WO1995033553A1 - Polymeric microbeads and method of preparation - Google Patents
Polymeric microbeads and method of preparation Download PDFInfo
- Publication number
- WO1995033553A1 WO1995033553A1 PCT/US1995/006879 US9506879W WO9533553A1 WO 1995033553 A1 WO1995033553 A1 WO 1995033553A1 US 9506879 W US9506879 W US 9506879W WO 9533553 A1 WO9533553 A1 WO 9533553A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- microbeads
- group
- microbead
- emulsion
- functionalized
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
- C08F8/34—Introducing sulfur atoms or sulfur-containing groups
- C08F8/36—Sulfonation; Sulfation
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/18—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns
- B01D15/1807—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns using counter-currents, e.g. fluidised beds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/06—Making microcapsules or microballoons by phase separation
- B01J13/14—Polymerisation; cross-linking
- B01J13/18—In situ polymerisation with all reactants being present in the same phase
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/06—Making microcapsules or microballoons by phase separation
- B01J13/14—Polymerisation; cross-linking
- B01J13/18—In situ polymerisation with all reactants being present in the same phase
- B01J13/185—In situ polymerisation with all reactants being present in the same phase in an organic phase
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/20—After-treatment of capsule walls, e.g. hardening
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/26—Synthetic macromolecular compounds
- B01J20/265—Synthetic macromolecular compounds modified or post-treated polymers
- B01J20/267—Cross-linked polymers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28002—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their physical properties
- B01J20/28004—Sorbent size or size distribution, e.g. particle size
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28002—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their physical properties
- B01J20/28011—Other properties, e.g. density, crush strength
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
- B01J20/28016—Particle form
- B01J20/28019—Spherical, ellipsoidal or cylindrical
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28054—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their surface properties or porosity
- B01J20/28069—Pore volume, e.g. total pore volume, mesopore volume, micropore volume
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28054—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their surface properties or porosity
- B01J20/28078—Pore diameter
- B01J20/28085—Pore diameter being more than 50 nm, i.e. macropores
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28054—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their surface properties or porosity
- B01J20/28088—Pore-size distribution
- B01J20/2809—Monomodal or narrow distribution, uniform pores
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/282—Porous sorbents
- B01J20/285—Porous sorbents based on polymers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to polymers
- B01J20/288—Polar phases
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/305—Addition of material, later completely removed, e.g. as result of heat treatment, leaching or washing, e.g. for forming pores
- B01J20/3064—Addition of pore forming agents, e.g. pore inducing or porogenic agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3202—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
- B01J20/3206—Organic carriers, supports or substrates
- B01J20/3208—Polymeric carriers, supports or substrates
- B01J20/321—Polymeric carriers, supports or substrates consisting of a polymer obtained by reactions involving only carbon to carbon unsaturated bonds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
- B01J20/3244—Non-macromolecular compounds
- B01J20/3246—Non-macromolecular compounds having a well defined chemical structure
- B01J20/3248—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such
- B01J20/3251—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such comprising at least two different types of heteroatoms selected from nitrogen, oxygen or sulphur
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J39/00—Cation exchange; Use of material as cation exchangers; Treatment of material for improving the cation exchange properties
- B01J39/26—Cation exchangers for chromatographic processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J41/00—Anion exchange; Use of material as anion exchangers; Treatment of material for improving the anion exchange properties
- B01J41/20—Anion exchangers for chromatographic processes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
- C07K1/042—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers characterised by the nature of the carrier
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
- C08F8/18—Introducing halogen atoms or halogen-containing groups
- C08F8/24—Haloalkylation
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
- C08F8/30—Introducing nitrogen atoms or nitrogen-containing groups
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
- C08F8/44—Preparation of metal salts or ammonium salts
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/0068—General culture methods using substrates
- C12N5/0075—General culture methods using substrates using microcarriers
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/36—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction
- B01D15/361—Ion-exchange
- B01D15/362—Cation-exchange
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/38—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups B01D15/265 - B01D15/36
- B01D15/3804—Affinity chromatography
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
- B01J2220/54—Sorbents specially adapted for analytical or investigative chromatography
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F2800/00—Copolymer characterised by the proportions of the comonomers expressed
- C08F2800/10—Copolymer characterised by the proportions of the comonomers expressed as molar percentages
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2533/00—Supports or coatings for cell culture, characterised by material
- C12N2533/30—Synthetic polymers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S521/00—Synthetic resins or natural rubbers -- part of the class 520 series
- Y10S521/902—Cellular polymer containing an isocyanurate structure
Definitions
- the present invention relates to microbeads of a crosslinked porous polymeric material and methods for preparing such microbeads.
- this invention is directed to a polymeric microbead of exceptionally high porosity.
- HIPEs crosslinked, homogeneous, porous polymeric materials are disclosed in U.S. Patent No. 4,522,953 (Barby et al., issued June 11, 1985).
- the disclosed polymeric materials are produced by polymerization of water-in-oil emulsions having a relatively high ratio of water to oil. These emulsions are termed "high internal phase emulsions" and are known in the art as "HIPEs".
- HIPEs comprise an oil continuous phase including a monomer and a crosslinking agent and an aqueous discontinuous phase.
- Such emulsions are prepared by subjecting the combined oil and water phases to agitation in the presence of an emulsifier. Polymers are produced from the resultant emulsion by heating. The polymers are then washed to remove any unpolymerized monomer/crosslinker.
- the disclosed porous polymers have rigid structures containing cavities interconnected by pores in the cavity walls.
- HIPE polymers with void volumes of 80% or more can be achieved. These materials thus have a very high capacity for absorbing and retaining liquids.
- U.S. Patent No. 4,536,521 discloses that HIPE polymers can be sulfonated to produce a sulfonated polymeric material that exhibits a high capacity for absorption of ionic solutions.
- Other functionalized HIPE polymers prepared by a similar process have been disclosed in U.S. Patent Nos. 4,611,014 (Jomes et al. , issued September 9, 1986) and 4,612,334 (Jones et al . , September 16, 1986) .
- HIPE polymerizable HIPE
- the preparation of useful HIPE polymers is not without its difficulties. Because the emulsions used to produce these polymers have a high ratio of water to oil, the emulsions tend to be unstable. Selection of the appropriate monomer/crosslinker concentration, emulsifier and emulsifier concentration, temperature, and agitation conditions are all important to forming a stable emulsion. Slight changes in any of these variables can cause the emulsion to "break" or separate into distinct oil and water phases. Furthermore, emulsion components and process conditions that produce a stable emulsion may not always yield HIPE polymers that are useful for their intended purpose.
- the present invention includes a material (hereinafter “microbeads”) wherein at least about 10% of the material is in the form of substantially spherical and/or substantially ellipsoidal beads.
- microbeads have a porous, crosslinked, polymeric structure, characterized by cavities joined by interconnecting pores. At least some of the cavities at the interior of each microbead communicate with the surface of the microbead.
- the present invention also includes a process for producing a porous, crosslinked polymeric microbead as well as the product of this process.
- the first step of this process is to combine an oil continuous phase (hereinafter an "oil phase") with an aqueous discontinuous phase to form an emulsion.
- the oil phase of the emulsion includes a substantially water- insoluble, monofunctional monomer, a substantially water-insoluble, polyfunctional crosslinking agent, and an emulsifier that is suitable for forming a stable water-in-oil emulsion.
- the second step of the process is to add the emulsion to an aqueous suspension medium to form an oil-in-water suspension of dispersed emulsion droplets.
- the final step of this process is polymerizing the emulsion droplets to form microbeads.
- a polymerization initiator is present in both the aqueous discontinuous phase of the HIPE and the aqueous suspension medium.
- a polymerization initiator can optionally be included in the oil phase as well.
- the oil phase includes styrene as the monomer, divinylbenzene as the crosslinking agent, and sorbitan monooleate as the emulsifier.
- the oil phase contains the oil-soluble polymerization initiator azoisobisbutyronitrile as well as dodecane, which promotes the formation of interconnecting pores.
- the aqueous discontinuous phase includes the water- soluble polymerization initiator potassium persulfate.
- the aqueous suspension medium includes a suspending agent comprising modified silica and gelatin as well as potassium persulfate.
- polymerization initiator is present only in the oil phase.
- the present invention also encompasses microbeads that have been modified for use in particular applications.
- the present invention includes microbeads functionalized for absorption of liquids; carboniferous structures produced from microbeads and a process for producing such structures; and microbeads having a gel or pre-gel within the microbead cavities as well as a process for producing such microbeads.
- the present invention includes the use of microbeads in a variety of applications including the use of microbeads as a substrate in separation and synthetic methods; the use of microbeads as a substrate for immobilizing a molecule such as a polypeptide or an oligonucleotide; and the use of microbeads in cell culture methods.
- the Microbeads includes a crosslinked porous polymeric material, termed "microbeads", wherein at least about 10% of the microbeads are substantially spherical and or substantially ellipsoidal.
- the present invention also includes a process for making such a material.
- a microbead is typically produced by suspension polymerization of a high internal phase emulsion, termed a "HIPE" .
- HIPE high internal phase emulsion
- the microbead of the present invention thus has many of the desirable physical characteristics of prior art HIPE polymers (such as those disclosed in U.S. Patent No. 4,522,953, Barby et al. , issued June 11, 1985, which is incorporated by reference herein in its entirety) .
- the microbead has a very low density due to the presence of cavities joined by interconnecting pores.
- the bulk density of a batch of microbeads in accordance with the present invention is typically less than about 0.2 gm/ml.
- the void volume of the microbead is high, preferably at least about 70% and, more preferably at least about 90%. This high porosity gives the microbead exceptional absorbency.
- the microbead provides an excellent substrate for use in biotechnology applications such as, for example, chromatographic separation of proteins and peptide synthesis.
- the average diameter of the microbead typically ranges from about 5 ⁇ m to about 5 mm. Preferred average diameters range from about 50 ⁇ m to about
- the process of the present invention can be used to produce microbeads of a relatively uniform size and shape, which allows the wash conditions to be optimized to ensure that each microbead in a batch has been thoroughly washed.
- the microbead unlike the prior art HIPE blocks, can be washed with relative ease. This feature of the present invention facilitates cost-efficient scale-up of HIPE polymer production.
- microbead is "skinless" such that some interior cavities and pores communicate with the surface of the microbead.
- the microbead offers the advantage over prior art HIPE polymers that a porous polymeric material can be produced directly upon polymerization, obviating the need for a skin-removal step.
- microbead The high porosity of the microbead renders it useful as an absorbent material and also as a solid support in a variety of biotechnology applications, including chromatographic separations, solid phase synthesis, immobilization of antibodies or enzymes, and cell culture. Moreover, many of the physical characteristics of the microbead, such as void volume and cavity size, are controllable. Therefore, different types of microbeads, specialized for different uses, can be produced. A description of the general process for producing the microbead is presented below, followed by a discussion of modifications for producing specialized microbeads.
- microbeads refers to a crosslinked porous polymeric material wherein at least about 10% of this material consists of substantially spherical and/or substantially ellipsoidal beads. Preferably at least about 20% and more preferably at least about 50% of this material consists of substantially spherical and/or substantially ellipsoidal beads.
- substantially water-insoluble indicates that any component present in the aqueous phase is present at such a low concentration that polymerization of aqueous monomer is less than about 5 weight percent of polymerizable monomer.
- the term "bulk density” refers to the value obtained by dividing the weight of a known volume of microbeads by that volume.
- void volume refers to the volume of a microbead that does not comprise polymeric material.
- the void volume of a microbead comprises the total volume of the cavities. Void volume is expressed either as a percentage of the total microbead volume or as a volume per gram of microbead material (cc/gm) .
- cavity size refers to the average diameter of the cavities present in a microbead.
- the term "porogen” refers to an organic compound that, when included in the oil phase of a HIPE, promotes the formation of pores connecting the cavities in a microbead.
- DVB refers to "divinylbenzene”
- AIBN refers to “azoisobisbutyronitrile”
- PVA refers to "poly(vinyl alcohol)", which is produced by hydrolysis of poly(vinyl acetate) .
- microbead Production The microbeads of the present invention are conveniently produced from a HIPE, which comprises an emulsion of an aqueous discontinuous phase in an oil phase. Once formed, the HIPE is added to an aqueous suspension medium to form a suspension of HIPE microdroplets in the suspension medium. Polymerization then converts the liquid HIPE microdroplets to solid microbeads.
- a HIPE which comprises an emulsion of an aqueous discontinuous phase in an oil phase.
- a polymerization initiator is present in both the aqueous discontinuous phase of the HIPE and the aqueous suspension medium.
- a polymerization initiator can optionally be included in the oil phase as well. In another embodiment, polymerization initiator is present only in the oil phase.
- the relative amounts of the two HIPE phases are, among other parameters, important determinants of the physical properties of the microbead.
- the percentage of the aqueous discontinuous phase affects void volume, density, cavity size, and surface area.
- the percentage of aqueous discontinuous phase is generally in the range of about 70% to about 98%, more preferably about 75% to about 95%, and most preferably about 80% to about 90%.
- the oil phase of the emulsion comprises a monomer, a crosslinking agent, and an emulsifier that is suitable for forming a stable water-in-oil emulsion.
- the monomer component does not differ from that of prior art HIPE polymers and can be any substantially water-insoluble, monofunctional monomer.
- the monomer type is a styrene-based monomer, such as styrene, 4-methylstyrene, 4-ethylstyrene, chloromethylstyrene,
- the monomer component can be a single monomer type or a mixture of types.
- the monomer component is typically present in a concentration of about 5% to about 90% by weight of the oil phase.
