JP2009138081A - Fine particle dispersion solution, method for producing the fine particle dispersion solution, and method for producing LnOX-LnX3 composite particles - Google Patents

Abstract

A fluorescent fine particle dispersion solution capable of efficiently producing a dispersion solution in which nanometer-sized fine particles are dispersed without performing mechanical dispersion and pulverization treatment, a method for producing the fine particle dispersion solution, and LnOX-LnX ₃ to provide a method of manufacturing composite particles.
The fine particle dispersion solution of the present invention uniformly disperses fine particles of LnOX (Ln is a rare earth element, X is a halogen) having an average particle size of nanometer size, so that an upconversion light emitting phosphor, a contrast agent, and a sensitization As an agent or the like, it can be used as a fluorescent label in the field of genetic diagnosis. Moreover, since the fine particle dispersion solution of the present invention can be produced by introducing the precursor LnOX-LnX ₃ composite particles into a solvent, it is simple without performing mechanical dispersion and pulverization treatment. And it can be obtained at low cost. Furthermore, the precursor can also be easily obtained by subjecting the rare earth halide hydrate to a two-step heat treatment.
[Selection] Figure 2

Description

The present invention relates to a fine particle dispersion solution, a method for producing the fine particle dispersion solution, and a method for producing LnOX-LnX ₃ composite particles. More specifically, the present invention relates to a fine particle dispersion solution in which nanometer-sized phosphor fine particles are uniformly dispersed in a solvent, a method for producing the fine particle dispersion solution, and a method for producing LnOX-LnX ₃ composite particles.

  As one of the clinical tests in the medical and biochemical research fields, specific cells and tissues are labeled with fluorescent substances such as organic dyes, visualized with fluorescence emitted when irradiated with ultraviolet light, and observed with an optical microscope. There is bioimaging. In this method, there is a problem that ultraviolet rays damage the fluorescent substance and the observation target, and it is difficult to observe for a long time.

  In order to solve such a problem, a method of using inorganic phosphor fine particles exhibiting up-conversion light emission by near-infrared irradiation for a fluorescent label is provided (for example, see Patent Document 1). With respect to the characteristics of the inorganic phosphor fine particles used in this method, for example, the particle size must be nanometer size, and it must be stably monodispersed in a solvent.

  As a method for producing a solution in which nanometer fine particles having such a particle size are dispersed, for example, a method in which nanometer-sized fine particles are mainly charged and stirred directly into a solution (for example, see Patent Document 2), or a micro. A method of pulverizing metric fine particles in a solution (see, for example, Patent Document 3 and Patent Document 4) and a method of depositing and growing nanometer-sized fine particles in a solution (for example, Patent Document 5 and Patent) Reference 6) has been applied.

JP 2004-107612 A JP 2006-249253 A Japanese Patent Laid-Open No. 11-35320 JP 2006-152032 A JP-A-6-271316 JP-A-7-313862

  Among the conventional techniques described above, in the method of directly introducing and stirring nanometer-size fine particles into a solution as disclosed in Patent Document 2, a step of producing nanometer-size fine particles in advance, sufficiently ultrasonicating the solution It is not efficient because it requires a step of moving and dispersing the particles by applying a step or a step of mechanically stirring by introducing a mill type disperser. In addition, in these methods, it is considered suitable to add a polymer dispersant and increase the viscosity of the solvent, but increasing the viscosity of the solvent is considered for use in bioimaging labeling Was not preferred. There is also a problem that it is very difficult to separate all the agglomerated solids into single particles.

  In addition, in the method of pulverizing micrometer-sized fine particles in a solution as disclosed in Patent Document 3 and Patent Document 4, it is generally mechanically resolved by a dedicated device such as a pulverizer or a mill. A method of granulating or a method of chemically atomizing by ablation is used. These devices are expensive, and there is a problem that the manufacturing process becomes complicated because the solution needs to be transferred to a dedicated container.

