Method for producing magnetic beads

Abstract

To provide a method for producing magnetic beads capable of increasing the content of magnetic particles in the magnetic beads.SOLUTION: A method for producing magnetic beads, comprising a step (A) of polymerizing a monomer in a suspension containing the monomer, magnetic particles, and a water-soluble polymerization inhibitor.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for producing magnetic beads. [Background technology]

[0002] As a technique relating to magnetic beads containing a polymer and magnetic particles, for example, the technique described in Patent Document 1 is known.

[0003] Patent document 1 describes a method for producing magnetic polymer particles, which is characterized by mixing 100 parts by weight of a radically polymerizable vinyl monomer containing 1 to 20% by weight of unsaturated carboxylic acid with 5 to 200 parts by weight of a magnetic material, dispersing the mixture in water, and then polymerizing the resulting particles with an oil-soluble initiator, and treating the resulting particles with an organic base and / or a water-soluble solvent. According to the method for producing magnetic polymer particles in Patent Document 1, it is described that many useful carboxyl groups are present on the surface of the particles, and particles with a large surface charge can be obtained. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Publication No. 10-87711 Summary of the Invention [Problem to be solved by the invention]

[0005] The present invention provides a method for producing magnetic beads that can increase the content of magnetic particles in the magnetic beads. [Means for solving the problem]

[0006] According to the present invention, there is provided the following method for producing magnetic beads.

[0007] [1] A method for producing magnetic beads, comprising: a step (A) of polymerizing a monomer in a suspension containing the monomer, magnetic particles, and a water-soluble polymerization inhibitor. [2] The method for producing magnetic beads according to [1] above, wherein the water-soluble polymerization inhibitor contains a nitrite. [3] The method for producing magnetic beads described in [2] above, wherein the nitrite comprises at least one selected from the group consisting of sodium nitrite, potassium nitrite, lithium nitrite, cesium nitrite, magnesium nitrite, calcium nitrite, barium nitrite, strontium nitrite, silver nitrite, ammonium nitrite, and dicyclohexylammonium nitrite. [4] The method for producing magnetic beads according to any one of [1] to [3], wherein the content of the water-soluble polymerization inhibitor in the suspension is 0.001% by mass or more and 1.0% by mass or less, when the entire suspension is taken as 100% by mass. [5] The method for producing magnetic beads according to any one of [1] to [4] above, wherein the monomer includes a monomer (a) having at least one selected from the group consisting of a vinyl group, a vinylidene group, and a (meth)acryloyl group. [6] The method for producing magnetic beads according to [5] above, wherein the monomer (a) includes at least one selected from the group consisting of styrene-based monomers and alkyl(meth)acrylates. [7] The method for producing magnetic beads according to any one of [1] to [6] above, wherein the magnetic particles include at least one selected from the group consisting of magnetite and maghemite. [8] The method for producing magnetic beads according to any one of [1] to [7] above, wherein the magnetic particles include magnetic particles modified with at least one selected from the group consisting of fatty acids and silane coupling agents. [9] The method for producing magnetic beads according to any one of [1] to [8] above, wherein the particle diameter of the magnetic particles is 1 nm or more and 5000 nm or less.

[10] a step (B) of preparing a monomer mixture containing the monomer and the magnetic particles before the step (A); The method for producing magnetic beads according to any one of [1] to [9] above, further comprising a step (C) of dispersing the monomer mixture in an aqueous medium containing the water-soluble polymerization inhibitor to prepare the suspension.

[11] The method for producing magnetic beads according to any one of [1] to

[10] , wherein the content of the magnetic particles in the magnetic beads is 1% by mass or more and 40% by mass or less, when the entire magnetic beads are taken as 100% by mass.

[12] The method for producing magnetic beads according to any one of [1] to

[11] above, wherein the particle diameter of the magnetic beads is 0.1 μm or more and 300 μm or less. [Effects of the Invention]

[0008] According to the present invention, it is possible to provide a method for producing magnetic beads that can increase the content of magnetic particles in the magnetic beads. DETAILED DESCRIPTION OF THE INVENTION

[0009] Hereinafter, embodiments of the present invention will be described. Unless otherwise specified, the numerical range "A to B" represents A or more and B or less. In this embodiment, the expression "(meth)acryloyl group" represents a concept that includes both methacryloyl group and acryloyl group. The same applies to similar expressions such as "(meth)acrylate."

[0010] [Magnetic bead manufacturing method] The method for producing magnetic beads of this embodiment includes a step (A) of polymerizing a monomer in a suspension containing a monomer, magnetic particles, and a water-soluble polymerization inhibitor.

