Fine particle and production method thereof

Abstract

To provide: a fine particle which has superparamagnetism and which does not deteriorate when brought into contact with water; and a production method thereof.SOLUTION: A fine particle (1) according to the present invention includes γ-Fe2O3(5) contained in a matrix phase (3) containing SiO2. In the fine particle, an atom ratio (Si / Fe) between a silicon atom derived from SiO2 and an iron atom derived from γ-Fe2O3 is preferably 0.050 to 0.500, a coercive force is preferably 480A / m or less, and a saturation magnetization is preferably 40A m2 / kg or more.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to superparamagnetic particles and a method for producing the same. [Background technology]

[0002] A widely used method for recovering biomolecules from a specimen (biological sample) containing biomolecules such as proteins and nucleic acids involves bringing the biological sample into contact with magnetic particles to capture the biomolecules on the magnetic particles, followed by recovery of the captured particles using magnetic force, separation of the biomolecules, quantification, etc. Magnetic particles used for such purposes are preferably superparamagnetic, and techniques such as those described in Patent Documents 1 to 4 are known.

[0003] Patent Document 1 discloses superparamagnetic particles characterized in that (a) they comprise stable, resolvable aggregates with a particle size in the range of 10 to 1,000 nanometers that exhibit a defined behavior in a magnetic field, and the aggregates are (b) aggregates of small superparamagnetic single-domain particles with a particle size of 3 to 20 nanometers, made of iron oxide, an iron oxide mixture, or iron, and (c) they can carry on their surface a chemically bonded substance selected from the group including phosphate, diphosphate, carboxylate, polyphosphate, thiophosphate, phosphonate, thiophosphonate, sulfate, sulfonate, mercapto, silanetriol, trialkoxysilane group-containing polyalkylene glycol, carbohydrate or phosphate group-containing nucleotide, its oligomer, or polymer, which may have additional binding sites.

[0004] In Patent Document 2, the average particle diameter d 50Disclosed are superparamagnetic single-domain particles having enhanced R1 relaxivity and surface stabilizing materials, which comprise iron hydroxide, iron oxide hydrate, iron oxide, mixed iron oxides, or iron, with particle sizes ranging from 1 to 10 nanometers, with an R2 / R1 relaxivity ratio of 2 to 50; having an R2 / R1 relaxivity ratio of 5 or less; and having a stabilizing material on their surface selected from aliphatic di- and polycarboxylic acids, their substitution products and derivatives; which prevent aggregation or sedimentation in gravitational or magnetic fields; and which optionally contain additional stabilizing materials, tissue-specific binding materials, pharmacologically active ingredients, pharmacologically active cells, pharmacologically active chelating agents, cell fusion mediators, or gene transfer mediators, and mixtures thereof.

[0005] Patent Document 3 discloses magnetic silica particles characterized by having immobilized on the surface thereof a substance to be measured, a substance similar to the substance to be measured, or a substance that specifically binds to the substance to be measured, and further having immobilized thereon arginine or an arginine derivative. Cited Document 1 also describes that the magnetic silica particles preferably contain 60 to 95% by weight of a superparamagnetic metal oxide having an average particle size of 1 to 15 nm and consisting of at least one oxide selected from the group consisting of magnetite, γ-hematite, magnetite-α-hematite intermediate iron oxide, and γ-hematite-α-hematite intermediate iron oxide.

[0006] Furthermore, Patent Document 4 discloses fine particles characterized by being composed of crystals containing iron atoms, oxygen atoms, and carbon atoms, the atomic ratio of the carbon atoms to the iron atoms (C / Fe) being 0.30 to 1.50, and having a Fe3O4 pattern or a mixture pattern of Fe3O4 and γ-Fe2O3 by X-ray diffraction (ray source: CuKα). [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Japanese Patent Application Publication No. 8-508721 [Patent Document 2] Japanese Patent Application Laid-Open No. 2000-507197 [Patent Document 3] Japanese Patent Application Laid-Open No. 2013-205263 [Patent Document 4] Japanese Patent Application Publication No. 2022-97228 Summary of the Invention [Problem to be solved by the invention]

