Magnetic beads and method for producing magnetic beads

Abstract

To provide magnetic beads capable of suppressing variation in light scattering in light scattering measurement.SOLUTION: A magnetic bead includes a polymer and a magnetic particle modified with a silane coupling agent, wherein the polymer includes a structural unit derived from a monomer (a) having at least one selected from the group consisting of a vinyl group, a vinylidene group, and a (meth)acryloyl group, and the silane coupling agent includes at least one selected from the group consisting of a vinyl group, a vinylidene group, a (meth)acryloyl group, and a styryl group.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to magnetic beads and 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 magnetic particles characterized by containing magnetic powder with polymer chains bonded to the surface via a coupling agent. The magnetic particles described in Patent Document 1 are described as being suitable for use as carriers and the like because they have good dispersibility, dispersion stability, and affinity with binder resins, are small in particle size with a narrow particle size distribution, and are excellent in heat resistance, abrasion resistance, etc., and are hard and not easily broken. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Publication No. 6-102708 Summary of the Invention [Problem to be solved by the invention]

[0005] The present invention provides magnetic beads that can suppress variations in light scattering in light scattering measurements. [Means for solving the problem]

[0006] According to the present invention, the following magnetic beads and a method for producing magnetic beads are provided.

[0007] [1] Magnetic beads comprising a polymer and magnetic particles modified with a silane coupling agent, the polymer contains a structural unit derived from a monomer (a) having at least one selected from the group consisting of a vinyl group, a vinylidene group, and a (meth)acryloyl group; The magnetic beads, wherein the silane coupling agent contains at least one selected from the group consisting of a vinyl group, a vinylidene group, a (meth)acryloyl group, and a styryl group. [2] The magnetic beads according to [1], wherein the silane coupling agent comprises at least one selected from the group consisting of 3-methacryloxypropyltrimethoxysilane, 3-acryloxypropyltrimethoxysilane, 3-methacryloxypropylmethyldimethoxysilane, 3-methacryloxypropylmethyldiethoxysilane, 3-methacryloxypropyltriethoxysilane, p-styryltrimethoxysilane, vinyltrimethoxysilane, and vinyltriethoxysilane. [3] The magnetic beads according to [1] or [2], wherein the magnetic particles include at least one selected from the group consisting of magnetite and maghemite. [4] The magnetic beads according to any one of [1] to [3] above, wherein the particle diameter of the magnetic particles is 1 nm or more and 5000 nm or less. [5] The magnetic beads according to any one of [1] to [4] above, wherein the monomer (a) includes at least one selected from the group consisting of styrene-based monomers and alkyl(meth)acrylates. [6] The magnetic beads according to any one of [1] to [5] above, wherein the polymer further contains a structural unit derived from a monomer (b) having a carboxy group. [7] The magnetic beads according to [6], wherein the monomer (b) comprises 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 succinate, and 2-acryloyloxyethyl succinate. [8] The magnetic beads according to any one of [1] to [7] above, which contain at least one group selected from the group consisting of a carboxy group, an ethynyl group, a hydroxy group, an amino group, and an epoxy group on the surface of the magnetic beads. [9] The magnetic beads according to any one of [1] to [8] above, wherein the average circularity of the magnetic beads is 0.80 or more and 1.00 or less.

[10] The magnetic beads according to any one of [1] to [9] above, wherein the particle diameter of the magnetic beads is 0.1 μm or more and 300 μm or less.

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

[10] above, wherein the shape of the magnetic beads is spherical.

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

[11] above, which contain the magnetic particles inside the polymer.

[13] The magnetic beads according to any one of [1] to

[12] , 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.

[14] The magnetic beads according to any one of [1] to

[13] , wherein the content of the polymer in the magnetic beads is 50% by mass or more and 98% by mass or less, when the entire magnetic beads are taken as 100% by mass.

[15] The magnetic beads according to any one of [1] to

[14] , wherein the content of the silane coupling agent in the magnetic beads is 0.01 parts by mass or more and 30 parts by mass or less when the content of the magnetic particles in the magnetic beads is 100 parts by mass.

