WO2017038712A1 - Fluorophore et son procédé de production, et procédé de bio-imagerie - Google Patents

Fluorophore et son procédé de production, et procédé de bio-imagerie Download PDF

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Publication number
WO2017038712A1
WO2017038712A1 PCT/JP2016/075058 JP2016075058W WO2017038712A1 WO 2017038712 A1 WO2017038712 A1 WO 2017038712A1 JP 2016075058 W JP2016075058 W JP 2016075058W WO 2017038712 A1 WO2017038712 A1 WO 2017038712A1
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phosphor
manganese
earth metal
alkaline earth
metal phosphate
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PCT/JP2016/075058
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English (en)
Japanese (ja)
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稲垣　徹
大観　光徳
雅 石垣
航 上原
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宇部興産株式会社
国立大学法人鳥取大学
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Priority to JP2017537860A priority Critical patent/JPWO2017038712A1/ja
Publication of WO2017038712A1 publication Critical patent/WO2017038712A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
    • C09K11/70—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing phosphorus
    • C09K11/71—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing phosphorus also containing alkaline earth metals

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  • the present invention relates to a phosphor suitable for a biological imaging method, a manufacturing method thereof, and a biological imaging method.
  • the light absorption rate of water and hemoglobin is shown in FIG.
  • the light absorptance 11 of water becomes smaller on the shorter wavelength side than 1200 nm.
  • the light absorption rate 12 of hemoglobin becomes smaller on the longer wavelength side than 700 nm. Therefore, since the living tissue containing these easily transmits near-infrared light having a wavelength of 700 to 1200 nm, this wavelength region is called a so-called “biological window”.
  • a phosphor that emits light in this wavelength region is injected into a living body and localized at a specific site, light emitted from the site can be observed from outside the living body through a window of the living body.
  • Such a method for observing a specific part is a so-called “biological imaging method”.
  • Non-Patent Document 1 describes a phosphor having a composition of Ba 3 (PO 4 ) 2 : Mn 5+ .
  • the peak wavelength of this phosphor is 1191 nm. Since 1191 nm is included in the window of the living body, this phosphor is suitable for the living body imaging method.
  • Non-Patent Document 1 if the particle size of the phosphor is too small, it is filtered by the kidney, and if the particle size of the phosphor is too large, it is filtered by the liver and discharged outside the body. Therefore, it is difficult to perform a stable biological imaging method. Therefore, in order to perform the biological imaging method stably, a more suitable phosphor is required.
  • Some aspects of the present invention have a low light absorption by water, have low toxicity to the living body, or are difficult to be discharged out of the body, and therefore are suitable for a stable in vivo imaging method and production of such a phosphor. It is an object to provide a method and a stable biological imaging method.
  • a first aspect of the present invention includes a manganese-activated alkaline earth metal phosphate, and each valence of phosphorus and manganese of the manganese-activated alkaline earth metal phosphate is pentavalent.
  • the phosphor is characterized in that the alkaline earth metal of the manganese-activated alkaline earth metal phosphate contains 80 mol% or more of Ca.
  • a phosphor containing manganese-activated alkaline earth metal phosphate, each of valences of phosphorus and manganese being pentavalent, and the alkaline earth metal containing 80 mol% or more of Ca is Ba 3 (PO 4 ) 2 :
  • the emission peak shifts to a shorter wavelength side than Mn 5+, light absorption by water is small, and toxicity to a living body is low, which is suitable for a stable living body imaging method.
