Polymer-coated magnetic metal particles and method of manufacturing the same

Abstract

To increase carrying capacity of a carrier substance bindable to a target substance and keep magnetic susceptibility at or above a certain level.SOLUTION: A polymer-coated magnetic metal particle is provided, comprising: a magnetic metal particle; a coating layer made of a silicon oxide and provided on a surface of the magnetic metal particle; and a polymer layer provided on a surface of the coating layer, the polymer layer containing a polymer of an alkoxysilane having a structural unit represented by a formula (1) and an acrylic or methacrylic group.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to polymer-coated metal magnetic particles and a method for producing the same.

Background Art

[0002] In the field of medical diagnosis, it may be necessary to separate, collect, and examine target substances such as various proteins, nucleic acids, and cells from a sample liquid such as blood. As this inspection method, for example, there is a method in which a carrier substance suitable for each target substance is supported on the surface of predetermined particles, and the particles after capturing the target substance are collected and analyzed.

[0003] As the particles for supporting the carrier substance, particles having magnetism may be used. According to the particles having magnetism, after supporting the carrier substance and capturing the target substance, the target substance can be recovered by applying a magnetic field from the outside.

[0004] As such magnetic particles, for example, magnetic polymer particles in which the surface of core polymer particles is sequentially coated with a coating layer containing a nano-magnetic material and silicon oxide and a polymer layer capable of binding a carrier substance have been proposed (see, for example, Patent Document 1).

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] Regarding the above-described inspection particles, from the viewpoint of improving inspection accuracy, it is important to have a large loading amount capable of supporting a carrier substance capable of binding to a target substance. In addition, the inspection particles are required to have a high saturation magnetization and to gather in a short time when a magnetic field is applied, that is, to have a high magnetic aggregability.

[0007] In this regard, even though a high loading amount could be achieved with the particles of Patent Document 1 described above, since the core is a polymer particle, the saturation magnetization tends to be low, and it may not be possible to obtain the desired magnetic aggregation property.

[0008] Therefore, an object of the present invention is to provide a technique for increasing the loading amount of a carrier substance capable of binding to a target substance and making the magnetic aggregation property equal to or more than a certain level.

Means for Solving the Problem

[0009] The first aspect of the present invention is metal magnetic particles, a coating layer provided on the surface of the metal magnetic particles and composed of silicon oxide, a polymer layer provided on the surface of the coating layer and containing a polymer of a structural unit represented by the formula (1) and an alkoxysilane having an acrylic group or a methacrylic group, polymer-coated metal magnetic particles.

Chemical Formula

[0010] The second aspect of the present invention is, in the first aspect, in the formula (1), R 2 is an ethylene group, and R 3 is an alkylene group, a phenylene group, or a cyclohexylene group.

[0011] The third aspect of the present invention is, in the second aspect, R 3 in the formula (1) is a phenylene group.

[0012] The fourth aspect of the present invention is, in any one of the first to third aspects, The alkoxysilane has an acrylic group or a methacrylic group and an alkylene group having 3 to 6 carbon atoms.

[0013] In a fifth aspect of the present invention, in the fourth aspect, The alkoxysilane has an acryloxypropyl group or a methacryloxypropyl group.

[0014] In a sixth aspect of the present invention, in any one of the first to fifth aspects, The metal magnetic particles are iron particles or iron-based alloy particles.

[0015] In a seventh aspect of the present invention, in any one of the first to sixth aspects, The saturation magnetization is 100 Am 2 / kg or more and 210 Am 2 / kg or less.

[0016] In an eighth aspect of the present invention, in any one of the first to seventh aspects, The volume-based cumulative 50% particle diameter measured by a laser diffraction particle size distribution measuring device is 0.2 μm to 10 μm.

[0017] In a ninth aspect of the present invention, in any one of the first to eighth aspects, The C content is 0.5% by mass or more and 10% by mass or less.

[0018] In a tenth aspect of the present invention, in any one of the first to ninth aspects, The C content is 0.1% by mass or more and 10% by mass or less.

[0019] An eleventh aspect of the present invention is A method for producing polymer-coated metal magnetic particles, comprising: A step of forming a coating layer composed of silicon oxide on the surface of the metal magnetic particles; After mixing the metal magnetic particles with the coating layer formed thereon, water, and an alkoxysilane having an acrylic group or a methacrylic group, a compound represented by the formula (2) is added and polymerized to form a polymer layer on the coating layer. Method for producing polymer-coated metal magnetic particles.

Chemical formula

[0020] The 12th aspect of the present invention is, in the 11th aspect, In the formula (2), R 2 is an ethylene group, and R 3 is an alkylene group, a phenylene group, or a cyclohexylene group.

[0021] The 13th aspect of the present invention is, in the 12th aspect, R 3 in the formula (2) is a phenylene group.

[0022] The 14th aspect of the present invention is, in any one of the 11th to 13th aspects, The alkoxysilane has an acrylic group or a methacrylic group and an alkylene group having 3 to 6 carbon atoms.

[0023] The 15th aspect of the present invention is, in the 14th aspect, The alkoxysilane has an acryloxypropyl group or a methacryloxypropyl group.

[0024] The 16th aspect of the present invention is, in any one of the 11th to 15th aspects, The metal magnetic particles are iron particles or iron-based alloy particles.

[0025] The 17th aspect of the present invention is as follows in any one of the 11th to 16th aspects: In the step of forming the polymer layer, a water-soluble azo polymerization initiator having a carboxyl group is used as the polymerization initiator.

Effects of the Invention

[0026] In the inspection particles, it is possible to increase the loading amount of the carrier substance capable of binding to the target substance and to make the superparamagnetism equal to or more than a certain level.

Modes for Carrying Out the Invention

[0027] <An Embodiment of the Present Invention> Hereinafter, a polymer-coated metal magnetic particle and a method for producing the same according to an embodiment of the present invention will be described. In this specification, a numerical range represented by "~" means a range including the numerical values described before and after "~" as the lower limit value and the upper limit value.

[0028] (1) Polymer-Coated Metal Magnetic Particles The polymer-coated metal magnetic particle of the present embodiment is configured such that a coating layer and a polymer layer are laminated in this order on the surface of the metal magnetic particle. Hereinafter, the polymer-coated metal magnetic particle is also simply referred to as an inspection particle.

