JP2006234417A - Magnetic particle dispersant, and particles for diagnostic agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a magnetic particle dispersant capable of making size reduction in the average particle size that is compatible with magnetic separability. <P>SOLUTION: This magnetic particle dispersant is a dispersant for a magnetic particle having 0.01-10μm of number-averaged particle size d, a volume ratio of the particles having 2d or larger of particle size is 2-70%, a volume ratio of the particles having larger than 0.5d to smaller than 2d of particle size is 28-98%, and the volume ratio of the particles having 0.5d or smaller is 2% or lower, from among the magnetic particles. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a magnetic particle dispersion and a diagnostic drug particle capable of achieving both a reduction in average particle size and excellent magnetic separation properties. The magnetic particle dispersion of the present invention can be used in a wide range of fields such as biochemistry, paints, paper, electrophotography, cosmetics, pharmaceuticals, agricultural chemicals, foods, and catalysts, and has particularly high sensitivity and excellent magnetic separation properties. Since they can be compatible, they are useful as diagnostic particles.

  In recent years, since magnetic particles with a small average particle size have a large surface area per unit weight, they can provide an excellent reaction field in an immune reaction between an antigen and an antibody or in a hybridization between DNA or DNA and RNA. In particular, it is actively applied to diagnostics and pharmaceutical research. However, conventionally, magnetic particles having a small particle diameter have a drawback of poor magnetic separation.

  An object of this invention is to provide the magnetic particle dispersion which can make an average particle size small and outstanding magnetic separation property.

  The inventor of the present patent application is a dispersion of magnetic particles having a number average particle size d of 0.01 to 10 μm, and among the magnetic particles, the volume fraction of particles having a particle size of 2d or more, The average particle size can be reduced because the volume fraction of particles larger than 0.5d and smaller than 2d and the volume fraction of particles smaller than 0.5d are each a predetermined ratio. In addition, the inventors have found that excellent magnetic separation can be obtained and have come up with the present invention.

  The magnetic particle dispersion of the present invention is a dispersion of magnetic particles having a number average particle diameter d of 0.01 to 10 μm, and among the magnetic particles, a volume fraction of particles having a particle diameter of 2d or more is 2. The volume fraction of particles having a particle size of 0.5 to less than 2d is 28 to 98%, and the volume fraction of particles having a particle size of 0.5d or less is 2%. It is as follows.

  Here, in the magnetic particle dispersion of the present invention, the magnetic particles may include magnetic fine particles having a primary particle size of 50 nm or less and nonmagnetic organic substances.

  The magnetic particle dispersion of the present invention is used for the diagnostic drug particle of the present invention.

  According to the magnetic particle dispersion of the present invention, a magnetic particle dispersion having a number average particle diameter d of 0.01 to 10 μm, and the volume fraction of particles having a particle diameter of 2d or more among the magnetic particles. Is 2 to 70%, the volume fraction of particles having a particle size larger than 0.5d and smaller than 2d is 28 to 98%, and the volume fraction of particles having a particle size of 0.5d or less is By being 2% or less, the average particle size is small, so the surface area per unit weight is large and the magnetic separation property is excellent.

  The magnetic particle dispersion of the present invention can be used in a wide variety 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.

  Hereinafter, the magnetic particle dispersion of the present invention will be described in detail.

1. Magnetic Particle Dispersion The magnetic particle dispersion of the present invention is a magnetic particle dispersion described below. In the magnetic particle dispersion of the present invention, magnetic particles are dispersed in an aqueous medium. Here, the aqueous medium is not particularly limited, and examples thereof include water and water containing an aqueous solvent. Examples of the aqueous solvent include alcohols (for example, ethanol, alkylene glycol, monoalkyl ether, etc.). By applying a magnetic force to the magnetic particle dispersion of the present invention, the magnetic particles can be aggregated.

  The magnetic particle dispersion of the present invention is a dispersion of magnetic particles having a large surface area per unit weight due to a small average particle diameter and excellent magnetic separation.

