JP4853769B2 - Magnetic silica particles and method for producing the same - Google Patents
Magnetic silica particles and method for producing the same Download PDFInfo
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 title claims description 210
- 238000004519 manufacturing process Methods 0.000 title claims description 12
- 239000002245 particle Substances 0.000 claims description 147
- 239000002923 metal particle Substances 0.000 claims description 63
- 239000000377 silicon dioxide Substances 0.000 claims description 60
- 239000007771 core particle Substances 0.000 claims description 49
- 230000005415 magnetization Effects 0.000 claims description 49
- UCNNJGDEJXIUCC-UHFFFAOYSA-L hydroxy(oxo)iron;iron Chemical compound [Fe].O[Fe]=O.O[Fe]=O UCNNJGDEJXIUCC-UHFFFAOYSA-L 0.000 claims description 48
- 229910010413 TiO 2 Inorganic materials 0.000 claims description 32
- 239000011247 coating layer Substances 0.000 claims description 18
- 229910052742 iron Inorganic materials 0.000 claims description 17
- 229910052759 nickel Inorganic materials 0.000 claims description 14
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N titanium dioxide Inorganic materials O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 5
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 claims description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 47
- 239000000843 powder Substances 0.000 description 46
- 238000000576 coating method Methods 0.000 description 36
- 239000011248 coating agent Substances 0.000 description 35
- 239000002184 metal Substances 0.000 description 35
- 229910052751 metal Inorganic materials 0.000 description 35
- 239000010419 fine particle Substances 0.000 description 22
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 description 20
- 239000000243 solution Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 238000005260 corrosion Methods 0.000 description 14
- 230000007797 corrosion Effects 0.000 description 14
- 239000011324 bead Substances 0.000 description 12
- 239000006249 magnetic particle Substances 0.000 description 12
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 description 11
- 238000006722 reduction reaction Methods 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 10
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- 238000007254 oxidation reaction Methods 0.000 description 8
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
- 235000011114 ammonium hydroxide Nutrition 0.000 description 7
- 230000007423 decrease Effects 0.000 description 7
- 229910052755 nonmetal Inorganic materials 0.000 description 7
- 229910052814 silicon oxide Inorganic materials 0.000 description 7
- 239000011812 mixed powder Substances 0.000 description 6
- 229910052710 silicon Inorganic materials 0.000 description 6
- 239000010703 silicon Substances 0.000 description 6
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- 239000010410 layer Substances 0.000 description 5
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- 238000002441 X-ray diffraction Methods 0.000 description 4
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229910045601 alloy Inorganic materials 0.000 description 3
- 239000000956 alloy Substances 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
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- 238000004062 sedimentation Methods 0.000 description 3
- 229910000859 α-Fe Inorganic materials 0.000 description 3
- 238000004438 BET method Methods 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 238000007399 DNA isolation Methods 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
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- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 description 1
- SJECZPVISLOESU-UHFFFAOYSA-N 3-trimethoxysilylpropan-1-amine Chemical compound CO[Si](OC)(OC)CCCN SJECZPVISLOESU-UHFFFAOYSA-N 0.000 description 1
- CNODSORTHKVDEM-UHFFFAOYSA-N 4-trimethoxysilylaniline Chemical compound CO[Si](OC)(OC)C1=CC=C(N)C=C1 CNODSORTHKVDEM-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 229910020599 Co 3 O 4 Inorganic materials 0.000 description 1
- 229910000990 Ni alloy Inorganic materials 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
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- 229910001566 austenite Inorganic materials 0.000 description 1
- 239000000560 biocompatible material Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000011258 core-shell material Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- JJQZDUKDJDQPMQ-UHFFFAOYSA-N dimethoxy(dimethyl)silane Chemical compound CO[Si](C)(C)OC JJQZDUKDJDQPMQ-UHFFFAOYSA-N 0.000 description 1
- YYLGKUPAFFKGRQ-UHFFFAOYSA-N dimethyldiethoxysilane Chemical compound CCO[Si](C)(C)OCC YYLGKUPAFFKGRQ-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000002149 energy-dispersive X-ray emission spectroscopy Methods 0.000 description 1
- 230000005307 ferromagnetism Effects 0.000 description 1
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- 229910052733 gallium Inorganic materials 0.000 description 1
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- 229910052732 germanium Inorganic materials 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 239000010977 jade Substances 0.000 description 1
- 230000005381 magnetic domain Effects 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- BFXIKLCIZHOAAZ-UHFFFAOYSA-N methyltrimethoxysilane Chemical compound CO[Si](C)(OC)OC BFXIKLCIZHOAAZ-UHFFFAOYSA-N 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- INJVFBCDVXYHGQ-UHFFFAOYSA-N n'-(3-triethoxysilylpropyl)ethane-1,2-diamine Chemical compound CCO[Si](OCC)(OCC)CCCNCCN INJVFBCDVXYHGQ-UHFFFAOYSA-N 0.000 description 1
- PHQOGHDTIVQXHL-UHFFFAOYSA-N n'-(3-trimethoxysilylpropyl)ethane-1,2-diamine Chemical compound CO[Si](OC)(OC)CCCNCCN PHQOGHDTIVQXHL-UHFFFAOYSA-N 0.000 description 1
- MQWFLKHKWJMCEN-UHFFFAOYSA-N n'-[3-[dimethoxy(methyl)silyl]propyl]ethane-1,2-diamine Chemical compound CO[Si](C)(OC)CCCNCCN MQWFLKHKWJMCEN-UHFFFAOYSA-N 0.000 description 1
- LIBWSLLLJZULCP-UHFFFAOYSA-N n-(3-triethoxysilylpropyl)aniline Chemical compound CCO[Si](OCC)(OCC)CCCNC1=CC=CC=C1 LIBWSLLLJZULCP-UHFFFAOYSA-N 0.000 description 1
- KBJFYLLAMSZSOG-UHFFFAOYSA-N n-(3-trimethoxysilylpropyl)aniline Chemical compound CO[Si](OC)(OC)CCCNC1=CC=CC=C1 KBJFYLLAMSZSOG-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000009832 plasma treatment Methods 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
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- 229910052703 rhodium Inorganic materials 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
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- 229910052709 silver Inorganic materials 0.000 description 1
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- 239000013076 target substance Substances 0.000 description 1
- 229910052714 tellurium Inorganic materials 0.000 description 1
- UQMOLLPKNHFRAC-UHFFFAOYSA-N tetrabutyl silicate Chemical compound CCCCO[Si](OCCCC)(OCCCC)OCCCC UQMOLLPKNHFRAC-UHFFFAOYSA-N 0.000 description 1
- LFQCEHFDDXELDD-UHFFFAOYSA-N tetramethyl orthosilicate Chemical compound CO[Si](OC)(OC)OC LFQCEHFDDXELDD-UHFFFAOYSA-N 0.000 description 1
- ZUEKXCXHTXJYAR-UHFFFAOYSA-N tetrapropan-2-yl silicate Chemical compound CC(C)O[Si](OC(C)C)(OC(C)C)OC(C)C ZUEKXCXHTXJYAR-UHFFFAOYSA-N 0.000 description 1
- ZQZCOBSUOFHDEE-UHFFFAOYSA-N tetrapropyl silicate Chemical compound CCCO[Si](OCCC)(OCCC)OCCC ZQZCOBSUOFHDEE-UHFFFAOYSA-N 0.000 description 1
- 229910052716 thallium Inorganic materials 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- CPUDPFPXCZDNGI-UHFFFAOYSA-N triethoxy(methyl)silane Chemical compound CCO[Si](C)(OCC)OCC CPUDPFPXCZDNGI-UHFFFAOYSA-N 0.000 description 1
- JCVQKRGIASEUKR-UHFFFAOYSA-N triethoxy(phenyl)silane Chemical compound CCO[Si](OCC)(OCC)C1=CC=CC=C1 JCVQKRGIASEUKR-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Description
本発明は、ＤＮＡや細胞などの生体物質を抽出するための磁気ビーズなど、広く磁気を利用して応用される微粒子に関する。 The present invention relates to fine particles that are widely applied using magnetism, such as magnetic beads for extracting biological substances such as DNA and cells.
近年、医療診断や生物学的検査において微小な磁性粒子が利用されている。検体を固定する固相として超常磁性磁気ビーズが用いられ、タンパク質、細胞、ＤＮＡの分離、分析等に利用されている（例えば特許文献１）。超常磁性磁気ビーズとは、酸化鉄等の磁性体を磁区の大きさよりも小さい微粒子にしてビーズ中に分散して含ませたものであり、外部磁場が印加された時のみ強磁性を示す性質を有する。上記用途において磁性粒子は酸性、中性またはアルカリ性溶液に曝されるため、表面が化学的に安定であることが好ましい。同時に目的物質を結合させる抗体が容易に張り付く表面であることが好ましい。そのためマグネタイト粒子にシリカ（ＳｉＯ２）をコートしたり（例えば、特許文献２）、酸化鉄粒子にポリマーをコートする（例えば、特許文献３）手法がある。 In recent years, fine magnetic particles have been used in medical diagnosis and biological examination. Superparamagnetic magnetic beads are used as a solid phase for immobilizing a specimen, and are used for separation, analysis, etc. of proteins, cells, and DNA (for example, Patent Document 1). Superparamagnetic magnetic beads are magnetic particles such as iron oxide that are smaller than the size of the magnetic domain and are dispersed in the beads. The superparamagnetic magnetic beads exhibit a property of exhibiting ferromagnetism only when an external magnetic field is applied. Have. In the above application, since the magnetic particles are exposed to an acidic, neutral or alkaline solution, the surface is preferably chemically stable. At the same time, the surface to which the antibody to which the target substance is bound easily sticks is preferable. Therefore, there is a method of coating magnetite particles with silica (SiO 2 ) (for example, Patent Document 2) or coating iron oxide particles with a polymer (for example, Patent Document 3).
従来の磁性シリカ粒子からなる磁気ビーズは超常磁性を発現する酸化鉄微粒子をコアとするため、磁化が本質的に低いという問題があった。すなわち磁石で磁気ビーズを回収する際、磁気ビーズの磁場応答性が低く、結果として回収速度が遅くなってしまうという問題があった。上記問題を解決するためには、高磁化を有するＦｅ、Ｃｏなどの金属磁性粒子をコアとして用いることが好ましいが、金属磁性粒子は非常に酸化活性であるため微粒子化するほど不安定となり、直ぐに酸化物へと変質してしまう。一方、酸化による変質をできるだけ避けるために金属磁性粒子の粒径を大きくすると粉末の比表面積が小さくなり、ＤＮＡ等の生体物質を回収する上で重要な磁気ビーズの有効表面積が実質的に小さくなるという問題があった。そこで、本発明は、金属磁性粒子を用いて、高い飽和磁化を有するとともに、比表面積を高めた磁性シリカ粒子を提供することを目的とする。 Conventional magnetic beads made of magnetic silica particles have a problem that their magnetization is essentially low because iron oxide fine particles exhibiting superparamagnetism are used as a core. That is, when collecting magnetic beads with a magnet, there is a problem that the magnetic field response of the magnetic beads is low, resulting in a slow collection speed. In order to solve the above problem, it is preferable to use high magnetic magnetization metal particles such as Fe and Co as the core. However, since the metal magnetic particles are very oxidatively active, they become unstable as they become finer, and soon It changes to oxide. On the other hand, if the particle size of the metal magnetic particles is increased in order to avoid alteration due to oxidation as much as possible, the specific surface area of the powder is reduced, and the effective surface area of the magnetic beads, which is important in recovering biological materials such as DNA, is substantially reduced. There was a problem. Accordingly, an object of the present invention is to provide magnetic silica particles having high saturation magnetization and increased specific surface area using metal magnetic particles.