- the concentration of the monomer component is preferably about 15% to about 50% of the oil phase, more preferably, about 16% to about 38%.
- the crosslinking agent can be selected from a wide variety of substantially water-insoluble, polyfunctional monomers.
- the crosslinking agent is difunctional. Suitable cross-linking agents do not differ from those of the prior art and include divinyl aromatic compounds, such as divinylbenzene (DVB) . Other types of cross-linking agents, such as di- or triacrylic compounds and triallyl isocyanurate, can also be employed.
- the crosslinking agent can be a single crosslinker type or a mixture of types.
- the crosslinking agent is generally present in a concentration of about 1% to about 90% by weight of the oil phase. Preferably, the concentration of the crosslinking agent is about 15% to about 50% of the oil phase. More preferably, the concentration is about 16% to about 38%.
- the oil phase comprises an emulsifier that promotes the formation of a stable emulsion.
- the emulsifier can be any nonionic, cationic, anionic, or amphoteric emulsifier or combination of emulsifiers that promotes the formation of a stable emulsion.
- Suitable emulsifiers do not differ from those of the prior art and include sorbitan fatty acid esters, polyglycerol fatty acid esters, and polyoxyethylene fatty acids and esters.
- the emulsifier is sorbitan monooleate (sold as SPAN 80) .
- the emulsifier is generally present at a concentration of about 4% to about 50% by weight of the oil phase.
- the concentration of the emulsifier is about 10% to about 25% of the oil phase. More preferably, the concentration is about 15% to about 20%.
- the oil phase also contains an oil-soluble polymerization initiator and a porogen.
- the initiator can be any oil- soluble initiator that permits the formation of a stable emulsion, such as an azo initiator.
- a preferred initiator is azoisobisbutyronitrile (AIBN) .
- the initiator can be present in a concentration of up to about 5 weight percent of total polymerizable monomer (monomer component plus crosslinking agent) in the oil phase.
- the concentration of the initiator is preferably about 0.5 to about 1.5 weight percent of total polymerizable monomer, more preferably, about 1.2 weight percent.
- the porogen of the present invention can be any nonpolymerizing organic compound or combination of compounds that permits the formation of a stable emulsion, provided that the compound is a good solvent for the monomers employed, but a poor solvent for the polymer produced.
- Suitable porogens include dodecane, toluene, cyclohexanol, n-heptane, isooctane, and petroleum ether.
- a preferred porogen is dodecane.
- the porogen is generally present in a concentration of about 10 to about 60 weight percent of the oil phase. The porogen concentration affects the size and number of pores connecting the cavities in the microbead.
- the porogen concentration increases the size and number of interconnecting pores; while decreasing the porogen concentration decreases the size and number of pores.
- the porogen concentration is about 25 to about 40 weight percent of the oil phase. More preferably, the concentration is about 30 to about 35 weight percent.
- the aqueous discontinuous phase of a HIPE generally comprises a water-soluble polymerization initiator.
- the initiator can be any suitable water-soluble initiator.
- Such initiators are well known and include peroxide compounds such as sodium, potassium, and ammonium persulfates; sodium peracetate; sodium percarbonate and the like.
- a preferred initiator is potassium persulfate.
- the initiator can be present in a concentration of up to about 5 weight percent of the aqueous discontinuous phase. Preferably, the concentration of the initiator is about 0.5 to about 2 weight percent of the aqueous discontinuous phase.
- the HIPE is added to an aqueous suspension medium to form an oil-in-water suspension.
- the aqueous suspension medium comprises a suspending agent and, in the first embodiment, a water- soluble polymerization initiator.
- the suspending agent can be any agent or combination of agents that promotes the formation of a stable suspension of HIPE microdroplets.
- Typical droplet stabilizers for oil-in- water suspensions include water-soluble polymers such as gelatin, natural gums, cellulose, and cellulose derivatives (e.g., hydroxyethylcellulose) polyvinylpyrrolidone and poly(vinyl alcohol) (PVA) .
- PVA suitable for use as the suspending agent is produced by partial (85-92%) hydrolysis of polyvinyl acetate. Also used are finely-divided, water-insoluble inorganic solids, such as clay, silica, alumina, and zirconia. Two or more different suspending agents can be combined. Indeed, in one embodiment, the suspending agent is a combination of gelatin or PVA (88% hydrolysis) and modified clay or silica particles.
- Modified inorganic solid particles are produced by treating the particles with an agent that increases the hydrophobicity of the particles, thus improving the ability of the particles to stabilize the suspension.
- the inorganic solid particles are modified by treating them with a surfactant, such as asphaltene, in the presence of a suitable organic solvent.
- Suitable organic solvents include toluene, heptane, and a mixture of the two.
- the relative concentrations of the inorganic solid and asphaltene can be varied to produce modified inorganic solids of varying hydrophobicities.
- One measure of particle hydrophobicity is "contact angle", which reflects how far a particle penetrates into a water phase at an oil- water interface.
- a contact angle of 90° indicates that the particle resides half in the oil phase and half in the water phase.
- a contact angle of less than 90° indicates that the particle penetrates further into the water phase, i.e., is more hydrophilic.
- the hydrophobicity of the inorganic solid particles is adjusted so that the particles promote the formation of a stable suspension.
- the contact angle of the modified inorganic solid particles is about 65°.
- the suspending agent can be present in the aqueous suspension medium in any concentration that promotes the formation of a stable suspension, typically about 0.1 to about 10 weight percent of the aqueous suspension medium.
- a stable suspension is obtained with a PVA concentration of about 0.5% to about 5% and a inorganic solid concentration of about 0.05 to about 0.3% by weight of the aqueous suspension medium.
- the aqueous suspension medium contains a water-soluble polymerization initiator in the first embodiment of the present invention.
- the initiator can be any suitable water-soluble initiator such as those described above for the aqueous discontinuous phase of the HIPE.
- the initiator is potassium persulfate, present in the suspension medium at a concentration of up to about 5 weight percent. More preferably, the concentration of the initiator is about 0.5% to about 2% by weight of the aqueous suspension medium.
- a HIPE can be prepared by any of the prior art methods, such as, for example, that disclosed in U.S. Patent No. 4,522,953 (Barby et al. , issued June 11, 1985) , which has been incorporated herein by reference. Briefly, a HIPE is formed by combining the oil and aqueous discontinuous phases while subjecting the combination to shear agitation. Generally, a mixing or agitation device such as a pin impeller is used.
- a HIPE is prepared using a Gifford-Wood Homogenizer-Mixer (Model 1-LV) , set at 1400 rpm. At this mixing speed, the HIPE is produced in approximately 5 minutes.
- a HIPE is prepared using an air-powered version of the above mixer (Model 1-LAV) , with air pressure set at 5-10 psi for approximately 5- 10 minutes.
- the HIPE can be formed in a batchwise or a continuous process, such as that disclosed in U.S. Patent No. 5,149,720 (DesMarais et al. , issued September 22, 1992) .
- the HIPE is added to the aqueous suspension medium.
- the HIPE must be added to the suspension medium in an amount and at a rate suitable for forming a suspension of HIPE microdroplets.
- the suspension is subjected to sufficient shear agitation to form a stable suspension.
- the mixing device used should provide a relatively uniform distribution of agitation force throughout the suspension.
- shear agitation is inversely related to microdroplet size, the agitation can be increased or decreased to obtain smaller or larger HIPE microdroplets, respectively. In this manner, one can control the size of the microbead produced upon polymerization.
- the HIPE is added to the suspension medium dropwise at a flow rate of up to about 500 ml/minute until the suspension comprises up to about 50% HIPE. Agitation can range from about 50 to about 500 rpm when a propeller- or paddle-style impeller with a diameter of approximately 1.5 to 3 inches is used. In one embodiment, the HIPE is added to the suspension medium in the 22 liter reactor at a flow rate of 20 ml/minute until the suspension comprises about 10% HIPE. Agitation of this mixture at about 250 rpm, followed by polymerization, yields microbeads with an average diameter ranging from about 100 to about 160 ⁇ m.
- HIPE Microdroplets Once a stable suspension of HIPE microdroplets is obtained, the temperature of the aqueous suspension medium is increased above ambient temperature, and polymerization is initiated. Polymerization conditions vary depending upon the composition of the HIPE. For example, the monomer or monomer mixture and the polymerization initiator(s) are particularly important determinants of polymerization temperature. Furthermore, the conditions must be selected such that a stable suspension can be maintained for the length of time necessary for polymerization. The determination of a suitable polymerization temperature for a given HIPE is within the level of skill in the art. In general, the temperature of the HIPE suspension should not be elevated above 85°C because high temperatures can cause the suspension to break. Preferably, when AIBN is the oil-soluble initiator and potassium persulfate is the water-soluble initiator, styrene monomers are polymerized by maintaining the suspension at 60°C overnight (approximately 18 hours) .
- the polymerization step converts a HIPE microdroplet to a solid microbead.
- this microbead is generally washed to remove any residual, unpolymerized components of the HIPE or the suspension medium.
- the microbead can be washed with any liquid that can solubilize the residual components without affecting the stability of the microbead. More than one cycle of washing may be required.
- the microbead is washed five times with water, followed by acetone extraction for roughly a day in a Soxhlet extractor.
- the microbead can then be dried in any conventional manner.
- the microbead is air-dried for two days or is dried under vacuum at 50°C overnight.
- the resultant microbeads typically have a bulk density of less than about 0.10 gm/ml.
- a polymeric microbead can be produced by a method wherein the polymerization initiator is present in the oil phase instead of the aqueous phase.
- Suitable initiators for this embodiment include oil-soluble initiators, such as AIBN, benzoyl peroxide, lauroyl peroxide, VAZO-type initiators (such as 1,1' -azobis(cyclohexanecarbonitrile, which is sold as VAZO catalyst 88 by Aldrich, Milwaukee, WI) , and the like.
- initiator is added to the oil phase to initiate a free radical reaction.
- Appropriate initiator concentrations for a given microbead preparation can readily be determined by one skilled in the art.
- the initiator is present in a concentration of up to about 5 weight percent of total polymerizable monomer (monomer component plus crosslinking agent) in the oil phase.
- the concentration of the initiator is preferably about 0.5 to about 3.0 weight percent of total polymerizable monomer, more preferably, about 2.2 weight percent.
- the second embodiment requires the use of a stabilizer capable of forming a boundary between the aqueous discontinuous phase of the HIPE and the aqueous suspension medium where these two aqueous media interface in the microdroplet suspension.
- This phenomenon is analogous to the situation in soap bubbles where a boundary formed by detergent molecules separates air on the inside of the bubble from outside air.
- the stabilizer reduces water loss from the HIPE microdroplets and helps prevent microdroplet coalescence.
- the stabilizer should be a film forming compound that is soluble in organic solvents and sufficiently hydrophilic to stabilize the interface between the aqueous discontinuous phase of the HIPE and the aqueous suspension medium.
- these characteristics are found in a variety of natural and synthetic polymers that can serve as stabilizers in this embodiment, including cellulose derivatives, such as methyl cellulose and ethyl cellulose, and PVA (less than about 70% hydrolysis) .
- Other suitable stabilizers can be determined empirically by those skilled in the art in accordance with the teachings herein.
- the stabilizer comprises ethyl cellulose.
- the stabilizer concentration must be sufficient to reduce water loss from the HIPE microdroplets and reduce microdroplet coalescence.
- Optimal concentrations vary with HIPE composition and are determined empirically. Suitable stabilizer concentrations typically range from about 0.01% to about 15% by weight of the oil phase. Higher stabilizer concentrations can be employed; however, at concentrations above 15%, the stabilizer is difficult to wash out of the polymerized microbeads.
- the stabilizer concentration is about 0.1% to about 1% of the oil phase, more preferably, about 0.2% to about 0.6%.
- the stabilizer is typically dissolved in an inert solvent, and the resulting solution is added to the oil phase of the HIPE.
- the inert solvent acts as a porogen.
- the inert solvent can be any solvent that is capable of solubilizing the stabilizer and that is miscible in the oil phase of the HIPE. Examples of inert solvents useful in the second embodiment include trichloroethane, toluene, chloroform, and other halogenated solvents, and the like. Sufficient inert solvent is added to the stabilizer to increase the solubility of the stabilizer to allow mixing of the stabilizer with the oil phase.
- the inert solvent concentration varies with the stabilizer and oil phase employed, and the determination of a suitable type and concentration of inert solvent to facilitate the mixing of a particular stabilizer with a given oil phase is within the level of skill in the art.
- the inert solvent concentration ranges from about 3% to about 60% by weight of the oil phase and, more preferably, from about 10% to about 40%.
- Suitable concentrations of monomer, crosslinking agent, and emulsifier are essentially as described above, except that the concentrations of any of these components can be reduced to accommodate the inclusion of the oil-soluble polymerization initiator, stabilizer, and the inert solvent in the oil phase.
- concentration ranges for these components in the second embodiment are as follows:
- a porogen can optionally be included in the oil phase, as described above for the first embodiment. If a porogen is included, the concentrations of monomer, crosslinking agent, and/or emulsifier can be reduced.
- the aqueous discontinuous phase and. the aqueous suspension medium of the second embodiment differ from those of the first embodiment in that the aqueous discontinuous phase and aqueous suspension medium of the second embodiment do not include a polymerization initiator.
- the aqueous discontinuous phase consists essentially of water.
- the aqueous suspension medium of this embodiment comprises a suspending agent that can be any agent or combination of agents that promotes the formation of a stable suspension of HIPE microdroplets. Examples of suitable suspending agents are discussed above. Natural gums, such as, for example, acacia gum (commercially available from Aldrich Chemical Co., Milwaukee, WI) , are preferred.