[0011] The present inventors have found that in conventional methods for producing magnetic beads using suspension polymerization, magnetic particles may aggregate together, preventing the magnetic particles from being encapsulated in the polymer, and making it impossible to obtain magnetic beads containing both the polymer and the magnetic particles. The reason for this is unclear, but the present inventors speculate as follows. In the manufacturing method of magnetic beads by suspension polymerization, competitive emulsion polymerization may occur. When emulsion polymerization occurs, monomers flow out of the emulsion into the water, causing the emulsion to shrink. As a result, the magnetic particles aggregate, and the magnetic particles are not encapsulated in the polymer, failing to obtain the desired magnetic beads containing both the polymer and the magnetic particles.

[0012] The present inventors conducted extensive research based on the above-mentioned assumed mechanism, and as a result, found that by adding a water-soluble polymerization inhibitor capable of suppressing emulsion polymerization to the suspension, it is possible to suppress aggregation of magnetic particles and increase the content of magnetic particles in the resulting magnetic beads.

[0013] The method for producing magnetic beads of this embodiment preferably further includes step (B) of preparing a monomer mixture containing a monomer and magnetic particles, and step (C) of dispersing the monomer mixture in an aqueous medium containing a water-soluble polymerization inhibitor to prepare a suspension.

[0014] First, the raw materials used in the method for producing magnetic beads of this embodiment, namely, the monomer, the magnetic particles, and the water-soluble polymerization inhibitor, will be specifically described.

[0015] <Monomer> The monomer of the present embodiment is not particularly limited, but preferably includes a monomer (a) having at least one selected from the group consisting of a vinyl group, a vinylidene group, and a (meth)acryloyl group.

[0016] The vinyl group-containing monomer includes, for example, at least one selected from the group consisting of styrene-based monomers, vinyl chloride, vinyl acetate, and the like. The monomer containing a (meth)acryloyl group includes, for example, at least one selected from the group consisting of alkyl (meth)acrylate, hydroxyalkyl (meth)acrylate, and aminoalkyl (meth)acrylate.

[0017] The monomer (a) preferably includes at least one selected from the group consisting of a styrene-based monomer and an alkyl(meth)acrylate.

[0018] The styrene-based monomer means styrene and styrene derivatives. The styrene-based monomer includes at least one selected from the group consisting of, for example, styrene, divinylbenzene, 2-methylstyrene, 3-methylstyrene, 4-methylstyrene, 2,4,6-trimethylstyrene, 4-tert-butoxystyrene, 4-methoxystyrene, 3-chlorostyrene, 4-aminostyrene, α-methylstyrene, 2,4-dimethylstyrene, ethylstyrene, isopropylstyrene, butylstyrene, phenylstyrene, cyclohexylstyrene, 4-chloromethylstyrene, crotylbenzene, trivinylbenzene, and vinylnaphthalene, and preferably includes at least one selected from the group consisting of styrene, divinylbenzene, and α-methylstyrene, more preferably includes at least one selected from the group consisting of styrene and divinylbenzene, and even more preferably includes styrene.

[0019] The alkyl (meth)acrylate includes, for example, at least one selected from the group consisting of methyl (meth)acrylate, ethyl (meth)acrylate, n-butyl (meth)acrylate, t-butyl (meth)acrylate, cyclohexyl (meth)acrylate, isobornyl (meth)acrylate, etc., preferably at least one selected from the group consisting of methyl (meth)acrylate, n-butyl (meth)acrylate, t-butyl (meth)acrylate, cyclohexyl (meth)acrylate, and isobornyl (meth)acrylate, and more preferably at least one selected from the group consisting of methyl methacrylate, n-butyl methacrylate, t-butyl methacrylate, cyclohexyl methacrylate, and isobornyl methacrylate.

[0020] The monomer of this embodiment preferably further contains a monomer (b) having a carboxy group. When the monomer of this embodiment contains the monomer (b), magnetic beads containing carboxy groups on the surface thereof can be obtained.

[0021] The monomer (b) is not particularly limited as long as it is a monomer having a carboxy group, but is preferably a monomer further having a polymerizable double bond. Monomer (b) preferably contains at least one selected from the group consisting of methacrylic acid, acrylic acid, mono-2-(methacryloyloxy)ethyl phthalate, mono-2-(acryloyloxy)ethyl phthalate, 2-methacryloyloxyethyl succinic acid, and 2-acryloyloxyethyl succinic acid, more preferably contains at least one selected from the group consisting of methacrylic acid and acrylic acid, and even more preferably contains methacrylic acid.