本発明者は上記目的を達成するために鋭意研究を重ねた結果本発明に至った。
本発明の磁性シリカ粒子は、Ｆｅ、Ｃｏ、Ｎｉのうち少なくとも一種を含む磁性金属粒子を芯粒子とし、前記芯粒子の外殻としてシリカを備えた磁性シリカ粒子であって、前記シリカは磁性酸化物粒子を包含し、前記磁性酸化物粒子の平均粒径が前記磁性シリカ粒子の平均粒子径の１／１０以下であることを特徴とする。また、本発明の別の磁性シリカ粒子は、Ｆｅ、Ｃｏ、Ｎｉのうち少なくとも一種を含む磁性金属粒子を芯粒子とし、前記芯粒子の外殻としてシリカを備えた磁性シリカ粒子であって、前記シリカは前記芯粒子よりも微細な磁性酸化物粒子を包含し、前記磁性シリカ粒子は前記磁性酸化物粒子に対応した凹凸を有することを特徴とする。磁性金属粒子を芯粒子とすることにより、酸化鉄微粒子を用いた従来の磁性シリカ粒子よりも高磁化が得られる。さらに、磁性金属粒子とは別の磁性酸化物粒子が外殻であるシリカに包含されるため、表面の凹凸が増え、単なるシリカを外殻とするよりも、比表面積をおおきくすることができる。また、シリカに包含される酸化物粒子に磁性酸化物粒子を用いることで、磁性シリカ粒子全体の飽和磁化低下の抑制に寄与する。
The inventor of the present invention has arrived at the present invention as a result of intensive studies to achieve the above object.
Magnetic silica particles of the present invention, Fe, Co, and the core particles of magnetic metal particles containing at least one of Ni, a magnetic silica particles comprising silica as an outer shell of the core particles, wherein the silica magnetic oxide The average particle size of the magnetic oxide particles is 1/10 or less of the average particle size of the magnetic silica particles . Another magnetic silica particle of the present invention is a magnetic silica particle comprising, as a core particle, a magnetic metal particle containing at least one of Fe, Co, and Ni, and silica as an outer shell of the core particle, Silica includes magnetic oxide particles finer than the core particles, and the magnetic silica particles have irregularities corresponding to the magnetic oxide particles. By using magnetic metal particles as core particles, higher magnetization can be obtained than conventional magnetic silica particles using iron oxide fine particles. Further, since magnetic oxide particles different from the magnetic metal particles are included in the outer shell silica, surface irregularities are increased, and the specific surface area can be increased as compared with a simple silica outer shell. In addition, by using magnetic oxide particles for the oxide particles included in silica, it contributes to suppression of a decrease in saturation magnetization of the entire magnetic silica particles.
また、前記磁性シリカ粒子において、磁性シリカ粒子の芯粒子となる磁性金属粒子は、その表面に非金属被覆層を有することが好ましい。上記非金属の被覆層を有することにより芯粒子の耐食性を向上させることができる。非金属被覆層とは、金属単体または合金以外の被覆層をいう。例えば、酸化物層、窒化物層、炭化物層、樹脂層などである。生体物質抽出の用途に用いる場合、前記非金属被覆層はＴｉ酸化物などの生体適合物質であることが好ましい。 In the magnetic silica particles, the magnetic metal particles that are the core particles of the magnetic silica particles preferably have a non-metal coating layer on the surface thereof. By having the non-metallic coating layer, the corrosion resistance of the core particles can be improved. The non-metal coating layer refers to a coating layer other than a single metal or an alloy. For example, an oxide layer, a nitride layer, a carbide layer, a resin layer, and the like. When used for biomaterial extraction, the non-metal coating layer is preferably a biocompatible material such as Ti oxide.
更に、前記磁性シリカ粒子において、前記非金属被覆層がルチル構造のＴｉＯ２を主体とするＴｉ酸化物であることが好ましい。ここでＴｉＯ２を主体とするとは、Ｘ線回折測定で検出されるＴｉ酸化物に相当する回折ピークの中で、ＴｉＯ２に相当するピークの強度が最大であることを意味する。ＴｉＯ２を主体とするＴｉ酸化物は結晶性が高いため、コアとなる磁性金属粒子をより完全に被覆して優れた耐食性を維持することができる。 Furthermore, in the magnetic silica particles, the non-metal coating layer is preferably a Ti oxide mainly composed of TiO 2 having a rutile structure. Here, the the TiO 2 mainly, among the diffraction peaks corresponding to Ti oxides detected by X-ray diffraction measurement, the intensity of the peak corresponding to TiO 2 is meant to be the maximum. Since the Ti oxide mainly composed of TiO 2 has high crystallinity, it is possible to maintain excellent corrosion resistance by more completely covering the core magnetic metal particles.
また、本発明の磁性シリカ粒子の平均粒径は０．２μｍ〜１０μｍが好ましい。これにより溶液中でも沈降が遅く分散性に優れた磁性シリカ粒子とすることができる。 The average particle size of the magnetic silica particles of the present invention is preferably 0.2 μm to 10 μm. This makes it possible to obtain magnetic silica particles that are slow to settle even in solution and have excellent dispersibility.
また、本発明の磁性シリカ粒子の保磁力が１０ｋＡ／ｍ以下であることが好ましい。保磁力が小さいことから残留磁化が小さく磁気凝集を抑制することができる。 The coercive force of the magnetic silica particles of the present invention is preferably 10 kA / m or less. Since the coercive force is small, the residual magnetization is small and magnetic aggregation can be suppressed.
また、本発明の磁性シリカ粒子の残留磁化Ｍｒと飽和磁化Ｍｓの比Ｍｒ/Ｍｓが０．０３以下であることが好ましい。高Ｍｓ、低Ｍｒとすることにより、磁気捕捉性に優れるともに、再分散性に優れた磁性シリカ粒子が得られる。 Moreover, it is preferable that the ratio Mr / Ms of the residual magnetization Mr to the saturation magnetization Ms of the magnetic silica particles of the present invention is 0.03 or less. By using high Ms and low Mr, magnetic silica particles having excellent magnetic capture properties and excellent redispersibility can be obtained.
本発明の磁性シリカ粒子の製造方法は、Ｆｅ、Ｃｏ、Ｎｉのうち少なくとも一種を含む磁性金属粒子を、前記磁性金属粒子の平均粒子径に対して１／１０以下の平均粒子径を有する磁性酸化物粒子を添加したシリカゾル中で攪拌し、前記シリカゾルを加水分解させて、前記磁性金属粒子の芯粒子に、磁性酸化物粒子を包含するシリカの外殻を形成することを特徴とする。本手法によれば、高磁化の磁性金属粒子を芯粒子とする磁性シリカ粒子において比表面積を大きくすることができる。 The method for producing magnetic silica particles of the present invention comprises magnetic oxidation of magnetic metal particles containing at least one of Fe, Co, and Ni having an average particle size of 1/10 or less with respect to the average particle size of the magnetic metal particles. was stirred in silica sol was added things particles, the silica sol is hydrolyzed, the core particles of the magnetic metal particles, and forming an outer shell of silica include magnetic oxide particles. According to this method, the specific surface area can be increased in the magnetic silica particles having the highly magnetized magnetic metal particles as the core particles.
また、前記磁性シリカ粒子の製造方法において、上記磁性酸化物粒子の添加量は、磁性金属粒子１００重量部に対して、前記磁性酸化物粒子が０．５〜８重量部であることを特徴とする。これにより磁性金属粒子による高磁化を維持しながら効果的に磁性シリカ粒子の表面積を増大させることができる。 In the method for producing magnetic silica particles, the magnetic oxide particles may be added in an amount of 0.5 to 8 parts by weight with respect to 100 parts by weight of the magnetic metal particles. To do. Thereby, the surface area of the magnetic silica particles can be effectively increased while maintaining high magnetization by the magnetic metal particles.
本発明によれば、高い磁化を有するとともに比表面積が大きいシリカ磁性粒子を提供することができる。これによりＤＮＡなどの生体物質を抽出する際には高速で高効率回収を実現することができる。 According to the present invention, silica magnetic particles having high magnetization and a large specific surface area can be provided. As a result, when extracting biological substances such as DNA, high-efficiency recovery can be realized at high speed.
以下本発明について具体的に説明する。本発明の磁性シリカ粒子は、Ｆｅ、Ｃｏ、Ｎｉのうち少なくとも一種を含む磁性金属粒子を芯粒子とし、前記芯粒子の外殻としてシリカを備え、前記シリカは磁性酸化物粒子を包含する。すなわち、芯粒子の外殻としてシリカを備える構造とは、磁性金属粒子をシリカが覆っている構造である。 The present invention will be specifically described below. The magnetic silica particles of the present invention include magnetic metal particles containing at least one of Fe, Co, and Ni as core particles, and include silica as an outer shell of the core particles, and the silica includes magnetic oxide particles. That is, the structure having silica as the outer shell of the core particles is a structure in which the magnetic metal particles are covered with silica.
（１）芯粒子
芯粒子はＦｅ、Ｃｏ、Ｎｉのうち少なくとも一種を含む磁性金属粒子とする。すなわちＦｅ、ＣｏおよびＮｉ、Ｆｅ、Ｃｏ、Ｎｉの合金、Ｆｅ、Ｃｏ、Ｎｉを含む化合物などである。高飽和磁化を得る観点からは、Ｆｅ、Ｆｅの一部を他の元素で置き換えた合金、或いはＦｅを含む化合物が好ましく、特にＦｅが好ましい。芯粒子である磁性金属粒子は、磁性金属のみで構成されていてもよく、その表面に非金属被覆層が形成されていてもよい。表面に被覆が形成されている場合は、耐酸化性や磁性シリカ粒子とした場合の耐食性にも有利である。また、不可避不純物の酸素を含有していてもよい。磁性金属のみで構成されている磁性金属粒子としては、例えばカルボニル鉄などの金属粉末を用いればよい。表面に非金属被覆層が形成されている磁性金属粒子としては、例えばＡｌ、Ｔｉ、Ｖ、Ｍｎ、Ｎｂ、Ｂなどの酸化物、窒化物、炭化物、炭素、樹脂などによって被覆されたものを用いることができる。このうちＴｉ酸化物は生体物質に対する適合性の点で優れているため、磁性金属粒子はＴｉ酸化物で被覆されていることが好ましい。
(1) Core particles The core particles are magnetic metal particles containing at least one of Fe, Co, and Ni. That is, Fe, Co and Ni, Fe, Co, Ni alloys, Fe, Co, Ni-containing compounds, and the like. From the viewpoint of obtaining high saturation magnetization, Fe, an alloy in which part of Fe is replaced with another element, or a compound containing Fe is preferable, and Fe is particularly preferable. The magnetic metal particles that are the core particles may be composed of only a magnetic metal, and a non-metal coating layer may be formed on the surface thereof. When a coating is formed on the surface, it is advantageous in terms of oxidation resistance and corrosion resistance when magnetic silica particles are used. Further, it may contain unavoidable oxygen. For example, metal powder such as carbonyl iron may be used as magnetic metal particles composed of only magnetic metal. As magnetic metal particles having a non-metal coating layer formed on the surface, for example, those coated with an oxide such as Al, Ti, V, Mn, Nb, B, nitride, carbide, carbon, resin, etc. are used. be able to. Among these, since Ti oxide is excellent in terms of compatibility with biological materials, the magnetic metal particles are preferably coated with Ti oxide.