  • the manganese-activated alkaline earth metal phosphate is M 10-X (HPO 4 ) 2X (PO 4 ) 6-2X (OH) 2 : Mn 5+ , M 10 -X (HPO 4 ) 2X (PO 4 ) 6-2X F 2 : Mn 5+ , M 10-X (HPO 4 ) 2X (PO 4 ) 6-2X Cl 2 : Mn 5+ , M 3 (PO 4 ) 2 : Mn 5+ , M 10 (PO 4 ) 6 O: Mn 5+ , M 4 (PO 4 ) 2 O: Mn 5+ , M (H 2 PO 4 ) 2 .H 2 O: Mn 5+ , M (PO 3 ) 2 : Mn 5+, MHPO 4 ⁇ 2H 2 O: Mn 5+, MHPO 4: Mn 5+, M 2 P 2 O 7: Mn 5+, M 4 P 2 O 9: Mn 5+ and M 8 H 2 (
  • the manganese-activated alkaline earth metal phosphate is M 10-X (HPO 4 ) 2X (PO 4 ) 6-2X (OH) 2 : Mn 5+ and M 3 It is more preferable to have one or more compositions selected from the group of (PO 4 ) 2 : Mn 5+ (provided that M is one or more selected from the group of Ca, Mg, Ba, Sr, and Ca is 80 Including at least mol%, and 0 ⁇ X ⁇ 2.) This is because the emission peak is shifted to the short wavelength side, the water absorption is further reduced, and the emission intensity is increased, so that the emission emitted from outside the living body is further increased.
  • the manganese-activated alkaline earth metal phosphate is Ca 10-X (HPO 4 ) 2X (PO 4 ) 6-2X (OH) 2 : Mn 5+ and Ca 3 It is particularly preferable to have one or more compositions selected from the group of (PO 4 ) 2 : Mn 5+ (provided that 0 ⁇ X ⁇ 2). This is because the emission peak is further shifted to the short wavelength side, water absorption is further reduced, and the emission intensity is further increased, so that the emission emitted from outside the living body is further increased.
  • Scherrer's formula represented by Formula 1 (where K is the Scherrer constant, ⁇ is the X-ray wavelength, ⁇ is the full width at half maximum of the peak (however, in radians), and ⁇ is
  • the crystallite size of the (002) plane is preferably 10 to 200 nm, which is determined using a Bragg angle (half the diffraction angle 2 ⁇ ) and ⁇ represents the average crystallite size. This is because a phosphor having a crystallite size of 10 to 200 nm is difficult to be filtered by the kidney and difficult to be filtered by the liver. Since such a phosphor is difficult to be discharged outside the body, it is suitable for a stable biological imaging method.
  • a second aspect of the present invention relates to a biological imaging method using the phosphor according to the first aspect of the present invention.
  • the phosphor according to the first aspect of the present invention By using the phosphor according to the first aspect of the present invention, light absorption by water is small, toxicity to the living body is weak, or it is difficult to be discharged outside the body, and thus a stable in vivo imaging method can be provided. .
  • a step for performing a phosphor, comprising a manganese-activated alkaline earth metal phosphate is suitable for a stable in vivo imaging method because the emission peak shifts to the short wavelength side, light absorption by water is small, toxicity to the living body is weak, or it is difficult to be discharged outside the body. Such a phosphor can be manufactured.
  • FIG. 2 shows an X-ray diffraction (XRD) pattern of the phosphor obtained in Example 1.
  • FIG. 2 shows a photoluminescence (PL) spectrum of the phosphor obtained in Example 1.
  • the XRD pattern of the fluorescent substance obtained in Example 2 is shown.
  • the comparison of the PL spectrum of the fluorescent substance obtained in Example 2 and Example 1 is shown.
  • the PL excitation spectrum of the fluorescent substance obtained in Example 2 is shown.
  • the XRD pattern of the fluorescent substance obtained in Example 3 is shown.
  • the scanning electron microscope (SEM) image of the fluorescent substance obtained in Example 3 is shown.
  • the PL spectrum of the fluorescent substance obtained in Example 3 is shown.
  • the diffuse reflection spectrum of the fluorescent substance obtained in Example 3 is shown.
  • the phosphor in the present embodiment contains a manganese-activated alkaline earth metal phosphate, each of valences of phosphorus and manganese is pentavalent, and the alkaline earth metal contains 80 mol% of Ca. Including above.
