JP4513463B2 - Magnetic particles and method for producing the same - Google Patents

Description

    The present invention relates to a magnetic particle particularly excellent in magnetic separation property and biochemical substance binding amount, and a method for producing the same. The magnetic particles of the present invention can be used in a wide range of fields such as biochemistry, paints, paper, electrophotography, cosmetics, pharmaceuticals, agrochemicals, foods, and catalysts, and can achieve both high sensitivity and excellent magnetic separation. It relates to particles for diagnostics and pharmaceutical research.

In recent years, magnetic particles can be easily separated and purified by magnetic force, and because of their large surface area per unit weight, they can provide an excellent reaction field for immune reactions between antigens and antibodies and hybridization between DNAs. In particular, application to diagnostic agents and pharmaceutical research is becoming active. However, conventionally, in order to increase the amount of biochemical substance binding, it has been necessary to reduce the particle size, which has the disadvantage of poor magnetic separation.
Japanese Patent No. 2736467

  An object of this invention is to provide the magnetic particle excellent in magnetic separation property and biochemical substance binding amount.

  According to the method of the present invention, magnetic particles having a large surface area per unit can be produced simply and efficiently. The magnetic particles can be used in a wide range of fields such as biochemical carriers such as diagnostic agents, paints, paper, electronic materials, electrophotography, cosmetics, pharmaceuticals, agricultural chemicals, foods, and catalysts. As an application example, the present invention can be applied to medical diagnostic agents, particularly to particles for automatic measuring instruments.

The present invention provides magnetic particles which are particles composed of a polymer and a magnetic material, have an average particle diameter of d μm, an average surface area of S μm ² and satisfy the following formula 1.
f · 4π (d / 2) ² = S f ≧ 2 Equation 1
In the present invention, the average particle diameter d (μm) of the magnetic particles is an area average diameter, and is calculated by Equation 2 from the individual particle diameters di of 300 particles measured from a scanning electron microscope (SEM) photograph.
d = (Σd _i ³ ) / (Σd _i ² ) Equation 2

The average surface area S (μm ² ) in the present invention is an average surface area per magnetic particle, and a surface area S1 [m ² / g] per unit weight is obtained using a gas adsorption measuring device using Ar gas. From the density ρ of the magnetic particles, it is calculated by Equation 3.
S = (4/3) π (d / 2) ³ ρS1… Equation 3
Here, the density ρ of the magnetic particles is determined by measuring the density ρ _d of an aqueous dispersion of magnetic particles having a solid content of c%, which is accurately measured from magnetic particles and water, at 20 ° C. using a vibration type densimeter. The density ρw = 0.99820 × 10 ⁻⁶ [g / m3] is obtained by solving Equation 4.
100 / ρ _d = (c / ρ) + ((100−c) / ρw) Equation 4

In the present invention, the surface area S1 per unit weight of the produced magnetic particles is determined using a gas adsorption measuring device. For this detailed explanation, weighed magnetic particles are set in a measuring instrument to adsorb Ar gas. The surface area S1 per unit weight is obtained from the amount of gas adsorbed at this time, and the average surface area S is obtained by substituting S1 into Equation 3.
At this time, if f = 1, it means that the magnetic particle has a smooth surface, and the larger f is, the rougher the surface of the magnetic particle is.
The range of f in the present invention is 2 or more, preferably 2 to 100, and more preferably 2 to 10. If f is less than 2, the balance between the magnetic separation property and the amount of biochemical substance binding is inferior. If it exceeds 100, the surface pore size is too small, and biological substances such as antibodies cannot bind due to the increased surface area.
The average particle diameter d of the magnetic particles produced according to the present invention is preferably 0.03 to 30 μm, more preferably 0.1 to 10 μm, and particularly preferably 0.3 to 6 μm. When d is less than 0.03 μm, the magnetic separation property is poor, and when it exceeds 30 μm, spontaneous sedimentation is fast.

  The CV (Coefficient of Variation) value of the number distribution in the particle diameter of the magnetic particles of the present invention is preferably 20% or less, more preferably 15% or less, and most preferably 10% or less. When the CV value exceeds 20%, the magnetic particles vary and the magnetic separation property deteriorates. The CV value is obtained by statistically processing the particle size of 300 magnetic particles measured by SEM photographs.