[0008] An object of the present invention is to provide superparamagnetic microparticles that do not denature when in contact with water, and a method for producing the same. [Means for solving the problem]

[0009] The present invention is illustrated below. [1] Microparticles characterized by containing γ-Fe2O3 in a matrix phase containing SiO2. [2] The fine particles according to the above [1], wherein the atomic ratio (Si / Fe) of silicon atoms derived from the SiO2 to iron atoms derived from the γ-Fe2O3 is 0.050 to 0.500. [3] The fine particles according to the above [1], which have a secondary particle diameter of 0.5 to 2.0 μm. [4] The coercive force is 480 A / m or less, and the saturation magnetization is 40 A m 2 / kg or more of the microparticles described in [1] above. [5] A method for producing the microparticles described in [1] above, comprising: a raw material preparation step of mixing nanoparticles made of Fe3O4, a dispersant, and an aqueous solution of silica to prepare a raw material liquid; and a pyrolysis step of subjecting the raw material liquid to spray pyrolysis. [Effects of the Invention]

[0010] The particles of the present invention have a coercive force of 480 A / m or less and a saturation magnetization of 40 A·m 2 / kg or more, and therefore can be suitably used as superparamagnetic microparticles. For example, when a composition is prepared using such superparamagnetic microparticles and water, the γ-Fe2O3 is not oxidized or otherwise denatured, and the composition is stable, so this composition is expected to be used in isolation, solidification, or purification of cells, nucleic acids, enzymes, antibodies, proteins, or peptides, as well as in phagocytic diagnosis in cell biology. According to the method for producing fine particles of the present invention, it is possible to efficiently produce fine particles in which γ-Fe2O3 is embedded in SiO2 without being exposed. [Brief explanation of the drawings]

[0011] [Figure 1] 1 is a schematic diagram showing a cross section of a fine particle of the present invention. [Figure 2] FIG. 1 is a schematic diagram showing an example of a spray pyrolysis apparatus used for producing fine particles. [Figure 3] 1 shows X-ray diffraction patterns of the fine particles (T1), (T2) and (T3) obtained in Examples 1, 2 and 3. [Figure 4] 1 is an SEM image of the fine particles (T1) obtained in Example 1. [Figure 5] 1 shows X-ray diffraction images of the fine particles (T1) obtained in Example 1 before and after contact with water in a water contact test. [Figure 6] 1 is an SEM image of the fine particles (T2) obtained in Example 2. [Figure 7] 1 is an SEM image of the fine particles (T3) obtained in Example 3. DETAILED DESCRIPTION OF THE INVENTION

[0012] The fine particles of the present invention are composite particles (fine particles containing γ-Fe2O3) in which γ-Fe2O3 is contained in a matrix phase containing SiO2. Whether the fine particles of the present invention contain γ-Fe2O3 can be confirmed by X-ray diffraction.

[0013] In the present invention, the atomic ratio (Si / Fe) of silicon atoms (silicon atoms derived from SiO2) to iron atoms (iron atoms derived from γ-Fe2O3), calculated based on the materials constituting the fine particles, is 0.050 to 0.500, preferably 0.060 to 0.400, and more preferably 0.061 to 0.352, from the viewpoint of superparamagnetism. In the fine particles having the above atomic ratio (Si / Fe) of 0.050 to 0.500, the coercive force (the magnetic field strength corresponding to zero magnetic flux density on the magnetic hysteresis curve) is preferably 480 A / m or less, more preferably 450 A / m or less. The saturation magnetization is preferably 40 A·m 2 / kg or more, preferably 41A·m 2 The coercive force and saturation magnetization can be measured, for example, by a vibrating sample magnetometer.