- the suspending agent can be present in any concentration that promotes the formation of a stable suspension, typically about 1% to about 30% by weight of the aqueous suspension medium. Preferably, the suspending agent concentration is between about 2% to about 15%.
- an oil phase is prepared by combining the oil-soluble polymerization initiator, stabilizer, and inert solvent with monomer, crosslinking agent, and emulsifier.
- a HIPE is formed by combining the oil and aqueous discontinuous phases while subjecting the combination to sufficient shear agitation to form a stable emulsion, as described above. Once formed, the HIPE is added to the aqueous suspension medium in an amount and at a rate suitable for forming a suspension of HIPE microdroplets. As the HIPE is added, the suspension is subjected to shear agitation as described above.
- polymerization is initiated by raising the temperature.
- polymerization conditions vary depending upon the composition of the HIPE, and the determination of suitable conditions for a given HIPE is within the level of skill in the art.
- lauroyl peroxide is the initiator, for example, polymerization is conveniently carried out for 20 hours at 50°C.
- microbead is useful for a variety of applications, notably, as an absorbent material and also as a solid support in biotechnology applications.
- a microbead-based absorbent can be used, for example, to transport solvents, to absorb body fluids, and as an adhesive microcarrier.
- Biotechnology applications include chromatographic separations, solid phase synthesis, immobilization of antibodies or enzymes, and microbial and mammalian cell culture.
- the basic microbead can be modified in a variety of ways to produce microbeads that are specialized for particular applications.
- a wide variety of ionic and polar functional groups can be added to the microbead to produce a polymeric microbead that can absorb large quantities of acidic liquids.
- Such microbeads generally have a greater capacity to absorb aqueous and/or organic acids compared with their capacity for the neutral oil methyl oleate.
- the ratio of aqueous and/or organic acid to methyl oleate absorption is generally greater than about 1.2.
- a preferred starting material for producing such a microbead is a microbead that is crosslinked from about 1% to about 50% and has a void volume of greater than about 70% in its solvent swollen state.
- the functionalized microbead comprises the structural unit:
- A represents a crosslinked carbon chain
- Y is an optional spacer group
- Z is an ionic or polar functional group.
- Z is selected from an amino or substituted amino group and an alkyl cationic ammonium group having eight or more carbon atoms (hereinafter "a higher alkyl”) or an alkyl cationic quaternary ammonium group of 8 carbons or less in the presence of an organic counterion having 8 or more carbon atoms.
- the functionalized microbead can comprise a single type of such structural units or a combination of different types.
- Z is selected from ionic or polar functional groups of structures 1-3:
- R 2 , R 3 , R 4 , R 5 , and R 6 can be the same or different and are selected from an alkyl, cycloalkyl, aryl, and hydroxyalkyl .
- R 2 and R 3 can form part of a ring system.
- Z is a cationic quaternary ammonium group (3)
- R 4 , R 5 , R 6 are preferably selected such that the number of carbons present in R 4 +R 5 +R 6 is 10 or more.
- Z is an amine salt group (2)
- R 4 and R 5 are preferably selected such that the number of carbons present in R 4 +R 5 is 8 or more.
- the counterion X ' for the cationic quaternary ammonium group (3) or the an amine salt group (2) is an organic or inorganic ion.
- the counterion for higher alkyl cationic groups is an inorganic species such as chloride, sulfate, or nitrate. Alternatively, the counterion is a long or short chain organic species such as acetate or oleate.
- R 4 , R 5 , and Re are lower alkyl groups such that the number of carbons present in R 4 +R 5 +Re is less than 10 for a cationic quaternary ammonium group (3) and the number of carbons present in R 4 +R 5 is less than 8 for an amine salt (2) .
- the counterion X " is preferably an organic group having 8 or more carbons, such as oleate.
- X " can also be OH " .
- the amount of solvent absorbed by the functionalized microbead increases with number of ionic or polar functional groups present, provided the level of crosslinking does not exceed approximately 15-20%.
- the level of crosslinking is controlled by altering the relative concentrations of monomer and crosslinker. Preferably, the level of crosslinking is in the range of about 2% to about 10%.
- the degree of functionalization is generally greater than about 30%, preferably greater than about 50%, and most preferably greater than about 70%.
- Functionalized microbeads are produced by the same methods that are used for producing functionalized HIPE polymers. Suitable methods are well known and are disclosed, for example, in U.S. Patent No. 4,611,014 (Jomes et al., issued September 9, 1986), which is incorporated by reference herein in its entirety. Briefly, the functionalized microbead is generally prepared indirectly by chemical modification of a preformed microbead bearing a reactive group such as bromo or chloromethyl .
- a microbead suitable for subsequent chemical modification can be prepared by polymerization of monomers such as chloromethylstyrene or 4-t-BOC-hydroxystyrene.
- monomers such as chloromethylstyrene or 4-t-BOC-hydroxystyrene.
- suitable monomers are styrene, ⁇ -methylstyrene, or other substituted styrene or vinyl aromatic monomers that, after polymerization, can be chloromethylated to produce a reactive microbead intermediate that can be subsequently converted to a functionalized microbead.
- the microbead can be incorporated into the microbead at levels up to about 20% or more.
- the concentration of the reactive monomer should generally be sufficiently high to ensure that the functionalized microbead generated after chemical modification bears ionic or polar functional groups on a minimum of about 30% of the monomer residues.
- microbeads bearing ionic or polar groups can be prepared directly by emulsification and polymerization of an appropriate substantially water-insoluble monomer.
- the microbead can be functionalized to produce a microbead that absorbs large quantities of aqueous solutions and that also acts as an ion exchange resin.
- the capacity of these microbeads to absorb a 10% sodium chloride solution is such that the ratio of 10% sodium chloride to water absorption is generally greater than about 0.1, preferably greater than about 0.5, and most preferably greater than about 0.7.
- the microbead functionalized for aqueous absorption comprises the structural unit :
- A is a crosslinked carbon chain
- Y is an optional spacer group
- Z is an ionic or polar functional group.
- Z is selected from an alkyl cationic ammonium group having ten carbon atoms or less, an alkyl amine salt having eight carbon atoms or less, an alkoxylate, a metal or ammonium or substituted ammonium salt of a sulfuric, carboxylic, phosphoric, or sulfonic acid group, provided that where Z is a sulfonic acid, Y does not have the structure :
- the functionalized microbead can comprise a single type of such structural units or a combination of different types.
- Z is selected from ionic or polar functional groups of structures 1-2:
- R 2 , R 3 , and R 4 can be the same or different and are selected from an alkyl, cycloalkyl, aryl, and hydroxyalkyl .
- R 2 and R 3 form part of a ring system.
- Z is a cationic quaternary ammonium group (1)
- R 2 , R 3 , R 4 are preferably selected such that the number of carbons present in R 2 +R 3 +R 4 is less than 10.
- Z is an amine salt group (2)
- R 2 and R 3 are preferably selected such that the number of carbons present in R 2 +R 3 is less than 8.
- the counterion X " for the cationic quaternary ammonium group (1) or the amine salt group (2) is an inorganic species such as chloride, sulfate, or nitrate.
- the counterion can be a carboxylate species having less than 8 carbon atoms, such as acetate or lactate.
- X " can also be OH " .
- Z is an alkoxylated chain of the type:
- Microbeads functionalized for aqueous absorption are produced by the same methods that are used for producing the corresponding functionalized HIPE polymers. Suitable methods are the same as those described above for producing microbeads functionalized for acid absorption for functional groups of the same basic type (e.g., amine salts).
- suitable monomers for producing a reactive microbead intermediate that can be functionalized for absorption of aqueous solutions include chloromethylstyrene, n-butyl methacrylate, t-butyl acrylate, 2-ethylhexyl acrylate, or other appropriate acrylate or methacrylate esters.
- monomers such as styrene, o.-methylstyrene, or other substituted styrenes or vinyl aromatic monomers can be polymerized and then chloromethylated, sulfonated, nitrated, or otherwise activated to produce a reactive microbead intermediate which can be subsequently converted to a functionalized microbead.
- Preferred exemplary methods for producing amine salt-, cationic quaternary ammonium-, alkoxylate, and sulfonate salt-functionalized microbeads are described in detail in Examples 5 to 8, respectively.
- a microbead can be converted to a porous carboniferous material that retains the original structure of microbead cavities and interconnecting pores. This material is useful, for example, as a sorption or filtration medium and as a solid support in a variety of biotechnology applications (described further in the next section) .
- the carboniferous microbead can be used as an electrode material in batteries and super-capacitors.
- Battery electrode materials preferably have a large lattice spacing, such as that of the microbead. A large lattice spacing reduces or eliminates lattice expansion and contraction during battery operation, extending battery cycle lifetimes.
- Super-capacitors require highly conductive electrodes.
- microbead is ideally suited for this application because the interconnectedness of the microbead renders it highly conductive.
- a stable microbead is heated in an inert atmosphere as disclosed for HIPE polymers in U.S. Patent No. 4,775,655 (Edwards et al . , issued October 4, 1988) , which is incorporated herein by reference in its entirety.
- the ability of the microbead to withstand this heat treatment varies depending on the monomer or monomers used. Some monomers, such as styrene-based monomers, yield microbeads that must be stabilized against de- polymerization during heating. The modification required to stabilize such microbeads can take many forms .
- Microbead components and process conditions can be selected to achieve a high level of cross-linking or to include chemical entities that reduce or prevent depolymerization under the heating conditions employed.
- Suitable stabilizing chemical entities include the halogens; sulfonates; and chloromethyl, methoxy, nitro, and cyano groups.
- the level of cross-linking is preferably greater than about 20% and the degree of any other chemical modification is at least about 50%.
- Stabilizing entities can be introduced into the microbead after its formation or by selection of appropriately modified monomers.
- the microbead is heated in an inert atmosphere to a temperature of at least about
- Example 9 Production of a Microbead for Use as a Substrate Many chromatographic and chemical synthesis techniques employ a substrate. In chromatographic separations, components of a solution are separated based on the ability of such components to interact with chemical groups linked to the substrate surface. In solid phase synthesis, the substrate serves as a platform to which a growing molecule, such as a polypeptide, is anchored. Both processes can be carried out in a batchwise or continuous manner.
- the substrate In batchwise processes, the substrate is contained in a vessel, and solutions comprising components to be separated or reactants are sequentially added and removed by filtration and washing. Alternatively, in continuous or semicontinuous processes, the substrate is contained in a column and solutions are sequentially passed through the column.
- the microbead is uniquely suited for use in such systems because the microbead provides a rigid framework that ensures open channels for liquid flow and permits solution components or reactants to diffuse in and out of the microbead.
- the microbead can be functionalized by providing chemical groups at the microbead surface that interact directly with components or reactants in a solution.
- the chemical groups at the microbead surface can serve as anchors for other reactive species, such as catalysts, enzymes, or antibodies.
- microbead for Use in Chromatography
- the microbead is useful as a substrate in a variety of chromatographic techniques, including ion-exchange, gel filtration, adsorption, and affinity chromatography.
- cation-exchange resins are characterized by the presence of negatively charged groups.
- anion-exchange resins are characterized by the presence of positively charged groups.
- a component that binds to an anion-exchange resin, for instance, is typically released from the resin by increasing the Ph of the column buffer or adding anions that compete with the component for binding to the column. Such a component elutes from the column ahead of components having a higher net negative charge and behind components having a lower net negative charge.
- Cation-exchange resins can be produced from microbeads by providing acidic groups on the microbead surfaces. Suitable groups include the strongly acidic sulfonate group as well as the weakly acidic carboxylate, carboxymethyl, phosphate, sulfomethyl, sulfoethyl, and sulfopropyl groups.
- Anion-exchange resins can be produced from microbeads by functionalizing the microbeads with basic groups ranging from the strongly basic quaternary ammoniums to weakly basic groups such as the aminoethyl, diethyaminoethyl, guanidoethyl, and epichlorhydrin- triethanolamine groups.
- Acidic or basic groups can be added to a preformed microbead as described above for functionalization of the microbead for absorption of acidic and aqueous solutions or by any other conventional method.
- a microbead bearing such groups can be prepared directly by polymerization of an appropriate monomer.
- the microbead functionalized for chromatography generally has a void volume of at least about 70% and a cavity size of up to about 50 ⁇ m.
- microbead has a void volume of about 70% to about 80%. This combination of features ensures rapid uptake of fluids, with relatively unobstructed flow through the microbead.
- the capacity of the microbead substrate can be increased by adding a gel to the microbead according to the methods disclosed in U.S. Patent No. 4,965,289
- the gel is formed in or added to the microbead cavities and is linked to the microbead surface.
- the gel bears either acidic or basic groups, depending on whether the microbead substrate is to serve as an anion-exchange resin or a cation-exchange resin, respectively.
- microbead is functionalized for use in solid phase synthesis by providing chemical groups linked to the microbead surfaces.
- the chemical groups are selected to interact with one of the reactants involved in the synthesis.
- microbead substrates can be specialized for chemical syntheses of species as diverse as peptides, olignucleotides, and oligosaccharides . Methods for adding appropriate chemical groups to functionalize the microbead for use in such syntheses do not differ from methods previously described for prior art HIPEs and other polymers .
- a microbead can be functionalized for peptide synthesis, for instance, as disclosed for HIPE polymers in U.S. Patent No. 4,965,289 (Sherrington, issued October 23, 1990) , which is incorporated herein by reference in its entirety. Briefly, a microbead is prepared such that the void volume is at least about 70% and the cavity size is up to about 50 ⁇ m. The microbead is preferably sufficiently cross-linked so that the microbead does not swell to more than twice its dry volume during use.