[0022] <Magnetic particles> The magnetic particles of this embodiment are not particularly limited as long as they are magnetic particles, and include, for example, at least one selected from the group consisting of magnetite (Fe3O4), maghemite (γ-Fe2O3), hematite (α-Fe2O3), manganese ferrite (MnFe2O4), cobalt ferrite (CoFe2O4), nickel ferrite (NiFe2O4), copper ferrite (CuFe2O4), Mn-Zn ferrite, Ni-Zn ferrite, Mn-Mg ferrite, Li ferrite, Cu-Zn ferrite, and goethite (FeO(OH)), and preferably include at least one selected from the group consisting of magnetite and maghemite, and more preferably include magnetite.

[0023] The magnetic particles of this embodiment preferably include magnetic particles modified with at least one selected from the group consisting of fatty acids and silane coupling agents, and more preferably include magnetic particles modified with fatty acids.

[0024] The fatty acid of this embodiment includes, for example, at least one selected from the group consisting of oleic acid, stearic acid, palmitic acid, linoleic acid, palmitoleic acid, and the like, and preferably includes oleic acid. An example of commercially available magnetic particles modified with a fatty acid is EMG1200 (manufactured by Ferrotec Corporation).

[0025] The silane coupling agent of the present embodiment is not particularly limited, but preferably contains at least one selected from the group consisting of a vinyl group, a vinylidene group, a (meth)acryloyl group, and a styryl group, and more preferably contains a (meth)acryloyl group.

[0026] The silane coupling agent containing a vinyl group includes, for example, at least one selected from the group consisting of vinyltrimethoxysilane, vinyltriethoxysilane, and dimethoxymethylvinylsilane. The silane coupling agent containing a (meth)acryloyl group includes, for example, at least one selected from the group consisting of 3-methacryloxypropyltrimethoxysilane, 3-acryloxypropyltrimethoxysilane, 3-methacryloxypropylmethyldimethoxysilane, 3-methacryloxypropylmethyldiethoxysilane, and 3-methacryloxypropyltriethoxysilane. Examples of silane coupling agents containing a styryl group include p-styryltrimethoxysilane.

[0027] The silane coupling agent of the present embodiment preferably contains at least one selected from the group consisting of 3-methacryloxypropyltrimethoxysilane, 3-acryloxypropyltrimethoxysilane, 3-methacryloxypropylmethyldimethoxysilane, 3-methacryloxypropylmethyldiethoxysilane, 3-methacryloxypropyltriethoxysilane, p-styryltrimethoxysilane, vinyltrimethoxysilane, and vinyltriethoxysilane, and more preferably contains at least one selected from the group consisting of 3-methacryloxypropyltrimethoxysilane, 3-acryloxypropyltrimethoxysilane, and 3-methacryloxypropyltriethoxysilane.

[0028] The method for producing the magnetic particles modified with the silane coupling agent of this embodiment is not particularly limited, and examples thereof include a method in which magnetic particles such as magnetite particles are reacted with a silane coupling agent in an arbitrary solvent.

[0029] The particle diameter of the magnetic particles of this embodiment is preferably 1 nm or more and 5000 nm or less, more preferably 2 nm or more and 1000 nm or less, even more preferably 3 nm or more and 300 nm or less, even more preferably 4 nm or more and 100 nm or less, and even more preferably 5 nm or more and 50 nm or less. Here, the particle diameter of the magnetic particles means the value measured using a transmission electron microscope (TEM), specifically, the value obtained by performing image analysis on a TEM image and calculating the arithmetic mean particle diameter of any 10 magnetic particles.

[0030] <Water-soluble polymerization inhibitor> The water-soluble polymerization inhibitor of the present embodiment is not particularly limited as long as it is a water-soluble polymerization inhibitor that can suppress emulsion polymerization, and includes, for example, at least one selected from the group consisting of nitrites, thiocyanates, isothiocyanates, dialkyldithiocarbamates, copper salts, hydroquinone compounds, phenols, tetrachols, amines, piperidine-1-oxyls, and nitro compounds, and preferably includes nitrites.

[0031] The nitrite salt of the present embodiment preferably includes at least one selected from the group consisting of sodium nitrite, potassium nitrite, lithium nitrite, cesium nitrite, magnesium nitrite, calcium nitrite, barium nitrite, strontium nitrite, silver nitrite, ammonium nitrite, and dicyclohexylammonium nitrite, more preferably includes at least one selected from the group consisting of sodium nitrite, potassium nitrite, lithium nitrite, and cesium nitrite, and even more preferably includes sodium nitrite.

[0032] Hereinafter, each step in the method for producing magnetic beads of this embodiment will be specifically described in the order in which the steps are performed.