[0014] The shape and size of the microparticles of the present invention are not particularly limited. The shape of the microparticles can typically be spherical, oval-spherical, or a modified form thereof, but is preferably spherical or a modified form thereof. The structure of the microparticles can be solid, hollow, porous, mesoporous, or the like, and the surface of the microparticles may have protrusions or depressions. Figure 1 is a schematic diagram showing the cross section of a microparticle 1 of the present invention, which typically contains a matrix phase 3 containing amorphous SiO2 and multiple dispersed phases 5 composed of γ-Fe2O3. While Figure 1 shows microparticles 1 with depressions, regardless of their depth, γ-Fe2O3 is not exposed on the surface of the microparticles 1; the surface of the microparticles 1 is made of SiO2. Because SiO2 is colorless, the microparticles 1 of the present invention exhibit a color derived from γ-Fe2O3.

[0015] The particle diameter (secondary particle diameter) of the microparticles of the present invention is preferably 0.5 to 2.0 μm, more preferably 0.6 to 1.5 μm, when the particle diameters of 20,000 microparticles are measured using a "Morphologi4" manufactured by Malvern Panalytical at a magnification of 50 times and the average value is then calculated. As described above, the microparticles of the present invention have superparamagnetism due to the presence of γ-Fe2O3 in a matrix phase containing SiO2 and the atomic ratio of carbon atoms to iron atoms (Si / Fe) being within a preferred range. Furthermore, the crystallite size obtained by the Scherrer formula using X-ray diffraction is also closely related to superparamagnetism, and the crystallite size of the γ-Fe2O3 in the microparticles of the present invention is preferably 11 nm or less, more preferably 10.7 nm or less. However, the lower limit is usually 6 nm.

[0016] The specific surface area of ​​the microparticles of the present invention is preferably 50 m 2 / g or more, more preferably 90m 2 This specific surface area can be measured by the BET method using nitrogen adsorption. The true density of the fine particles of the present invention is preferably 2.5 to 5.0 g / cm 3 , more preferably 2.8 to 4.5 g / cm 3 This true density can be measured by a method conforming to JIS M 8717 (2017).

[0017] The method for producing microparticles of the present invention comprises a raw material preparation step of mixing nanoparticles made of Fe3O4 (hereinafter referred to as "Fe3O4 nanoparticles"), a dispersant, and an aqueous solution of silica (SiO2) to prepare a raw material liquid, and a pyrolysis step of subjecting this raw material liquid to spray pyrolysis.

[0018] The Fe3O4 nanoparticles used in the raw material preparation step are particles having a particle diameter, measured by observation with a transmission electron microscope, of preferably 3 to 10 nm, more preferably 5 to 8 nm. The shape of the Fe3O4 nanoparticles is not particularly limited, and may be spherical, ellipsoidal, or a modified shape thereof.

[0019] The method for producing Fe3O4 nanoparticles is not particularly limited. In the raw material preparation step, for example, a reaction product (solid component) obtained by mixing an aqueous solution of iron (II) chloride, an aqueous solution of iron (III) chloride, and aqueous ammonia can be suitably used as Fe3O4 nanoparticles.

[0020] Examples of dispersants used in the raw material preparation step include ammonium polyacrylate and ammonia. The amount of the dispersant used is preferably 0.5 to 2 parts by mass, and more preferably 0.8 to 1.5 parts by mass, based on 100 parts by mass of the Fe3O4 nanoparticles used.

[0021] The silica (SiO2) aqueous solution used in the raw material preparation step is an aqueous solution having a silica concentration of preferably 1 to 15 mass %, more preferably 3 to 10 mass %. The pH of the aqueous solution is not particularly limited, but is usually 10 to 13.

[0022] The amount of the aqueous silica solution used is set so that the amount of silica is preferably 2 to 25 parts by mass, more preferably 4 to 20 parts by mass, based on 100 parts by mass of the Fe3O4 nanoparticles used.

[0023] In the raw material preparation step, when mixing FeO nanoparticles, a dispersant, and an aqueous silica solution, a mixer such as a ball mill, a bead mill, a homogenizer, a paint shaker, an ultrasonic disperser, a plowshare mixer, or a planetary ball mill can be used. Multiple mixers may be used in the raw material preparation step.

