JP4811658B2 - Coated metal fine particles and production method thereof, - Google Patents
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Description
磁気テープや磁気記録ディスク等の磁気記録媒体、電波吸収体、インダクタ、プリント基板等の電子デバイス、ヨーク等の軟磁性体、光触媒、核酸抽出用やたんぱく質捕捉用の磁気ビーズ、医療用マイクロスフィア等に用いる被覆磁性金属粒子、およびその製造方法に関する。 Magnetic recording media such as magnetic tapes and magnetic recording disks, electronic devices such as radio wave absorbers, inductors and printed boards, soft magnetic materials such as yokes, photocatalysts, magnetic beads for nucleic acid extraction and protein capture, medical microspheres, etc. The present invention relates to a coated magnetic metal particle used in the above and a manufacturing method thereof.
電子機器の高性能化及び小型軽量化に伴い、電子デバイスの高性能化及び小型軽量化とともに、電子デバイスを構成する材料の高性能化及びナノサイズ化も要求されている。例えば磁気テープに塗布する磁性粒子は、磁気記録密度の向上を目的として、ナノサイズ化と磁化の向上が同時に要求されている。 As electronic devices become more sophisticated and smaller and lighter, there is a demand for higher performance and smaller size and weight of electronic devices, as well as higher performance and nano-size of materials constituting electronic devices. For example, magnetic particles applied to magnetic tape are required to be nanosized and magnetized at the same time for the purpose of improving magnetic recording density.
ナノ磁性粒子は主に共沈法や水熱合成法等の液相合成法により製造されている。液相法で得られるナノ磁性粒子はフェライトやマグネタイト等の酸化物粒子である。最近では有機金属化合物の熱分解を利用した方法も採用されており、例えばFe(CO)5からFeのナノ粒子が製造されている。 Nanomagnetic particles are mainly produced by a liquid phase synthesis method such as a coprecipitation method or a hydrothermal synthesis method. Nanomagnetic particles obtained by the liquid phase method are oxide particles such as ferrite and magnetite. Recently, a method using thermal decomposition of an organometallic compound has also been adopted. For example, Fe nanoparticles are produced from Fe (CO) 5.
金属の磁性粒子は酸化物磁性粒子に比べて磁化が大きいため、工業的利用への期待が大きい。例えば、金属Feの飽和磁化は218A・m2/kgと酸化鉄に比べて非常に大きいので、磁場応答性に優れ、信号強度が大きくとれるという利点がある。しかし金属Fe等の金属粒子は容易に酸化し、例えば100μm以下、特に1μm以下の微粒子状にすると、比表面積の増大により大気中で激しく燃えるので、乾燥状態で取り扱うのが難しい。そのため、フェライトやマグネタイト等の酸化物粒子が広く利用されてきた。 Since metal magnetic particles have a larger magnetization than oxide magnetic particles, they are highly expected for industrial use. For example, the saturation magnetization of metallic Fe is 218 A · m 2 / kg, which is much larger than that of iron oxide, and therefore has the advantages of excellent magnetic field response and high signal strength. However, metal particles such as metallic Fe readily oxidize. For example, if they are made into fine particles of 100 μm or less, particularly 1 μm or less, they burn intensely in the atmosphere due to an increase in specific surface area, so it is difficult to handle them in a dry state. Therefore, oxide particles such as ferrite and magnetite have been widely used.
乾燥金属粒子を取り扱う場合、金属粒子を直接大気（酸素）に触れさせないように粒子表面に被膜を付与することが不可欠である。しかし、自身の金属酸化物で表面を被覆する方法は、少なからず金属を酸化劣化させる。また、特許文献１に示す方法のように高温でグラファイトの被膜を形成する方法では、工程や装置が複雑となり、生産性の点で十分ではない。その上、グラファイトはグラフェンシートが積層した構造を有するため、球状の金属粒子を被覆した場合、必ず格子欠陥が導入される。これらの欠陥が存在する被覆では、磁気ビーズ等、高耐食性が要求される用途では不満足である。そのため、高耐食性の金属微粒子、及びそれを安価に製造し得る工業生産性に優れた方法が望まれている。これに対して、本発明者らは簡便な方法により、酸化物で被覆された耐食性等に優れた金属微粒子を提供する方法を見出した（例えば特許文献２）。すなわち、金属Ｍ１の酸化物粉末と、酸化物の標準生成自由エネルギーがΔＧＭ１−Ｏ＞ΔＧＭ２−Ｏの関係を満たす元素Ｍ２を含む粉末とを混合し、その混合粉末を非酸化性雰囲気中で熱処理することにより、元素Ｍ２によって還元された金属Ｍ１の金属微粒子の表面をＭ２、Ｍ２の酸化物、Ｍ２の窒化物の少なくとも一つによって被覆された金属微粒子が提供される。 When handling dry metal particles, it is essential to provide a coating on the particle surface so that the metal particles are not directly exposed to the atmosphere (oxygen). However, the method of coating the surface with its own metal oxide causes oxidative degradation of the metal. Further, in the method of forming a graphite film at a high temperature as in the method disclosed in Patent Document 1, the process and the apparatus are complicated, which is not sufficient in terms of productivity. In addition, since graphite has a structure in which graphene sheets are laminated, lattice defects are always introduced when spherical metal particles are coated. Coatings with these defects are unsatisfactory for applications that require high corrosion resistance, such as magnetic beads. Therefore, a highly corrosion-resistant metal fine particle and a method excellent in industrial productivity capable of producing it at low cost are desired. In contrast, the present inventors have found a method for providing metal fine particles excellent in corrosion resistance and the like coated with an oxide by a simple method (for example, Patent Document 2). That is, the oxide powder of the metal M1 and the powder containing the element M2 in which the standard free energy of formation of the oxide satisfies the relationship of ΔG M1-O > ΔG M2-O are mixed, and the mixed powder is mixed in a non-oxidizing atmosphere. By performing the heat treatment, metal fine particles in which the surface of the metal fine particles of the metal M1 reduced by the element M2 is coated with at least one of M2, M2 oxide, and M2 nitride are provided.
特許文献２の製造方法によれば、簡便な方法で被覆された金属微粒子を提供することが可能であるが、金属微粒子には安定で、耐食性の高いものが要求される。金属微粒子を安定かつ完全に被覆して高耐食性を発現するためには、被覆層を厚くする必要がある。しかし被覆層を単純に厚くすると全体の粒子径が大きくなってしまう。粒子径の増大は比表面積の低下を招き、例えば医療用マイクロスフィアとして用いる場合には目的物質との反応性が低下してしまう。すなわち金属微粒子の耐食性を向上させることと、比表面積を大きくすることとの両立は困難であった。 According to the production method of Patent Document 2, it is possible to provide metal fine particles coated by a simple method, but the metal fine particles are required to be stable and have high corrosion resistance. In order to stably and completely coat the metal fine particles to develop high corrosion resistance, it is necessary to increase the thickness of the coating layer. However, if the coating layer is simply thickened, the overall particle size will increase. The increase in the particle diameter causes a decrease in the specific surface area. For example, when used as a medical microsphere, the reactivity with the target substance decreases. That is, it is difficult to improve the corrosion resistance of the metal fine particles and increase the specific surface area.
上記問題に鑑み、本発明は、耐食性に優れ、かつ比表面積が大きい被覆金属微粒子、及びかかる被覆金属微粒子を製造する方法を提供することを目的とした。 In view of the above problems, an object of the present invention is to provide coated metal fine particles having excellent corrosion resistance and a large specific surface area, and a method for producing such coated metal fine particles.
本発明の被覆金属微粒子の製造方法は、以下の３つの工程を有する。第１の工程は、Tiを含む粉末（ただしTi酸化物粉末を除く）と、酸化物の標準生成自由エネルギーがΔGM-O＞ΔGTiO2の関係を満たす金属Ｍの酸化物粉末とを混合する、混合工程である。第２の工程は、得られた混合粉末を非酸化性雰囲気中で650〜900℃で熱処理することによって、前記金属Ｍの酸化物を還元するとともに、得られた金属Ｍの微粒子の表面をＴｉＯ２を主体とするＴｉ酸化物で被覆して被覆金属微粒子を得る熱処理工程である。ここで「ＴｉＯ2を主体とする」とは、Ｘ線回折測定で検出されるＴｉＯ2以外のTi酸化物（例えば不定比組成のＴｉnＯ2n-1）も含む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。均一性の観点から、実質的にＴｉＯ2からなるのが好ましい。ここで「実質的にＴｉＯ2からなる」とは、Ｘ線回折パターンでＴｉＯ2以外のＴｉ酸化物のピークが明確に確認できない程度にＴｉＯ2の割合が多いことを言う。従って、Ｘ線回折パターンでノイズ程度にＴｉＯ2以外のＴｉ酸化物のピークがあっても、「実質的にＴｉＯ2からなる」の条件は満たす。第３の工程は、得られた前記被覆金属微粒子を生体擬似液に浸漬する、浸漬処理工程である。この浸漬処理工程によって、凹凸の構造、例えば花弁状の凹凸を前記被覆金属微粒子の表面に形成することができる。ここで、生体擬似液とは、血漿を模倣して作製された水溶液であり、生理食塩水、ＰＢＳバッファー、ハンクス液、擬似体液（Simulated Body Fluid／ＳＢＦ液）が挙げられる。より好ましくはNa＋、K＋、Mg2+、Ca2+、Cl-、HCO3-、HPO4 -、SO4 2-を含む水溶液であることが好ましく、ハンクス液およびＳＢＦ液がこれに相当する。 The method for producing coated metal fine particles of the present invention includes the following three steps. The first step is to mix a powder containing Ti (excluding a Ti oxide powder) and a metal M oxide powder whose standard free energy of formation satisfies the relationship of ΔG MO > ΔG TiO2. It is a process. In the second step, the obtained mixed powder is heat-treated at 650 to 900 ° C. in a non-oxidizing atmosphere to reduce the metal M oxide, and the surface of the obtained metal M fine particles is coated with TiO 2. This is a heat treatment step of obtaining coated metal fine particles by coating with a Ti oxide mainly composed of 2 . Here, “mainly composed of TiO 2 ” means diffraction corresponding to Ti oxide including Ti oxide other than TiO 2 detected by X-ray diffraction measurement (for example, Ti n O 2n-1 having non-stoichiometric composition). It means that the intensity of the peak corresponding to TiO 2 is the maximum among the peaks. From the viewpoint of uniformity, it is preferable that it is substantially made of TiO 2 . Here, “substantially composed of TiO 2 ” means that the proportion of TiO 2 is so large that a peak of Ti oxides other than TiO 2 cannot be clearly confirmed in the X-ray diffraction pattern. Therefore, even if there is a peak of Ti oxide other than TiO 2 in the X-ray diffraction pattern to the extent of noise, the condition of “substantially consisting of TiO 2 ” is satisfied. The third step is an immersion treatment step in which the obtained coated metal fine particles are immersed in a biological simulated liquid. By this dipping process, an uneven structure, such as a petal-like unevenness, can be formed on the surface of the coated metal fine particles. Here, the biological simulated fluid is an aqueous solution prepared by imitating plasma, and examples thereof include physiological saline, PBS buffer, Hank's solution, and simulated body fluid (Simulated Body Fluid / SBF solution). More preferably, it is an aqueous solution containing Na + , K + , Mg 2+ , Ca 2+ , Cl − , HCO 3− , HPO 4 − , SO 4 2− , and Hanks solution and SBF solution correspond to this. To do.
