask or mask design can be printed or painted on the surface of the film in contact with the PPA.

In addition, the effect of PPA on depth can be controlled by varying the concentration of PPA. By changing the driving force of diffusion, the effects on various depths can be considered at the same contact.

Further, the PPA can be applied in a printable format so that the area to be printed is not modified in the subsequent surface modification polymerization. The PPA may be included in the liquid as a solution or dispersion, or the PPA can be used as a pure substance.

In some embodiments, a mask or mask pattern can be applied to both outer surface surfaces of the same or different patterns to create pattern layers on both sides.

Other embodiments using a combination of methods described above can be configured by one of ordinary skill in the art to produce a layer-modified membrane not expressly described herein.

An important feature of the present invention is the use of PPA to control free radical polymerization to the desired degree. In the prior art, any attempt at control depends on the extent to which the reaction mixture can penetrate the membrane. However, while osmosis moves the reaction mixture deeper into the deeper parts of the membrane, the outer outer surface and adjacent regions are constantly exposed to the reaction mixture. Relatively long reaction times can cause differences in the properties of different regions of depth, making product control difficult. On the contrary, the present invention uses PPA to prevent polymerization when surface modification is not desirable. As a result, the polymerization can be uniformly caused at a depth that does not contain PPA.

The steps of the general method are: the step of giving the porous membrane support layer; the step of washing the porous membrane support layer with a wet liquid in some cases and wetting the surface thereof; the step of wetting the surface of the wet porous membrane support layer; the wet porous membrane support layer is a second wet liquid. In some cases, it is washed to replace the first wetting liquid and make the porous membrane support layer wet with the second liquid; at least one outer surface of the porous membrane support layer. Steps of contact with a solution containing a monofunctional free radical polymerizable monomer, at least one polyfunctional free radical polymerizable monomer, and optionally one or more polymerization initiators; at least one outer surface The step of contacting the membrane from the membrane with a substance that diffuses from its outer surface, namely the antipolymerization agent (PPA); the step of controlling the depth of diffusion of the PPA to prevent polymerization from occurring in the volume in which the PPA is diffused. Includes a step of polymerizing the monomer to form a crosslinked coating in the volume of the membrane not occupied by PPA; and a step of washing the membrane. If desired, a mask is used for pattern diffusion.

Porous membranes are available in a variety of materials. Porous membranes are industrially produced from ceramic, carbon, and metallic materials. Polymer membranes are a preferred embodiment of the present invention. Representative polymers that can be used to produce the porous membranes useful in the present invention include polysulfone polymers, preferably aromatic sulfone polymers, such as polysulfone and polyethersulfone polymers. Other useful polymers include perfluorinated thermoplastic polymers including polytetrafluoroethylene and polyvinylidene difluoride, polyolefin polymers such as polyethylene, ultrahigh molecular weight polyethylene and polypropylene, cellulose polymers such as cellulose acetate and cellulose nitrate, Polyesters such as polyvinyl chloride, polyvinyl fluoride, polyacrylonitrile, polyamide, and polyethylene terephthalate and polycarbonate. In a particularly preferred embodiment, the porous membrane is a polydifluorovinylidene membrane. Those skilled in the art will be able to easily identify other polymers useful in the formation of porous membranes suitable for the present invention.

The porous membrane may be a hydrophobic or hydrophilic membrane. The porous membrane may be a membrane with a modified surface.

As used herein, the term "porous membrane" includes both pore membranes and ultrafiltration membranes. The ultrafiltration membranes and pore membranes of the present invention may be in any form, including sheets, tubes and hollow fibers.

As used herein, the term "outer surface" shall mean one or both of the first and second surfaces. When discussing surface modifications, "one surface" or "plurality of surfaces" shall mean the outer surface and the interstitial surface.