[0024] In the raw material preparation step, it is preferable to mix the raw materials in an inert gas atmosphere, and it is particularly preferable to introduce an inert gas into the raw material mixture and stir it while bubbling.

[0025] Next, the mixed liquid obtained in the raw material preparation step, i.e., the raw material liquid according to the present invention, is subjected to a pyrolysis step and is spray pyrolyzed.

[0026] In the method for producing fine particles of the present invention, the apparatus for applying spray pyrolysis is not particularly limited, and for example, a fine particle production apparatus 10 shown in Fig. 2 can be used. The fine particle production apparatus 10 in Fig. 2 includes a droplet production means (X) that generates droplets 14 from a raw material liquid 13, a carrier gas supply means (not shown) that supplies the droplets 14 formed by the droplet production means (X) into a heating means (Y) by a carrier gas (air, nitrogen, etc.), a heating means (Y) that has, for example, a cylindrical structure and thermally decomposes the droplets 14 supplied thereto by the carrier gas to generate fine particles 17, and a fine particle collection means (Z) that collects the fine particles 17 obtained by the heating means (Y) in a collector 16.

[0027] 2, when preparing droplets 14 by the droplet-forming means (X), an ultrasonic method equipped with an ultrasonic vibrator or a nozzle method using a spray nozzle such as a two-fluid nozzle or a pressure spray nozzle can be applied. The size, shape, etc. of the droplets 14 to be formed are not particularly limited.

[0028] The droplets 14 are then supplied into the heating means (Y) by a carrier gas from a carrier gas supply means (not shown). The flow rate of the carrier gas is appropriately selected depending on the structure of the heating means (Y) and is preferably 3 to 20 L / min, more preferably 5 to 10 L / min.

[0029] In the heating means (Y), the droplets 14 are heated in the cylinder while being flowed by the carrier gas, and are thermally decomposed to form fine particles 17. In FIG. 2, the cylinder is linear, but it may be spiral. The heating temperature (maximum temperature) of the droplets 14 in the heating means (Y) is usually selected from the range of 150°C to 400°C. The heating means (Y) may be an electric furnace or the like. 2 has a preferred configuration in the present invention and is equipped with four heating means 15a, 15b, 15c, and 15d, and the heating temperature can be set to increase in this order to thermally decompose the droplets 14. The temperatures of the heating means are preferably 100°C to 150°C for heating means 15a, more than 150°C to 200°C for heating means 15b, more than 200°C to 300°C for heating means 15c, and more than 300°C to 400°C for heating means 15d. In the present invention, the droplets 14 can also be thermally decomposed by a heating means (Y) set at a constant temperature.

[0030] Thereafter, the fine particles 17 obtained by the heating means (Y) are carried by the carrier gas and collected in the collector 16. The structure and constituent materials of the collector 16 are not particularly limited, but a heat-resistant collector or the like can be used. [Example]

[0031] In order to more specifically describe the configuration and effects of the present invention, examples are given below, but the present invention is not limited to these examples. In the following examples and comparative examples, "parts" and "%" are all based on mass.

[0032] 1. Preparation of raw material solution for microparticle production The raw material solution for producing fine particles used in the examples described later was prepared by the following method. The silica aqueous solution used in combination with the Fe3O4 microparticles was prepared by placing 16.1 parts of silicon dioxide n-hydrate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), 24.5 parts of tetramethylammonium aqueous solution (manufactured by Kanto Chemical Co., Ltd.), and 29 g of water in a fluororesin inner cylindrical pressure vessel, heating it at 100°C for 12 hours to form an aqueous solution, and then diluting it with water to a SiO2 content of 5% (pH 13).

