JP2007084407A - Metal colloid solution and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To have excellent magnetic sensitivity and redispersibility in an inorganic dispersion medium such as water after magnetic aggregation, and non-specifically adsorbing with biological substances to inhibit its function. No metal colloid solution is provided.
A metal colloid solution is composed of metal particles such as magnetite, cobalt ferrite, or zinc ferrite having magnetic sensitivity, and an inorganic dispersion medium such as water in which the metal particles are dispersed. The pH of the dispersion medium is adjusted to 0.5 to 10. The average particle diameter of the metal particles is 10 nm to 200 nm. The saturation magnetization of the metal particles is 70 emu / g or more, and the residual magnetization is 10 Oe or less.
[Selection figure] None

Description

  The present invention relates to a colloidal metal solution having magnetic sensitivity and a method for producing the same, and more specifically, it is used as an adsorbent used for separation of biological materials, and is preferably used for various assays and diagnosis. The present invention relates to a colloidal metal solution and a method for producing the same. More specifically, cancer hyperthermia (Magnetic Fluid Hyperthermia), Magnetic Resonance Imaging (MRI), Drug Delivery System (DDS), advanced biosensor, useful substance separation and purification system, advanced functionality The present invention relates to a metal colloid solution that can be suitably used in a system such as a fine chemical, an environmental load reduction system, or an environmental hormone substance measurement system, and a method for producing the same.

  In metal colloid solutions using water as a dispersion medium, a method of using an organic substance as a dispersant is widely used in order to stably disperse metal particles in a solvent. For example, when a noble metal such as gold or silver is used as the metal particles of the metal colloid solution, the organic substance is an oil, a surfactant, an organic low molecule such as citric acid or alkanethiol, or a polymer. . In this case, it is difficult to obtain a stable metal colloid solution when the content of the organic substance with respect to the metal particles is several weight% or less.

  In addition, when the metal particles of the metal colloid solution are composed of a metal exhibiting magnetic sensitivity, aggregation occurs between the particles due to magnetism, and thus it is necessary to disperse the metal particles using a larger amount of organic matter.

For example, as an example of using an organic substance to prevent magnetic aggregation and maintain the dispersibility of metal particles in a metal colloid solution, iron oxide superparamagnetic fine particles having unsaturated fatty acids adsorbed on the metal particle surfaces are used. (For example, refer to Patent Document 1). Further, a water-dispersible ultrafine particle magnetite having a surfactant adsorbed on the surface of metal particles is also used (see, for example, Patent Document 2). In addition, biomaterial labeling magnetic fine particles in which dextran is adsorbed on the surface of metal particles are also used (see, for example, Patent Document 3). Further, between the iron oxide superparamagnetic fine particles and the coating layer made of unsaturated fatty acid covering the particles, there is Al or Si, or any of oxides or hydroxides of Al and Si. Iron oxide superparamagnetic fine particles are also used (see, for example, Patent Document 4).
JP-A-3-247514 (published on November 5, 1991) Japanese Patent Laid-Open No. 2-206694 (published August 16, 1990) JP-A-6-92640 (published April 5, 1994) JP 5-310429 A (published on November 22, 1993)

  However, when a metal colloid solution is used for a biological material, in the methods described in Patent Document 1 and Patent Document 2, unsaturated fatty acids and surfactants adsorb nonspecifically to the target biological material, It has the effect of modifying the original structure of biological material and harming its function. Therefore, it is difficult to use in the field of detection, diagnosis or treatment targeting a biological substance.

  In the method described in Patent Document 3, the dextran layer covering the surface of the metal particles is present in a thickness of several tens of times the diameter of the metal particles. As a result, the particle size of the metal colloid particles is increased, making it difficult to handle in a minute space.

  Further, in the method described in Patent Document 4, since the saturation magnetization is about 50 emu / g, it is difficult to accurately implement them in various diagnoses, detections, or treatments.

  The present invention has been made in view of the above-described conventional problems, and its purpose is excellent in magnetic sensitivity and good redispersibility in an inorganic dispersion medium such as water after magnetic aggregation. Another object of the present invention is to provide a metal colloid solution and a method for producing the same, which do not adsorb non-specifically to biological substances and do not inhibit the function thereof.