[0029] (Metal Magnetic Particles) The metal magnetic particle is the core of the inspection particle and is a ferromagnetic particle composed of a metal or an alloy. As the metal magnetic particle composed of a pure metal, for example, iron particles, nickel particles, or cobalt particles can be used. As the metal magnetic particle composed of an alloy, for example, iron-based alloy particles can be used. In this specification, the iron-based alloy refers to an alloy containing 50% by mass or more of iron. As the iron alloy iron-based alloy particles, for example, Fe-B-based alloy particles, Fe-Si-based alloy particles, Fe-N-based alloy particles, Fe-Ni-based alloy particles, Fe-C-based alloy particles, etc. can be used. From the viewpoint of ensuring excellent saturation magnetization of the inspection particles, it is preferable to use iron particles or iron-based alloy particles as the metal magnetic particles.

[0030] The particle diameter of the metal magnetic particles is preferably 0.2 μm to 10.0 μm. According to the test particles provided with such metal magnetic particles, when added to a sample solution, the self-weight and buoyancy of the test particles can be balanced, and appropriate dispersibility in the sample solution can be realized. As a result, the attachment of the carrier substance to the test particles and the binding of the target substance to the carrier substance can be performed more reliably. Here, the particle diameter refers to the volume-based cumulative 50% particle diameter measured by a laser diffraction particle size distribution analyzer. Hereinafter, the particle diameter indicates a numerically measured in the same manner.

[0031] (Coating layer) The coating layer is provided on the surface of the metal magnetic particles and is composed of silicon oxide. The coating layer acts to cover the metal magnetic particles and suppress the elution of the metal component from the metal magnetic particles when forming the polymer layer.

[0032] The thickness of the coating layer is not particularly limited. However, if it is excessively thin, it may not be able to uniformly cover the surface of the metal magnetic particles. Therefore, from the viewpoint of more reliably suppressing the elution of components from the metal magnetic particles during the formation of the polymer layer, the thickness of the coating layer is preferably 1 nm or more. On the other hand, if the coating layer is excessively thick, the magnetic properties of the test particles, such as saturation magnetization and coercive force, may decrease. Therefore, from the viewpoint of maintaining high magnetic properties, the thickness of the coating layer is preferably 80 nm or less. The thickness of the coating layer can be measured, for example, by observing the cross-section of the coating layer with a transmission electron microscope (TEM) or a scanning electron microscope (SEM) and taking the average film thickness. Specifically, a TEM photograph or SEM photograph of the cross-section can be taken, and the average film thickness can be obtained from the average value of 50 measurement points for any particle.

[0033] (Polymer layer) The polymer layer is provided on the surface of the coating layer. The polymer layer contains a polymer of a structural unit represented by formula (1) and an alkoxysilane having an acrylic group or a methacrylic group, and is configured to be capable of binding to a carrier substance that captures a target substance. Here, the target substance is, for example, a substance to be examined such as a protein, nucleic acid, or cell contained in blood. The carrier substance is not particularly limited as long as it can capture the target substance, and can be appropriately changed according to the type of the target substance. As the carrier substance, for example, streptavidin, protein A, protein G, an antibody, or the like can be used.

[0034]

Chemical formula

[0035] The polymer has a carboxyl group (—COOH group) at the end of the structural unit of formula (1), and binds to the carrier substance through the carboxyl group. Further, as shown in formula (1), the polymer has R 2 and R 3 in its chemical structure, and its molecular chain is long and bulky. Therefore, the polymer is likely to bind to a carrier substance having a large molecular size such as streptavidin. That is, according to the polymer layer, the amount (loading amount) of the carrier substance attached to the surface can be increased. Regarding the alkylene groups of R 2 and R 3 , when the number of carbon atoms of each is 1, there is a concern that the molecular chain becomes short and the loading amount becomes small, so it is not preferable. When the number of carbon atoms of each is 7 or more, the hydrophobicity increases and it becomes difficult to carry out the polymerization reaction in the polymer layer formation step, and there is a possibility that the productivity decreases, so it is not preferable.

[0036] In the structural unit of formula (1), R 2 is an ethylene group, and R 3is preferably an alkylene group or a phenylene group. Also, R 3 is more preferably a phenylene group. According to such a structural unit, while forming the polymer more stably, the loading amount of the carrier substance can be more surely increased.

[0037] The silane coupling agent for forming the polymer is not particularly limited as long as it is an alkoxysilane having an acrylic group or a methacrylic group so that it can polymerize with the compound of formula (2). In the polymer layer, from the viewpoint of more surely increasing the loading amount of the carrier substance, it is preferable that the silane coupling agent has a long molecular chain and a bulky chemical structure. Specifically, the silane coupling agent is preferably an alkoxysilane having an acrylic group or a methacrylic group and an alkylene group having 3 to 6 carbon atoms. Also, from the viewpoint of enhancing the reactivity with the compound of formula (2) and polymerizing the polymer more surely, it is preferable that the silane coupling agent has an acryloxypropyl group or a methacryloxypropyl group.

[0038] (C content) The amount of the polymer contained in the test particles can be simply quantitatively evaluated as the C content. The C content of the test particles is preferably 0.1% by mass to 10% by mass, and may be 0.5% by mass to 10% by mass from the viewpoint of ensuring high magnetic properties. If the C content is excessively low, the surface of the coating layer cannot be uniformly covered with the polymer layer, and the loading amount of the carrier substance may not be maintained high. On the other hand, if the C content becomes excessively high, the ratio of the magnetic component in the test particles becomes low, and the magnetic properties may not be maintained high. In this regard, by setting the C content within the above range, the loading amount of the carrier substance and the magnetic properties can be realized well in balance at a high level. The C content indicates the content of carbon derived from the polymer layer in 100 parts by mass of the test particles (polymer-coated metal magnetic particles). The C content can be measured using a carbon-sulfur analyzer as described later in the examples, for example.

[0039] (Particle size) The particle size of the inspection particles is not particularly limited, but is preferably 0.2 μm to 10 μm. When the particle size becomes smaller, the volume of the magnetic particles also becomes smaller, and it becomes difficult to obtain the magnetic aggregability when a magnetic field is applied, which is not preferable. On the other hand, if the particle size becomes too large, the inspection particles tend to settle in the solution, which is not preferable.

[0040] (Characteristic) The inspection particles of the present embodiment are configured by sequentially laminating a coating layer and a polymer layer on the surface of metal magnetic particles as the core. Thereby, the inspection particles exhibit the following characteristics.

[0041] In the inspection particles, the polymer layer contains a polymer of a structural unit represented by the formula (1) and an alkoxysilane having an acrylic group or a methacrylic group, and is likely to bind to a carrier substance that captures a target substance. That is, the inspection particles are configured so that the amount of the carrier substance supported increases. Specifically, streptavidin is supported on the inspection particles as a carrier substance, and ALP-biotin (alkaline phosphatase-biotin) and a luminescent dye (for example, Lumiphos Plus) are bound to 50 μg of the streptavidin-immobilized particles, and the luminescence intensity is measured. A calibration curve showing the correlation between the luminescence intensity and the ALP-biotin concentration is created, the ALP-biotin concentration is calculated from the luminescence intensity, and the biotin binding amount is obtained. The inspection particles of the present embodiment have a large biotin binding amount and excellent carrier substance supporting ability.