The preferred method for producing magnetic particles of the present invention includes a step of polymerizing a polymerizable monomer in the presence of particles having a magnetic substance in the polymer particles and / or on the surface of the polymer particles, and an organic solvent. The method for producing magnetic particles according to claim 1.
As a preferred method for producing the magnetic particles of the present invention, a step of forming a coating layer by physically adsorbing a hydrophobic magnetic material on the surface of the mother particles, and a step of forming a polymer layer on the coating layer by polymerization Including. The base particle is basically a non-magnetic substance, and any of an organic substance and an inorganic substance can be used, and can be appropriately selected depending on the purpose of use of the magnetic particle.
As a typical example of the organic substance, for example, a polymer can be mentioned. As such a polymer, a vinyl polymer is particularly preferable, and as a vinyl monomer used for the production thereof, aromatic vinyl monomers such as styrene, α-methylstyrene, halogenated styrene, divinylbenzene, vinyl acetate, propion are used. Vinyl esters such as vinyl acid, unsaturated nitriles such as acrylonitrile, methyl acrylate, ethyl acrylate, ethyl methacrylate, butyl acrylate, butyl methacrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, lauryl acrylate, lauryl methacrylate, ethylene glycol diacrylate Ethylenically unsaturated carboxylic acid alkyls such as ethylene glycol dimethacrylate, cyclohexyl acrylate, cyclohexyl methacrylate, etc. It can be exemplified esters and the like. This vinyl polymer may be a homopolymer or a copolymer composed of two or more monomers selected from the vinyl monomers. Also, the above vinyl monomers and conjugated diolefins such as butadiene and isoprene, acrylic acid, methacrylic acid, acrylamide, methacrylamide, glycidyl acrylate, glycidyl methacrylate, N-methylol acrylamide, N-methylol methacrylamide, 2-hydroxyethyl acrylate, A copolymer with a copolymerizable monomer such as 2-hydroxyethyl methacrylate, diallyl phthalate, allyl acrylate, allyl methacrylate, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, or the like can also be used.
The polymer particles as the mother particles described above can also be obtained, for example, by emulsion polymerization, suspension polymerization, or polymer bulk pulverization of the above-mentioned vinyl monomers. As a method for producing mother particles having a uniform particle size, swelling polymerization described in JP-B-57-24369, polymerization described in Journal of Polymer Science, Polymer Letter Edition (J. Polym. Sci., Polymer Letter Ed.) Or a polymerization method previously proposed by the present inventors (Japanese Patent Laid-Open Nos. 61-215602, 61-215603, and 61-215604).

As the mother particles of the present invention, in addition to the above polymer particles, particulate pharmaceuticals, agricultural chemicals, foods, fragrances, dyes, pigments, metals and the like can also be used. Further, after absorbing or adsorbing a liquid substance or solid substance fine powder on the porous particles, the porous particles can be used as mother particles. When such mother particles are used, magnetic particles containing the liquid substance or solid substance therein can be obtained. The absorption or adsorption of the substance means absorption, adsorption or adhesion on the particle surface and inside the pores, and this absorption and adsorption can be carried out by a conventionally known method such as impregnation. .
The material of the mother particles in the present invention is preferably an organic substance such as a polymer from the viewpoint of processability and lightness.

The magnetic material used in the present invention is not particularly limited, but iron oxide-based substances are typical, and MFe ₂ O ₄ (M = Co, Ni, Mg, Cu, Li _0.5 Fe _0.5 Etc.), ferrite expressed by Fe ₃ O ₄ , and γFe ₂ O ₃ . In particular, γFe ₂ O ₃ and Fe ₃ O ₄ are preferable as magnetic materials having strong saturation magnetization and low residual magnetization.
The magnetic substance used in the present invention has an average particle diameter of preferably 1/5 or less, more preferably 1/10 or less, and still more preferably 1/20 or less of the average particle diameter of the mother particles. When the average particle diameter of the magnetic material exceeds 1/5 of the average particle diameter of the mother particles, it is difficult to form a coating layer having a uniform and sufficient thickness on the surface of the mother particles.
The weight ratio of the mother particles to the magnetic material (mother particles: magnetic material) in the present invention is preferably 95: 5 to 10:90. When the amount of the magnetic material is less than this range, the magnetic separation property may be insufficient. On the other hand, when the amount of the magnetic material is larger than this range, the amount of the base particles becomes excessive, and the number of magnetic materials that are not combined increases.