[0033] Preparation example 1 8.52 g of iron(II) chloride 4H2O and 15.60 g of iron(III) chloride 6H2O were dissolved in 100 mL of ion-exchanged water. The resulting solution was placed in a container with 400 mL of 0.89 mol / L ammonia water, and the mixture was heated to 25°C. The mixture was then stirred with a stirrer for 1 hour while bubbling with argon gas to produce Fe3O4. The resulting reaction solution was then centrifuged, and the precipitated Fe3O4 particles were collected and washed with distilled water. The average particle size of the Fe3O4 particles was measured using a transmission electron microscope and found to be 8 nm. Thereafter, the Fe3O4 microparticles, the 5% silica aqueous solution, and ammonium polyacrylate (dispersant) were dispersed and peptized using a ball mill at 200 rpm for 5 hours to obtain a raw material liquid for producing microparticles (hereinafter referred to as "raw material liquid for producing microparticles (M1)"). The amounts of the silica aqueous solution and ammonium polyacrylate used were 94 parts and 5 parts, respectively, based on 100 parts of the Fe3O4 microparticles used.

[0034] Preparation example 2 The Fe3O4 microparticles obtained in Preparation Example 1, the above 5% aqueous silica solution, and 0.4 mol / L aqueous ammonia (dispersant) were dispersed and deflocculated using a homogenizer at 10,000 rpm for 30 minutes to obtain a raw material liquid for producing microparticles (hereinafter referred to as "raw material liquid for producing microparticles (M2)"). The amounts of the aqueous silica solution and the aqueous ammonia used were 362 parts and 250 parts, respectively, based on 100 parts of the Fe3O4 microparticles used.

[0035] Preparation example 3 8.52 g of iron(II) chloride 4H2O and 15.60 g of iron(III) chloride 6H2O were dissolved in 300 mL of ion-exchanged water. The resulting solution was placed in a container with 500 mL of 0.71 mol / L tetraammonium hydroxide solution, and the mixture was heated to 25°C. The mixture was stirred with a stirrer for 1 hour while bubbling with argon gas to produce Fe3O4. The resulting reaction solution was then centrifuged, and the precipitated Fe3O4 particles were collected and washed with distilled water. The average particle diameter of the Fe3O4 particles was measured using a transmission electron microscope and found to be 9 nm. Then, the Fe3O4 microparticles and the 5% silica aqueous solution were mixed using a stirring rod to obtain a raw material solution for producing microparticles (hereinafter referred to as "raw material solution for producing microparticles (M3)"). The amount of silica aqueous solution used was 155 parts when the amount of Fe3O4 microparticles used was 100 parts.

[0036] 2. Production and evaluation of microparticles In the following Examples 1 to 3, fine particles 17 were produced by subjecting droplets 14 of a raw material liquid 13 for producing fine particles to spray pyrolysis using a fine particle production apparatus 10 shown in FIG. 2 includes a droplet generating means (X) that converts raw material liquid 13 in raw material liquid storage tank 11 into droplets 14 using an ultrasonic generator 12 equipped with an ultrasonic vibrator (up to 1.7 MHz), a carrier gas supply means (not shown) that supplies the droplets 14 formed by the droplet generating means (X) into heating means (Y) using a carrier gas (air), a cylindrical heating means (Y) that thermally decomposes the droplets 14 supplied thereto by the carrier gas to generate fine particles 17, and a collector 16 that collects the fine particles 17 produced by heating means (Y). Heating means (Y) includes four electric furnaces 15a, 15b, 15c, and 15d (each with a length of 300 mm) so that the heating temperature increases stepwise from the upstream side to the downstream side (collector 16 side) along which the droplets 14 flow while being thermally decomposed.

[0037] Example 1 The raw material liquid (M1) for producing microparticles obtained in Preparation Example 1 was formed into droplets using the droplet-forming means (X), and the resulting droplets 14 were guided to the heating means (Y) by a carrier gas (air) at a flow rate of 10 L / min. The droplets 14 were then thermally decomposed in the heating means (Y) to form microparticles 17 (hereinafter referred to as "microparticles (T1)"), which were then collected in the collector 7 of the collection means (Z). The microparticles (T1) were brown in color. The temperatures of the four electric furnaces in the heating means (Y), from the upstream side, were set to 100°C (15a in FIG. 2), 150°C (15b in FIG. 2), 200°C (15c in FIG. 2), and 300°C (15d in FIG. 2).