1.1. Magnetic particles 1.1.1. Physical Properties of Magnetic Particles The number average particle diameter d of the magnetic particles in the magnetic particle dispersion of the present invention is 0.01 μm to 10 μm, preferably 0.1 μm to 5 μm, and most preferably 0.5 μm to 3 μm. When the number average particle size is less than 0.01 μm, the magnetic separation property may be inferior. On the other hand, when the number average particle size is more than 10 μm, the surface area per unit weight may be reduced, resulting in inferior sensitivity as diagnostic agent particles. In the present invention, the number average particle diameter of the magnetic particles can be measured by a known method. For example, the number average particle diameter of the magnetic particles can be obtained by measuring the size of the magnetic particles from an electron micrograph. Further, when the magnetic particles are non-spherical, the number average particle diameter is calculated with the average value of the major axis and the minor axis as the particle diameter of one particle.

  In the magnetic particles in the magnetic particle dispersion of the present invention, the volume fraction of particles having a particle size of 2d or more is 2 to 70%, preferably 5 to 60%, and most preferably 10 to 50%. When the volume fraction of particles having a particle size of 2d or more is less than 2%, the magnetic separation property may be inferior. On the other hand, when the volume fraction exceeds 70%, the sensitivity as a diagnostic agent particle may be inferior.

  The magnetic particles in the magnetic particle dispersion of the present invention have a particle volume fraction of 28-98%, preferably 39-95%, most preferably 50-90, with a particle size of more than 0.5d and less than 2d. %. When the volume fraction of particles having a particle size larger than 0.5d and smaller than 2d is less than 28%, the sensitivity as a diagnostic agent particle may be inferior, while when it exceeds 98%, the magnetic separation property may be inferior.

  In the magnetic particles in the magnetic particle dispersion of the present invention, the volume fraction of particles having a particle size of 0.5 d or less is 2% or less, preferably 1% or less, preferably 0.5% or less. More preferably. When the volume fraction of particles having a particle size of 0.5 d or less exceeds 2%, the magnetic separation property may be inferior.

  Here, the volume fraction of the magnetic particles having a particle size contained in the magnetic particle dispersion of the present invention in a predetermined range can be calculated by a known method. For example, the volume of each magnetic particle is calculated from the size of each magnetic particle obtained from an electron micrograph, the volume of magnetic particles having a particle size within a predetermined range is integrated, and the magnetic particle dispersion of the present invention is added. By dividing by the total volume of all the contained magnetic particles, the volume fraction of magnetic particles having a particle size in a predetermined range can be obtained.

  When the magnetic particle dispersion of the present invention is magnetically separated and observed with a microscope, magnetic particles having a large particle diameter and magnetic particles having a small particle diameter are mixed together to form a thread-like aggregate. Can be confirmed. According to the magnetic particle dispersion of the present invention, it is considered that the magnetic particles having a large particle size with a short magnetic separation time increase the moving speed of the filamentous aggregate in the filamentous aggregate. For this reason, the magnetic particle dispersion of the present invention is excellent in magnetic separation.

  In the magnetic particle dispersion of the present invention, the number average particle diameter d of the magnetic particles is 0.01 to 10 μm, and among the magnetic particles, the volume fraction of particles having a particle diameter of 2d or more is 2 to 70%. And the volume fraction of particles having a particle size larger than 0.5d and smaller than 2d is 28 to 98%, and the volume fraction of particles having a particle size of 0.5d or less is 2% or less. Since the average particle size can be reduced, the surface area per unit weight can be increased. Therefore, according to the magnetic particle dispersion of the present invention, it is possible to achieve both a reduction in average particle size and excellent magnetic separation properties.

1.1.2. Production of magnetic particles In order to obtain the magnetic particle dispersion of the present invention, for example, magnetic particles having a number average particle diameter d and magnetic particles having a number average particle diameter of 2d or more may be separately produced and then mixed. Or you may produce | generate two or more types of magnetic particles from which a number average particle diameter differs in a series of manufacturing processes.