  As a result of intensive studies in view of the above problems, the present inventor has produced a metal colloid solution having excellent dispersion stability without containing organic substances by adding an inorganic dispersion medium to metal particles having magnetic sensitivity. Found that it is possible to do. The colloidal metal solution of the present invention does not aggregate due to residual magnetism even after applying a magnetic field, has excellent redispersibility, and does not settle spontaneously even after several months or more, and has excellent dispersion stability. Have. Moreover, the metal colloid solution of this invention can control aggregation of particle | grains by adjusting the pH of a dispersion medium with an acidic regulator, for example.

  That is, the metal colloid solution of the present invention is characterized by being composed of metal particles having magnetic sensitivity and an inorganic dispersion medium in which the metal particles are dispersed.

  In the metal colloid solution of the present invention, the metal particles are preferably magnetite, cobalt ferrite, or zinc ferrite.

  In the metal colloid solution of the present invention, the dispersion medium is preferably water.

  In the metal colloid solution of the present invention, the pH of the water is preferably 0.5-10.

  In the metal colloid solution of the present invention, the metal particles preferably have an average particle size of 10 nm to 200 nm.

  In the metal colloid solution of the present invention, the saturation magnetization of the metal particles is preferably 70 emu / g or more, and the residual magnetization is preferably 10 Oe or less.

  Further, the method for producing a metal colloid solution of the present invention includes a precipitation step of depositing magnetic particles having magnetic sensitivity, a recovery step of recovering the precipitated metal particles, and using the recovered metal particles as an inorganic dispersion medium. And a suspension step for suspending.

  In the method for producing a metal colloid solution of the present invention, the dispersion medium is preferably water.

  In the method for producing a metal colloid solution of the present invention, the pH of the water is preferably 0.5-10.

  As described above, the metal colloid solution of the present invention is composed of metal particles having magnetic sensitivity and an inorganic dispersion medium. As a result, it is possible to provide a metal colloid solution having excellent magnetic sensitivity and excellent redispersibility in an inorganic dispersion medium such as water after magnetic aggregation. In addition, since the metal colloid solution of the present invention does not contain an organic substance, when used on a biological material, it does not adsorb nonspecifically with the biological material and does not inhibit the function of the biological material.

  An embodiment of the present invention will be described with reference to FIGS. 1 to 3 as follows.

[Composition of metal colloid solution]
The metal colloid solution of the present invention is composed of metal particles having magnetic sensitivity and an inorganic dispersion medium in which the metal particles are dispersed.

  In the present specification, “magnetic sensitivity” means a property that can be attracted by a permanent magnet. That is, it is a feature of a substance called a ferromagnetic material, which means that magnetization is generated by applying a certain magnetic field, and thereafter, the magnetization is saturated and becomes saturated magnetization.

The metal particles having magnetic sensitivity are not particularly limited as long as they have magnetic sensitivity. Specifically, the metal particles are preferably magnetite (M = Fe) or cobalt ferrite (M = Co) represented by MFe ₂ O ₄ . Most preferred is magnetite. Incidentally, the metal particles may if it contains magnetite or cobalt ferrite represented by _MFe 2 _{O 4,} may include such _γ-Fe 2 _{O 4.}

  In the metal colloid solution of the present invention, water is preferably used as the inorganic dispersion medium. Furthermore, the pH of the dispersion medium is preferably adjusted to 0.5 to 10 by adding an acid adjusting agent. Further, the pH is more preferably adjusted to 1 to 9, and most preferably 7 to 8.

  The acid regulator is not particularly limited as long as it is dissociated as ions in water and liberates hydrogen ions. Specifically, hydrochloric acid, acetic acid, sulfuric acid or nitric acid can be used.

  In the metal colloid solution of the present invention, the average particle diameter of the metal particles is not particularly limited, but is preferably 10 nm to 200 nm. Although it is possible to produce a metal colloid solution in which the particle size of the metal particles is smaller than 10 nm, it is not practical from the viewpoint of production cost. Moreover, although it is possible to produce a metal colloid solution having an average particle size of metal particles larger than 200 nm, in this case, the dispersion stability of the metal colloid solution is lowered. The method for measuring the particle size of the metal particles is not particularly limited, and any known method can be used as appropriate. Specifically, it is preferable to measure using a dynamic light scattering method or the like.

