EP1303566A1 - Polymerisats en perles superparamagnetiques - Google Patents

Polymerisats en perles superparamagnetiques

Info

Publication number
EP1303566A1
EP1303566A1 EP01960401A EP01960401A EP1303566A1 EP 1303566 A1 EP1303566 A1 EP 1303566A1 EP 01960401 A EP01960401 A EP 01960401A EP 01960401 A EP01960401 A EP 01960401A EP 1303566 A1 EP1303566 A1 EP 1303566A1
Authority
EP
European Patent Office
Prior art keywords
meth
bead polymers
polymers according
acrylate
amino
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP01960401A
Other languages
German (de)
English (en)
Inventor
Kamelia Karlou-Eyrisch
Wolfgang Podszun
Rainer Neumann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer AG
Original Assignee
Bayer AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bayer AG filed Critical Bayer AG
Publication of EP1303566A1 publication Critical patent/EP1303566A1/fr
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K9/00—Use of pretreated ingredients
    • C08K9/08—Ingredients agglomerated by treatment with a binding agent
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K9/00—Use of pretreated ingredients
    • C08K9/10—Encapsulated ingredients
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/54326—Magnetic particles
    • G01N33/5434—Magnetic particles using magnetic particle immunoreagent carriers which constitute new materials per se
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2446/00—Magnetic particle immunoreagent carriers
    • G01N2446/10—Magnetic particle immunoreagent carriers the magnetic material being used to coat a pre-existing polymer particle but not being present in the particle core
    • 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
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/31504—Composite [nonstructural laminate]
    • Y10T428/31855—Of addition polymer from unsaturated monomers
    • 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
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/32—Composite [nonstructural laminate] of inorganic material having metal-compound-containing layer and having defined magnetic layer