In general, the porous membrane may be a skin layer or a non-skin layer. The skin layer is a relatively thin, dense surface layer integrated with the underlying structure of the membrane. In the skin layer membrane, most of the resistance to membrane passage is provided in the thin skin layer. When present in both pore membranes and ultrafiltration membranes, the surface skin layer comprises pores in the porous structure portion of the membrane beneath the skin layer that is continuous from the outer surface surface. For the pore membrane and ultrafiltration membrane of the skin layer, the pores are part of the outer surface area. In contrast, non-skin layers are porous over most of the outer surface. The porosity of the outer surface of the membrane (ie, the arrangement of pores on the outer surface of the membrane, as seen by, for example, the scanning electron microscope "SEM") is monoporous, relatively uniformly distributed on the outer surface of the membrane. It may be one, or the porosity of the discontinuous region, or a mixture thereof. As used herein, the term "surface porosity" applied to the outer surface of a membrane is the ratio of the area defined by the pore openings on the outer surface to the total surface area of the outer surface.

Pore membranes useful in carrying out the present invention refer to the uniformity of pore size in the thick portion of the membrane, or in the porous wall of the fiber with respect to tubular or hollow fibrous membranes, symmetrical or Classified as asymmetric. As used herein, the term "symmetric membrane" means a membrane having a substantially uniform pore size in the cross section of the membrane. The term "asymmetric membrane" means a membrane in which the average pore size in the membrane cross section is not constant. For example, in an asymmetric membrane, the size of the pores can change smoothly or discontinuously as a function of position in the membrane cross section. As will be understood, the definition of "asymmetric membrane" includes a membrane having a ratio of the size of a hole on one outer surface to the size of a hole on the opposite outer surface, which is significantly greater than 1. Is.

The reaction solution should preferably wet the entire surface of the porous membrane. If the surface tension of the reaction solution is not low enough to wet the membrane surface sufficiently, a pre-wetting or washing step can be performed. In some preferred embodiments, the porous membrane is first cleaned with a cleaning solution that completely wets the entire surface of the porous membrane. The cleaning solution preferably does not wet or dissolve the porous membrane, and it is also preferable that it can be replaced with a reaction solution. In a preferred embodiment using an aqueous reaction solution, the wetting solution may be an organic solution or an organic-water composition having a surface tension less than the surface tension required to wet the porous membrane. Examples of suitable wettable solutions are lower monohydric alcohols (methanol, ethanol, isopropanol) and alcohol-aqueous solutions, preferably methanol-water, ethanol-water, or isopropanol-aqueous solution. When performing a cleaning step, it may be desirable to perform a second cleaning step. For example, if one or more components of the wetting solution can interfere with the polymerization or cross-linking reaction, a second cleaning step can be used to remove the cleaning solution, which can be polymerized or It can be replaced with a second cleaning solution that does not inhibit the cross-linking reaction. The second cleaning solution is usually the solvent used in the reaction solution. For example, when an aqueous reaction solution is used, the porous membrane that has been washed and is wet with the described wet liquid is then washed with water to remove the first wet liquid to produce a water-filled porous membrane. Let me. The wet porous membrane is then contacted with the reaction solution (eg, by immersing it in the reaction solution) to produce the desired reaction composition in the pores of the porous membrane and on the outer surface. The first and second washing steps are preferably performed at an ambient temperature of, for example, 20 ° C to 30 ° C, and preferably for a period of seconds to minutes.

When the reaction solution for coating formation sufficiently wets the porous membrane to contain the desired organic solvent, or the concentration of the reactants in the reaction solution reduces the surface tension of the solution to make the reaction solution into the porous membrane. If it is low enough to be completely moistened, therefore no washing step is required. Thus, the reaction solution may contain one or more additives that reduce the surface tension of the reaction solution sufficiently to avoid such washing steps and do not inhibit subsequent polymerization reactions. Preferred examples of such additives include ethylhexyldiol, propylene carbonate, tripropylene glycol methyl ether, and 2-methyl-2,4-pentanediol. The amount of additive to the reaction solution required to obtain proper wetting depends on the amount and type of monomer and polymerization initiator used and can be easily determined by one of ordinary skill in the art without the need for undue experimentation. Will. The reaction solution for coating comprises a solvent, at least one monofunctional monomer, at least one polyfunctional crosslinked monomer, and optionally one or more polymerization initiators. The choice of solvent for the reaction solution depends on the choice of monomer and optional polymerization initiator. The solvent preferably dissolves the reactants and optionally the polymerization initiator, does not inhibit or interfere with the polymerization reaction, and does not attack the porous membrane. A particularly preferred solvent is water.