[0038] The obtained microparticles (T1) were subjected to various analyses, measurements, and evaluations. Table 1 shows the measurement results of the Fe state, Si / Fe ratio, crystallite size, secondary particle diameter, specific surface area, true density, coercive force, saturation magnetization, zeta potential, etc.

[0039] (1)XRD measurement XRD measurements were carried out using a Rigaku X-ray diffractometer "RINT2200" (model name) with a CuKα X-ray source. The X-ray diffraction image of the microparticles (T1) obtained in Example 1 is shown in Figure 3. The X-ray diffraction image in Figure 3 shows the pattern of γ-Fe2O3, indicating that the microparticles (T1) contain γ-Fe2O3.

[0040] (2)Si / Fe ratio The Si and Fe amounts were quantified using an Agilent Technologies ICP optical emission spectrometer "5800VDV" (model name), and the atomic ratio (Si / Fe ratio) was found to be 0.061.

[0041] (3) Crystallite size The crystallite size was calculated from the Scherrer equation using X-ray diffraction.

[0042] (4) Secondary particle size The fine particles (T1) were observed using a scanning electron microscope "SU8000" (model name) manufactured by Hitachi High-Technologies Corporation. An image of the microparticles (T1) is shown in Figure 4. From Figure 4, it can be seen that the microparticles (T1) have an uneven surface. Furthermore, using a "Morphologi4" manufactured by Malvern Panalytical, observation was performed with an objective lens of 50x magnification, and the particle diameters of 20,000 microparticles were measured. The average value was calculated, and the particle diameter (secondary particle diameter) of the microparticles (T1) was found to be 1.20 ± 0.25 μm.

[0043] (5) Specific surface area The specific surface area was measured by the BET method using nitrogen adsorption.

[0044] (6)True density In accordance with JIS R 1620, the true density was measured by the gas substitution method using He gas.

[0045] (7) Magnetic properties The magnetic properties (coercive force and saturation magnetization) of the fine particles (T1) at 27°C were measured using a vibrating sample magnetometer.

[0046] (8) Zeta potential The fine particles (T1) were dispersed in a 10 mM NaCl aqueous solution (pH 5.5), and the zeta potential was measured by electrophoretic light scattering.

[0047] (9) Water contact test Approximately 1 g of microparticles (T1) was placed in a transparent glass container with 30 mL of ultrapure water, sealed, and left at 25°C in a bright location for 6 months. After 1 month, 3 months, 5 months, and 6 months, the microparticles (T1) were removed and dried, and XRD measurements were performed under the conditions described in (1) above. Figure 5 shows the X-ray diffraction patterns of the microparticles (T1) after 1 month, 3 months, 5 months, and 6 months of contact with water. Figure 5 shows that the X-ray diffraction patterns remained unchanged after contact with water, demonstrating that the γ-Fe2O3, which could be oxidized, was embedded in the SiO2 and not exposed on the surface of the microparticles (T1). Furthermore, the color of the microparticles (T1) after 6 months of contact with water remained brown, unchanged from before the test.

[0048] Example 2 Microparticles (hereinafter referred to as "microparticles (T2)") were obtained by the same procedure as in Example 1, except that the microparticle production raw material liquid (M2) obtained in Preparation Example 2 was used instead of the microparticle production raw material liquid (M1).

[0049] The X-ray diffraction pattern of the fine particles (T2) is shown in Figure 3. In Figure 3, the X-ray diffraction pattern of Example 2 shows the pattern of γ-Fe2O3, which indicates that the fine particles (T2) contain γ-Fe2O3. Elemental analysis of the fine particles (T2) revealed that the Si / Fe ratio was 0.352.

[0050] Next, an image of the fine particles (T2) taken with a scanning electron microscope is shown in Figure 6. From Figure 6, it can be seen that the fine particles (T2) have uneven surfaces. Furthermore, when the particle diameter (secondary particle diameter) was measured, the average value was 1.21 ± 0.28 μm.