Definitions

  • the invention relates to crosslinked bead polymers doped with superparamagnetic iron oxide, a process for producing the bead polymers, and their use in nucleic acid diagnostics.
  • Genetic diagnostics has found its way into the diagnostics of human diseases (e.g. detection of infectious agents, detection of mutations in the genome,
  • EP 0 707 077 describes a method for isolating nucleic acids from biological material using soluble, weakly basic polymer.
  • a precipitate is generated from the soluble, weakly basic polymer and the nucleic acid in an acidic pH range, the precipitate from the unprecipitated components of the biological material is separated and washed and the nucleic acid is released from the precipitate by adjusting a basic pH.
  • a disadvantage of the method according to EP 0707 077 is that the handling, in particular the separation and purification of the precipitation product is difficult and very time-consuming. This method can also not be carried out or only under difficult conditions with the aid of automated analysis devices.
  • US 4339337 and US 5356713 describe methods for producing magnetic beads from vinyl aromatic polymer using magnetic particles.
  • these bead polymers do not contain any functional groups for binding nucleic acids.
  • the beads show a clear residual magnetism (remanence), which makes their dispersibility more difficult.
  • WO 8303920 describes a method for producing magnetic polymer particles, in which polymer particles are treated with solutions of, for example, iron salt, the iron being precipitated in the form of iron hydroxide. In this method, the precipitated iron compound is found both in the polymer particles and on the surface of the polymer particles.
  • US 5206159 discloses a process for producing superparamagnetic polyacrylamide supports. However, these supports are unsuitable for the separation of nucleic acids.
  • a method for binding DNA to magnetic microparticles is known from US 5705628.
  • the magnetic microparticles preferably have a particle size of 1 ⁇ m and have a surface coated with carboxyl groups.
  • special salt con- concentration are used and polyethylene glycol is added in a defined concentration and with a special molecular weight.
  • the invention relates to crosslinked bead polymers doped with superparamagnetic iron oxide and containing basic amino groups, which are characterized in that the bead polymers receive copolymerized units of hydrophilic (meth) acrylate and amino (meth) acrylates.
  • (meth) acrylate means the derivatives of acrylic acid and methacrylic acid.
  • Hydropile (meth) acrylates are those whose homopolymers are more than 2.5% soluble in water at 25 ° C. Examples are mentioned. 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, 2-hydroxyethyl acrylate, 2-hydroxypropyl acrylate, triethylene glycol monomethacrylate, tetraethylene glycol monomethacrylate,
  • Glycerol monomethacrylate acrylamide, methacrylamide and N, N-dimethylacrylamide.
  • Acrylamide is preferred.
  • Amino (meth) acrylates in the context of the present invention are derivatives of acrylic acid and methacrylic acid with preferably secondary and tertiary amino groups.
  • the amino groups can also be part of a cycloaliphatic or aromatic ring.
  • Suitable amino (meth) acrylates are, for example, N- (3-aminopropyl) methacrylamide, N- (3-imidazoylpropyl) methacrylamide, N- (2-imidazoyl-ethyl) methacrylamide, N- (3-aminopropyl) acrylamide, N- (3-imidazoylpropyl) acrylamide, N- (2-imidazoylethyl) acrylamide, N- (l, l-dimethyl-3-imidazoylpropyl) methacrylamide, N- (l, 1-dimethyl-3-imidazoylpropyl) acrylamide, N- (3-benzimidazole zoylpropyl)
  • Preferred amino (meth) acrylates are aminoalkyl (meth) acrylates, such as, for example, N, N-dimethylaminoethyl methacrylate, N, N-dimethylaminopropyl methacrylate, N, N-dimethylaminoethyl acrylate, and N-tert-butylaminopropyl methacrylate.
  • N, N-dimethylaminoethyl methacrylate and N, N-dimethylaminopropyl methacrylate are particularly preferred.
  • the amino groups in the bead polymers according to the invention can be wholly or partly in protonated form, for example as hydrochlorides.