[0042] In addition, since the core of the inspection particles is metal magnetic particles, for example, compared with magnetic polymer particles in which the core is polymer particles and magnetic particles are attached to the periphery thereof, the ratio of the magnetic component in the particles is configured to be high. Therefore, the inspection particles have a high saturation magnetization. Specifically, the saturation magnetization of the inspection particles is preferably 100 Am 2 / kg or more. The upper limit value is not particularly limited, but for example, it may be 210 Am 2 / kg or less. According to the inspection particles having such a saturation magnetization, the magnetic aggregability is high, and the time for recovering the inspection particles by applying a magnetic field can be shortened. The method for measuring the saturation magnetization will be described in detail in the examples.

[0043] In addition, since the core of the inspection particles is composed of metal magnetic particles, the inspection particles are configured to have a lower coercive force than the magnetic polymer particles. Specifically, the coercive force Hc of the inspection particles is preferably 20 Oe or less. The lower limit is not particularly limited, but is, for example, 3 Oe or more. According to the inspection particles having such a coercive force, the dispersibility of the particles can be enhanced.

[0044] (2) Method for producing polymer-coated metal magnetic particles Next, the method for producing polymer-coated metal magnetic particles will be described. The production method of the present embodiment includes a preparation step, a coating layer formation step, and a polymer layer formation step. Hereinafter, each step will be described in detail.

[0045] (Preparation step) First, metal magnetic particles serving as the core are prepared. The saturation magnetization of the metal magnetic particles to be prepared is preferably 100 A·m 2 / kg or more and 210 A·m 2 / kg or less. Further, from the viewpoint of ensuring excellent saturation magnetization of the obtained inspection particles, it is preferable to use iron particles or iron-based alloy particles as the metal magnetic particles.

[0046] (Coating layer formation step) Subsequently, a coating layer composed of silicon oxide is formed on the surface of the metal magnetic particles. As this formation method, for example, the sol-gel method can be adopted.

[0047] Specifically, first, metal magnetic particles are added to a solvent containing water to obtain a slurry in which the metal magnetic particles are dispersed. Subsequently, while stirring this slurry, silicon alkoxide is added thereto. The silicon alkoxide generates a silanol derivative by hydrolysis of the alkoxy group due to the action of water. The addition amount of the silicon alkoxide is preferably 0.1 part by mass to 5.0 parts by mass as Si mass with respect to 100 parts by mass of the metal magnetic particles. The silanol derivative adheres to the surface of the metal magnetic particles to form a reaction layer. Subsequently, after a predetermined time has elapsed since the addition of the silicon alkoxide, while stirring the solvent containing the slurry, a hydrolysis catalyst is added. Thereby, the alkoxy group remaining in the silanol derivative is hydrolyzed. Also, together with the addition of the hydrolysis catalyst, the solvent is heated. By heating, the silanol derivative condenses or polymerizes to form a polysiloxane structure, and further heating forms silica (SiO2). Then, the solvent is dried to obtain silica-coated particles having a coating layer composed of silicon oxide formed on the surface of the metal magnetic particles.

[0048] As the silicon alkoxide, conventionally known ones can be used. For example, trimethoxysilane, tetramethoxysilane, triethoxysilane, tetraethoxysilane, tripropoxysilane, tetrapropoxysilane, tributoxysilane, tributoxysilane, etc. can be used.

[0049] From the viewpoint of suppressing the dissolution of the metal component constituting the metal magnetic particles, it is preferable to use an alkali catalyst as the hydrolysis catalyst. As the alkali catalyst, for example, aqueous ammonia can be used.

[0050] In addition, the addition amounts of the silicon alkoxide and the hydrolysis catalyst, and the reaction times of the silicon alkoxide and the hydrolysis catalyst may be appropriately changed according to the thickness of the coating layer. For example, they may be appropriately adjusted so that the thickness of the coating layer is 1 nm to 80 nm. Further, from the viewpoint of the reactivity of hydrolysis of the silicon alkoxide and the adhesion of the silanol derivative to the surface of the metal magnetic particles, the heating temperature of the solvent containing the slurry may be, for example, 20°C to 70°C. As the solvent, only water or a mixed solvent containing water and an organic solvent can be used.

[0051] (Polymer layer forming step) Subsequently, a polymer layer is formed on the surface of the silica-coated particles.

[0052] Specifically, first, the silica-coated particles and a solvent containing water are mixed to prepare a dispersion. Subsequently, while stirring this dispersion, an alkoxysilane having an acrylic group or a methacrylic group is added as a silane coupling agent and mixed. It is considered that the alkoxy group of the alkoxysilane is hydrolyzed by reaction with water and binds to the coating layer composed of silicon oxide. After adding the silane coupling agent, preferably an alkali such as NaOH or NH3 is added to adjust the pH of the solution to 8 or higher, and then the compound represented by the formula (2) is added. This addition of alkali has the effect of improving the reactivity of the silane coupling agent and the solubility of the compound of the formula (2) in water. Starting from the silane coupling agent bonded to the coating layer, the acrylic group or methacrylic group of this silane coupling agent binds to the acrylic group or methacrylic group in the chemical structure of the compound of the formula (2), or the acrylic group or methacrylic group in the unbonded silane coupling agent, whereby a polymer layer is considered to be formed. The polymer constituting the polymer layer has the structural unit represented by the above formula (1) and the chemical structure derived from the silane coupling agent.

[0053] [Chemical formula] In the formula (2), R 1 represents a hydrogen atom or a methyl group, and R 2represents a linear or branched alkylene group having 2 to 6 carbon atoms, and R 3 represents an alkylene group having 2 to 6 carbon atoms, a cyclohexylene group, or a phenylene group. For the alkylene groups of R 2 and R 3 when each has 1 carbon atom, there is a concern that the molecular chain becomes short and the loading amount of the carrier substance decreases, so it is not preferable. When each has 7 or more carbon atoms, the hydrophobicity increases and it becomes difficult to carry out the polymerization reaction, which may lead to a decrease in productivity, so it is not preferable.

[0054] As the compound of formula (2), from the viewpoints of reactivity with the silane coupling agent and enhancing the bonding property between the polymer layer and the carrier substance to increase the loading amount, R 2 is preferably an ethylene group, and R 3 is preferably an alkylene group or a phenylene group. From the viewpoint of further increasing the loading amount of the carrier substance on the polymer layer, as shown in the examples described later, R 3 is more preferably a phenylene group.