Ｆｅ、Ｃｏ、Ｎｉの少なくとも一種を含む磁性金属粒子の製造方法について、Ｔｉ酸化物の被覆を有する場合を例に説明する。なお、非金属被覆層は、既知のゾルゲル法、プラズマ処理法、樹脂コート法などの方法を用いて形成することができるが、下記方法は金属部分の酸化を抑えることができる点、被覆層の耐食性に優れた膜が形成できる点、簡易な方法である点で特に優れる。Ｆｅ、Ｃｏ、Ｎｉの少なくとも一種を含む金属Ｍの酸化物粉末とＴｉを含む粉末（但し、Ｔｉ酸化物粉末を除く）とを混合し、その混合粉末を非酸化性雰囲気中で熱処理する。これにより、Ｔｉによって還元された金属Ｍが粒子として生成し、同時に当該還元反応において生成したＴｉ酸化物が金属Ｍの粒子の表面を被覆する。 A method for producing magnetic metal particles containing at least one of Fe, Co, and Ni will be described by taking as an example the case of having a Ti oxide coating. The non-metal coating layer can be formed by using a known sol-gel method, plasma treatment method, resin coating method, or the like. However, the following method can suppress oxidation of the metal part, It is particularly excellent in that a film excellent in corrosion resistance can be formed and in that it is a simple method. A metal M oxide powder containing at least one of Fe, Co, and Ni and a powder containing Ti (excluding the Ti oxide powder) are mixed, and the mixed powder is heat-treated in a non-oxidizing atmosphere. Thereby, the metal M reduced by Ti is generated as particles, and at the same time, the Ti oxide generated in the reduction reaction covers the surfaces of the metal M particles.
この製法において用いられる金属Ｍの酸化物粉末は、目標とする磁性金属粒子の粒径に合わせてその粒径を自由に選択することができる。金属Ｍの酸化物粉末の粒子径は０．００１μｍ〜５μｍの範囲から選ばれることが好ましい。粒径が０．００１μｍ未満の酸化物粒子は合成が困難で高コスト化を招くだけでなく、２次凝集が激しいためにその後の製造プロセスでの取り扱いが困難になる。また５μｍを越える粒子は比表面積が小さくなり、結果として還元反応が進行しにくくなる。実用的には０．００１μｍ〜1μｍの範囲が好適である。また金属Ｍとしては上述のようにＦｅ、Ｃｏ、Ｎｉ、またはこれらを含む合金等が好ましく、その酸化物粉末としてはＦｅ２Ｏ３、Ｆｅ３Ｏ４、ＣｏＯ、Ｃｏ３Ｏ４、ＮｉＯが挙げられる。このうち、Ｆｅは飽和磁化が高いため、金属Ｍとして特に好ましい。また、その酸化物のＦｅ２Ｏ３が安価である点でも好ましい。ＴｉはＦｅに比べて酸化物の標準生成エネルギーが小さいため、Ｆｅの酸化物を効率よくかつ確実に還元することができる。 The particle size of the metal M oxide powder used in this production method can be freely selected according to the target particle size of the magnetic metal particles. The particle diameter of the metal M oxide powder is preferably selected from the range of 0.001 μm to 5 μm. Oxide particles having a particle size of less than 0.001 μm are difficult to synthesize, leading to high costs, and are difficult to handle in subsequent manufacturing processes due to severe secondary aggregation. Moreover, the particle | grains exceeding 5 micrometers have a small specific surface area, and as a result, a reductive reaction becomes difficult to advance. Practically, a range of 0.001 μm to 1 μm is preferable. As described above, the metal M is preferably Fe, Co, Ni, or an alloy containing these, and examples of the oxide powder include Fe 2 O 3 , Fe 3 O 4 , CoO, Co 3 O 4 , and NiO. It is done. Among these, Fe is particularly preferable as the metal M because of its high saturation magnetization. Further, Fe 2 O 3 of the oxide is also preferable in that it is inexpensive. Since Ti has a lower standard energy of oxide formation than Fe, it is possible to efficiently and reliably reduce the oxide of Fe.
Ｔｉを含む粉末（但し、Ｔｉ酸化物粉末を除く）とは、Ｔｉ単体粉の他、Ｔｉ−Ｘ（Ｘ：Ａｇ、Ａｕ、Ｂ、Ｂｉ、Ｃ、Ｃｕ、Ｃｓ、Ｃｄ、Ｇｅ、Ｇａ、Ｈｇ、Ｋ、Ｎ、Ｎａ、Ｐｄ、Ｐｔ、Ｒｂ、Ｒｈ、Ｓ、Ｓｎ、Ｔｌ、Ｔｅ、Ｚｎから少なくとも一つ）等のＴｉ化合物、あるいはそれらの混合物であっても良い。Ｔｉの酸化物は還元剤として機能しないので好ましくない。Ｘの限定理由は、Ｘの酸化物生成の標準生成自由エネルギーΔＧＸ−ＯがＴｉＯ２の生成標準自由エネルギーΔＧＴｉＯ２よりも大きい物質である。もしΔＧＸ−Ｏ＜ΔＧＴｉＯ２なる元素Ｘを選択すると元素Ｘが還元剤として作用し、Ｔｉ酸化物が生成しなくなる。Ｍ酸化物を還元するに足るＴｉが含まれていれば、Ｘの含有量は特に限定されない。また、Ｔｉを含む粉末に限らず、Ａｌ、Ｖ、Ｍｎ、Ｎｂ、Ｂ等を含む粉末を用いてＴｉを含む粉末の場合と同様の原理を用いてＡｌ酸化物等の被覆を形成することができる。さらにＴｉを含む粉末の代わりにＢ、Ｃの粉末を用いれば、ＢＮやＣの被覆も形成することができる。 Powder containing Ti (excluding Ti oxide powder) is Ti-X (X: Ag, Au, B, Bi, C, Cu, Cs, Cd, Ge, Ga, Hg, in addition to Ti simple powder. , K, N, Na, Pd, Pt, Rb, Rh, S, Sn, Tl, Te, Zn) or a Ti compound, or a mixture thereof. Ti oxide is not preferable because it does not function as a reducing agent. Reasons for limiting the X is standard free energy .DELTA.G X-O oxide generation of X is greater substance than generating the standard free energy .DELTA.G TiO2 of TiO 2. If the element X satisfying ΔG X-O <ΔG TiO 2 is selected, the element X acts as a reducing agent and no Ti oxide is generated. The content of X is not particularly limited as long as Ti is sufficient to reduce the M oxide. Further, not only the powder containing Ti but also the powder containing Al, V, Mn, Nb, B, etc. can be used to form a coating such as Al oxide using the same principle as the case of powder containing Ti. it can. Further, if a powder of B or C is used instead of the powder containing Ti, a coating of BN or C can be formed.
Ｔｉを含む非酸化物粉末の粒径は１ｎｍ〜１ｍｍの範囲のものを用いることができるが、還元反応を効率的に行なうためには１ｎｍ〜０．１ｍｍの範囲が好ましい。０．１ｍｍを超える粒径となると還元反応温度が高温となり、昇降温に時間がかかるために熱処理サイクルが長くなって効率が落ちる、あるいは炉自体の部材に耐熱品を使用しなければならず、設備コストが高くなる、などの短所が顕著となる。さらに好ましくは、０．０１μｍ〜２０μｍの範囲であり、特に好ましくは０．１μｍ〜５μｍである。粒子径が０．０１μｍ未満であると大気中で取り扱う際にＴｉの酸化が著しくなり、還元剤として機能しにくくなる。２０μｍ超であると比表面積が小さく、還元反応が十分かつ均一に進行しない。特に０．１μｍ〜５μｍの範囲であれば、大気中での酸化を抑制しつつ、還元反応の十分な進行を図ることができる。 The particle size of the non-oxide powder containing Ti can be in the range of 1 nm to 1 mm, but the range of 1 nm to 0.1 mm is preferable for efficient reduction reaction. When the particle diameter exceeds 0.1 mm, the reduction reaction temperature becomes high, and it takes time to raise and lower the temperature, so the heat treatment cycle becomes long and the efficiency decreases, or a heat-resistant product must be used as a member of the furnace itself, Disadvantages such as increased equipment costs become significant. More preferably, it is the range of 0.01 micrometer-20 micrometers, Most preferably, it is 0.1 micrometer-5 micrometers. When the particle diameter is less than 0.01 μm, the oxidation of Ti becomes remarkable when handled in the air, and it becomes difficult to function as a reducing agent. If it exceeds 20 μm, the specific surface area is small, and the reduction reaction does not proceed sufficiently and uniformly. In particular, when the thickness is in the range of 0.1 μm to 5 μm, the reduction reaction can proceed sufficiently while suppressing oxidation in the atmosphere.
上記Ｍ酸化物の粉末とＴｉ含有粉末（但し、Ｔｉ酸化物粉末を除く）との混合比は、ＴｉがＭ酸化物を還元する化学量論比近傍が好ましく、より好ましくはＴｉが上記化学量論比よりも過剰となることが好ましい。Ｔｉが不足すると、熱処理中にＭ酸化物粉末が焼結してしまい、最終的にバルク化してしまうので適さない。例えばＴｉ含有粉末としてＴｉＣ、Ｍ酸化物としてＦｅ２Ｏ３を用いる場合、ＴｉＣは混合粉全体の２５〜６０ｍａｓｓ％が好ましい。２５ｍａｓｓ％未満であると還元が不十分となり、６０ｍａｓｓ％超とするとＦｅの比率が低下して磁化低下の原因となり相応しくない。より好ましくは３０〜５０ｍａｓｓ％である。上記Ｍ酸化物の粉末とＴｉ含有非酸化物粉末との混合には、乳鉢、スターラー、Ｖ字型ミキサー、ボールミル、振動ミル、その他一般的な攪拌機の中から選択できる。 The mixing ratio of the M oxide powder and the Ti-containing powder (excluding the Ti oxide powder) is preferably near the stoichiometric ratio where Ti reduces the M oxide, and more preferably, Ti is the above stoichiometric ratio. It is preferable that it becomes excessive rather than a theoretical ratio. If Ti is insufficient, the M oxide powder is sintered during the heat treatment and eventually bulked, which is not suitable. For example, when TiC is used as the Ti-containing powder and Fe 2 O 3 is used as the M oxide, TiC is preferably 25 to 60 mass% of the entire mixed powder. If it is less than 25 mass%, the reduction is insufficient, and if it exceeds 60 mass%, the ratio of Fe is lowered, causing a decrease in magnetization, which is not suitable. More preferably, it is 30-50 mass%. The mixing of the M oxide powder and the Ti-containing non-oxide powder can be selected from a mortar, a stirrer, a V-shaped mixer, a ball mill, a vibration mill, and other general stirrers.
