KR0167755B1 - Porous polymer beads and process thereof - Google Patents

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Description

Porous Polymer Beads and Manufacturing Method Thereof

1 is a micrograph showing a surface free of epidermis, a 500-fold magnification of the microporous spherical polymer-copolymer beads of the present invention;

FIG. 2 is a 2000x magnification of the cross section of the microporous beads of FIG. 1 showing a high pore volume of 97% and uniform, non-cellular pore morphology;

3 is a 1,440-fold magnification micrograph of a polymer-copolymer bead cross section according to the present invention illustrating a non-cellular pore morphology of uniform diameter, pore volume of 97% and substantial mattress uniformity.

4 is a 2000x magnification of a cross section of a prior art polypropylene foam (Castro, US Pat. No. 4,519,909, 67) showing a 75 pore volume microporous noncellular structure. This structure is not a bead.

FIG. 5 is a micrograph of a 111-fold magnification of the cross-section of a prior art polyacrylonitrile particle (Story, US Pat. No. 4,110,529, Example 1) showing a non-spherical disk-shaped bead having a shell on its outer surface.

FIG. 6 is a 442x enlarged micrograph of a cross section of a prior art polyacrylonitrile particle (Story, US Pat. No. 4,110,529, Example 2) showing beads having extremely large internal pores of 20-40 micron diameter.

FIG. 7 is a micrograph 50 times the cross section of the prior art polyacrylonitrile particle (Stoy, US Patent No. 4,110,529, Example 2) showing non-uniform pore structure.

8 is a 437 magnification of a prior art polyacrylonitrile particle (Matt Sumoto, US Pat. No. 4,486,549) showing a non-uniform disc-like structure.

The present application relates to serial number 07 / 275,170 for the porous polymer beads and methods of Michael Timothy Cook and Laura Jean Hiscock and to a series of porous polyacrylonitrile beads and processes for Michael Timothy Cook and Laura Jean Hiscock. No. 07 / 275,317, to a commonly assigned and concurrently filed application.

The present invention relates to isotropic porous polymer beads (substantially free of epidermis) having a pore diameter of 0.002 to 5 microns and a pore volume not substantially less than 1.5 ml / g. Beads are prepared from polymer or copolymer solutions by thermal derived phase separation processes. The morphology of the beads makes them ideally suited for use in chromatography, particularly for biomolecule separation processes such as protein separation.

The phase separation process of the polymer solution is very useful for the production of porous low density microcellular plastic foams, mainly in the form of fibers, sheets and blocks or slabs.

In British patent specification 938,694, finely divided thermoplastics are mixed with a gel forming solvent therefor, raising the temperature of the mixture above their gelling point, lowering the temperature at which the gel is formed, Microporous materials are prepared by removing the gel forming solvent from the mixture by treating with a solvent instead of a solvent. In this British patent example, 35% by volume of polyethylene resin was heated with 65% by volume of xylene at 140 ° C. and cooled to room temperature to form a gelled material. The material was cut into sheets and xylene was extracted with ethanol. After ethanol is removed with water, a microporous foam sheet is obtained, which has a pore size of about 1.0 micron or less and a total porosity of about 65%, and the sheet is useful, for example, as a separator for a battery.

US Pat. No. 4,430,451 to Young et al. Uses methanol, for example, to remove bibenzyl remaining in the resin from a solvent comprising poly (4-methyl-1-pentene) resin and bibenzyl. Such processes were used to produce low density foams in the form of brittle microbubbles, low density foams having a broadly disclosed pore volume of 90-99% and a particularly illustrated pore volume of about 94%. Such foams are processed into blocks for laser fusion objects.

In US Pat. Nos. 4,247,498 and 4,519,909 to Cast, thermally induced phase separation techniques are used to produce microporous foams in the form of blocks or complex shapes from films. 909 in Col. 6, lines 34-35 describe that mixing or other shear forces are not applied while the solution is cooled when cooling the solution to the desired shape. This strongly suggests that beads are not considered. Castro, col. 909 patent. 27-28 also describe microporous polymers containing functional liquids. Such polymers are said to have a cellular or non-cellular structure containing liquids. Cellular structure is described by Col. It is defined in 7 and has a series of included cells that are substantially spherical with pores or passages that are internally connected to adjacent cells, wherein the diameter of the cells is at least twice the pore diameter. Such morphology is not ideal for adsorbing macromolecules because the passageway is not a passage of uniform diameter, which presents a severe disadvantage for macromolecule absorption and desorption.