- the chemical group linked to the microbead surface can be any group that binds to the first reactant in the synthesis.
- the chemical group is any group that binds the first amino acid of the peptide to be produced.
- the chemical group should be selected such that the chemical group binds at a position on the amino acid other than the amine group.
- the chemical group comprises an amine that reacts with the carboxyl group of the first amino acid.
- Chemical groups can be added to a preformed microbead or, alternatively, a microbead bearing chemical groups can be prepared directly by emulsification and polymerization of an appropriate substantially water-insoluble monomer. If desired, chemical groups can be further modified to provide spacer groups that interact with the first amino acid of the peptide. Peptide synthesis is initiated by binding the first amino acid to suitable chemical groups on the microbead surface. The amine groups of the amino acid reactants are generally protected, and thus chain elongation occurs by alternating rounds of deprotection and coupling of amino acids. The process is terminated by detachment of the peptide from the substrate, after which the peptide is typically purified.
- the capacity of the microbead substrate can be increased by adding a gel to the microbead according to the methods disclosed in U.S. Patent No. 4,965,289 (Sherrington, issued October 23, 1990) .
- a suitable microbead is prepared as described above, and a gel or pre-gel is deposited and retained within the microbead cavities.
- the gel is generally a highly solvent-swollen, cross-linked gel and can, for example, be a soft deformable polyamide gel .
- the gel is generally adapted to interact with a reactant in the synthesis.
- the ratio of swollen gel to porous material can range from about 60:40 to about 95:5 (weight:weight) and is more preferably from about 75:25 to about 95:5. The most preferred ratio is about 80:20.
- the gel can be deposited and retained in the pre-formed microbead by any of the prior art methods for producing gel-filled HIPE polymers, such as those disclosed in U.S. Patent No. 4,965,289 (Sherrington, issued October 23, 1990), for example.
- the gel is formed from pre-gel materials within the microbead cavities. Most preferably, the gel is retained or anchored in the microbead cavities during gel formation.
- the gel can be retained by chain entanglement and/or interpenetration between the gel and the microbead surfaces.
- the gel can be retained by a process that is believed to involve chemical binding between the gel and the microbead surfaces. Combinations of the above mechanisms are also possible.
- the microbead is contacted with a solution comprising pre-gel components and a swelling solvent for the microbead.
- a solution comprising pre-gel components and a swelling solvent for the microbead.
- the microbead swells, entrapping portions of the forming gel by polymer chain interpenetration between the swollen polymeric material of the microbead and the forming gel.
- Suitable swelling solvents depend on the nature of the microbead polymer and can be readily determined by one skilled in the art. The details of a preferred exemplary method for producing a gel-filled microbead by polymer chain entanglement are set forth in Example 10.
- retention by chemical bonding can be achieved by reacting the gel or pre-gel components with anchor groups on the microbead.
- Suitable gel anchor groups do not differ from those known in the art, including groups that have double bonds available for interaction with a gel or pre-gel components.
- Such anchor groups can be introduced into the microbead by modification after microbead formation or by selection of appropriately modified monomers.
- a gel-filled microbead can be produced by reacting an amino methyl-functionalized microbead with acryloyl chloride to produce an acrylated microbead.
- acryloyl chloride Upon heating in the presence of pre-gel components to initiate gel polymerization, the double bonds of the acrylate group are believed to interact with the forming gel, resulting in covalent linkage of the gel to the microbead.
- suitable pre-gel monomers include, for example, acryloyl tyramine acetate and acryloyl sarcosine methyl ester.
- anchor groups can be introduced into the microbead by modification after microbead formation or by selection of appropriately modified monomers.
- the microbead can be used as a substrate for a wide variety of molecules including polypeptides and oligonucleotides.
- the microbead is particularly useful for immobilizing antibodies, lectins, enzymes, and haptens. Methods for attaching such molecules to polymeric substrates are well known. (See, e . g. , Tijssen, P. Laboratory Techniques in Biochemistry and Molecular Biology: Practice and
- a polypeptide can be attached to the microbead via non-covalent adsorption or by covalent bonding. Non- covalent adsorption is generally attributed to non- specific hydrophobic interactions and is independent of the net charge of the polypeptide.
- a polypeptide is attached to the microbead by treating the microbead with a buffer solution containing the polypeptide. Suitable buffers include 50 Mm carbonate, pH 9.6; 10 mM Tris-HCL, pH 8.5, containing 100 mM sodium chloride; and phosphate buffered saline. Polypeptide concentration is generally between 1 and 10 ⁇ g/ml . The microbead is typically incubated in this solution overnight at 4°C in a humid chamber.
- Polypeptide adsorption levels can be increased by partial denaturation of the polypeptide, for example, by exposing the polypeptide to high temperature, low pH (e.g., 2.5) , or denaturants (e.g., urea) .
- a polypeptide having a free amino group can be attached to a styrene-based microbead, for example, by treating the microbead with glutaraldehyde at low pH. The polypeptide is then added and the pH of the solution is increased to between about 8.0 and about 9.5 with 100 mM carbonate. The increase in pH increases the reactivity of the glutaraldehyde which binds the polypeptide to the microbead surface. Ethylchloroformate can be substituted for or used in combination with glutaraldehyde in the above procedure.
- the microbeads can be functionalized for covalent attachment of polypeptides.
- a microbead provides anchor groups that bind to the polypeptide of interest .
- Suitable anchor groups for attaching polypeptides to polymers are well known and include hydrazide groups, alkylamine groups, and Sanger's reagent. Anchor groups can be introduced into the microbead by modification after microbead formation or by selection of appropriately modified monomers.
- a polypeptide can be attached to the microbead via a bridging molecule. This method of attachment is useful for polypeptides that bind poorly to the microbead.
- Such polypeptides are conjugated to a bridging molecule that has a high affinity for plastic, such as, for example, bovine serum albumin (BSA) .
- BSA bovine serum albumin
- the microbead serves as a substrate for an oligonucleotide.
- the oligonucleotide can be adsorbed to a microbead by treating the microbead with a polycationic substance such as methylated BSA, poly-L-lysine, or protamine sulfate.
- a polycationic substance such as methylated BSA, poly-L-lysine, or protamine sulfate.
- the microbead is typically treated for about 90 minutes with a 1% aqueous solution of protamine sulfate, followed by several distilled water washes. The microbead is then allowed to dry.
- An oligonucleotide is adsorbed onto the treated microbead by adding the oligonucleotide to the microbead at a concentration of about 10 ⁇ g/ml in a buffer such as 50 mM Tris-HCl, pH 7.5, containing 10 mM ethylenediaminetetraacetic acid (EDTA) and 10 mM ethylene glycol-bis(j3-amino ethyl ether)N,N,N' ,N' - tetracetic acid (EGTA) .
- a treatment time of 60 minutes provides suitable results.
- the microbead is also useful in cell culture.
- High density cell culture generally requires that cells be fed by continuous perfusion with growth medium. Suspension cultures satisfy this requirement, however, shear effects limit aeration at high cell concentration.
- the microbead protects cells from these shear effects and can be used in conventional stirred or airlift bioreactors.
- the microbead is generally sterilized by any of the many well-known sterilization methods. Suitable methods include irradiation, ethylene oxide treatment, and, preferably, autoclaving. Sterile microbeads are then placed in a culture vessel with the growth medium suitable for the cells to be cultured. Suitable growth media are well known and do not differ from prior art growth media for suspension cultures. An inoculum of cells is added and the culture is maintained under conditions suitable for cell attachment to the microbeads. The culture volume is then generally increased, and the culture is maintained in the same manner as prior art suspension cultures.
- Microbeads can be used in cell culture without modification, however, the microbeads can also be modified to improve cell attachment, growth, and the production of specific proteins.
- a variety of bridging molecules can be used to attach cells to the microbeads. Suitable bridging molecules include antibodies, lectins, glutaraldehyde, and poly- L-lysine.
- sulfonation of microbeads increases cell attachment rates.
- Example 11 illustrates the use sulfonated microbeads in an exemplary mammalian cell culture.
- Exemplary preferred microbeads were prepared according to the following protocol.
- the final concentration of each component of the HIPE and the aqueous suspension medium is shown in Table 1, Study 4.
- Table 1 also shows studies in which the following protocol was varied as indicated. The results of these studies are set forth in Table 2.
- aqueous discontinuous phase by adding 0.78 gm potassium persulfate to 94.3 ml of distilled water. 3. Stir the oil phase at approximately 1400 rpm, and then add the aqueous discontinuous phase to the oil phase at a flow rate of 20 ml/minute. Stir the combined phases at 1400 rpm for approximately 5-10 minutes to form a stable HIPE.
- microbead Production Using an Oil-Phase Initiator Exemplary preferred microbeads were prepared according to the following alternative protocol. The final concentration of each component of the HIPE and the aqueous suspension medium is shown in Table 3, Study 7. Table 3 also shows studies in which the following protocol was varied as indicated. The results of these studies are set forth in Table 4.
- microbeads polymerize the suspension by raising the temperature' to 45°C for approximately 20 hours under constant stirring.
- the oil phase also contained 1.2 wt% azoisobisbutyronitrile (wt% of total polymerizable monomer). ** The aqueous discontinuous phase contained 0.8 gm potassium persulfate, for final concentrations ranging between 0.1 and 0.8 wt%.
- the suspension medium also contained 0.07 wt% potassium persulfate.
- the oil phase contained approximately 2 wt% lauroyl peroxide (wt% of total polymerizable monomer).
- the aqueous discontinuous phase is water.
- VBC vinylbenzyl chloride
- TCE 1,1,1-trichloroethane.
- EXAMPLE 2 Functionalization of Microbeads for Absorption of Acids Using Amine Groups
- Diethylamine-functionalized microbeads are produced from chloromethylstyrene microbeads prepared as described in Example 1. The microbeads are air- dried overnight and Soxhlet extracted for 15 hours with 200 ml hexane to remove residual unpolymerized components. 5 gm of microbeads are then refluxed with 150 ml aqueous diethylamine for 20 hours. The resultant diethylamine-functionalized microbeads are 85% substituted and have a capacity of 1.5 mM/gm. 1 gm of this material absorbs 20 ml of 1 N sulfuric acid.
- dihexylamine- functionalized microbeads are prepared as described above in Example 3 for diethylamine-functionalized microbeads. 1 gm dihexylamine-functionalized microbeads are then added to 100 ml methanolic HCl and stirred for 30 minutes. The counterion of the resultant salt is chloride. The dihexylammonium chloride-functionalized microbeads are collected by filtration, washed with 3 times with 50 ml methanol, and air-dried overnight. The resultant microbeads are 70% substituted.
- EXAMPLE 4 Functionalization of Microbeads for Absorption of Acids Using Quaternary Ammonium Groups
- chloromethylstyrene microbeads are prepared as described in Example 1.
- the microbeads are air-dried overnight and Soxhlet extracted with hexane to remove residual unpolymerized components.
- 1 gm microbeads are then filled under vacuum with a 10-fold molar excess of ethanolic amine and refluxed for 7 hours.
- the counterion of the resultant salt is chloride.
- the dimethyldecylammonium chloride-functionalized microbeads are collected by filtration, washed twice with 50 ml ethanol and twice with 50 ml methanol, and then air-dried overnight. The resultant microbeads are 70% substituted.
- EXAMPLE 5 Functionalization of Microbeads for Absorption of Aqueous Solutions Using Amine Salts To produce a dimethylammonium salt, diethylamine- functionalized microbeads are prepared as described in Example 3. The microbeads are air-dried overnight and Soxhlet extracted with hexane to remove residual unpolymerized components. 1 gm microbeads are then added to 100 ml methanolic HCl and stirred for 30 minutes. The counterion of the resultant salt is chloride. The diethylamine chloride-functionalized microbeads are 85% substituted.
- EXAMPLE 6 Functionalization of Microbeads for Absorption of Aqueous Solutions Using Quaternary Ammonium Groups
- chloromethylstyrene microbeads prepared as described in Example 1.
- the microbeads are air-dried overnight and Soxhlet extracted with hexane to remove residual unpolymerized components.
- 1 gm microbeads are then treated with 100 ml aqueous amine for 30 minutes.
- the resultant dimethyldecylammonium chloride-functionalized microbeads are 85% substituted.
- Ethoxylated microbeads are prepared from chloromethylstyrene microbeads prepared as described in Example 1. The microbeads are air-dried overnight and Soxhlet extracted with hexane to remove residual unpolymerized components. 1 gm microbeads are then treated with 100 ml of the anionic form of a polyethylene glycol (PEG) containing 8-9 ethylene glycol monomers in excess PEG as solvent. The reactants are heated at 95°C for 2 hours. The resultant ethoxylated microbeads are 90% substituted.
- PEG polyethylene glycol
- Sulfonate-functionalized microbeads were produced from styrene microbeads prepared as described in Example 1. The microbeads were dried under vacuum at 50°C for two days. 10 gm of microbeads were then added to a 500 ml flask containing a mixture of 200 ml of chloroform and 50 ml of chlorosulfonic acid. The flask is shaken at room temperature for two days. The sulfonate-functionalized microbeads are collected by filtration and washed sequentially with 250 ml each of chloroform, methylene chloride, acetone, and methanol.
- microbeads are soaked in 300 ml 10% aqueous sodium hydroxide overnight and then washed with water until the eluate reaches neutral pH.
- the bulk density of the resultant material is 0.067 gm/ml of dried microbeads and the capacity is 2.5 mM/gm. 1 gm of this material absorbs 23.5 gm of water.