1.1.3. Internal composition and internal structure of magnetic particles 1.1.3a. The internal composition of the magnetic particles The composition of the magnetic particles in the magnetic particle dispersion of the present invention preferably includes magnetic fine particles having a primary particle size (single particle size) of 50 nm or less and a nonmagnetic organic substance. More preferably, it consists of magnetic fine particles having a primary particle size of 30 nm or less and a nonmagnetic organic substance. If the magnetic particles in the magnetic particle dispersion of the present invention contain magnetic fine particles having a primary particle size exceeding 50 nm, the redispersibility after magnetic separation may be inferior.

The composition of the magnetic fine particles having a primary particle size of 50 nm or less 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 or the like), magnetite represented by Fe ₃ O ₄ , or 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. Such magnetic fine particles having a primary particle size of 50 nm or less can be industrially obtained as a magnetic fluid.

  The non-magnetic organic substance is preferably a polymer (polymer compound), and the contents thereof are disclosed in JP-A-9-208788, JP-A-61-93603, JP-A-2004-205481, and the like. ing. In any production method, the particle surface layer is preferably coated with a polymer.

  The polymer that can be used as the non-magnetic organic substance is particularly preferably a vinyl polymer, and the vinyl monomer used for the production thereof is an aromatic vinyl monomer such as styrene, α-methylstyrene, halogenated styrene, or divinylbenzene. , Vinyl esters such as vinyl acetate and 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 Ethylene unsaturated compounds such as methacrylate, ethylene glycol diacrylate, ethylene glycol dimethacrylate, cyclohexyl acrylate, cyclohexyl methacrylate, etc. The like can be exemplified carboxylic acid alkyl ester. The vinyl polymer may be a homopolymer or a copolymer composed of two or more monomers selected from the vinyl monomers.

  In addition, vinyl monomers and conjugated diolefins such as butadiene and isoprene, mono- or dicarboxylic acid compounds such as acrylic acid, methacrylic acid, itaconic acid, maleic acid, and crotonic acid, acrylamide, methacrylamide, glycidyl acrylate, glycidyl methacrylate, N-methylolacrylamide, N-methylolmethacrylamide, N-isopropylacrylamide, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, glycerol monoacrylate, glycerol monomethacrylate, ethylene glycol Diacrylate, ethylene glycol dimethacrylate, polyethylene glycol having 2 to 40 chains, or (Meth) acrylate having polypropylene glycol as a side chain, diallyl phthalate, allyl acrylate, allyl methacrylate, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, styrenesulfonic acid and its sodium salt, 2-acrylamido-2-methylpropanesulfone Copolymers with copolymerizable monomers such as acid and its sodium salt, isoprene sulfonic acid and its sodium salt can also be used.

  Polymers that can be used as non-magnetic organic substances require a copolymerizable monomer as the main raw material and a polymerization initiator, emulsifier, dispersant, surfactant, electrolyte, cross-linking agent, molecular weight regulator, etc. as auxiliary raw materials. It is formed by performing polymerization in a liquid added accordingly. By forming the polymer by polymerization in this way, it is possible to introduce a desired functional group onto the surface of the polymer, and the surface processability is excellent.

  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 a large amount of new particles in which only a hydrophobic polymerization monomer not containing magnetic material-coated particles is polymerized are generated. Examples of oil-soluble polymerization initiators include benzoyl peroxide, lauroyl peroxide, tertiary butyl peroxy 2-ethylhexanate, 3,5,5-trimethylhexanoyl peroxide, azobisisobutyronitrile and other peroxide compounds or azo compounds. Can be mentioned. Examples of the water-soluble initiator include persulfates such as potassium persulfate, ammonium persulfate, and sodium persulfate, hydrogen peroxide, 2,2-azobis (2-aminopropane) mineral acid salt, azobiscyanovaleric acid and alkali metal salts thereof. And ammonium salts, and redox initiators that combine persulfate, hydrogen peroxide salt with sodium bisulfite, sodium thiosulfate, ferrous chloride, etc. It is done. The ratio of these polymerization initiators to the whole monomer is preferably in the range of 0.01 to 8% by weight.