Ｍ酸化物粉末とＴｉ含有粉末（但し、Ｔｉ酸化物粉末を除く）の混合粉を非酸化性雰囲気中で熱処理すると、Ｍ酸化物粉末とＴｉ含有粉末との接触部で還元反応が開始され、最終的にはＴｉＯ２を主体とするＴｉ酸化物で被覆された金属Ｍの粒子が生成する。以下、金属Ｍの粒子を「Ｍ金属粒子」と記載する。熱処理時の雰囲気は非酸化性雰囲気が好ましい。例えばＡｒ，Ｈｅなどの不活性ガスやＮ２、ＣＯ２、ＮＨ３などを使用することができるが、これらに限定されない。また熱処理温度は６５０℃〜９００℃が好ましい。６５０℃未満であると還元反応が十分に進行せず好ましくない。９００℃超であると還元反応は進行するが、ＴｉＯ２ではなく、不定比組成のＴｉｎＯ２ｎ−１が主として生成してしまう場合がある。ＴｉｎＯ２ｎ−１は、９００℃以下で還元された金属Ｍが９００℃超の高温でＴｉＯ２から再び酸素を取り込んで除酸化されることにより生成する。これは金属Ｍの還元が結果として十分進行していない状態となる。あるいは被覆層が劣化してしまい、Ｍ金属粒子の被覆が不十分となってしまう。すなわち、熱処理温度を６５０〜９００℃の範囲とすることは、処理温度が低く、生産性にも優れるうえに、Ｔｉ酸化物によって完全に被覆することによりＭ金属粒子の耐食性を維持する上で特に好ましいのである。 When a mixed powder of M oxide powder and Ti-containing powder (excluding Ti oxide powder) is heat-treated in a non-oxidizing atmosphere, a reduction reaction is started at the contact portion between the M oxide powder and Ti-containing powder, Eventually, particles of metal M coated with a Ti oxide mainly composed of TiO 2 are generated. Hereinafter, the metal M particles are referred to as “M metal particles”. The atmosphere during the heat treatment is preferably a non-oxidizing atmosphere. For example, an inert gas such as Ar or He, N 2 , CO 2 , NH 3, or the like can be used, but is not limited thereto. The heat treatment temperature is preferably 650 ° C to 900 ° C. If it is lower than 650 ° C., the reduction reaction does not proceed sufficiently, which is not preferable. Reduction reaction with a 900 ° C. greater proceeds but, in TiO 2 rather, there is a case where Ti n O 2n-1 of the nonstoichiometric composition will be mainly produced. Ti n O 2n-1 is produced by deoxidizing the metal M reduced at 900 ° C. or less by taking oxygen again from TiO 2 at a high temperature exceeding 900 ° C. This results in a state where the reduction of the metal M does not proceed sufficiently. Or a coating layer will deteriorate and the coating | cover of M metal particle will become inadequate. That is, when the heat treatment temperature is in the range of 650 to 900 ° C., the treatment temperature is low, the productivity is excellent, and the corrosion resistance of the M metal particles is particularly maintained by completely covering with the Ti oxide. Is preferred.
上記芯粒子において、被覆物質とＭ金属粒子は、必ずしもコアーシェル構造になっている必要はなく、ＴｉＯ２を主体とするＴｉ酸化物粒子の中に２個以上のＭ金属粒子が分散した構造であっても構わない。すなわちＴｉＯ２を主体とするＴｉ酸化物粒子の中にＭ金属粒子が２個以上含まれている構成によれば、Ｍ金属粒子を確実に被覆しやすく、耐食性を向上するうえで好ましい。また、金属粒子部分は、必ずしも、完全にＴｉＯ２を主体とするＴｉ酸化物で被覆されている必要はなく、部分的に金属粒子が表面に露出している粒子が含まれていても構わないが、完全にＴｉＯ２を主体とするＴｉ酸化物で被覆されていることがより好ましい。 In the above core particles, the coating substance and the M metal particles do not necessarily have a core-shell structure, but have a structure in which two or more M metal particles are dispersed in Ti oxide particles mainly composed of TiO 2. It doesn't matter. That is, according to the structure in which two or more M metal particles are contained in Ti oxide particles mainly composed of TiO 2 , it is preferable for easily covering the M metal particles and improving the corrosion resistance. In addition, the metal particle portion does not necessarily need to be completely covered with a Ti oxide mainly composed of TiO 2 and may contain particles in which the metal particles are partially exposed on the surface. However, it is more preferable that it is completely covered with a Ti oxide mainly composed of TiO 2 .
上記製造方法により、Ｔｉ含有粉末（但し、Ｔｉ酸化物粉末を除く）とＭ酸化物の粉末との混合粉末を非酸化性雰囲気で上記条件で熱処理することにより、Ｔｉによって還元された金属Ｍの微粒子であって、表面をＴｉＯ２を主体とするＴｉ酸化物によって被覆されていることを特徴とする磁性金属粒子を得ることができる。該磁性金属粒子の平均粒径は、０.１μｍ〜６μｍが好ましい。０．１μｍ未満であると十分な厚さの被覆を確保できずM金属粒子が剥き出しとなる部分が多くなるため耐食性が低下する。また６μｍを超えると液体中での沈降速度が速くなり、分散性が低下する。なお、本発明における平均粒径は、特に断りのない限り、レーザー回折による湿式粒度測定器で測定したｄ５０の値を用いる。また、平均粒径が０.１μｍ以下となるような微細なものに対しては、ＳＥＭ写真において、粒子の最大径と最小径の平均を１００粒の粒子についてとって平均粒径とする。また、ＴｉＯ２を主体とするＴｉ酸化物被覆の厚さは１〜１００００ｎｍが好ましい。１ｎｍ未満であると十分な耐食性が得られない。また、１００００ｎｍ超であると、粒子全体の粒径が大きくなり液中での分散性が低下する他、磁性金属微粒子の場合は飽和磁化が減少する。より、好ましくは５〜５０００ｎｍである。なお、被覆の厚さは粒子を直接観察した透過電子顕微鏡（ＴＥＭ）写真または断面が観察できるように加工した粒子のＴＥＭ写真から算出し、厚さが不均一な場合は、最大厚さと最小厚さの平均を被覆の厚さとする。 By the heat treatment of the mixed powder of the Ti-containing powder (excluding the Ti oxide powder) and the M oxide powder in a non-oxidizing atmosphere by the above production method, the metal M reduced by Ti is obtained. Magnetic metal particles which are fine particles and whose surfaces are covered with a Ti oxide mainly composed of TiO 2 can be obtained. The average particle diameter of the magnetic metal particles is preferably 0.1 μm to 6 μm. If the thickness is less than 0.1 μm, a sufficient thickness of the coating cannot be secured, and the portion where the M metal particles are exposed increases, resulting in a decrease in corrosion resistance. On the other hand, if the thickness exceeds 6 μm, the sedimentation rate in the liquid increases and the dispersibility decreases. In addition, unless otherwise indicated, the value of d50 measured with the wet particle size measuring device by laser diffraction is used for the average particle diameter in this invention. In addition, for a fine one having an average particle diameter of 0.1 μm or less, the average of the maximum diameter and the minimum diameter of the particles is taken as an average particle diameter for 100 particles in the SEM photograph. The thickness of the Ti oxide coating mainly composed of TiO 2 is preferably 1 to 10,000 nm. If the thickness is less than 1 nm, sufficient corrosion resistance cannot be obtained. On the other hand, if it exceeds 10,000 nm, the particle size of the whole particle becomes large and the dispersibility in the liquid decreases, and in the case of magnetic metal fine particles, the saturation magnetization decreases. More preferably, it is 5 to 5000 nm. The coating thickness is calculated from a transmission electron microscope (TEM) photograph in which the particles are directly observed or a TEM photograph of the particles processed so that the cross section can be observed. If the thickness is not uniform, the maximum thickness and the minimum thickness are calculated. The average thickness is taken as the thickness of the coating.
また、本発明では、Ｍ酸化物の還元によるＭ金属微粒子の生成とＴｉＯ２を主体とするＴｉ酸化物被覆の形成を同一の熱処理工程で行なうため、熱処理で得られた被覆磁性金属粒子の、Ｍ金属部分とＴｉＯ２を主体とするＴｉ酸化物被覆との間にＭ金属の酸化層は明確には確認されない。また、６５０℃以上に加熱した熱処理を施すため、被覆の結晶性が高く、被覆層は主にルチル構造のＴｉＯ２で構成される。したがって当該被覆層はゾル−ゲル法等によって得られるアモルファス或いは結晶性の低い被覆に比べて緻密であり高耐食性を発揮する。上記被覆層は複数（２個以上）の結晶粒で構成されており、ルチル構造のＴｉＯ２とＭ金属粒子との間には特定の結晶方位関係はないが、あっても良い。 Further, in the present invention, the formation of M metal fine particles by reduction of M oxide and the formation of a Ti oxide coating mainly composed of TiO 2 are performed in the same heat treatment step. The M metal oxide layer is not clearly identified between the M metal portion and the Ti oxide coating mainly composed of TiO 2 . Further, since heat treatment is performed at 650 ° C. or higher, the crystallinity of the coating is high, and the coating layer is mainly composed of TiO 2 having a rutile structure. Therefore, the coating layer is denser and exhibits higher corrosion resistance than an amorphous or low-crystalline coating obtained by a sol-gel method or the like. The coating layer is composed of a plurality of (two or more) crystal grains, and there is no specific crystal orientation relationship between the rutile TiO 2 and the M metal particles, but they may be present.
金属微粒子の部分が磁性金属Ｆｅである場合、前記製法によって得られた磁性金属粒子は、１１０〜１８０Ａ・ｍ２／ｋｇの範囲の飽和磁化を有することが好ましい。金属Ｆｅの飽和磁化（＝２１８Ａ・ｍ２／ｋｇ）との比をとることによりＦｅの含有率が計算されるが、前記磁性金属粒子中におけるＦｅの含有率は質量比で５０〜８３％であることに相当する。したがって被覆層を形成しているＴｉＯ２を主体とするＴｉ酸化物の含有率は１７〜５０％である。前記磁性金属粒子の飽和磁化が１１０Ａ・ｍ２／ｋｇ未満であると飽和磁化が小さいので、磁性粒子として十分機能しないので好ましくない。また１８０Ａ・ｍ２／ｋｇ超であるとＴｉＯ２を主体とするＴｉ酸化物の含有率が１７％未満と小さくなり、金属Ｆｅ粒子を十分被覆することができず磁気特性が酸化劣化してしまうので好ましくない。したがって、高い飽和磁化を得るためには非磁性部分である被覆はなるべく薄いことが好ましいが、十分な耐食性を得るためには、十分な被覆厚を有していることが好ましく、その場合の飽和磁化は１８０Ａ・ｍ２／ｋｇ以下とする。また前記磁性金属粒子はＴｉＯ２を主体とするＴｉ酸化物の非磁性成分を過剰に含んでいる場合があるため、永久磁石を用いて磁性粒子だけを回収する磁気分離操作を施すことが好ましい。磁性金属粒子において、コアとなる金属ＭをＦｅとしてＴｉＯ２を主体とするＴｉ酸化物で被覆することにより、高い耐食性を実現することができる。 When the portion of the metal fine particles is magnetic metal Fe, the magnetic metal particles obtained by the above production method preferably have a saturation magnetization in the range of 110 to 180 A · m 2 / kg. The Fe content is calculated by taking the ratio with the saturation magnetization of metal Fe (= 218 A · m 2 / kg). The Fe content in the magnetic metal particles is 50 to 83% by mass ratio. It corresponds to a certain thing. Therefore, the content of Ti oxide mainly composed of TiO 2 forming the coating layer is 17 to 50%. If the saturation magnetization of the magnetic metal particles is less than 110 A · m 2 / kg, the saturation magnetization is small, so that it does not function sufficiently as magnetic particles. Further, if it exceeds 180 A · m 2 / kg, the content of Ti oxide mainly composed of TiO 2 becomes as small as less than 17%, so that the metal Fe particles cannot be sufficiently covered and the magnetic characteristics are deteriorated by oxidation. Therefore, it is not preferable. Therefore, in order to obtain high saturation magnetization, the coating that is a non-magnetic part is preferably as thin as possible, but in order to obtain sufficient corrosion resistance, it is preferable to have a sufficient coating thickness, in which case the saturation The magnetization is 180 A · m 2 / kg or less. In addition, since the magnetic metal particles may contain an excessive amount of a non-magnetic component of Ti oxide mainly composed of TiO 2 , it is preferable to perform a magnetic separation operation in which only the magnetic particles are recovered using a permanent magnet. In the magnetic metal particles, high corrosion resistance can be achieved by coating the metal M as a core with Ti oxide mainly composed of TiO 2 as Fe.