[0055] As the silane coupling agent, an alkoxysilane having an acrylic group or a methacrylic group is used so that it can polymerize with the compound of formula (2). In the polymer layer, from the viewpoint of more surely increasing the loading amount of the carrier substance, this alkoxysilane preferably has a long molecular chain and a bulky chemical structure. Specifically, it preferably has an acrylic group or a methacrylic group and an alkylene group having 3 to 6 carbon atoms. Also, from the viewpoint of enhancing the reactivity with the compound of formula (2) and more surely polymerizing the polymer, this alkoxysilane preferably has an acryloxypropyl group or a methacryloxypropyl group.

[0056] The addition amounts of the silane coupling agent and the compound of formula (2) may be adjusted within a range where the polymer layer can be formed to a desired thickness. For example, the addition amount of the silane coupling agent is preferably 0.1 part by mass to 40 parts by mass, more preferably 5.0 parts by mass to 40 parts by mass, still more preferably 15 parts by mass to 40 parts by mass, and may be 0.1 part by mass to 10 parts by mass, based on 100 parts by mass of the metal magnetic particles having the coating layer. By setting the addition amount of the silane coupling agent to 15 parts by mass to 40 parts by mass based on 100 parts by mass of the metal magnetic particles having the coating layer, the storage stability of the metal magnetic particles can be enhanced. Also, the addition amount of the compound of formula (2) is preferably 100 parts by mass to 700 parts by mass, and may be 100 parts by mass to 500 parts by mass, based on 100 parts by mass of the metal magnetic particles having the coating layer. Further, the addition amount of the compound of formula (2) is preferably 10 to 100 times as much as the addition amount of the silane coupling agent in terms of mass. Note that the storage stability indicates a stability such that the carrier substance supported on the polymer-coated metal magnetic particles can be maintained in a supported state without desorbing even after the passage of time. Specifically, the maintenance rate α of the supported amount, which is an index of the storage stability, is calculated as α = B / A × 100 [%], where A is the initial supported amount when the carrier substance is supported on the polymer-coated metal magnetic particles, and B is the supported amount after the passage of a predetermined time. When the storage stability is high, it indicates that the supported amount B after the passage of a predetermined time does not vary significantly from the initial supported amount A. The maintenance rate α is not particularly limited, but may be, for example, 30% or more.

[0057] When forming the polymer, it is preferable to add the polymerization initiator after adding the compound of formula (2). By adding the polymerization initiator, the bonding between the silane coupling agent and the compound of formula (2) can be further promoted. From the viewpoint of reactivity, it is preferable to use a water-soluble azo polymerization initiator having a carboxyl group as the polymerization initiator. Note that the addition amount of the polymerization initiator is preferably 10 parts by mass to 100 parts by mass, based on 100 parts by mass of the metal magnetic particles having the coating layer.

[0058] After the polymerization reaction is completed, the test particles with a polymer layer formed on the surface of the coating layer are recovered from the solvent using, for example, a magnet and washed. Thereby, the test particles of the present embodiment are obtained.

[0059] The method for measuring a target substance using the above-described test particles is as follows, for example. First, a carrier substance is bound to the test particles to obtain carrier substance-immobilized particles. These carrier substance-immobilized particles are added to a sample solution. Subsequently, the target substance contained in the sample solution is captured by the carrier substance-immobilized particles. Then, the carrier substance-immobilized particles dispersed in the sample solution are collected and recovered by magnetism. And the target substance captured by the recovered carrier substance-immobilized particles is measured by a conventionally known method.

[0060] As described above, the embodiments of the present invention have been specifically described, but the present invention is not limited to the above-described embodiments, and various modifications can be made without departing from the gist thereof.

Example

[0061] Next, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples. In this example, a coating layer and a polymer layer were formed on the surface of metal magnetic particles to produce polymer-coated metal magnetic particles.

[0062] <Example 1> (1) Preparation of polymer-coated metal magnetic particles First, as the metal magnetic particles, carbonyl iron powder (manufactured by BASF, HS grade D50: 2.3 μm) was prepared.

[0063] Subsequently, a coating layer composed of silicon oxide was formed on the surface of carbonyl iron powder. Specifically, first, 5451 g of isopropyl alcohol and 820 g of pure water were added to a 10 L reaction vessel and stirred in a nitrogen atmosphere. 1650 g of carbonyl iron powder (hereinafter also referred to as Fe particles) was added to this solution and stirred at 40°C. Subsequently, 257.4 g of tetraethoxysilane (manufactured by Wako Pure Chemical Industries, Ltd.) and 50 g of isopropyl alcohol were added and stirred as it was for 5 minutes. Thereafter, 567.3 g of 25% by mass aqueous ammonia was added over 90 minutes. Simultaneously with the start of the addition of the aqueous ammonia, a liquid feeding pump was operated to feed the liquid to a high-pressure homogenizer (manufactured by SMT Co., Ltd., LAB1000). Simultaneously with the liquid feeding, the high-pressure homogenizer was set to a pressure of 150 bar to perform a dispersion treatment. The reaction liquid after the dispersion treatment was set to return to the 10 L reaction vessel. After the addition of the aqueous ammonia, it was stirred as it was for 60 minutes. The dispersion treatment was carried out until the reaction was completed. The obtained slurry was filtered, and the cake was dried in nitrogen at 110°C. As a result, silica-coated particles having a coating layer of silicon oxide formed on the surface of the carbonyl iron powder were obtained.

[0064] Next, a polymer layer was formed on the surface of the silica-coated particles. Specifically, 1.88 g of silica-coated particles (silica content: 0.04 g) and 30 g of pure water were mixed, and ultrasonic treatment was performed for 30 minutes. The ultrasonically treated suspension and 204.76 g of pure water were placed in a 300 mL separable beaker, and bubbling was carried out with nitrogen gas at 0.1 L / min for 30 minutes. The flow path of the nitrogen gas was changed from bubbling into the liquid to flow into the upper space of the liquid, and stirring was carried out while raising the temperature to 35°C. After the temperature was raised, 0.119 g of 3-methacryloxypropyltrimethoxysilane (manufactured by Shin-Etsu Chemical Co., Ltd.) shown in the following formula (3) was added as a silane coupling agent, and stirring was carried out for 30 minutes. Further, as the compound (monomer) represented by formula (2), 6.67 g of 2-methacryloyloxyethyl phthalate (Tokyo Chemical Industry Co., Ltd.) shown in the following formula (4) and 5 mL of a 5 wt% aqueous sodium hydroxide solution were added, and stirring was carried out for 30 minutes. Then, stirring was further carried out for 30 minutes while raising the temperature to 65°C. 0.994 g of 2,2'-azobis[N-(2-carboxyethyl)-2-methylpropionamidine] n-hydrate (manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in 5 g of pure water and added to the reaction vessel. After the addition, stirring was carried out as it was for 4 hours. After completion of the polymerization reaction, the particles were collected with a magnet and the supernatant was removed. This was redispersed in 50 g of pure water, the particles were collected with a magnet, and the supernatant was removed. The washing operation from redispersion in pure water to removal of the supernatant was repeated 4 more times, and the obtained particles were dispersed in pure water. Thereby, a slurry in which the polymer-coated metal magnetic particles of Example 1 were dispersed was obtained.