Stoy US Pat. No. 4,110,529 describes spherical polyacrylonitrile beads formed by a process of dispersing a polymer solution into a liquid that disperses a medium that is non-solvent for the polymeric material and incompatible with the solvent. The emulsion solidifies the polymer material. It is added to the polymeric material by stirring it into an excess of coagulating liquid which is non-solvent, miscible with the solvent, and incompatible with the dispersion medium. In order to adopt the traditional method of making the beads, the applicant here can quench the same by forming a high temperature emulsion of the polymer solution in the inorganic oil and adding it to the inorganic oil at low temperature. Applicants therefore do not use coagulation batches which are immiscible with the polymer solution and miscible with the dispersion medium. However, even with a pore content of 95% or less, the main disadvantage with the Stoy process is that, as described in Col 3, lines 30-41, the surface of droplets at the very beginning of solidification begins. A non-stick surface is formed on the phase. Such epidermis cannot be controlled by such a process and can only be partially permeated, thereby substantially preventing the production and desorption of the macromolecules, thereby greatly inhibiting the production of microporous beads that are unskinned or controllable. Hope it. Furthermore, as will be shown later in the comparative examples, beads prepared using the process described in Stoy have anisotropic pores with macropores concentrated therein, and therefore, applications to size exclusion chromatography and macromolecules. It is not effective for desorption.

US Pat. No. 4,486,549 to Matt Sumoto generally discloses porous fibers and filaments, but in Example 1 of the patent also directs the formation of polyacrylonitrile particles by dropping the polymer solution into an atomizer. However, the beads produced in this method had a low pore volume of 0.90 ml / g, as shown in Comparative Example 1A of this application because of the low dose. Particles tend to be flat and non-spherical as shown in FIG. 8, which causes excessive pressure drop.

One of general interest is porous bodies, such as fibers, hollow filaments, tubes, tubing, rods, blocks and powder bodies from polyolefins, poly (vinyl esters), polyamides, polyurethanes and polycarbonates. US Patent No. 4,594,207 to Josef Peak's group of techniques for the preparation of ethylene. By varying the solvent ratio, the overall pore volume, pore size and pore wall produced are adjusted; Exemplary pore volumes range from 75-77.5%. Josephiac has published shaping of viscous solutions by a method that does not require shear during cooling. Example 1-5 of the Josephpiak patent describes forming a hollow filament by rotating and then cooling the solution through a hollow filament nozzle; Examples 5-7 describe the formation of the membrane by coating the pane with solution and then cooling. See also Joseph Piac, US Patent No. 4,666,607 Col. 2, line 43 to Col. Line 3, line 14 teaches the difference between using a strong shearing force during cooling. Josephiaq did not consider the use of lubrication while cooling anywhere in the technology, which strongly suggests that beads cannot be expected from this technology. In contrast to the present invention, shear forces are used in solution before and during cooling to form droplets that are cooled with beads. These beads surprisingly have a high separation capacity, low resistance to chromatographic flow rates and excellent compressive strength in the application of chromatography, and provide excellent morphological advantages for column filling applications such as substantially spherical. Zwick, Applied Polymer Symposia, No. 6, 109-149, 1967 used a similar method for producing microporous fibers using polymer concentrates in the wet spinning range of 10-25% for the production of microporous structures having a pore volume of 75-90%. do.

U.S. Patent No. 3,983,001 to Cupek et al. Discloses a method for isolating biologically active compounds by affinity chromatography. Isolated compounds include enzymes, coenzymes, enzyme inhibitors, antibodies, antigens, hormones, carbohydrates, lipids, peptides and proteins as well as vitamins such as nucleotides, hexanes and vitamin B. Macroporous porous carriers require a secondary shaping process to form particles from the gels obtained by practicing the present invention, and are particularly inferior in other chromatography processes such as size exclusion chromatography.

로 판매되는 고 다공성 친수성 수징 의해 대표된다. 이들은 고 다공성 친수성 비닐 중합체로 구성된 경질의 구형 겔 비이드를 포함하는 것으로 언급되어 있다. 이들은 120 미크론의 평균 지름 및 1.6ml/g 보다 적은 기공 부피를 갖는다. 또한 동일 회사에서 디비닐 벤젠과 가교 결합된 스티렌으로 구성된 DIAION

고 다공성 중합체 비이드를 생산한다. 그러한 비이드는 협소한 기공 크기 분포를 가질 수 있고 이들의 기공 부피는 1.2ml/g보다 적다.The current state of the art in the field of microporous beads for purification, chromatography, enzymatic binding, etc. is trademarked by Mitsubishi Chemical Industries Limited.