（２）磁性シリカ粒子
次に、外殻としてのシリカについて説明する。本発明に係る磁性シリカ粒子は、Ｆｅ、Ｃｏ、Ｎｉの少なくとも一種を含む磁性金属粒子を芯粒子とし、磁性酸化物粒子を包含したシリカを外殻とする粒子構造である。図５に本発明に係る磁性シリカ粒子の構造の模式図を示す。図５に示すように、芯粒子１の周りには、該芯粒子覆うように外殻としてシリカ２が存在する。そしてシリカは磁性酸化物粒子を包含している。図５に示すように、芯粒子である磁性金属粒子が、磁性酸化物粒子よりも大きい構造である。磁性酸化物粒子によって磁性シリカ粒子の表面の凸凹が顕著になり、比表面積を増大させる。また、該粒子構造では、シリカの外殻が一つの芯粒子を被覆するものでよいし（図５（ａ））、シリカの外殻が２以上の芯粒子を包含するものでもよい（図５（ｂ））。
(2) Magnetic silica particles Next, silica as an outer shell will be described. The magnetic silica particles according to the present invention have a particle structure in which magnetic metal particles containing at least one of Fe, Co, and Ni are used as core particles, and silica containing magnetic oxide particles is used as an outer shell. FIG. 5 shows a schematic diagram of the structure of the magnetic silica particles according to the present invention. As shown in FIG. 5, silica 2 is present around the core particle 1 as an outer shell so as to cover the core particle. Silica includes magnetic oxide particles. As shown in FIG. 5, the magnetic metal particles that are the core particles have a larger structure than the magnetic oxide particles. The unevenness of the surface of the magnetic silica particles becomes remarkable due to the magnetic oxide particles, and the specific surface area is increased. In the particle structure, the outer shell of silica may cover one core particle (FIG. 5A), or the outer shell of silica may include two or more core particles (FIG. 5). (B)).
上記磁性シリカ粒子（Ａ粒子）はシリカ被覆工程で磁性酸化物粒子を添加することにより、（１）で記載した芯粒子を単独でシリカ被覆した粒子（Ｂ粒子）よりも比表面積を大きくすることができる。本発明のＡ粒子の比表面積はＢ粒子の比表面積よりも１％〜６０％増加することが好ましい。比表面積の増加が１％未満であると増分が小さすぎて磁性酸化物微粒子を添加した効果が期待できない。また比表面積の増加が６０％超とするためには磁性酸化物粒子を芯粒子に対して質量比で８％以上添加しなければならず、結果として磁気凝集を招くため、好ましくない。ここで比表面積とはＢＥＴ法により測定した値を指す。 The magnetic silica particles (A particles) have a specific surface area larger than the particles (B particles) obtained by coating the core particles described in (1) with silica by adding magnetic oxide particles in the silica coating step. Can do. The specific surface area of the A particles of the present invention is preferably increased by 1% to 60% than the specific surface area of the B particles. If the increase in specific surface area is less than 1%, the increment is too small to expect the effect of adding magnetic oxide fine particles. In order to increase the specific surface area to more than 60%, the magnetic oxide particles must be added in a mass ratio of 8% or more with respect to the core particles, resulting in magnetic aggregation, which is not preferable. Here, the specific surface area refers to a value measured by the BET method.
Ｆｅ、Ｃｏ、Ｎｉの少なくとも一種を含む磁性金属粒子が、その表面にＴｉ酸化物などの酸化物、窒化物、炭素等の被覆を有する場合、高い耐食性を示す。磁性金属がＴｉ酸化物等で被覆されているだけでなく、磁性酸化物粒子を包含するシリカで被覆されているため、直接的に大気または溶液が上記磁性金属粒子に接触することがなく、酸化性環境下であっても高い耐食性を維持することができる。すなわち、上記磁性シリカ粒子は磁性金属粒子によってその磁性を発現しているにもかかわらず、高い耐食性を示す。更には本発明の磁性シリカ粒子の最表面は、磁性酸化物微粒子を包含したシリカで構成されているため、表面性状が従来の磁気ビーズと酷似している。なおかつ芯粒子の磁性金属粒子によって高い磁化を発現するため、従来にない磁気捕集性に優れた磁気ビーズを提供することができる。 When the magnetic metal particle containing at least one of Fe, Co, and Ni has a coating of oxide such as Ti oxide, nitride, carbon, etc. on the surface thereof, it exhibits high corrosion resistance. Since the magnetic metal is not only coated with Ti oxide etc., but also coated with silica including magnetic oxide particles, the atmosphere or solution does not directly contact the magnetic metal particles, and oxidation High corrosion resistance can be maintained even in a natural environment. That is, the magnetic silica particles exhibit high corrosion resistance even though the magnetic metal particles exhibit their magnetism. Furthermore, since the outermost surface of the magnetic silica particles of the present invention is composed of silica containing magnetic oxide fine particles, the surface properties are very similar to conventional magnetic beads. In addition, since the magnetic metal particles of the core particles exhibit high magnetization, it is possible to provide a magnetic bead that has an excellent magnetic trapping property that has not been conventionally obtained.
上記磁性シリカ粒子の平均粒径は０．２μｍ〜１０μｍであることが好ましい。平均粒径が０．２μｍ未満であると１粒子当たりの磁化が極端に小さくなり、外部磁場と粒子との相互作用が極めて小さくなるので好ましくない。また平均粒径が１０μｍを越えると１粒子の重量が極端に重くなるため、溶液中に分散させた場合は沈降が速く直ぐに沈殿してしまう。このため磁性シリカ粒子が溶液中の生体物質と反応する確率が小さくなり、例えば血液からＤＮＡを抽出する際に上記磁性シリカ粒子が抽出できるＤＮＡ量が極めて少なくなる。高い磁場応答性を維持しつつ、溶液中における生体物質と本発明の粒子とを十分反応させるためには、上記磁性シリカ粒子の平均粒径は０．２μｍ〜１０μｍであることが好ましく、より好ましくは０．５μｍ〜７μｍである。 The average particle diameter of the magnetic silica particles is preferably 0.2 μm to 10 μm. If the average particle size is less than 0.2 μm, the magnetization per particle becomes extremely small, and the interaction between the external magnetic field and the particle becomes extremely small, which is not preferable. If the average particle size exceeds 10 μm, the weight of one particle becomes extremely heavy, so that when dispersed in a solution, the sedimentation is quick and precipitates immediately. For this reason, the probability that the magnetic silica particles react with the biological material in the solution is reduced, and for example, when extracting DNA from blood, the amount of DNA that can be extracted by the magnetic silica particles is extremely small. In order to sufficiently react the biological material in the solution and the particles of the present invention while maintaining high magnetic field responsiveness, the average particle diameter of the magnetic silica particles is preferably 0.2 μm to 10 μm, more preferably. Is 0.5 μm to 7 μm.
また、前記磁性シリカ粒子において、磁性酸化物粒子の平均粒径が磁性シリカ粒子の平均粒子径の１／１０以下であることが好ましい。このような微細な磁性酸化物粒子をシリカ外殻に包含させることにより、比表面積を大きくしやすい。この場合、磁性シリカ粒子のＴＥＭ写真において、シリカ膜中に含まれる磁性酸化物粒子の最大径と最小径の平均をもってその粒子の粒径とし、該粒径の個数平均を算出して磁性酸化物粒子の平均粒径とする。磁性シリカ粒子の平均粒径は、上述のようにレーザー回折による湿式粒度測定器で測定したｄ５０の値である。また、磁性シリカ粒子において、芯粒子である磁性金属粒子は、磁性酸化物粒子よりも大きいことが好ましい。飽和磁化および比表面積を高く維持するためである。かかる大小関係は、ＳＥＭ写真またはＴＥＭ写真において、それぞれの粒子の最大径と最小径の平均で比較する。 In the magnetic silica particles, the average particle diameter of the magnetic oxide particles is preferably 1/10 or less of the average particle diameter of the magnetic silica particles. By including such fine magnetic oxide particles in the silica outer shell, the specific surface area can be easily increased. In this case, in the TEM photograph of the magnetic silica particles, the average of the maximum diameter and the minimum diameter of the magnetic oxide particles contained in the silica film is used as the particle diameter of the particles, and the number average of the particle diameters is calculated to calculate the magnetic oxide. The average particle size of the particles. The average particle diameter of the magnetic silica particles is a value of d50 measured by a wet particle size measuring device by laser diffraction as described above. In the magnetic silica particles, the magnetic metal particles that are core particles are preferably larger than the magnetic oxide particles. This is to keep the saturation magnetization and specific surface area high. Such a magnitude relationship is compared with the average of the maximum diameter and the minimum diameter of each particle in an SEM photograph or a TEM photograph.
