Polymer-coated metal magnetic particles and method for producing the same

Abstract

A polymer-coated metal magnetic particle comprises: a metal magnetic particle; a coating layer disposed on the surface of the metal magnetic particle and composed of silicon oxide; and a polymer layer disposed on the surface of the coating layer, comprising a polymer of a structural unit of formula (1) and an alkoxysilane having an acryloyl group or a methacryloyl group.

Description

Technical Field

[0001] This invention relates to polymer-coated metallic magnetic particles and their manufacturing method. Background Technology

[0002] In the field of medical diagnostics, various target substances such as proteins, nucleic acids, and cells are sometimes separated and collected from blood or other sample solutions for testing. As a testing method, for example, there are methods that load a carrier substance suitable for each target substance onto the surface of specified particles, recover the particles after capturing the target substance, and then analyze them.

[0003] Sometimes, magnetic particles are used as the carrier material. Based on these magnetic particles, after the carrier material has been loaded and the target material has been captured, the target material can be recovered by applying a magnetic field from the outside.

[0004] As such magnetic particles, for example, a magnetic polymer particle has been proposed, which is formed by sequentially coating the surface of a polymer particle, which serves as the core, with a coating layer comprising a nanomagnetic material and silicon oxide, and a polymer layer capable of binding a carrier material (see, for example, Patent Document 1).

[0005] Existing technical documents

[0006] Patent documents

[0007] Patent Document 1: Japanese Patent Application Publication No. 2021-60339 Summary of the Invention

[0008] The problem the invention aims to solve

[0009] In the aforementioned inspection particles, from the viewpoint of improving inspection accuracy, it is important to have a high loading of carrier material capable of binding with the target substance. Furthermore, for inspection particles, high saturation magnetization and rapid aggregation upon application of a magnetic field are required, i.e., high magnetization.

[0010] Regarding this point, in the particles of the aforementioned Patent Document 1, even if a high loading can be achieved, since the core is a polymer particle, there is a tendency for low saturation magnetization, and sometimes the desired magnetism cannot be obtained.

[0011] Therefore, the object of the present invention is to provide a technique for increasing the loading of a carrier substance that can bind to a target substance and making the magnetism a certain value or above.

[0012] Solution for solving the problem

[0013] The first aspect of the present invention is a polymer-coated metallic magnetic particle, comprising:

[0014] Metallic magnetic particles;

[0015] A coating layer, disposed on the surface of the metallic magnetic particles, is composed of silicon oxide; and

[0016] A polymer layer disposed on the surface of the coating layer comprises a polymer of a structural unit of formula (1) and an alkoxysilane having an acryloyl group or a methacryloyl group.

[0017]

[0018] (In equation (1), R) 1 R represents a hydrogen atom or a methyl group. 2 R represents a straight-chain or branched alkylene group with 2 or more but less than 6 carbon atoms. 3 This refers to alkylene, cyclohexylene, or phenylene compounds with 2 or more but fewer than 6 carbon atoms.

[0019] The second aspect of the present invention is the same as the first aspect.

[0020] In the above formula (1), R 2 It is ethylene, R 3 It is an alkylene, phenylene, or cyclohexylene group.

[0021] The third aspect of the present invention is the same as the second aspect.

[0022] R in equation (1) 3 It is a phenylene oxide.

[0023] The fourth aspect of the present invention is any one of the first to third aspects.

[0024] The alkoxysilane has an acryloyl or methacryloyl group and an alkylene group having 3 to 6 carbon atoms.

[0025] The fifth aspect of the present invention is the same as the fourth aspect.

[0026] The alkoxysilane has an acryloyloxypropyl group or a methacryloyloxypropyl group.

[0027] The sixth aspect of the present invention is any one of the first to fifth aspects.

[0028] The metallic magnetic particles are iron particles or iron-based alloy particles.

[0029] The seventh aspect of the present invention is any one of the first to sixth aspects.

[0030] Saturation magnetization is 100 Am 2 / kg or more and 210Am 2 / kg or less.

[0031] The eighth aspect of the present invention is any one of the first to seventh aspects.

[0032] The cumulative 50% particle size of the volume standard, as measured by a laser diffraction particle size distribution measuring device, is 0.2 μm to 10 μm.

[0033] The ninth aspect of the present invention is any one of the first to eighth aspects.

[0034] The C content is 0.5% by mass or more and 10% by mass or less.

[0035] The tenth aspect of the present invention is any one of the first to ninth aspects.

[0036] The C content is 0.1% by mass or more and 10% by mass or less.

[0037] The eleventh aspect of the present invention is a method for manufacturing polymer-coated metallic magnetic particles, comprising:

[0038] The process of forming a coating layer of silicon oxide on the surface of metallic magnetic particles; and,

[0039] The process of mixing metallic magnetic particles with the coating layer, water and alkoxysilane having acryloyl or methacryloyl groups, and then adding the compound shown in formula (2) to polymerize it, thereby forming a polymer layer on the coating layer.

[0040]

[0041] (In equation (2), R) 1 R represents a hydrogen atom or a methyl group. 2 R represents a straight-chain or branched alkylene group with 2 or more but less than 6 carbon atoms. 3 This refers to alkylene, cyclohexylene, or phenylene compounds with 2 or more but fewer than 6 carbon atoms.

[0042] The 12th aspect of the present invention is the same as the 11th aspect.

[0043] In equation (2), R 2 It is ethylene, R 3 It is an alkylene, phenylene, or cyclohexylene group.

[0044] The 13th aspect of the present invention is the same as the 12th aspect.

[0045] R in equation (2) 3 It is a phenylene oxide.

[0046] The 14th aspect of the present invention is any one of the 11th to 13th aspects.

[0047] The alkoxysilane has an acryloyl or methacryloyl group and an alkylene group having 3 to 6 carbon atoms.

[0048] The 15th aspect of the present invention is the same as the 14th aspect.

[0049] The alkoxysilane has an acryloyloxypropyl group or a methacryloyloxypropyl group.

[0050] The 16th aspect of the present invention is any one of the 11th to 15th aspects.

[0051] The metallic magnetic particles are iron particles or iron-based alloy particles.

[0052] The 17th aspect of the present invention is any one of the 11th to 16th aspects.

[0053] In the process of forming the polymer layer, a water-soluble azo polymerization initiator with a carboxyl group is used as the polymerization initiator.