また、本発明の被覆金属微粒子は、金属のコア粒子がＴｉＯ２を主体とするＴｉ酸化物で被覆された被覆金属微粒子であって、前記金属は、その酸化物の標準生成自由エネルギーがΔGM-O＞ΔGTiO2の関係を満たす金属Ｍであり、前記被覆金属微粒子は表面に凹凸を有し、前記凹凸は薄片状の構造体が入り組んだ状態がなす花弁状の凹凸である被覆金属微粒子であることを特徴とする。この花弁状凹凸を粒子表面に付与することにより、比表面積が増大し、１粒子あたりの反応性が向上する。例えばたんぱく質を捕捉する磁気ビーズとして用いる際には、捕捉率が向上するため、前記被覆金属微粒子は、生体物質分離などの用途に用いられる磁気ビーズに好適である。 The coated metal fine particle of the present invention is a coated metal fine particle in which a metal core particle is coated with a Ti oxide mainly composed of TiO 2 , and the metal has a standard free energy of formation of ΔG MO > A metal M satisfying the relationship of ΔG TiO 2, the coated metal fine particles have irregularities on the surface, and the irregularities are coated metal fine particles that are petal-shaped irregularities formed by a state in which flaky structures are intricate It is characterized by. By imparting the petal-like irregularities to the particle surface, the specific surface area is increased and the reactivity per particle is improved. For example, when used as a magnetic bead for capturing a protein, the capture rate is improved, so that the coated metal fine particle is suitable for a magnetic bead used for applications such as biological material separation.
また、本発明の他の被覆金属微粒子は、金属のコア粒子がＴｉＯ２を主体とするＴｉ酸化物で被覆された被覆金属微粒子であって、前記金属は、その酸化物の標準生成自由エネルギーがΔGM-O＞ΔGTiO2の関係を満たす金属Ｍであり、前記被覆金属微粒子は表面に凹凸を有し、前記凹凸は金属Ｍの酸化物を主体とするナノワイヤであることを特徴とする。前記ナノワイヤの形成により、被覆金属微粒子の比表面積が増大し、１粒子あたりの表面反応性が向上する。かかる構成の被覆金属微粒子も、前記被覆金属微粒子と同様に磁気ビーズ用途に好適である。 Another coated metal fine particle of the present invention is a coated metal fine particle in which a metal core particle is coated with a Ti oxide mainly composed of TiO 2 , and the metal has a standard free energy of formation of the oxide. It is a metal M satisfying a relationship of ΔG MO > ΔG TiO 2, the coated metal fine particles have irregularities on the surface, and the irregularities are nanowires mainly composed of an oxide of the metal M. The formation of the nanowire increases the specific surface area of the coated metal fine particles and improves the surface reactivity per particle. The coated metal fine particles having such a configuration are also suitable for magnetic bead use like the coated metal fine particles.
さらに、前記被覆金属微粒子において、前記被覆金属微粒子の密度と比表面積から換算される平均粒子径＜ｄ＞と、レーザー回折型粒径分布測定器で測定したｄ５０との比＜ｄ＞／ｄ５０が０．０７以下であることが好ましい。なお、ここで平均粒径＜ｄ＞とは、被覆金属微粒子の粉末を、粒径が等しい球体の集合体と仮定し、密度と比表面積の値から換算される平均粒子径である。＜ｄ＞／ｄ５０が０．０７超であると比表面積が小さくなり、１粒子当たりの反応有効面積が低下し、抗体などのたんぱく質捕捉能向上が十分ではなくなる。より好ましくは＜ｄ＞／ｄ５０が０．０６以下、さらに好ましくは０．０５以下である。 Further, in the coated metal fine particles, the ratio <d> / d50 between the average particle diameter <d> converted from the density and specific surface area of the coated metal fine particles and d50 measured by a laser diffraction type particle size distribution measuring instrument is It is preferable that it is 0.07 or less. Here, the average particle diameter <d> is an average particle diameter converted from values of density and specific surface area, assuming that the powder of coated metal fine particles is an aggregate of spheres having the same particle diameter. When <d> / d50 is more than 0.07, the specific surface area becomes small, the reaction effective area per particle is lowered, and the ability to capture proteins such as antibodies is not sufficient. More preferably, <d> / d50 is 0.06 or less, more preferably 0.05 or less.
さらに、前記被覆金属微粒子において、Ｘ線回折パターンにおいてＴｉＯ２の最大ピークの半値幅が０．３°以下であり、かつ金属Ｍの最大ピークに対するＴｉＯ2の最大ピークの強度比が０．０３以上であることが好ましい。該構成は、ＴｉＯ２の結晶性が高いとともに、被覆であるＴｉＯ2の割合が高いことを意味し、コアとなる金属微粒子を十分強固に保護することができる。 Furthermore, in the coated metal fine particles, the half-width of the maximum peak of TiO 2 is 0.3 ° or less in the X-ray diffraction pattern, and the intensity ratio of the maximum peak of TiO 2 to the maximum peak of metal M is 0.03 or more. It is preferable that The arrangement may be in conjunction with high crystallinity of the TiO 2, which means that the percentage of TiO 2 is high is coated, fully firmly protect the metal fine particles as a core.
さらに、前記被覆金属微粒子において、抗体（ＩｇＧ）濃度２００ μｇ/ｍｌの溶液１ｍｌ中に前記被覆金属微粒子１０ｍｇを加え１６時間攪拌したときのＩｇＧ吸着量が前記被覆金属微粒子１ｍｇあたり１０μｇ以上であることが好ましい。前記被覆金属微粒子は高耐食性かつ高比表面積を有することから、高い抗体捕捉能を発揮する。かかる高い捕捉能を有する被覆金属微粒子は、抗体も含めたたんぱく質等の生体物質分離用磁気ビーズとして好適である。 Further, in the coated metal fine particles, the IgG adsorption amount when 10 mg of the coated metal fine particles are added to 1 ml of an antibody (IgG) concentration of 200 μg / ml and stirred for 16 hours is 10 μg or more per 1 mg of the coated metal fine particles. Is preferred. Since the coated metal fine particles have high corrosion resistance and a high specific surface area, they exhibit high antibody capture ability. Such coated metal fine particles having a high capture ability are suitable as magnetic beads for separating biological substances such as proteins including antibodies.
さらに、前記被覆金属微粒子において、前記金属ＭがＦｅであることが好ましい。高飽和磁化の被覆金属微粒子が得られる。 Furthermore, in the coated fine metal particles, the metal M is preferably Fe. Highly saturated magnetized coated metal fine particles are obtained.
さらに、前記被覆金属微粒子において、濃度６Ｍのグアニジン塩酸塩水溶液１ｍｌ中に前記被覆金属微粒子２５ｍｇを２４時間浸漬した後で、Ｆｅのイオン溶出量が１００ｍｇ/ｌ以下であることが好ましい。前記構成のように、Ｆｅをコアの金属とすることで高い飽和磁化を有するとともに、高い耐食性も有する被覆金属微粒子は、生体物質分離用磁気ビーズとして特に好適である。磁気ビーズとしての性能を維持し、生体物質分離能への影響を抑えるためには、前記Ｆｅのイオンの溶出量は５０ｇ/ｍｌがより好ましい。 Furthermore, in the coated metal fine particles, it is preferable that the amount of Fe ion elution is 100 mg / l or less after 25 mg of the coated metal fine particles are immersed in 1 ml of a 6 M guanidine hydrochloride aqueous solution for 24 hours. As described above, coated metal fine particles having high saturation magnetization and high corrosion resistance by using Fe as a core metal are particularly suitable as magnetic beads for separating biological materials. In order to maintain the performance as a magnetic bead and suppress the influence on the biological substance separation ability, the elution amount of the Fe ions is more preferably 50 g / ml.
本発明によれば、耐食性に優れ、かつ比表面積が大きい被覆金属微粒子、及びかかる被覆金属微粒子の製造方法を提供することができる。 According to the present invention, it is possible to provide coated metal fine particles having excellent corrosion resistance and a large specific surface area, and a method for producing such coated metal fine particles.