The magnetic material used in the present invention has a hydrophobized surface from the viewpoints of affinity and compatibility between the mother particles and the polymerizable monomer used in the subsequent step. Examples of the method for hydrophobizing the surface of the magnetic material include a method in which a compound having an extremely high affinity with the magnetic material and a hydrophobic portion in the molecule is brought into contact with and bonded to the magnetic material. Examples of such compounds include silane compounds represented by silane coupling agents. Hydrophobization with silane compounds is excellent in chemical resistance, especially alkali resistance, and peeling of the magnetic material due to dropping of the hydrophobized layer during use, problems of deterioration of magnetic performance, or detached magnetic material and surface activity It is possible to effectively prevent the occurrence of a problem that contaminants enter the system due to the floating agent. Further, in the present invention, it can be said that the hydrophobized magnetic substance is sufficiently hydrophobized when it can be well dispersed in, for example, toluene.
Examples of silane compounds represented by silane coupling agents include vinyltrichlorosilane, vinyltrimethoxysilane, vinyltris (β-methoxyethoxy) silane, β- (3,4-epoxycyclohexyl) ethyltrimethoxysilane, and γ-glycid. Oxypropyltrimethoxysilane, γ-methacryloxypropyltrimethoxysilane, N-β (aminoethyl) γ-aminopropylmethyldimethoxysilane, N-β (aminoethyl) γ-aminopropyltrimethoxysilane, dodecyltrimethoxysilane, Hexyltrimethoxysilane, methyltrimethoxysilane, methyltriethoxysilane, phenyltrimethoxysilane, dodecyltrichlorosilane, hexyltrichlorosilane, methyltrichlorosilane, phenyltrichlorosilane, etc. The

  As a method for bonding these silane compounds to a magnetic substance, for example, the magnetic substance and the silane compound are mixed in an inorganic medium such as water or an organic medium such as alcohol, ether, ketone, ester, and heated with stirring. Then, a means for separating the magnetic material by decantation or the like and removing the inorganic medium or the organic medium by drying under reduced pressure can be mentioned. Alternatively, the magnetic substance and the silane compound may be directly mixed and heated to bond them together. In these means, the heating temperature is usually 30 to 100 ° C., and the heating temperature is about 0.5 to 2 hours. Moreover, although the usage-amount of a silane compound is suitably determined by the surface area of a magnetic body, it is 1-50 weight part normally with respect to 100 weight part of magnetic bodies, Preferably it is 2-30 weight part.

Further, if necessary, a nonmagnetic substance other than a magnetic substance may be added as a substance for forming the coating layer of the mother particles at the time of compounding. There are no particular restrictions on the type of such a non-magnetic substance, and it can be appropriately selected from an organic substance or an inorganic substance depending on the purpose of compositing the mother particles.
For example, when imparting conductivity to the mother particles, non-magnetic substances include carbon black, various metal powders such as copper and aluminum, inorganic materials such as copper iodide and ruthenium oxide, and conductive materials such as polyacetylene, polypyrrole, and polythienylene. Can be used.
On the other hand, when the mother particles are conductive and it is desired to increase the electrical resistance by surface modification to impart chargeability, a polymer, preferably a thermoplastic polymer, is preferably used as the nonmagnetic substance. The thermoplastic polymer can be appropriately selected from the vinyl polymers according to the purpose. The thermoplastic polymer particles preferably have a particle size of 1 to 60% of the particle size of the mother particles, a weight average molecular weight of 10,000 to 1,000,000, and an acrylic material. As the nonmagnetic substance particles used in the present invention (hereinafter referred to as “nonmagnetic fine particles”), it is preferable to use particles having a uniform particle diameter as in the case of the mother particles.