  As the non-magnetic organic substance, a silane coupling agent and a surfactant used as a surface treatment agent for the magnetic fine particles are also preferable. Specifically, an industrially available surface-treated magnetic fluid is used. By drying, pulverizing and sphering to a desired particle size, magnetic particles in which magnetic particles and non-magnetic organic substances (silane coupling agent or surfactant) are combined can be obtained.

  By subjecting the magnetic fine particles to a surface treatment using a silane coupling agent or a surfactant, the surface of the magnetic fine particles can be hydrophobized. As a result, it is excellent in chemical resistance, especially alkali resistance, and the magnetic performance is lowered when the magnetic fine particles are peeled off from the magnetic particles during use as a diagnostic agent, and the detached magnetic fine particles float in the diagnostic reagent reaction solution. This makes it possible to effectively prevent contamination from occurring. In the present invention, it can be said that the hydrophobized magnetic fine particles are sufficiently hydrophobized when they can be satisfactorily 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, dodecyltrimethoxy Silane, hexyltrimethoxysilane, methyltrimethoxysilane, methyltriethoxysilane, phenyltrimethoxysilane, dodecyltrichlorosilane, hexyltrichlorosilane, methyltrichlorosilane, phenyltrichlorosilane, etc. There is.

  As a method for bonding these silane compounds to magnetic fine particles, for example, the magnetic fine particles 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 fine particles 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 fine particles and the silane compound may be directly mixed and heated to bond both. In these means, the heating temperature is usually 30 to 100 ° C., and the heating temperature is about 0.5 to 2 hours. The amount of the silane compound used is appropriately determined depending on the surface area of the magnetic fine particles, but is usually 1 to 50 parts by weight, preferably 2 to 30 parts by weight with respect to 100 parts by weight of the magnetic fine particles.

  As the surfactant, a commonly used anionic surfactant or nonionic surfactant can be used alone or in combination. For example, as an anionic surfactant, long chain (C8-24) saturated hydrocarbon carboxylic acid (salt), long chain (C8-24) unsaturated hydrocarbon carboxylic acid (salt), higher alcohol sulfate alkali metal Salt, alkali metal salt of alkylbenzene sulfonic acid, alkali metal salt of succinic acid dialkyl ester sulfonic acid, alkali metal salt of alkyl diphenyl ether disulfonic acid, polyoxyethylene alkyl (or alkylphenyl) ether sulfate ester salt, polyoxyethylene alkyl ( Alternatively, phosphoric acid ester salts of alkylphenyl) ethers, formalin condensates of sodium naphthalene sulfonate, and the like.

  Examples of nonionic surfactants include polyoxyethylene alkyl ether and polyoxyethylene alkylphenyl ether.

  The method for adding the monomer to the polymerization system in the formation of a polymer that can be used as a non-magnetic organic substance is not particularly limited, and may be any of a batch method, a divided 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. In addition, after the formation of the polymer, the functional group can be modified by a method such as alkali hydrolysis of ethylenically unsaturated carboxylic acid alkyl ester or alkali saponification of vinyl ester.

1.1.3b. Internal structure and production of magnetic particles The internal structure of magnetic particles having an inhomogeneous internal composition is not particularly limited. For example, a structure in which magnetic fine particles are dispersed in a continuous phase of a nonmagnetic organic substance, Examples include a structure in which the secondary aggregate is a core and a non-magnetic organic substance is a shell, and a structure in which a non-magnetic organic substance is a core and the secondary aggregate of magnetic fine particles is a shell. That is, in the magnetic particles constituting the magnetic particle dispersion of the present invention, magnetic fine particles can be dispersed in all or part of the magnetic particles.