本発明の被覆粒子の製造方法は、Ｔｉを含む粉末（ただしＴｉ酸化物粉末を除く）と、酸化物の標準生成自由エネルギーがΔGM-O＞ΔGTiO2の関係を満たす金属Ｍの酸化物粉末とを混合する工程と、得られた混合粉末を非酸化性雰囲気中で６５０〜９００℃の温度で熱処理することによって、前記金属Ｍの酸化物を還元するとともに、得られた金属Ｍの微粒子の表面をＴｉＯ２を主体とするＴｉ酸化物で被覆して被覆金属微粒子を得る工程と、前記被覆金属微粒子を生体擬似液に浸漬する工程を有する。以下、本発明について具体的に説明する。 The method for producing coated particles according to the present invention comprises a powder containing Ti (excluding a Ti oxide powder) and an oxide powder of metal M satisfying a relationship of ΔG MO > ΔG TiO2 with a standard free energy of formation of the oxide. The step of mixing and heat-treating the obtained mixed powder at a temperature of 650 to 900 ° C. in a non-oxidizing atmosphere, thereby reducing the metal M oxide and the surface of the obtained metal M fine particles. The method includes a step of obtaining coated metal fine particles by coating with a Ti oxide mainly composed of TiO 2 and a step of immersing the coated metal fine particles in a biological simulated liquid. Hereinafter, the present invention will be specifically described.
（１）被覆金属微粒子の製造工程
まず、Tiを含む粉末（ただしTi酸化物粉末を除く）と酸化物の標準生成自由エネルギーがΔGM-O＞ΔGTiO2の関係を満たす金属Mの酸化物粉末とを混合し、得られた混合粉末を非酸化性雰囲気中で熱処理することにより、金属Mの酸化物をTiにより還元するとともに、得られた金属Mの微粒子の表面をTiO2を主体とするTi酸化物で被覆する。
(1) Production process of coated metal fine particles First, a powder containing Ti (excluding a Ti oxide powder) and an oxide powder of metal M satisfying the relation of ΔG MO > ΔG TiO2 where the standard free energy of formation of the oxide is ΔG MO > ΔG TiO2 By mixing and heat-treating the resulting mixed powder in a non-oxidizing atmosphere, the oxide of metal M is reduced with Ti, and the surface of the obtained metal M fine particles is oxidized with Ti mainly consisting of TiO 2 Cover with objects.
金属Mの酸化物粉末の粒径は、被覆金属微粒子の目標粒径に合わせて選択し得るが、0.001〜5μmの範囲内であるのが好ましい。粒径が0.001μm未満では、金属酸化物粉末の「かさ」が大きくなるだけでなく二次凝集が激しいため、以下の製造工程での取り扱いが困難である。また5μm超だと、金属酸化物粉末の比表面積が小さすぎ、還元反応が進行しにくい。金属酸化物粉末の実用的な粒径は0.005〜1μmである。金属Mは、例えば遷移金属、貴金属及び希土類金属から選ばれるが、磁気ビーズ用途など磁性材料として用いる場合であればFe、Co、Ni又はこれら合金が好ましい。この場合、その酸化物としてはFe2O3、Fe3O4、CoO、Co3O4、NiO等を用いればよい。特にFeは飽和磁化が高い点、酸化物としてはFe2O3が安価である点、後述する凹凸が粒子表面に効率よくが形成する点で好ましい。より高い磁化を得ることを目的としてＦｅＣｏ合金生成のためにＦｅ２Ｏ３とＣｏ３Ｏ４を所定の比率で混合してもよい。酸化物の標準生成自由エネルギーがΔGM-O＞ΔGTiO2の関係を満す金属Mの酸化物であれば、Tiを含む非酸化物粉末によって還元することができる。ΔGM-Oは金属Mの酸化物の標準生成エネルギーであり、ΔGTiO2（−889 kJ/mol）はTiの酸化物の標準生成エネルギーである。例えばFe2O3（ΔGFe2O3＝−740 kJ/mol）はΔGFe2O3＞ΔGTiO2を満たす。すなわち、TiはFeより酸化物の標準生成エネルギーが小さいため、Fe酸化物を効率良くかつ確実に還元することができる。TiO2の被覆が形成されていることにより、金属微粒子の比重が低下する。さらに、TiO2は親水性であるので、TiO2被覆金属微粒子は、例えば磁気ビーズ用のように水中に分散させる場合に好適である。 The particle size of the metal M oxide powder can be selected according to the target particle size of the coated metal fine particles, but is preferably in the range of 0.001 to 5 μm. When the particle size is less than 0.001 μm, not only the “bulk” of the metal oxide powder becomes large but also the secondary aggregation is severe, and therefore handling in the following production process is difficult. If it exceeds 5 μm, the specific surface area of the metal oxide powder is too small and the reduction reaction does not proceed easily. The practical particle size of the metal oxide powder is 0.005 to 1 μm. The metal M is selected from, for example, transition metals, noble metals, and rare earth metals, but Fe, Co, Ni, or alloys thereof are preferable when used as a magnetic material such as magnetic beads. In this case, Fe 2 O 3 , Fe 3 O 4 , CoO, Co 3 O 4 , NiO or the like may be used as the oxide. In particular, Fe is preferable in that saturation magnetization is high, Fe 2 O 3 is inexpensive as an oxide, and irregularities described later are efficiently formed on the particle surface. For the purpose of obtaining higher magnetization, Fe 2 O 3 and Co 3 O 4 may be mixed at a predetermined ratio in order to produce an FeCo alloy. If the standard free energy of formation of the oxide is an oxide of metal M satisfying the relationship of ΔG MO > ΔG TiO2 , it can be reduced by a non-oxide powder containing Ti. ΔG MO is the standard formation energy of the metal M oxide, and ΔG TiO2 (−889 kJ / mol) is the standard formation energy of the Ti oxide. For example Fe 2 O 3 (ΔG Fe2O3 = -740 kJ / mol) satisfies ΔG Fe2O3> ΔG TiO2. That is, since Ti has a lower standard generation energy of oxide than Fe, Fe oxide can be reduced efficiently and reliably. Due to the formation of the TiO 2 coating, the specific gravity of the metal fine particles is lowered. Furthermore, since TiO 2 is hydrophilic, the TiO 2 coated metal fine particles are suitable when dispersed in water, for example, for magnetic beads.
Tiを含む粉末は、Ti単体粉末の他、Ti-X（ただしXは、標準酸化物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より大きい元素である。）により表されるTi化合物又はそれらの混合物の粉末である。具体的には、XはAg、Au、B、Bi、C、Cu、Cs、Cd、Ge、Ga、Hg、K、N、Na、Pd、Pt、Rb、Rh、S、Sn、Tl、Te及びZnからなる群から選ばれた少なくとも一種である。Ti酸化物は還元剤として機能しないので、Tiを含む粉末から除く。ΔGX-O＜ΔGTiO2を満たす元素Xの場合、元素Xが還元剤として作用するので、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。Ti-XとしてはTiCが好ましい。反応後にTiO2以外の相が形成されにくいからである。還元反応を効率的に行なうためには、Tiを含む非酸化物粉末の粒径は0.01μm〜20μmであるのが好ましい。0.01μm未満の粒径であると、大気中でTiを含む非酸化物粉末が酸化し易いので、ハンドリングが難しい。また２０μｍ超であると比表面積が小さく、還元反応が進行しにくい。特に０.１μｍ〜５μｍの粒径がより好ましい。該範囲の粒径の粉末を用いれば、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 powder containing Ti is represented by Ti-X (where X is an element in which the standard oxide formation free energy ΔG XO is larger than the generation standard free energy ΔG TiO2 of TiO 2 ) in addition to the Ti simple powder. It is a powder of a compound or a mixture thereof. Specifically, X is Ag, Au, B, Bi, C, Cu, Cs, Cd, Ge, Ga, Hg, K, N, Na, Pd, Pt, Rb, Rh, S, Sn, Tl, Te And at least one selected from the group consisting of Zn. Since Ti oxide does not function as a reducing agent, it is removed from powders containing Ti. In the case of the element X satisfying ΔG XO <ΔG TiO2 , since the element X acts as a reducing agent, no Ti oxide is generated. The content of X is not particularly limited as long as Ti is sufficient to reduce the M oxide. Ti-X is preferable as Ti-X. This is because phases other than TiO 2 are hardly formed after the reaction. In order to perform the reduction reaction efficiently, the particle size of the non-oxide powder containing Ti is preferably 0.01 μm to 20 μm. When the particle diameter is less than 0.01 μm, the non-oxide powder containing Ti is easily oxidized in the atmosphere, so that handling is difficult. If it exceeds 20 μm, the specific surface area is small and the reduction reaction does not proceed easily. In particular, a particle size of 0.1 μm to 5 μm is more preferable. If a powder having a particle size in this range is used, the reduction reaction can proceed sufficiently while suppressing oxidation in the atmosphere.
M酸化物の粉末に対するTi含有粉末の割合は、少なくとも還元反応の化学量論比であることが好ましい。Tiが不足すると、熱処理中にM酸化物粉末が焼結し、バルク化してしまう。例えばFe2O3とTiCとの組合せの場合、Fe2O3＋TiCに対してTiCは25質量％以上であることが好ましい。TiCが25質量％未満であると、TiCによるFe2O3の還元が不十分である。一方、TiCの比率が高くなりすぎると、Feの比率が低下し、得られるTiO2被覆Fe微粒子の飽和磁化が低下し、保磁力が増大する。従って、TiCの上限は50質量％が好ましい。Fe2O3＋TiCに対するTiCの割合はより好ましくは30〜50質量％であり、さらに好ましくは30〜40質量％であり、特に好ましくは30〜35質量％である。保磁力は、TiCが35質量％になると8 kA/mに達し、40質量％になると10 kA/mに達し、50質量％になると15 kA/mに達する。M酸化物粉末とTi含有非酸化物粉末との混合には、乳鉢、スターラ、Ｖ字型ミキサ、ボールミル、振動ミル等の攪拌機を用いる。 The ratio of the Ti-containing powder to the M oxide powder is preferably at least the stoichiometric ratio of the reduction reaction. When Ti is insufficient, the M oxide powder is sintered and bulked during the heat treatment. For example, in the case of a combination of Fe 2 O 3 and TiC, it is preferred for Fe 2 O 3 + TiC TiC is at least 25 mass%. When TiC is less than 25% by mass, reduction of Fe 2 O 3 by TiC is insufficient. On the other hand, if the TiC ratio becomes too high, the Fe ratio decreases, the saturation magnetization of the resulting TiO 2 -coated Fe fine particles decreases, and the coercive force increases. Therefore, the upper limit of TiC is preferably 50% by mass. The ratio of TiC to Fe 2 O 3 + TiC is more preferably 30 to 50% by mass, still more preferably 30 to 40% by mass, and particularly preferably 30 to 35% by mass. The coercive force reaches 8 kA / m when TiC is 35% by mass, reaches 10 kA / m at 40% by mass, and reaches 15 kA / m at 50% by mass. For mixing the M oxide powder and the Ti-containing non-oxide powder, a stirrer such as a mortar, stirrer, V-shaped mixer, ball mill, vibration mill or the like is used.