[0033] <Process (B)> The method for producing magnetic beads of this embodiment preferably includes a step (B) of preparing a monomer mixture containing a monomer and magnetic particles.

[0034] The content of the monomer in the monomer mixture of this embodiment is preferably 50% by mass or more and 98% by mass or less, more preferably 70% by mass or more and 96% by mass or less, and even more preferably 80% by mass or more and 94% by mass or less, when the entire monomer mixture is taken as 100% by mass.

[0035] The content of monomer (a) in the monomer mixture of this embodiment is preferably 70 parts by mass or more and 100 parts by mass or less, more preferably 80 parts by mass or more and 99 parts by mass or less, and even more preferably 90 parts by mass or more and 97 parts by mass or less, when the total content of the monomer components in the monomer mixture is taken as 100 parts by mass. The content of monomer (a) in the monomer mixture of this embodiment is preferably 70 parts by mass or more, more preferably 80 parts by mass or more, even more preferably 90 parts by mass or more, and preferably 100 parts by mass or less, more preferably 99 parts by mass or less, and even more preferably 97 parts by mass or less, when the total content of the monomer components in the monomer mixture is taken as 100 parts by mass. When the monomer mixture of this embodiment contains monomer (b), the content of monomer (b) in the monomer mixture of this embodiment is preferably 0.1 parts by mass or more and 15 parts by mass or less, more preferably 1 part by mass or more and 10 parts by mass or less, and even more preferably 3 parts by mass or more and 8 parts by mass or less, when the total content of the monomer components in the monomer mixture is 100 parts by mass.

[0036] The content of magnetic particles in the monomer mixture of this embodiment is preferably 0.1% by mass or more and 30% by mass or less, more preferably 0.5% by mass or more and 20% by mass or less, and even more preferably 1% by mass or more and 10% by mass or less, when the entire monomer mixture is 100% by mass.

[0037] The monomer mixture of this embodiment preferably further contains a polymerization initiator. The polymerization initiator preferably includes a thermal polymerization initiator, and more preferably includes a thermal radical polymerization initiator. The thermal radical polymerization initiator includes, for example, at least one selected from the group consisting of an azo polymerization initiator, a peroxide, and the like, and more preferably includes an azo polymerization initiator. The azo polymerization initiator includes at least one selected from the group consisting of, for example, 2,2'-azobis(isobutyronitrile), 2,2'-azobis(2-methylbutyronitrile), 2,2'-azobis(2,4-dimethylvaleronitrile), 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile), 1,1'-azobis(cyclohexane-1-carbonitrile), and dimethyl azobis(isobutyrate), and preferably includes 2,2'-azobis(isobutyronitrile).

[0038] The content of the polymerization initiator in the monomer mixture of the present embodiment is preferably 0.1 parts by mass or more and 10 parts by mass or less, more preferably 0.5 parts by mass or more and 8 parts by mass or less, and even more preferably 1 part by mass or more and 5 parts by mass or less, when the total content of the monomer components in the monomer mixture is 100 parts by mass.

[0039] In the step (B), the method for preparing the monomer mixture is not particularly limited, but is preferably a method in which the following steps (i) to (iii) are carried out in order. (i) Mixing the monomer components. (ii) A polymerization initiator is dissolved in the mixed monomer components. (iii) Magnetic particles are added to the monomer components and dispersed to obtain a monomer mixture.

[0040] <Process (C)> The method for producing magnetic beads of this embodiment preferably includes a step (C) of dispersing the monomer mixture in an aqueous medium containing a water-soluble polymerization inhibitor to prepare a suspension. Step (C) is carried out after step (B). An optional step may be included between step (B) and step (C).

[0041] The aqueous medium of the present embodiment contains water, and preferably contains ion-exchanged water.

[0042] The aqueous medium of the present embodiment contains a water-soluble polymerization inhibitor. In this embodiment, the content of the water-soluble polymerization inhibitor in the aqueous medium is preferably 0.001% by mass or more and 1.0% by mass or less, more preferably 0.005% by mass or more and 0.8% by mass or less, even more preferably 0.008% by mass or more and 0.5% by mass or less, or 0.008% by mass or more and 0.2% by mass or less, when the entire aqueous medium is taken as 100% by mass, from the viewpoint of further improving the content of magnetic particles in the magnetic beads.

[0043] The aqueous medium of this embodiment preferably contains a dispersion stabilizer. The dispersion stabilizer is not particularly limited, but preferably contains at least one selected from the group consisting of polyvinylpyrrolidone-based dispersion stabilizers and polyvinyl alcohol-based dispersion stabilizers, and more preferably contains a polyvinylpyrrolidone-based dispersion stabilizer.