[0065]

Chemical formula

[0066]

Chemical formula

[0067] Note that the production conditions of Example 1 are shown in Table 1 below.

[0068]

Table 1

[0069] (2) Evaluation For the prepared polymer-coated metal magnetic particles, the amount of the carrier substance supported, the saturation magnetization and coercive force as magnetic properties, the C content, and the particle diameter were evaluated by the following methods.

[0070] (Supported amount) The loading amount of the carrier substance was evaluated by the amount of biotin bound per unit mass of the test particles. Hereinafter, EDC is 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Hydrochloride manufactured by Tokyo Chemical Industry Co., Ltd., MES is 2-(N-morpholino)ethanesulfonic acid, NHS is N-Hydroxysuccinimide manufactured by Wako Pure Chemical Industries, Ltd., PBS is phosphate buffered saline, TBS is Tris buffered saline, and TBST is TBS containing Tween20. First, a slurry in which the polymer-coated metal magnetic particles were dispersed was heated and dried to obtain polymer-coated metal magnetic particles. To 1 mg of the obtained polymer-coated metal magnetic particles, 1 mL of a 0.01 mol / L MES buffer solution with an EDC concentration of 5 mg / mL was added, and the mixture was stirred with a vortex mixer for 30 minutes. After stirring, the magnetic particles were separated by a magnet and washed three times with 1 mL of a 0.01 mol / L MES buffer solution. Subsequently, 1 mL of a 0.01 mol / L MES buffer solution with an NHS concentration of 0.8 mg / mL was added, and the mixture was stirred with a vortex mixer for 30 minutes. After stirring, the magnetic particles were separated by a magnet and washed three times with 1 mL of a 0.01 mol / L MES buffer solution. Subsequently, 1 mL of a 0.01 mol / L PBS buffer solution (pH 5.7) with a streptavidin (manufactured by Wako Pure Chemical Industries, Ltd.) concentration of 0.2 mg / mL was added, and the mixture was stirred with a vortex mixer for 30 minutes. After stirring, the magnetic particles were separated by a magnet and washed three times with 1 mL of a 0.01 mol / L PBS buffer solution to obtain streptavidin-immobilized particles. Subsequently, 100 μL of a 1×TBS buffer solution with an ALP-Biotin (manufactured by Thermo Fisher) concentration of 0.01 mg / mL was added to 50 μg of the streptavidin-immobilized particles, and the mixture was allowed to stand for 30 minutes. Then, the magnetic particles were separated by a magnet and washed three times with 200 μL of the TBST buffer solution. Then, the particles were suspended in 50 μL of TBS, transferred to a well plate, 50 μL of Lumiphos plus (manufactured by Wako Pure Chemical Industries, Ltd.) as a luminescent dye was added, and after 5 minutes, the luminescence intensity was measured with a microplate reader. Then, a calibration curve of the luminescence intensity and the ALP-biotin concentration was created, and the ALP-biotin concentration was calculated from the calibration curve to obtain the biotin binding amount.The biotin binding amount per unit mass of the test particles in Comparative Example 1 described below was taken as 100, and the biotin binding amount was calculated as a relative value. When this relative value is 130 or more, it is evaluated that the biotin binding amount is large and the loading amount of the carrier substance is large. In the measurement of luminescence intensity, a microplate reader ("SH-9000Lab" manufactured by Corona Electric Co., Ltd.) was used, and as measurement conditions, the measurement method was luminescence and the gate time was 1.0 second.

[0071] (Storage stability) The storage stability was evaluated using the streptavidin-immobilized particles obtained by the above-described evaluation method of the loading amount. In this example, for the streptavidin-immobilized particles obtained by the above-described evaluation method of the loading amount, the initial biotin binding amount and the biotin binding amount after a predetermined time were determined, and the maintenance rate was calculated. Specifically, for the streptavidin-immobilized particles obtained by the above-described evaluation method of the loading amount, the calculated biotin binding amount was used as the initial biotin binding amount. On the other hand, the streptavidin-immobilized particles were allowed to stand and held in an environment at 37°C for 4 days. After storage for a predetermined time, 100 μL of a 1×TBS buffer solution with an ALP-Biotin (manufactured by Thermo Fisher) concentration of 0.01 mg / mL was added to 50 μg of the streptavidin-immobilized particles, and they were allowed to stand and held for 30 minutes. Then, magnetic separation was performed, and they were washed 3 times with 200 μL of the TBST buffer solution. Then, they were suspended in 50 μL of TBS, transferred to a well plate, 50 μL of Lumiphos plus (manufactured by Wako Pure Chemical Industries, Ltd.) as a luminescent dye was added, and after 5 minutes, the luminescence intensity was measured with a microplate reader. Then, a calibration curve of the luminescence intensity and the ALP-biotin concentration was created, the ALP-biotin concentration was calculated from the calibration curve, and it was used as the biotin binding amount. This biotin binding amount was used as the biotin binding amount after 4 days at 37°C. Then, the storage stability was evaluated by the maintenance rate calculated by the following formula. In this example, if the above maintenance rate is 30% or more, it was evaluated that the storage stability is excellent. (Maintenance rate [%]) = (Biotin binding amount after 4 days at 37°C) / (Initial biotin binding amount) × 100

[0072] (Magnetic properties) A slurry in which polymer-coated metal magnetic particles were dispersed was heated and dried to obtain polymer-coated metal magnetic particles. The obtained polymer-coated metal magnetic particles were measured for magnetic properties such as saturation magnetization and coercive force using a vibrating sample magnetometer (VSM) (VSM-5 manufactured by Toei Industry Co., Ltd.) with an applied magnetic field of 798 kA / m (10 kOe), an M measurement range of 0.05 A·m 2 (50 emu), a time constant of 0.03 seconds, and a wait time of 0.1 seconds. For this measurement, the attached software (Ver. 2.1) manufactured by Toei Industry Co., Ltd. was used. In this example, if the saturation magnetization is 100 Am 2 / kg or more, the polymer-coated metal magnetic particles can be collected in a short time when a magnetic field is applied, and it is determined that they have excellent magnetic collection properties. If the coercive force is 20 Oe or less, it is determined that the time until the polymer-coated metal magnetic particles disperse after being separated from the magnetic field is short and they have excellent dispersibility. In Table 1, the coercive force Hc is listed in both units of [Oe] and [kA / m].