[0054] The effects of the invention

[0055] In the particles used for inspection, the loading of carrier material that can bind to the target substance can be increased, and the magnetic properties can be increased to a certain level. Detailed Implementation

[0056] <An embodiment of the present invention>

[0057] The following describes a polymer-coated metallic magnetic particle and its manufacturing method according to one embodiment of the present invention. It should be noted that the numerical range indicated by "~" in this description refers to the range including the values ​​before and after "~" as both the lower and upper limits.

[0058] (1) Polymer-coated metallic magnetic particles

[0059] The polymer-coated metallic magnetic particles of this embodiment are formed by sequentially stacking a coating layer and a polymer layer on the surface of metallic magnetic particles. Hereinafter, the polymer-coated metallic magnetic particles will also be referred to as inspection particles.

[0060] (Magnetic metallic particles)

[0061] The metallic magnetic particles, which serve as the core of the inspection particles, are ferromagnetic particles composed of metals or alloys. Examples of metallic magnetic particles composed of pure metals include iron, nickel, or cobalt particles. Examples of metallic magnetic particles composed of alloys include iron-based alloy particles. In this specification, an iron-based alloy refers to an alloy containing 50% by mass or more iron. Examples of iron-based alloy particles include Fe-B alloy particles, Fe-Si alloy particles, Fe-N alloy particles, Fe-Ni alloy particles, and Fe-C alloy particles. From the viewpoint of ensuring excellent saturation magnetization of the inspection particles, iron particles or iron-based alloy particles are preferred as the metallic magnetic particles.

[0062] The particle size of the metallic magnetic particles is preferably 0.2 μm to 10.0 μm. With inspection particles possessing such metallic magnetic particles, when added to the sample solution, the weight and buoyancy of the inspection particles can be balanced, achieving appropriate dispersibility in the sample solution. As a result, the attachment of the carrier material to the inspection particles and the bonding of the target material to the carrier material can be performed more reliably. Here, particle size refers to the cumulative 50% particle size of the volume reference measured by a laser diffraction particle size distribution measuring device. Hereafter, particle size refers to the same measured value.

[0063] (Covering layer)

[0064] The coating layer, composed of silicon oxide, is disposed on the surface of the metallic magnetic particles. The coating layer coats the metallic magnetic particles to inhibit the dissolution of metallic components from the magnetic particles during the formation of the polymer layer.

[0065] The thickness of the coating layer is not particularly limited, but if it is too thin, it may not be able to uniformly cover the surface of the metallic magnetic particles. Therefore, from the viewpoint of more reliably suppressing the dissolution of components from the metallic magnetic particles during polymer layer formation, the thickness of the coating layer is preferably 1 nm or more. On the other hand, if the coating layer is too thick, the magnetic properties of the particles being inspected, such as saturation magnetization and coercivity, may sometimes decrease. Therefore, from the viewpoint of maintaining high magnetic properties, the thickness of the coating layer is preferably 80 nm or less. It should be noted that the thickness of the coating layer can be measured, for example, by observing the cross-section of the coating layer using a transmission electron microscope (TEM) or a scanning electron microscope (SEM), and by measuring its average film thickness. Specifically, a TEM or SEM image of the cross-section can be taken, and for any particle, the average film thickness can be calculated by averaging 50 measurement points.

[0066] (Polymer layer)

[0067] A polymer layer is disposed on the surface of the coating layer. The polymer layer comprises a polymer of the structural unit shown in formula (1) and an alkoxysilane having an acryloyl group or a methacryloyl group, configured to bind with a carrier substance capable of capturing the target substance. Here, the target substance refers to substances such as proteins, nucleic acids, and cells contained in blood that are the objects of examination. 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 target substance. As a carrier substance, for example, streptavidin, protein A, protein G, antibodies, etc. can be used.

[0068]

[0069] In equation (1), R 1 R represents a hydrogen atom or a methyl group. 2 R represents a straight-chain or branched alkylene group with 2 or more but less than 6 carbon atoms. 3 It indicates an alkylene, cyclohexylene, or phenylene group with 2 or more but less than 6 carbon atoms.

[0070] The polymer has a carboxyl group (-COOH group) at the end of the structural unit of formula (1), which binds to the carrier substance. Additionally, as shown in formula (1), the polymer has an R group in its chemical structure. 2 and R 3 This results in molecules with long molecular chains and large volumes. Therefore, polymers readily bind to carrier substances with large molecular sizes, such as streptavidin. That is, based on the polymer layer, the amount of carrier substance attached to its surface (loading capacity) can be increased. Regarding R... 2 and R 3 When the alkylene groups have only 1 carbon atom, the molecular chain becomes shorter, and the loading may be less, so this is not preferred. When the number of carbon atoms is 7 or more, the hydrophobicity increases, making it difficult to carry out the polymerization reaction in the polymer layer formation process, and the productivity may decrease, so this is also not preferred.

[0071] In the structural unit of equation (1), R is preferred. 2 It is ethylene, R 3 It is an alkylene or phenylene. Furthermore, R is more preferably preferred. 3 It is a phenylene group. Based on this structural unit, polymers can be formed more stably, and the loading of carrier material can be increased more reliably.

[0072] As a silane coupling agent for forming the polymer, there is no particular limitation as long as it is an alkoxysilane having an acryloyl or methacryloyl group that can polymerize with the compound of formula (2). In the polymer layer, from the viewpoint of more reliably increasing the loading of the carrier material, the silane coupling agent preferably has a chemical structure with a long molecular chain and a large volume. Specifically, the silane coupling agent is preferably an alkoxysilane having an acryloyl or methacryloyl group and having an alkylene group having 3 to 6 carbon atoms. In addition, from the viewpoint of improving the reactivity with the compound of formula (2) and more reliably polymerizing the polymer, the silane coupling agent preferably has an acryloyloxypropyl or methacryloyloxypropyl group.

[0073] (Quantity C)

[0074] The amount of polymer contained in the test particles can be easily quantitatively evaluated in the form of carbon (C). From the viewpoint of ensuring high magnetic properties, the C content of the test particles is preferably 0.1% to 10% by mass, or 0.5% to 10% by mass. If the C content is too low, the surface of the coated layer cannot be uniformly covered by the polymer layer, and sometimes it is not possible to maintain a high loading of the carrier material. On the other hand, if the C content is too high, the proportion of magnetic components in the test particles becomes low, and sometimes it is not possible to maintain high magnetic properties. In this regard, by setting the C content within the above range, the loading of the carrier material and magnetic properties can be achieved at a high level of uniformity. It should be noted that the C content represents the content of carbon from the polymer layer in 100 parts by mass of the test particles (polymer-coated metallic magnetic particles). The C content can be determined, for example, using a carbon and sulfur analysis device as described later in the examples.