  • crosslinkers are: ethylene glycol, butanediol dimethacrylate, hexanediol, Pentaerytritoldimethacrylat, 1,2-glycerol, 1,3-glycerol, triethylene, tetra etylenglycoldimethacrylat trimethacrylate, Pentaerytritoltrimeth- acrylate, Pentaerytritoltetramethacrylat, ethylene glycol, butanediol, Pentaerytritoldiacrylat, 1,3-glycerol diacrylate, triethylene glycol diacrylate, trimethylol propane triacrylate, pentaerytritol triacrylate, pentaerytritol tetraacrylate, allyl methacrylate,
  • the amount of hydrophilic (meth) acrylate is 30 to 89% by weight, preferably 40 to 75% by weight, the amount and amino (meth) acrylates 10 to 69% by weight, preferably 20 to 50% by weight and the amount of Crosslinker 1 to 25% by weight, based in each case on the sum of hydrophilic (meth) acrylate, amino (meth) acrylates and crosslinker.
  • the iron oxide content in the superparamagnetic bead polymers according to the invention is 2 to 80% by weight, preferably 4 to 50% by weight, particularly preferably 5 to 35% by weight, based on the weight of the unswollen bead polymers.
  • the bead polymers according to the invention are superparamagnetic, that is to say they have a low residual magnetization (remanence) and a small coercive force. Their magnetic saturation is high, they are strongly attracted to an inhomogeneous magnetic field. After switching off the magnetic field, they can be easily and completely dispersed in water or aqueous buffer solutions.
  • the particle size of the superparamagnetic bead polymers according to the invention is 1 to 200 ⁇ m, preferably 5 to 100, particularly preferably 10 to 50 ⁇ m. Microscopic image analysis is well suited for determining the average particle size (0) and the particle size distribution.
  • Invention mean D ⁇ Dz ⁇ 2.5, preferably D ⁇ / Dz 2 2, particularly preferably D ⁇ / Dz
  • bead polymers according to the invention with a narrow particle size distribution are particularly well suited for the isolation of nucleic acids and, in the case of amplification processes, give particularly well reproducible results on the surface of the bead polymers.
  • the bead polymers according to the invention have a swellability in water. They have a swelling index of 1.25 to 8, preferably 2 to 6 (measured at
  • the quotient of the volume of the swollen bead polymer and the volume of the non-swollen bead polymer is defined as the swelling index.
  • Another object of the present invention is a process for the preparation of crosslinked bead polymers, which is characterized in that a monomer mixture of hydrophilic (meth) acrylate, amino (meth) acrylate, crosslinking agent and, if appropriate, further monomer is polymerized to beads by reverse suspension polymerization and then polymerized doped with superparamagnetic iron oxide by an aftertreatment with iron salt solution.
  • Reverse suspension polymerization in the sense of the invention is understood to mean a process in which the monomer mixture of hydrophilic (meth) acrylate, amino (meth) acrylate, crosslinking agent and, if appropriate, further monomer is activated with a radical generator which is soluble in the monomer mixture, and the activated monomer mixture is activated under Addition of a dispersing agent is emulsified into droplets in a non-aqueous solvent and then the droplets formed are cured by increasing the temperature.
  • the hydrophilic (meth) acrylate, the amino (meth) acrylate and the crosslinking agent correspond to the compounds mentioned above.
  • the amino (meth) acrylate can advantageously be used at least partially in the ammonium form, for example as the hydrochloride.
  • As a further monomer in amounts of up to about 25% by weight, based on the total monomer mixture for example N-vinylpyrrolidone, vinylimidazole, styrene, alfa-methylstyrene, chloromethylstyrene, acrylonitrile, vinyl acetate and maleic anhydride are suitable. It is convenient to dilute the monomer mixture with water or water-alcohol mixtures. Suitable amounts of diluent are, for example, 10 to 200% by weight, preferably 50 to 150% by weight, based on the monomer mixture.
  • Azo compounds and peroxy compounds are suitable as radical formers.
  • radical formers are the azo compounds, such as 2,2'-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride and 2,2'-azobis (2-amidino-propane) dihydrochloride.
  • the radical generator is used in amounts of 0.02 to 2.5% by weight, preferably 0.1 to 1% by weight, based on the total monomer mixture.
  • the non-aqueous solvent used is primarily hydrocarbons and halogenated hydrocarbons, and also low-viscosity silicone oils.