[0044] The aqueous medium of the present embodiment may or may not contain a surfactant. The surfactant is not particularly limited, but preferably includes an anionic surfactant, more preferably includes sodium dodecyl sulfate.

[0045] The contents of the dispersion stabilizer and surfactant in the aqueous medium of this embodiment are not particularly limited, and may be adjusted appropriately taking into consideration the contents of the dispersion stabilizer and surfactant in the suspension of this embodiment.

[0046] In step (C), the method for dispersing the monomer mixture in the aqueous medium is not particularly limited, but examples include a method in which the monomer mixture is added to the aqueous medium and stirred using a homogenizer to obtain a suspension.

[0047] The mixing ratio of the monomer mixture to the aqueous medium is, for example, monomer mixture:aqueous medium=1:99 to 25:75 by mass.

[0048] <Process (A)> The method for producing magnetic beads of this embodiment includes a step (A) of polymerizing a monomer in a suspension containing a monomer, magnetic particles, and a water-soluble polymerization inhibitor.

[0049] The content of the monomer in the suspension of this embodiment is preferably 0.1% by mass or more and 20% by mass or less, more preferably 0.5% by mass or more and 15% by mass or less, and even more preferably 1% by mass or more and 10% by mass or less, when the entire suspension is taken as 100% by mass.

[0050] The content of monomer (a) in the suspension of this embodiment is preferably 70 parts by mass or more and 100 parts by mass or less, more preferably 80 parts by mass or more and 99 parts by mass or less, and even more preferably 90 parts by mass or more and 97 parts by mass or less, when the total content of the monomer components in the suspension is taken as 100 parts by mass. The content of monomer (a) in the suspension of this embodiment is preferably 70 parts by mass or more, more preferably 80 parts by mass or more, even more preferably 90 parts by mass or more, and preferably 100 parts by mass or less, more preferably 99 parts by mass or less, and even more preferably 97 parts by mass or less, when the total content of the monomer components in the suspension is taken as 100 parts by mass. When the suspension of this embodiment contains monomer (b), the content of monomer (b) in the suspension of this embodiment is preferably 0.1 parts by mass or more and 15 parts by mass or less, more preferably 1 part by mass or more and 10 parts by mass or less, and even more preferably 3 parts by mass or more and 8 parts by mass or less, when the total content of the monomer components in the suspension is 100 parts by mass.

[0051] The content of magnetic particles in the suspension of this embodiment is preferably 0.01% by mass or more and 3.00% by mass or less, more preferably 0.05% by mass or more and 1.00% by mass or less, and even more preferably 0.10% by mass or more and 0.60% by mass or less, when the entire suspension is taken as 100% by mass.

[0052] The content of the water-soluble polymerization inhibitor in the suspension of this embodiment is preferably 0.001% by mass or more and 1.0% by mass or less, more preferably 0.005% by mass or more and 0.8% by mass or less, even more preferably 0.008% by mass or more and 0.5% by mass or less, or 0.008% by mass or more and 0.2% by mass or less, when the entire suspension is taken as 100% by mass, from the viewpoint of further improving the content of magnetic particles in the magnetic beads.

[0053] The content of the polymerization initiator in the suspension of the present embodiment is preferably 0.1 parts by mass or more and 10 parts by mass or less, more preferably 0.5 parts by mass or more and 8 parts by mass or less, and even more preferably 1 part by mass or more and 5 parts by mass or less, when the total content of the monomer components in the suspension is 100 parts by mass.

[0054] The content of the dispersion stabilizer in the suspension of this embodiment is preferably 0.01% by mass or more and 10% by mass or less, more preferably 0.05% by mass or more and 5% by mass or less, and even more preferably 0.1% by mass or more and 3.6% by mass or less, when the entire suspension is taken as 100% by mass.

[0055] The suspension of this embodiment may or may not contain a surfactant. When the suspension of the present embodiment contains a surfactant, the content of the surfactant in the suspension of the present embodiment is preferably 0.01% by mass or more and 3.0% by mass or less, more preferably 0.05% by mass or more and 1.0% by mass or less, and even more preferably 0.1% by mass or more and 0.5% by mass or less, when the entire suspension is taken as 100% by mass.

[0056] Specific aspects of the polymerization initiator, dispersion stabilizer, and surfactant contained in the suspension of this embodiment are the same as those described in steps (B) and (C).

[0057] In step (A), the polymerization conditions are not particularly limited, but may be, for example, a temperature of 50° C. or higher and 90° C. or lower, and a time of 1 hour or higher and 30 hours or lower.