[0075] (particle size)

[0076] The particle size of the particles used for inspection is not particularly limited, but is preferably 0.2 μm to 10 μm. When the particle size decreases, the volume of the magnetic particles also decreases, making it difficult to obtain the desired magnetism when a magnetic field is applied, which is not preferred. Furthermore, if the particle size is too large, the particles used for inspection are prone to settling in the solution, which is also not preferred.

[0077] (characteristic)

[0078] The inspection particles of this embodiment are constructed by sequentially layering a coating layer and a polymer layer on the surface of a metallic magnetic particle serving as a core. As a result, the inspection particles exhibit the following characteristics.

[0079] In the test particles, the polymer layer comprises a polymer of the structural unit shown in formula (1) and an alkoxysilane having an acryloyl or methacryloyl group, which readily binds to the carrier material that captures the target substance. That is, the test particles are constructed in a manner that increases the loading amount of the carrier material. Specifically, streptavidin, as the carrier material, is loaded onto the test particles, and 50 μg of the streptavidin-immobilized particles are bound to ALP-biotin (alkaline phosphatase-biotin) and a luminescent pigment (e.g., Lumi-Phos Plus), and the luminescence intensity is measured. A calibration curve showing the relationship between luminescence intensity and ALP-biotin concentration is prepared, and the ALP-biotin concentration is calculated from the luminescence intensity as the biotin binding amount. The test particles of this embodiment have a high biotin binding amount and excellent carrier material loading capacity.

[0080] Furthermore, since the core is a metallic magnetic particle, the inspection particles are constructed with a higher proportion of magnetic components compared to magnetic polymer particles with a polymer core surrounded by magnetic particles. Therefore, the inspection particles have a high saturation magnetization. Specifically, the saturation magnetization of the inspection particles is preferably 100 Am. 2 / kg or above. There is no specific upper limit; for example, it could be 210Am. 2 / kg or less. Inspection particles with such saturation magnetization exhibit high magnetism, enabling a shorter time to recover the inspection particles when a magnetic field is applied. It should be noted that the method for measuring saturation magnetization is detailed in the examples.

[0081] Furthermore, since the core is made of metallic magnetic particles, the inspection particles are configured with lower coercivity compared to magnetic polymer particles. Specifically, the coercivity Hc of the inspection particles is preferably 20 Oe or less. There is no particular limitation on the lower limit, for example, it can be 3 Oe or more. Inspection particles with such coercivity can improve particle dispersibility.

[0082] (2) Method for manufacturing polymer-coated metal magnetic particles

[0083] Next, the method for manufacturing polymer-coated metallic magnetic particles will be described. The manufacturing method of this embodiment includes a preparation step, a coating layer formation step, and a polymer layer formation step. Each step will be described in detail below.

[0084] (Preparation process)

[0085] First, prepare the metallic magnetic particles to serve as the core. The saturation magnetization of the prepared metallic magnetic particles is preferably 100 Am. 2 / kg or more and 210Am 2 / kg or less. Furthermore, from the viewpoint of ensuring excellent saturation magnetization of the obtained inspection particles, iron particles or iron-based alloy particles are preferred as metallic magnetic particles.

[0086] (Coating formation process)

[0087] Next, a coating layer composed of silicon oxide is formed on the surface of the metallic magnetic particles. For example, a sol-gel method can be used for this formation.

[0088] Specifically, firstly, metallic magnetic particles are added to a solvent containing water to obtain a slurry in which the metallic magnetic particles are dispersed. Next, while stirring the slurry, a silanol salt is added. The silanol salt is hydrolyzed by alkoxy groups in the presence of water to generate a silanol derivative. The amount of silanol added, relative to 100 parts by mass of the metallic magnetic particles, is preferably 0.1 to 5.0 parts by mass of Si. The silanol derivative adheres to the surface of the metallic magnetic particles to form a reaction layer. Next, after adding the silanol salt and allowing a predetermined time, a hydrolysis catalyst is added while stirring the solvent containing the slurry. This hydrolyzes any residual alkoxy groups in the silanol derivative. Furthermore, the solvent is heated while adding the hydrolysis catalyst. Through heating, the silanol derivative undergoes condensation or polymerization, thereby forming a polysiloxane structure, which is further heated to form silicon dioxide (SiO2). Then, the solvent is dried to obtain silicon dioxide coated particles with a coating layer composed of silicon oxide formed on the surface of the metallic magnetic particles.

[0089] As a silanol, conventionally known silanols can be used, such as trimethoxysilane, tetramethoxysilane, triethoxysilane, tetraethoxysilane, tripropoxysilane, tetrapropoxysilane, tributoxysilane, tributoxysilane, etc.

[0090] From the viewpoint of suppressing the dissolution of the metal components constituting the magnetic metal particles, an alkaline catalyst is preferred as a hydrolysis catalyst. Ammonia water can be used as an example of an alkaline catalyst.

[0091] It should be noted that the amount of silanol salt and / or hydrolysis catalyst added, and the reaction time of the silanol salt and / or hydrolysis catalyst, can be appropriately varied according to the thickness of the coating layer. For example, the thickness of the coating layer can be appropriately adjusted to 1 nm to 80 nm. Furthermore, from the viewpoint of the reactivity of silanol salt hydrolysis and the adhesion of silanol derivatives to the surface of metallic magnetic particles, the heating temperature of the solvent containing the slurry can be set, for example, to 20°C to 70°C. As the solvent, water alone can be used, or a mixed solvent containing water and an organic solvent can be used.

[0092] (Polymer layer formation process)

[0093] Next, a polymer layer is formed on the surface of the silica-coated particles.