  • Linear, branched and cyclic aliphatic hydrocarbons are preferred. Examples include hexane, heptane, n-octane, iso-octane, iso-dodecane and cyclohexane. Of course, mixtures of different hydrocarbons can also be used.
  • Oil-soluble polymers with a molecular weight of 2,000 to 1,000,000 are suitable as dispersants.
  • Polymers with a proportion of polymerized units of C 6 -C 22 -alkyl (meth) acrylates and / or vinyl esters of C 6 -C 22 -carboxylic acids are preferred.
  • Polymers with polymerized units of stearyl methacrylate, lauryl methacrylate and vinyl stearate may be mentioned as examples.
  • Copolymers of C 6 -C 2 -alkyl- are particularly well suited
  • hydrophilic monomers are understood as meaning polymerizable olefinically unsaturated compounds which are wholly or partly soluble in water (more than 2.5% by weight > at 20 ° C.). Examples include: acrylic acid and its alkali and ammonium salts, methacrylic acid and its
  • Alkali and ammonium salts hydroxyethyl methacrylate, hydroxyethyl acrylate, diethylene glycol monoacrylate, diethylene glycol monomethacrylate, triethylene glycol monoacrylate, triethylene glycol monomethacrylate, tetraethylene glycol monoacrylate, tetraethylene glycol monomethacrylate, amininoethyl amide methacrylate, aminomethyl acrylamide, methacrylate, methacrylate, methacrylate, methacrylate, methacrylate, methacrylate, methacrylate, methacrylate Hydroxyethyl methacrylate, aminoethyl methacrylate, N, N-dimethylaminoethyl methacrylate, acrylamide, methacrylamide, vinyl pyrolidone and vinyl imidazole.
  • Particularly preferred dispersing aids are copolymers of
  • hydrophilic monomer from the group of hydroxyethyl methacrylate, aminoethyl methacrylate, N, N-dimethylaminoethyl methacrylate, acrylic amide, methacrylamide, vinyl pyrolidone and vinyl imidazole.
  • the amount of dispersant used is generally 0.1 to 8, preferably 0.5 to 5% by weight, based on the non-aqueous solvent.
  • the stirring speed during the polymerization is important for the adjustment of the
  • the size of the bead polymers obtained decreases with increasing stirrer speed.
  • the exact stirring speed for setting a certain predetermined bead size depends in individual cases on the reactor size, the reactor geometry and the stirrer geometry. It has proven to be expedient to determine the necessary stirring speed experimentally.
  • Laboratory reactors with a reaction volume of 0.51, which are equipped with a lattice stirrer, are generally obtained with the use of copolymers of methacrylic acid co-ester and hydroxyethyl methacrylic as dispersing agents with a bead diameter of 10 to 25 ⁇ m at speeds of 800 to 1000 rpm.
  • the polymerization temperature depends on the decomposition temperature of the initiator used and the boiling temperature of the non-aqueous solvent. It is generally between 50 to 150 ° C, preferably between 55 and 100 ° C. The polymerization takes 0.5 to a few hours (for example 10 hours). After the polymerization, the polymer can be isolated using customary methods, for example by filtration or decanting, and optionally dried after one or more washing processes. It is possible to fractionate the resulting polymer by physical methods in order to set a narrower particle size distribution. Suitable fractionation methods are, for example, sieving, sedimentation and air classification.
  • the aftertreatment for doping with superparamagnetic iron oxide is carried out using mixtures of aqueous Fe 2+ and Fe 3+ salt solutions.
  • the corresponding chlorides are particularly suitable.
  • the molar ratio of Fe 2+ : Fe 3+ should be 2: 1 to 1: 2. It is possible to start from iron salt solutions with a different Fe 2+ : Fe 3+ ratio and to set the optimal ratio of Fe 2+ : Fe 3+ by using oxidizing or reducing agents.
  • oxidizing agents are peroxo and nitro compounds, for example sodium bisulfite is suitable as reducing agent.
  • concentration of the iron salt solutions is generally
  • the iron salt solution is preferably brought into contact with dried, water-free bead polymer. It is particularly advantageous if the entire iron salt solution swells into the bead polymer and no excess iron salt solution remains in the interstices of the beads or on the surface of the beads.
  • the iron salts swollen in the bead polymer are converted into the corresponding iron hydroxides by adding bases.
  • Alkaline are well suited
  • the bead polymer is heated to convert the iron hydroxide into iron oxide (dehydration).