  Furthermore, the method for depositing and growing nanometer-sized fine particles in a solution as disclosed in Patent Document 5 and Patent Document 6 does not require the mechanical dispersion treatment and the pulverization treatment as described above. While a solution in which fine particles are dispersed can be obtained directly, in the precipitated state, in many cases, a part of the solvent remains inside the particle or a hydroxyl group remains on the surface, which causes upconversion emission. There was a problem of greatly reducing the efficiency. In order to remove these solvents and hydroxyl groups, it is effective to collect the precipitates once and calcinate them at a high temperature with an electric furnace or the like. However, this is not preferable because it may reach a micrometer size and eventually the above-described pulverization work may be required.

  And if there is a pulverization step, it is difficult to make all the particles uniform, so there is a method to add a step of selecting only those with an appropriate particle size if necessary . In view of this, a method for efficiently performing nanometer sizing of the particle size and dispersion of the solution has been sought.

The present invention has been made as a result of research in view of the above problems, and efficiently produces a dispersion solution in which nanometer-size fine particles are dispersed without performing mechanical dispersion and pulverization treatment. The present invention provides a fluorescent fine particle dispersion solution, a production method of the fine particle dispersion solution, and a production method of LnOX-LnX ₃ composite particles as a precursor.

  In order to solve the above-mentioned problem, the fine particle dispersion solution according to claim 1 of the present invention has LnOX (Ln is a rare earth element, X is a halogen) fine particles having an average particle diameter of 1 to 800 nm uniformly dispersed in a solvent. It is characterized by being.

  The fine particle dispersion solution according to a second aspect of the present invention is the fine particle dispersion solution according to the first aspect, wherein the Ln (rare earth element) is lanthanum (La), erbium (Er), holmium (Ho), praseodymium (Pr), thulium ( Tm), neodymium (Nd), gadolinium (Gd), europium (Eu), ytterbium (Yb), samarium (Sm) and at least one selected from the group consisting of cerium (Ce).

  The fine particle dispersion according to claim 3 of the present invention is characterized in that, in the above-described claim 1 or 2, the solvent contains a water-soluble polymer and / or a surfactant.

The method for producing LnOX-LnX ₃ composite particles according to claim 4 of the present invention is a rare earth halide hydrate LnX ₃ .nH ₂ O (Ln is a rare earth element, X is a halogen, n is an integer of 1 to 7) ) At 100 to 350 ° C. for 1 hour or longer to obtain a temporary sintered body, and the temporary sintered body obtained by the first heat treatment is heated at 400 ° C. or higher for 1 hour or longer. And a second heat treatment.

The method for producing LnOX-LnX ₃ composite particles according to claim 5 of the present invention is characterized in that, in the above-described claim 4, heating in the first heat treatment is performed stepwise.

The method for producing a fine particle dispersion according to claim 6 of the present invention is characterized in that the LnOX-LnX ₃ composite particles obtained in claim 4 or 5 described above are introduced into a solvent.

  The fine particle dispersion solution according to claim 1 of the present invention uniformly distributes LnOX fine particles that are oxyhalides of rare earth elements (Ln) that are excited by near-infrared irradiation and exhibit up-conversion luminescence with an average particle size of nanometer size. Since it is dispersed, as an up-conversion luminescent phosphor, contrast agent, sensitizer, video display device, fluorescent immunoassay probe, bioimaging probe, single molecule imaging probe, etc., genetic diagnosis field, immunodiagnosis field, medical development field, It can be used as a fluorescent label in the environmental test field, biotechnology field, fluorescence test, and the like.

  In the fine particle dispersion according to claim 2 of the present invention, Ln constituting the oxyhalide of rare earth element (Ln), which is fine particles to be dispersed, is selected from specific rare earth elements. These fine particles emit light efficiently, and an optimal fine particle dispersion solution can be provided for applications such as up-conversion light-emitting phosphors.