[0058] <Other processes> The method for producing magnetic beads of this embodiment may further include steps other than steps (A) to (C). Other steps include, for example, a step of separating the magnetic beads from the suspension, a step of washing the magnetic beads with acid, and the like. Methods for separating the magnetic beads from the suspension include, for example, centrifugation and magnetic separation.

[0059] [Magnetic beads] Hereinafter, preferred embodiments of the magnetic beads obtained by the method for producing magnetic beads of this embodiment will be described.

[0060] The magnetic beads of this embodiment include a polymer and magnetic particles. The magnetic beads of this embodiment preferably contain magnetic particles inside a polymer.

[0061] The polymer content in the magnetic beads of this embodiment, when the entire magnetic beads are taken as 100% by mass, is preferably 50% by mass or more, more preferably 60% by mass or more, even more preferably 70% by mass or more, and even more preferably 75% by mass or more, from the viewpoint of further increasing the functional groups on the surface of the magnetic beads, and is preferably 98% by mass or less, more preferably 95% by mass or less, even more preferably 93% by mass or less, and even more preferably 90% by mass or less, from the viewpoint of further increasing the functional groups on the surface of the magnetic beads and further improving the magnetic properties of the magnetic beads, and is preferably 50% by mass or more and 98% by mass or less, more preferably 60% by mass or more and 95% by mass or less, even more preferably 70% by mass or more and 93% by mass or less, and even more preferably 75% by mass or more and 90% by mass or less, from the viewpoint of further increasing the functional groups on the surface of the magnetic beads and further improving the magnetic properties of the magnetic beads.

[0062] The content of magnetic particles in the magnetic beads of this embodiment, when the entire magnetic beads are taken as 100% by mass, is preferably 1% by mass or more, more preferably 3% by mass or more, even more preferably 5% by mass or more, and even more preferably 8% by mass or more, from the viewpoint of further improving the magnetic properties of the magnetic beads, and is preferably 40% by mass or less, more preferably 30% by mass or less, even more preferably 25% by mass or less, and even more preferably 20% by mass or less, from the viewpoint of further increasing the functional groups on the surface of the magnetic beads, and is preferably 1% by mass or more and 40% by mass or less, more preferably 3% by mass or more and 30% by mass or less, even more preferably 5% by mass or more and 25% by mass or less, and even more preferably 8% by mass or more and 20% by mass or less, from the viewpoint of further improving the magnetic properties of the magnetic beads and further increasing the functional groups on the surface of the magnetic beads.

[0063] The magnetic beads of this embodiment may further contain components other than the polymer and the magnetic particles.

[0064] The particle size of the magnetic beads of this embodiment is preferably 0.1 μm or more and 300 μm or less, more preferably 1 μm or more and 200 μm or less, and even more preferably 5 μm or more and 100 μm or less. The particle size of the magnetic beads refers to the particle size obtained when a particle size distribution of a 1% by mass magnetic bead dispersion is measured using a laser diffraction particle size analyzer. Here, the 1% by mass magnetic bead dispersion can be, for example, a 1% by mass aqueous solution of magnetic beads using water as the solvent. The above-mentioned preferred range of particle size of the magnetic beads means that at least some of the particle sizes of the magnetic beads obtained by the above-mentioned measurement method are within the above-mentioned range.

[0065] The volume average particle size of the magnetic beads of this embodiment is preferably 0.5 μm or more and 110 μm or less, more preferably 1 μm or more and 80 μm or less, even more preferably 5 μm or more and 60 μm or less, and even more preferably 10 μm or more and 40 μm or less. The volume average particle size of magnetic beads refers to the volume average particle size (MV) obtained when a particle size distribution of a 1% by mass magnetic bead dispersion is measured using a laser diffraction particle size analyzer. Here, the 1% by mass magnetic bead dispersion can be, for example, a 1% by mass aqueous solution of magnetic beads using water as the solvent.

[0066] The surface of the magnetic beads of this embodiment preferably contains at least one selected from the group consisting of a carboxy group, an ethynyl group, a hydroxy group, an amino group, and an epoxy group, more preferably contains at least one selected from the group consisting of a carboxy group and an ethynyl group, and even more preferably contains a carboxy group. When the magnetic beads of this embodiment contain such functional groups on their surfaces, they can be reacted with a substance capable of binding to the functional groups (hereinafter referred to as the target substance) to immobilize the target substance. Magnetic beads containing such functional groups are preferred from the viewpoint of their potential application in medical and biomedical fields, such as diagnostic agents.