Moreover, the following pigments can be used as the fine particles for coloring when the mother particles are combined.
Black pigment Carbon black, acetylene black, lamp black, aniline black, magnetite Yellow pigment Yellow lead, zinc yellow, cadmium yellow, yellow iron oxide, mineral fast yellow, nickel titanium yellow, navel swallow, naphthol yellow S, Hanser yellow G , Hansa Yellow 10G, Benzine Yellow G, Benzine Yellow Yellow GR, Quinoline Yellow Lake, Permanentero Yellow NCG, Tartra Gin Brown Pigment Reddish Yellow Lead, Molybdenum Orange, Permanent Range GTR, Pyrazolone Orange, Vulcan Orange, Indanthren Brilliant Orange RK , Benzidine Orange G, Indanthren Brilliant Orange GK
Red Pigment Bengala, Cadmium Red, Red Plum, Mercury Cadmium, Permanent Red 4R, Risor Red, Pyrazolone Red, Watching Red Calcium Salt, Lake Red D, Brilliant Carmine 6B, Eosin Lake, Rhodamine Lake B, Alizarin Lake, Brilliant Carmine JB
Purple Pigment Manganese Purple, Fast Violet B, Methyl Violet Lake Blue Pigment Bitumen, Cobalt Blue, Alkaline Blue Lake, Metal Phthalocyanine Blue, Phthalocyanine Blue Partial Chlorides, Fast Sky Blue, Indanthrene Blue BC
Green pigment Chrome green, chromium oxide, pigment green B, malachite green lake, final yellow green White pigment Zinc white, titanium oxide, antimony white, zinc sulfide Body pigment Barite powder, barium carbonate, clay, silica, white carbon, talc, alumina For the purpose of controlling the chargeability of the white mother particles, various dyes such as nigrosine, methylene blue, rose bengal, quinoline yellow, and ultra blue can be used as the nonmagnetic fine particles.
Depending on the purpose, various functional materials such as a fluorescent substance, hydroxyapatite, and zirconia can be used as the nonmagnetic fine particles.

The nonmagnetic fine particles for forming the coating layer are not limited to single species, and can be used in combination of two or more. In particular, when using non-magnetic fine particles that are difficult to melt, such as inorganic substances, it is preferable to mix these inorganic substance particles and thermoplastic polymer particles for better formation of the coating layer. Also, mixed particles of two or more kinds of synthetic polymers can be used. In this case also, at least one of them is preferably a thermoplastic polymer particle. The amount of these nonmagnetic fine particles added is desirably 100 parts by weight or less with respect to 100 parts by weight of the base particles.
Alternatively, the magnetic particles composed of a multi-layered coating layer having a plurality of coating layers can be produced by performing a plurality of composites using the same or different types of magnetic fine particles and / or non-magnetic fine particles. For example, after forming a first coating layer using mother particles and a magnetic substance, polymer particles are further added and physically adsorbed on the first coating layer to form a second coating layer. A plurality of coating layers can be formed by repeating this as necessary. As described above, polymer particles, preferably thermoplastic polymer particles, are preferably used as components of the non-magnetic fine particles used when forming the coating layer having a multilayer structure. The thermoplastic polymer particles can be appropriately selected from the vinyl polymers according to the purpose. The thermoplastic polymer particles preferably have a particle size of 1 to 60% of the particle size of the mother particles, a weight average molecular weight of 10,000 to 1,000,000, and an acrylic material. The addition amount of these polymer components is preferably 100 parts by weight or less with respect to 100 parts by weight of the base particles. In this case, if the type of the polymer that is non-magnetic fine particles is changed to the mother particles, it becomes easy to adhere by frictional charging and the formation of the coating layer becomes easier.