- EXAMPLE 9 Production of Stable Carbon Structures from Chloromethylstyrene Microbeads 3-chloromethylstyrene microbeads are prepared as described in Example 1 such that the level of crosslinking is between 20-40% and the void volume is 90%. 1 gm microbeads are then placed in an electrically heated tube furnace, and the temperature is increased to 600°C in an oxygen-free nitrogen atmosphere. The rate of heating is generally maintained below 5°C per minute, and in the range of 180°C to 380°C, the rate of heating does not exceed 2°C per minute. After the heating process, the microbeads are cooled to ambient temperature in an inert atmosphere to prevent oxidation by air.
- Microbeads with a void volume of 90%, a bulk density of 0.047 gm/ml, an average cavity diameter in the range of 1-50 ⁇ m, and which are 10% crosslinked are prepared as described in Example 1.
- the gel employed is poly(N- (2- (4-acetoxyphenyl) ethyl) -acrylamide) .
- To produce a solution of gel precursors 2.5 gm of monomer, 0.075 gm of the crosslinking agent ethylene bis (acrylamide) , and 0.1 gm of the initiator AIBN is added to 10 ml of the swelling agent dichloroethane.
- the gel precursor solution' is then deoxygenated by purging with nitrogen.
- microbeads 0.7 gm of microbeads is added to the gel precursor solution and polymerization is initiated by heating the mixture at 60°C while rotating the sample on a rotary evaporator modified for reflux.
- the dichloroethane swells the microbeads, allowing the gel precursors to penetrate the microbead and form a polyamide that becomes interpenetrated with the polymer chains of the microbead.
- the gel-filled microbeads (hereinafter "composite") are washed with 50 ml dimethyl formamide (DMF) and 50 ml diethyl ether and then vacuum dried.
- the yield of composite is 2.7 gm.
- microbeads suitable for mammalian cell culture sulfonated microbeads are prepared as described in Example 8 and are then wetted in a 70% ethanol solution and autoclaved at 121°C for 15 minutes. The microbeads are then washed twice with sterile phosphate-buffered saline and once with complete growth medium. 500 mg of the sterile microbeads are placed in a 500 ml roller bottle that has been siliconized to prevent attachment of the cells to the bottle.
- An inoculum of 5 x 10 7 baby hamster kidney cells in 50 ml of growth medium (containing 10% fetal calf serum) is added to the roller bottle.
- the inoculum is incubated with the microbeads for 8 hours at 37°C with periodic agitation to allow cell attachment to the microbeads.
- the culture volume is then increased to 100 ml, and the roller bottle is gassed with an air-CO 2 (95:5) mixture and placed in a roller apparatus. Growth medium is replaced whenever the glucose concentration drops below 1 gm/liter.
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU26937/95A AU702241B2 (en) | 1994-06-06 | 1995-06-06 | Polymeric microbeads and method of preparation |
JP8501165A JPH10501173A (en) | 1994-06-06 | 1995-06-06 | Polymer microbeads and method for producing the same |
DE69531617T DE69531617T3 (en) | 1994-06-06 | 1995-06-06 | POLYMIC MICROBUGS AND MANUFACTURING METHOD |
EP95922150A EP0764047B2 (en) | 1994-06-06 | 1995-06-06 | Polymeric microbeads and method of preparation |
US08/630,834 US5760097A (en) | 1994-06-06 | 1996-04-10 | Methods of preparing polymeric microbeds |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US254,303 | 1981-04-15 | ||
US08/254,303 US5583162A (en) | 1994-06-06 | 1994-06-06 | Polymeric microbeads and method of preparation |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1995033553A1 true WO1995033553A1 (en) | 1995-12-14 |
WO1995033553B1 WO1995033553B1 (en) | 1996-02-08 |
Family
ID=22963748
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1995/006879 WO1995033553A1 (en) | 1994-06-06 | 1995-06-06 | Polymeric microbeads and method of preparation |
Country Status (8)
Country | Link |
---|---|
US (5) | US5583162A (en) |
EP (1) | EP0764047B2 (en) |
JP (2) | JPH10501173A (en) |
CN (1) | CN1150764A (en) |
AU (1) | AU702241B2 (en) |
CA (1) | CA2190731A1 (en) |
DE (1) | DE69531617T3 (en) |
WO (1) | WO1995033553A1 (en) |
Cited By (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH09227690A (en) * | 1996-02-26 | 1997-09-02 | Reika Kogyo Kk | Porous particle and its preparation |
WO2000034454A3 (en) * | 1998-12-05 | 2000-11-09 | Univ Newcastle | Microcellular polymers as cell growth media and novel polymers |
US6315767B1 (en) | 1998-08-19 | 2001-11-13 | Gambro, Inc. | Cell storage maintenance and monitoring system |
WO2004005355A1 (en) | 2002-07-09 | 2004-01-15 | Galip Akay | Microporous polymers |
US6750261B1 (en) | 2003-04-08 | 2004-06-15 | 3M Innovative Properties Company | High internal phase emulsion foams containing polyelectrolytes |
US7282237B2 (en) | 1999-06-06 | 2007-10-16 | Ge Healthcare Bio-Sciences Ab | Method for surface modification, a novel support matrix and the use of the matrix |
WO2010040996A3 (en) * | 2008-10-07 | 2010-06-03 | University Of Newcastle | Synthetic symbiotic system as soil additives to deliver active ingredients through plant roots for enhanced plant and crop yield |
WO2013016080A3 (en) * | 2011-07-28 | 2013-07-04 | Eastman Kodak Company | Crosslinked organic porous particles |
WO2013109825A1 (en) * | 2012-01-19 | 2013-07-25 | Natrix Separations Inc. | Chromatographic media for storage and delivery of therapeutic biologics and small molecules |
RU2492487C2 (en) * | 2008-09-30 | 2013-09-10 | Сони Корпорейшн | Method of obtaining microbeeds and microbeeds |
US9283035B2 (en) | 2005-04-28 | 2016-03-15 | Boston Scientific Scimed, Inc. | Tissue-treatment methods |
US9295928B2 (en) | 2004-02-05 | 2016-03-29 | Emd Millipore Corporation | Porous adsorptive or chromatographic media |
US9334381B2 (en) | 2011-07-28 | 2016-05-10 | Eastman Kodak Company | Crosslinked organic porous particles |
US9433922B2 (en) | 2007-08-14 | 2016-09-06 | Emd Millipore Corporation | Media for membrane ion exchange chromatography based on polymeric primary amines, sorption device containing that media, and chromatography scheme and purification method using the same |
US9463426B2 (en) | 2005-06-24 | 2016-10-11 | Boston Scientific Scimed, Inc. | Methods and systems for coating particles |
CN106040121A (en) * | 2016-05-25 | 2016-10-26 | 中国科学院大学 | Method for synthesizing skeleton microsphere material |
US9592458B2 (en) | 2013-12-26 | 2017-03-14 | Dionex Corporation | Ion exchange foams to remove ions from samples |
CN110117341A (en) * | 2018-02-07 | 2019-08-13 | 江苏集萃智能液晶科技有限公司 | A kind of preparation method of porous functionalized polymer microsphere |
US10921298B2 (en) | 2014-12-30 | 2021-02-16 | Dionex Corporation | Vial cap and method for removing matrix components from a liquid sample |
Families Citing this family (171)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE69521997T2 (en) * | 1994-05-15 | 2002-04-04 | Apbiotech Ab Uppsala | METHOD FOR PRODUCING PARTICLES AND PARTICLES THAT CAN BE MANUFACTURED BY THIS PROCESS |
US5583162A (en) * | 1994-06-06 | 1996-12-10 | Biopore Corporation | Polymeric microbeads and method of preparation |
US6066258A (en) | 1997-12-05 | 2000-05-23 | Transgenomic, Inc. | Polynucleotide separations on polymeric separation media |
US6355791B1 (en) | 1995-11-13 | 2002-03-12 | Transgenomic, Inc. | Polynucleotide separations on polymeric separation media |
EP0902792A1 (en) * | 1996-05-30 | 1999-03-24 | Shell Oil Company | Process to prepare low density porous cross-linked polymeric materials |
US7138518B1 (en) | 1996-11-13 | 2006-11-21 | Transgenomic, Inc. | Liquid chromatographic separation of polynucleotides |
US7927595B1 (en) * | 1997-02-21 | 2011-04-19 | The United States Of America As Represented By The Secretary Of The Navy | Methods for downregulating CCR5 in T cells with anti-CD3 antibodies and anti-CD28 antibodies |
US6174443B1 (en) | 1997-04-14 | 2001-01-16 | The Research Foundation Of State University Of New York | Purification of wheat germ agglutinin using macroporous or microporous filtration membrane |
US5993661A (en) * | 1997-04-14 | 1999-11-30 | The Research Foundation Of State University Of New York | Macroporous or microporous filtration membrane, method of preparation and use |
US6048908A (en) | 1997-06-27 | 2000-04-11 | Biopore Corporation | Hydrophilic polymeric material |
US6228340B1 (en) | 1997-08-25 | 2001-05-08 | The Regents Of The University Of California | Method for the production of macroporous ceramics |
GB9718415D0 (en) * | 1997-08-29 | 1997-11-05 | Smithkline Beecham Plc | Formulation |
US6451953B1 (en) | 1997-12-18 | 2002-09-17 | Sun Drilling Products, Corp. | Chain entanglement crosslinked polymers |
CA2322457A1 (en) | 1998-03-13 | 1999-09-16 | The Procter & Gamble Company | Absorbent structures comprising fluid storage members with improved ability to dewater distribution members |
US6570057B1 (en) | 1998-03-13 | 2003-05-27 | The Procter & Gamble Company | Absorbent articles with improved distribution properties under sur-saturation |
DE69934536T2 (en) * | 1998-04-09 | 2007-10-04 | Nippon Shokubai Co. Ltd. | Crosslinked polymer particles and process for its preparation and use |
US6713661B1 (en) | 1998-04-28 | 2004-03-30 | The Procter & Gamble Company | Absorbent articles providing improved fit when wet |
GB2339573A (en) * | 1998-07-15 | 2000-02-02 | Amersham Pharm Biotech Ab | Support media e.g. for chromatography |
US6908770B1 (en) | 1998-07-16 | 2005-06-21 | Board Of Regents, The University Of Texas System | Fluid based analysis of multiple analytes by a sensor array |
US6268803B1 (en) * | 1998-08-06 | 2001-07-31 | Altra Technologies Incorporated | System and method of avoiding collisions |
US6238565B1 (en) * | 1998-09-16 | 2001-05-29 | Varian, Inc. | Monolithic matrix for separating bio-organic molecules |
AU1429701A (en) | 1999-07-16 | 2001-02-05 | Board Of Regents, The University Of Texas System | General signaling protocols for chemical receptors in immobilized matrices |
US6423666B1 (en) * | 1999-10-05 | 2002-07-23 | Bio-Rad Laboratories, Inc. | Large-pore chromatographic beads prepared by suspension polymerization |
US7169298B2 (en) | 2000-01-26 | 2007-01-30 | Transgenomic, Inc. | Method and apparatus for separating polynucleotides using monolithic capillary columns |
AU2001247195A1 (en) * | 2000-01-31 | 2001-08-07 | Board Of Regents, The University Of Texas System | Method and system for collecting and transmitting chemical information |
DE10012615A1 (en) * | 2000-03-15 | 2001-09-27 | Ulrich Kunz | Polymer/support solid phase reactants, useful for a range of organic reactions and purification processes comprise funtionalized polymer particles in the pores of a porous support |
CN101708165A (en) | 2000-03-24 | 2010-05-19 | 生物领域医疗公司 | Microspheres for active embolization |
US20030212022A1 (en) * | 2001-03-23 | 2003-11-13 | Jean-Marie Vogel | Compositions and methods for gene therapy |
US6475602B1 (en) | 2000-06-30 | 2002-11-05 | Eastman Kodak Company | Ink jet recording element |
EP1373874A4 (en) * | 2001-01-31 | 2004-03-31 | Univ Texas | Method and apparatus for the confinement of materials in a micromachined chemical sensor array |
WO2002063270A2 (en) * | 2001-02-05 | 2002-08-15 | Board Of Regents, The University Of Texas System | The use of mesoscale self-assembly and recognition to effect delivery of sensing reagent for arrayed sensors |
EP1386938B8 (en) * | 2001-04-13 | 2010-07-28 | Organo Corporation | Electrodeionization water purification device |
JP2004538352A (en) * | 2001-08-14 | 2004-12-24 | ポリイー インコーポレイテッド | High internal phase polymeric emulsion composition |
US6841580B2 (en) * | 2001-12-21 | 2005-01-11 | Organo Corporation | Organic porous material, process for manufacturing the same, and organic porous ion exchanger |
SE0200010D0 (en) * | 2002-01-02 | 2002-01-02 | Amersham Biosciences Ab | A method of producing hierarchical porous beads |