It is represented by a highly porous hydrophilic hydrating sold. They are said to include hard spherical gel beads composed of highly porous hydrophilic vinyl polymers. They have an average diameter of 120 microns and a pore volume of less than 1.6 ml / g. DIAION also consists of styrene crosslinked with divinyl benzene at the same company

Produces highly porous polymer beads. Such beads may have a narrow pore size distribution and their pore volume is less than 1.2 ml / g.

Therefore, the main drawback of many microporous polymer structures is that it is typically difficult to increase mechanical strength, as shown by Castro, but with less pore volume, typically up to 2-75% or 90% of the polymer structure. It becomes self-evident from. Lower pore volumes improve mechanical strength but provide lower capacity when used in structures such as chromatographic adsorbents. Other prior art structures are in the form of fibers, filaments or membranes and may not be used effectively to fill a chromatography column, requiring a costly secondary molding device. Many prior art structures are not rigid and swell with varying ionic strength or solvent, making column packing and conditioning difficult.

Substantially spherical microporous beads with very high pore volume, substantially epidermal surface, large pore diameter and high mechanical strength can now be produced by thermally induced phase separation by appropriate selection of process technology. I found it. Such beads are novel and their unexpected properties are totally unexpected in the sense of their prior art and the best materials produced commercially available to date. Unepidermed beads of the present invention allow the access of macromolecules to their internal surface area. They are prepared by processes that do not involve chemical reactions, such as difficulties in controlling the formation of porous beads from monomers. The morphology of the beads makes them ideally suited for most chromatography applications, in particular for the chromatography of proteins. They can also be used for enzyme immobilization and many other uses.

According to the present invention there is provided a substantially epidermal, highly porous beads comprising polymers or copolymers, wherein the beads are substantially non-swellable and substantially isotropic in water and are less than about 5 microns in diameter. It has pores that are not substantially large, and the pore volume is not substantially less than about 1.5 ml / g.

The present invention also contemplates porous polymeric beads in which the pores are at least partially filled with a compound of polymer size and the beads are substantially spherical.

In a preferred mode of making beads, the polymer or copolymer is dissolved in a solvent compound where only the polymer can be dissolved at high temperatures. The solvent mixture contains a good solvent for the polymer mixed with at least one additive that reduces the solvability of the solvent. This additive may be nonsolvent for the polymer. The homogeneous polymer solution is then suspended in a hot inert dispersion. To form the droplets, the two phase liquid mixture is stirred correctly and mixed. Stir the droplets and introduce into the cooling inert liquid. The droplets are then collected and the polymer solvent is extracted to produce the porous beads of the present invention. The beads are isotropic with a diameter of 0.002 to 5 microns. Cells associated with the pores as described in many prior art are not visible. The cell diameter to pore diameter ratio C / P is thus 1.0, which distinguishes them from the preferred embodiment of the Castro patent. It is believed that uniform microporosity is due to the selection of the appropriate solvent / non-solvent composition. The addition of nonsolvent increases the rate of phase separation. In order to provide a pore volume of at least 90%, it is preferred to use up to about 10% by weight of the polymer in the solution. It was entirely unpredictable that the beads were substantially free of epidermis, did not adhere to each other, and had excellent control strength, even at high pore volumes.

Porous beads of the invention can be prepared from a wide variety of thermoplastic organic polymers, including vinyl addition polymers, condensation polymers, and oxidizing polymers. The only requirement is that the polymers should be soluble in the liquefied medium and they typically form a hard structure at the temperature at which the beads will be used. Therefore, all useful condensation and additions made from, for example, vinyl and acrylic esters and ethers, or other esters of unsaturated acids and alcohols such as polyacetals, polyamides, polyesters, polyurethanes, polysiloxanes, polyoxiranes, polydienes and the like It is not necessary to list the polymers. This is because a polymer that is physically soluble in itself is not excluded. Exemplary polymers are particularly well known, as will be apparent from the prior art mentioned above. However, preferably the polymer comprises a vinyl addition polymer or copolymer, wherein the term copolymer includes terpolymers as well as from four or more comonomers, more preferably the vinyl addition polymer or copolymer is poly (C ₂ -C ₆ mono-olefin), vinyl aminoaromatic, poly (vinyl aromatic), poly (vinyl halide), poly (C ₁ -C ₆ alkyl (meth) acrylate), N-hydroxy-containing (C ₁ -C ₆ ) alkyl (meth) acrylamides or polyolefins such as poly (ethylene), poly (propylene); Blends of any of the foregoing polymers, such as poly (styrene), poly (vinyl chloride), poly (methyl methacrylate), and the like. Polyacrylonitrile or copolymers thereof may also be used in the embodiments of the present invention.