当該磁性シリカ粒子は保磁力が１０ｋＡ／ｍ（１１０Ｏｅ）以下であることが好ましい。さらに残留磁化Ｍｒと飽和磁化Ｍｓとの比Ｍｒ/Ｍｓが０.０３以下であることが好ましい。Ｍｒ/Ｍｓが０.０３を超えて残留磁化が大きくなると、粒子同士が磁気的に凝集してしまう。また、保磁力が１０ｋＡ／ｍを越える値であるとＭｒが大きくなり、前記磁気凝集を引き起こす。この粒子凝集が顕著になると、生体物質と反応し得る有効な表面積が少なくなるだけでなく、溶液中における粒子の沈降が速くなってしまい、溶液中の生体物質と反応する時間が限られるため、好ましくない。高分散性を得るためには、保磁力が１０ｋＡ／ｍ以下であって、Ｍｒ／Ｍｓが０.０３以下であることが好ましい。より好ましくはＭｒ／Ｍｓは０.０２３以下である。また、本発明に係る磁性シリカ粒子は、磁性金属を用いるので、１００Ａ・ｍ２／ｋｇ以上の飽和磁化Ｍｓを実現することが可能である。マグネタイトＦｅ３Ｏ４の飽和磁化は９２Ａ・ｍ２／ｋｇ程度であるから、被覆を設けた状態での磁性シリカ粒子の飽和磁化を１００Ａ・ｍ２／ｋｇ以上とすることによって、磁性酸化物粒子では実現できなかった、高飽和磁化を有する、すなわち磁気捕集速度に優れた磁性シリカ粒子を実現することができる。逆にＭｓが１００Ａ・ｍ２／ｋｇ未満であると外部磁場との相互作用が小さくなり、例えば溶液中に分散させた磁性シリカ粒子を磁気捕集する際に時間が掛かる、あるいは所定の時間内に十分回収できなくなるので好ましくない。磁性シリカ粒子のＭｓを１００Ａ・ｍ２／ｋｇ以上、保磁力を１０ｋＡ／ｍ以下、かつＭｒ／Ｍｓを０.０３以下とすることによって、高飽和磁化を維持しつつ、分散性も高められる。これは、よりいっそう高速で高効率の生体物質回収にも寄与する。 The magnetic silica particles preferably have a coercive force of 10 kA / m (110 Oe) or less. Furthermore, the ratio Mr / Ms between the residual magnetization Mr and the saturation magnetization Ms is preferably 0.03 or less. When Mr / Ms exceeds 0.03 and the residual magnetization increases, the particles are magnetically aggregated. On the other hand, if the coercive force exceeds 10 kA / m, Mr increases and causes the magnetic aggregation. When this particle aggregation becomes significant, not only the effective surface area that can react with the biological material is reduced, but also the sedimentation of the particles in the solution becomes faster, and the time for reacting with the biological material in the solution is limited. It is not preferable. In order to obtain high dispersibility, it is preferable that the coercive force is 10 kA / m or less and the Mr / Ms is 0.03 or less. More preferably, Mr / Ms is 0.023 or less. Further, since the magnetic silica particles according to the present invention use a magnetic metal, it is possible to realize a saturation magnetization Ms of 100 A · m 2 / kg or more. Since the saturation magnetization of magnetite Fe 3 O 4 is 92A · m 2 / kg approximately, by the saturation magnetization of the magnetic silica particles in a state in which a coating with 100A · m 2 / kg or more, magnetic oxide particles Thus, it is possible to realize magnetic silica particles having high saturation magnetization, that is, having an excellent magnetic collection speed, which could not be realized by the above method. On the other hand, when Ms is less than 100 A · m 2 / kg, the interaction with the external magnetic field is reduced, and for example, it takes time to magnetically collect magnetic silica particles dispersed in a solution, or within a predetermined time. It is not preferable because it cannot be sufficiently recovered. By setting Ms of the magnetic silica particles to 100 A · m 2 / kg or more, a coercive force of 10 kA / m or less, and Mr / Ms to 0.03 or less, dispersibility can be improved while maintaining high saturation magnetization. This also contributes to faster and more efficient recovery of biological material.
本発明の磁性シリカ粒子は例えば以下の製造方法によって製造される。上述した芯粒子と磁性酸化物微粒子とをアルコール溶液中に分散させ、ケイ素アルコキシドの加水分解反応を当該アルコール溶液中で進行させることにより、上記芯粒子に磁性酸化物微粒子を包含するシリカ被覆を施す。また、（１）上述した芯粒子をアルコール溶液中に分散させ、ケイ素アルコキシドの加水分解反応を当該アルコール溶液中で進行させることにより、上記芯粒子にシリカ被覆を施し、（２）上記シリカ被覆粒子と磁性酸化物微粒子とをアルコール溶液中に分散させ、ケイ素アルコキシドの加水分解反応を再び当該アルコール溶液中で進行させる、という二段階にわけて外殻であるシリカ被覆を形成してもよい。 The magnetic silica particles of the present invention are produced, for example, by the following production method. The core particles and the magnetic oxide fine particles are dispersed in an alcohol solution, and a silicon alkoxide hydrolysis reaction is allowed to proceed in the alcohol solution, whereby the core particles are coated with silica containing the magnetic oxide fine particles. . (1) The core particles described above are dispersed in an alcohol solution, and the hydrolysis reaction of silicon alkoxide is allowed to proceed in the alcohol solution, whereby the core particles are coated with silica. (2) The silica-coated particles The silica coating, which is the outer shell, may be formed in two steps, in which the magnetic oxide particles and the magnetic oxide particles are dispersed in an alcohol solution and the hydrolysis reaction of the silicon alkoxide proceeds again in the alcohol solution.
ケイ素アルコキシドの具体例としては、テトラメトキシシラン、テトラエトキシシラン、テトライソプロポキシシラン、テトラブトキシシラン、メチルトリメトキシシラン、メチルトリエトキシシラン、アミノフェニルトリメトキシシラン、アミノプロピルトリメトキシシラン、Ｎ−２−アミノエチル−３−アミノプロピルトリメトキシシランなどが挙げられる。また、３−トリエトキシシリルーンー（１，３−ジメチルーブチリデン）プロピルアミン、Ｎ−２−アミノエチル−３−アミノプロピルトリエトキシシラン、Ｎ−２−アミノエチル−３−アミノプロピルメチルジメトキシシラン、Ｎ−フェニルー３−アミノプロピルトリエトキシシラン、Ｎ−フェニルー３−アミノプロピルトリメトキシシラン、アミノプロピルトリエトキシシラン、ジメチルジエトキシシラン、ジメチルジメトキシシラン、テトラプロポキシシラン、フェニルトリエトキシシラン等でも良い。シリカ（ケイ素酸化物）は、例えばテトラエトキシシランの加水分解反応で得られ、シリカを析出させるテトラエトキシシランの加水分解反応を制御することで、磁性シリカ粒子は再現性をもって製造することができる。 Specific examples of the silicon alkoxide include tetramethoxysilane, tetraethoxysilane, tetraisopropoxysilane, tetrabutoxysilane, methyltrimethoxysilane, methyltriethoxysilane, aminophenyltrimethoxysilane, aminopropyltrimethoxysilane, N-2 -Aminoethyl-3-aminopropyltrimethoxysilane and the like. In addition, 3-triethoxysilylene- (1,3-dimethylbutylidene) propylamine, N-2-aminoethyl-3-aminopropyltriethoxysilane, N-2-aminoethyl-3-aminopropylmethyldimethoxy Silane, N-phenyl-3-aminopropyltriethoxysilane, N-phenyl-3-aminopropyltrimethoxysilane, aminopropyltriethoxysilane, dimethyldiethoxysilane, dimethyldimethoxysilane, tetrapropoxysilane, phenyltriethoxysilane, etc. may be used. . Silica (silicon oxide) is obtained, for example, by a hydrolysis reaction of tetraethoxysilane, and magnetic silica particles can be produced with reproducibility by controlling the hydrolysis reaction of tetraethoxysilane to precipitate silica.
アルコール溶液としては、例えばエタノール、メタノール、イソプロパノールなどの低級アルコールが挙げられる。ケイ素アルコキシドとしてテトラエトキシシランを用いる場合には、テトラエトキシシランの加水分解反応を促進させるために触媒としてアンモニア水を添加する。アンモニア水はテトラエトキシシランを理論上１００％加水分解可能な量以上の水を含む。具体的にはテトラエトキシシラン１ｍｏｌに対して水２ｍｏｌ以上である。アルコール溶液の使用割合は、テトラエトキシシラン１００重量部に対して１００〜１００００重量部が好ましい。さらに、テトラエトキシシランの使用割合は、金属微粒子１００重量部に対してテトラエトキシシランが５〜８０重量部が好ましい。さらに好ましくはテトラエトキシシランが１０〜６０重量部である。テトラエトキシシランが５重量部以下であると、金属微粒子の表面がケイ素酸化物被覆により均一に被覆することが困難となる。一方、テトラエトキシシランの使用割合が８０重量部を超える場合は、磁性シリカ粒子の外殻を形成するシリカの他に、ケイ素酸化物単体の微粒子が形成されてしまう。テトラエトキシシランの加水分解に用いられる水の使用割合は、テトラエトキシシラン１００重量部に対して、好ましくは１〜１０００重量部である。この割合が１重量部未満の場合には、テトラエトキシシランの加水分解の進行が遅くなり、作製効率が悪くなる。一方、１０００重量部を越えると、ケイ素酸化物を主体として構成されるケイ素酸化物の単離球が形成されてしまうため、好ましくない。触媒として用いられるアンモニア水の使用割合は、例えば、アンモニア水の濃度が２８％の場合には、テトラエトキシシラン１００重量部に対して、１０〜１００重量部が好ましい。１０重量部よりも少ない場合には、触媒としての作用が発揮されないため、好ましくない。また、１００重量部よりも多い場合には、ケイ素酸化物を主体として構成されるケイ素酸化物の単離球が形成されてしまうため、好ましくない。上記手法において、溶媒中にはアンモニア水およびケイ素アルコキシドが含まれるため、ｐＨが約１１と弱アルカリ性である。そのため、金属粒子が腐食することが懸念されるが、上述の芯粒子を適用することにより、金属を粒子核としているにも関わらず、金属核の腐食を防ぐことができる。 Examples of the alcohol solution include lower alcohols such as ethanol, methanol, and isopropanol. When tetraethoxysilane is used as the silicon alkoxide, ammonia water is added as a catalyst in order to accelerate the hydrolysis reaction of tetraethoxysilane. Ammonia water contains water in an amount that can theoretically 100% hydrolyze tetraethoxysilane. Specifically, it is 2 mol or more of water with respect to 1 mol of tetraethoxysilane. The use ratio of the alcohol solution is preferably 100 to 10,000 parts by weight with respect to 100 parts by weight of tetraethoxysilane. Furthermore, the use ratio of tetraethoxysilane is preferably 5 to 80 parts by weight of tetraethoxysilane with respect to 100 parts by weight of metal fine particles. More preferably, tetraethoxysilane is 10 to 60 parts by weight. When the tetraethoxysilane is 5 parts by weight or less, it becomes difficult to uniformly coat the surface of the metal fine particles with the silicon oxide coating. On the other hand, when the proportion of tetraethoxysilane used exceeds 80 parts by weight, fine particles of silicon oxide alone are formed in addition to the silica that forms the outer shell of the magnetic silica particles. The ratio of water used for the hydrolysis of tetraethoxysilane is preferably 1 to 1000 parts by weight with respect to 100 parts by weight of tetraethoxysilane. When this ratio is less than 1 part by weight, the progress of hydrolysis of tetraethoxysilane is slowed, resulting in poor production efficiency. On the other hand, if it exceeds 1000 parts by weight, silicon oxide isolated spheres composed mainly of silicon oxide are formed, which is not preferable. For example, when the ammonia water concentration is 28%, the usage ratio of the ammonia water used as the catalyst is preferably 10 to 100 parts by weight with respect to 100 parts by weight of tetraethoxysilane. When the amount is less than 10 parts by weight, the effect as a catalyst is not exhibited, which is not preferable. On the other hand, when the amount is more than 100 parts by weight, silicon oxide isolated spheres mainly composed of silicon oxide are formed, which is not preferable. In the above method, since the solvent contains aqueous ammonia and silicon alkoxide, the pH is about 11 and is weakly alkaline. Therefore, although there is a concern that the metal particles corrode, by applying the above-described core particles, it is possible to prevent the metal cores from being corroded even though the metal is a particle nucleus.