Ｍ酸化物粉末とＴｉ含有粉末（Ｔｉ酸化物粉末を除く）の混合粉末を非酸化性雰囲気中で熱処理すると、Ｍ酸化物粉末とＴｉ含有粉末との還元反応が起こり、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。熱処理雰囲気は非酸化性であるのが好ましい。非酸化性雰囲気としては、例えばAr，He等の不活性ガスや、N2、CO2、NH3等が挙げられるが、これらに限定されない。但し、量産性の観点からは、安価なN2が好ましい。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、また９００℃超であると不定比組成のTinO2n-1が主として生成することがある。TinO2n-1は、９００℃超で金属MがTiO2から酸素を取り込むか、TiO2が非酸化性雰囲気中に酸素を放出することにより生成する。その結果、金属Mの還元が不十分であるか、被覆層が不完全となる。熱処理温度が650〜900℃の場合に、欠陥が少なく、均一性の高いほぼTiO2からなる被膜が形成される。TiO2からなる被膜は、光触媒用の被覆金属微粒子を作製するのにも好適である。 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 occurs between the M oxide powder and Ti-containing powder, and TiO 2 is the main component. Metal M particles coated with Ti oxide are produced. The heat treatment atmosphere is preferably non-oxidizing. Examples of the non-oxidizing atmosphere include, but are not limited to, inert gases such as Ar and He, N 2 , CO 2 , and NH 3 . However, inexpensive N 2 is preferable from the viewpoint of mass productivity. The heat treatment temperature is preferably 650 to 900 ° C. When the temperature is lower than 650 ° C., the reduction reaction does not proceed sufficiently, and when it is higher than 900 ° C., Ti n O 2n-1 having a non - stoichiometric composition may be mainly produced. Ti n O 2n-1 is generated when the metal M takes in oxygen from TiO 2 at over 900 ° C. or TiO 2 releases oxygen into a non-oxidizing atmosphere. As a result, the reduction of the metal M is insufficient or the coating layer is incomplete. When the heat treatment temperature is 650 to 900 ° C., a coating film of almost TiO 2 with few defects and high uniformity is formed. A film made of TiO 2 is also suitable for producing coated metal fine particles for a photocatalyst.
被覆金属微粒子の表面に花弁状の凹凸を付与するために、被覆金属微粒子を生体擬似液に浸漬させることが好ましい（生体擬似液浸漬処理）。生体擬似液は、血漿を模倣して作製された水溶液であり、Na＋、K＋、Mg2+、Ca2+、Cl-、HCO3-、HPO4 -、SO4 2-を含む水溶液であることが好ましい。より好ましくは擬似体液（Simulated Body Fluid; SBF）やハンクス液（Hank’s balanced salt solution）である。生体擬似液浸漬処理の手法は、被覆金属微粒子を２５〜１００℃の温度で生体擬似液に浸漬させることが好ましい。例えば生体擬似液に被覆金属微粒子を投入し、湯浴等で加温することにより処理することができる。温度が２５℃未満であると被覆金属微粒子と生体擬似液との反応が進行しにくくなり好ましくない。１００℃を越えると水が蒸発するため実効的ではない。より好ましくは３０〜６０℃であり、更に好ましくはヒト体温付近である３０〜４０℃である。上記生体擬似液浸漬処理により、被覆金属微粒子表面に凹凸として、被覆金属微粒子本体に比べて微細な花弁状の凹凸（花弁状構造体）を付与することができる（花弁状粒子）。花弁状の凹凸とは、薄片状の構造体が入り組んだ状態がなす凹凸である。 In order to give petal-like irregularities on the surface of the coated metal fine particles, it is preferable to immerse the coated metal fine particles in the simulated biological fluid (biological simulated fluid immersion treatment). The simulated biological fluid is an aqueous solution that mimics plasma and is an aqueous solution that contains Na + , K + , Mg 2+ , Ca 2+ , Cl − , HCO 3− , HPO 4 − , SO 4 2−. Preferably there is. More preferred are simulated body fluid (SBF) and Hank's balanced salt solution. As a technique of the biological simulated liquid immersion treatment, it is preferable that the coated metal fine particles are immersed in the biological simulated liquid at a temperature of 25 to 100 ° C. For example, the treatment can be performed by introducing coated metal fine particles into a simulated biological fluid and heating in a hot water bath or the like. When the temperature is lower than 25 ° C., the reaction between the coated metal fine particles and the biological simulated liquid is difficult to proceed, which is not preferable. If it exceeds 100 ° C., it is not effective because water evaporates. More preferably, it is 30-60 degreeC, More preferably, it is 30-40 degreeC which is human body temperature vicinity. By the biological simulated liquid immersion treatment, fine petal-like irregularities (petal-like structures) can be imparted as irregularities on the surface of the coated metal fine particles as compared with the coated metal fine particle main body (petal-like particles). The petal-like irregularities are irregularities formed by a state in which flaky structures are complicated.
表面に凹凸を有する本発明に係る被覆金属微粒子についてさらに詳述する。本発明に係る被覆金属微粒子は、金属のコア粒子がＴｉＯ２を主体とするＴｉ酸化物で被覆された被覆金属微粒子であって、前記金属は、その酸化物の標準生成自由エネルギーがΔGM-O＞ΔGTiO2の関係を満たす金属Ｍであり、前記被覆金属微粒子は表面に凹凸を有する。この凹凸は、うねりや空孔などの、前記生体擬似液浸漬処理前の被覆であるＴｉＯ２そのものの凹凸とは構造が異なる。前記凹凸は例えば花弁状の凹凸である。該花弁状の凹凸は、被覆金属微粒子の表面に連続的に形成され、該表面の少なくとも一部を覆うように形成されるが、被覆粒子の表面全体を覆うように形成されていることがより好ましい。かかる構成の被覆金属微粒子は、前記製造方法によって、得ることができる。この花弁状の凹凸は金属Ｍの酸化物を主体としている。前記花弁状の凹凸は、この花弁状の凹凸によって比表面積が大きくなる。 The coated metal fine particles according to the present invention having irregularities on the surface will be further described in detail. The coated metal fine particle according to the present invention is a coated metal fine particle in which a metal core particle is coated with a Ti oxide mainly composed of TiO 2 , and the metal has a standard free energy of formation of an oxide of ΔG MO > The metal M satisfies the relationship of ΔG TiO2 , and the coated metal fine particles have irregularities on the surface. This unevenness differs in structure from the unevenness of TiO 2 itself, which is a coating before the biological simulated liquid immersion treatment, such as undulations and holes. The unevenness is, for example, a petal-like unevenness. The petal-like irregularities are continuously formed on the surface of the coated metal fine particles and are formed so as to cover at least a part of the surface, but are more preferably formed so as to cover the entire surface of the coated particles. preferable. The coated metal fine particles having such a configuration can be obtained by the production method. The petal-like irregularities are mainly composed of metal M oxide. The petal-like unevenness increases the specific surface area due to the petal-like unevenness.