The ratio of the amount of crosslinked monomer to the total amount of monofunctional monomer is about 1 to about 10, more preferably about 2 to about 6.

The polymerization of the monofunctional monomer and the crosslinked polyfunctional monomer of the present invention can be carried out by initiating free radical polymerization and a growth reaction. In some preferred embodiments, one or more free radical polymerization initiators can be included in the reaction solution containing the monomers to facilitate polymerization: any widely known in the art. Various polymerization initiators will find use in the present invention. In some preferred embodiments, the one or more polymerization initiators are water soluble. In another preferred embodiment, for example, when using a wet reaction solution, a small amount of water-soluble polymerization initiator is preferred.

One of ordinary skill in the art will be able to readily determine a suitable polymerization initiator for a given reaction solution. Examples of suitable polymerization initiators are, for example, ammonium persulfate, potassium persulfate, azobis (4-cyanovaleric acid, Irgacre 2959 (Ciba Specialty Chemicals, Hawthorn, NY), 2,2'-azobis (2-amidinopropane)). Dihydrochloride and the like. One or more polymerization initiators are preferably used in the range of about 0.1% by weight to about 1% by weight with respect to the entire reaction solution.

After the surface of the porous membrane is brought into contact with the reaction solution (ie, saturated with the reaction solution), excess reaction solution is removed from the outer surface while leaving such an outer surface wet with the solution. For small sheets, the excess reaction solution can be removed, for example by placing a saturated sheet between the two layers of the plastic film and using a rubber roll, such as a hand-printed roller, to remove the excess liquid. When processing a continuous sheet of porous membranes, excess liquid can be removed using an air knife that directs the flow of air toward the outer surface. Excess reaction solution is removed by the force of the air flow. One preferred technique is to have two pressure controlled contact rolls, at least one of which is elastomerically coated and the sheet is placed between rolls that rotate in the same direction as the sheet. The amount of liquid left in the sheet can be precisely controlled by adjusting the pressure of the contact rolls. Other means of removing excess reaction solution are readily available to those of skill in the art.

Monomers that can be polymerized by free radical polymerization and can be crosslinked by free radical polymerizable polyfunctional monomers can be used in this method to form modified films. A complete list of suitable polymerizable monomers will appear to be overly extensive, but those skilled in the art will be familiar with the chemical properties required to produce the desired functionality or desired surface properties. .. Such monomers include 1-hydroxyprop-2-yl acrylate and 2-hydroxyprop-1-yl acrylate, hydroxypropyl methacrylate, 2, There are, but are not limited to, hydroxyalkyl acrylates or methacrylates, or mixtures thereof, including, but not limited to, 3-dihydroxypropyl acrylate, hydroxyethyl acrylate, hydroxyethyl methacrylate, and the like. Other polymerizable monomers that can be used are acrylamide, methacrylamide, ethanerylamide, including dimethylacrylamide, and diacetoneacrylamide. Vinylpyrrolidone can be used. Monomers containing positively or negatively charged ions, monomers with affinity groups, or monomers with significant hydrophobicity, such as (3- (methacryloylamino) propyl) trimethyl-ammonium chloride, (3-acrylamide propyl) trimethyl Ammonium chloride, 2-acrylamide-2-methyl-1-propanesulfonic acid, aminopropylmethacrylamide and the like can be used. Examples of cross-linking agents for acrylates, acrylamides, methacrylates or methacrylamides include bifunctional acrylates, methacrylates or acrylamides such as tetraethylene glycol diacrylates, glycidyl diacrylates, ethoxylated trimethylolpropane triacrylates or methylenebisacrylamide. For some cross-linking agents with bifunctionality or higher functionality, these materials can be used in the coating of the present invention without additional monomers.