  In order to form a coating layer of a magnetic material on the surface of the mother particle by the method of the present invention, first, the mother particle and the magnetic material are mixed, and the magnetic material is physically adsorbed on the surface of the mother particle. The physical adsorption method described in the present invention refers to an adsorption method and a bonding method that do not involve a chemical reaction. In principle, hydrophobic / hydrophobic adsorption, melt bonding or adsorption, fusion bonding or adsorption, hydrogen bonding, This refers to van der Waals coupling. For example, when hydrophobic / hydrophobic adsorption is used, the surface of the mother particle and the surface of the magnetic material are selected to be hydrophobic or hydrophobized and either dry blended or both the mother particle and the magnetic material are used. And a method of volatilizing the solvent under mixing conditions after sufficiently dispersing in a well-dispersible solvent such as toluene and hexane. In addition, by selecting a material or solvent that slightly dissolves the surface of the mother particle and the surface of the magnetic material and / or selecting temperature conditions during mixing, it is possible to make a composite using fusion bonding or adsorption, fusion bonding, or adsorption. .

  It is also effective to realize compounding by applying a physically strong force from the outside. For example, a mortar, an automatic mortar, a ball mill, a blade pressurizing powder compression method, a mechanochemical effect such as a mechanofusion method, or a jet mill or a hybridizer using a high-speed airflow impact method. It is desirable that the physical adsorption force is strong in order to efficiently and firmly perform the composite. The method may be carried out in a vessel equipped with a stirring blade at a peripheral speed of the stirring blade of preferably 15 m / second or more, more preferably 30 m / second or more, and further preferably 40 to 150 m / second. If the peripheral speed of the stirring blade is lower than 15 m / sec, sufficient energy for forming the coating layer may not be obtained. In addition, although there is no restriction | limiting in particular about the upper limit of the circumferential speed of a stirring blade, It determines automatically from points, such as an apparatus to be used and energy efficiency.

Next, a polymer layer (hereinafter also referred to as “coating polymer layer”) formed on the coating layer for coating will be described.
In the presence of particles having a coating layer formed on the surface of the mother particles (hereinafter referred to as “magnetic material-coated particles”), the polymer layer includes a polymerizable monomer as a main material and a polymerization initiator as a sub-material, An emulsifier, a dispersant, a surfactant, an electrolyte, a cross-linking agent, a molecular weight regulator and the like are added as necessary, and polymerization is performed in a liquid. By forming the coating polymer layer by polymerization in this way, it is possible to introduce a desired functional group onto the surface of the polymer layer, and the surface processability is excellent.
As a component of the polymer layer, a vinyl polymer is particularly preferable, and vinyl monomers used for the production thereof are aromatic vinyl monomers such as styrene, α-methylstyrene, halogenated styrene, divinylbenzene, vinyl acetate, Vinyl esters such as vinyl propionate, unsaturated nitriles such as acrylonitrile, methyl acrylate, ethyl acrylate, ethyl methacrylate, butyl acrylate, butyl methacrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, lauryl acrylate, lauryl methacrylate, ethylene glycol di Ethylenically unsaturated carboxylic acid alkyls such as acrylate, ethylene glycol dimethacrylate, cyclohexyl acrylate, cyclohexyl methacrylate, etc. It can be exemplified esters and the like. This vinyl polymer may be a homopolymer or a copolymer composed of two or more monomers selected from the vinyl monomers.
Also, the above vinyl monomers and conjugated diolefins such as butadiene and isoprene, acrylic acid, methacrylic acid, acrylamide, methacrylamide, glycidyl acrylate, glycidyl methacrylate, N-methylol acrylamide, N-methylol methacrylamide, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, diallyl phthalate, allyl acrylate, allyl methacrylate, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, styrenesulfonic acid and its sodium salt, 2-acrylamido-2-methylpropanesulfonic acid and its sodium salt, Copolymers with copolymerizable monomers such as isoprene sulfonic acid and its sodium salt should also be used. Can.