[0067] [Uses of magnetic beads] The uses of the magnetic beads of this embodiment are not particularly limited, and they can be used in, for example, diagnostic agents, bacterial separation, cell culture, drug delivery, magnetic toner, magnetic ink, magnetic paint, and the like. The magnetic beads of this embodiment are preferably magnetic beads that can be used as diagnostic agents. The use of the magnetic beads of this embodiment preferably does not include at least one use selected from the group consisting of magnetic toner, developer, and electrophotographic carrier.

[0068] [Method of manufacturing dispersion liquid] The method for producing a dispersion of this embodiment includes a step of obtaining magnetic beads by the method for producing magnetic beads of this embodiment, and a step of mixing the magnetic beads with a solvent to obtain a dispersion.

[0069] The dispersion of this embodiment contains the magnetic beads of this embodiment and a solvent. The solvent includes, for example, at least one selected from the group consisting of water, methanol, ethanol, isopropyl alcohol, propylene glycol monomethyl ether, and propylene glycol monomethyl ether acetate, and preferably includes water.

[0070] The concentration of the dispersion of this embodiment is, for example, 0.01% by mass to 20% by mass, preferably 0.1% by mass to 15% by mass, and more preferably 0.5% by mass to 10% by mass.

[0071] Although the embodiments of the present invention have been described above, these are merely examples of the present invention, and various other configurations can also be adopted. Furthermore, the present invention is not limited to the above-described embodiment, and modifications and improvements within the scope of achieving the object of the present invention are included in the present invention. [Example]

[0072] The present invention will be specifically explained below with reference to examples, but the present invention is not limited to these examples as long as the gist of the invention is not changed.

[0073] [Example 1] 2.0 parts by weight of styrene monomer (Denka Co., Ltd.) was added with 0.04 parts by weight of 2,2'-azobis(isobutyronitrile) (Fujifilm Wako Pure Chemical Industries, Ltd.) as a polymerization initiator, and the mixture was treated in an ultrasonic bath to completely dissolve the polymerization initiator. 0.17 parts by weight of magnetic particles (Ferrotec Material Technologies Corp., biomedical magnetic nanoparticles EMG1200) coated with a fatty acid surfactant were added, and the mixture was treated in an ultrasonic bath (BM Kiki Co., Ltd., product name: Bioruptor II (TYPE 24)) for 15 minutes to completely disperse the magnetic particles, obtaining a monomer mixture.

[0074] Separately, 95.76 parts by mass of ion-exchanged water was placed in a four-neck separable flask, and 0.012 parts by mass of sodium nitrite (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.) as a water-soluble polymerization inhibitor, 0.20 parts by mass of sodium dodecyl sulfate (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.) as a surfactant, and 1.83 parts by mass of polyvinylpyrrolidone (manufactured by Tokyo Chemical Industry Co., Ltd., K value: 30) as a dispersion stabilizer were dissolved therein to obtain an aqueous medium. The monomer mixture obtained above was added to the aqueous medium obtained, and the mixture was stirred in an ice bath at 3000 rpm for 10 minutes using a rotor / stator homogenizer (manufactured by IKA Japan Co., Ltd., product name: T18 digital ULTRA-TURRAX, shaft generator: S18N-19G), to obtain a suspension in which the monomer mixture was dispersed as droplets in the aqueous medium.

[0075] Next, this four-neck separable flask was equipped with a stirring blade, reflux condenser, nitrogen purge tube, and thermometer. The flask was immersed in a water bath, and nitrogen gas was blown into it for 30 minutes while rotating the stirring blade at 150 rpm to replace the atmosphere with nitrogen. The temperature of the water bath was then raised to 70°C, and suspension polymerization was carried out for 5 hours to obtain magnetic beads.

[0076] After the polymerization, the suspension was passed through a filter (manufactured by Yotoriyama Co., Ltd., 200 mesh) to remove aggregates. Next, the suspension was centrifuged and water was added three times, ethanol was added once, and water was added once to wash the magnetic beads. Magnetic separation was then performed using a magnet, and the dried material was placed in a vacuum device (manufactured by AS ONE Corporation, product name: AVO-200NS) and evacuated using a vacuum pump (manufactured by Sato Vacuum Co., Ltd., product name: P135D, 0.67 Pa or less). The dried material was then vacuum dried overnight at 50 °C under reduced pressure to obtain a dry powder. 10 parts by mass of 6N hydrochloric acid (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) was added to 0.5 parts by mass of the resulting dry powder, and the mixture was exposed to the acid for 2 minutes. The treated magnetic beads were then washed and purified by magnetic separation, and finally water was added and ultrasonicated for 1 minute to obtain a purified suspension.