After removing the excess reaction solution, the wet porous membrane is then exposed to an energy source such as heat, ultraviolet light, electron beam or gamma radiation to initiate polymerization of the reaction solution. Heat-initiated free radical polymerization involves heating the saturated membrane to at least about 60 ° C and keeping it at that temperature for about 0.1 to about 10 minutes, preferably about 1 and about 2 minutes. Usually done. Depending on the combination of polymerization initiator and monomer used, high temperatures can be used until boiling or premature evaporation adversely affects the polymerization reaction.

In some preferred embodiments, ultraviolet light is used to initiate the polymerization reaction in situ. It is preferred to irradiate the porous membrane saturated with the reaction solution (possibly containing one or more polymerization initiators) with an ultraviolet light source such as Fusion Systems F600 (Rockville, MD) with an "H" bulb. Filters can be used to reduce or eliminate unwanted wavelengths that can cause unwanted damage to the porous membrane being modified. Those skilled in the art will appreciate that the balance between exposure time to UV light and lamp intensity for optimizing polymerization conditions is a matter of normal experimentation. In general, for a 600 watt source, an exposure time of about 2 seconds to about 10 seconds, preferably about 3 seconds to about 5 seconds would be appropriate.

In some preferred embodiments, the polymerization is initiated using electron beam technology, eg, by the method described in US Pat. No. 4,944,879. Usually, the web or individual samples are passed through an electron curtain generated by an electron beam processor. The processing device delivers the desired dose at about 100 kV to about 200 kV. The web or sample to be moved is carried at a speed suitable for giving the desired exposure time under the curtain. The exposure time and dose determine the dose rate. The normal exposure time is about 0.5 seconds to about 10 seconds. The dose rate is generally from 0.05 kGy (kilo gray) to about 5 kGy.

In another preferred embodiment, the polymerization of the monomers in the reaction solution can be initiated by gamma radiation. Usually, this method irradiates a take-up roll of a monomer-saturated porous membrane. The roll can be passed through the reaction solution and wound up, or the winding roll can be pre-immersed in the reaction solution. It is preferable to degas the reaction solution, that is, to remove air, particularly oxygen from the solution. In some preferred embodiments, degassing is performed by replacing the air with an inert gas such as helium, nitrogen or argon. In another preferred embodiment, degassing is performed by, for example, using a vacuum pump to reduce the pressure of the monomer solution. The roll containing the degassed monomer solution is then sealed with a sealing material to keep it degassed and then irradiated with the desired dose. It is preferable that the sealing material is not deteriorated by irradiation and does not significantly interfere with gamma radiation. A wide range of materials useful as sealing materials, such as many plastics and borosilicate glass, are known in the art.

Usually, a total dose of about 0.02 to about 1.0 kGy is appropriate. A normal exposure of about 5 to about 500 kilorads per hour, more preferably about 5 to about 150 kilorads per hour, can be used with a normal irradiation time of about 4 to about 60 hours. One of ordinary skill in the art will be able to easily determine the proper balance between dose rate and time to reach total dose.

It is known that the presence of oxygen adversely affects the free radical polymerization reaction. It is an aspect of the invention to use this usually detrimental effect to control the polymerization of the desired volume or space within the membrane. In a preferred embodiment, for a flat sheet membrane, the sheet containing the reaction solution has one outer surface covered with an oxygen permeable film, while the other outer surface is exposed to atmospheric air. is there. Oxygen from the atmosphere diffuses into the solution to a controllable depth. The depth of diffusion depends on several variables, including the diffusion rate of oxygen in the reaction solution, the concentration of oxygen in the surrounding atmosphere, and the contact time between the exposed surface and the atmosphere. Those skilled in the art can, in principle, change the depth by changing the diffusivity when such changes are practical, for example by changing the solvent. The oxygen content can be controlled by diluting with an inert gas such as nitrogen or by adding oxygen to the surrounding atmosphere. The contact time can be changed by changing the speed of the process if there is a continuous web process.