前記凹凸の他の形態として、金属Ｍの酸化物を主体とするナノワイヤとしてもよい。ここで、ナノワイヤとは、直径がナノサイズ、すなわち１μｍ未満のワイヤである。金属Ｍの酸化物を主体とするナノワイヤを粒子表面に生成させるためには、前記被覆金属微粒子をアルカリ源含有水溶液に浸漬させることが好ましい。この浸漬処理においては、表面に剥き出しの金属Ｍが水溶液と反応することによって金属Ｍの酸化物がナノワイヤ状に生成する。ナノワイヤ状とならず粒子表面に酸化膜として金属Ｍの酸化物が形成することもある。このため、前記アルカリ浸漬処理は被覆金属微粒子の耐食性を向上させる効果もある。アルカリ浸漬処理に用いるアルカリ源は、水溶液としたときアルカリ性を呈する化合物であれば良く、例えばNaOH、KOHの他、アルカリ性界面活性剤等が挙げられる。より好ましくはNaOHである。十分アルカリ浸漬処理の効果を発揮するためにはNaOH濃度は0.3〜10Mが好ましい。0.3M未満であると希薄のためアルカリ浸漬処理の効果が発現し難い。１０Ｍ以上では安全に取り扱うことが困難である。アルカリ浸漬処理は、例えばボールミル等を用いて、アルカリ水溶液に被覆金属微粒子を浸漬し、攪拌することにより行なうことができる。また被覆金属微粒子を加温したアルカリ水溶液中に保持してもよい。温度は２５℃以上、１００℃未満が好ましい。２５℃未満であるとアルカリ水溶液と被覆金属微粒子との反応が進行しにくくなる。１００℃以上は水が蒸発するため実効的でない。より好ましくは３０〜７０℃である。加温処理は、例えばアルカリ水溶液と被覆金属微粒子を投入したポリ容器を湯浴で加温することにより行なうことができる。上記加温処理によって、被覆金属微粒子の表面に金属Ｍの酸化物を主体とするナノワイヤ（以下、Ｍ酸化物ナノワイヤ）が形成される。このＭ酸化物ナノワイヤにより比表面積が大きくなる。Ｍ酸化物ナノワイヤの直径は０.０５〜０.１μｍ、長さは０.５〜３μｍであるのが好ましい。これより大きいと、被覆金属微粒子の飽和磁化の低下や、Ｍ酸化物ナノワイヤの遊離が起きやすくなる。 As another form of the unevenness, a nanowire mainly composed of an oxide of metal M may be used. Here, the nanowire is a wire having a diameter of nano-size, that is, less than 1 μm. In order to generate nanowires mainly composed of an oxide of metal M on the particle surface, the coated metal fine particles are preferably immersed in an aqueous solution containing an alkali source. In this dipping treatment, the metal M exposed on the surface reacts with the aqueous solution, whereby an oxide of the metal M is generated in the form of nanowires. The metal M oxide may be formed on the particle surface as an oxide film without forming a nanowire shape. For this reason, the alkali immersion treatment also has an effect of improving the corrosion resistance of the coated metal fine particles. The alkali source used in the alkali dipping treatment may be any compound that exhibits alkalinity when it is made into an aqueous solution, and examples thereof include alkaline surfactants in addition to NaOH and KOH. More preferably, it is NaOH. In order to sufficiently exhibit the effect of the alkali immersion treatment, the NaOH concentration is preferably 0.3 to 10M. If it is less than 0.3M, the effect of the alkali dipping treatment is difficult to be exhibited due to the dilution. At 10M or more, it is difficult to handle safely. The alkali immersion treatment can be performed by immersing the coated fine metal particles in an alkaline aqueous solution using, for example, a ball mill, and stirring. Further, the coated metal fine particles may be held in a heated alkaline aqueous solution. The temperature is preferably 25 ° C. or more and less than 100 ° C. When the temperature is lower than 25 ° C., the reaction between the aqueous alkali solution and the coated metal fine particles is difficult to proceed. Above 100 ° C is not effective because water evaporates. More preferably, it is 30-70 degreeC. The heating treatment can be performed, for example, by heating a polycontainer charged with an alkaline aqueous solution and coated metal fine particles in a hot water bath. By the heating treatment, nanowires mainly composed of an oxide of metal M (hereinafter referred to as M oxide nanowires) are formed on the surface of the coated metal fine particles. This M oxide nanowire increases the specific surface area. The diameter of the M oxide nanowire is preferably 0.05 to 0.1 μm, and the length is preferably 0.5 to 3 μm. If it is larger than this range, the saturation magnetization of the coated metal fine particles tends to decrease and the M oxide nanowires are likely to be released.
（２）被覆金属微粒子の構造及び特性
上記方法により得られる被覆金属微粒子の粒径は、M酸化物粉末の粒径に依存する。高い耐食性及び分散性を得るためには、被覆金属微粒子の平均粒径d50は0.1μm〜10μmが好ましく、0.1〜6μmがより好ましい。平均粒径が0.1μm未満であると、被覆金属微粒子は十分な厚さの被膜を確保できずに耐食性が低くなるだけでなく、1粒子当たりの磁化が極めて小さくなり磁気応答性が低くなってしまう。また平均粒径が10μmを超えると、液体中での被覆金属微粒子の分散性が低下する。平均粒径d50はレーザー回折による湿式粒径測定器で測定した値を用いる。また被覆金属微粒子の密度と比表面積から換算される平均粒子径を<d>とすると<d>/d50は０．０７以下が好ましい。０．０７を越える値であると被覆金属微粒子の比表面積が小さくなり、磁気ビーズとしての機能が低下する。十分な磁気応答性を確保しつつ、磁気ビーズ性能を高めるためには、<d>/d50が0.06以下であることがより好ましい。
(2) Structure and characteristics of coated metal fine particles The particle diameter of the coated metal fine particles obtained by the above method depends on the particle diameter of the M oxide powder. In order to obtain high corrosion resistance and dispersibility, the average particle diameter d50 of the coated metal fine particles is preferably 0.1 μm to 10 μm, more preferably 0.1 to 6 μm. If the average particle size is less than 0.1 μm, the coated metal fine particles cannot ensure a sufficiently thick coating and not only have low corrosion resistance, but also have extremely small magnetization per particle and low magnetic response. End up. On the other hand, when the average particle size exceeds 10 μm, the dispersibility of the coated metal fine particles in the liquid is lowered. The average particle size d50 is a value measured by a wet particle size measuring device using laser diffraction. Further, when the average particle diameter converted from the density and specific surface area of the coated metal fine particles is <d>, <d> / d50 is preferably 0.07 or less. When the value exceeds 0.07, the specific surface area of the coated metal fine particles decreases, and the function as a magnetic bead deteriorates. In order to improve the magnetic bead performance while ensuring sufficient magnetic response, it is more preferable that <d> / d50 is 0.06 or less.
Ｍ金属粒子とＴｉ酸化物被覆層とは１対１のコア−シェル構造になっている必要はなく、TiO2を主体とするＴｉ酸化物層中に２個以上のＭ金属粒子が分散した構造であっても良い。Ｔｉ酸化物の中に２個以上のＭ金属粒子が含まれていると、金属Ｍは高含有率で、かつ確実に被覆されるので好ましい。本発明では、Ｍ酸化物の還元によるＭ金属微粒子の形成と、Ｔｉ酸化物被膜の形成とが同時に行われるので、Ｍ金属微粒子とＴｉ酸化物被膜との間にＭ金属酸化物層が認められない。また６５０℃以上の熱処理により得られるＴｉ酸化物被膜の結晶性は高く、ゾル−ゲル法等により得られる非晶質又は低結晶性のＴｉ酸化物被膜より高い耐食性を示す。また、TiO2を主体とした被膜を有する本発明の被覆金属微粒子は、被膜に欠陥が少ないので、不定比組成のTinO2n-1の被膜を有するものよりも高い耐食性を示す。 The M metal particles and the Ti oxide coating layer do not need to have a one-to-one core-shell structure, but a structure in which two or more M metal particles are dispersed in a Ti oxide layer mainly composed of TiO 2. It may be. It is preferable that two or more M metal particles are contained in the Ti oxide because the metal M has a high content and is reliably coated. In the present invention, the formation of M metal fine particles by the reduction of M oxide and the formation of a Ti oxide film are simultaneously performed, so that an M metal oxide layer is observed between the M metal fine particles and the Ti oxide film. Absent. Further, the Ti oxide film obtained by heat treatment at 650 ° C. or higher has high crystallinity, and shows higher corrosion resistance than the amorphous or low crystalline Ti oxide film obtained by a sol-gel method or the like. Further, the coated metal fine particles of the present invention having a coating mainly composed of TiO 2 have a higher corrosion resistance than those having a coating of Ti n O 2n-1 having a non - stoichiometric composition because the coating has few defects.
被覆金属微粒子のX線回折パターンにおけるTiO2の最大ピークの半値幅が0.3°以下で、金属Mの最大ピークに対するTiO2の最大ピークの強度比が0.03以上である場合に、Ti酸化物の結晶性が良い（従って、被覆金属微粒子の耐食性も良い）と判断した。非晶質又は低結晶性の場合、ピークは観察されないかブロードであるため、最大ピーク強度比は小さく、半値幅は広い。最大ピーク強度比はより好ましくは0.05以上である。最大ピーク強度比が高くなると被膜の割合が多くなり、飽和磁化が低下する。そのため、最大ピーク強度比は3以下が好ましい。 When the half-width of the maximum peak of TiO 2 in the X-ray diffraction pattern of the coated metal fine particle is 0.3 ° or less and the intensity ratio of the maximum peak of TiO 2 to the maximum peak of metal M is 0.03 or more, the crystal of Ti oxide Therefore, it was determined that the coating metal fine particles had good corrosion resistance. In the case of amorphous or low crystallinity, since the peak is not observed or is broad, the maximum peak intensity ratio is small and the half width is wide. The maximum peak intensity ratio is more preferably 0.05 or more. As the maximum peak intensity ratio increases, the ratio of the coating increases and the saturation magnetization decreases. Therefore, the maximum peak intensity ratio is preferably 3 or less.
金属Ｍが磁性金属Ｆｅの場合、前記製法により得られた被覆金属微粒子は５０〜１８０A・m2/kgの範囲の飽和磁化を有し、磁性粒子として機能する。これは、被覆金属微粒子が磁性金属FeとTiO2から形成されている場合、Fe＋Tiに対するTiの割合が11〜67質量％であることに相当する。Ｔｉの割合は、Ｘ線回折パターンから被覆金属微粒子がFeとTiO2からなることを確認した後で、被覆金属微粒子の飽和磁化の測定値から算出できる。磁性粒子の飽和磁化が50 A・m2/kg未満と小さいと、磁界に対する応答が鈍い。また１８０A・m2/kg超であるとTiO2を主体とするTi酸化物の含有率が小さく（Ｆｅ＋Ｔｉに対するＴｉの質量比率が１１％未満）、金属Ｆｅ粒子を十分にＴｉ酸化物で被覆できないために耐食性が低く、磁気特性が劣化しやすい。従って、高い飽和磁化及び十分な耐食性を同時に得るために、被覆金属微粒子の飽和磁化は１８０A・m2/kg以下とするのが好ましい。磁気ビーズ等に用いる場合の回収効率や磁気分離性能に優れるためには、被覆金属微粒子の飽和磁化は９５〜１８０A・m2/kgであるのがより好ましい。この範囲の飽和磁化は、９２A・m2/kg程度の飽和磁化しか有さないマグネタイト（Fe3O4）では得られない。分散性の観点から、被覆金属微粒子の保磁力は15 kA/m以下が好ましく、８kA/m（100 Oe）以下がより好ましく、６kA/m以下が最も好ましい。保磁力が大きい場合でもTiO2被膜を厚くすれば高分散性が得られるが、そうすると被覆金属微粒子の飽和磁化が低下してしまう。保磁力が８kA/mを超えると、磁性粒子は無磁場でも磁気的に凝集しやすくなるので、液中での分散性が低下する。 When the metal M is a magnetic metal Fe, the coated metal fine particles obtained by the above production method have a saturation magnetization in the range of 50 to 180 A · m 2 / kg and function as magnetic particles. This corresponds to a ratio of Ti to Fe + Ti of 11 to 67 mass% when the coated metal fine particles are formed of magnetic metal Fe and TiO 2 . The ratio of Ti can be calculated from the measured value of saturation magnetization of the coated metal fine particles after confirming that the coated metal fine particles are composed of Fe and TiO 2 from the X-ray diffraction pattern. When the saturation magnetization of magnetic particles is as small as less than 50 A · m 2 / kg, the response to a magnetic field is dull. Further, if it exceeds 180 A · m 2 / kg, the content of Ti oxide mainly composed of TiO 2 is small (the mass ratio of Ti to Fe + Ti is less than 11%), and metal Fe particles cannot be sufficiently covered with Ti oxide. Therefore, the corrosion resistance is low, and the magnetic characteristics are likely to deteriorate. Accordingly, in order to obtain high saturation magnetization and sufficient corrosion resistance at the same time, the saturation magnetization of the coated metal fine particles is preferably 180 A · m 2 / kg or less. In order to be excellent in recovery efficiency and magnetic separation performance when used for magnetic beads or the like, the saturation magnetization of the coated metal fine particles is more preferably 95 to 180 A · m 2 / kg. Saturation magnetization in this range cannot be obtained with magnetite (Fe 3 O 4 ) having only saturation magnetization of about 92 A · m 2 / kg. From the viewpoint of dispersibility, the coercive force of the coated metal fine particles is preferably 15 kA / m or less, more preferably 8 kA / m (100 Oe) or less, and most preferably 6 kA / m or less. Even if the coercive force is large, if the TiO 2 film is thickened, high dispersibility can be obtained, but if so, the saturation magnetization of the coated metal fine particles is lowered. When the coercive force exceeds 8 kA / m, the magnetic particles tend to be magnetically aggregated even in the absence of a magnetic field, so that the dispersibility in the liquid decreases.