  As a preferable method for producing magnetic particles having a structure in which magnetic fine particles are dispersed in a continuous phase of a nonmagnetic organic substance, for example, the method disclosed in JP-A-9-208788 can be mentioned.

  As a preferred method for producing magnetic particles having a structure in which a nonmagnetic organic substance is used as a core and a secondary aggregate of magnetic fine particles is used as a shell, for example, Japanese Patent Application Laid-Open Nos. 61-93603 and 2004-205481 are disclosed. And the method disclosed in the above. More specifically, for example, first, a magnetic particle is physically adsorbed on the surface of the core by mixing a core (mother particle) made of a nonmagnetic organic substance and a magnetic particle. In the present invention, the physical adsorption method refers to an adsorption method that does not involve a chemical reaction.

  In order to adsorb the magnetic fine particles on the surface of the mother particle, a method of realizing the composite by applying a physically strong force from the outside is also effective. 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, a hybridizer, or the like using a high-speed air current impact method.

  In order to efficiently and strongly adsorb the magnetic fine particles on the surface of the base particle, for example, the peripheral speed of the stirring blade is preferably 15 m / second or more, more preferably 30 m / second or more, more preferably in a vessel with a stirring blade. Can be mixed with mother particles and magnetic fine particles by stirring at 40 to 150 m / sec. When the peripheral speed of the stirring blade is lower than 15 m / sec, it may not be possible to obtain sufficient energy to form a layer made of magnetic fine particles on the surface of the mother particle. 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.

  The magnetic particles are composed of magnetic fine particles having a primary particle diameter of 50 nm or less and a non-magnetic organic substance, the number average particle diameter d is 0.01 to 10 μm, and among the magnetic particles, the particle diameter is 2d or more. Particles having a volume fraction of 2 to 70%, a volume fraction of particles larger than 0.5d and smaller than 2d is 28 to 98%, and particles having a particle size of 0.5d or less. A magnetic particle dispersion having a volume fraction of 2% or less can also be obtained by a method in which two or more types of magnetic particles having a number average particle size of two or more different are produced separately by the above-mentioned method and then mixed. .

  As another method, two or more kinds of magnetic particles having a number average particle size that is two or more times different may be generated by a series of manufacturing steps, for example, physically strong disclosed in JP-A-2004-205481 By applying force from the outside, the magnetic fine particles and the polymer mother particles are combined by a method that combines the magnetic fine particles and the polymer mother particles, especially by using a high-speed air impact method such as a jet mill or a hybridizer. A secondary aggregate of magnetic particles having a particle size of 2d or more can be obtained as a by-product together with the magnetic particles.

  Further, for example, after the obtained magnetic particle dispersion is allowed to stand for a predetermined time, the upper layer is taken out by decantation, whereby a magnetic particle dispersion having a smaller particle diameter can be obtained. Alternatively, for example, a magnetic particle dispersion having a larger particle size can be obtained by dispersing the obtained magnetic particle dispersion in an aqueous solution containing a dispersing agent, allowing to stand for a predetermined time, and then removing the precipitated layer. it can. The magnetic particle dispersion of the present invention can be obtained by mixing the magnetic particle dispersion having a smaller particle diameter obtained by the above method and the magnetic particle dispersion having a larger particle diameter at a predetermined ratio. .

1.2. Applications One of the main applications of the magnetic particle dispersion of the present invention is diagnostic particles. In this application, it is required that the average particle size is small and the magnetic separation time is short. Since the magnetic particle dispersion of the present invention meets such requirements, it is suitable for diagnostic particles.