US7094369B2 (en) * | 2002-03-29 | 2006-08-22 | Scimed Life Systems, Inc. | Processes for manufacturing polymeric microspheres |
US7131997B2 (en) * | 2002-03-29 | 2006-11-07 | Scimed Life Systems, Inc. | Tissue treatment |
US7462366B2 (en) * | 2002-03-29 | 2008-12-09 | Boston Scientific Scimed, Inc. | Drug delivery particle |
US7053134B2 (en) * | 2002-04-04 | 2006-05-30 | Scimed Life Systems, Inc. | Forming a chemically cross-linked particle of a desired shape and diameter |
GB0209315D0 (en) * | 2002-04-24 | 2002-06-05 | Univ Liverpool | Porous polymer material and method of production thereof |
CA2523626A1 (en) | 2002-04-26 | 2003-11-06 | Board Of Regents, The University Of Texas System | Method and system for the detection of cardiac risk factors |
US7459164B2 (en) * | 2002-05-28 | 2008-12-02 | Botulinum Toxin Research Associates, Inc. | Composition for therapeutic and cosmetic botulinum toxin |
US7691394B2 (en) * | 2002-05-28 | 2010-04-06 | Botulinum Toxin Research Associates, Inc. | High-potency botulinum toxin formulations |
US20060165647A1 (en) * | 2002-05-30 | 2006-07-27 | Kazuo Teramoto | Immunosuppressive substance adsorbent, extracorporeal cicrulation column and method of treating cancer |
CA2492339A1 (en) | 2002-06-12 | 2003-12-24 | Boston Scientific Limited | Bulking agents |
US7332160B2 (en) * | 2002-07-12 | 2008-02-19 | Boston Scientific Scimed, Inc. | Medical device and method for tissue removal and repair |
EP1546367A4 (en) * | 2002-07-24 | 2006-08-16 | Univ Texas | Capture and detection of microbes by membrane methods |
GB2399084B (en) * | 2002-07-30 | 2007-01-31 | Univ Liverpool | Porous beads and method of production thereof |
US7842377B2 (en) * | 2003-08-08 | 2010-11-30 | Boston Scientific Scimed, Inc. | Porous polymeric particle comprising polyvinyl alcohol and having interior to surface porosity-gradient |
US7449236B2 (en) * | 2002-08-09 | 2008-11-11 | Boston Scientific Scimed, Inc. | Porous polymeric particle comprising polyvinyl alcohol and having interior to surface porosity-gradient |
US8012454B2 (en) | 2002-08-30 | 2011-09-06 | Boston Scientific Scimed, Inc. | Embolization |
US7588825B2 (en) * | 2002-10-23 | 2009-09-15 | Boston Scientific Scimed, Inc. | Embolic compositions |
US7883490B2 (en) | 2002-10-23 | 2011-02-08 | Boston Scientific Scimed, Inc. | Mixing and delivery of therapeutic compositions |
MXPA05006690A (en) * | 2002-12-20 | 2006-02-17 | Botulinum Toxin Res Ass Inc | Pharmaceutical botulinum toxin compositions. |
US9317922B2 (en) | 2003-05-16 | 2016-04-19 | Board Of Regents The University Of Texas System | Image and part recognition technology |
US7651850B2 (en) * | 2003-05-16 | 2010-01-26 | Board Of Regents, The University Of Texas System | Image and part recognition technology |
US7976823B2 (en) | 2003-08-29 | 2011-07-12 | Boston Scientific Scimed, Inc. | Ferromagnetic particles and methods |
US7901770B2 (en) | 2003-11-04 | 2011-03-08 | Boston Scientific Scimed, Inc. | Embolic compositions |
FR2862976B1 (en) * | 2003-11-28 | 2006-01-13 | Commissariat Energie Atomique | VERY LOW DENSITY POLYMER FOAMS AND METHOD OF MANUFACTURING THE SAME |
CA2549190A1 (en) * | 2003-12-11 | 2005-06-30 | Board Of Regents, The University Of Texas System | Method and system for the analysis of saliva using a sensor array |
US8105849B2 (en) * | 2004-02-27 | 2012-01-31 | Board Of Regents, The University Of Texas System | Integration of fluids and reagents into self-contained cartridges containing sensor elements |
US8101431B2 (en) | 2004-02-27 | 2012-01-24 | Board Of Regents, The University Of Texas System | Integration of fluids and reagents into self-contained cartridges containing sensor elements and reagent delivery systems |
US20060257854A1 (en) * | 2004-02-27 | 2006-11-16 | Mcdevitt John T | Membrane assay system including preloaded particles |
US7781226B2 (en) * | 2004-02-27 | 2010-08-24 | The Board Of Regents Of The University Of Texas System | Particle on membrane assay system |
US20060257941A1 (en) * | 2004-02-27 | 2006-11-16 | Mcdevitt John T | Integration of fluids and reagents into self-contained cartridges containing particle and membrane sensor elements |
US20060257991A1 (en) * | 2004-02-27 | 2006-11-16 | Mcdevitt John T | Integration of fluids and reagents into self-contained cartridges containing particle-based sensor elements and membrane-based sensor elements |
US7736671B2 (en) | 2004-03-02 | 2010-06-15 | Boston Scientific Scimed, Inc. | Embolization |
US8173176B2 (en) | 2004-03-30 | 2012-05-08 | Boston Scientific Scimed, Inc. | Embolization |
US20050238870A1 (en) * | 2004-04-22 | 2005-10-27 | Marcia Buiser | Embolization |
US7311861B2 (en) | 2004-06-01 | 2007-12-25 | Boston Scientific Scimed, Inc. | Embolization |
US20060071357A1 (en) * | 2004-09-27 | 2006-04-06 | Pilon Laurent G | Method and apparatus for liquid microencapsulation with polymers using ultrasonic atomization |
US8425550B2 (en) | 2004-12-01 | 2013-04-23 | Boston Scientific Scimed, Inc. | Embolic coils |
GB0501116D0 (en) * | 2005-01-19 | 2005-02-23 | Polymer Lab Ltd | Chromatographic material |
US7858183B2 (en) | 2005-03-02 | 2010-12-28 | Boston Scientific Scimed, Inc. | Particles |
US7727555B2 (en) | 2005-03-02 | 2010-06-01 | Boston Scientific Scimed, Inc. | Particles |
AU2006220803A1 (en) | 2005-03-07 | 2006-09-14 | Align Technology, Inc. | Variations of dental aligners |
US7378260B2 (en) * | 2005-04-01 | 2008-05-27 | Applera Corporation | Products and methods for reducing dye artifacts |
US8226926B2 (en) | 2005-05-09 | 2012-07-24 | Biosphere Medical, S.A. | Compositions and methods using microspheres and non-ionic contrast agents |
US8377398B2 (en) | 2005-05-31 | 2013-02-19 | The Board Of Regents Of The University Of Texas System | Methods and compositions related to determination and use of white blood cell counts |
US20070004973A1 (en) * | 2005-06-15 | 2007-01-04 | Tan Sharon M L | Tissue treatment methods |
EP2508867A1 (en) * | 2005-06-24 | 2012-10-10 | Board Of Regents, The University Of Texas System | Systems and methods including self-contained cartridges with detection systems and fluid delivery systems |
US20090215646A1 (en) * | 2005-07-01 | 2009-08-27 | The Board Of Regents Of The University Of Texas Sy | System and method of analyte detection using differential receptors |
CN100562530C (en) * | 2005-07-27 | 2009-11-25 | 中国科学院过程工程研究所 | Preparation method of a kind of super large pore polymer microsphere and products thereof |
US20070083219A1 (en) * | 2005-10-12 | 2007-04-12 | Buiser Marcia S | Embolic coil introducer sheath locking mechanisms |
US8007509B2 (en) | 2005-10-12 | 2011-08-30 | Boston Scientific Scimed, Inc. | Coil assemblies, components and methods |
US20070116680A1 (en) * | 2005-11-18 | 2007-05-24 | Rensselaer Polytechnic Institute | Stem cells within gel microenvironments |
US8101197B2 (en) | 2005-12-19 | 2012-01-24 | Stryker Corporation | Forming coils |
US8152839B2 (en) | 2005-12-19 | 2012-04-10 | Boston Scientific Scimed, Inc. | Embolic coils |
US20070142859A1 (en) * | 2005-12-19 | 2007-06-21 | Boston Scientific Scimed, Inc. | Embolic coils |
US7501179B2 (en) * | 2005-12-21 | 2009-03-10 | Boston Scientific Scimed, Inc. | Block copolymer particles |
US7947368B2 (en) | 2005-12-21 | 2011-05-24 | Boston Scientific Scimed, Inc. | Block copolymer particles |
US20070142560A1 (en) * | 2005-12-21 | 2007-06-21 | Young-Ho Song | Block copolymer particles |
ATE520427T1 (en) * | 2006-01-30 | 2011-09-15 | Biosphere Medical Inc | POROUS INTRAVASCULAR EMBOLIZATION PARTICLES AND METHOD FOR THE PRODUCTION THEREOF |
US20080033366A1 (en) * | 2006-01-30 | 2008-02-07 | Surgica Corporation | Compressible intravascular embolization particles and related methods and delivery systems |
US20070299461A1 (en) * | 2006-06-21 | 2007-12-27 | Boston Scientific Scimed, Inc. | Embolic coils and related components, systems, and methods |
US20080026955A1 (en) * | 2006-07-25 | 2008-01-31 | Halliburton Energy Services, Inc. | Degradable particulates and associated methods |
WO2008019940A1 (en) * | 2006-08-17 | 2008-02-21 | Unilever Nv | Aqueous media purification method and device comprising a functionalised polyhipe resin |
EP1889811A1 (en) * | 2006-08-17 | 2008-02-20 | Unilever N.V. | Aqueous media purification method and device comprising a functionalised polyhipe resin |
US8414927B2 (en) | 2006-11-03 | 2013-04-09 | Boston Scientific Scimed, Inc. | Cross-linked polymer particles |
US8940172B2 (en) * | 2006-12-01 | 2015-01-27 | Institute Of Process Engineering, Chinese Academy Of Sciences | Super-macroporous polymeric microspheres and preparation method thereof |
US20080145658A1 (en) * | 2006-12-15 | 2008-06-19 | Boston Scientific Scimed, Inc. | Freeze Thaw Methods For Making Polymer Particles |
US7887984B2 (en) * | 2007-01-18 | 2011-02-15 | Eastman Kodak Company | Toner porous particles containing hydrocolloids |
WO2008131039A2 (en) * | 2007-04-16 | 2008-10-30 | Board Of Regents, The University Of Texas System | Cardibioindex/cardibioscore and utility of salivary proteome in cardiovascular diagnostics |
US8476324B2 (en) * | 2007-04-19 | 2013-07-02 | Kurita Water Industries Ltd. | Method for manufacturing anion exchange resin, anion exchange resin, method for manufacturing cation exchange resin, cation exchange resin, mixed bed resin, and method for manufacturing ultrapure water for washing electronic component material |
EP2195372A2 (en) * | 2007-09-05 | 2010-06-16 | Sunstorm Research Corporation | Highly porous, large polymeric particles and methods of preparation and use |
US20090130738A1 (en) * | 2007-11-19 | 2009-05-21 | Mikhail Kozlov | Media for membrane ion exchange chromatography |
US8252523B2 (en) * | 2007-12-10 | 2012-08-28 | Bayer Healthcare Llc | Porous particle reagent compositions |
WO2009128982A2 (en) * | 2008-04-18 | 2009-10-22 | Saint-Gobain Abrasives, Inc. | High porosity abrasive articles and methods of manufacturing same |
WO2010033200A2 (en) | 2008-09-19 | 2010-03-25 | President And Fellows Of Harvard College | Creation of libraries of droplets and related species |
WO2010046286A1 (en) * | 2008-10-24 | 2010-04-29 | Basf Se | Method for the manufacture of microparticles comprising an effect substance |
US20110212179A1 (en) * | 2008-10-30 | 2011-09-01 | David Liu | Micro-spherical porous biocompatible scaffolds and methods and apparatus for fabricating same |
EP2364168A1 (en) | 2008-12-04 | 2011-09-14 | Botulinum Toxin Research Associates, Inc. | Extended length botulinum toxin formulation for human or mammalian use |
US20120309851A1 (en) * | 2009-05-04 | 2012-12-06 | Nai-Hong Li | Process for Reducing Residual Surface Material from Porous Polymers |
US9138308B2 (en) | 2010-02-03 | 2015-09-22 | Apollo Endosurgery, Inc. | Mucosal tissue adhesion via textured surface |
US9162161B2 (en) | 2010-03-31 | 2015-10-20 | Jsr Corporation | Filler for affinity chromatography |
KR20130055569A (en) | 2010-03-31 | 2013-05-28 | 제이에스알 가부시끼가이샤 | Filler for affinity chromatography |
ES2623475T3 (en) | 2010-05-11 | 2017-07-11 | Allergan, Inc. | Porogen compositions, methods for making them and uses |
CN103180368B (en) * | 2010-10-25 | 2015-09-23 | 国防研究与发展组织 | Use the low poly-tetraethyl silicate of strong acid heterophase polymerization catalyzer |
JP5913368B2 (en) * | 2011-01-06 | 2016-04-27 | サイトソーベンツ・コーポレーション | Compositions and methods useful in the selective modification of internal and external surfaces of porous polymer beads |
US8394647B2 (en) | 2011-02-17 | 2013-03-12 | Siemens Healthcare Diagnostics Inc. | Reducing non-covalently bound polysaccharide on supports |
KR101481859B1 (en) * | 2011-05-20 | 2015-01-14 | 에스케이케미칼주식회사 | Method for preparing microparticles with reduced initial drug release and microparticles prepare thereby |
WO2013120028A1 (en) | 2012-02-09 | 2013-08-15 | Georgia Pacific Chemicals Llc | Methods for making polymer particulates in gel form |