[0094] Specifically, firstly, silica-coated particles are mixed with a solvent containing water to prepare a dispersion. Then, while stirring the dispersion, an alkoxysilane having acryloyl or methacryloyl groups is added as a silane coupling agent and mixed. It is assumed that the alkoxysilane undergoes alkoxy hydrolysis through reaction with water, binding to the coating layer composed of silicon oxides. After adding the silane coupling agent, preferably a base such as NaOH or NH3 is added to bring the pH of the liquid to 8 or higher before adding the compound shown in formula (2). This base addition improves the reactivity of the silane coupling agent and the solubility of the compound in formula (2) in water. It is assumed that, starting with the silane coupling agent bound to the coating layer, the acryloyl or methacryloyl group of the silane coupling agent binds to the acryloyl or methacryloyl group in the chemical structure of the compound in formula (2), or to the acryloyl or methacryloyl group in the unbound silane coupling agent, thereby forming a polymer layer. The polymer constituting the polymer layer has the structural unit shown in the above formula (1) and the chemical structure derived from the silane coupling agent.

[0095]

[0096] In equation (2), R 1 R represents a hydrogen atom or a methyl group. 2 R represents a straight-chain or branched alkylene group with 2 or more but less than 6 carbon atoms. 3 This indicates an alkylene, cyclohexylene, or phenylene group with 2 or more but fewer than 6 carbon atoms. (Regarding R...) 2 and R 3 When the alkylene groups have only 1 carbon atom, the molecular chain becomes shorter, which may reduce the loading capacity of the carrier material, making it undesirable. When the alkylene groups have 7 or more carbon atoms, the hydrophobicity increases, making polymerization difficult and potentially reducing productivity, which is also undesirable.

[0097] As the compound of formula (2), from the viewpoint of improving reactivity with the silane coupling agent, improving the binding between the polymer layer and the carrier material, and increasing the loading, R is preferred. 2 Ethylene, R 3 It is an alkylene or phenylene. From the viewpoint of further increasing the loading of the carrier material onto the polymer layer, as shown in the examples described later, R is more preferably preferred. 3 It is a phenylene oxide.

[0098] As a silane coupling agent, an alkoxysilane having an acryloyl or methacryloyl group is used in order to polymerize with the compound of formula (2). In the polymer layer, from the viewpoint of more reliably increasing the loading of the carrier material, the alkoxysilane preferably has a long molecular chain and a large chemical structure; specifically, it preferably has an acryloyl or methacryloyl group and an alkylene group having 3 to 6 carbon atoms. Furthermore, from the viewpoint of improving reactivity with the compound of formula (2) and more reliably polymerizing the polymer, the alkoxysilane preferably has an acryloyloxypropyl or methacryloyloxypropyl group.

[0099] The amount of silane coupling agent and the compound of formula (2) added can be adjusted within a range that allows the polymer layer to be formed with the desired thickness. For example, the amount of silane coupling agent added is preferably 0.1 to 40 parts by mass relative to 100 parts by mass of the coated metal magnetic particles, more preferably 5.0 to 40 parts by mass, even more preferably 15 to 40 parts by mass, and may also be 0.1 to 10 parts by mass. By setting the amount of silane coupling agent added to 15 to 40 parts by mass relative to 100 parts by mass of the coated metal magnetic particles, the storage stability of the metal magnetic particles can be improved. In addition, the amount of compound of formula (2) added is preferably 100 to 700 parts by mass relative to 100 parts by mass of the coated metal magnetic particles, and may also be 100 to 500 parts by mass. Furthermore, the amount of compound of formula (2) added is preferably 10 to 100 times by mass relative to the amount of silane coupling agent added. It should be noted that storage stability refers to the stability of the carrier material loaded onto the polymer-coated metallic magnetic particles, ensuring that the loaded state remains intact even after a certain period of time. Specifically, the retention rate α, an indicator of storage stability, is calculated by setting the initial loading amount (A) when the carrier material is loaded onto the polymer-coated metallic magnetic particles as A, and the loading amount after a specified time as B, using α = B / A × 100 [%). High storage stability means that the loading amount B after the specified time does not deviate significantly from the initial loading amount A. The retention rate α is not particularly limited; for example, it can be 30% or higher.

[0100] 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, a water-soluble azo polymerization initiator having a carboxyl group is preferred as the polymerization initiator. It should be noted that the amount of polymerization initiator added is preferably 10 to 100 parts by mass relative to 100 parts by mass of the coated metallic magnetic particles.

[0101] After the polymerization reaction is complete, the inspection particles on which the polymer layer has been formed on the surface of the coated layer are recovered from the solvent using, for example, a magnet, and then washed. Thus, the inspection particles of this embodiment are obtained.

[0102] The method for determining the target substance using the aforementioned test particles is as follows. 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. Next, 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 using magnetic force. Finally, the target substance captured by the recovered carrier substance immobilized particles is determined using conventionally known methods.

[0103] The embodiments of the present invention have been described in detail above, but the present invention is not limited to the above embodiments, and various modifications can be made without departing from its spirit.

[0104] Example

[0105] Next, the present invention will be described in more detail based on embodiments, but the present invention is not limited to these embodiments. In this embodiment, a coating layer and a polymer layer are formed on the surface of the metallic magnetic particles to create polymer-coated metallic magnetic particles.

[0106] <Example 1> (1) Fabrication of polymer-coated metal magnetic particles

[0107] First, carbonyl iron powder (manufactured by BASF, HS grade D50: 2.3μm) is prepared as metallic magnetic particles.

[0108] Next, a coating of silicon oxide was formed on the surface of the carbonyl iron powder. Specifically, first, 5451g of isopropanol and 820g of pure water were added to a 10L reaction tank and stirred under a nitrogen atmosphere. Then, 1650g of carbonyl iron powder (hereinafter also referred to as Fe particles) was added to the solution and stirred at 40°C. Next, 257.4g of tetraethoxysilane (Wako Pure Chemical Industries, Ltd.) and 50g of isopropanol were added, and stirring was maintained for 5 minutes. Then, 567.3g of 25% ammonia solution was added over 90 minutes. Simultaneously with the addition of ammonia solution, the pump was started to deliver the solution to a high-pressure homogenizer (SMT Corporation, LAB1000). The high-pressure homogenizer was set to 150 bar for dispersion treatment while the solution was being delivered. The system was set to return the dispersed reaction solution to the 10L reaction tank. After adding ammonia solution, stirring was maintained for 60 minutes. The dispersion treatment continued until the reaction was complete. The obtained slurry was filtered, and the filter cake was dried in nitrogen at 110°C. This yielded silica-coated particles with a silicon oxide coating on the surface of carbonyl iron powder.