モル濃度が6 Mのグアニジン塩酸塩水溶液1 ml中に、金属MがFeである被覆金属微粒子25 mgを25℃で24時間浸漬したときのFeイオン溶出量は100 mg/l以下であるのが好ましい。この被覆金属微粒子は高カオトロピック塩濃度においても高い耐食性を示すため、カオトロピック塩水溶液中での処理を必要とするDNA抽出等の用途に好適である。Feイオン溶出量が100 mg/l以下の耐食性レベルは、アルカリ浸漬処理を施さない場合でも発現することがあるが、確実に上記耐食性レベルを得るためにはアルカリ浸漬処理を行うのが好ましい。 The amount of Fe ion elution when a coated metal fine particle of 25 mg in which M metal is Fe is immersed in 1 ml of a 6 M guanidine hydrochloride aqueous solution at 25 ° C. for 24 hours is 100 mg / l or less. preferable. Since the coated metal fine particles exhibit high corrosion resistance even at a high chaotropic salt concentration, they are suitable for uses such as DNA extraction that requires treatment in an aqueous chaotropic salt solution. Although the corrosion resistance level with Fe ion elution amount of 100 mg / l or less may appear even when the alkali immersion treatment is not performed, it is preferable to perform the alkali immersion treatment in order to reliably obtain the above corrosion resistance level.
本発明の被覆金属微粒子は、高耐食性を有し、水溶液中で安定である上、比表面積が大きいためDNAやたんぱく質などの生体物質を効率良く吸着させることができる。例えばたんぱく質を吸着させるために被覆金属微粒子表面を以下のように機能化することができる。第1処理としてゾル-ゲル法によって被覆金属微粒子をシリカで被覆することが好ましいが、本処理は省略することもできる。第2処理として、被覆金属微粒子を無水コハク酸と混和することにより、上記被覆金属微粒子の表面にカルボキシル基を導入する。このカルボキシルを導入した被覆金属微粒子10 mgをカルボジイミドで活性化させた後、200 μg/mlに調整したIgG抗体の緩衝溶液1 mlに投入して室温で16時間攪拌することにより、被覆金属微粒子1mgあたりIgG抗体を１０μg以上吸着させることができる。本発明の被覆金属微粒子は比表面積が大きく、特にナノワイヤや花弁状構造体によって極めて大きい比表面積を有する為、生体物質を被覆金属微粒子表面に吸着させる磁気ビーズ用途に好適である。 The coated metal fine particles of the present invention have high corrosion resistance, are stable in an aqueous solution, and have a large specific surface area, so that biological substances such as DNA and proteins can be adsorbed efficiently. For example, the surface of the coated metal fine particles can be functionalized as follows in order to adsorb proteins. As the first treatment, it is preferable to coat the coated metal fine particles with silica by a sol-gel method, but this treatment can be omitted. As a second treatment, the coated metal fine particles are mixed with succinic anhydride to introduce carboxyl groups on the surface of the coated metal fine particles. After activating 10 mg of this coated metal fine particle into which carboxyl was introduced with carbodiimide, 1 mg of the coated metal fine particle was added to 1 ml of IgG antibody buffer adjusted to 200 μg / ml and stirred at room temperature for 16 hours. It is possible to adsorb 10 μg or more of IgG antibody. The coated metal fine particles of the present invention have a large specific surface area, and in particular have a very large specific surface area due to nanowires or petal-like structures, and therefore are suitable for magnetic beads for adsorbing biological materials on the surface of the coated metal fine particles.
（実施例1）
平均粒径0.03μmのα-Fe2O3粉末と、平均粒径1μmのTiC粉末とを、7：3の質量比（TiC：30質量％）でボールミルにより10時間混合し、得られた混合粉末をアルミナボート内で、窒素ガス中で８００℃で８時間熱処理し、室温まで冷却した。得られた試料粉末をリガク社：ＲＩＮＴ２５００にてＣｕ−Ｋα線を線源としてＸ線回折測定したところ、Ｘ線回折パターンに出現した回折ピークはα−Ｆｅ及びルチル構造のＴｉＯ２と同定された。酸化物の標準生成エネルギーは、ΔGFe2O3＝−740 kJ/molに対して、ΔGTiO2＝−889 kJ/molであるため、TiO2の標準生成エネルギーの方が小さい。従って、α-Fe2O3がTiにより還元され、TiO2が生成したと言える。さらにこの試料粉末5 gとイソプロピルアルコール（IPA）５０ｍｌとを１００ｍｌのビーカに投入し、１０分間超音波を照射した。次いで永久磁石をビーカの外面に1分間接触させ、磁性粒子だけをビーカ内壁に吸着させ、黒灰色の上澄み液を除去した。この磁気分離操作を５０回繰り返し、得られた精製磁性粒子を室温で乾燥させた。
(Example 1)
Α-Fe 2 O 3 powder with an average particle size of 0.03μm and TiC powder with an average particle size of 1μm were mixed at a mass ratio of 7: 3 (TiC: 30% by mass) for 10 hours using a ball mill, and the resulting mixture was obtained. The powder was heat-treated in an alumina boat at 800 ° C. for 8 hours in nitrogen gas and cooled to room temperature. The obtained sample powder was subjected to X-ray diffraction measurement with RINT2500 using Cu-Kα rays as a radiation source, and the diffraction peaks appearing in the X-ray diffraction pattern were identified as α-Fe and rutile TiO 2 . . The standard generation energy of oxide is ΔG TiO2 = -889 kJ / mol versus ΔG Fe2O3 = -740 kJ / mol, so the standard generation energy of TiO 2 is smaller. Therefore, it can be said that α-Fe 2 O 3 was reduced by Ti to produce TiO 2 . Further, 5 g of this sample powder and 50 ml of isopropyl alcohol (IPA) were put into a 100 ml beaker and irradiated with ultrasonic waves for 10 minutes. Next, the permanent magnet was brought into contact with the outer surface of the beaker for 1 minute to adsorb only the magnetic particles on the inner wall of the beaker, and the black-grey supernatant was removed. This magnetic separation operation was repeated 50 times, and the resulting purified magnetic particles were dried at room temperature.