[0077] [Examples 2 to 5 and Comparative Example 1] The magnetic beads of Examples 2 to 5 and Comparative Example 1 were each produced in the same manner as in Example 1, except that the amounts of each material in the monomer mixture and aqueous medium were changed to the amounts shown in Table 1. In Table 1, "divinylbenzene" is DVB-810 manufactured by Nippon Steel Chemical & Material Co., Ltd., and "methacrylic acid" is methacrylic acid manufactured by Tokyo Chemical Industry Co., Ltd.

[0078] [measurement] <Content of magnetic particles in magnetic beads> A portion of the purified suspension was collected with a pipette and dried under vacuum to obtain a dried powder of the purified suspension, which was then subjected to thermogravimetric thermal analysis (TG-DTA). The content of magnetic particles in the magnetic beads was determined under the following conditions. Measuring device: 2000SR (NETZSCH) Atmosphere: Nitrogen Heating rate: 10℃ / min Sample measurement container: Made of platinum 5 mg of the purified suspension dry powder was placed in a platinum cell and set in the measurement unit. The measurement unit was then heated to 800°C while nitrogen was injected. The temperature of the measurement unit was held at 800°C for 2 minutes, after which the weight of the residue was taken as the weight of the magnetic particles, and the content of magnetic particles in the magnetic beads was calculated. The content of magnetic particles in the magnetic beads is shown in Table 1.

[0079] <Volume average particle size of magnetic beads> After the polymerization, the suspension was passed through a filter, and after removing the aggregates, a portion of the filtrate was collected with a pipette and used as a measurement sample. The particle size distribution of the measurement sample was measured using a laser diffraction particle size distribution analyzer (manufactured by Beckman Coulter, product name: LS 13 320) to obtain the volume average particle size (MV). The volume average particle diameter of the magnetic beads is shown in Table 1.

[0080] [Table 1]

[0081] The magnetic beads obtained by the magnetic bead manufacturing method of the example had an improved content of magnetic particles in the magnetic beads compared to the magnetic beads obtained by the magnetic bead manufacturing method of the comparative example. That is, according to the method for producing magnetic beads of this embodiment, the content of magnetic particles in the magnetic beads can be increased.

Claims

1. A method for producing magnetic beads, comprising: a step (A) of polymerizing a monomer in a suspension containing the monomer, magnetic particles, and a water-soluble polymerization inhibitor.

2. The method for producing magnetic beads according to claim 1 , wherein the water-soluble polymerization inhibitor contains a nitrite.

3. 3. The method for producing magnetic beads according to claim 2, wherein the nitrite comprises at least one selected from the group consisting of sodium nitrite, potassium nitrite, lithium nitrite, cesium nitrite, magnesium nitrite, calcium nitrite, barium nitrite, strontium nitrite, silver nitrite, ammonium nitrite, and dicyclohexylammonium nitrite.

4. 3. The method for producing magnetic beads according to claim 1, wherein the content of the water-soluble polymerization inhibitor in the suspension is 0.001% by mass or more and 1.0% by mass or less, when the entire suspension is taken as 100% by mass.

5. 3. The method for producing magnetic beads according to claim 1, wherein the monomer comprises a monomer (a) having at least one group selected from the group consisting of a vinyl group, a vinylidene group, and a (meth)acryloyl group.

6. 6. The method for producing magnetic beads according to claim 5, wherein the monomer (a) includes at least one selected from the group consisting of a styrene-based monomer and an alkyl(meth)acrylate.

7. The method for producing magnetic beads according to claim 1 or 2, wherein the magnetic particles include at least one selected from the group consisting of magnetite and maghemite.

8. The method for producing magnetic beads according to claim 1 or 2, wherein the magnetic particles include magnetic particles modified with at least one selected from the group consisting of fatty acids and silane coupling agents.

9. The method for producing magnetic beads according to claim 1 or 2, wherein the particle diameter of the magnetic particles is 1 nm or more and 5000 nm or less.

10. a step (B) of preparing a monomer mixture containing the monomer and the magnetic particles before the step (A); 3. The method for producing magnetic beads according to claim 1, further comprising a step (C) of dispersing the monomer mixture in an aqueous medium containing the water-soluble polymerization inhibitor to prepare the suspension.

11. The method for producing magnetic beads according to claim 1 or 2, wherein the content of the magnetic particles in the magnetic beads is 1% by mass or more and 40% by mass or less, when the total mass of the magnetic beads is 100% by mass.

12. The method for producing magnetic beads according to claim 1 or 2, wherein the particle diameter of the magnetic beads is 0.1 μm or more and 300 μm or less.

Images