  In the fine particle dispersion solution according to claim 3 of the present invention, the surface of the fine particles is modified by the solvent containing a modified product such as a water-soluble polymer and / or a surfactant, so that the fine particles are easily adsorbed on the observation target.

In the method for producing LnOX-LnX ₃ composite particles according to claim 4 of the present invention, the rare earth halide hydrate LnX ₃ · nH ₂ O is heat-treated in two stages, so that a dispersion solution is prepared. LnOX-LnX ₃ composite particles that are precursors for the purpose can be easily obtained.

In the method for producing LnOX-LnX ₃ composite particles according to claim 5 of the present invention, heating in the first heat treatment is performed stepwise, so that the reaction in the heat treatment can be reliably advanced. It is also possible to control the particle size of LnOCl particles obtained by self-hydrolysis by controlling the volume of residual hydrate by controlling the degree of dehydration of water from hydrated crystals. is there.

The method for producing a fine particle dispersion according to claim 6 of the present invention is the state obtained in claim 4 or claim 5, in which hardly soluble LnOX fine particles are present, and the outside is covered with soluble LnX ₃ The LnOX-LnX ₃ composite particles can be produced by introducing them into a solvent, so that the average particle size can be reduced to nanometers without carrying out the mechanical dispersion and pulverization treatment required in the conventional production. A fine particle dispersion solution in which size LnOX fine particles are uniformly dispersed in a solvent can be obtained easily and at low cost.

  Hereinafter, one embodiment of the present invention will be described. The fine particle dispersion solution of the present invention is obtained by uniformly dispersing fine particles of an oxyhalide (LnOX: Ln is a rare earth element, X is a halogen) of a rare earth element (Ln) having an average particle diameter of 1 to 800 nm in a solvent.

  In the fine particle dispersion of the present invention, the fine particles to be dispersed are composed of an oxyhalide (LnOX) of a rare earth element (Ln). As applicable Ln (rare earth element), for example, lanthanum (La), erbium (Er), holmium (Ho), praseodymium (Pr), thulium (Tm), neodymium (Nd), gadolinium (Gd), europium ( Eu), ytterbium (Yb), samarium (Sm), cerium (Ce) and the like. One of these may be used alone, or two or more of these may be used in combination.

  The average particle diameter of the dispersed rare earth element oxyhalide fine particles is in the nanometer order range of 1 to 800 nm. The average particle diameter is a value obtained by extracting 100 phosphor fine particles from an electron micrograph such as a scanning electron microscope (SEM) or a transmission electron microscope (TEM) and averaging the respective particle diameters.

Rare earth elements in oxyhalide rare earth element constituting the fine particles to be dispersed (Ln) (LnOX) (Ln ) , which can be selected depending on properties required from that described above, for example, Ln _a As in Ln _b OX, two (or more) rare earth elements (Ln) may exist for one fine particle. In the case where two (or more) rare earth elements exist for one fine particle, the kind of rare earth elements and the ratio (molar fraction) are appropriately determined according to required properties and applications. For example, when up-conversion luminescence is used for fine particles dispersed in a solution, erbium (Er) or thulium (Tm) is 10% or less (molar fraction; the same shall apply hereinafter), and ytterbium is used as a sensitizer. (Yb) is preferably 10% or less. In order to use fine particles as a contrast agent, it is preferable to contain 40% or more of Gd.

  On the other hand, the halogen element (X) is not particularly limited, and Cl (chlorine), Br (boron), I (iodine) and the like can be used, but for more efficient light emission. It is preferable to use Br or I.

  In the fine particle dispersion solution, water, ethanol, an organic solvent of methanol, or the like can be used as a solvent for dissolving the rare earth element oxyhalide. Further, the solvent may be added with a modified product such as a surfactant or a water-soluble polymer. When the solvent contains these modified products, the surface of the fine particles is modified and easily adsorbed on the observation target. Become. These modified products may be added in an amount of approximately 0.01 to 1.0% by mass with respect to the entire solution, but are not particularly limited.