[0073] (C content) A slurry in which polymer-coated metal magnetic particles were dispersed was heated and dried to obtain polymer-coated metal magnetic particles. The carbon content of the obtained polymer-coated metal magnetic particles was measured using a carbon and sulfur analyzer (EMIA-920V2 manufactured by Horiba, Ltd.).

[0074] (Particle size) The particle size of the polymer-coated metal magnetic particles was measured using a laser diffraction / scattering particle size distribution measuring device ("SYNC" manufactured by Microtrac Bell Co., Ltd.) for the particle size distribution of the slurry in which the polymer-coated metal magnetic particles were dispersed, and based on the obtained volume-based particle size distribution, the D50 (unit: μm), which is the cumulative 50% diameter, was determined.

[0075] (3) Evaluation results The results of each evaluation are summarized in Table 2.

[0076]

Table 2

[0077] As shown in Table 2, the polymer-coated metal magnetic particles of Example 1 had a D50 of 2.2 μm, a biotin binding amount of 303, a saturation magnetization of 197 A·m 2 / kg, a coercive force Hc of 5 Oe, and a C content of 3%. That is, in Example 1, it was confirmed that the supported amount of the carrier substance was large, the saturation magnetization was high and the magnetic collection property was excellent, and the coercive force was low and the magnetic separation property was excellent. When the thickness of the coating layer was observed with a transmission electron microscope, it was confirmed that the thickness was in the range of 1 nm to 80 nm.

[0078] The reason why the supported amount could be increased was that a polymer layer was formed using an alkoxysilane having an acrylic group or a methacrylic group and 2-methacryloyloxyethyl phthalic acid as the compound of formula (2). In Example 1, the polymer forming the polymer layer was composed of a structural unit derived from 2-methacryloyloxyethyl phthalic acid and a structural unit derived from a predetermined alkoxysilane so as to satisfy formula (1). The structural unit derived from 2-methacryloyloxyethyl phthalic acid has a long molecular chain due to an ethyl group, a methacrylic group, and a phenylene group. Therefore, the polymer layer can easily bind streptavidin and increase its supported amount. Also, in Example 1, since the core was Fe particles, it is considered that the saturation magnetization was increased to improve the magnetic collection property, while the coercive force was decreased to improve the magnetic separation property. Also, the C content derived from the polymer layer was 0.5 mass% to 10 mass%, and it is considered that the supported amount and the magnetic properties could be balanced by forming the polymer layer with an appropriate thickness.

[0079] Also, it was confirmed that the polymer-coated metal magnetic particles of Example 1 had a high retention rate of the supported amount of 37% and excellent storage stability. This is considered to be because the polymer layer could be uniformly formed on the coating layer by setting the addition amount of the silane coupling agent to 5.0 parts by mass to 40 parts by mass with respect to 100 parts by mass of the metal magnetic particles on which the coating layer was formed, and the addition amount of the compound of formula (2) to 100 parts by mass to 500 parts by mass with respect to 100 parts by mass of the metal magnetic particles on which the coating layer was formed.

[0080] (Examples 2 to 5) In Examples 2 to 5, as shown in Table 1, polymer-coated metal magnetic particles were produced in the same manner as in Example 1, except that the types of alkoxysilane, the compound of formula (2), and metal magnetic particles were appropriately changed.

[0081] As the alkoxysilane, 3-acryloxypropyltrimethoxysilane represented by the following formula (5) was used.

[0082]

Chemical formula

[0083] As the compound of formula (2), 2-acryloyloxyethyl succinic acid represented by the following formula (6) was used.

[0084]

Chemical formula

[0085] As the metal magnetic particles, Fe-B alloy particles or Fe-Ni alloy particles were used. The Fe-B alloy particles were produced as follows. First, 11.3 g of iron chloride (FeCl2), 15.9 g of ammonium chloride, and 62.3 g of sodium gluconate were dissolved in 285.7 g of water at 30 °C in a 500 ml beaker. Subsequently, 28.2 g of 25% aqueous ammonia was added to adjust the pH of the raw material solution to 9. Subsequently, the liquid temperature was adjusted to 50 °C, and while stirring at 300 rpm, a solution prepared by mixing 21.7 g of sodium borohydride in 214.2 g of water was added and aged for 10 minutes. The generated particles were collected with a magnet and washed with ethanol to obtain Fe-B alloy particles. The boron content was 9.2 wt%. As the Fe-Ni alloy particles, particles with an Fe content of 50% and a Ni content of 50% were used.

[0086] The polymer-coated metal magnetic particles of Examples 2 to 5 were evaluated in the same manner as in Example 1. As a result, as shown in Table 2, it was confirmed that in Examples 2 to 5, the amount of biotin binding was large, the saturation magnetization was high, and the coercive force was low, similar to Example 1. Also, in Examples 2 to 5, it was confirmed that the thickness of the coating layer and the storage stability were at the same level as in Example 1.

[0087] Also, in Examples 1 to 5, since an alkoxysilane having an acrylic group or a methacrylic group and an alkylene group having 3 to 6 carbon atoms was used as the silane coupling agent, specifically, since an alkoxysilane having an acryloxypropyl group or a methacryloxypropyl group was used, it was confirmed that the loading amount in the polymer-coated metal magnetic particles could be further increased.

[0088] Also, when comparing Examples 1 to 5, as the compound of formula (2), in Examples 1, 3, and 4 using phthalic acid of formula (4) in which R 3 is a phenylene group, it was confirmed that the amount of biotin binding could be made higher than in Examples 2 and 5 using succinic acid of formula (6) in which R 3 is an alkylene group. From this, it is considered that by introducing a more bulky chemical structure in the polymer layer, the loading amount of streptavidin can be increased, and as a result, more biotin can be captured.