（３）磁性酸化物粒子
前記磁性酸化物粒子としては、Ｆｅ３Ｏ４（マグネタイト）、γ―Ｆｅ２Ｏ３（マグヘマイト）、ＦｅＯ（ウスタイト）、各種フェライト（ＺＯ・Ｆｅ２Ｏ３で表される組成、ＺはＭｎ２＋、Ｆｅ２＋、Ｃｏ２＋、Ｎｉ２＋、Ｃｕ２＋、Ｚｎ２＋の少なくとも一つ）、またはこれらの混合物が挙げられる。
(3) Magnetic oxide particles The magnetic oxide particles are represented by Fe 3 O 4 (magnetite), γ-Fe 2 O 3 (maghemite), FeO (wustite), various ferrites (ZO · Fe 2 O 3 ). that composition, Z is Mn 2+, Fe 2 +, Co 2+, Ni 2+, Cu 2+, at least one), or a mixture of these Zn 2+ and the like.
添加する磁性酸化物粒子の平均粒径は、用いる芯粒子の平均粒子径に対して１／１０以下であることが好ましい。平均粒径を１／１０以下とすることにより、シリカ被覆層内に上記酸化物微粒子を内包させることができ、最終的に得られる磁性シリカ粒子の比表面積を効率的に増大させることができる。前記大小関係は、磁性シリカ粒子内においても維持される。したがって、磁性酸化物粒子の平均粒径を、用いる芯粒子の平均粒子径に対して１／１０以下とすることによって得られた磁性シリカ粒子は、外殻であるシリカ被覆内に芯粒子である磁性金属微粒子よりも微細な磁性酸化物粒子を包含する構造となる。上記磁性酸化物粒子は完全にシリカ膜中に埋め込まれている必要はなく、芯粒子表面にシリカを介して接着された状態でも構わない。上記磁性酸化物微粒子の平均粒子径が上述の芯粒子の平均粒子径に対して１／１０を越える大きさであると、当該酸化物粒子は芯粒子に付着することなく単独でシリカ被覆されてしまう。上記単独シリカ被覆粒子の磁性は酸化物粒子が担っているため、その飽和磁化が極めて小さく、磁気応答性が低いため好ましくない。ここで磁性酸化物を用いる理由は、最終的に得られる磁性シリカ粒子において飽和磁化を出来る限り高く維持するためである。 The average particle size of the magnetic oxide particles to be added is preferably 1/10 or less with respect to the average particle size of the core particles used. By setting the average particle size to 1/10 or less, the oxide fine particles can be included in the silica coating layer, and the specific surface area of the finally obtained magnetic silica particles can be efficiently increased. The magnitude relationship is maintained even in the magnetic silica particles. Therefore, the magnetic silica particles obtained by setting the average particle size of the magnetic oxide particles to 1/10 or less of the average particle size of the core particles used are core particles in the silica coating that is the outer shell. The structure includes magnetic oxide particles finer than magnetic metal fine particles. The magnetic oxide particles need not be completely embedded in the silica film, and may be in a state of being bonded to the core particle surface via silica. When the average particle size of the magnetic oxide fine particles is larger than 1/10 of the average particle size of the core particles, the oxide particles are independently coated with silica without adhering to the core particles. End up. Since the single silica-coated particles are magnetized by the oxide particles, the saturation magnetization is extremely small and the magnetic responsiveness is low. The reason why the magnetic oxide is used here is to maintain the saturation magnetization as high as possible in the finally obtained magnetic silica particles.
当該磁性酸化物粒子の添加量は、上述の芯粒子となる磁性金属粒子１００重量部に対して０．５〜８重量部であることが好ましい。０．５重量部未満であると磁性酸化物微粒子を添加した効果が顕著に現れないため好ましくない。一方、８重量部を越えると磁性シリカ粒子の飽和磁化が低下するだけでなく、酸化物微粒子自身の保磁力が作用して残磁が大きくなり、磁気凝集してしまうので好ましくない。あるいはシリカ被覆された磁性酸化物粒子が単独で存在する割合が増加するため、好ましくない。より効果的には、当該磁性酸化物粒子を質量比で１〜６重量部の割合で添加することが好ましい。 The addition amount of the magnetic oxide particles is preferably 0.5 to 8 parts by weight with respect to 100 parts by weight of the magnetic metal particles serving as the core particles. If it is less than 0.5 part by weight, the effect of adding magnetic oxide fine particles does not appear remarkably, which is not preferable. On the other hand, when the amount exceeds 8 parts by weight, not only the saturation magnetization of the magnetic silica particles is lowered, but also the coercive force of the oxide fine particles themselves acts to increase the residual magnetism and cause magnetic aggregation, which is not preferable. Or since the ratio in which the silica-coated magnetic oxide particle exists independently increases, it is not preferable. More effectively, the magnetic oxide particles are preferably added at a mass ratio of 1 to 6 parts by weight.
前記芯粒子に均一にシリカを被覆するためには、モーター攪拌機、V型混合機、ボールミル混合機やディゾルバー攪拌機または超音波装置などを用いて、溶液と芯粒子を十分混合する。混合時間はテトラエトキシシランの加水分解反応が十分に進行する時間以上必要である。生成する残留水和物を除去し、被覆膜の強度を増加させるためには熱処理を行うことが望ましい。更に当該シリカ被覆粒子に前記磁性酸化物微粒子を所定量添加し、この混合粉を同様にシリカ被覆することにより、本発明に係る磁性シリカ粒子が得られる。 In order to uniformly coat the core particles with silica, the solution and the core particles are sufficiently mixed using a motor stirrer, a V-type mixer, a ball mill mixer, a dissolver stirrer, an ultrasonic device, or the like. The mixing time is required to be at least the time for which the tetraethoxysilane hydrolysis reaction proceeds sufficiently. In order to remove the residual hydrate that forms and increase the strength of the coating film, it is desirable to perform heat treatment. Furthermore, the magnetic silica particles according to the present invention can be obtained by adding a predetermined amount of the magnetic oxide fine particles to the silica-coated particles and similarly coating the mixed powder with silica.
（実施例１）
まず、芯粒子となる磁性金属粒子を作製する。平均粒径０．０３μｍのα−Ｆｅ２Ｏ３粉と平均粒径１μｍのＴｉＣ粉を質量比で７：３となるように秤量し、ボールミル混合機で５０時間混合した。得られた混合粉をアルミナボートに適量充填し、窒素ガス中にて８００℃×２時間の熱処理を行なった。室温まで冷却した後にアルミナボートを取り出し、熱処理された試料粉末を回収した。
Example 1
First, magnetic metal particles to be core particles are prepared. Α-Fe 2 O 3 powder having an average particle diameter of 0.03 μm and TiC powder having an average particle diameter of 1 μm were weighed so as to have a mass ratio of 7: 3 and mixed for 50 hours by a ball mill mixer. An appropriate amount of the obtained mixed powder was filled in an alumina boat, and heat treatment was performed in nitrogen gas at 800 ° C. for 2 hours. After cooling to room temperature, the alumina boat was taken out and the heat-treated sample powder was collected.
上記試料粉末のＸ線回折パターンを図１に示す。図１のグラフの横軸は回折の２θ（°）に相当し、縦軸は回折の強度（相対値）に相当する。ＭＤＩ社製解析ソフト「Ｊａｄｅ，ｖｅｒ．５」にて解析すると、図１の回折パターンはα−Ｆｅ、ＴｉＯ２（ルチル構造）に同定された。ＴｉＯ２に対応した回折ピークの強度が最大となるのは、２θ＝２７．５°の時であり、この回折ピークの半値幅は０．１４であり、ピーク強度のα−Ｆｅ（１１０）ピーク強度に対する比率は０．１８であった。これによりＴｉＯ２が高い結晶性を有することが分かる。上記試料粉末の平均粒径をレーザー回折粒度分布測定機（ＨＯＲＩＢＡ製ＬＡ−９２０）にて測定した結果、ｄ５０は１．３μｍであった。 The X-ray diffraction pattern of the sample powder is shown in FIG. The horizontal axis of the graph in FIG. 1 corresponds to 2θ (°) of diffraction, and the vertical axis corresponds to the intensity of diffraction (relative value). When analyzed with analysis software “Jade, ver. 5” manufactured by MDI, the diffraction pattern of FIG. 1 was identified as α-Fe, TiO 2 (rutile structure). The intensity of the diffraction peak corresponding to TiO 2 is maximized when 2θ = 27.5 °, the half-value width of this diffraction peak is 0.14, and the α-Fe (110) peak of the peak intensity The ratio to strength was 0.18. This shows that TiO 2 has high crystallinity. As a result of measuring the average particle size of the sample powder with a laser diffraction particle size distribution analyzer (LA-920 manufactured by HORIBA), d50 was 1.3 μm.
また図２は上記試料粉末をＴＥＭにより直接観察した像を表す。粒子中央部に観察される黒色コントラストの粒子はＦｅ粒子であり、Ｆｅ粒子の周囲に見られる半透明の被覆層はＴｉＯ２である。Ｆｅ及びＴｉＯ２の同定はＥＤＸ分析により実施した。以上、Ｘ線回折測定及びＴＥＭ解析により、上記試料粉末はルチル構造のＴｉＯ２で被覆されたＦｅ粒子であることが確認された。すなわち、上記方法によって、表面にＴｉＯ２を主体とするＴｉ酸化物の被覆を有する磁性金属粒子を得た。 FIG. 2 shows an image obtained by directly observing the sample powder with a TEM. The black contrast particles observed at the center of the particles are Fe particles, and the translucent coating layer around the Fe particles is TiO 2 . The identification of Fe and TiO 2 was performed by EDX analysis. As described above, it was confirmed by X-ray diffraction measurement and TEM analysis that the sample powder was Fe particles covered with TiO 2 having a rutile structure. That is, magnetic metal particles having a Ti oxide coating mainly composed of TiO 2 on the surface were obtained by the above method.
更に上記試料粉末の磁気特性をＶＳＭ（振動型磁力計）により測定した。最大印加磁界を１．６ＭＡ／ｍとして測定した結果、飽和磁化Ｍｓ：１３２Ａ・ｍ２／ｋｇ、保磁力Ｈｃ：４．８ｋＡ／ｍであった。飽和磁化の値はバルクＦｅの飽和磁化値（＝２１８Ａ・ｍ２／ｋｇ）の６０．５％に相当するため、本実施例試料のＦｅ含有率は質量比で６０．５％、ＴｉＯ２含有率は３９．５％である。 Further, the magnetic properties of the sample powder were measured with a VSM (vibrating magnetometer). As a result of measuring the maximum applied magnetic field at 1.6 MA / m, the saturation magnetization Ms was 132 A · m 2 / kg, and the coercive force Hc was 4.8 kA / m. Since the saturation magnetization value corresponds to 60.5% of the saturation magnetization value (= 218 A · m 2 / kg) of bulk Fe, the Fe content of the sample of this example is 60.5% by mass ratio and contains TiO 2. The rate is 39.5%.