US9409777B2 (en) | 2012-02-09 | 2016-08-09 | Basf Se | Preparation of polymeric resins and carbon materials |
WO2013120009A1 (en) * | 2012-02-09 | 2013-08-15 | Georgia-Pacific Chemicals Llc | Preparation of polymeric resins and carbon materials |
JP2013208596A (en) * | 2012-03-30 | 2013-10-10 | Toshiba Corp | Adsorbent, and method for manufacturing the same |
US9393291B2 (en) | 2012-04-12 | 2016-07-19 | Botulinum Toxin Research Associates, Inc. | Use of botulinum toxin for the treatment of cerebrovascular disease, renovascular and retinovascular circulatory beds |
JP5727962B2 (en) * | 2012-04-16 | 2015-06-03 | 三光株式会社 | Method for producing non-expandable hollow polymer fine particles |
CN103374143B (en) * | 2012-04-28 | 2015-08-19 | 中国科学院过程工程研究所 | A kind of super large pore polymer microsphere and preparation method thereof |
CN102675516B (en) * | 2012-05-16 | 2014-09-10 | 华南理工大学 | Intercommunicated porous magnetic polymer microsphere and preparation method thereof |
US9809466B2 (en) * | 2012-05-29 | 2017-11-07 | Indian Institute Of Technology Kanpur | Bi-metal nanoadsorbents and methods for their preparation and use |
WO2014022657A1 (en) | 2012-08-02 | 2014-02-06 | Allergan, Inc. | Mucosal tissue adhesion via textured surface |
WO2014052724A1 (en) | 2012-09-28 | 2014-04-03 | Allergan, Inc. | Porogen compositions, methods of making and uses |
IN2013DE02463A (en) | 2013-08-20 | 2015-06-26 | Indian Inst Technology Kanpur | |
EP3076170B1 (en) | 2013-11-27 | 2023-09-06 | JSR Corporation | Solid-phase carrier and production method for filler for affinity chromatography |
US9815959B2 (en) * | 2014-02-27 | 2017-11-14 | Gwo Xi Stem Cell Applied Technology Co., Ltd. | Method for manufacturing novel hollow particles |
US9950303B2 (en) * | 2014-05-14 | 2018-04-24 | Konica Minolta, Inc. | Method for production of hollow particle |
EP3162809B1 (en) | 2014-06-27 | 2021-08-04 | JSR Corporation | Carrier for affinity chromatography |
US9901627B2 (en) | 2014-07-18 | 2018-02-27 | Revance Therapeutics, Inc. | Topical ocular preparation of botulinum toxin for use in ocular surface disease |
US11484580B2 (en) | 2014-07-18 | 2022-11-01 | Revance Therapeutics, Inc. | Topical ocular preparation of botulinum toxin for use in ocular surface disease |
EP3020380B1 (en) | 2014-11-14 | 2018-07-25 | The Procter and Gamble Company | Method for producing composite structures with a plurality of absorbent foam particulates |
CN104607118B (en) * | 2014-12-30 | 2016-04-20 | 西南科技大学 | The method of collagen polypeptide nanosphere prepared by leather-making waste collagen |
JP6520139B2 (en) * | 2015-01-22 | 2019-05-29 | コニカミノルタ株式会社 | Method for producing hollow resin particles |
WO2016147641A1 (en) * | 2015-03-13 | 2016-09-22 | 日東電工株式会社 | Ionomer resin and ionomer solution containing same, laminate, member, electrochemical element, and electrochemical device |
CN105642345B (en) * | 2015-04-03 | 2018-08-10 | 江苏大学 | A kind of preparation method of hydrophobic multi-stage porous solid acid-base bifunctional catalyst |
JP6641724B2 (en) * | 2015-05-11 | 2020-02-05 | コニカミノルタ株式会社 | Hollow resin particles and method for producing the same |
US10729600B2 (en) | 2015-06-30 | 2020-08-04 | The Procter & Gamble Company | Absorbent structure |
WO2017066231A1 (en) * | 2015-10-13 | 2017-04-20 | President And Fellows Of Harvard College | Systems and methods for making and using gel microspheres |
JP6443302B2 (en) * | 2015-10-30 | 2018-12-26 | コニカミノルタ株式会社 | Method for producing porous resin particles |
CA3004318C (en) | 2015-11-04 | 2021-06-08 | The Procter & Gamble Company | Absorbent structure comprising a heterogeneous mass |
CN108348387B (en) | 2015-11-04 | 2021-05-28 | 宝洁公司 | Absorbent structure |
CN106832269B (en) * | 2015-12-04 | 2019-05-14 | 中国科学院大连化学物理研究所 | Azepine Michael's addition polymerize the method for preparing porous whole separating material |
CN105542088A (en) * | 2015-12-28 | 2016-05-04 | 常州亚环环保科技有限公司 | Method for preparing oil-displacing agent by modified charged polymer microspheres |
KR20180134949A (en) * | 2016-04-13 | 2018-12-19 | 카스트롤 리미티드 | Removal of aromatics from hydrocarbon fluids |
CN105968402B (en) * | 2016-06-07 | 2019-01-25 | 成都大学 | A kind of 3D porous support materials prepared using Pickering High Internal Phase Emulsion as template |
CN106732217B (en) * | 2016-11-14 | 2019-06-11 | 昆明理工大学 | A kind of preparation method of polymer microballoon |
CN108164631B (en) * | 2018-01-12 | 2019-07-19 | 东华大学 | Styrene-bifunctionality monomer copolymer hollow porous micro sphere and preparation method |
CN108192298B (en) * | 2018-01-12 | 2021-04-13 | 浙江东太新材料有限公司 | PET matte film and preparation method thereof |
CN108435107B (en) * | 2018-03-14 | 2020-10-23 | 嘉兴杰赛生物科技有限公司 | Preparation and application of DNA affinity nano-microspheres |
EP3794055A1 (en) | 2018-05-17 | 2021-03-24 | King Abdullah University of Science and Technology | <sup2/>? <sub2/>?2?supported onium salts as initiators for the synthesis of polycarbonates by copolymerization of cowith epoxides |
JP2021534402A (en) * | 2018-08-17 | 2021-12-09 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Particle-containing droplet system with monodisperse fluid volume |
CN109320972A (en) * | 2018-09-27 | 2019-02-12 | 江南大学 | A kind of preparation method of porous polyethylene imines microballoon |
US11961998B2 (en) * | 2019-05-06 | 2024-04-16 | Honeycomb Battery Company | Method of producing protected anode active material particles for rechargeable lithium batteries |
EP4134425A1 (en) * | 2020-09-15 | 2023-02-15 | Lg Chem, Ltd. | Microcarrier for cell culture, method for producing same, and cell culture composition using same |
CN112129517B (en) * | 2020-11-24 | 2021-04-09 | 北京天创凯睿科技有限公司 | Microsphere material for detecting fastening condition of aircraft external accessory |
WO2022186260A1 (en) * | 2021-03-03 | 2022-09-09 | 株式会社クレハ | Hollow particles and method for producing same |
WO2022252071A1 (en) * | 2021-05-31 | 2022-12-08 | Suzhou Sepax Technologies, Inc | A synthetic polymeric porous medium with hierarchical multiple layer structure, its design, synthesis, modification, and liquid chromatographic applications |
WO2022253175A1 (en) * | 2021-05-31 | 2022-12-08 | Suzhou Sepax Technologies, Inc | Synthetic polymeric porous medium with hierarchical multiple layer structure, its design, synthesis, modification, and liquid chromatographic applications |
WO2023055068A1 (en) * | 2021-09-28 | 2023-04-06 | 주식회사 엘지화학 | Microcarrier for cell culture, method for producing same, and cell culture composition using same |
US20230194914A1 (en) * | 2021-12-20 | 2023-06-22 | E Ink Corporation | Multi-layer device comprising a repair layer having conductive a hydrogel film or beads |
CN115058414B (en) * | 2022-08-09 | 2023-05-26 | 苏州赛分科技股份有限公司 | Method for purifying plasmid DNA |
CN115475284B (en) * | 2022-09-14 | 2024-02-02 | 华东理工大学 | Microsphere with three-dimensional porous structure and preparation method thereof |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4611014A (en) * | 1984-03-05 | 1986-09-09 | Lever Brothers Company | Porous polymers |
US4742086A (en) * | 1985-11-02 | 1988-05-03 | Lion Corporation | Process for manufacturing porous polymer |
US4775655A (en) * | 1985-11-18 | 1988-10-04 | Internationale Octrooi Maatschappij "Octropa" | Porous carbon structures and methods for their preparation |
EP0288310A2 (en) * | 1987-04-24 | 1988-10-26 | Unilever Plc | Substrate and process for making a substrate |
Family Cites Families (69)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1137554B (en) * | 1961-06-21 | 1962-10-04 | Bayer Ag | Process for the polymerization of water-insoluble monomers |
US3460972A (en) * | 1965-09-29 | 1969-08-12 | Battelle Development Corp | Liquid encapsulation |
US3933579A (en) * | 1968-11-28 | 1976-01-20 | Dulux Australia Limited | Vesiculated polymer granules |
AU439432B2 (en) * | 1968-11-28 | 1972-08-15 | Dulux Australia Ltd | Polymer and coating composition |
BE759698A (en) * | 1969-12-01 | 1971-06-01 | Balm Paints Ltd | VESICULOUS POLYMER |
US3822224A (en) * | 1969-12-22 | 1974-07-02 | Balm Paints Ltd | Process of preparing vesiculated crosslinked polyester resin granules |
GB1332469A (en) * | 1969-12-22 | 1973-10-03 | Balm Paints Ltd | Polymer and process |
DE2009218C3 (en) † | 1970-02-27 | 1980-07-17 | Roehm Gmbh, 6100 Darmstadt | Process for the bead polymerization of ethylenically unsaturated monomers |
DE2010115A1 (en) * | 1970-03-04 | 1971-09-16 | Farbenfabriken Bayer Ag, 5090 Leverkusen | Process for the production of micro-granules |
JPS528795B2 (en) * | 1971-12-30 | 1977-03-11 | ||
JPS5146150B2 (en) * | 1972-03-17 | 1976-12-07 | ||
DE2237316C3 (en) † | 1972-07-29 | 1985-08-29 | Roehm Gmbh, 6100 Darmstadt | Process for the production of bead-shaped, crosslinked, water-insoluble copolymers and their use |
AR206777A1 (en) * | 1972-11-13 | 1976-08-23 | Dulux Australia Ltd | PROCEDURE FOR PREPARING AQUEOUS SUSPENSION OF VESICULAR GRANULES OF POLYESTER RESIN RESICULARS OF RETAINED POLYESTER RESIN |
US4137380A (en) * | 1972-11-13 | 1979-01-30 | Dulux Australia Ltd. | Polyester granules and process |
US3988508A (en) * | 1973-03-08 | 1976-10-26 | Petrolite Corporation | High internal phase ratio emulsion polymers |
AU481144B2 (en) * | 1973-10-04 | 1977-02-21 | Dulux Australia Ltd. | POLYMER BEAD PROCESS Specification |
JPS50122564A (en) * | 1974-03-12 | 1975-09-26 | ||
US4001147A (en) † | 1975-03-03 | 1977-01-04 | The Dow Chemical Company | Oxazoline and/or oxazine-modified polymers |
FR2461376A1 (en) * | 1979-07-09 | 1981-01-30 | Alsthom Cgee | CONTACT SOCKET WITH LOCKING TABS |
AU533959B2 (en) * | 1979-12-07 | 1983-12-22 | Orica Australia Pty Ltd | Polymerisation to form granules of unsaturated polyester resin |
US4401456A (en) * | 1980-01-09 | 1983-08-30 | The United States Of America As Represented By The Secretary Of Agriculture | Controlled release of bioactive materials using alginate gel beads |
US4384975A (en) * | 1980-06-13 | 1983-05-24 | Sandoz, Inc. | Process for preparation of microspheres |
DE3106456A1 (en) † | 1981-02-21 | 1982-10-07 | Röhm GmbH, 6100 Darmstadt | METHOD FOR THE PRODUCTION OF PEARL-SHAPED, HYDROPHILIC, POLYMER-BASED POLYMERS TO PROTEINS |
ZA821586B (en) * | 1981-03-11 | 1983-10-26 | Unilever Plc | Low density porous cross-linked polymeric materials and their preparation and use as carriers for included liquids |
NZ199916A (en) * | 1981-03-11 | 1985-07-12 | Unilever Plc | Low density polymeric block material for use as carrier for included liquids |
ZW17683A1 (en) * | 1982-08-10 | 1985-03-06 | Dulux Australia Ltd | Process of preparing vesiculated polyester granules |
NZ205449A (en) * | 1982-09-07 | 1986-10-08 | Unilever Plc | Sulphonated,porous,cross-linked polymeric material |
JPS59193901A (en) * | 1983-04-20 | 1984-11-02 | Pola Chem Ind Inc | Production of spherical polymer having spherical cavity |
US4818542A (en) * | 1983-11-14 | 1989-04-04 | The University Of Kentucky Research Foundation | Porous microspheres for drug delivery and methods for making same |
US4690825A (en) * | 1985-10-04 | 1987-09-01 | Advanced Polymer Systems, Inc. | Method for delivering an active ingredient by controlled time release utilizing a novel delivery vehicle which can be prepared by a process utilizing the active ingredient as a porogen |
US5246714A (en) * | 1985-10-11 | 1993-09-21 | Aktiebolaget Hassle | Drug preparation |
JPS62106902A (en) * | 1985-11-02 | 1987-05-18 | Lion Corp | Production of porous polymer |
US5145675A (en) * | 1986-03-31 | 1992-09-08 | Advanced Polymer Systems, Inc. | Two step method for preparation of controlled release formulations |
US4629742A (en) * | 1986-01-27 | 1986-12-16 | Akzo America Inc. | Hydrolysis of fats |
GB8607535D0 (en) * | 1986-03-26 | 1986-04-30 | Unilever Plc | Elastic cross-linked polymeric materials |
US4741872A (en) * | 1986-05-16 | 1988-05-03 | The University Of Kentucky Research Foundation | Preparation of biodegradable microspheres useful as carriers for macromolecules |