  • the manganese-activated alkaline earth metal phosphate is M 10-X (HPO 4 ) 2X (PO 4 ) 6-2X (OH) 2 : Mn 5+ , M 10-X (HPO 4 ) 2X (PO 4 ) 6-2X F 2 : Mn 5+ , M 10-X (HPO 4 ) 2X (PO 4 ) 6-2X Cl 2 : Mn 5+ , M 3 (PO 4 ) 2 : Mn 5+ , M 10 (PO 4 ) 6 O: Mn 5+ , M 4 (PO 4 ) 2 O: Mn 5+ , M (H 2 PO 4 ) 2 .H 2 O: Mn 5+ , M (PO 3 ) 2 : Mn 5+ , MHPO 4 2H 2 O: Mn 5+ , MHPO 4 : Mn 5+ , M 2 P 2 O 7 : Mn 5+ , M 4 P 2 O 9 : Mn 5+ and M 8
  • the manganese-activated alkaline earth metal phosphate is M 10-X (HPO 4 ) 2X (PO 4 ) 6-2X (OH) 2 : Mn 5+ and M 3 (PO 4 ) 2 : It is more preferable to have at least one composition selected from the group of Mn 5+ . This is because the emission peak shifts to the short wavelength side, the water absorption becomes smaller, and the emission intensity becomes larger.
  • M preferably contains 90 mol% or more of Ca, and most preferably contains 100 mol% of Ca. This is because the emission peak shifts to the short wavelength side, so that the water absorption is further reduced and the emission intensity is particularly increased, so that the emission emitted from outside the living body becomes stronger.
  • pentavalent Mn emits light as an activator.
  • the Mn content is preferably 0.01 to 50 mol%, more preferably 0.1 to 10 mol%, and even more preferably 1 to 8 mol%. If the Mn content is too small, the luminous efficiency is lowered. On the other hand, when the Mn content exceeds 50 mol%, the emission efficiency decreases because the emission centers come close to each other and cancel each other (concentration quenching).
  • the Scherrer equation represented by Equation 1 (where K is the Scherrer constant, ⁇ is the X-ray wavelength, ⁇ is the full width at half maximum of the peak (in radians)), and ⁇ is the Bragg angle (times
  • the crystallite size of the (002) plane is preferably in the range of 10 to 200 nm, which is obtained using (half the folding angle 2 ⁇ ) and ⁇ represents the average crystallite size).
  • the lower limit of the crystallite size is 1 nm or more, more preferably 10 nm or more. This is because the larger the crystallite size, the larger the particle size of the phosphor, and the more difficult the phosphor is filtered by the kidney.
  • the upper limit of the crystallite size is more preferably 100 nm or less, and still more preferably 80 nm or less. This is because the smaller the crystallite size, the smaller the particle size of the phosphor, and the more difficult the phosphor is to be filtered by the liver. Since the phosphor of the present embodiment is not easily discharged outside the body, it is suitable for a stable biological imaging method.
  • the particle size measured using a dynamic light scattering particle size distribution device is preferably in the range of 1 to 100 nm.
  • the lower limit of the particle size is more preferably 10 nm or more, and further preferably 20 nm or more. This is because the larger the particle size of the phosphor, the more difficult it is to be filtered by the kidney.
  • the upper limit of the particle size is more preferably 90 nm or less, still more preferably 80 nm or less. This is because the smaller the particle size of the phosphor, the more difficult it is to be filtered by the liver. Since the phosphor of the present embodiment is not easily discharged outside the body, it is suitable for a stable biological imaging method.
  • a suitable raw material is appropriately selected from each material of M compound, P compound and Mn compound, and weighed and mixed to prepare a mixture of raw materials.
  • M compound known materials such as oxides, carbonates, nitrates and sulfates can be used, but carbonates (including basic carbonates) are preferable.
  • M is at least one selected from the group consisting of Ca, Mg, Ba, and Sr, and contains 80 mol% or more of Ca.