[0089] (Comparative Examples 1 to 5) In Comparative Examples 1 to 5, as shown in Table 1, polymer-coated metal magnetic particles were prepared in the same manner as in Example 1, except that the type of alkoxysilane was appropriately changed to the following formulas (7) to (8), and the type of the compound of formula (2) was appropriately changed to the compounds of the following formulas (9) to (11). Formula (7) represents trimethoxy-4-vinylphenylsilane, and formula (8) represents triethoxyvinylsilane. Formula (9) represents styrene, formula (10) represents 2-carboxyethyl acrylate, and formula (11) represents 4-vinylbenzoic acid. The polymer-coated metal magnetic particles of Comparative Examples 1 to 5 were evaluated in the same manner as in Example 1. The results are shown in Table 2.

[0090] [Chemical formula]

[0091]

Chem.

[0092]

Chem.

[0093]

Chem.

[0094]

Chem.

[0095] As shown in Table 2, in Comparative Examples 1 to 3, although the saturation magnetization was high and the coercive force was low, it was confirmed that the biotin binding amount was lower compared to Examples 1 to 5. This is because in the formation of the polymer layer, styrene, 2-carboxyethyl acrylate, and 4-vinylbenzoic acid were used without using the compound satisfying formula (2). It is presumed that in Comparative Examples 1 to 3, as in Examples 1 to 5, a chemical structure with a long molecular chain and large volume could not be introduced into the polymer layer, and thus the binding with streptavidin could not be achieved efficiently.

[0096] In Comparative Examples 4 and 5, as shown in Table 2, it was confirmed that the biotin binding amount was low and the magnetic properties were also low as compared with Examples 1 to 5. This is because in the formation of the polymer layer, an alkoxysilane having an acrylic group or a methacrylic group was not used as the silane coupling agent, and trimethoxy-4-vinylphenylsilane or triethoxyvinylsilane having no acrylic group or methacrylic group was used. In Comparative Examples 4 and 5, it is presumed that the polymer layer cannot be configured to easily bind streptavidin and the C content cannot be configured to be 0.5 mass% to 10 mass%. Since Comparative Examples 1 to 5 have a small biotin binding amount, the storage stability has not been evaluated.

[0097] (Examples 6 to 16) In Examples 6 to 16, as shown in Table 3, polymer-coated metal magnetic particles were produced in the same manner as in Example 1, except that the types of alkoxysilane (silane coupling agent), the compound of formula (2), and the metal magnetic particles were appropriately changed. Then, the produced polymer-coated metal magnetic particles were evaluated in the same manner as in Example 1. The evaluation results for Examples 6 to 16 are summarized in Table 4.

[0098] As the alkoxysilane, 3-methacryloxypropylmethyldimethoxysilane represented by the following formula (12) or 3-methacryloxypropylmethyldiethoxysilane represented by the following formula (13) was used.

[0099] [Chemical formula]

[0100] [Chemical formula]

[0101] In addition, as the compound of formula (2), 2-methacryloyloxyethyl succinic acid represented by the following formula (14), 2-acryloyloxyethyl phthalic acid represented by the following formula (15), and 2-acryloyloxyethyl hexahydrophthalic acid represented by the following formula (16) were used.

[0102]

Chemical formula

[0103]

Chemical formula

[0104]

Chemical formula

[0105]

Table 3

[0106] In Example 6, similar to Example 5, a coating layer of silicon oxide was formed on the surface of Fe-Ni alloy particles with a Fe content of 50% and a Ni content of 50% to obtain silica-coated particles. Subsequently, a polymer layer was formed on the surface of the silica-coated particles. Specifically, 8.00 g of silica-coated particles (silica content 0.16 g) and 40 g of pure water were mixed and subjected to ultrasonic treatment for 10 minutes. The ultrasonically treated suspension and 488.63 g of pure water were charged into a 1 L beaker and bubbled with nitrogen gas at 0.1 L / min for 30 minutes. The nitrogen gas flow path was changed from bubbling into the liquid to flow into the upper space of the liquid, and the mixture was stirred while heating to 35°C. After heating, 1.61 g of 3-methacryloxypropylmethyldimethoxysilane (manufactured by Shin-Etsu Chemical Co., Ltd.) shown in the above formula (12) was charged as a silane coupling agent and stirred for 30 minutes. Further, 44.94 g of 2-methacryloyloxyethyl phthalate (Tokyo Chemical Industry Co., Ltd.) shown in the above formula (15) was dissolved in 150 g of pure water and 70 g of a 10 wt% aqueous sodium hydroxide solution as the compound (monomer) shown in formula (2), charged into the reaction tank, and stirred for 30 minutes. Then, it was further stirred for 30 minutes while heating to 65°C. 6.69 g of 2,2‘-azobis[N-(2-carboxyethyl)-2-methylpropionamidine] n hydrate (Wako Pure Chemical Industries, Ltd.) was dissolved in 30 g of pure water and charged into the reaction tank. After addition, it was stirred as it was for 4 hours. After completion of the polymerization reaction, the particles were collected with a magnet and the supernatant was removed, redispersed in 200 g of pure water, and the particles were collected with a magnet and the supernatant was removed. The washing operation from redispersion in pure water to removal of the supernatant was repeated 4 more times, and the obtained particles were dispersed in pure water. Thereby, a slurry in which the polymer-coated metal magnetic particles of Example 6 were dispersed was obtained.

[0107] In Examples 7 to 9, as shown in Table 3, polymer-coated metal magnetic particles were produced in the same manner as in Example 6 except that the type of the compound (monomer) represented by formula (2) was appropriately changed.

[0108] In Example 10, a polymer layer was formed on the surface of the silica-coated particles prepared in the same manner as in Example 1. Specifically, 8.00 g of silica-coated particles (silica content: 0.16 g) and 40 g of pure water were mixed, and ultrasonic treatment was performed for 10 minutes. The ultrasonically treated suspension and 517.94 g of pure water were placed in a 1-L beaker, and bubbling was performed with nitrogen gas at 0.1 L / min for 30 minutes. The flow path of the nitrogen gas was changed from bubbling into the liquid to flow in the upper space of the liquid, and the mixture was stirred while heating to 35°C. After heating, 1.84 g of 3-methacryloxypropylmethyldimethoxysilane (manufactured by Shin-Etsu Chemical Co., Ltd.) represented by the above formula (12) was added as a silane coupling agent, and the mixture was stirred for 30 minutes. Further, 30.8 g of 2-methacryloyloxyethyl phthalate (manufactured by Tokyo Chemical Industry Co., Ltd.) represented by the above formula (15) as a compound (monomer) represented by the formula (2) was dissolved in 150 g of pure water and 55 g of a 10 wt% aqueous sodium hydroxide solution, and the solution was added to the reaction tank and stirred for 30 minutes. Thereafter, the mixture was further stirred for 30 minutes while heating to 65°C. 4.59 g of 2,2'-azobis[N-(2-carboxyethyl)-2-methylpropionamidine] n hydrate (manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in 20 g of pure water and added to the reaction tank. After the addition, the mixture was stirred for 4 hours as it was. After completion of the polymerization reaction, the particles were collected with a magnet and the supernatant was removed. The particles were redispersed in 200 g of pure water, and the particles were collected with a magnet and the supernatant was removed. The washing operation from redispersion in this pure water to removal of the supernatant was repeated 4 more times, and the obtained particles were dispersed in pure water. Thereby, a slurry in which the polymer-coated metal magnetic particles of Example 10 were dispersed was obtained.