前記磁性粒子１ｇを１Ｍ濃度のＮａＯＨ水溶液５０ｍｌ中に投入し、６０℃で２４時間保持するアルカリ浸漬処理を行なった。アルカリ浸漬処理後、磁性粒子を純水で洗浄し乾燥させて試料粉末を得た。得られた試料粉末のｄ５０をレーザー回折型粒径分布測定器（ＨＯＲＩＢＡ：ＬＡ−９２０）にて測定したところ、２．０μｍであった。また磁気特性を、最大印加磁界を１．６ＭＡ/ｍとしてＶＳＭ（振動型磁力計）により測定したところ、飽和磁化（Ｍｓ）は１１２Ａｍ２／ｋｇ、保磁力（Ｈｃ）は５．３ｋＡ／ｍであった。上記試料粉末をＳＥＭにより観察した結果を図１に示す。粒子以外に繊維状のナノワイヤ１が多数析出している様子が分かる。上記ナノワイヤの直径は５０〜２００ｎｍの範囲、その長さは０．５〜１μｍの範囲であるものが多い。上記ナノワイヤの形状は直線状であり、その直径は全長に渡ってほぼ一定である。上記ナノワイヤは被覆金属微粒子に接触しているものが多く、被覆金属微粒子から成長したことを表している。また、その成長方向はランダムであり、カーボンナノチューブに見られるような同方向にナノワイヤ同士が配向したバンドル構造は見られない。このナノワイヤをアルバック・ファイ製PHI700TMにてオージェ電子分光分析した。図２はナノワイヤから得たオージェ電子スペクトルであるが、FeとOに相当するスペクトルが主要であり、微量のTiも検出した。なお、Cは不可避不純物、Alは試料を設置しているAlステージから検出されたものであり、ナノワイヤに含まれるものではない。図２より、ナノワイヤが酸化鉄主体であることが分かる。また上記ナノワイヤを透過型電子顕微鏡（ＴＥＭ）付属のエネルギー分散Ｘ線分析装置（ＥＤＸ）で組成分析した。結果を図３に示す。O、Fe及びTiを検出した。なお、CuはTEM観察用試料を保持しているメッシュから検出されるものであり、ナノワイヤに含まれる元素ではない。このスペクトルから算出した各元素の原子比率はFe：Ti：O=38.0：2.3：59.7であった。以上、EDXの結果からも、上記ナノワイヤは酸素以外の元素の中でＦｅの原子割合が最も大きく、酸化鉄主体であることが分かる。また、このナノワイヤは５％以下の微量のTiが含まれていることが分かる。また、得られた試料粉末について測定したＸ線回折パターンを図４に示す。各回折ピークはα-Ｆｅ、ルチル構造のＴｉＯ２、Ｆｅ３Ｏ４に相当する。Ｆｅ３Ｏ４はアルカリ浸漬処理によって析出したものである。２θ＝２７．４°のとき得られたＴｉＯ２の最大回折ピークの半値幅は０．１４°であり、ＴｉＯ２の最大回折ピーク強度のα−Ｆｅの最大回折ピーク［（110）ピーク］強度に対する比は０．０６であった。これから、ＴｉＯ２が高い結晶性を有することが分かる。上記試料粉末２５ｍｇを濃度６Mのグアニジン塩酸塩水溶液１ｍｌ中に２５℃で２４時間浸漬させた（浸漬試験）後のＦｅイオン溶出量をＩＣＰ分析（エスアイアイナノテクノロジー社：ＳＰＳ３１００Ｈ）により測定した。結果を表１に示す。 1 g of the magnetic particles was put into 50 ml of 1M NaOH aqueous solution and subjected to an alkali dipping treatment that was maintained at 60 ° C. for 24 hours. After the alkali immersion treatment, the magnetic particles were washed with pure water and dried to obtain a sample powder. It was 2.0 micrometers when d50 of the obtained sample powder was measured with the laser diffraction type particle size distribution measuring device (HORIBA: LA-920). The magnetic properties were measured with a VSM (vibrating magnetometer) with a maximum applied magnetic field of 1.6 MA / m. The saturation magnetization (Ms) was 112 Am 2 / kg and the coercive force (Hc) was 5.3 kA / m. there were. The result of observing the sample powder with SEM is shown in FIG. It can be seen that many fibrous nanowires 1 are deposited in addition to the particles. In many cases, the nanowire has a diameter of 50 to 200 nm and a length of 0.5 to 1 μm. The shape of the nanowire is linear, and its diameter is almost constant over the entire length. Many of the nanowires are in contact with the coated metal fine particles, indicating that the nanowires have grown from the coated metal fine particles. Further, the growth direction is random, and a bundle structure in which nanowires are oriented in the same direction as seen in carbon nanotubes is not seen. This nanowire was subjected to Auger electron spectroscopic analysis using PHI700 TM manufactured by ULVAC-PHI. FIG. 2 shows the Auger electron spectrum obtained from the nanowire, and the spectrum corresponding to Fe and O is main, and a trace amount of Ti was also detected. Note that C is an inevitable impurity, and Al is detected from the Al stage on which the sample is placed, and is not included in the nanowire. FIG. 2 shows that the nanowire is mainly composed of iron oxide. The composition of the nanowire was analyzed with an energy dispersive X-ray analyzer (EDX) attached to a transmission electron microscope (TEM). The results are shown in FIG. O, Fe and Ti were detected. Cu is detected from the mesh holding the sample for TEM observation and is not an element contained in the nanowire. The atomic ratio of each element calculated from this spectrum was Fe: Ti: O = 38.0: 2.3: 59.7. As described above, EDX results also show that the nanowire has the largest atomic ratio of Fe among elements other than oxygen and is mainly composed of iron oxide. Moreover, it turns out that this nanowire contains a trace amount Ti of 5% or less. Moreover, the X-ray diffraction pattern measured about the obtained sample powder is shown in FIG. Each diffraction peak corresponds to α-Fe, rutile TiO 2 , and Fe 3 O 4 . Fe 3 O 4 is precipitated by alkali dipping treatment. The half-width of the maximum diffraction peak of TiO 2 obtained when 2θ = 27.4 ° is 0.14 °, and the maximum diffraction peak intensity of α-Fe [(110) peak] intensity of the maximum diffraction peak intensity of TiO 2 The ratio to 0.06 was 0.06. From this, it can be seen that TiO 2 has high crystallinity. The amount of Fe ion elution after immersion of 25 mg of the sample powder in 1 ml of an aqueous guanidine hydrochloride solution having a concentration of 6 M at 25 ° C. for 24 hours (immersion test) was measured by ICP analysis (SII Nanotechnology Inc .: SPS3100H). The results are shown in Table 1.
（比較例１）
実施例１と同様にして得た精製磁性粒子にアルカリ浸漬処理を施さずに、ｄ５０、磁気特性、Ｆｅイオン溶出量を評価した。結果を表１に示す。
(Comparative Example 1)
The purified magnetic particles obtained in the same manner as in Example 1 were evaluated for d50, magnetic properties, and Fe ion elution amount without subjecting to alkaline dipping treatment. The results are shown in Table 1.
ここで上記被覆金属微粒子の製造工程において、アルカリ源の濃度を変化させた場合の特性の変化を表２に示す。アルカリ源であるＮａＯＨの濃度を変えることにより、Ｆｅイオン溶出量を低減することが可能である。ＮａＯＨ濃度０．２Ｍ以上でＦｅイオン溶出量は１００ｍｇ／ｌ以下、０．４Ｍ以上で５０ｍｇ／ｌ以下となり、耐食性が向上する。このようにアルカリ源の濃度を変えることにより、被覆金属微粒子に高耐食性を付与することができる。ＮａＯＨ濃度が１Ｍである実施例１の被覆金属微粒子では、２５ｍｇ／ｌ以下のＦｅイオン溶出量となっており、比較例１に比べて高い耐食性を示している。 Table 2 shows changes in characteristics when the concentration of the alkali source is changed in the production process of the coated metal fine particles. It is possible to reduce the amount of Fe ion elution by changing the concentration of NaOH as an alkali source. When the NaOH concentration is 0.2M or more, the Fe ion elution amount is 100 mg / l or less, and when it is 0.4M or more, it is 50 mg / l or less. Thus, by changing the concentration of the alkali source, high corrosion resistance can be imparted to the coated metal fine particles. The coated metal fine particles of Example 1 having a NaOH concentration of 1 M have an Fe ion elution amount of 25 mg / l or less, and show higher corrosion resistance than Comparative Example 1.
（実施例２）
混合粉末の熱処理温度を９００℃、熱処理時間を８ｈに変えた以外は実施例１と同様にして被覆金属微粒子を作製した。この試料粉末の磁気特性を実施例１と同様にして測定したところ、飽和磁化は１２０Ａｍ２／ｋｇであったため、含有されるＦｅは５５ｍａｓｓ％と算出された。上記試料粉末がＦｅとＴｉＯ２から成ることを考慮してこの試料粉末の粒子密度ρを以下の計算式を用いて算出した。
１／ρ＝０．５５／ρＦｅ＋０．４５／ρＴｉＯ２
ここで、ρＦｅ＝７．８Ｍｇ／ｍ3、ρＴｉＯ２＝５．０７Ｍｇ／ｍ3を用いた。その結果、ρ＝６．７Ｍｇ／ｍ3であった。またこの試料粉末のｄ５０を実施例１と同様にして測定した。またこの試料粉末の比表面積を(株)マウンテック製Macsorb-Hmmodel-1201を用いてBET法によって測定した。結果を表３に示す。また密度６．７Ｍｇ／ｍ3を用いて比表面積値Ｓから平均粒子径を換算した。すなわち、
Ｓ＝６／（＜ｄ＞・ρ）
の式から換算粒径＜ｄ＞を求めた。＜ｄ＞／ｄ５０の値と共に表３に示す。
(Example 2)
Coated metal fine particles were produced in the same manner as in Example 1 except that the heat treatment temperature of the mixed powder was changed to 900 ° C. and the heat treatment time was changed to 8 h. When the magnetic properties of the sample powder were measured in the same manner as in Example 1, the saturation magnetization was 120 Am 2 / kg, and therefore the contained Fe was calculated to be 55 mass%. Considering that the sample powder is composed of Fe and TiO 2 , the particle density ρ of the sample powder was calculated using the following formula.
1 / ρ = 0.55 / ρ Fe + 0.45 / ρ TiO 2
Here, ρ Fe = 7.8 Mg / m 3 and ρ TiO 2 = 5.07 Mg / m 3 were used. As a result, ρ = 6.7 Mg / m 3 . Further, d50 of this sample powder was measured in the same manner as in Example 1. The specific surface area of the sample powder was measured by BET method using Macsorb-Hmmodel-1201 manufactured by Mountec Co., Ltd. The results are shown in Table 3. The average particle size was converted from the specific surface area value S using a density of 6.7 Mg / m 3 . That is,
S = 6 / (<d> · ρ)
The converted particle size <d> was determined from the formula of It shows in Table 3 with the value of <d> / d50.