  The metal colloid solution of the present invention contains metal particles having magnetic sensitivity as described above. The metal particles having the magnetic sensitivity have properties of saturation magnetization and remanent magnetization. The value of the saturation magnetization is not particularly limited, but is preferably 70 emu / g or more. At this time, the value of the saturation magnetization is preferably as large as possible. For example, when magnetite is used as the metal particles, the upper limit value of the saturation magnetization is about 92 emu / g. Therefore, when magnetite is used as the metal particles, the saturation magnetization value of the metal colloid solution of the present invention is preferably as close to 92 emu / g.

  The value of the residual magnetization is not particularly limited, but is preferably 10 Oe or less in order to improve the dispersibility of the metal particles. The value of the residual magnetization is preferably as small as possible and closer to 0 Oe. In addition, a well-known method can be used suitably as the measuring method of the said saturation magnetization and residual magnetization.

  As described above, the metal colloid solution of the present invention is composed of metal particles having magnetic sensitivity and an inorganic dispersion medium in which the metal particles are dispersed. In other words, the metal colloid solution of the present invention does not include an organic substance for stably dispersing metal particles having magnetic sensitivity in a dispersion medium. Here, “comprising an organic substance” means that the metal colloid solution of the present invention contains an organic substance in a manner capable of contacting the metal particles. Specifically, the organic substance includes dextran, various surfactants, various unsaturated fatty acids, and the like.

[Method of preparing metal colloid solution]
The metal colloid solution of the present invention can be prepared according to the steps 1) to 4) described below.

1) Precipitation step 2) Recovery step 3) Suspension step 4) Removal step The steps 1) to 4) are described below.

<1: Precipitation process>
The deposition step is a step of depositing metal particles having magnetic sensitivity. As the process, for example, the case where the metal particles are magnetite will be described as an example.

This step is a step of depositing magnetite by adding Fe ³⁺ and Fe ²⁺ to water having an alkaline pH and stirring. The pH may be a value larger than 7, and is not particularly limited, but is preferably in the range of 9-13. Further, the pH is more preferably 11.5 to 12.5.

  The alkaline regulator for making the pH of the water alkaline is not particularly limited as long as the pH of the water can be adjusted to alkaline. Specifically, sodium hydroxide, potassium hydroxide, ammonium hydroxide, ammonia water, ammonium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, or potassium hydrogen carbonate can be used as the alkaline regulator. It is.

As the supply source of the Fe ^3+, it was dissolved in water as long as it can supply Fe ^3+, and is not particularly limited. Specifically, iron (III) chloride hexahydrate can be used. Moreover, these may be used independently and 2 or more types may be used together.

Sources of the Fe ^2+, dissolved in water as long as it can supply Fe ^2+, but is not particularly limited. Specifically, iron (II) chloride tetrahydrate or iron (II) sulfate heptahydrate can be used. Moreover, these may be used independently and 2 or more types may be used together.

Moreover, the amount of each supply source of Fe ³⁺ and Fe ²⁺ added to water is not particularly limited, but it is preferable to add each amount in water so that Fe ²⁺ ≧ Fe ³⁺ .

<2: Recovery process>
The recovery step is a step for recovering the metal particles precipitated in the step described in 1) above. The method used in this step is not particularly limited as long as it can recover the metal particles. Specifically, a known method such as a filter filtration method or a centrifugal separation method can be used.

  When the filter filtration method is used, the filter may be a filter selected in accordance with the particle diameter of the metal particles deposited in the process described in 1) above, and a known filter can be used as appropriate.

  Moreover, when using the centrifugation method, the conditions of centrifugation should just be the conditions which can precipitate the metal particle which precipitated in the process of said 1), and are not specifically limited. Specifically, it is preferable to perform centrifugation at 3300 rpm for 5 minutes.

<3: Suspension process>
The suspending step is a step of suspending the metal particles recovered in the step described in 2) above after adding a dispersion medium whose pH is adjusted with an acid regulator.

  Since the specific composition of the dispersion medium whose pH is adjusted by the acid regulator used here has been described above, the description thereof will be omitted.