Oxygen is the preferred PPA, but other reagents with the same effect may be added to the atmosphere. Ozone and chlorine gas are examples of gaseous reagents that could be used as PPA.

It is also conceivable that a sheet containing the reaction solution can be placed on one outer surface and treated in an immiscible solution containing PPA dissolved in the immiscible solution. Examples of possible liquid-mediated PPA are diphenylpicrylhydrazil, and copper chloride. Other examples are given in "Principles of Polymerization" 3rd Ed, page 263, George Odian; Wiley-interscience, John Wiley &amp; Sons; Publishers.

Other methods take advantage of the fact that PPA reacts with an optional free radical polymerization initiator. As shown in Example 5, the present inventor further allows control of the depth of PPA diffusion by controlling the concentration of the optional free radical polymerization initiator. This is due to the fact that PPA is used to diffuse in proportion to the concentration of any free radical polymerization initiator used.

To generate a pattern using the techniques of the invention, one of ordinary skill in the art will cover one of the outer surfaces described above with an impermeable film or sheet and the opposing outer surface of the desired pattern with a sheet having openings. .. Diffusion of PPA occurs through the openings and forms a pattern within the depth at which polymerization did not occur.

Those skilled in the art will be able to make choices for pattern formation on both sides of the flat sheet membrane by applying pattern sheets, which may be the same or different patterns, to each side. .. In addition, one of ordinary skill in the art would be able to make choices to uncoat both outer surfaces and form deformations inside the membrane.

Those skilled in the art are not limited to one variant. For example, a first polymer coating can be used to homogenically modify the membrane, and a second coating can be used to spatially modify it. Further, the first spatial coating can be covered with a second spatial coating that covers only the sub-patterns of the first pattern.

It will be apparent to those skilled in the art that many modifications of membrane modification can be made by the methods of the invention.

The method of the present invention is applicable to the production of tubular and hollow fibrous membranes. The coating method is known from the spun fiber and monofilament industry and can be constructed into the method of the present invention.

An object of discussing the present invention is not to present all possible combinations, substitutions or modifications in a comprehensive manner, but to present representative methods for enlightening one of ordinary skill in the art. Representative examples are presented to demonstrate practices and should not be construed as limiting the scope of the invention. The inventor attempts to embrace a wide range of aspects of the invention in a wide range of known methods in making the claims.

Method Electroscan ESEM3 (available from Philips Electron Optics) was used to evaluate the wettability of membrane samples. A portion of the membrane from the treated sample was freeze-fractured (as described further below) and then placed on a Peltier stage cooled to 5 ° C for cross-section analysis. The cross-section sample had the hydrophobic side facing the top of the image frame. The ESEM chamber was pumped down from atmospheric pressure to a set pressure of 5 tolls, then washed with steam and made to 10 tolls using a flood control. The flood control was then released. When the chamber pressure reached 5 torr again, the chamber was washed again with steam to 10 toll. This procedure was repeated 3 times to replace the air in the chamber with water vapor. The chamber pressure was then set to 7 tolls. Little control over chamber pressure and stage temperature was used to keep liquid water in the sample protrusions. A representative image was obtained after the membrane was wet. Images were obtained using a beam acceleration voltage of 15 KV at 500x magnification. The image is Orion Image Acquisition Obtained by System.

Cross-sectional images showed dark, featureless, wettable areas. This is because the ESEM beam does not pass through water and condenses in the hydrophilic region.

Sample preparation (ie, freeze-splitting) begins by laying the sample flat on a suitable sample preparation table. Cut a rectangular piece measuring about 3 to 5 mm x 15 to 20 mm from the sample. Hold the rectangular piece with tweezers about 1/4 from its bottom and LN until the sample temperature reaches equilibrium.₂Sink inside. Equilibrium usually occurs for about 10 seconds. The sample is then removed from the liquid nitrogen bath and immediately chopped by bending using a second pair of tweezers. Place the chopped pieces flat on the sample preparation table and cut about 2 mm perpendicular to the chopped portion. For the cut sample, a conductive adhesive is used to place the protruding part of the sample upward (with the cut end facing up), and then sputter-coated with a conductive metal to a thickness of about 20-30 Å. As a result, it is inherently easy to place in the SEM chamber to obtain an image. The degree of magnification is, of course, sample-dependent.