[0109] Next, a polymer layer is formed on the surface of the silica-coated particles. Specifically, 1.88 g of silica-coated particles (0.04 g silica content) is mixed with 30 g of pure water and ultrasonically treated for 30 minutes. The ultrasonically treated suspension and 204.76 g of pure water are added to a 300 mL detachable beaker and bubbled with nitrogen gas at 0.1 L / min for 30 minutes. The flow path of nitrogen gas is changed from bubbling into the liquid to flowing into the upper space of the liquid, and the temperature is raised to 35 °C while stirring. After heating, 0.119 g of 3-methacryloyloxypropyltrimethoxysilane (manufactured by Shin-Etsu Chemical Co., Ltd.) as the following formula (3) is added as a silane coupling agent and stirred for 30 minutes. Then, 6.67 g of 2-methacryloyloxyethyl phthalic acid (Tokyo Chemical Industry Co., Ltd.) as the following formula (monomer) and 5 mL of 5 wt% sodium hydroxide aqueous solution are added and stirred for 30 minutes. Then, the mixture was heated to 65°C and stirred for another 30 minutes. 0.994 g of 2,2'-azobis[N-(2-carboxyethyl)-2-methylpropanediamine]n hydrate (Wako Pure Chemical Industries, Ltd.) was dissolved in 5 g of pure water and added to the reaction vessel. After addition, stirring was maintained for 4 hours. After the polymerization reaction was complete, the particles were recovered using a magnet, the supernatant was removed, and the particles were redispersed in 50 g of pure water. The particles were recovered using a magnet, and the supernatant was removed. This washing operation, from redispersing in pure water to removing the supernatant, was repeated four times, and the resulting particles were dispersed in pure water. Thus, the slurry of polymer-coated metallic magnetic particles dispersed in Example 1 was obtained.

[0110]

[0111]

[0112] It should be noted that the production conditions of Example 1 are shown in Table 1 below.

[0113] [Table 1]

[0114]

[0115] (2) Evaluation

[0116] For the fabricated polymer-coated metallic magnetic particles, the following methods were used to evaluate the loading of the carrier material, the saturation magnetization and coercivity as magnetic properties, the carbon content, and the particle size.

[0117] (Load)

[0118] The loading of the carrier material was evaluated by examining the amount of biotin bound per unit mass of the particles. Hereinafter, EDC was 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride manufactured by Tokyo Chemical Industry Co., Ltd., MES was 2-(N-morpholino)ethanesulfonic acid, NHS was N-hydroxysuccinimide manufactured by Wako Pure Chemical Industries Co., Ltd., PBS was phosphate-buffered saline, TBS was Tris-buffered saline, and TBST was TBS containing Tween 20. First, the slurry containing the polymer-coated metallic magnetic particles was heated and dried to obtain the polymer-coated metallic magnetic particles. 1 mL of 0.01 mol / L MES buffer solution with an EDC concentration of 5 mg / mL was added to 1 mg of the obtained polymer-coated metallic magnetic particles, and the mixture was stirred using a vortex mixer for 30 minutes. After stirring, the magnetic particles were magnetically sieved and washed three times with 1 mL of 0.01 mol / L MES buffer solution. Next, 1 mL of 0.01 mol / L MES buffer solution with an NHS concentration of 0.8 mg / mL was added, and the mixture was stirred using a vortex mixer for 30 minutes. After stirring, the particles were magnetically sieved and washed three times with 1 mL of 0.01 mol / L MES buffer solution. Next, 1 mL of 0.01 mol / L PBS buffer solution (pH 5.7) with a streptavidin concentration of 0.2 mg / mL was added, and the mixture was vortexed for 30 minutes. After stirring, the particles were magnetically sieved and washed three times with 1 mL of 0.01 mol / L PBS buffer solution to obtain streptavidin-immobilized particles. Next, 100 μL of 1×TBS buffer (0.01 mg / mL ALP-Biotin, Thermo Fisher Scientific) was added to 50 μg of streptavidin-immobilized particles, and the mixture was allowed to stand for 30 minutes. Then, magnetic screening was performed, followed by washing three times with 200 μL of TBST buffer. The particles were then resuspended in 50 μL of TBS, transferred to a well plate, and 50 μL of Lumiphos plus (Wako Pure Chemical Industries, Ltd.) was added as the luminescent dye. After 5 minutes, the luminescence intensity was measured using a microplate reader. A calibration curve was then constructed comparing the luminescence intensity with the ALP-Biotin concentration, and the ALP-Biotin concentration was calculated from this curve as the biotin binding amount. For the test particles used in Comparative Example 1 described later, the biotin binding amount per unit mass was set at 100, and the biotin binding amount was calculated as a relative value. A relative value of 130 or higher was considered an evaluation of high biotin binding amount and high carrier loading.It should be noted that in the determination of luminescence intensity, an ELISA reader (CORONA ELECTRIC Co., Ltd. "SH-9000Lab") was used as the measurement conditions, and the measurement mode was set to luminescence and the gating time was 1.0 second.

[0119] (Maintain stability)

[0120] The stability was evaluated using streptavidin-immobilized particles obtained by the above-described loading method. In this embodiment, for the streptavidin-immobilized particles obtained by the above-described loading method, the initial biotin binding amount and the biotin binding amount after a specified time were calculated, and the maintenance rate was determined.

[0121] Specifically, for streptavidin immobilized particles obtained by the above-mentioned loading evaluation method, the calculated biotin binding amount is used as the initial biotin binding amount.

[0122] On the other hand, the streptavidin-immobilized particles were incubated at 37°C for 4 days. After the specified incubation period, 100 μL of 1×TBS buffer (0.01 mg / mL ALP-Biotin, Thermo Fisher Scientific) was added to 50 μg of the streptavidin-immobilized particles, and the mixture was incubated for 30 minutes. Then, magnetic screening was performed, followed by washing three times with 200 μL of TBST buffer. The particles were then resuspended in 50 μL of TBS, transferred to a well plate, and 50 μL of Lumiphos plus (Wako Pure Chemical Industries, Ltd.) was added as the luminescent dye. After 5 minutes, the luminescence intensity was measured using a microplate reader. A calibration curve was then constructed comparing the luminescence intensity with the ALP-Biotin concentration, and the ALP-Biotin concentration was calculated from this curve as the biotin binding amount. This biotin binding amount was taken as the biotin binding amount after 4 days at 37°C.

[0123] Then, the preservation stability is evaluated by the retention rate calculated using the formula shown below. In this embodiment, if the retention rate is 30% or higher, the preservation stability is evaluated as excellent.