  • the heat treatment can be carried out in a simple manner aqueous suspension at 65 to 100 ° C. Suitable times for heating are 0.5 to 5 hours.
  • the conversion of iron hydroxide to iron oxide can be recognized by a change in color from light brown to dark brown to black.
  • the bead polymer is then separated off and dried.
  • the dried bead polymers doped with superparamagnetic iron oxide can be treated again in the manner described above, the content of superparamagnetic iron oxide being increased. In this way it is possible to set iron oxide contents of more than 50% by weight.
  • the present invention further provides a method for isolating nucleic acids from a sample, comprising the following steps
  • the bead polymer is doped with superparamagnetic iron oxide and contains polymerized units of hydrophilic (meth) acrylate and amino (meth) acrylates.
  • the method according to the invention is used to isolate and / or purify nucleic acids of different origins, for example from cells, tissue materials, Blood or infectious agents.
  • the material to be examined is digested by techniques known per se, such as digestion by protease digestion, a sample suitable for the further steps A to C, a lysate, being obtained. If necessary, the biological material is lysed in an intermediate step after process step A). Further suitable digestion processes have been described in DE-A-4 333 805.
  • the sample is mixed with the bead polymer according to the invention at a pH of 7 or less, preferably in the range from 2 to 6, particularly preferably in the range from 2 to 3 at room temperature.
  • Bead polymers are made using a magnetic field.
  • the complex of nucleic acid and bead polymer thus obtained can now be cleaned by washing with suitable buffers.
  • the pH of the complex is then adjusted to pH values above 7, preferably from 8 to 14, particularly preferably in the range from 12 to 14.
  • the bead polymers according to the invention provide higher adsorption and re-release rates than the soluble polymers according to EP-A-0 707 077.
  • the isolation is easier, i.e. perform with fewer steps and in shorter times.
  • the purity of the isolated nucleic acids is higher, in particular they contain fewer inhibiting by-products, so that the nucleic acids can be amplified particularly well, for example by means of the so-called "PCR reaction” and "RT-PCR”.
  • the method according to the invention is also superior to the method described in EP-A-0 707 077 with regard to digestion of the nucleic acids obtained by means of restriction enzymes.
  • the bead polymers according to the invention are also well suited for strengthening the adsorbed nucleic acids, for example by means of the so-called Perform "Taqman PCR reaction" directly on the bead polymers (ie without step C).
  • This reaction mixture was mixed with 0.063 g of potassium peroxydisulfate, dissolved in a mixture of 4.25 g of water and 2 g of methanol, and flushed with nitrogen gas at 450 rpm for 10 minutes. The stirring speed was then increased to 1000 rpm and the
  • the bead polymer treated with iron salt solution was mixed with 300 ml of water and stirred under a stream of air for 30 minutes and then heated to 72.degree.
  • the pH was adjusted to 9 throughout the process by adding ammonia solution. Then the solution was 0.155 g
  • This reaction mixture was mixed with 0.313 g of 2,2'-azobis (2-amidinopropane) dihydrochloride, dissolved in a mixture of 4.25 g of water and 2 g of methanol, and flushed with nitrogen gas at 450 rpm for 10 minutes. The temperature was then raised to 60 ° C. at 800 rpm within 1 hour and allowed to react at this temperature for 10 hours. After cooling, the resulting polymer was separated from the reaction solution by decanting and cleaned three times each with cyclohexane, water and methanol and dried at 40 ° C. in a vacuum drying cabinet. 15 g of dried polymer beads with an average particle size of 20 ⁇ m and a swelling index of 5 at 25 ° C. in water were obtained.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Polymers & Plastics (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Biotechnology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
  • Solid-Sorbent Or Filter-Aiding Compositions (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Compositions Of Macromolecular Compounds (AREA)
  • Polymerisation Methods In General (AREA)