[16] The method includes a step (A) of polymerizing a monomer (a) having at least one selected from the group consisting of a vinyl group, a vinylidene group, and a (meth)acryloyl group in a suspension containing magnetic particles modified with a silane coupling agent, A method for producing magnetic beads, wherein the silane coupling agent contains at least one selected from the group consisting of a vinyl group, a vinylidene group, a (meth)acryloyl group, and a styryl group.

[17] a step (B) of preparing a monomer mixture containing the monomer (a) and the magnetic particles modified with the silane coupling agent, prior to the step (A); The method for producing magnetic beads according to

[16] above, further comprising a step (C) of dispersing the monomer mixture in an aqueous medium to prepare the suspension.

[18] The method for producing magnetic beads according to

[16] or

[17] above, wherein the suspension further contains a monomer (b) having a carboxy group.

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

[16] to

[18] above, wherein the silane coupling agent comprises at least one selected from the group consisting of 3-methacryloxypropyltrimethoxysilane, 3-acryloxypropyltrimethoxysilane, 3-methacryloxypropylmethyldimethoxysilane, 3-methacryloxypropylmethyldiethoxysilane, 3-methacryloxypropyltriethoxysilane, p-styryltrimethoxysilane, vinyltrimethoxysilane, and vinyltriethoxysilane.

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

[16] to

[19] above, wherein the magnetic particles include at least one selected from the group consisting of magnetite and maghemite. [twenty one] The method for producing magnetic beads according to any one of claims

[16] to

[20] , wherein the particle diameter of the magnetic particles is 1 nm or more and 5000 nm or less. [Effects of the Invention]

[0008] According to the present invention, magnetic beads can be provided that can suppress variations in light scattering in light scattering measurements. [Brief explanation of the drawings]

[0009] [Figure 1] 1 is an example of an SEM image of the magnetic beads of Example 1. [Figure 2] 1 is an example of an SEM image of the magnetic beads of Example 1. [Figure 3] 1 is an example of an SEM image of the magnetic beads of Comparative Example 1. [Figure 4] 1 is an example of an SEM image of the magnetic beads of Comparative Example 2. DETAILED DESCRIPTION OF THE INVENTION

[0010] 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 groups and acryloyl groups. The same applies to similar expressions such as "(meth)acrylate."

[0011] Magnetic beads, which contain a polymer and magnetic particles, are known and are used in, for example, diagnostic agents, bacterial isolation, cell culture, drug delivery, magnetic toners, magnetic inks, and magnetic paints. Furthermore, in medical and biomedical applications such as diagnostic reagents, dispersions containing magnetic beads are sometimes subjected to light scattering measurements such as flow cytometry, and it is required that such magnetic beads suppress variations in light scattering during light scattering measurements. The present invention provides magnetic beads that can suppress variations in light scattering in light scattering measurements.

[0012] [Magnetic beads] The magnetic beads of this embodiment are magnetic beads comprising a polymer and magnetic particles modified with a silane coupling agent, wherein the polymer comprises a structural unit derived from a monomer (a) having at least one selected from the group consisting of a vinyl group, a vinylidene group, and a (meth)acryloyl group, and the silane coupling agent comprises at least one selected from the group consisting of a vinyl group, a vinylidene group, a (meth)acryloyl group, and a styryl group.

[0013] The present inventors have discovered for the first time that magnetic beads comprising a polymer and magnetic particles can be provided that are capable of suppressing variations in light scattering in light scattering measurements by including magnetic particles modified with a specific silane coupling agent as the magnetic particles.

[0014] The magnetic beads of this embodiment preferably contain magnetic particles inside a polymer.

[0015] The average circularity of the magnetic beads of this embodiment is preferably 0.80 or more and 1.00 or less, more preferably 0.85 or more and 1.00 or less, and even more preferably 0.88 or more and 1.00 or less, from the viewpoint of further suppressing variations in light scattering in light scattering measurements. Here, the average circularity of the magnetic beads means the average circularity calculated by performing image analysis on an SEM image of the magnetic beads using the method described in the Examples.