  • Examples of the P compound include diammonium hydrogen phosphate ((NH 4 ) 2 HPO 4 ), ammonium dihydrogen phosphate ((NH 4 H 2 PO 4 )), ammonium phosphate ((NH 4 ) 3 PO 4 ), and the like.
  • Known materials can be used, but diammonium hydrogen phosphate ((NH 4 ) 2 HPO 4 ) is preferred.
  • Mn compound known materials such as oxides, carbonates, nitrates and sulfates can be used, but carbonates (including basic carbonates) are preferable.
  • the M compound, P compound and Mn compound may each be selected from one material as a raw material, or two or more materials may be used in combination as a raw material.
  • the purity of the raw material is preferably 99% by mass or more.
  • the selected raw material is weighed according to the target composition, and the mixing ratio is adjusted.
  • mixing method for example, a known method such as dry mixing using a mortar or wet mixing in which a solvent such as pure water is added can be used.
  • a known device such as a ball mill, a vibration mill, or a rocking mill can be used.
  • the preparation step further includes a drying step of drying the mixture.
  • a drying method for example, a known method such as a spray dryer, heat drying, freeze drying, or natural drying can be used.
  • the preparation step may further include a step of pulverizing the mixture of raw materials. By making the particle size of the mixture of raw materials fine and uniform, a solid phase reaction in the firing step is likely to occur, and a uniform phosphor can be obtained.
  • the target phosphor is produced by firing the mixture of raw materials obtained in the preparation step.
  • Firing conditions such as atmosphere, temperature, and time are appropriately determined according to the selected raw material, the target composition, and the like.
  • the firing atmosphere is preferably air.
  • the firing temperature is generally in the range of 300 ° C. to 1200 ° C.
  • the firing time is generally in the range of 0.5 to 6 hours. Firing may be performed in a plurality of times. In this case, the calcined body obtained by firing may be fired again after being ground and mixed using a mortar or the like.
  • the solid phase method may further include a grinding step for grinding the phosphor after the firing step.
  • a pulverization method for example, a known method such as a planetary ball mill or a jet mill can be used.
  • the pulverization step may further include a step of classifying the pulverized phosphor.
  • a phosphor having an average particle diameter of 100 nm or more and 200 nm or less can be obtained when the maximum distance between two opposing grain boundaries is defined as the particle diameter of the particle. .
  • By controlling the average particle size of the phosphor in this way for example, when the phosphor is injected into the living body as a dispersion, it can be made difficult to be discharged out of the body.
  • liquid phase method an aqueous solution is prepared by dissolving the M compound, P compound and Mn compound in water (preparation step), and the pH of the aqueous solution is adjusted to a range of 7.0 or higher.
  • hydrothermal synthesis step hydroothermal synthesis step.
  • the liquid phase method further includes a step (separation step) of separating the product from the hydrothermal synthesis step using centrifugation, lyophilization, or the like, if necessary.
  • a suitable raw material is appropriately selected from each material of M compound, P compound and Mn compound, weighed and dissolved in water.
  • M is at least one selected from the group consisting of Ca, Mg, Ba, and Sr, and contains 80 mol% or more of Ca.
  • M is most preferably Ca 100 mol% (Ca compound).
  • Ca compound calcium nitrate (Ca (NO 3 ) 2 ), calcium chloride (CaCl 2 ), calcium acetate ((CH 3 COO) 2 Ca) and hydrates thereof can be used. Hydrates are preferred.
  • P compounds include sodium dihydrogen phosphate (NaH 2 PO 4 ), trisodium phosphate (Na 3 PO 4 ), diammonium hydrogen phosphate ((NH 4 ) 2 PO 4 ), ammonium dihydrogen phosphate (NH 4 H 2 PO 4 ) can be used, but sodium dihydrogen phosphate is preferred.