  The surfactant that can be used is not particularly limited, and for example, cationic, anionic, nonionic, amphoteric, silicone, and fluorine surfactants can be used. Examples of the water-soluble polymer that can be used include polyethylene glycol, polyacrylic acid, and phospholipid. One of these may be used alone, or two or more of these may be used in combination.

  The content of the fine particles in the fine particle dispersion solution of the present invention may be appropriately determined according to the type of fine particles, required characteristics, etc., but an appropriate amount is contained in the entire solution, and is generally 0.5 to 10.0. It is preferable to contain about mass%, and it is especially preferable to contain about 0.5-5.0 mass%.

  The “uniformly dispersed” state in the fine particle dispersion of the present invention means that the fine particle dispersion is placed in a predetermined container (capacity is about 1 to 1000 mL) and stirred or shaken for a predetermined time (for example, 1 This means that the dispersion state can be maintained even after being left standing.

The fine particle dispersion solution of the present invention is obtained by dispersing rare earth element (Ln) oxyhalide (LnOX) fine particles in a solvent. In this case, LnOX-LnX ₃ composite particles having a slightly soluble LnOX fine particle and having the outside covered with soluble LnX ₃ may be added to or added to the solvent. In general, it is very difficult to disperse nanometer-sized LnOX in a solvent. However, LnOX-LnX ₃ composite in which hardly soluble LnOX fine particles exist inside and soluble LnX ₃ covers the outside. When body particles are introduced into a solvent, due to the difference in solubility (dissolution behavior) of both, soluble LnX ₃ is dissolved in the solvent, while hardly soluble LnOX fine particles are uniformly dispersed in the solvent. It becomes.

In addition, the LnOX-LnX ₃ composite particles in which the precursor LnOX fine particles are present inside the precursor and the outside is covered with the soluble LnX ₃ are rare earth halide hydrates LnX ₃ · nH. ₂ O (n is an integer of 1 to 7) and the first heat treatment of heating for 1 hour or more at 100 to 350 ° C. relative to, after the first heat treatment, a second heating 1 hour or more at 400 ° C. or higher By performing the heat treatment, it can be easily obtained.

A rare earth halide hydrate (LnX ₃ .nH ₂ O) as a starting material can be easily obtained by dissolving the corresponding rare earth halide (LnX ₃ ) in water such as pure water. Further, the form of the starting material is not particularly limited, but in order to precipitate the LnOX fine particles efficiently in the precursor, it is preferably in the form of particles, and a rare earth halide hydrate (LnX ₃ .nH ₂ O ) Is preferably set in advance to a micrometer size (approximately 1 to 20 μm). As a method for making the crystal grain size of such a hydrate a micrometer size, for example, a starting material dissolved in a solvent such as water is rapidly heated at a temperature of about 100 to 200 ° C. It can be conveniently obtained by rapid evaporation and drying.

In addition, the rare earth halide hydrate (LnX ₃ .nH ₂ O) as a starting material may be used alone, for example, Ln _a X ₃ .nH ₂ O, Ln Two types (or more) such as _b X ₃ · nH ₂ O may be used in combination. In the latter case, the resulting precursors are of two types (or Ln _a Ln _b OX-Ln _a Ln _b LnX ₃ complex particles (Ln _a : Ln _b OCl—Ln _a : Ln _b Cl ₃ complex)) Thus, composite particles containing rare earth elements can be obtained. Further, a fine particle dispersion solution in which Ln _a Ln _b OX (Ln _a : Ln _b OCl) is a fine particle in which two types (or more) of rare earth elements are present as the fine particles in the dispersion solution is obtained.

As rare earth halide hydrates (LnX ₃ .nH ₂ O), rare earth halide hydrates Ln _a Ln _b X ₃ .nH ₂ O in which two types of Ln (rare earth elements) are present, 3 You may make it use the hydrate of the rare earth halide in which the rare earth element more than a kind exists.