US4788255A (en) * | 1986-09-29 | 1988-11-29 | Ppg Industries, Inc. | Powder coating compositions |
US4755655A (en) * | 1986-12-04 | 1988-07-05 | General Electric Company | Thermal protection arrangement for solid disk glass cooktop |
GB8709688D0 (en) * | 1987-04-24 | 1987-05-28 | Unilever Plc | Porous material |
GB8715020D0 (en) † | 1987-06-26 | 1987-08-05 | Ebdon J R | Chromatographic supports |
US4898734A (en) * | 1988-02-29 | 1990-02-06 | Massachusetts Institute Of Technology | Polymer composite for controlled release or membrane formation |
ZA892859B (en) * | 1988-04-22 | 1989-12-27 | Advanced Polymer Systems Inc | Porous particles in preparations involving immiscible phases |
US4873091A (en) * | 1988-05-23 | 1989-10-10 | Advanced Polymer Systems, Inc. | Controlled release formulating employing resilient microbeads |
US5047438A (en) * | 1988-09-26 | 1991-09-10 | Supelco, Inc. | Porous rigid resins and process of preparation |
US5840293A (en) * | 1988-11-16 | 1998-11-24 | Advanced Polymer Systems, Inc. | Ionic beads for controlled release and adsorption |
US5135872A (en) * | 1989-04-28 | 1992-08-04 | Sangstat Medical Corporation | Matrix controlled method of delayed fluid delivery for assays |
US5073365A (en) * | 1989-06-01 | 1991-12-17 | Advanced Polymer Systems | Clinical and personal care articles enhanced by lubricants and adjuvants |
JPH0681771B2 (en) * | 1989-08-25 | 1994-10-19 | 株式会社白石中央研究所 | Method for producing porous crosslinked polyester particles |
KR920702928A (en) * | 1989-11-09 | 1992-12-17 | 원본미기재 | Oral-delivery composition to which flavor is added, and preparation method thereof |
IT1237904B (en) * | 1989-12-14 | 1993-06-18 | Ubaldo Conte | CONTROLLED SPEED RELEASE TABS OF ACTIVE SUBSTANCES |
US4968562A (en) * | 1990-02-27 | 1990-11-06 | Minnesota Mining And Manufacturing Company | Hollow acid-free acrylate polymeric microspheres having multiple small voids |
DE69114006T2 (en) * | 1990-06-20 | 1996-05-02 | Advanced Polymer Systems Inc | COMPOSITIONS AND METHODS FOR THE CONTROLLED RELEASE OF SOLUBLE ACTIVE SUBSTANCES. |
GB9014689D0 (en) * | 1990-07-02 | 1990-08-22 | Tioxide Group Services Ltd | Supports for active entities |
US5147345A (en) * | 1991-08-12 | 1992-09-15 | The Procter & Gamble Company | High efficiency absorbent articles for incontinence management |
US5149720A (en) * | 1991-08-12 | 1992-09-22 | The Procter & Gamble Company | Process for preparing emulsions that are polymerizable to absorbent foam materials |
US5268224A (en) * | 1991-08-12 | 1993-12-07 | The Procter & Gamble Company | Absorbent foam materials for aqueous body fluids and absorbent articles containing such materials |
US5168104A (en) * | 1991-09-13 | 1992-12-01 | Chembiomed, Ltd. | Macroporous particles as biocompatible chromatographic supports |
US5200433A (en) * | 1992-04-20 | 1993-04-06 | Shell Oil Company | Process for preparing low density porous crosslinked polymeric materials |
US5393528A (en) * | 1992-05-07 | 1995-02-28 | Staab; Robert J. | Dissolvable device for contraception or delivery of medication |
US5189070A (en) * | 1992-05-29 | 1993-02-23 | Shell Oil Company | Process for preparing low density porous crosslinked polymeric materials |
US5252619A (en) * | 1992-05-29 | 1993-10-12 | Shell Oil Company | Process for preparing low density porous crosslinked polymeric materials |
US5268097A (en) * | 1992-06-19 | 1993-12-07 | Sepracor Inc. | Passivated and stabilized porous mineral oxide supports and method for the preparation and use of same |
US5306733A (en) * | 1993-08-30 | 1994-04-26 | Shell Oil Company | Low density porous crosslinked polymeric materials |
US5306734A (en) * | 1993-09-08 | 1994-04-26 | Shell Oil Company | Use of viscosity as an in-line diagnostic for high internal phase emulsion generation |
US5425265A (en) * | 1993-12-20 | 1995-06-20 | Jaisinghani; Rajan A. | Apparatus and method for measuring the capillary pressure distribution of porous materials |
AU7094094A (en) * | 1994-05-13 | 1995-12-05 | University Of Cincinnati, The | Microporous fast response gels and methods of use |
DE69521997T2 (en) * | 1994-05-15 | 2002-04-04 | Apbiotech Ab Uppsala | METHOD FOR PRODUCING PARTICLES AND PARTICLES THAT CAN BE MANUFACTURED BY THIS PROCESS |
US5571531A (en) * | 1994-05-18 | 1996-11-05 | Mcmaster University | Microparticle delivery system with a functionalized silicone bonded to the matrix |
US5583162A (en) * | 1994-06-06 | 1996-12-10 | Biopore Corporation | Polymeric microbeads and method of preparation |
-
1994
- 1994-06-06 US US08/254,303 patent/US5583162A/en not_active Expired - Lifetime
-
1995
- 1995-06-06 CN CN95193484.8A patent/CN1150764A/en active Pending
- 1995-06-06 JP JP8501165A patent/JPH10501173A/en active Pending
- 1995-06-06 AU AU26937/95A patent/AU702241B2/en not_active Expired
- 1995-06-06 DE DE69531617T patent/DE69531617T3/en not_active Expired - Lifetime
- 1995-06-06 WO PCT/US1995/006879 patent/WO1995033553A1/en active IP Right Grant
- 1995-06-06 EP EP95922150A patent/EP0764047B2/en not_active Expired - Lifetime
- 1995-06-06 CA CA002190731A patent/CA2190731A1/en not_active Abandoned
- 1995-06-07 US US08/485,494 patent/US5653922A/en not_active Expired - Lifetime
-
1996
- 1996-04-10 US US08/630,834 patent/US5760097A/en not_active Expired - Lifetime
- 1996-06-27 US US08/672,209 patent/US5863957A/en not_active Expired - Lifetime
-
1998
- 1998-10-02 US US09/165,520 patent/US6100306A/en not_active Expired - Lifetime
-
2008
- 2008-12-17 JP JP2008321673A patent/JP2009057578A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4611014A (en) * | 1984-03-05 | 1986-09-09 | Lever Brothers Company | Porous polymers |
US4742086A (en) * | 1985-11-02 | 1988-05-03 | Lion Corporation | Process for manufacturing porous polymer |
US4775655A (en) * | 1985-11-18 | 1988-10-04 | Internationale Octrooi Maatschappij "Octropa" | Porous carbon structures and methods for their preparation |
EP0288310A2 (en) * | 1987-04-24 | 1988-10-26 | Unilever Plc | Substrate and process for making a substrate |
Non-Patent Citations (1)
Title |
---|
See also references of EP0764047A4 * |
Cited By (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH09227690A (en) * | 1996-02-26 | 1997-09-02 | Reika Kogyo Kk | Porous particle and its preparation |
US6315767B1 (en) | 1998-08-19 | 2001-11-13 | Gambro, Inc. | Cell storage maintenance and monitoring system |
US6726671B2 (en) | 1998-08-19 | 2004-04-27 | Gambro, Inc. | Cell storage maintenance and monitoring system |
WO2000034454A3 (en) * | 1998-12-05 | 2000-11-09 | Univ Newcastle | Microcellular polymers as cell growth media and novel polymers |
US7282237B2 (en) | 1999-06-06 | 2007-10-16 | Ge Healthcare Bio-Sciences Ab | Method for surface modification, a novel support matrix and the use of the matrix |
WO2004005355A1 (en) | 2002-07-09 | 2004-01-15 | Galip Akay | Microporous polymers |
US6750261B1 (en) | 2003-04-08 | 2004-06-15 | 3M Innovative Properties Company | High internal phase emulsion foams containing polyelectrolytes |
US6890963B2 (en) | 2003-04-08 | 2005-05-10 | 3M Innovative Properties Company | High internal phase emulsion foams containing polyelectrolytes |
US9295928B2 (en) | 2004-02-05 | 2016-03-29 | Emd Millipore Corporation | Porous adsorptive or chromatographic media |
US9283035B2 (en) | 2005-04-28 | 2016-03-15 | Boston Scientific Scimed, Inc. | Tissue-treatment methods |
US9463426B2 (en) | 2005-06-24 | 2016-10-11 | Boston Scientific Scimed, Inc. | Methods and systems for coating particles |
US9433922B2 (en) | 2007-08-14 | 2016-09-06 | Emd Millipore Corporation | Media for membrane ion exchange chromatography based on polymeric primary amines, sorption device containing that media, and chromatography scheme and purification method using the same |
RU2492487C2 (en) * | 2008-09-30 | 2013-09-10 | Сони Корпорейшн | Method of obtaining microbeeds and microbeeds |
WO2010040996A3 (en) * | 2008-10-07 | 2010-06-03 | University Of Newcastle | Synthetic symbiotic system as soil additives to deliver active ingredients through plant roots for enhanced plant and crop yield |
US9334381B2 (en) | 2011-07-28 | 2016-05-10 | Eastman Kodak Company | Crosslinked organic porous particles |
WO2013016080A3 (en) * | 2011-07-28 | 2013-07-04 | Eastman Kodak Company | Crosslinked organic porous particles |
WO2013109825A1 (en) * | 2012-01-19 | 2013-07-25 | Natrix Separations Inc. | Chromatographic media for storage and delivery of therapeutic biologics and small molecules |
US9592458B2 (en) | 2013-12-26 | 2017-03-14 | Dionex Corporation | Ion exchange foams to remove ions from samples |
US10076756B2 (en) | 2013-12-26 | 2018-09-18 | Dionex Corporation | Ion exchange foams to remove ions from samples |
US10921298B2 (en) | 2014-12-30 | 2021-02-16 | Dionex Corporation | Vial cap and method for removing matrix components from a liquid sample |
CN106040121A (en) * | 2016-05-25 | 2016-10-26 | 中国科学院大学 | Method for synthesizing skeleton microsphere material |
CN110117341A (en) * | 2018-02-07 | 2019-08-13 | 江苏集萃智能液晶科技有限公司 | A kind of preparation method of porous functionalized polymer microsphere |
CN110117341B (en) * | 2018-02-07 | 2020-10-23 | 江苏集萃智能液晶科技有限公司 | Preparation method of porous functional polymer microspheres |
Also Published As
Publication number | Publication date |
---|---|
CA2190731A1 (en) | 1995-12-14 |
DE69531617T3 (en) | 2009-02-05 |
EP0764047B1 (en) | 2003-08-27 |
EP0764047B2 (en) | 2008-10-01 |
US6100306A (en) | 2000-08-08 |
JPH10501173A (en) | 1998-02-03 |
US5863957A (en) | 1999-01-26 |
JP2009057578A (en) | 2009-03-19 |
EP0764047A1 (en) | 1997-03-26 |
US5583162A (en) | 1996-12-10 |
DE69531617T2 (en) | 2004-08-12 |
DE69531617D1 (en) | 2003-10-02 |
US5653922A (en) | 1997-08-05 |
CN1150764A (en) | 1997-05-28 |
AU702241B2 (en) | 1999-02-18 |
US5760097A (en) | 1998-06-02 |
AU2693795A (en) | 1996-01-04 |
EP0764047A4 (en) | 1998-01-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5760097A (en) | Methods of preparing polymeric microbeds | |
US5288763A (en) | Porous, polymer beads and process of their preparation | |
US6048908A (en) | Hydrophilic polymeric material | |
KR101518090B1 (en) | Porous polymeric resins | |
AU767704B2 (en) | New molecularly imprinted polymers grafted on solid supports | |
JP2769000B2 (en) | Porous polymer beads and method for producing the same | |
JP2839144B2 (en) | Composite polymers, their preparation, and their use in liquid phase chromatography | |
US20080033073A1 (en) | Polymer Films | |
US5168104A (en) | Macroporous particles as biocompatible chromatographic supports | |
US20110091512A1 (en) | Highly porous, large polymeric particles and methods of preparation and use | |
US5096593A (en) | Separation material derived from glucomannan for blood coagulation factor, preparation and use thereof | |
US20120309851A1 (en) | Process for Reducing Residual Surface Material from Porous Polymers | |
ÇIçek | Nucleotide isolation by boronic acid functionalized hydrogel beads | |
JPH05500856A (en) | Improved cellulose chromatography support | |
MXPA99003366A (en) | Polymer-protein composites and methods for their preparation and use |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 95193484.8 Country of ref document: CN |
|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AM AT AU BB BG BR BY CA CH CN CZ DE DK EE ES FI GB GE HU IS JP KE KG KP KR KZ LK LR LT LU LV MD MG MN MW MX NO NZ PL PT RO RU SD SE SG SI SK TJ TM TT UA UG UZ VN |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): KE MW SD SZ UG AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2190731 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1995922150 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1995922150 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWG | Wipo information: grant in national office |
Ref document number: 1995922150 Country of ref document: EP |