  • Mn compound potassium permanganate (KMn 4 ), manganese nitrate (Mn (NO 3 ) 2 ), manganese chloride (MnCl 2 ), manganese acetate ((CH 3 COO) 2 Mn) and hydrates thereof are used. However, potassium permanganate is preferred.
  • M compound (Ca compound), P compound and Mn compound may each be selected from one material as a raw material, or two or more materials may be used in combination as a raw material.
  • the purity of the raw material is preferably 99% by mass or more.
  • the selected raw materials are weighed according to the target composition, the mixing ratio is adjusted, dissolved in water, and an aqueous solution is prepared.
  • (2-2-2) Hydrothermal synthesis step In the hydrothermal synthesis step, a basic substance is dropped into the aqueous solution prepared in the preparation step, and the pH is adjusted to 7.0 or higher to carry out hydrothermal synthesis.
  • a known material can be used as the basic substance. In this embodiment, sodium hydroxide was used.
  • the pH is preferably 8.0 or more, more preferably 9.5 or more, and particularly preferably 11.0 or more. By adjusting the pH to the above range, the emission intensity of the product (phosphor) obtained by hydrothermal synthesis can be increased.
  • the separation step the product (phosphor) obtained in the hydrothermal synthesis step is subjected to centrifugation, freeze-drying, or the like as necessary.
  • the phosphor can be separated by rotating at a rate of 5000 to 15000 times per minute for 0.5 to 2 hours. More preferably, the centrifugation is performed a plurality of times.
  • the separated material (phosphor) separated by centrifugation is frozen at ⁇ 10 to ⁇ 50 ° C., depressurized to 20 to 40 Pa, and then sublimated at ⁇ 50 to ⁇ 60 ° C. to remove water.
  • a phosphor can be obtained.
  • the phosphor in the present embodiment can be used in the following biological imaging method. That is, the phosphor of the present embodiment is combined with a substance that is selectively localized at a specific site to be observed in the living body and injected into the living body to thereby make the phosphor of the present embodiment a specific site in the living body. To localize. In this state, the phosphor is excited and light emitted from the phosphor is observed from outside the living body.
  • the surface of the phosphor is modified with saccharides or proteins. Glucose is particularly preferable as the saccharide. This is because cancer cells abnormally consume glucose for cell division, so that the phosphor can be localized in the cancer cells.
  • the cancer cells can be observed from outside the body.
  • a method of modifying the surface of the phosphor with a saccharide for example, an amphiphilic coating that coats the surface of the phosphor by adding glucose to the dispersion of the phosphor surface-treated with an amphiphilic polymer and stirring it.
  • a method of attaching glucose to a polymer can be mentioned.
  • a known material can be used as the amphiphilic polymer, and examples thereof include polyethylene glycol (PEG).
  • Example 1 The composition of the target phosphor is Ca 3 (P 0.975 Mn 0.025 O 4 ) 2, and calcium carbonate (CaCO 3 ), ammonium phosphate ((NH 4 ) 2 HPO 4 ) and manganese carbonate (MnCO) are used as raw materials. 3 ) was selected. These raw materials were weighed so that the molar ratio was 60: 39: 1 (mass ratio was 53.3: 45.7: 1) and mixed using a mortar to obtain a mixture of raw materials. The obtained mixture of raw materials was heated in the atmosphere at 400 ° C. for 4 hours, and then fired in the atmosphere at 800 ° C. for 3 hours to obtain a phosphor.
  • CaCO 3 calcium carbonate
  • ammonium phosphate (NH 4 ) 2 HPO 4 )
  • MnCO manganese carbonate
  • Example 2 The composition of the target phosphor is Ca 10 (P 0.985 Mn 0.015 O 4 ) 6 (OH) 2, and calcium carbonate (CaCO 3 ), ammonium phosphate ((NH 4 ) 2 HPO 4 ) and Manganese carbonate (MnCO 3 ) was selected. These raw materials were weighed so that the molar ratio was 57.4: 34.0: 8.6, and mixed using a mortar to obtain a mixture of raw materials. The obtained mixture of raw materials was heated in air at 400 ° C. for 4 hours and then calcined in air at 700 ° C. for 3 hours to obtain a calcined body. The calcined body was pulverized and mixed using a mortar, and then fired at 700 ° C. for 12 hours in the air to obtain a phosphor.