[0109] In Examples 11 to 14, as shown in Table 3, polymer-coated metal magnetic particles were prepared in the same manner as in Example 10, except that the type of the compound (monomer) represented by the formula (2) was appropriately changed.

[0110] In Example 15, as shown in Table 3, polymer-coated metal magnetic particles were prepared in the same manner as in Example 10, except that 2.05 g of 3-methacryloxypropylmethyldiethoxysilane represented by the above formula (13) was used as the silane coupling agent when forming the polymer layer.

[0111] In Example 16, as shown in Table 3, when forming the polymer layer, except that 1.85 g of 3-acryloxypropyltrimethoxysilane represented by the above formula (5) was changed as the silane coupling agent, polymer-coated metal magnetic particles were produced in the same manner as in Example 10.

[0112]

Table 4

[0113] As shown in Table 4, in Examples 6 to 9, it was confirmed that, similar to Example 5, the amount of biotin bound was large, the saturation magnetization was high, and the coercive force was low. Also, in Examples 10 to 16, it was confirmed that, similar to Example 1, the amount of biotin bound was large, the saturation magnetization was high, and the coercive force was low. In addition, in Examples 6 to 16, it was confirmed that the thickness of the coating layer was equivalent to that in Example 1.

[0114] Also, in Examples 6 to 16, it was confirmed that the retention rate of the loading amount was high compared to Examples 1 to 5, and the storage stability was excellent. In Examples 6 and the like, it is presumed that the addition amount of the silane coupling agent was made larger than that in Example 1, and the polymer layer could be formed thickly and uniformly on the coating layer.

[0115] As described above, in the polymer-coated metal magnetic particles, by configuring the polymer layer to include a polymer of a structural unit represented by the formula (1) and an alkoxysilane having an acrylic group or a methacrylic group, it is easy to bind a carrier substance, for example, streptavidin, that can capture a target substance to be inspected, and the loading amount thereof can be increased. Further, by using a metal magnetic particle as the core, the ratio of the magnetic metal in the polymer-coated metal magnetic particles can be increased, and the magnetic aggregation property and the magnetic separability can be improved.

Claims

1. Metal magnetic particles, a coating layer provided on the surface of the metal magnetic particles and composed of silicon oxide, a polymer layer provided on the surface of the coating layer and containing a polymer of a structural unit represented by formula (1) and an alkoxysilane having an acrylic group or a methacrylic group, Polymer-coated metal magnetic particles. 【Chemical 1】 (In formula (1), R １ represents a hydrogen atom or a methyl group, and R ２ represents a linear or branched alkylene group having 2 to 6 carbon atoms, and R ３ represents an alkylene group having 2 to 6 carbon atoms, a cyclohexylene group, or a phenylene group.)

2. In the formula (1), R ２ is an ethylene group, and R ３ is an alkylene group, a phenylene group or a cyclohexylene group. The polymer-coated metal magnetic particles according to Claim 1.

3. R in the formula (1) above ３ is a phenylene group The polymer-coated metal magnetic particles according to Claim 2.

4. The alkoxysilane has an acrylic group or a methacrylic group and an alkylene group having 3 to 6 carbon atoms, The polymer-coated metal magnetic particles according to Claim 1 or Claim 2.

5. The alkoxysilane has an acryloxypropyl group or a methacryloxypropyl group, The polymer-coated metal magnetic particles according to Claim 4.

6. The metal magnetic particles are iron particles or iron-based alloy particles, The polymer-coated metal magnetic particles according to Claim 1 or 2.

7. The saturation magnetization is 100 A·m ２ / kg or more and 210 A·m ２ / kg or less, The polymer-coated metal magnetic particles according to Claim 1 or 2.

8. The cumulative 50% particle diameter based on volume measured by a laser diffraction particle size distribution measuring device is 0.2 μm to 10 μm, The polymer-coated metal magnetic particles according to Claim 1 or 2.

9. The C content is 0.5% by mass or more and 10% by mass or less, The polymer-coated metal magnetic particles according to Claim 1 or 2.

10. The C content is 0.1% by mass or more and 10% by mass or less, The polymer-coated metal magnetic particles according to Claim 1 or 2.

11. A method for producing polymer-coated metal magnetic particles, a step of forming a coating layer composed of silicon oxide on the surface of the metal magnetic particles, after mixing the metal magnetic particles on which the coating layer is formed, water, and an alkoxysilane having an acrylic group or a methacrylic group, adding a compound represented by formula (2) and polymerizing to form a polymer layer on the coating layer, A method for producing polymer-coated metal magnetic particles. 【Chemical 2】 (In formula (2), R １ represents a hydrogen atom or a methyl group, and R ２ represents a linear or branched alkylene group having 2 to 6 carbon atoms, and R ３ represents an alkylene group having 2 to 6 carbon atoms, a cyclohexylene group, or a phenylene group.)

12. In the formula (2), R ２ is an ethylene group, and R ３ is an alkylene group, a phenylene group or a cyclohexylene group, The method for producing polymer-coated metal magnetic particles according to Claim 11.

13. R in the formula (2) above ３ is a phenylene group The method for producing polymer-coated metal magnetic particles according to Claim 12.

14. The alkoxysilane has an acrylic group or a methacrylic group and an alkylene group having 3 to 6 carbon atoms, The method for producing polymer-coated metal magnetic particles according to Claim 11 or Claim 12.

15. The alkoxysilane has an acryloxypropyl group or a methacryloxypropyl group, The method for producing polymer-coated metal magnetic particles according to claim 14.

16. The method for producing polymer-coated metal magnetic particles according to claim 11 or claim 12, wherein the metal magnetic particles are iron particles or iron-based alloy particles. The method for producing polymer-coated metal magnetic particles according to claim 11 or claim 12.

17. The method for producing polymer-coated metal magnetic particles according to claim 11 or claim 12, wherein in the step of forming the polymer layer, a water-soluble azo polymerization initiator having a carboxyl group is used as the polymerization initiator. The method for producing polymer-coated metal magnetic particles according to claim 11 or claim 12.

Images