As the solvent for the polymer, any organic or inorganic liquid which can dissolve them without permanent chemical change can be used. These include aqueous solutions of dimethyl sulfoxide, dimethyl formamide, dimethyl sulfone, sodium thiocyanate and zinc chloride when polyacrylonitrile is used as the polymer.

The nonsolvent may include any liquid medium that is immiscible with the polymer or copolymer. If polyacrylonitrile is used as the polymer, the nonsolvent may comprise urea, water, glycerin, propylene glycol, ethylene glycol or mixtures thereof.

The nonsolvent dispersion can include any liquid medium that is incompatible with the polymer or copolymer and the polymer solvent. Usually, they will include low polar liquids such as aliphatic, aromatic or hydrogenated aromatic hydrocarbons and their hydrogenated derivatives, low molecular weight polysiloxanes, olefins, ethers and analogs of such compounds.

The choice of solvent and nonsolvent cannot be easily described herein. Because they depend not only on the choice of polymer or copolymer used, but also on each other. If polyacrylonitrile is used as the polymer, the preferred solvent-non-solvent system consists of a solvent mixture of added water, ethylene glycol or propylene glycol and dimethyl sulfone-urea-water or dimethyl sulfoxide or dimethyl sulfone and is selected. Hot inert liquids which are inorganic oils, bottom oil petroleum solvents or hydrogenated aromatic aromatic hydrocarbons such as ketocene, aromatics, lower aliphatic. Preferred as extractant are lower ketones such as lower alkanol or acetone and water such as methanol or ethanol.

The morphology of the present invention is very difficult to obtain by conventional phase separation techniques of solvents. In such cases, solvent diffusion results in the formation of asymmetrical forms or the pores are much smaller. US Pat. No. 4,486,549, Example 1, wherein the porous polyacrylonitrile particles formed from atomizer cups and quenched in aqueous dimethyl formamide using a solvent phase inversion process provide low pore volume and non-spherical particles. Purple.

In the usual manner, the polymer or copolymer is dissolved in a hot solvent / non-solvent mixture designed to dissolve only the polymer or copolymer at high temperatures. The composition of the mixture required to meet this condition is determined by performing cloud point expertiment, which measures the temperature at which phase separation occurs. If polyacrylonitrile is used as the polymer, preferably the solvent will be dimethyl sulfoxide or dimethyl sulfone and the nonsolvent is selected from water, urea, glycerin, ethylene glycol, propylene glycol or combinations thereof. Preferably, typical total solvent / non-solvent ratios will vary from 95/5 to 65/35 (weight). Typical polymer concentrations will be from 0.5 to about 20 weight percent, preferably up to 10 weight percent of the total polymer solids in the polymer / non-solvent mixture.

The hot polymer solution is agitated and dispersed in a liquid, such as inorganic oil, which is substantially incompatible with the solution. Typically the volume of the polymer solution is dispersed within 4 volumes of the inorganic oil. The droplets are then cooled to below the phase separation temperature. The polymer phase is separated from the solvent / non-solvent solution and then precipitates as droplets of the solid polymer and solvent. The solid droplet is then removed from the mineral oil.

The collected droplets are then extracted as a material that is miscible with the solvent / non-solvent mixture but is not a solvent for the polymer to make the porous beads. The extracted beads are dried to produce a microporous product. The pore size of the beads can vary from 0.002 microns to 5 microns by varying the concentration and shape of the copolymer composition or nonsolvent used. The total pore volume is determined by the minimum concentration of polymer in the solvent / nonsolvent solution. It is also contemplated by the present invention to remove the solvent material from the solidified beads by any other conventional method such as simple washing in the case of liquid solvents.

Particular application of the technique will be illustrated in detail later in the art.

As used herein and in the appended claims, the term pore volume means milliliters of pores per gram of polymer. Pore volume is a direct function of polymer concentration. Particular preference is given to beads having a pore volume of at least 1.5 ml / g. Pore volume is measured by conventional means, such as mercury porosimetry.