  • CaCO 3 calcium carbonate
  • Ammonium phosphate (NH 4 ) 2 HPO 4 )
  • MnCO 3 Manganese carbonate
  • Example 3 The composition of the target phosphor is Ca 10 (PO 4 ) 6 (OH) 2, and calcium nitrate tetrahydrate (Ca (NO 3 ) 2 .4H 2 O), sodium dihydrogen phosphate (NaH 2 PO) as raw materials 4 ), potassium permanganate (KMnO 4 ) was selected. These raw materials were weighed so that the molar ratio was 57.4: 34.0: 8.6, and dissolved in ion-exchanged water to prepare an aqueous solution. A sodium hydroxide aqueous solution was added dropwise to this aqueous solution to adjust the pH to 11.9, and then hydrothermal synthesis was carried out by holding at 150 ° C. for 6 hours while stirring 500 times per minute in an autoclave. Next, centrifugation was performed 3 times for 1 hour at 12,000 times per minute, and then freeze-dried to obtain a phosphor.
  • Ca 10 (PO 4 ) 6 (OH) 2 calcium nitrate tetrahydrate
  • Example 4 A phosphor was obtained in the same manner as in Example 3 except that the pH was adjusted to 11.1.
  • Example 5 A phosphor was obtained in the same manner as in Example 3 except that the pH was adjusted to 5.0.
  • FIG. 3 shows the PL spectrum of the phosphor obtained in Example 1.
  • the wavelength of the excitation light was 600 nm.
  • the peak wavelength is 1157 nm, which belongs to the 3d-3d core transition ( 1 E ⁇ 3 A 2 ) of Mn 5+ . Therefore, the valence of Mn contained in the phosphor is pentavalent. Since the peak wavelength of the phosphor having the composition of the conventional Ba 3 (PO 4 ) 2 : Mn 5+ is 1191 nm, the phosphor of the present embodiment has less light absorption of water than the conventional one, and FIG. It can be seen that it is suitable for the method.
  • FIG. 5 shows the PL spectrum 13 of the phosphor obtained in Example 2.
  • the wavelength of the excitation light was 600 nm.
  • the peak wavelength of the PL spectrum 13 of the phosphor obtained in Example 2 is also 1157 nm, which is attributed to the 3d-3d core transition ( 1 E ⁇ 3 A 2 ) of Mn 5+ as in Example 1. Therefore, the valence of Mn contained in the phosphor is pentavalent.
  • a PL spectrum 14 of the phosphor obtained in Example 1 is shown in FIG. Since the peak intensity of the PL spectrum 13 of the phosphor obtained in Example 2 is about 10 times the peak intensity of the PL spectrum 14 of the phosphor obtained in Example 1, it was obtained in Example 2. It can be seen that the phosphor is very suitable for biological imaging methods.
  • FIG. 6 shows a PL excitation spectrum of the phosphor obtained in Example 2.
  • the detection wavelength of the PL excitation spectrum was 1157 nm. From the PL excitation spectrum, 2 A 3 ⁇ 1 A 1 (690 nm) and 2 A 3 ⁇ 3 T 1 ( 3 F) (651 nm), which are transitions of Mn 5+ as the emission center, can be confirmed.
  • FIG. 7 show the XRD pattern of the phosphor obtained in Example 3 and the crystal data of Ca 10 (PO 4 ) 6 (OH) 2 of ICSD, respectively. Both agree well, and it can be seen that the obtained phosphor is an almost single phase of Ca 10 (PO 4 ) 6 (OH) 2 . From the above formula 3, the valence of P is pentavalent. From the results of energy dispersive X-ray analysis, it was confirmed that the ratio of Ca and P was 1.55, which was lower than the stoichiometric ratio of 1.67.