In the production method of the present invention, a rare earth halide hydrate (LnX ₃ .nH ₂ O) as a starting material is subjected to a two-step heat treatment. First, heat treatment is performed at 100 to 350 ° C. for 1 hour or longer (first heat treatment). By heating under such conditions, anhydrous LnX ₃ is generated on the surface of the obtained particle by the reaction of the following formula (I), while an amount of LnX ₃ · H corresponding to the heating temperature and heating time is generated inside the particle. A pre-sintered body in which ₂ O remains is produced.

Here, when the heating temperature (holding temperature) is lower than 100 ° C., the reaction does not proceed, and a desired amount of anhydrous LnX ₃ is not generated. On the other hand, when the heating temperature is higher than 350 ° C., most of the rare earth halide hydrate (LnX ₃ .nH ₂ O) becomes LnOX in the first heat treatment stage, and the anhydrous LnX ₃ serving as the matrix becomes It will not exist and will produce unstable particles.

When the heating time (holding time) is shorter than 1 hour, the reaction does not proceed and a desired amount of anhydrous LnX ₃ is not produced. If the heating time is long, a pre-sintered body in which an amount of anhydrous LnX ₃ corresponding to the heating time is produced will be produced, but it is preferably about 1 to 100 hours, more preferably 1 to 50 hours. It is preferably 1 to 5 hours, particularly preferably. Further, the rate of temperature increase in the first heat treatment is not particularly limited, but may be about 50 to 100 ° C./hour.

  Further, the first heat treatment may be performed stepwise at a temperature between 100 ° C. and 350 ° C. By performing the heating stepwise, the reaction can be surely progressed, and by controlling the volume of residual hydrate by controlling the degree of dehydration of water from the hydrated crystals, The particle size of the LnOCl particles obtained by self-hydrolysis can be controlled. The temperature difference at each stage is preferably 20 to 80 ° C, particularly preferably 30 to 60 ° C. In addition, the holding time for each stage is preferably 1 to 10 hours, and particularly preferably 1 to 5 hours per stage.

Next, as the second heat treatment, the temporary sintered body obtained by the first heat treatment is heated at a temperature of 400 ° C. or higher for 1 hour or longer. By heating at a high temperature as compared with the first heat treatment, LnX ₃ · nH ₂ O remaining in the temporary sintered body obtained by the first heat treatment is reduced by the reaction of the following formula (II). Change to LnOX. As a result, innumerable LnOX fine particles having an average particle diameter of nanometer size, which are dispersed inside, are present, and LnOX-LnX ₃ composite particles in which the outside is covered with anhydrous LnX ₃ are obtained.

  The heating temperature (holding temperature) may be 400 ° C. or higher. When the heating temperature is lower than 400 ° C., the reaction does not proceed and a desired amount of anhydrous LnOX is not generated. If the heating temperature is high, the reaction proceeds. However, in order to make LnOX into nanometer-sized fine particles, it may be about 400 to 500 ° C.

If the heating time (holding time) is shorter than 1 hour, the reaction does not proceed and a desired amount of anhydrous LnOX is not produced. If the heating time is long, a precursor (LnOX-LnX ₃ composite particles) in which an amount of LnOX has been produced is produced, but it is preferably about 1 to 5 hours, preferably 1 to 2 hours. It is particularly preferable that

  The temperature increase rate in the second heat treatment is not particularly limited, but the average particle diameter of the fine particles contained in the precursor can suppress the crystal growth as the temperature increase rate in the second heat treatment increases. Therefore, the average particle size of the fine particles contained in the finally obtained fine particle dispersion solution can be controlled. The rate of temperature rise may be about 50 to 100 ° C./hour.

  In the first heat treatment and the second heat treatment described above, the atmosphere is preferably a vacuum atmosphere or an inert gas atmosphere such as nitrogen or argon in order to efficiently prepare the precursor. The heating means in the first heat treatment and the second heat treatment may be performed using a known heating means such as an electric furnace.