[0016] 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.

[0017] 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 50 μm or less, even more preferably 5 μm or more and 25 μm or less, and even more preferably 7 μm or more and 18 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.

[0018] The magnetic beads of this embodiment are preferably spherical in shape. The magnetic beads of this embodiment are preferably solid in shape.

[0019] 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.

[0020] Each component contained in the magnetic beads of this embodiment will be specifically described below.

[0021] <Polymer> The magnetic beads of this embodiment include a polymer. The polymer of this embodiment contains structural units derived from a monomer (a) having at least one selected from the group consisting of a vinyl group, a vinylidene group, and a (meth)acryloyl group.

[0022] (Monomer (a)) The monomer (a) is a monomer having at least one selected from the group consisting of a vinyl group, a vinylidene group, and a (meth)acryloyl group.

[0023] The monomer having a vinyl group 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, aminoalkyl (meth)acrylate, and the like.

[0024] The monomer (a) of this embodiment preferably includes at least one selected from the group consisting of a styrene-based monomer and an alkyl(meth)acrylate.

[0025] 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, and more preferably includes styrene and divinylbenzene.

[0026] 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.

[0027] (Monomer (b)) The polymer of this embodiment preferably further contains a structural unit derived from a monomer (b) having a carboxy group. When the polymer of this embodiment further contains a structural unit derived from the monomer (b) having a carboxy group, magnetic beads having a carboxy group on the surface thereof can be obtained.

[0028] 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.

[0029] 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, even more preferably 80% by mass or more, and even more preferably 85% 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, and even more preferably 93% by mass or less, from the viewpoint of further improving the magnetic properties of the magnetic beads. 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 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 80% by mass or more and 93% 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.

[0030] The method for synthesizing the polymer of this embodiment is not particularly limited, but suspension polymerization is preferred. Detailed synthesis conditions may be, for example, the conditions described in the method for producing magnetic beads described below.

[0031] <Magnetic particles modified with a silane coupling agent> The magnetic beads of this embodiment contain magnetic particles modified with a silane coupling agent.

[0032] (Silane coupling agent) The silane coupling agent of the present embodiment 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 preferably contains a (meth)acryloyl group.

[0033] 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.

[0034] 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.

[0035] (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.

[0036] The particle diameter of the magnetic particles of this embodiment is preferably 1 nm or more and 5000 nm or less, more preferably 3 nm or more and 1000 nm or less, and even more preferably 10 nm or more and 300 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.

[0037] 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 20% by mass or less, and even more preferably 15% by mass or less, from the viewpoint of further increasing the functional groups on the surface of the magnetic beads. 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 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 20% by mass or less, and even more preferably 8% by mass or more and 15% 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.

[0038] The content of the silane coupling agent in the magnetic beads of this embodiment is preferably 0.01 parts by mass or more and 30 parts by mass or less, more preferably 0.05 parts by mass or more and 20 parts by mass or less, and even more preferably 0.1 parts by mass or more and 10 parts by mass or less, from the viewpoint of further suppressing the variation in light scattering in light scattering measurements, when the content of magnetic particles in the magnetic beads is 100 parts by mass.

[0039] The method for producing the magnetic particles modified with the silane coupling agent of this embodiment is not particularly limited, but examples thereof include the methods described in the examples.

[0040] <Other ingredients> The magnetic beads of this embodiment may further contain components other than the polymer and the magnetic particles modified with a silane coupling agent.

[0041] [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 in diagnostic agents, from the viewpoint of being able to further suppress variations in light scattering in light scattering measurements. 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.

[0042] [Dispersion] 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.

[0043] 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.

[0044] [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 (a) having at least one selected from the group consisting of a vinyl group, a vinylidene group, and a (meth)acryloyl group, and magnetic particles modified with a silane coupling agent, wherein the silane coupling agent contains at least one selected from the group consisting of a vinyl group, a vinylidene group, a (meth)acryloyl group, and a styryl group.

[0045] The method for producing magnetic beads of this embodiment preferably further includes, before step (A), step (B) of preparing a monomer mixture containing monomer (a) and magnetic particles modified with the silane coupling agent, and step (C) of dispersing the monomer mixture in an aqueous medium to prepare a suspension.