  • FIG. 8 shows an SEM image of the phosphor obtained in Example 3. It can be seen from the SEM image that the crystal grows in the c-axis direction.
  • FIG. 9 and 10 show the PL spectrum and diffuse reflection spectrum of the phosphor obtained in Example 3.
  • the wavelength of the excitation light in the PL spectrum was 600 nm.
  • the PL spectral peak wavelength is 1157 nm, which is attributed to the 3d-3d core transition ( 1 E ⁇ 3 A 2 ) of Mn 5+ . Therefore, the valence of Mn contained in the phosphor is pentavalent. According to existing reports, there are transitions of Mn 5+ from ground states 3 A 2 to 3 T 2 , 1 A 1 , 3 T 1 ( 3 F), etc., which are consistent with the diffuse reflectance spectrum results of FIG.
  • Table 1 shows the emission intensity of PL of the phosphors obtained in Example 3, Example 4, and Example 5.
  • the wavelength of the excitation light in the PL spectrum was 600 nm.
  • the emission intensity is the emission intensity at the peak of the PL spectrum, and is expressed as a relative value when the emission intensity of the phosphor obtained in Example 3 is set to 100. It can be seen that the higher the pH, the higher the emission intensity, which is suitable for the biological imaging method.

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Abstract

La présente invention concerne un fluorophore adapté pour un procédé de bio-imagerie stable en raison d'une faible absorption de lumière par l'eau et une faible toxicité pour le corps. Le fluorophore comprend un phosphate de métal alcalino-terreux activé par le manganèse; la valence de chacun du phosphore et du manganèse dans le phosphate de métal alcalino-terreux activé par le manganèse est de cinq, et le métal alcalino-terreux du phosphate de métal alcalino-terreux activé par le manganèse comprend 80 % en moles ou plus de Ca.
PCT/JP2016/075058 2015-08-28 2016-08-26 Fluorophore et son procédé de production, et procédé de bio-imagerie WO2017038712A1 (fr)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2021527339A (ja) * 2018-06-12 2021-10-11 フィジー グループ ビー．ブイ． 太陽放射変換デバイスの為の無機発光物質

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09511520A (ja) * 1994-04-11 1997-11-18 マリンクロッド・メディカル・インコーポレイテッド カルシウム／オキシアニオン含有粒子の微流体化
JP2005307035A (ja) * 2004-04-22 2005-11-04 Toshiba Corp ハロリン酸塩蛍光体、発光素子
CN104449713A (zh) * 2014-11-03 2015-03-25 天津理工大学 一种非稀土掺杂黄色荧光体及其制作方法和应用

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09511520A (ja) * 1994-04-11 1997-11-18 マリンクロッド・メディカル・インコーポレイテッド カルシウム／オキシアニオン含有粒子の微流体化
JP2005307035A (ja) * 2004-04-22 2005-11-04 Toshiba Corp ハロリン酸塩蛍光体、発光素子
CN104449713A (zh) * 2014-11-03 2015-03-25 天津理工大学 一种非稀土掺杂黄色荧光体及其制作方法和应用

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BASSIERE,AURELIE. ET AL.: "How to induce red persistent luminescence in biocompatible Ca3(P04)2", JOURNAL OF MATERIALS CHEMISTRY C, vol. 1, no. 6, 2013, pages 1252 - 1259, XP055374073 *
WU,HAO. ET AL.: "Fabrication and Properties of Rare Earth Phosphors and Their Applications in White-light LED", CHINESE JOURNAL OF LUMINESCENCE, vol. 27, no. 2, 2006, pages 201 - 205 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2021527339A (ja) * 2018-06-12 2021-10-11 フィジー グループ ビー．ブイ． 太陽放射変換デバイスの為の無機発光物質

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