The term substantially non-swellable in water means that in water the volume will increase to about 5% or less through swelling. Non-swellable beads are preferred because in column chromatography applications the bulk volume must remain essentially constant, resulting in a constant flow rate and negligible head pressure loss. The term without epidermis is intended to mean porous particles that do not show a surface epidermis and are effective for the direct absorption of high molecular weight molecules. The bulk density of the polymer beads is measured in a conventional manner, such as by tapping a constant volume. The beads of the present invention preferably have a bulk density of greater than about 5 ml / g. Lower bulk densities are undesirable because of their tendency to have lower capacities. The upper limit of bulk density is about 15 ml / g. Above this level no further economic advantages can be found and the mechanical strength is reduced. The average bead diameter can vary widely depending on its use. Preferably from about 5 microns to about 2 milliliters, more preferably from about 5 microns to about 150 microns. Special mention is made for bead diameters of about 5 microns, which are only suitable for analytical high pressure liquid chromatography. Bead particle sizes of about 5 to about 150 microns are generally preferred for other chromatography applications, in particular 5 to 20 microns, particularly preferably 20 to 100 microns. Bead size can be measured by conventional methods such as the use of a particle size analyzer. The average pore diameter is preferably from about 0.002 to about 5 microns, particularly preferably from about 0.1 to about 1 micron, although the pore size can vary widely and is measured in conventional methods by nitrogen adsorption or mercury intrusion. Also preferred are beads having an average pore diameter of about 0.002 to about 0.1 microns.

When the beads are used to contain a compound, the compound preferably comprises a protein, enzyme, peptide, hexane, polysaccharide, dye, pigment or any mixture of the above, with particular preference being a protein. Beads may be filled by the physical entrapment, physical adsorption or chemical bonding depending on the compound. In any case, the porous beads used will preferably have a pore diameter that is at least about three times the diameter of the compound.

Conventional techniques are used to exploit the adsorption capacity of the porous beads of the present invention. Beads can be used to adsorb other bioactive materials, for example, from vitamins, antibiotics, enzyme steroids and fermentation solutions. These can be used to decolorize various sugar solutions. These can be used to decolor the saccharified wood solution. They can be used as column packing for gas chromatography, size exclusion chromatography, affinity chromatography, ion exchange chromatography, reverse phase or hydrophobic interaction applications. They are useful for removing phenols and removing various surface active agents. They can adsorb various fragrances. They can bleach waste effluents in paper pulp production and bleach and purify various chemicals.

Beads of the invention are particularly useful for protein isolation. Particularly suitable proteins for purification using the beads of the invention are alpha-lactoalbumin, albumin, gamma-globulin, albumin interferon and the like.

The following examples illustrate the invention. The claims should not be construed as limited thereto. SEM micrographs were examined to determine the pore size in Examples 4-8.

Example 1

5 g wet copolymer containing 99 mol% polyacrylonitrile and 1 mol% dimethyl sulfoxide (copolymer: water = 1: 1 by weight) was ground and powdered by grinding with 5 g urea and 30 g dimethyl sulfone Formed a mixture. The mixture was placed in a 1 liter flask with 100 ml of mineral oil heated to 160 ° C. The mixture was stirred by stirring until two liquid phases were present, one phase being a homogeneous polymer solution and the other inorganic. The mixture is stirred quickly with an overhead paddle stirrer to provide a suspension consisting of droplets of a hot (about 120 ° C.) polymer solution in mineral oil. Through the cannula the suspension was transferred to a second stirred mixture consisting of 500 ml of mineral oil, 6 g of dimethylsulfone and 1 g of urea maintained at 70 ° C. to cool the droplets. When contacted with cold mineral oil, the droplets solidify. The mixture was stirred and cooled to room temperature and diluted with methylene chloride to reduce oil viscosity. Droplets were collected on a Buchner funner, washed with methylene chloride and the solvent extracted with 200 ml of acetone at room temperature for 1.5 hours. The resulting beads were examined by scanning electron microscopy (SEM) and appear to be very porous with a relatively uniform pore diameter of about 0.5 microns. The pores extend to the outer surface of the bead. Beads range in size from 10 microns to several millimeters. SEM photographs of these bead cross sections are shown in FIG.