Abstract

L'invention concerne des polymérisats en perles réticulés dopés avec de l'oxyde de fer superparamagnétique, un procédé permettant de produire des polymérisats en perles, ainsi que leur utilisation dans le diagnostic d'acides nucléiques.
EP01960401A 2000-07-11 2001-06-27 Polymerisats en perles superparamagnetiques Withdrawn EP1303566A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10033583A DE10033583A1 (de) 2000-07-11 2000-07-11 Superparamagnetische Perlpolymerisate
DE10033583 2000-07-11
PCT/EP2001/007326 WO2002004555A1 (fr) 2000-07-11 2001-06-27 Polymerisats en perles superparamagnetiques

Publications (1)

Publication Number Publication Date
EP1303566A1 true EP1303566A1 (fr) 2003-04-23

Family

ID=7648487

Family Applications (1)

Application Number Title Priority Date Filing Date
EP01960401A Withdrawn EP1303566A1 (fr) 2000-07-11 2001-06-27 Polymerisats en perles superparamagnetiques

Country Status (6)

Country Link
US (2) US20050014027A1 (fr)
EP (1) EP1303566A1 (fr)
JP (1) JP2004502851A (fr)
AU (1) AU2001281904A1 (fr)
DE (1) DE10033583A1 (fr)
WO (1) WO2002004555A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1470164A1 (fr) * 2002-01-08 2004-10-27 Commonwealth Scientific And Industrial Research Organisation Resines complexantes et leur procede de preparation

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AUPM959994A0 (en) * 1994-11-22 1994-12-15 Ici Australia Operations Proprietary Limited Water treatment process
DE10033583A1 (de) * 2000-07-11 2002-01-24 Bayer Ag Superparamagnetische Perlpolymerisate
DE10105103A1 (de) * 2001-02-05 2002-08-08 Bayer Ag Verfahren zur Herstellung von gelförmigen Kationenaustauschern
GB0116359D0 (en) * 2001-07-04 2001-08-29 Genovision As Preparation of polymer particles
DE10224352A1 (de) * 2002-06-01 2003-12-11 Mueller Schulte Detlef Thermosensitive Polymerträger mit veränderbarer physikalischer Struktur für die biochemische Analytik, Diagnostik und Therapie
KR100487167B1 (ko) * 2002-10-30 2005-05-03 (주)바이오니아 바이오칩 및 이의 제조방법
AU2003901583A0 (en) 2003-04-04 2003-05-01 Orica Australia Pty Ltd A process
DE10327112A1 (de) * 2003-06-13 2004-12-30 Bayer Chemicals Ag Verfahren zur Herstellung von Eisenoxid- und/oder Eisenoxihydroxyd-haltigen Ionenaustauschern
DE10327110A1 (de) * 2003-06-13 2005-01-05 Bayer Chemicals Ag Arsenadsorbierende Ionenaustauscher
US7098253B2 (en) * 2004-05-20 2006-08-29 3M Innovative Properties Company Macroporous ion exchange resins
AU2005266851B2 (en) 2004-07-28 2011-06-02 Ixom Operations Pty Ltd Plug-flow regeneration process
AT501380B1 (de) * 2005-02-07 2007-11-15 Vitali Dipl Ing Dshemelinski Verfahren zur reinigung der dna/rna von proteinen und zellulären reststoffen im zellenlysat
US7674835B2 (en) * 2005-12-21 2010-03-09 3M Innovative Properties Company Method of making macroporous anion exchange resins
US7683100B2 (en) * 2005-12-21 2010-03-23 3M Innovative Properties Company Method of making macroporous cation exchange resins
US8252339B2 (en) * 2006-04-11 2012-08-28 Massachusetts Institute Of Technology Medical treatment applications of swellable and deformable microspheres
US7794755B2 (en) * 2006-04-11 2010-09-14 E.I. Du Pont De Nemours And Company Process for preparation of swellable and deformable microspheres
US8062673B2 (en) * 2006-04-11 2011-11-22 E I Du Pont De Nemours And Company Process for embolization using swellable and deformable microspheres
US7674836B2 (en) * 2006-07-28 2010-03-09 3M Innovative Properties Company Method of making macroporous cation exchange resins
JP5256590B2 (ja) * 2006-08-04 2013-08-07 東亞合成株式会社 重合体微粒子の製造方法
US7887846B2 (en) * 2007-08-07 2011-02-15 E. I. Du Pont De Nemours And Company Process for preparation of swellable and degradable microspheres
US7894151B2 (en) * 2008-02-15 2011-02-22 Broadcom Corporation “Flat analog” AFE coupled with an all digital architecture compensation read channel
DE102008038295B4 (de) * 2008-08-18 2013-11-28 Eads Deutschland Gmbh Granulierung und Stabilisierung von Harzsystemen zur Verwendung bei der Herstellung von Faserverbundbauteilen
JP5941588B2 (ja) * 2014-09-01 2016-06-29 Ｄｏｗａエレクトロニクス株式会社 接合材およびそれを用いた接合方法
GB201700983D0 (en) * 2017-01-20 2017-03-08 Life Tech As Polymeric particles
TWI725686B (zh) 2018-12-26 2021-04-21 財團法人工業技術研究院 用於產生液珠的管狀結構及液珠產生方法