In order to produce the magnetic particles of the present invention, it is preferable to contain a crosslinkable monomer as the polymerizable monomer.
Crosslinkable vinyl monomers are preferred, and vinyl monomers used for the production thereof include polyethylene glycol diacrylate, diethylene glycol diacrylate, 1,3-butylene glycol diacrylate, polytetramethylene glycol diacrylate, poly (ethylene glycol-tetra Methylene glycol) diacrylate, poly (propylene glycol-tetramethylene glycol) diacrylate, polyethylene glycol-polypropylene glycol-polyethylene glycol diacrylate, propylene oxide modified bisphenol A diacrylate, propylene oxide modified bisphenol A diacrylate, ethylene oxide-propylene Oxide-modified bisphenol A diacrylate, 1,6-butylene Recall diacrylate, 1,6-hexylene glycol diacrylate, neopentyl glycol diacrylate, polypropylene diacrylate, 2,2′-bis (4-acryloxypropyloxyphenyl) propane, 2,2′-bis (4- Diacrylate compounds such as (acryloxydiethoxyphenyl) propane, triacrylate compounds such as trimethylolpropane triacrylate, trimethylolethane triacrylate, tetramethylolmethane triacrylate, ditrimethylolpropane tetraacrylate, tetramethylolmethane tetraacrylate, pentaerythritol Tetraacrylate compounds such as tetraacrylate, ethylene glycol dimethacrylate, glycerin dimethacrylate, diethylene glycol Cold dimethacrylate, 2-hydroxy-3-acryloyloxypropyl methacrylate, triethylene glycol dimethacrylate, polytetramethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, poly (ethylene glycol-tetramethylene glycol) dimethacrylate, poly (propylene glycol) Rutetramethylene glycol) dimethacrylate, polyethylene glycol-polypropylene glycol-polyethylene glycol dimethacrylate, ethylene oxide modified bisphenol A dimethacrylate, propylene oxide modified bisphenol A dimethacrylate, ethylene oxide-propylene oxide modified bisphenol A dimethacrylate, propylene oxide ethylene oxide ( Block type) Modified bisphenol A dimethacrylate, 1,3-butylene glycol dimethacrylate, 1,4-butylene glycol dimethacrylate, 1,6-hexane glycol dimethacrylate, neopentyl glycol dimethacrylate, dipropylene glycol dimethacrylate, polypropylene glycol Dimethacrylate, methacrylate compounds such as 2,2-bis (4-methacryloxydiethoxyphenyl) propane, trimethacrylate compounds such as trimethylolpropane trimethacrylate and trimethylolethane trimethacrylate, methylenebisacrylamide and divinylbenzene . These vinyl polymers may be homopolymers or copolymers composed of two or more monomers selected from the above vinyl monomers.
These crosslinkable monomers are preferably used in a proportion of usually 5 to 100% by weight of the polymerizable monomer.

Furthermore, in the method for producing magnetic particles of the present invention, the polymerizable monomer is polymerized in the presence of an organic solvent. Here, the organic solvent preferably has low solubility in water.
Specific examples of organic solvents include hydrocarbon organic solvents such as pentane, hexane, cyclohexane, petroleum ether, petroleum benzine, isooctane, octane, benzene, toluene, xylene, chloroform, 1,2-dichloroethane, 1,2-dibromo. Halogenated compounds such as ethane, 1,1,2-trichloro-1,2,2-trifluoroethane, chlorobenzene, bromobenzene, o-dichlorobenzene, 1-propanol, 2-propanol, 2,2,2, -Alcohols such as trifluoroethanol, 1-butanol, 2-butanol, isobutyl alcohol, isoventyl alcohol, cyclohexanol, propylene glycol and benzyl alcohol, and ethers such as diethyl ether and diisopropyl ether.
The amount of the organic solvent used is usually 5 to 200% by weight of the polymerizable monomer.

As a polymerization initiator for the polymerizable monomer, an oil-soluble polymerization initiator or a water-soluble initiator can be used.
Examples of oil-soluble polymerization initiators include benzoyl peroxide, lauroyl peroxide, tertiary butyl peroxy 2-ethyl hexanate, 3,5,5-trimethylhexanoyl peroxide, peroxide compounds such as azobisisobutyronitrile, and azo compounds. Can be mentioned.
The polymerization initiator is preferably an oil-soluble polymerization initiator from the viewpoint of solubility in water. When a water-soluble polymerization initiator is used, there is a tendency that not only polymerization on the surface of the composite particles but also a large amount of new particles in which only a hydrophobic polymerization monomer not containing magnetic substance-coated particles is polymerized.
The ratio of these polymerization initiators to the whole monomer is preferably in the range of 0.01 to 8% by weight.