Comparative Example 1A

Particles were prepared by the procedure indicated in Example 1 of Matsumoto, US Pat. No. 4,486,549. 120 g of polyacrylonitrile homopolymer was dissolved in 1800 ml of dimethylformamide and 20% aqueous dimethylform at a rate of 20 ml / min in a rotary atomizer cup (Model PPH 306 OOD supplied by Sames Electrostatic Inc.). The resulting solution was added dropwise to the amide solution to obtain polyacrylonitrile particles. The SEM photograph (Fig. 8) shows a different shape and morphology from that obtained by the process of the embodiment of the present invention.

Comparative Example 1B-1C

Beads were prepared according to the description of Stoy's US Pat. No. 4,110,529. According to Stoy's general procedure of Example 1, polyacrylonitrile was dissolved in dimethylsulfoxide, dispersed in paraffin oil and poured into water in a thin stream at 15 ° C. Then, Example 2 of Stoy was repeated (emulsion was poured into water at 60 ° C). Spherical porous beads were separated and photographed with a scanning electron microscope. Photographs are shown in FIGS. 5 and 6. Unlike the present invention, wherein the beads are substantially isotropic, the beads have pores that penetrate very largely outside and inside the porous.

Example 2

Poly (sulfone) and dimethyl formamide as solvent mixture components for forming microporous beads according to the present invention; Dimethyl formamide, water; And the process of Example 1 was repeated using N-methylpyrrolidone, water.

Example 3

The procedure of Example 1 was repeated using 9% of the polymer of Example 2 and 21% of water. Microporous beads with an average pore size of 0.8 microns were obtained.

Example 4

The procedure of Example 1 was routinely repeated using 15% of the polymer of Example 2 and 15% of water. Instead, the polymer dispersion was pipetted into a flask filled with inorganic oil at room temperature. Partially epidermal beads were obtained that were microporous with an average pore size of 0.7 microns.

Example 5

The procedure of Example 4 was repeated using 15% polymer consisting of 95.5 mol% acrylonitrile, 3.4 mol% methyl methacrylate and 1.1 mol% acrylamidomethylpropyl sulfonic acid and 15% water as nonsolvent; Partially epidermal beads were obtained that were microporous with an average pore size of 0.2-0.3 microns.

Example 6

The procedure of Example 4 was repeated using 15% of the polymer of Example 5 and 20% of water as the nonsolvent; Partially epidermal beads were obtained that were microporous with an average pore size of 0.7 microns.

Example 7

The procedure of Example 4 was repeated using 15% copolymer consisting of 90 mol% acrylonitrile and 10 mol% methacrylate units, with a partially epidermal microporous with an average pore size of 3.5 to 6.5 microns. Beads were obtained.

Comparative Example 1D

The procedure of Example 4 was repeated using 15% polymer consisting of 50 mol% acrylonitrile and 50 mol% methyl methacrylate units and 15% water as nonsolvent. Microporous beads having an average pore size of about 10 microns were obtained.

Example 8

The procedure of Example 1 was repeated using 3% 99 mol% acrylonitrile-1 mol% methyl acrylate copolymer and 11% water as nonsolvent. According to the present invention, epidermal-free microporous polymer beads were obtained as described in FIG.

Example 9

The procedure of Example 1 was repeated with 3% 99 mol% acrylonitrile-1 mol% methyl acrylate copolymer and 4% water and 13% urea. Microporous beads were obtained in accordance with the present invention, the cross-sectional view of the beads being shown 1,440 times in FIG.

Example 10

In order to produce the microporous beads according to the present invention, dimethyl sulfoxide, dimethyl sulfone, water urea, glycerin, ethylene glycol and propylene glycol are used as the solvent mixture component and contain 50 to 8 mol% of acrylonitrile. The thermal phase separation technique of Example 1 was repeated with the polyacrylonitrile copolymer.

Example 11

A 1 g dry copolymer consisting of 99 mol% acrylonitrile and 1 mol% methyl acrylate was ground using a pestle in mortar with 1 g deionized water, 2 g urea and 12 g dimethylsulfone. The mixture was heated to 125 ° C. to form a homogeneous polymer solution. Hot mineral oil (60 ml, 150 ° C.) was shaken in setting 7 (to 4 amps) in Branson Sonifier Model S75. Hot polymer solution was added slowly to increase the current to 6 amps. The suspension was mixed for a few minutes and then diluted with 180 ml (120 ° C.) of mineral oil containing 2.4 g of dimethylsulfone and 0.4 g of urea. The flask was placed in a water bath to cool the suspension. Turn off Sonyfire when the suspension reaches 110 ° C. After cooling to room temperature the oil was diluted with methylene chloride and the droplets collected on a Buchner funnel and washed with methylene chloride. The beads were extracted with 60 ml of acetone for 16 hours at room temperature and then collected again, but this time washed with methanol. The beads were dried at room temperature under vacuum. The beads were tested by scanning electron microscopy and found to have high pore volume, pore diameter of about 1 micron and high surface porosity. The average bead diameter is about 50 microns.