（実施例３〜７）
実施例２で得た試料粉末2gを擬似体液（Simulated Body Fluid/SBF液）50ml中に投入し、表3に示す各条件で浸漬させた（実施例３〜７）。水洗後、乾燥して試料粉末を得た。実施例1と同様にして測定したd50及び実施例２と同様にして測定した比表面積、<d>及び<d>/d50の値を表３に示す。また実施例６の試料粉末をＳＥＭ観察すると、花弁状の表面凹凸２を有する粒子（以下、花弁状粒子）が観察された。結果を図５に示す。花弁状の凹凸を詳細に観察すると、厚さ１０ｎｍ程度の燐片上の凹凸が複雑に共存した表面構造であり、サブミクロンサイズの花弁が幾重にも重なったように観察される。この花弁状凹凸は粒子表面に均一に生成している。図５に示すような表面を有する粒子が実施例３〜５、７の試料にも見られた。また実施例６の試料粉末について実施例１と同様にしてＸ線回折パターンを測定したところ、図４と同様のパターンを得た。２θ＝２７．４°のとき得られたＴｉＯ２の最大回折ピークの半値幅は０．１６°であり、ＴｉＯ２の最大回折ピーク強度のα−Ｆｅの最大回折ピーク［（110）ピーク］強度に対する比は０．０６であった。これから、ＴｉＯ２が高い結晶性を有することが分かる。
(Examples 3 to 7)
2 g of the sample powder obtained in Example 2 was put into 50 ml of simulated body fluid (Simulated Body Fluid / SBF liquid) and immersed under the conditions shown in Table 3 (Examples 3 to 7). After washing with water and drying, a sample powder was obtained. Table 3 shows values of d50 measured in the same manner as in Example 1 and specific surface areas, <d> and <d> / d50, measured in the same manner as in Example 2. Further, when the sample powder of Example 6 was observed by SEM, particles having petal-like surface irregularities 2 (hereinafter referred to as petal-like particles) were observed. The results are shown in FIG. When the petal-like irregularities are observed in detail, it is a surface structure in which the irregularities on the flakes with a thickness of about 10 nm coexist in a complicated manner, and the petal-like irregularities are observed as if the submicron-sized petals overlapped. The petal-like irregularities are uniformly formed on the particle surface. Particles having a surface as shown in FIG. 5 were also observed in the samples of Examples 3 to 5 and 7. Moreover, when the X-ray-diffraction pattern was measured like Example 1 about the sample powder of Example 6, the pattern similar to FIG. 4 was obtained. The half-width of the maximum diffraction peak of TiO 2 obtained when 2θ = 27.4 ° is 0.16 °, and the maximum diffraction peak intensity of α-Fe [(110) peak] intensity of the maximum diffraction peak intensity of TiO 2 The ratio to 0.06 was 0.06. From this, it can be seen that TiO 2 has high crystallinity.
（実施例８）
実施例２で得た試料粉末2gをハンクス液50ml中に投入し、表３に示す条件で浸漬させた。実施例1 と同様にしてd50、実施例２と同様にして比表面積、<d>、<d>/d50を求めた。結果を表３に示す。
(Example 8)
2 g of the sample powder obtained in Example 2 was put into 50 ml of Hanks solution and immersed under the conditions shown in Table 3. In the same manner as in Example 1, d50 was obtained, and in the same manner as in Example 2, specific surface areas, <d> and <d> / d50 were obtained. The results are shown in Table 3.
（実施例９）
比較例１で得た試料粉末２ｇを実施例６と同様にＳＢＦ液中に浸漬させ、実施例１と同様にしてd50、実施例２と同様にして比表面積、<d>、<d>/d50を求めた。結果を表３に示す。
Example 9
2 g of the sample powder obtained in Comparative Example 1 was dipped in the SBF solution in the same manner as in Example 6, d50 in the same manner as in Example 1, and the specific surface area, <d>, <d> / in the same manner as in Example 2. d50 was determined. The results are shown in Table 3.
表３より、本発明の試料においてはd50に比べて<d>が非常に小さく、<d>/d50が０．０６以下であることが分かる。図２で示したナノワイヤの生成が比表面積の増大（<d>の微細化）の原因であると推察される。特に生体擬似液中に試料粉末を浸漬させることによって比表面積が増大しており、<d>/d50は０．０４以下まで低下している。これは図５で示した花弁状粒子が比表面積の増大に寄与しているためである。 From Table 3, it can be seen that in the sample of the present invention, <d> is very small compared to d50, and <d> / d50 is 0.06 or less. It is surmised that the generation of nanowires shown in FIG. 2 is responsible for the increase in specific surface area (miniaturization of <d>). In particular, the specific surface area is increased by immersing the sample powder in the simulated biological fluid, and <d> / d50 is decreased to 0.04 or less. This is because the petal-like particles shown in FIG. 5 contribute to the increase in specific surface area.
（実施例１０）
実施例６で作成した試料粉末に、以下に説明する手法で抗体を吸着させた。上述の試料粉末と体積比１％の３−アミノプロピルトリエトキシシラン(APS)水溶液とを混和し、1時間攪拌した。さらに、大気中において120 ℃で3時間加熱処理を施した。得られた試料粉末のd50を実施例1と同様にして測定したところ、3.7μmであった。次に、無水コハク酸と混和することにより、上記磁性粒子の表面にカルボキシル基を導入した（以後、カルボキシル基コート磁気ビーズ）。前記カルボキシル基コート磁気ビーズに抗体を吸着させた。すなわちこの磁気ビーズ10mgをカルボジイミドで活性化させた後、クエン酸緩衝液により200μg/mlに調整したＩｇＧ抗体（Rabbit-IgG）溶液1 mlを投入し室温で16時間攪拌した。攪拌後磁気分離により上澄み液を分取した。カルボキシル基コート磁気ビーズ1 mgあたりのIgG吸着量は投入したIgG量（200 μg）から上記上澄み液に残留したIgGの量を引き10で割ることにより求めた。上澄み液に残留したIgG濃度、および加えたIgG溶液の濃度は吸光度を測定し定量、調整した。IgG濃度は260 nmの吸光度（A260）、280 nmの吸光度（A280）および320 nmの吸光度（A320）を日立ハイテクノロジーズ社製ダイオードアレー型バイオ光度計U-0080D（1cmの光路長セルを使用）にて測定し、以下の式に従い算出した。
IgG濃度（mg/ml）＝（A280-A320）×1.55-(A260-A320)×0.76
その結果、磁気ビーズ1 mgあたりのIgG吸着量10.4μgであった。
(Example 10)
The antibody was adsorbed to the sample powder prepared in Example 6 by the method described below. The above sample powder and a 1% volume ratio 3-aminopropyltriethoxysilane (APS) aqueous solution were mixed and stirred for 1 hour. Furthermore, heat treatment was performed at 120 ° C. for 3 hours in the air. When d50 of the obtained sample powder was measured in the same manner as in Example 1, it was 3.7 μm. Next, by mixing with succinic anhydride, carboxyl groups were introduced on the surface of the magnetic particles (hereinafter, carboxyl group-coated magnetic beads). The antibody was adsorbed on the carboxyl group-coated magnetic beads. That is, after activating 10 mg of the magnetic beads with carbodiimide, 1 ml of an IgG antibody (Rabbit-IgG) solution adjusted to 200 μg / ml with a citrate buffer was added and stirred at room temperature for 16 hours. After stirring, the supernatant was separated by magnetic separation. The amount of IgG adsorbed per 1 mg of carboxyl group-coated magnetic beads was determined by subtracting the amount of IgG remaining in the supernatant from the amount of IgG charged (200 μg) and dividing by 10. The IgG concentration remaining in the supernatant and the concentration of the added IgG solution were quantified and adjusted by measuring absorbance. IgG concentration is 260 nm absorbance (A260), 280 nm absorbance (A280) and 320 nm absorbance (A320). Hitachi High-Technologies diode array type biophotometer U-0080D (using 1cm optical path length cell) And calculated according to the following formula.
IgG concentration (mg / ml) = (A280-A320) x 1.55- (A260-A320) x 0.76
As a result, the IgG adsorption amount per 1 mg of magnetic beads was 10.4 μg.
（実施例１１）
実施例６で作成した試料粉末を、以下に説明する手法でシリカ被覆処理を施した。上述の試料粉末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、シリカ被覆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。このシリカ被覆処理を合計3回繰り返した後、イソプロピルアルコールで溶媒置換を行い、ドラフト内で乾燥させた。このシリカ被覆磁性粒子に実施例１０と同様にしてカルボキシル基を導入し、ＩｇＧ抗体の吸着性能を評価した。結果を表４に示す。
(Example 11)
The sample powder prepared in Example 6 was subjected to silica coating treatment by the method described below. 5 g of the above sample powder 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 liquid was removed while trapping the silica-coated magnetic particles on the inner wall of the beaker with a magnet. This silica coating treatment was repeated a total of 3 times, followed by solvent replacement with isopropyl alcohol and drying in a fume hood. Carboxyl groups were introduced into the silica-coated magnetic particles in the same manner as in Example 10 to evaluate the IgG antibody adsorption performance. The results are shown in Table 4.
（比較例２）
比較例１で得た試料粉末について実施例１０と同様にしてカルボキシル基を導入し、ＩｇＧ抗体の吸着性能を評価した。結果を表４に示す。
(Comparative Example 2)
The sample powder obtained in Comparative Example 1 was introduced with a carboxyl group in the same manner as in Example 10 to evaluate the IgG antibody adsorption performance. The results are shown in Table 4.
（比較例３）
比較例１で作成した試料粉末に実施例１１と同様の手法でシリカ被覆処理を施し、実施例１０と同様にしてカルボキシル基を導入し、ＩｇＧ抗体の吸着性能を評価した。結果を表４に示す。
(Comparative Example 3)
The sample powder prepared in Comparative Example 1 was subjected to silica coating treatment in the same manner as in Example 11, and carboxyl groups were introduced in the same manner as in Example 10 to evaluate the adsorption performance of IgG antibody. The results are shown in Table 4.
以上より、本発明の磁気ビーズは1mgあたりＩｇＧ抗体を１０μg以上吸着し、優れた抗体吸着性能を示すことが分かる。また、さらに表面にシリカ被覆を形成することにより、ＩｇＧ抗体の吸着量は１５μｇ以上となり、いっそう優れた抗体吸着性能を発揮していることがわかる。 From the above, it can be seen that the magnetic beads of the present invention adsorb 10 μg or more of IgG antibody per mg and show excellent antibody adsorption performance. Furthermore, it can be seen that by further forming a silica coating on the surface, the amount of IgG antibody adsorbed is 15 μg or more, and it exhibits even better antibody adsorption performance.
１：ナノワイヤ ２：花弁状の表面凹凸 1: Nanowire 2: Petal-like surface irregularities
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