As the emulsifier, a commonly used anionic surfactant or nonionic surfactant can be used alone or in combination. For example, reactive anionic surfactants include alkali metal salts of higher alcohol sulfates, alkali metal salts of alkylbenzene sulfonic acids, alkali metal salts of succinic acid dialkyl ester sulfonic acids, alkali metal salts of alkyl diphenyl ether disulfonic acids, In addition to anionic surfactants such as sulfuric acid ester salt of oxyethylene alkyl (or alkylphenyl) ether, phosphoric acid ester salt of polyoxyethylene alkyl (or alkylphenyl) ether, formalin condensate of sodium naphthalene sulfonate, etc. S-180A (manufactured by Kao Corporation), Eleminol JS-2 (manufactured by Sanyo Chemical Co., Ltd.), Aqualon HS-10, KH-10 (manufactured by Daiichi Kogyo Seiyaku Co., Ltd.), Adekaria Soap SE-10N, SR-10 (Asahi Denka Kogyo) KK)), and the like.
Examples of the nonionic surfactant include polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, Aqualon RS-20 (manufactured by Daiichi Kogyo Seiyaku Co., Ltd.), Adekari Soap NE-20 ( Reactive nonionic surfactants such as Asahi Denka Kogyo Co., Ltd.).

  The method for adding the monomer to the polymerization system in the formation of the coating polymer layer is not particularly limited, and may be any of a batch method, a division method, or a continuous addition method. The polymerization temperature varies depending on the polymerization initiator, but is usually 10 to 90 ° C, preferably 30 to 85 ° C, and the time required for the polymerization is usually about 1 to 30 hours.

  One of the main uses of the magnetic particles obtained by the method of the present invention is diagnostic carrier particles. In this application, it is not desirable to elute impurities from the particles, or from the magnetic substance itself, or from the magnetic substance. However, the magnetic particles obtained in the present invention do not have such inconvenience, so that they can be used as carrier particles for diagnostic agents. Is preferred. In the use of such diagnostic agent carrier particles, the surface characteristics of the coating polymer layer can be selected according to the purpose. Other uses of the magnetic particles obtained by the method of the present invention will be described later.

EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated further in detail, this invention is not restrict | limited by these.
Parts are based on weight.
1. Preparation of mother particles Swelling polymerization method described in JP-B-57-24369, polymerization method described in Journal of Polymer Science, Polymer Letter Ed., JP-A-61-215602, The following particles were prepared with reference to 61-215603 and 61-215604. The following mother particles were obtained by removing only the particles by centrifugation after polymerization, further washing with water, drying and pulverizing.

Base particle 1; styrene / divinylbenzene = 80/20 copolymer
(Average particle size 1.5 μm CV value 2.3%)

Base particle 2; styrene / divinylbenzene = 80/20 copolymer
(Average particle size 11 μm CV value 5.0%)

Base particle 3; styrene / divinylbenzene = 80/20 copolymer
(Average particle size 0.8μm CV value 3.0%)

2. Coating method As a method for coating the mother particles, 10 g of the hydrophobic magnetic material is mixed with 10 g of the mother particles, and this mixture is used with a hybridization system NHS-0 type (manufactured by Nara Machinery Co., Ltd.). It was treated for 5 minutes at a peripheral speed of 100 m / sec (16200 rpm) of (stirring blade).

Example 1
Reaction of 100 parts of magnetic coated particles using mother particle 1 with 7.5 parts of SDS, 7.5 parts of E150, 25 parts of ethylene glycol dimethacrylate, 12.5 parts of methacrylic acid, 1.25 parts of perbutyl O, 10 parts of isooctane, and 3000 parts of ion-exchanged water The vessel was charged and then heated while blowing nitrogen gas, heated to 80 ° C. and reacted for 4 hours. The average particle size of the obtained magnetic particles was measured and found to be 2.6 μm. The surface area per unit weight S ₁ determined from gas adsorption measurement was 11.0 m ² / g. The density of the magnetic particles obtained by an vibration density meter DMA4500 manufactured by Anton Paar was ρ = 1.5. The surface area per particle determined using Equation 3 was S = 152 pm ² . From the above, f = 7.2.
5 mg of avidinized magnetic particles obtained by chemically bonding magnetic particles and avidin were reacted with 500 pmol of biotin labeled with fluorescence. At this time, the fluorescence intensity of fluorescent biotin that did not react with avidin was measured, and the amount of avidin bound to the particles was evaluated.
In addition, the magnetic particles are dispersed in an aqueous solution containing 0.1 wt% E150 surfactant, and the magnetic separation of the magnetic particles is measured by measuring the time when the absorbance is 0.1 when the magnet is brought close to the absorbance 1.0. Compared. The results are shown in Table 1.