次に上述の方法で得られた磁性金属粒子に以下に説明する手法で３回シリカ被覆処理を施し、磁性シリカ粒子を作製した。第１処理として、上述の磁性金属粒子の試料粉末５ｇをエタノール溶媒１００ｍｌ中に分散し、これにテトラエトキシシランを１ｍｌ添加した。次にこの溶媒を攪拌しながら純水２２ｇとアンモニア水４ｇの混合溶液を添加し、上記混合溶液を１時間攪拌した。攪拌後、磁性粒子を磁石でビーカ内壁に捕捉しながら上澄み液を除去した。第２処理として、上述の第１処理後の粉末をエタノール溶媒１００ｍｌ中に分散し、更に平均粒径１００ｎｍのＦｅ３Ｏ４（マグネタイト）粒子を０．０５ｇ（１重量部）添加し、これにテトラエトキシシランを１ｍｌ添加して５分間攪拌した。次にこの溶媒を攪拌しながら純水２２ｇとアンモニア水４ｇの混合溶液を添加し、上記混合溶液を１時間攪拌した。攪拌後、磁性粒子を磁石でビーカ内壁に捕捉しながら上澄み液を除去した。第３処理として、第２処理によって得られた粉末に対して第１処理と同様にしてシリカ被覆処理を行なった。上記３回シリカ被覆処理後、イソプロピルアルコールで溶媒置換を行い、磁性シリカ粒子をドラフト内で乾燥させた。 Next, the magnetic metal particles obtained by the above-described method were subjected to silica coating treatment three times by the method described below to produce magnetic silica particles. As a first treatment, 5 g of the sample powder of magnetic metal particles described above was dispersed in 100 ml of ethanol solvent, and 1 ml of tetraethoxysilane was added thereto. Next, a mixed solution of 22 g of pure water and 4 g of aqueous ammonia was added while stirring the solvent, and the mixed solution was stirred for 1 hour. After stirring, the supernatant was removed while trapping the magnetic particles on the inner wall of the beaker with a magnet. As the second treatment, the powder after the first treatment is dispersed in 100 ml of ethanol solvent, and 0.05 g (1 part by weight) of Fe 3 O 4 (magnetite) particles having an average particle diameter of 100 nm is further added thereto. 1 ml of tetraethoxysilane was added and stirred for 5 minutes. Next, a mixed solution of 22 g of pure water and 4 g of aqueous ammonia was added while stirring the solvent, and the mixed solution was stirred for 1 hour. After stirring, the supernatant was removed while trapping the magnetic particles on the inner wall of the beaker with a magnet. As the third treatment, a silica coating treatment was performed on the powder obtained by the second treatment in the same manner as the first treatment. After the above silica coating treatment three times, the solvent was replaced with isopropyl alcohol, and the magnetic silica particles were dried in a fume hood.
Ｎ２ガスを用いたＢＥＴ法により、上記磁性シリカ粒子の比表面積を測定した結果、４.２ｍ２／ｇを得た。また前記磁性金属粒子と同様に上記磁性シリカ粒子の試料粉末の平均粒径を測定した結果、５.３μｍを得た。また実施例１と同様に上記試料粉末の磁気特性をＶＳＭにて測定した結果、飽和磁化Ｍｓ：１２７Ａｍ２／ｋｇ、保磁力Ｈｃ：５．５ｋＡ／ｍを得た。また残留磁化ＭｒとＭｓとの比を算出した結果、Ｍｒ／Ｍｓは０.０２であった。各測定結果を表１にまとめた。 As a result of measuring the specific surface area of the magnetic silica particles by the BET method using N 2 gas, 4.2 m 2 / g was obtained. Further, as a result of measuring the average particle diameter of the sample powder of the magnetic silica particles in the same manner as the magnetic metal particles, 5.3 μm was obtained. As in Example 1, the magnetic properties of the sample powder were measured by VSM. As a result, saturation magnetization Ms: 127 Am 2 / kg and coercive force Hc: 5.5 kA / m were obtained. Further, as a result of calculating the ratio between the residual magnetization Mr and Ms, Mr / Ms was 0.02. The measurement results are summarized in Table 1.
（実施例２、３、４）
マグネタイト粒子の添加量を２重量部（実施例２）、４重量部（実施例３）、６重量部（実施例４）とした以外は実施例１と同様にしてシリカ被覆処理を実施した。得られた試料粉末の各測定値を表１にまとめた。マグネタイト粒子の添加量が１〜６重量部である実施例１〜４の磁性シリカ粒子は飽和磁化Ｍｓが１００Ａｍ２／ｋｇ以上、具体的には１２３Ａｍ２／ｋｇ以上の高い飽和磁化を示している。また、実施例１〜４の磁性シリカ粒子では、保磁力は８.０ｋＡ／ｍ以下、残留磁化Ｍｒは３．５Ａｍ２／ｋｇ以下、Ｍｒ／Ｍｓは０.０２８以下と低く、ともに良好な値を示した。また、実施例１〜４ではいずれも、後述する比較例1に比べて比表面積であるＢＥＴ値が２％以上増加した。これは磁性シリカ粒子が磁場中で高い磁化を発現するにも関わらず、無磁場での残留磁化が小さいために磁気凝集が極めて小さいことを表している。
(Examples 2, 3, and 4)
The silica coating treatment was performed in the same manner as in Example 1 except that the amount of magnetite particles added was 2 parts by weight (Example 2), 4 parts by weight (Example 3), and 6 parts by weight (Example 4). The measured values of the obtained sample powder are summarized in Table 1. The magnetic silica particles of Examples 1 to 4 in which the added amount of magnetite particles is 1 to 6 parts by weight shows a high saturation magnetization with a saturation magnetization Ms of 100 Am 2 / kg or more, specifically 123 Am 2 / kg or more. . In the magnetic silica particles of Examples 1 to 4, the coercive force is 8.0 kA / m or less, the residual magnetization Mr is 3.5 Am 2 / kg or less, and Mr / Ms is 0.028 or less, both of which are good values. showed that. In each of Examples 1 to 4, the BET value, which is the specific surface area, increased by 2% or more compared to Comparative Example 1 described later. This indicates that although the magnetic silica particles exhibit high magnetization in a magnetic field, the magnetic aggregation is extremely small due to the small residual magnetization in the absence of a magnetic field.
（比較例１）
マグネタイト粒子を無添加とした以外は実施例１と同様にシリカ被覆処理を実施し、磁性シリカ粒子を得た。表１に各測定データをまとめた。
(Comparative Example 1)
A silica coating treatment was carried out in the same manner as in Example 1 except that no magnetite particles were added to obtain magnetic silica particles. Table 1 summarizes each measurement data.
また、本発明の磁性粒子のＤＮＡ抽出性能を評価するため、Ｒｏｃｈ社製ＤＮＡ抽出キット「ＭａｇＮＡ Ｐｕｒｅ ＬＣ ＤＮＡ Ｉｓｏｌａｔｉｏｎ Ｋｉｔ Ｉ」を用いて馬血１００μｌからＤＮＡを精製した。実施例１〜４、比較例１の磁性シリカ粒子１２ｍｇをそれぞれイソプロピルアルコール（ＩＰＡ）１５０μｌ中に分散させた溶液を各々磁気ビーズ液として用いた以外は上記Ｋｉｔのプロトコルに準拠してＤＮＡを抽出した。結果を表２に示す。マグネタイトを添加した実施例１〜４の磁性シリカ粒子は、マグネタイトを添加していない比較例１に比べてＤＮＡを８％以上多く抽出していることが分かる。Ｆｅ３Ｏ４微粒子を添加したことによる比表面積の増加により高抽出能が発現している。 Further, in order to evaluate the DNA extraction performance of the magnetic particles of the present invention, DNA was purified from 100 μl of horse blood using a DNA extraction kit “MagNA Pure LC DNA Isolation Kit I” manufactured by Roch. DNA was extracted according to the above Kit protocol, except that 12 mg of the magnetic silica particles of Examples 1 to 4 and Comparative Example 1 were each dispersed in 150 μl of isopropyl alcohol (IPA) as the magnetic bead solution. . The results are shown in Table 2. It can be seen that the magnetic silica particles of Examples 1 to 4 to which magnetite was added extracted more DNA by 8% or more than Comparative Example 1 to which no magnetite was added. High extraction ability is manifested by an increase in specific surface area due to the addition of Fe 3 O 4 fine particles.
（実施例５、６）
マグネタイト粒子の添加量を１０重量部（実施例５）、２０重量部（実施例６）とした以外は実施例１と同様にしてシリカ被覆処理を実施し、磁性シリカ粒子を得た。表２に各測定データをまとめた。実施例５、６とも、マグネタイト無添加の比較例１に比べて比表面積が増大し、また１２０Ａｍ２／ｋｇ以上の飽和磁化も維持している。但し、実施例１〜４に比べて飽和磁化がやや減少するとともに、保磁力Ｈｃが増加し、１０ｋＡ／ｍを超えていることが分かる。Ｈｃの増加に伴い残留磁化Ｍｒも増加し、結果としてＭｒ／Ｍｓの値も０.０３を超える値となっている。
(Examples 5 and 6)
The silica coating treatment was performed in the same manner as in Example 1 except that the addition amount of the magnetite particles was changed to 10 parts by weight (Example 5) and 20 parts by weight (Example 6) to obtain magnetic silica particles. Table 2 summarizes each measurement data. In both Examples 5 and 6, the specific surface area is increased as compared with Comparative Example 1 without addition of magnetite, and the saturation magnetization of 120 Am 2 / kg or more is maintained. However, it can be seen that the saturation magnetization is slightly reduced as compared with Examples 1 to 4, and the coercive force Hc is increased to exceed 10 kA / m. As the Hc increases, the remanent magnetization Mr also increases. As a result, the value of Mr / Ms also exceeds 0.03.
また上記磁性シリカ粒子のＤＮＡ抽出性能を実施例１〜４と同様にして評価した。結果を表２に示す。実施例５、６では保磁力及びＭｒ／Ｍｓが大きいことから、粒子の磁気凝集が激しいと予測され、ＤＮＡ抽出量としては低くなった。 The DNA extraction performance of the magnetic silica particles was evaluated in the same manner as in Examples 1 to 4. The results are shown in Table 2. In Examples 5 and 6, since the coercive force and Mr / Ms were large, it was predicted that the magnetic aggregation of the particles was intense, and the amount of extracted DNA was low.
（比較例２）
市販の磁性シリカ粒子（Ｒｏｃｈｅ製、ＭａｇＮＡＰｕｒｅ ＬＣ ＤＮＡ Ｉｓｏｌａｔｉｏｎ Ｋｉｔ Ｉに付属）について比表面積、平均粒径、磁気特性を測定した結果を表１にまとめた。
(Comparative Example 2)
Table 1 summarizes the results of measurement of specific surface area, average particle diameter, and magnetic properties of commercially available magnetic silica particles (Roche, attached to MagNAPure LC DNA Isolation Kit I).
また実施例３および比較例１の磁性シリカ粒子をそれぞれ５０，０００倍でＳＥＭ観察した結果を図３および図４に示す。実施例３ではＦｅ３Ｏ４微粒子に対応した微細な凹凸が観察された（図３中黄色で囲んだ部分）。この微細な凹凸により比較例１よりも表面積を大きく保つことができ、効率的にＤＮＡなどの生体物質を吸着させることができる。 3 and 4 show the results of SEM observation of the magnetic silica particles of Example 3 and Comparative Example 1 at a magnification of 50,000 times, respectively. In Example 3, fine irregularities corresponding to Fe 3 O 4 fine particles were observed (portion surrounded by yellow in FIG. 3). Due to the fine irregularities, the surface area can be kept larger than that of Comparative Example 1, and biological substances such as DNA can be efficiently adsorbed.
１：芯粒子 ２：シリカ ３：磁性酸化物粒子
1: Core particles 2: Silica 3: Magnetic oxide particles
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