[0124] (Maintenance rate [%)) = (Biotin binding amount after 4 days at 37℃) / (Initial biotin binding amount) × 100

[0125] (magnetic properties)

[0126] The slurry containing polymer-coated metallic magnetic particles was heated and dried to obtain polymer-coated metallic magnetic particles. The obtained polymer-coated metallic magnetic particles were then tested using a vibrating sample magnetometer (VSM) (Dongying Industrial Co., Ltd., VSM-5) with an applied magnetic field of 798 kA / m (10 kOe) and a measurement range of 0.05 A·m. 2The magnetic properties of saturation magnetization and coercivity were measured using a time constant of 0.03 seconds and a waiting time of 0.1 seconds (50 emu). Furthermore, this measurement utilized supplementary software (Ver. 2.1) manufactured by Toei Industrial Co., Ltd. In this embodiment, if the saturation magnetization is 100 Am... 2 If the coercivity is above 20 Oe, the polymer-coated metal magnetic particles can be collected in a short time when a magnetic field is applied, which is considered to be excellent magnetic coercivity. If the coercivity is below 20 Oe, the time from when the polymer-coated metal magnetic particles leave the magnetic field until they disperse is short, which is considered to be excellent dispersibility. In addition, in Table 1, the coercivity Hc is listed in both units of [Oe] and [kA / m].

[0127] (Quantity C)

[0128] The slurry containing polymer-coated metallic magnetic particles was heated and dried to obtain polymer-coated metallic magnetic particles. The carbon content of the obtained polymer-coated metallic magnetic particles was determined using a carbon-sulfur analyzer (EMIA-920V2 manufactured by Horiba, Ltd.).

[0129] (particle size)

[0130] Regarding the particle size of the polymer-coated metallic magnetic particles, the particle size distribution of the slurry containing the polymer-coated metallic magnetic particles was measured using a laser diffraction / scattering particle size distribution measuring device (“SYNC” manufactured by MicrotracBEL Co., Ltd.). Based on the obtained volume-based particle size distribution, the D50 (unit: μm) was calculated as the cumulative 50% particle size.

[0131] (3) Evaluation Results

[0132] The evaluation results are summarized in Table 2.

[0133] [Table 2]

[0134]

[0135] As shown in Table 2, the D50 of the polymer-coated metal magnetic particles in Example 1 was confirmed to be 2.2 μm, the biotin binding amount was 303, and the saturation magnetization was 197 Am. 2 / kg, coercivity Hc is 5Oe, and carbon content is 3%. That is, in Example 1, it was confirmed that the carrier material has a high loading capacity, high saturation magnetization, excellent magnetism, low coercivity, and excellent magnetic separation properties. It should be noted that the thickness of the coating layer was observed using a transmission electron microscope, confirming that its thickness is in the range of 1nm to 80nm.

[0136] The reason for the increased loading capacity is that a polymer layer is formed by using an alkoxysilane having an acryloyl or methacryloyl group and 2-methacryloyloxyethyl phthalic acid as a compound of formula (2). In Example 1, the polymer forming the polymer layer comprises: a structural unit derived from 2-methacryloyloxyethyl phthalic acid that satisfies formula (1); and a structural unit derived from a specified alkoxysilane. The structural unit derived from 2-methacryloyloxyethyl phthalic acid has a long molecular chain through ethyl and / or methacryloyl groups and phenylene groups. Therefore, the polymer layer readily binds streptavidin, thereby increasing its loading capacity. In addition, it is believed that in Example 1, since the core is set as an Fe particle, the saturation magnetization can be increased to improve the magnetic field strength, and the coercivity can be reduced to improve the magnetic separation. Furthermore, it is believed that the C content derived from the polymer layer is 0.5% to 10% by mass, and the polymer layer is formed with a moderate thickness, thereby achieving a balance between loading capacity and magnetic properties.

[0137] Furthermore, it was confirmed that the loading rate of the polymer-coated metal magnetic particles of Example 1 was maintained at as high as 37%, demonstrating excellent storage stability. This is believed to be because by adding 5.0 to 40 parts by mass of silane coupling agent relative to 100 parts by mass of the coated metal magnetic particles and adding 100 to 500 parts by mass of the compound of formula (2) relative to 100 parts by mass of the coated metal magnetic particles, a polymer layer can be uniformly formed on the coating.

[0138] (Examples 2-5)

[0139] In Examples 2-5, as shown in Table 1, the alkoxysilane, the compound of formula (2), and the type of metallic magnetic particles were appropriately changed. Otherwise, the polymer-coated metallic magnetic particles were prepared in the same manner as in Example 1.

[0140] As an alkoxysilane, 3-acryloyloxypropyltrimethoxysilane as shown in formula (5) below is used.

[0141]

[0142] As the compound of formula (2), 2-acryloyloxyethyl succinic acid as shown in formula (6) is used.

[0143]

[0144] Fe-B alloy particles or Fe-Ni alloy particles were used as metallic magnetic particles.

[0145] Fe-B alloy particles were prepared as follows: First, in a 500ml beaker, 11.3g of ferric chloride (FeCl2), 15.9g of ammonium chloride, and 62.3g of sodium gluconate were dissolved in 285.7g of water at 30℃. Next, 28.2g of 25% ammonia water was added to adjust the pH of the raw material solution to 9. Then, the liquid temperature was adjusted to 50℃, and while stirring at 300rpm, a solution containing 21.7g of sodium borohydride in 214.2g of water was added, and the mixture was allowed to mature for 10 minutes. The resulting particles were collected using a magnet and washed with ethanol to obtain Fe-B alloy particles. It should be noted that the boron content was 9.2wt%.

[0146] As Fe-Ni alloy particles, particles with a Fe content of 50% and a Ni content of 50% were used.

[0147] The polymer-coated metallic magnetic particles of Examples 2-5 were evaluated in the same manner as in Example 1. The results are shown in Table 2. Similar to Example 1, Examples 2-5 confirmed higher biotin binding, higher saturation magnetization, and lower coercivity. Furthermore, in Examples 2-5, the coating thickness and storage stability were confirmed to be similar to those of Example 1.

[0148] It was further confirmed that in Examples 1-5, alkoxysilanes having an acryloyl group or a methacryloyl group and having an alkylene group with 3 to 6 carbon atoms were used as silane coupling agents. Specifically, alkoxysilanes having an acryloyloxypropyl group or a methacryloyloxypropyl group were used, thus further increasing the loading amount in the polymer-coated metal magnetic particles.