Example

Hydrophilic 0.65u Durapore (polyvinylidene fluoride pore membrane, Millipore Corporation, Bedford; MA), 3.5% zonylfluoroacrylate (ie, 2- (N-ethylperfluorooctane sulfonamide) ethyl acrylate and analog, ZonylTAN Under the trade name of DuPont Corporation, Wilmington, Delaware), 0.5% hexanediol diacrylate, and 0.1% Irgacure 621 (ie 2,2 dimethoxy-2-phenylacetophenone, Ciba Specialty Chemicals, Hawthorn, New York). A formulation consisting of a solution of (available from) in decamethyltetrasiloxane.<u style="single">To contact</u>processing<u style="single">To</u>To do. Place this membrane on a sheet of polyethylene. No cover sheet is applied to the facing outer surface. Through a Fusion Systems F600 (Rockville, MD) UV device, move the membrane at 10 feet per minute, exposing UV light only to the side covered by the polyethylene sheet. The uncoated side is not directly exposed and is in direct contact with the atmosphere, especially containing oxygen and ozone. Immediately after emergence from the device, the membrane is placed in methanol to wash away unreacted species and other non-covalent molecules.

After drying, the film exhibits two-sided properties. The side exposed to oxygen and ozone remained highly hydrophilic, while the other side was highly hydrophobic. A drop of water placed on the hydrophilic side travels in the radial direction and spreads rapidly. Methanol does not wet the hydrophobic side. Environmentally controlled scanning electron microscopy (ESEM) reveals that about half (60 microns) of the membrane is hydrophilic, while the other half is hydrophobic. A copy of the ESEM is shown in Figure 1. The dark, homogeneous layer is the hydrophilic region.

Hydrophilic 0.65u Durapore (DVPP) is treated with a hyperhydrophobic formulation consisting of 3.5% DuPont zonylfluoroacrylate, 0.5% hexanediol diacrylate, and 0.1% Irgacure 621 dissolved in decamethyltetrasiloxane. .. Place this membrane on a sheet of polyethylene. Apply a polyethylene cover sheet with an opening space corresponding to the pattern. This pattern may have any shape. In this example, a pattern is made by cutting a lane with a width of about 2 mm ending in a circle with a diameter of about 5 mm from a polyethylene sheet. Through the Fusion Systems UV device, move the membrane at 10 feet per minute, exposing the membrane to UV light only towards the side covered by the non-patterned polyethylene sheet. The side covered by the patterned polyethylene sheet is not directly exposed and is in direct contact with the atmosphere, especially containing oxygen and ozone. Immediately after emergence from the device, the membrane is placed in methanol to wash away unreacted species and other non-covalent molecules.

The entire membrane is hydrophobic except for the region corresponding to the cut pattern. This region is hydrophilic and gets wet with water to a depth of about 60 microns.

In this example, the depth of the hydrophobic layer or region is reduced by varying the concentration of formulation components. The concentration of active ingredient in the formulation is reduced to make the hydrophobic region smaller. Hydrophilic 0.65u Durapore (DVPP) is treated with a hyperhydrophobic formulation consisting of 2% DuPont zonylfluoroacrylate, 0.32% hexanediol diacrylate, and 0.056% Irgacure 621 dissolved in decamethyltetrasiloxane. .. Place this membrane on a sheet of polyethylene. No cover sheet is applied to the facing outer surface. Through the Fusion Systems UV device, move the membrane at 10 feet per minute, exposing only the UV rays to the side covered by the polyethylene sheet. The uncoated side is not directly exposed and is in direct contact with the atmosphere, especially containing oxygen and ozone. Immediately after emergence from the device, the membrane is placed in methanol to wash away unreacted species and other non-covalent molecules.