[0051] Furthermore, when the microparticles (T2) were subjected to a water contact test and XRD measurement was performed after 6 months, no change was observed in the X-ray diffraction pattern (not shown), as with the microparticles (T1). Furthermore, the color of the microparticles (T2) after 6 months of contact with water remained brown, the same as before the test.

[0052] Table 1 also shows the measurement results of the crystallite size, specific surface area, true density, coercive force, saturation magnetization, zeta potential, etc.

[0053] Example 3 The raw material liquid (M3) for producing microparticles obtained in Production Example 3 was formed into droplets by droplet-forming means (X), and the resulting droplets 14 were guided to heating means (Y) by a carrier gas (air) at a flow rate of 10 L / min. The droplets 14 were then thermally decomposed in heating means (Y) to form microparticles 17 (hereinafter referred to as "microparticles (T3)"), which were then collected by collector 7 of collection means (Z). The temperatures of the four electric furnaces in heating means (Y) were set to, from the upstream side, 150°C (15a in FIG. 2), 200°C (15b in FIG. 2), 300°C (15c in FIG. 2), and 400°C (15d in FIG. 2).

[0054] The X-ray diffraction pattern of the fine particles (T3) is shown in Figure 3. In Figure 3, the X-ray diffraction pattern of Example 3 shows the pattern of γ-Fe2O3, which indicates that the fine particles (T3) contain γ-Fe2O3. Elemental analysis of the fine particles (T3) revealed that the Si / Fe ratio was 0.096.

[0055] Next, an image of the microparticles (T3) taken with a scanning electron microscope is shown in Figure 7. From Figure 7, it can be seen that the microparticles (T3) are in a state where the secondary particles are destroyed and the primary particles are dispersed. Furthermore, when the particle diameter (secondary particle diameter) was measured, the average value was 0.089 ± 0.018 μm.

[0056] Furthermore, when the microparticles (T3) were subjected to a water contact test and XRD measurement was performed after 6 months, no change was observed in the X-ray diffraction pattern (not shown), as with the microparticles (T1). Furthermore, the color of the microparticles (T3) after 6 months of contact with water remained brown, the same as before the test.

[0057] Table 1 also shows the measurement results of the crystallite size, specific surface area, true density, coercive force, saturation magnetization, zeta potential, etc.

[0058] [Table 1] [Industrial Applicability]

[0059] The microparticles of the present invention are superparamagnetic and do not denature when in contact with water, and therefore can be widely used in isolation, solidification, or purification of cells, nucleic acids, enzymes, antibodies, proteins, or peptides, as well as in phagocytic cell diagnosis in cell biology. [Explanation of symbols]

[0060] 10: Fine particle production equipment 11: Raw material liquid storage tank 12: Ultrasonic generator 13: Raw material liquid 14:Droplet 16: Collector 17: Fine particles X: Droplet production means Y: Heating means Z: Particulate collection means

Claims

1. SiO ２ The matrix phase contains γ-Fe ２ O ３ Microparticles comprising:

2. The SiO ２ silicon atoms derived from the γ-Fe ２ O ３ 2. The fine particles according to claim 1, wherein the atomic ratio of iron atoms (Si / Fe) derived from the above is 0.050 to 0.

500.

3. 2. The fine particles according to claim 1, wherein the secondary particle diameter is 0.5 to 2.0 μm.

4. The coercive force is 480 A / m or less, and the saturation magnetization is 40 A / m ２ 10. The microparticles according to claim 1, wherein the microparticles have a molecular weight of 1000 or more.

5. 10. A method for producing the microparticles of claim 1, comprising: Fe ３ O ４ a raw material preparation step of mixing nanoparticles consisting of the above, a dispersant, and an aqueous solution of silica to prepare a raw material liquid; a pyrolysis step of subjecting the raw material liquid to spray pyrolysis; A method for producing microparticles, comprising:

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