  The concentration of the metal particles in the dispersion medium after adding the dispersion medium is not particularly limited as long as the metal particles can be stably dispersed. For example, the metal particles It is preferable that the concentration be such that it can be easily pulled when drawn using a rare earth magnet or the like and can be easily resuspended when the rare earth magnet is released.

  In addition, when the dispersion medium is added to the metal particles, a dispersion medium whose pH has already been adjusted may be added, or after adding a dispersion medium whose pH has not been adjusted to the metal particles, an acid regulator is added thereto. The pH may be adjusted. In order to easily adjust the concentration of the metal particles in the dispersion medium, it is preferable to add a dispersion medium whose pH has already been adjusted to the metal particles.

  In this step, the metal particles are then resuspended in the dispersion medium. The method of resuspension is not particularly limited, and a known method can be appropriately used. Specifically, it can be resuspended by ultrasonic treatment or the like.

<4: Removal step>
The removal step is a step of removing the metal particles that have not been resuspended in the step described in 3) above. Therefore, in the step described in 3) above, when the metal particles are sufficiently suspended, this step can be omitted. The method used in this step is not particularly limited as long as it is a method capable of removing the metal particles that have not been resuspended, and known methods such as filter filtration and centrifugation are used. It is possible to use.

  When the filter filtration method is used, a filter having an opening enough to pass the resuspended metal particles but not the resuspended metal particles may be selected. As such a filter, a known filter can be appropriately used. And the metal colloid solution of this invention is obtained by allowing the said filter to pass through.

  When the centrifugation method is used, the conditions for the centrifugation may be selected such that the resuspended metal particles are not precipitated, but the resuspended metal particles are precipitated. Specifically, it is preferable to perform centrifugation at 3300 rpm for 5 minutes. And the metal colloid solution of this invention is obtained by remove | excluding a deposit.

  It should be noted that the specific embodiments and the following examples made in the section of the best mode for carrying out the invention are intended to clarify the technical contents of the present invention, and to such specific examples. It is not to be construed as limiting in any way whatsoever, and those skilled in the art can implement the invention within the spirit of the invention and the scope of the appended claims.

  Moreover, all the academic literatures and patent literatures described in this specification are incorporated herein by reference.

[Example 1]
To 100 ml of water having a pH of 11.8, 50 ml of an aqueous solution in which 1.1 g of iron (III) chloride hexahydrate and 0.78 g of iron (II) chloride tetrahydrate were dissolved was added and stirred. The precipitated black product was centrifuged at 3300 rpm for 5 minutes, and then the supernatant was discarded and the sediment was collected. Next, an aqueous hydrochloric acid solution having pH = 1.1 was added, shaken and sonicated, and then centrifuged at 3300 rpm for 5 minutes. Thereafter, a colloidal metal solution was obtained by collecting the supernatant black-brown dispersion.

[Example 2]
To 100 ml of water having a pH of 11.8, 50 ml of an aqueous solution in which 1.1 g of iron (III) chloride hexahydrate and 0.78 g of iron (II) chloride tetrahydrate were dissolved was added and stirred. The precipitated black product was centrifuged at 3300 rpm for 5 minutes, and then the supernatant was discarded and the sediment was collected. Next, water of pH = 7-8 was added and shaken and sonicated, and then centrifuged at 3300 rpm for 5 minutes. Thereafter, a colloidal metal solution was obtained by collecting the supernatant black-brown dispersion.

Example 3
To 100 ml of water having a pH of 11.8, 50 ml of an aqueous solution in which 1.1 g of iron (III) chloride hexahydrate and 0.78 g of iron (II) chloride tetrahydrate were dissolved was added and stirred. The precipitated black product was centrifuged at 3300 rpm for 5 minutes, and then the supernatant was discarded and the sediment was collected. Next, an aqueous hydrochloric acid solution having pH = 4.0 was added and shaken and sonicated, and then centrifuged at 3300 rpm for 5 minutes. Thereafter, a colloidal metal solution was obtained by collecting the supernatant black-brown dispersion.