After drying, the film exhibits two-sided properties. One side is very hydrophilic and the other side is very hydrophobic. A drop of water placed on the hydrophilic side travels in the radial direction and spreads rapidly. Methanol does not wet the hydrophobic side. Environmentally controlled scanning electron microscopy (ESEM) reveals that approximately 85% of the membrane forms a hydrophilic layer, while the remaining 15% is hydrophobic. A copy of the ESEM is shown in Figure 2. The dark, homogeneous layer is the hydrophilic region.

Hydrophilic 0.65u Durapore (DVPP) is treated with a formulation containing positively charged monomers. This formulation is from 12% acrylamide propyltrimethylammonium chloride, 1% methylenebisacrylamide, 0.2% Irgacre 2959 (ie 4- (2-hydroxyethoxy) phenyl- (2-propyl) ketone, Ciba Specialty Chemicals. Available), and consists of 86.8% water. Place this membrane on a sheet of polyethylene. No cover sheet is applied. Through the Fusion Systems UV device, move the membrane at 10 feet per minute, exposing the film to UV light only towards the side covered by the polyethylene sheet. The uncoated side is not directly exposed and is in direct contact with the atmosphere, especially containing oxygen and ozone. Immediately after emergence from the device, the membrane is placed in water to wash away unreacted species and other non-covalent molecules.

The sample membrane was subjected to a negatively charged dye, Ponceau S (ie, (3-hydroxy-4- (2-sulfo-4- (4-sulfophenylazo) -phenylazo) -2,7 naphthalenedisulfonic acid tetrasodium salt). Place in a solution of (available from Sigma-Aldrich, Milwaukee, Wisconsin). After treating the sample for 15 minutes and washing with water until no more dye is removed, this sample allows the side covered by the polyethylene sheet to be The side stained red and thus positively charged, while the side not covered by polyethylene is shown to remain unstained and colorless.

This example demonstrates the ability to control the thickness of a layer or region by varying the concentration of free radical polymerization initiator in the modified formulation. The first formulation of the system consisted of 7.0% DuPont zonylfluoroacrylate, 1.0% hexanediol diacrylate, and 0.2% Irgacure 621 dissolved in decamethyltetrasiloxane. The photopolymerization initiator, Irgacre 651, was reduced by diluting the starting formulation. The thickness of the hydrophobic layer gradually decreased, and in the control method, the membrane of Example 1 was treated in the same manner as described in Example 1. This is shown in Table 1 below.

<tables num="1"><img file="JP5069397B2_D0001.tif" /></tables>

The purpose of this experiment is to show that PPA dissolved in a liquid carrier can be used. The PPA in this example is 2,2'-diphenyl-1-picrylhydrazyl (DPPH) (Sigma-Aldrich). Immerse an ink-free felt-tip pen or equivalent in a 1% methanol solution of DPPH and use it to mark on a sheet of hydrophilic DVPP membrane. The solution is applied in several locations in a delivery volume that is completely or partially permeable to the membrane. Evaporate methanol. The membrane is treated with the solution from Example 1 and placed between two polyethylene sheets so that both sides of the membrane are covered to prevent oxygen from diffusing from one side and acting as a PPA. The sample is then exposed to UV light as in Example 1, washed and dried.

When water is applied to both sides of the membrane, wetting occurs only in the form of marks only in the place where DPPH is applied. This is due to the fact that DPPH interferes with the polymerization. Deformations of the hydrophobic surface are then formed in the membrane except where DPPH acts as a PPA. At the position where the methanol solution permeates the entire depth portion, the wetting liquid permeates the entire thickness portion of the membrane. At the position where the methanol solution only partially penetrated, the wettable powder also partially penetrated into the deep part of the membrane.

<figref num="1">It is a figure which shows the cross section of the film of Example 1.</figref><figref num="2">It is a figure which shows the cross section of the film of Example 3. FIG.</figref>