[0046] 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.

[0047] <Process (B)> The method for producing magnetic beads of this embodiment preferably includes a step (B) of preparing a monomer mixture containing monomer (a) and magnetic particles modified with a silane coupling agent.

[0048] The content of monomer (a) 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 95% by mass or less, and even more preferably 80% by mass or more and 90% by mass or less, when the entire monomer mixture is taken as 100% by mass.

[0049] The content of magnetic particles modified with a silane coupling agent 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 taken as 100% by mass.

[0050] The monomer mixture of this embodiment preferably further contains a monomer (b) having a carboxy group.

[0051] In this embodiment, the content of monomer (b) in the monomer mixture 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, from the viewpoint of further suppressing aggregation of beads during polymerization, when the content of monomer (a) in the monomer mixture is taken as 100 parts by mass.

[0052] 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).

[0053] 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 1 part by mass or more and 8 parts by mass or less, and even more preferably 2 parts by mass or more and 6 parts by mass or less, when the total content of the monomer components in the monomer mixture is 100 parts by mass.

[0054] 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) The magnetic particles modified with a silane coupling agent are added to the monomer component, and the magnetic particles modified with the silane coupling agent are dispersed to obtain a monomer mixture.

[0055] <Process (C)> The method for producing magnetic beads of this embodiment preferably further includes a step (C) of dispersing the monomer mixture in an aqueous medium to prepare a suspension. Step (C) is carried out after step (B). An optional step may be included between step (B) and step (C).

[0056] The aqueous medium of the present embodiment is not particularly limited as long as it is an aqueous medium that can be used in suspension polymerization. The aqueous medium of the present embodiment contains water, and preferably contains ion-exchanged water.

[0057] The aqueous medium of this embodiment preferably contains a dispersion stabilizer. The dispersion stabilizer is not particularly limited, but preferably contains a polyvinyl alcohol-based dispersion stabilizer, more preferably contains a partially saponified polyvinyl alcohol-based dispersion stabilizer.

[0058] 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.

[0059] The aqueous medium of the present embodiment may or may not contain a polymerization inhibitor. When the aqueous medium of the present embodiment contains a polymerization inhibitor, emulsion polymerization that occurs simultaneously with suspension polymerization can be suppressed. The polymerization inhibitor is not particularly limited, but preferably contains an inorganic salt, more preferably contains a nitrite, and further preferably contains sodium nitrite.

[0060] The content of each component in the aqueous medium of this embodiment is not particularly limited, and may be adjusted appropriately taking into consideration the content of each component in the suspension of this embodiment.

[0061] 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.

[0062] 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.

[0063] <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 (a) and magnetic particles modified with a silane coupling agent.

[0064] The content of monomer (a) 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.

[0065] The content of magnetic particles modified with a silane coupling agent 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 0.50% by mass or less, when the entire suspension is taken as 100% by mass.

[0066] The suspension of this embodiment preferably further contains a monomer (b) having a carboxy group. In this embodiment, the content of monomer (b) in the suspension 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, from the viewpoint of further suppressing aggregation of beads during polymerization, when the content of monomer (a) in the suspension is taken as 100 parts by mass.

[0067] 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 1 part by mass or more and 8 parts by mass or less, and even more preferably 2 parts by mass or more and 6 parts by mass or less, when the total content of the monomer components in the suspension is 100 parts by mass.

[0068] The content of the dispersion stabilizer in the suspension of this embodiment is preferably 0.1% by mass or more and 10% by mass or less, more preferably 0.5% by mass or more and 5% by mass or less, and even more preferably 1% by mass or more and 3% by mass or less, when the entire suspension is taken as 100% by mass.

[0069] 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.

[0070] The suspension of this embodiment may or may not contain a polymerization inhibitor. When the suspension of the present embodiment contains a polymerization inhibitor, the content of the polymerization inhibitor in the suspension of the present 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 0.5% by mass or less, and even more preferably 0.01% by mass or more and 0.1% by mass or less, when the entire suspension is taken as 100% by mass.