  As particles for diagnostic drugs, for example, an antigen such as protein or an antibody is bound to the magnetic particle dispersion of the present invention, and the turbidity change of the solution due to passive agglutination reaction based on the antibody or antigen-antibody reaction with the antigen is measured. Quantitative and qualitative detection applications used, antibody is bound to the magnetic particle dispersion of the present invention, and antigens such as viruses, bacteria, cells, hormones, dioxins, etc. are bound to the antibody to collect and concentrate Use, binding a nucleic acid analog such as DNA to the magnetic particle dispersion of the present invention, and using nucleic acid to bind the nucleic acid analog to the nucleic acid analog for recovery and detection, or a protein or dye that binds to the nucleic acid, etc. The chemical substance is bound to the nucleic acid analog for recovery / detection, avidin or biotin is bound to the magnetic particle dispersion of the present invention, For detection by binding biotin or avidin molecules to gin or biotin, and for detecting immunosorbents by binding antibodies or antigens to the magnetic particle dispersion of the present invention and using colorimetry or chemiluminescence Examples of the use of the magnetic particle dispersion of the present invention as the carrier of the present invention. Conventionally, any diagnostic item that uses a 96-well plate or the like as a carrier can be replaced with an automatic analyzer using magnetism by using the magnetic particle dispersion of the present invention. Substances to be diagnosed include biological proteins, hormones such as luteinizing hormone, thyroid stimulating hormone, various cancer cells, proteins that serve as cancer markers such as prostate-specific markers and bladder cancer markers, and hepatitis B virus Viruses such as hepatitis C virus and herpes simplex virus, bacteria such as Neisseria gonorrhoeae and MRSA, fungi such as Candida and cryptocox, protozoa and parasites such as Toxoplasma, or viruses, bacteria, fungi, protozoa and parasites Examples of such components include environmental pollutants such as proteins, nucleic acids, and dioxins, and chemical substances such as pharmaceuticals such as antibiotics and antiepileptics.

  In addition, the magnetic particle dispersion of the present invention is not limited to the above-mentioned use, and can be used in various fields such as paints, paper, electronic materials, electrophotography, cosmetics, pharmaceuticals, agricultural chemicals, foods, and catalysts. .

2. Examples Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto. In addition, the particle size and magnetic separation time of the magnetic particles in the magnetic particle dispersions obtained in the following Examples and Comparative Examples were measured by the following methods.

2.1. Measuring method 2.1.1. Measurement of particle diameter Using a transmission electron microscope (100SX manufactured by JEOL Ltd.), the magnetic particle dispersion to be measured is photographed, and the particle diameter of 300 magnetic particles constituting the magnetic particle dispersion is determined by a ruler. And the average was obtained as the number average particle diameter d. Further, among 300 magnetic particles, there are three groups of magnetic particles having a particle size of 2d or more, magnetic particles having a particle size of more than 0.5d and less than 2d, and magnetic particles having a particle size of 2d or less. The total volume of the magnetic particles in each group was calculated, and the total volume of the magnetic particles in each group was divided by the volume of all the magnetic particles to determine the volume fraction of the magnetic particles in each group.

2.1.2. Evaluation of magnetic separation time The obtained magnetic particle dispersion was diluted with water to prepare a test solution containing 0.01% by weight of the magnetic particle dispersion. This test solution is well dispersed and placed in a square optical cell having an optical path length of 1 cm, set in a spectrophotometer (manufactured by JASCO Corporation, model V-550), and a surface magnetic density of 2900 gauss is placed beside this cell holder The time until the absorbance at 550 nm was attenuated to the initial 50% was measured with the time when the neodymium magnet was placed as 0, and this time was defined as the magnetic separation time.

2.2. Comparative Example 1
With reference to the polymerization method described in JP-A-07-238105, a styrene / divinylbenzene = 80/20 copolymer (average particle size 1.5 μm) was polymerized and washed with water three times by centrifugation. 100 g of this hydrous slurry was dried with a dryer at 60 ° C. for 24 hours to obtain polymer mother particle powder.

  Acetone is added to an oily magnetic fluid (trade name: “EXP series”, manufactured by Ferrotec Co., Ltd.), which is a dispersion of magnetic fine particles having an average particle diameter of 20 nm, and the particles are precipitated and dried. As a result, a ferrite-based magnetic fine particle powder having a hydrophobized surface was obtained. The magnetic fine particle powder has a surface that has been hydrophobized with a silane coupling agent and a surfactant.