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1145696B (it) 1979-08-24 1986-11-05 Rhone Poulenc Ind Procedimento di preparazione di perle magnetiche di polimeri vinilaromatici
NO155316C (no) 1982-04-23 1987-03-11 Sintef Fremgangsmaate for fremstilling av magnetiske polymerpartikler.
US4474866A (en) * 1983-09-28 1984-10-02 Xerox Corporation Developer composition containing superparamagnetic polymers
US5206159A (en) * 1984-11-01 1993-04-27 Miles Inc., As Legal Successor By Merger With Technicon Instruments Corp. Polymer particles containing colloidal iron oxide granules for use as a magnetically responsive reagent carrier
US5219554A (en) * 1986-07-03 1993-06-15 Advanced Magnetics, Inc. Hydrated biodegradable superparamagnetic metal oxides
US4988568A (en) * 1988-03-30 1991-01-29 Nippon Zeon Co., Ltd. Hydrophilic fine gel particles and process for production thereof
US4965007A (en) * 1988-05-10 1990-10-23 Eastman Kodak Company Encapsulated superparamagnetic particles
FR2645160B1 (fr) 1989-03-31 1992-10-02 Rhone Poulenc Chimie
IT1252628B (it) * 1991-12-06 1995-06-19 Pier Giorgio Righetti Formulazioni per matrici poliacrilamidiche in metodiche elettrocinetiche
WO1994021240A2 (fr) * 1993-03-17 1994-09-29 Silica Gel Ges.M.B.H Particules supraparamagnetiques, leur procede de production et leur utilisation
US5648124A (en) * 1993-07-09 1997-07-15 Seradyn, Inc. Process for preparing magnetically responsive microparticles
JP3451667B2 (ja) 1993-08-24 2003-09-29 東ソー株式会社 核酸抽出及び特定核酸配列の検出方法
US5582988A (en) * 1994-09-15 1996-12-10 Johnson & Johnson Clinical Diagnostics, Inc. Methods for capture and selective release of nucleic acids using weakly basic polymer and amplification of same
US5705628A (en) * 1994-09-20 1998-01-06 Whitehead Institute For Biomedical Research DNA purification and isolation using magnetic particles
US5750412A (en) * 1995-08-25 1998-05-12 Solid Phase Sciences Corporation Paramagnetic scintillation particles and assay
JP3627342B2 (ja) * 1996-01-31 2005-03-09 Ｊｓｒ株式会社 磁性ポリマー粒子およびその製造方法
FR2749082B1 (fr) * 1996-05-24 1998-06-26 Bio Merieux Particules superparamagnetiques et monodispersees
JPH11176622A (ja) * 1997-12-08 1999-07-02 Jsr Corp 磁性粒子および非特異性核酸結合用担体
DE19912799B4 (de) * 1998-03-12 2004-12-30 AGOWA Gesellschaft für molekularbiologische Technologie mbH Superparamagnetisches Adsorptionsmaterial und seine Verwendung
DE10033583A1 (de) * 2000-07-11 2002-01-24 Bayer Ag Superparamagnetische Perlpolymerisate

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0204555A1 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1470164A1 (fr) * 2002-01-08 2004-10-27 Commonwealth Scientific And Industrial Research Organisation Resines complexantes et leur procede de preparation
EP1470164A4 (fr) * 2002-01-08 2006-04-12 Commw Scient Ind Res Org Resines complexantes et leur procede de preparation

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AU2001281904A1 (en) 2002-01-21
JP2004502851A (ja) 2004-01-29
DE10033583A1 (de) 2002-01-24
WO2002004555A1 (fr) 2002-01-17
US20050014027A1 (en) 2005-01-20
US20020106659A1 (en) 2002-08-08
US6590094B2 (en) 2003-07-08

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