[0071] Specific aspects of the polymerization initiator, dispersion stabilizer, surfactant, and polymerization inhibitor contained in the suspension of this embodiment are the same as those described in steps (B) and (C).

[0072] 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.

[0073] <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.

[0074] Preferred aspects of the magnetic beads obtained by the method for producing magnetic beads of this embodiment are the same as the preferred aspects of the magnetic beads of this embodiment. Furthermore, the specific aspects of the raw materials, monomer (a), monomer (b) and magnetic particles modified with a silane coupling agent, in the method for manufacturing magnetic beads of this embodiment are the same as the aspects of the magnetic particles modified with monomer (a), monomer (b) and silane coupling agent in the description of the magnetic beads of this embodiment.

[0075] 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]

[0076] 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.

[0077] [Example 1] <Production of magnetic particles modified with a silane coupling agent> A separable flask was charged with 60 g of FeCl2·4H2O (Fujifilm Wako Pure Chemical Industries, Ltd.) and 135 g of FeCl3·6H2O (Fujifilm Wako Pure Chemical Industries, Ltd.), followed by 1500 mL of pure water that had been previously purged with nitrogen by nitrogen bubbling, to dissolve the FeCl2·4H2O and FeCl3·6H2O. 400 mL of 28 wt% aqueous ammonia was poured into the flask, and the mixture was stirred at 200 rpm for 30 minutes in a 30°C oil bath to obtain magnetic particles. The resulting magnetic particles were magnetically recovered, the supernatant was removed, and water was added. This process was repeated five times to wash the magnetic particles.

[0078] The magnetic particles obtained above were magnetically recovered, and water was added to prepare a magnetic particle aqueous slurry such that the magnetic particles in the magnetic particle aqueous slurry were 20 parts by mass when the total amount of the magnetic particle aqueous slurry was 100 parts by mass. 320 g of diethylamine and 64 g of the magnetic particle aqueous slurry were added to a reaction vessel and treated in an ultrasonic bath for 15 minutes. 9.1 g of distilled water and 31.4 g of 3-methacryloxypropyltrimethoxysilane (Tokyo Chemical Industry Co., Ltd.) as a silane coupling agent were added, and the mixture was treated in an ultrasonic bath for 30 minutes. The reaction vessel was then placed on a shaker and stirred at 100 rpm for 24 hours. The magnetic particles were then recovered by centrifugation. Acetone was added to the recovered magnetic particles, and the centrifugation procedure was repeated three times to wash the magnetic particles. The mixture was air-dried to obtain magnetic particles modified with a silane coupling agent.

[0079] <Magnetic Bead Manufacturing> 2.4 parts by weight of styrene monomer (Denka Co., Ltd.), 2.4 parts by weight of divinylbenzene (Nitto Steel Chemical & Material Co., Ltd., product name: DVB-810), and 0.24 parts by weight of methacrylic acid (Tokyo Chemical Industry Co., Ltd.) were mixed, and 0.19 parts by weight of 2,2'-azobis(isobutyronitrile) (Fujifilm Wako Pure Chemical Industries, Ltd.) was added as a polymerization initiator. The mixture was then treated in an ultrasonic bath (Yamato Scientific Co., Ltd., tabletop ultrasonic cleaner, product name: CPX5800H-J) to completely dissolve the polymerization initiator. 0.27 parts by weight of the magnetic particles (median diameter 146 nm) modified with a silane coupling agent obtained above were then added, and the mixture was treated in an ultrasonic bath for 15 minutes to completely disperse the magnetic particles modified with the silane coupling agent, yielding a monomer mixture.

[0080] Separately, 92.27 parts by mass of ion-exchanged water was placed in a four-neck separable flask, and 0.03 parts by mass of sodium nitrite (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.), 0.2 parts by mass of sodium dodecyl sulfate (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd.), and 2.0 parts by mass of partially saponified polyvinyl alcohol (manufactured by FUJIFILM Wako Pure Chemical Industries, Ltd., saponification degree: 88 mol%, polymerization degree: 1500) 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.