Precursors (LnOX-LnX ₃ composite particles) obtained by such two-stage heat treatment become particles having a particle size of 1 to 1000 μm, and the average particle size is within the soluble host (LnX ₃ ) serving as a matrix. Is innumerable insoluble fine particles (LnOX) of 1 to 800 nm. In addition, it is considered that the precursor obtained is crystalline both of the LnOX fine particles which are the rare earth acid halide fine particles and the LnX ₃ which is the rare earth halide. In addition, it is considered that innumerable LnOX fine particles are monodispersed in LnX _{3 serving as} a matrix per one complex. For example, if the size of LnX ₃ particles as the matrix is about 1 [mu] m, the surface is pure LnX ₃ next to the particles, water molecules remaining part of the internal, the self-hydrolysis, pure LnX ₃ Particles with a volume smaller than 1 μm are excluded. Degree to which water escapes from the surface of the particles by the degree of heat treatment of the changes, reduces LnX 3 · _H 2 _O while increasing that much pure LnX ₃ by which long-term heat treatment, LnX ₃ · As a result The volume of LnOCl formed by self-hydrolysis of H ₂ O, that is, the particle size of LnOCl is reduced.

Then, an appropriate amount of LnOX-LnX ₃ composite particles in which the slightly soluble LnOX fine particles exist inside and the outside is covered with soluble LnX ₃ in a solvent such as water or an organic solvent such as methanol or ethanol ( For example, the composite particle is preferably about 0.5 to 10.0% by mass, particularly preferably about 0.5 to 5.0% by mass) with respect to the entire solution. Soluble LnX ₃ present in the solvent is dissolved in the solvent, and a fine particle dispersion solution in which the slightly soluble LnOX fine particles having an average particle diameter of 1 to 800 nm are uniformly dispersed is obtained. As described above, as a solvent, in addition to water or the like, a surfactant, a water-soluble polymer, or the like may be added as a modified product.

  The fine particle dispersion solution of the present invention has an average particle size of nanometer size, and uniformly disperses LnOX fine particles, which are oxyhalides of rare earth elements (Ln) that are excited by near-infrared irradiation and exhibit upconversion emission, Upconversion phosphors, contrast agents, sensitizers, video display devices, fluorescent immunoassay probes, bioimaging probes, single-molecule imaging probes, etc., genetic diagnosis field, immunodiagnosis field, medical development field, environmental test field, biotechnology It can be used as a fluorescent label in a field, a fluorescence test, etc., and can greatly contribute to a wide range of fields from future biochemical research to clinical diagnosis.

In addition, in the fine particle dispersion solution of the present invention, LnOX-LnX ₃ composite particles in which a slightly soluble LnOX fine particle is present inside and soluble LnX ₃ is covered outside are used as a solvent. Therefore, the LnOX fine particles having an average particle diameter of nanometer size were uniformly dispersed in the solvent without performing mechanical dispersion and pulverization treatment required in the conventional production. A fine particle dispersion solution can be obtained simply and at low cost. Therefore, a solution in which fine particles are uniformly monodispersed and can be applied as a fluorescent label for bioimaging in a wide range of fields from biochemical research to medical diagnosis can be provided without going through a pulverization step and a selection step.

Further, such precursors (LnOX-LnX ₃ composite particles) can also be easily obtained by subjecting the rare earth halide hydrate LnX ₃ .nH ₂ O to two-step heat treatment.

  EXAMPLES Hereinafter, although an Example and a comparative example are given and this invention is demonstrated more concretely, this invention is not restrict | limited at all by these Examples.

[Example 1]
Using LaCl ₃ · 6H ₂ O and ErCl ₃ · 6H ₂ O as starting materials, Er: LaOCl fine particle dispersion solution (La _0.99 Er _0.01 OCl fine particles), which is the fine particle dispersion solution of the present invention, by the following method Dispersion solution) was prepared.