Example 4
To 100 ml of water having a pH of 11.8, 50 ml of an aqueous solution in which 1.1 g of iron (III) chloride hexahydrate and 0.78 g of iron (II) chloride tetrahydrate were dissolved was added and stirred. The precipitated black product was centrifuged at 3300 rpm for 5 minutes, and then the supernatant was discarded and the sediment was collected. Next, an aqueous hydrochloric acid solution having pH = 5.0 was added, shaken and subjected to ultrasonic treatment, and then centrifuged at 3300 rpm for 5 minutes. Thereafter, a colloidal metal solution was obtained by collecting the supernatant black-brown dispersion.

[Comparative Example 1]
To 5 g of magnetite F (Mitsui Mining & Smelting Co., Ltd., SEM particle size: 100 to 400 nm), add 50 ml of hydrochloric acid aqueous solution having a pH of 1.1, shake and mix for 10 minutes, and then sonicate for 3 days. I put it. The precipitate was shaken well to obtain a suspension, followed by centrifugation at 3300 rpm for 5 minutes. However, the supernatant was a yellow transparent solution, and a colloidal solution could not be obtained. Further, even if the rotational speed of the centrifugation was reduced by half, a colloidal solution could not be obtained.

[Evaluation of metal particles and metal colloid solutions]
As shown in FIG. 1, the black solid content (metal particles) obtained by drying the metal colloid solutions obtained in Example 1 and Example 2 was found to be Fe ₃ O as a result of X-ray analysis (XRD). ₄ (magnetite). Moreover, the organic matter content was 0.1 wt% or less according to the results of TG / DTA (thermogravimetric) analysis and elemental analysis. Moreover, as a result of measurement by a transmission electron microscope (TEM), the particle size of the metal particles was 5 to 10 nm. The magnetic properties of the metal particles were measured with an oscillating magnetometer (VSM) with an external magnetic field up to 10 kOe. As a result, as shown in FIG. 2, the metal particles were superparamagnetic fine particles having a saturation magnetization of 70 emu / g or more and a residual magnetization of almost 0 Oe.

  Moreover, the particle size of the metal particles was evaluated by dynamic light scattering (DLS) measurement. As a result, in Example 1, the average particle diameter was 20 to 30 nm as shown in FIG. 3A, and in Example 2, the average particle diameter was 100 nm as shown in FIG. It was. Further, the metal particles were attracted and aggregated when the rare earth magnet was brought closer, and dispersed easily when the rare earth magnet was released. In addition, all the said metal colloid solutions existed stably for more than half a year at room temperature and stationary.

  The colloidal metal solution of the present invention and the preparation method thereof are cancer thermotherapy (Magnetic Fluid Hyperthermia), nuclear magnetic resonance imaging (MRI), drug delivery system (DDS), highly functional biosensor, useful It can be suitably used for a substance separation and purification system, a high-performance fine chemical, an environmental load reduction system, an environmental hormone substance measurement system, or the like.

In an Example, it is a chart which shows the result of the X-ray analysis of the black solid content obtained by drying the metal colloid solution. In an Example, it is a chart which shows the result of the magnetic characteristic of the metal colloid solution measured using the vibration type magnetization measuring apparatus. In an Example, it is a chart which shows the result of the average particle diameter of the metal colloid solution calculated | required by the dynamic light scattering measurement.

Claims (9)

  A metal colloid solution comprising metal particles having magnetic sensitivity and an inorganic dispersion medium in which the metal particles are dispersed.   The metal colloid solution according to claim 1, wherein the metal particles are magnetite, cobalt ferrite, or zinc ferrite.   The metal colloid solution according to claim 1 or 2, wherein the dispersion medium is water.   The metal colloid solution according to claim 3, wherein the water has a pH of 0.5 to 10.   The metal colloid solution according to any one of claims 1 to 4, wherein the average particle diameter of the metal particles is 10 nm to 200 nm.   The metal colloid solution according to any one of claims 1 to 5, wherein the saturation magnetization of the metal particles is 70 emu / g or more and the residual magnetization is 10 Oe or less. A deposition step of depositing magnetic particles with magnetic sensitivity;
A recovery step of recovering the deposited metal particles;
A suspension step of suspending the recovered metal particles in an inorganic dispersion medium;
A method for producing a metal colloid solution, comprising:   The method for producing a metal colloid solution according to claim 7, wherein the dispersion medium is water.   The method for producing a metal colloid solution according to claim 8, wherein the pH of the water is 0.5 to 10.

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