[0081] Next, a 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 in 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.

[0082] 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 transferred to a 50 mL glass bottle was placed in a vacuum device (manufactured by AS ONE Corporation, product name: AVO-250NS-D). The material was then evacuated using a vacuum pump (manufactured by Sato Vacuum Co., Ltd., product name: P135D, 0.67 Pa or less) and 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 ultrasonically irradiated to obtain a purified suspension.

[0083] [Example 2] The magnetic beads of Example 2 were produced in the same manner as in Example 1, except that 34.9 g of 3-methacryloxypropyltriethoxysilane (manufactured by Tokyo Chemical Industry Co., Ltd.) was used as the silane coupling agent instead of 31.4 g of 3-methacryloxypropyltrimethoxysilane.

[0084] [Example 3] The magnetic beads of Example 3 were produced in the same manner as in Example 1, except that 28.1 g of 3-acryloxypropyltrimethoxysilane (manufactured by Tokyo Chemical Industry Co., Ltd.) was used as the silane coupling agent instead of 31.4 g of 3-methacryloxypropyltrimethoxysilane.

[0085] [Comparative Example 1] The magnetic beads of Comparative Example 1 were produced in the same manner as in Example 1, except that in Example 1, magnetic particles modified with a fatty acid (manufactured by Ferrotec Corporation, product name: EMG1200) were used instead of the magnetic particles modified with a silane coupling agent, and the amounts of each material in the monomer mixture and aqueous medium were set to the amounts listed in Table 1.

[0086] Comparative Example 2 Magnetic beads of Comparative Example 2 were produced in the same manner as in Comparative Example 1, except that the amounts of the monomer mixture and the aqueous medium were changed to the amounts shown in Table 1.

[0087] Comparative Example 3 The magnetic beads of Comparative Example 3 were produced in the same manner as in Example 1, except that 34.9 g of dodecyltrimethoxysilane (manufactured by Shin-Etsu Chemical Co., Ltd.) was used as the silane coupling agent instead of 31.4 g of 3-methacryloxypropyltrimethoxysilane, and the amounts of each material in the monomer mixture and aqueous medium were as shown in Table 1.

[0088] [Measurement and Evaluation] The magnetic beads obtained in each example and comparative example were measured and evaluated. The results are shown in Table 1.

[0089] <Shape of magnetic beads, etc.> The resulting purified suspension was placed on a sample stage, air-dried for at least 30 minutes, and then coated with osmium. The resultant suspension was then observed under a scanning electron microscope (SEM, manufactured by JEOL Ltd., product name: JCM-6000Plus) to evaluate the shape, interior, and presence or absence of particles inside the magnetic beads.

[0090] Figures 1 and 2 are example SEM images of magnetic beads of Example 1. Figure 3 is an example SEM image of magnetic beads of Comparative Example 1. Figure 4 is an example SEM image of magnetic beads of Comparative Example 2. Magnetic beads having shell particles with hollow portions as shown in Figures 3 and 4 were evaluated as "capsule-type." Furthermore, the capsule-type magnetic beads were evaluated for the presence or absence of particles inside the hollow portions. Furthermore, particles with crater-like irregularities visible on the surface as shown in Figure 3 were evaluated as "angular."

[0091] <Average circularity of magnetic beads> As in the above <Shape of magnetic beads, etc.>, an image was taken by SEM. The circularity was determined by binarizing the image taken by SEM using image analysis software (Image J) to make the particle area white and the background black, determining the area and perimeter of the particle, and applying this to the following formula: The average circularity was determined by calculating the average circularity of 10 particles. Circularity = perimeter of a circle with the same projected area / perimeter of the particle Perimeter of a circle with the same projected area: When a particle is observed from directly above, the area of ​​the particle's shadow projected onto the plane below is calculated, and the length of the outline of that circle is calculated. Particle perimeter: The length of the outline of the particle's shadow projected onto a plane below when the particle is observed from directly above

[0092] <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).

[0093] <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.