(1) Preparation of LaCl ₃ · 6H ₂ O aqueous solution and ErCl ₃ · 6H ₂ O aqueous solution:
As a starting material, LaCl ₃ · 6H ₂ O was used and dissolved in water to prepare a LaCl ₃ aqueous solution having a concentration of 1.345 mol / L.
_{(2) ErCl 3 · 6H 2} O aqueous solution preparation of:
As a starting material, ErCl ₃ · 6H ₂ O was used and dissolved in water to prepare an ErCl ₃ aqueous solution having a concentration of 0.873 mol / L.

(3) Preparation of temporary sintered body (first heat treatment):
(1) The LaCl ₃ aqueous solution obtained in (2) and the ErCl ₃ · 6H ₂ O aqueous solution obtained in (2) were weighed so that the molar ratio was LaCl ₃ / ErCl ₃ = 99/1. And mixed to obtain a mixed solution. To obtain a particulate hydrate _{(La 0.99 Er 0.01 Cl 3 ·} 6H 2 O) by the resulting mixed solution is heated for 3 hours at 80 ° C. The.

The obtained hydrate is put in an alumina fireproof boat, and heated from room temperature to 120 ° C, 180 ° C, 240 ° C, and 300 ° C at a heating rate of 50 ° C / min using an electric furnace in a nitrogen gas atmosphere. the temperature was raised by holding for 3 hours at each temperature, anhydrous _La 0.99 _{Er 0.01} Cl ₃ particle outside, in the inside of the grain _{La 0.99 Er 0.01 Cl 3 · H} 2 O As a result, a pre-sintered body was obtained.

(4) Preparation of precursor (second heat treatment):
The pre-sintered body obtained in (3) is heated at 400 ° C. for 3 hours using the electron furnace in the nitrogen gas atmosphere used in (3), whereby La _0.99 Er ₀ inside the particles. _.01 Cl ₃ · _{H 2} O is _La 0.99 _Er 0.01 OCl _next, La _{0.99 Er} 0.01 OCl is covered with _La 0.99 Er0.01Cl ₃ precursor (Er: LaOCl-Er : LaCl ₃ composite particles) (average particle size: 1-1000 μm).

The precursor obtained in (4) was pulverized in an agate mortar and the crystal phase was analyzed with a powder X-ray diffractometer (XRD-6100: manufactured by Shimadzu Corporation) (X-ray diffraction pattern). Shown in As shown in FIG. 1, the X-ray diffraction pattern showed a LaCl ₃ phase and a LaOCl phase, and it was confirmed that the precursor was a complex of Er: LaOCl phase-Er: LaCl ₃ phase.

(5) Preparation of fine particle dispersion solution:
The precursor obtained in (4) is poured into water as a solvent to be dissolved and dispersed, and an Er: LaOCl fine particle dispersion solution (La _0.99) containing 10.0% by mass of the precursor with respect to the entire solution. Er _0.01 OCl fine particle dispersion solution) was obtained. The obtained fine particle dispersion solution is such that Er: LaOCl fine particles are uniformly dispersed in the solution, and the obtained dispersion solution is dispersed even after being placed in a screw tube having a capacity of 50 mL and left to stand for 1 hour. The state was maintained.

For the fine particle dispersion obtained in (5), a series of steps consisting of centrifugation, redispersion of the precipitate in distilled water, and ultrasonic cleaning is repeated three times, and the precipitate obtained by centrifugation is converted to P ₂ O. _A powder sample was obtained by vacuum drying over ₅ . About the obtained powder sample, the result of having analyzed the crystal phase with the powder X-ray-diffraction apparatus (XRD-6100: Shimadzu Corp. make) was shown in FIG. As shown in FIG. 2, only the LaOCl phase pattern was observed from the obtained X-ray diffraction pattern, and it was confirmed that the fine particles dispersed in the fine particle dispersion were Er: LaOCl fine particles.

Furthermore, when the obtained powder sample was irradiated with infrared rays of 980 nm, yellow up-conversion luminescence was exhibited. When this luminescence was analyzed with a fluorescence spectrometer (RF-5000: manufactured by Shimadzu Corporation), it was found that the emission was green luminescence around 550 nm and red luminescence around 660 nm, as shown in FIG. . This is considered to be light emission from Er ³⁺ ions in the powder.