15 g of polymer mother particle powder and 15 g of the above-mentioned hydrophobized magnetic fine particle powder are mixed well with a mixer, and this mixture is used with a hybridization system NHS-O type (manufactured by Nara Machinery Co., Ltd.). Then, it was treated at a peripheral speed of 100 m / sec (16200 rpm) of the blade (stirring blade) for 5 minutes to obtain 30 g of a magnetic material-coated molecule. Next, 30 g of the obtained magnetic material-coated particles, a nonionic emulsifier (trade name: “Emulgen 150”, manufactured by Kao Corporation) 0.5% and an anionic emulsifier (trade name: “Emar 0”), as a dispersant, 750 g of an aqueous solution containing 0.5% (manufactured by Kao Corporation) was put into a 1 L separable flask and sufficiently dispersed. In a separate container, nonionic emulsifier (trade name: “Emulgen 150”, manufactured by Kao Corporation) 0.5% and anionic emulsifier (trade name: “Emar 0”, manufactured by Kao Corporation) 0.5% A 150 g aqueous solution containing 15 g of cyclohexyl methacrylate and 4 g of methacrylic acid as a monomer, and tertiary butyl peroxy 2-ethylhexanate as a polymerization initiator (trade name: “Perbutyl O”, manufactured by NOF Corporation) 0.5 g Were added and mixed to prepare a monomer emulsion. The reaction liquid in the separable flask was stirred at 200 rpm using a squid stirring blade and heated to 60 ° C. while purging with N ₂ gas, and then the monomer emulsion was added to the separable flask over 2 hours. Was added continuously. After completion of the continuous addition, stirring was continued at 80 ° C. for 2 hours to complete the reaction. Next, the total amount of the obtained polymer was magnetically purified. Subsequently, the dispersion prepared to a solid content concentration of 5% was allowed to stand at 25 ° C. for 18 hours, and then the upper layer was taken out by decantation. The body 20g was obtained. The number average particle diameter d of the magnetic particles in the magnetic particle dispersion produced in Comparative Example 1 was 2.1 μm, and the magnetic separation time was 20 seconds. In addition, the magnetic particle dispersion produced in this comparative example contains 0.0% by volume of magnetic particles having a particle size of 4.2 μm (2d) or more, and is 1.05 μm (0 Magnetic particles having a particle size of 99.9% in terms of volume fraction and having a particle size of 1.05 μm (0.5 d) or less and having a particle size larger than .5d) and smaller than 4.2 μm (2d) The particles contained 0.1% by volume.

2.3. Example 1
Using a hybridization system NHS-O type (manufactured by Nara Machinery Co., Ltd.), 15 g of the hydrophobized magnetic fine particle powder obtained during the manufacturing process of Comparative Example 1 was used. Was processed for 5 minutes at a peripheral speed of 100 m / sec (16200 rpm) to obtain a pulverized product of magnetic fine particles. Next, 10 g of the obtained magnetic fine particle powder pulverized product and 200 g of an aqueous solution containing 0.5% nonionic emulsifier (trade name: “Emulgen 120”, manufactured by Kao Corporation) as a dispersing agent in a beaker. The resulting mixture was sufficiently dispersed, magnetically purified, and further allowed to stand at 25 ° C. for 2 hours. Then, 1 g of a precipitate layer was taken out by decantation. When this was observed with an electron microscope, it was a secondary aggregate of magnetic particles having an average particle diameter of 6 μm. The magnetic separation time was 5 seconds.