Comparative Example 1
100 parts of magnetic material coated particles using mother particles 1, 7.5 parts of SDS, 7.5 parts of E150, 25 parts of ethylene glycol dimethacrylate, 12.5 parts of methacrylic acid, 1.25 parts of perbutyl O, 3000 parts of ion-exchanged water are charged in a reaction vessel, The mixture was heated while blowing nitrogen gas, heated to 80 ° C. and reacted for 4 hours. The average particle size of the obtained magnetic particles was measured and found to be 2.4 μm. The surface area S ₁ per unit weight determined from gas adsorption measurement was 1.67 m ² / g. The density of the magnetic particles obtained by an vibration density meter DMA4500 manufactured by Anton Paar was ρ = 1.5. Was the surface area S = 23.0pm ² per particles determined using Equation 3. From the above, f = 1.3. In the same manner as in Example 1, the amount of biotin bound and the magnetic separation were measured.

Example 2
100 parts of magnetic material coated particles using mother particle 2, 7.5 parts of SDS, 7.5 parts of E150, 25 parts of trimethylolpropane trimethacrylate, 12.5 parts of methacrylic acid, 1.25 parts of perbutyl O, 20 parts of isooctane, 3000 parts of ion-exchanged water The reaction vessel was charged and then heated while blowing nitrogen gas, heated to 80 ° C. and reacted for 4 hours. The average particle size of the obtained magnetic particles was measured and found to be 12.0 μm. The surface area per unit weight S ₁ determined from gas adsorption measurement was 3.00 m ² / g. The density of the magnetic particles obtained by an vibration density meter DMA4500 manufactured by Anton Paar was ρ = 1.5. The surface area per particle determined using Equation 3 was 1.36 nm ² . From the above, f = 9.0. In the same manner as in Example 1, the amount of biotin bound and the magnetic separation were measured.

Comparative Example 2
100 parts of magnetic material coated particles using mother particles 3, 7.5 parts of SDS, 7.5 parts of E150, 25 parts of ethylene glycol dimethacrylate, 12.5 parts of methacrylic acid, 1.25 parts of perbutyl O, and 3000 parts of ion-exchanged water are charged in a reaction vessel. Next, the mixture was heated while blowing nitrogen gas, heated to 80 ° C., and reacted for 4 hours. The average particle size of the obtained magnetic particles was measured and found to be 1.0 μm. The surface area S ₁ per unit weight determined from gas adsorption measurement was 41.9 m ² / g. Anton Paar Vibrating Density Meter
The density of the magnetic particles determined by DMA4500 was ρ = 1.5. It was the surface area S = 3.27pm ² per one particles determined using Equation 3. From the above, f = 1.04. In the same manner as in Example 1, the amount of biotin bound and the magnetic separation were measured.

Claims (4)

Particles having a magnetic substance in the polymer particles and / or on the surface of the polymer particles, and particles made of a polymer and a magnetic substance obtained by polymerizing a vinyl monomer in the presence of an organic solvent. A magnetic particle having d μm, an average surface area of S μm ² and satisfying the following formula 1.
f · 4π (d / 2) ² = S f ≧ 2 Equation 1   2. The magnetic particle according to claim 1, wherein d is 0.03 to 30 [mu] m.   3. The magnetic particle according to claim 1, wherein the CV value of the particle size distribution is 20% or less.   4. The magnetic particle according to claim 1, wherein the polymer is a polymer of at least one monomer selected from an aromatic vinyl compound and a (meth) acrylic acid ester.