  And when the average particle diameter was observed about the obtained powder sample using the field emission scanning electron microscope (S-4200: Hitachi High Technology Co., Ltd. product), the obtained powder sample (fine particles in the dispersion) It was confirmed that the fine particles had an average particle diameter of 30 to 300 nm.

From the above results, the prepared precursor is a composite of Er: LaOCl fine particles-Er: LaCl ₃ host, and by dissolving this in water, an Er: LaOCl fine particle dispersion solution having an average particle size of 30 to 300 nm is obtained. It was confirmed that it was obtained.

[Comparative Example 1]
Example 1 is the same as Example 1 except that the heat treatment of (3) and (4) is one step, the heating temperature is 900 ° C., and the heating time is 40 minutes (temperature increase rate: 1350 ° C./hour). The precursor was prepared under conditions.

FIG. 4 shows the results of powder X-ray diffraction measurement performed on the precursor obtained in Comparative Example 1. As shown in FIG. 4, in the precursor obtained in Comparative Example 1, only the pattern of Er: LaOCl phase was observed, and the pattern of Er: LaCl ₃ phase was not observed. From the above, it was confirmed that the Er: LaOCl—Er: LaCl ₃ complex could not be obtained when the heat treatment temperature was 900 ° C. and heated in one step.

  A fine particle dispersion solution was prepared in the same manner as in Example 1 using the precursor obtained in Comparative Example 1. On the other hand, after the obtained fine particle dispersion was placed in a screw tube and shaken for 1 hour, the fine particles settled and the dispersion state could not be maintained.

  According to the present invention, for example, a label used for bioimaging using X-rays or fluorescent light emission can be provided easily and at low cost, so that genetic diagnosis field, immunodiagnosis field, medical development field, environmental test field It can be advantageously used in the biotechnology field, fluorescence inspection, and the like.

2 is a diagram showing an X-ray diffraction pattern of a precursor obtained in Example 1. FIG. 2 is a diagram showing an X-ray diffraction pattern of fine particles extracted from the fine particle dispersion obtained in Example 1. FIG. It is the figure which showed the up-conversion emission spectrum when the microparticles | fine-particles extracted from the microparticle dispersion solution obtained in Example 1 were excited by infrared rays of 980 nm. 4 is a diagram showing an X-ray diffraction pattern of a precursor obtained in Comparative Example 1. FIG.

Claims (6)

  A fine particle dispersion solution in which fine particles of LnOX (Ln is a rare earth element, X is a halogen) having an average particle diameter of 1 to 800 nm are uniformly dispersed in a solvent.   The Ln (rare earth element) is lanthanum (La), erbium (Er), holmium (Ho), praseodymium (Pr), thulium (Tm), neodymium (Nd), gadolinium (Gd), europium (Eu), ytterbium ( The fine particle dispersion solution according to claim 1, comprising at least one selected from the group consisting of Yb), samarium (Sm), and cerium (Ce).   The fine particle dispersion solution according to claim 1, wherein the solvent contains a water-soluble polymer and / or a surfactant. A rare earth halide hydrate LnX ₃ .nH ₂ O (Ln is a rare earth element, X is a halogen, n is an integer of 1 to 7) is heated at 100 to 350 ° C. for 1 hour or more to obtain a pre-sintered body. 1 heat treatment;
A second heat treatment for heating the temporary sintered body obtained by the first heat treatment at 400 ° C. or more for 1 hour or more;
LnOX-LnX ₃ manufacturing method of composite particles comprising a. The method for producing LnOX-LnX ₃ composite particles according to claim 4, wherein the heating in the first heat treatment is performed stepwise. A method for producing a fine particle dispersion solution, wherein the LnOX-LnX ₃ composite particles obtained in claim 4 or 5 are charged into a solvent.

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