[0149] Furthermore, when comparing Examples 1-5, it was confirmed that the compound of formula (2) was used with R 3 In Examples 1, 3, and 4, phthalic acid of formula (4) being phenylene, compared with the use of R 3 Compared to Examples 2 and 5, which use succinic acid of formula (6) as an alkylene group, the biotin binding capacity is increased. It is therefore believed that by introducing a larger chemical structure into the polymer layer, the streptavidin loading can be increased, resulting in further biotin capture.

[0150] (Comparative Examples 1-5)

[0151] In Comparative Examples 1-5, as shown in Table 1, the types of alkoxysilanes were appropriately changed to those of formulas (7)-(8) below, and the types of compounds of formula (2) were appropriately changed to those of formulas (9)-(11) below. Otherwise, polymer-coated metallic magnetic particles were prepared in the same manner as in Example 1. 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 metallic magnetic particles of Comparative Examples 1-5 were evaluated in the same manner as in Example 1. The results are shown in Table 2.

[0152]

[0153]

[0154]

[0155]

[0156]

[0157] As shown in Table 2, in Comparative Examples 1-3, it was confirmed that although the saturation magnetization was high and the coercivity was low, the biotin binding amount was lower compared to Examples 1-5. This is because, in the formation of the polymer layer, compounds satisfying formula (2) were not used; instead, styrene, 2-carboxyethyl acrylate, and 4-vinylbenzoic acid were used. It is speculated that this is because, in Comparative Examples 1-3, it was not possible to introduce long-chain, large-volume chemical structures into the polymer layer as in Examples 1-5, thus hindering efficient binding with streptavidin.

[0158] Furthermore, in Comparative Examples 4 and 5, as shown in Table 2, it was confirmed that compared to Examples 1-5, there was a tendency for lower biotin binding and lower magnetic properties. This is because, in the formation of the polymer layer, alkoxysilanes having acryloyl or methacryloyl groups were not used as silane coupling agents; instead, trimethoxy-4-vinylphenylsilanes or triethoxyvinylsilanes without acryloyl or methacryloyl groups were used. It is speculated that this is because in Comparative Examples 4 and 5, the polymer layer could not be constructed in a manner that facilitates streptavidin binding, and it was also impossible to construct it with a C content of 0.5% to 10% by mass. It should be noted that the biotin binding in Comparative Examples 1-5 was low, therefore, storage stability was not evaluated.

[0159] (Examples 6-16)

[0160] In Examples 6-16, as shown in Table 3, the alkoxysilane (silane coupling agent), the compound of formula (2), and the type of metallic magnetic particles were appropriately changed. Otherwise, the polymer-coated metallic magnetic particles were prepared in the same manner as in Example 1. Then, the polymer-coated metallic magnetic particles were evaluated in the same manner as in Example 1. The evaluation results for Examples 6-16 are summarized in Table 4.

[0161] As alkoxysilanes, 3-methacryloyloxypropylmethyldimethoxysilane as shown in formula (12) or 3-methacryloyloxypropylmethyldiethoxysilane as shown in formula (13) were used.

[0162]

[0163]

[0164] In addition, as compounds of formula (2), 2-methacryloyloxyethyl succinic acid as shown in formula (14), 2-acryloyloxyethyl phthalic acid as shown in formula (15), and 2-acryloyloxyethyl hexahydrophthalic acid as shown in formula (16) were used.

[0165]

[0166]

[0167]

[0168] [Table 3]

[0169]

[0170] In Example 6, similar to Example 5, a silicon oxide coating layer 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. Next, 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) was mixed with 40 g of pure water and subjected to ultrasonic treatment for 10 minutes. The ultrasonically treated suspension and 488.63 g of pure water were added to a 1 L beaker and bubbled 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 flowing into the upper space of the liquid, and the temperature was raised to 35°C while stirring. After heating, 1.61 g of 3-methacryloyloxypropylmethyldimethoxysilane (manufactured by Shin-Etsu Chemical Industry Co., Ltd.) as shown in formula (12) above was added as a silane coupling agent, and the mixture was stirred for 30 minutes. Next, 44.94 g of 2-methacryloyloxyethyl phthalic acid (Tokyo Chemical Industry Co., Ltd.), the monomer of formula (2), as shown in formula (15), was dissolved in 150 g of pure water and 70 g of 10 wt% sodium hydroxide aqueous solution, and added to the reaction vessel and stirred for 30 minutes. Then, the mixture was further stirred for 30 minutes while heating to 65°C. 6.69 g of 2,2'-azobis[N-(2-carboxyethyl)-2-methylpropanediamine]n hydrate (Wako Pure Chemical Industries Co., Ltd.) was dissolved in 30 g of pure water and added to the reaction vessel. After addition, stirring was maintained for 4 hours. After the polymerization reaction was completed, the particles were recovered using a magnet, the supernatant was removed, and the particles were redispersed in 200 g of pure water. The particles were recovered using a magnet, and the supernatant was removed. This washing operation from redispersing in pure water to removing the supernatant was repeated 4 times, and the resulting particles were dispersed in pure water. Thus, the slurry containing polymer-coated metallic magnetic particles dispersed in Example 6 was obtained.

[0171] In Examples 7-9, as shown in Table 3, the types of compounds (monomers) represented by Formula (2) were appropriately changed, and polymer-coated metallic magnetic particles were prepared in the same manner as in Example 6.

[0172] In Example 10, a polymer layer was formed on the surface of 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) was mixed with 40 g of pure water and subjected to ultrasonic treatment for 10 minutes. The ultrasonically treated suspension and 517.94 g of pure water were added to a 1 L beaker and bubbled with nitrogen gas at 0.1 L / min for 30 minutes. The flow path of nitrogen gas was changed from bubbling into the liquid to flowing into the upper space of the liquid, and the temperature was raised to 35°C while stirring. After heating, 1.84 g of 3-methacryloyloxypropylmethyldimethoxysilane (manufactured by Shin-Etsu Chemical Industry Co., Ltd.) as shown in Formula (12) above was added as a silane coupling agent and stirred for 30 minutes. Next, 30.8 g of 2-methacryloyloxyethyl phthalic acid (Tokyo Chemical Industry Co., Ltd.), the monomer of formula (2), as shown in formula (15), was dissolved in 150 g of pure water and 55 g of 10 wt% sodium hydroxide aqueous solution, and added to the reaction vessel and stirred for 30 minutes. Then, the mixture was further stirred for 30 minutes while heating to 65°C. 4.59 g of 2,2'-azobis[N-(2-carboxyethyl)-2-methylpropanediamine]n hydrate (Wako Pure Chemical Industries Co., Ltd.) was dissolved in 20 g of pure water and added to the reaction vessel. After addition, stirring was maintained for 4 hours. After the polymerization reaction was completed, the particles were recovered using a magnet, the supernatant was removed, and the particles were redispersed in 200 g of pure water. The particles were recovered using a magnet, and the supernatant was removed. This washing operation from redispersing in pure water to removing the supernatant was repeated 4 times, and the resulting particles were dispersed in pure water. Thus, the slurry of Example 10, in which polymer-coated metallic magnetic particles are dispersed, is obtained.