Example 12

The procedure of Example 1 was repeated using 9% of the polymer of Example 11 and 21% of water. A microporous product with an average pore size of 0.8 microns was obtained.

The above patents and publications are hereby incorporated by reference.

Many modifications will be suggested to those skilled in the art in light of the above detailed description. For example, glucose and sucrose solutions can be discolored by contact with the microporous beads of the present invention; Fatty acids such as butanoic acid, propionic acid and acetic acid can be adsorbed from aqueous solutions by their use. Soaps and detergents can be adsorbed to them from solution. The enzymes can be used to catalyze the reaction in a substrate, such as fermented broth, which has been adsorbed into them and then passed through beads containing such base enzymes. All such obvious changes are within the total intended scope of the appended claims.

Claims (20)

A substantially epidermal, high porosity bead comprising an organic polymer or copolymer, the beads are substantially non-swellable, substantially isotropic in water, substantially less than 5 microns in diameter, and substantially bulky High porosity beads with pores greater than 1.5 ml / g. The porous bead of claim 1, wherein the porous bead is substantially spherical. The method of claim 1, wherein the polymer or copolymer is a (C ₂ -C ₆ ) monoolefin, vinyl aromatic, vinylaminoaromatic, vinyl halide, (C ₁ -C ₆ ) alkyl (meth) acrylate, (meth ) Acrylamide, vinyl pyrrolidone, vinylpyridine, (C ₁ -C ₆ ) hydroxyalkyl (meth) acrylate, (meth) acrylic acid, acrylamidomethylpropylsulfonic acid, N-hydroxy-containing (C _1- C ₆ ) Porous beads comprising alkyl (meth) acrylamide, acrylonitrile or mixtures thereof. The porous bead of claim 3, wherein the copolymer comprises 45 to 99.5 mol% of polymerized methyl methacrylate or polysulfone. The porous bead of claim 1, wherein the pores are substantially isotropic throughout the beads. The porous bead of claim 1, wherein the pore volume is 5 ml / g or less. The porous bead of claim 1, wherein the average bead diameter is between 5 microns and 2 millimeters. The porous bead of claim 7, wherein the average bead diameter is 5 to 150 microns. The porous bead of claim 1, wherein the average pore diameter is from 0.002 microns to 5 microns. The porous bead of claim 1, wherein the average pore diameter is from 0.002 microns to 0.1 microns. The porous bead of claim 8, wherein the average pore diameter is from 0.1 micron to 1 micron. The porous bead of claim 1, wherein the pores are partially or fully filled with a compound selected from proteins, enzymes, peptides, polysaccharides, nucleic acids, dyes, pigments, or mixtures thereof. 13. The porous bead of claim 12, wherein said compound consists of a protein. The porous bead of claim 12, wherein the pore diameter is at least three times the diameter of the compound. (i) heating and mixing the polymer or copolymer with a mixture comprising a solvent and a nonsolvent for the polymer to form a homogeneous solution; (ii) straightening the homogeneous solution into droplets; (iii) cooling the droplets in the presence or absence of an inert liquid to cause phase separation and solidification of the polymer in the droplets; (iv) separating the droplets from any inert liquid and solvent-non-solvent mixture to produce isotropic porous beads. The process of claim 15 wherein the solvent comprises dimethyl sulfone and the non-solvent comprises urea, water, propylene glycol, ethylene glycol or mixtures thereof and step (i) is carried out at a temperature of at least 130 ° C. Way. The method of claim 15, wherein the inert liquid comprises inorganic oil, heptane or mixtures thereof. The method of claim 16 wherein said beads are extracted with a nonsolvent for polymers comprising acetone, methanol, water or mixtures thereof. The method of claim 15, wherein the polymer comprises polymeric methyl methacrylate, acrylonitrile or polysulfone. The method of claim 15, wherein said homogeneous solution contains less than 10% by weight of a polymer or copolymer.

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