  1 g of the secondary aggregate of magnetic particles and 3 g (solid content) of the magnetic particle dispersion obtained in Comparative Example 1 were mixed to obtain a new magnetic particle dispersion 4 g according to this example. The number average particle diameter d of the magnetic particles in the magnetic particle dispersion produced in this example was 2.1 μm, and the magnetic separation time was 16 seconds. In addition, the magnetic particle dispersion produced in this example contains 24.3% by volume of magnetic particles having a particle size of 4.2 μm (2d) or more, and is 1.05 μm (0 Magnetic particles having a particle size of 75.7% in terms of volume fraction and having a particle size of 1.05 μm (0.5 d) or less and having a particle size larger than .5d) and smaller than 4.2 μm (2d) The particles contained 0.1% by volume.

  From the above, it was confirmed that the magnetic particle dispersion produced in this example had a sufficiently small average particle size and excellent magnetic separation properties.

2.4. Example 2
In Example 1, 1 g of secondary aggregates of magnetic particles having an average particle diameter of 6 μm were mixed with 0.3 g (solid content) of the magnetic particle dispersion obtained in Comparative Example 1, and a new magnetic material according to this example was obtained. 1.3 g of a particle dispersion was obtained. The number average particle diameter d of the magnetic particles in the magnetic particle dispersion produced in this example was 2.3 μm, and the magnetic separation time was 10 seconds. In addition, the magnetic particle dispersion produced in this example contains 62.9% of the magnetic particles having a particle size of 4.6 μm (2d) or more in the volume fraction of 1.15 μm (0 Magnetic particles having a particle size of 37.0% in terms of volume fraction and having a particle size of 1.15 μm (0.5 d) or less and having a particle size larger than .5d) and smaller than 4.6 μm (2d) The particles contained 0.1% by volume. Compared with the magnetic particle dispersion of Example 1, the magnetic particle dispersion of this example had a faster sedimentation due to standing.

2.5. Comparative Example 2
Using a hybridization system NHS-O type (manufactured by Nara Machinery Co., Ltd.), 15 g of the hydrophobized magnetic fine particle powder obtained during the manufacturing process of Comparative Example 1 was used. Was processed for 5 minutes at a peripheral speed of 100 m / sec (16200 rpm) to obtain a pulverized product of magnetic fine particles. Next, 10 g of the obtained magnetic fine particle powder pulverized product and 200 g of an aqueous solution containing 0.5% nonionic emulsifier (trade name: “Emulgen 120”, manufactured by Kao Corporation) as a dispersing agent in a beaker. Was added and dispersed sufficiently. When this was observed with an electron microscope, it was mainly a mixture of magnetic particle aggregates having an average particle diameter of 0.8 μm and a small amount of magnetic particle aggregates having an average particle diameter of 6 μm. The magnetic separation time was 180 seconds.

  1 g of the magnetic particles and 5 g (solid content) of the magnetic particle dispersion obtained in Comparative Example 1 were mixed to obtain a new magnetic particle dispersion 6 g according to this example. The number average particle diameter d of the magnetic particles in the magnetic particle dispersion produced in this example was 1.3 μm, and the magnetic separation time was 120 seconds. In addition, the magnetic particle dispersion produced in this example contains 17.5% of the magnetic particles having a particle size of 2.6 μm (2d) or more in terms of volume fraction of 0.65 μm (0 Magnetic particles having a particle size of 76.2% in terms of volume fraction and having a particle size of 0.65 μm (0.5 d) or less and having a particle size larger than 0.5 d) and smaller than 2.6 μm (2 d) The particles contained 6.3% by volume fraction.

Claims (3)

A dispersion of magnetic particles having a number average particle diameter d of 0.01 to 10 μm,
Among the magnetic particles, the volume fraction of particles having a particle size of 2d or more is 2 to 70%, and the volume fraction of particles having a particle size larger than 0.5d and smaller than 2d is 28 to 98%. A magnetic particle dispersion in which the volume fraction of particles having a particle size of 0.5 d or less is 2% or less. In claim 1,
The magnetic particle dispersion is a magnetic particle dispersion comprising magnetic fine particles having a primary particle diameter of 50 nm or less and a nonmagnetic organic substance. A diagnostic drug particle using the magnetic particle dispersion according to claim 1.