[0173] In Examples 11-14, as shown in Table 3, the types of compounds (monomers) represented by Formula (2) were appropriately changed, and polymer-coated metallic magnetic particles were prepared in the same manner as in Example 10.

[0174] In Example 15, as shown in Table 3, when forming the polymer layer, the silane coupling agent was changed to 2.05 g of 3-methacryloyloxypropylmethyldiethoxysilane as shown in Formula (13) above. Otherwise, the polymer-coated metal magnetic particles were prepared in the same manner as in Example 10.

[0175] In Example 16, as shown in Table 3, when forming the polymer layer, the silane coupling agent was changed to 1.85g of 3-acryloyloxypropyltrimethoxysilane as shown in Formula (5) above. Otherwise, the polymer-coated metal magnetic particles were prepared in the same manner as in Example 10.

[0176] [Table 4]

[0177]

[0178] As shown in Table 4, similar to Example 5, Examples 6-9 exhibited higher biotin binding amounts, higher saturation magnetization, and lower coercivity. Furthermore, similar to Example 1, Examples 10-16 exhibited higher biotin binding amounts, higher saturation magnetization, and lower coercivity. It should be noted that in Examples 6-16, the coating thickness was confirmed to be the same as in Example 1.

[0179] Furthermore, in Examples 6-16, it was confirmed that the loading retention rate was higher and the storage stability was excellent compared to Examples 1-5. This is presumably because in Examples 6 and the like, the amount of silane coupling agent added was greater than in Example 1, enabling the formation of a thick and uniform polymer layer on the coating.

[0180] As described above, in polymer-coated metallic magnetic particles, by forming a polymer layer comprising the structural units shown in formula (1) and alkoxysilanes having acryloyl or methacryloyl groups, it is easy to incorporate carrier substances capable of capturing the target substance being inspected, such as streptavidin, thereby increasing its loading capacity. Furthermore, by making the core a metallic magnetic particle, the proportion of magnetic metal in the polymer-coated metallic magnetic particles can be increased, improving its magnetic cohesion and magnetic separation properties.

Claims

1. A polymer-coated metallic magnetic particle, comprising: Metallic magnetic particles; A coating layer, disposed on the surface of the metallic magnetic particles, is composed of silicon oxide; and A polymer layer disposed on the surface of the coating layer, comprising a polymer of structural units of formula (1) and alkoxysilanes having acryloyl or methacryloyl groups. In equation (1), R 1 R represents a hydrogen atom or a methyl group. 2 R represents a straight-chain or branched alkylene group with 2 or more but less than 6 carbon atoms. 3 It indicates an alkylene, cyclohexylene, or phenylene group with 2 or more but less than 6 carbon atoms.

2. The polymer-coated metallic magnetic particles according to claim 1, wherein, In the above formula (1), R 2 It is ethylene, R 3 It is an alkylene, phenylene, or cyclohexylene group.

3. The polymer-coated metallic magnetic particles according to claim 2, wherein, R in equation (1) 3 It is a phenylene oxide.

4. The polymer-coated metallic magnetic particles according to claim 1 or 2, wherein, The alkoxysilane has an acryloyl or methacryloyl group and an alkylene group having 3 to 6 carbon atoms.

5. The polymer-coated metallic magnetic particles according to claim 4, wherein, The alkoxysilane has an acryloyloxypropyl group or a methacryloyloxypropyl group.

6. The polymer-coated metallic magnetic particles according to claim 1 or 2, wherein, The metallic magnetic particles are iron particles or iron-based alloy particles.

7. The polymer-coated metallic magnetic particles according to claim 1 or 2, Its saturation magnetization is 100 Am. 2 / kg or more and 210Am 2 / kg or less.

8. The polymer-coated metallic magnetic particles according to claim 1 or 2, wherein, The cumulative 50% particle size of the volume standard, as measured by a laser diffraction particle size distribution measuring device, is 0.2 μm to 10 μm.

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

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

11. A method for manufacturing polymer-coated metallic magnetic particles, comprising: The process of forming a coating layer of silicon oxide on the surface of metallic magnetic particles; and, The process of forming a polymer layer on the coating layer by mixing metallic magnetic particles on which the coating layer is formed, water, and an alkoxysilane having an acryloyl group or a methacryl group, and then adding a compound of formula (2) to polymerize it. In equation (2), R 1 R represents a hydrogen atom or a methyl group. 2 R represents a straight-chain or branched alkylene group with 2 or more but less than 6 carbon atoms. 3 It indicates an alkylene, cyclohexylene, or phenylene group with 2 or more but less than 6 carbon atoms.

12. The method for manufacturing polymer-coated metallic magnetic particles according to claim 11, wherein, In equation (2), R 2 It is ethylene, R 3 It is an alkylene, phenylene, or cyclohexylene group.

13. The method for manufacturing polymer-coated metallic magnetic particles according to claim 12, wherein, R in equation (2) 3 It is a phenylene oxide.

14. The method for manufacturing polymer-coated metallic magnetic particles according to claim 11 or 12, wherein, The alkoxysilane has an acryloyl or methacryloyl group and an alkylene group having 3 to 6 carbon atoms.

15. The method for manufacturing polymer-coated metallic magnetic particles according to claim 14, wherein, The alkoxysilane has an acryloyloxypropyl group or a methacryloyloxypropyl group.

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

17. The method for manufacturing polymer-coated metallic magnetic particles according to claim 11 or 12, wherein, In the process of forming the polymer layer, a water-soluble azo polymerization initiator with a carboxyl group is used as the polymerization initiator.