[0094] <Flow cytometry evaluation> A portion of the purified suspension was pipetted, water was added to a concentration of 50,000 particles / μL, and the mixture was subjected to a flow cytometer (Becton Dickinson, product name: BD LSRFortessa X-20). A scatter plot of forward scattered light (FSC) versus side scattered light (SSC) detected when the sample was run through the flow cytometer was created and evaluated according to the following criteria. A (Good): Narrow distribution of intensities in the scatter plot B (bad): Wide distribution of intensities in the scatter plot First, Example 1 was evaluated as "A (good)." Then, when the intensity distribution in the scatter diagram was equal to or narrower than Example 1, it was evaluated as "A (good)," and when it was wider than Example 1, it was evaluated as "B (poor)."

[0095] [Table 1]

[0096] The magnetic beads of the examples were all evaluated favorably by flow cytometry. That is, it can be seen that the magnetic beads of this embodiment can provide magnetic beads that can suppress variations in light scattering in light scattering measurements.

Claims

1. Magnetic beads comprising a polymer and magnetic particles modified with a silane coupling agent, the polymer contains a structural unit derived from a monomer (a) having at least one selected from the group consisting of a vinyl group, a vinylidene group, and a (meth)acryloyl group; The magnetic beads, wherein the silane coupling agent contains at least one selected from the group consisting of a vinyl group, a vinylidene group, a (meth)acryloyl group, and a styryl group.

2. The magnetic beads according to claim 1, wherein the silane coupling agent comprises at least one selected from the group consisting of 3-methacryloxypropyltrimethoxysilane, 3-acryloxypropyltrimethoxysilane, 3-methacryloxypropylmethyldimethoxysilane, 3-methacryloxypropylmethyldiethoxysilane, 3-methacryloxypropyltriethoxysilane, p-styryltrimethoxysilane, vinyltrimethoxysilane, and vinyltriethoxysilane.

3. The magnetic beads according to claim 1 or 2, wherein the magnetic particles comprise at least one selected from the group consisting of magnetite and maghemite.

4. 3. The magnetic beads according to claim 1, wherein the particle diameter of the magnetic particles is 1 nm or more and 5000 nm or less.

5. 3. The magnetic beads according to claim 1, wherein the monomer (a) comprises at least one selected from the group consisting of a styrene-based monomer and an alkyl(meth)acrylate.

6. The magnetic beads according to claim 1 or 2, wherein the polymer further comprises a structural unit derived from a monomer (b) having a carboxy group.

7. The magnetic beads according to claim 6, wherein the monomer (b) comprises 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.

8. 3. The magnetic beads according to claim 1, wherein the surface of the magnetic beads comprises at least one group selected from the group consisting of a carboxy group, an ethynyl group, a hydroxy group, an amino group, and an epoxy group.

9. 3. The magnetic beads according to claim 1, wherein the average circularity of the magnetic beads is 0.80 or more and 1.00 or less.

10. 3. The magnetic beads according to claim 1, wherein the particle diameter of the magnetic beads is 0.1 μm or more and 300 μm or less.

11. The magnetic beads according to claim 1 or 2, wherein the magnetic beads are spherical in shape.

12. The magnetic beads according to claim 1 or 2, which contain the magnetic particles inside the polymer.

13. 3. The magnetic beads according to claim 1, 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.

14. 3. The magnetic beads according to claim 1, wherein the content of the polymer in the magnetic beads is 50% by mass or more and 98% by mass or less, when the entire magnetic beads are taken as 100% by mass.

15. The magnetic beads according to claim 1 or 2, wherein the content of the silane coupling agent in the magnetic beads is 0.01 parts by mass or more and 30 parts by mass or less when the content of the magnetic particles in the magnetic beads is 100 parts by mass.

16. The method includes a step (A) of polymerizing a monomer (a) having at least one selected from the group consisting of a vinyl group, a vinylidene group, and a (meth)acryloyl group in a suspension containing magnetic particles modified with a silane coupling agent, A method for producing magnetic beads, wherein the silane coupling agent contains at least one selected from the group consisting of a vinyl group, a vinylidene group, a (meth)acryloyl group, and a styryl group.

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