CN112195026B - Europium-doped beta-tricalcium phosphate fluorescent nano-particles and preparation method and application thereof - Google Patents
Europium-doped beta-tricalcium phosphate fluorescent nano-particles and preparation method and application thereof Download PDFInfo
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- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
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Abstract
The invention discloses europium-doped beta-tricalcium phosphate fluorescent nano-particles and a preparation method and application thereof. The preparation method comprises the following steps: preparing a mixed solution of polyacrylic acid and phosphate ions, and adjusting the pH value to 11-12 by using ammonia water; adding Ca 2+ 、Eu 3+ And mixing the ion mixed solution into a mixed solution of polyacrylic acid and phosphate radical ions through ultrasonic spraying, simultaneously stirring by magnetic force, and then performing freeze drying and high-temperature calcination to obtain the europium-doped beta-tricalcium phosphate fluorescent nano-particles. The invention is Ca 2+ 、Eu 3+ Converting the ion mixed solution into mist-shaped liquid drops; meanwhile, polyacrylic acid is adsorbed on the surface of calcium phosphate (europium) particles through electrostatic interaction, so that the particles are prevented from agglomerating and growing, and the polyacrylic acid plays a role in blocking in the high-temperature calcination process, reduces the agglomeration degree of the particles in the calcination process and inhibits the growth of the particles. The fluorescent nano-particles prepared by the invention have good fluorescence performance and can be used as a fluorescence developer for cell marking.
Description
Technical Field
The invention relates to the field of preparation of fluorescent nanoparticles, in particular to europium-doped beta-tricalcium phosphate fluorescent nanoparticles and a preparation method and application thereof.
Background
Beta-tricalcium phosphate (beta-TCP) is a biological ceramic material with good biocompatibility and degradability, the solubility of the beta-tricalcium phosphate is about 10 to 20 times higher than that of hydroxyapatite, the beta-tricalcium phosphate can be directly chemically bonded with bone tissues, degradation products are nontoxic, rich calcium and phosphorus can be provided for new bone generation, the growth of the new bone is promoted, and the beta-tricalcium phosphate is widely applied to the field of clinical bone repair. Calcium ions in beta-TCP crystal lattices are easily replaced by other metal ions, and rare earth Eu with fluorescence property is doped 3+ Ions can impart unique fluorescent properties to β -TCP. Thus, eu 3+ Doped beta-TCP fluorescenceThe optical nano-particles are expected to become a biosafety and degradable developer and are used in the field of biomedicine.
Research shows that the particle size is less than 200nm, cell phagocytosis is easy, and particularly after the particle size reaches the nanometer level, the particle size shows better tumor targeting capability based on EPR effect (namely, enhanced permeability and retention effect of solid tumor). However, β -TCP is a high temperature phase of calcium phosphate and requires high temperature heat treatment to obtain it. While the high-temperature heat treatment promotes the formation of a beta-TCP crystal phase, the high-temperature heat treatment also causes the growth and agglomeration of the beta-TCP particle size. This is not favorable for the cell pair Eu 3+ Phagocytosis of the doped beta-TCP fluorescent nanoparticles influences the application of biological imaging of the doped beta-TCP fluorescent nanoparticles.
At present, the methods for preparing beta-TCP mainly include solid-phase reaction, chemical precipitation, alcohol compound method, etc. The solid-phase reaction method usually takes calcium hydrogen phosphate dihydrate and calcium carbonate as raw materials, and the calcium hydrogen phosphate dihydrate and the calcium carbonate are prepared through high-temperature solid-phase reaction, the obtained powder has a crystal structure without lattice shrinkage and good crystallinity, but powder grains are coarse (micron-sized), have uneven composition and often have impurity phases; the alcohol compound method is to generate phosphate by utilizing the reaction between calcium alcoholates, and the prepared beta-TCP powder has high purity and good chemical uniformity, but the used organic solvent has toxicity and pollutes the environment; the chemical precipitation method is characterized in that the growth of crystal nuclei is controlled by regulating the mixed concentration of calcium ions and phosphorus ions, and then the target product is obtained by high-temperature calcination, the reaction is simple and easy to operate, the product purity is high, the particles are still easy to agglomerate, and the size of the agglomerated particles is usually more than 500nm. Thus, for Eu 3+ The key of the application of the doped beta-TCP particles as the fluorescent developing agent is that the preparation method is improved, the particle agglomeration is reduced, the particle size is reduced, and the particle nanocrystallization is realized.
Disclosure of Invention
In view of the above, there is a need to provide europium-doped β -tricalcium phosphate fluorescent nanoparticles, and a preparation method and an application thereof, so as to solve the technical problems of large size and easy agglomeration of the existing europium-doped β -tricalcium phosphate fluorescent nanoparticles in the prior art.
The first aspect of the invention provides a preparation method of europium-doped beta-tricalcium phosphate fluorescent nanoparticles, which comprises the following steps:
preparing a mixed solution of polyacrylic acid and phosphate ions, and adjusting the pH value to 11-12 by using ammonia water;
preparation of Ca 2+ 、Eu 3+ An ion mixed solution;
adding the above Ca 2+ 、Eu 3+ And mixing the ion mixed solution into the mixed solution of the polyacrylic acid and the phosphate ions through ultrasonic spraying, simultaneously stirring by magnetic force to obtain milky white suspension, freeze-drying to obtain powder, and calcining at high temperature to obtain the europium-doped beta-tricalcium phosphate fluorescent nano-particles.
The second aspect of the present invention provides a europium-doped β -tricalcium phosphate fluorescent nanoparticle, which is obtained by the method for preparing the europium-doped β -tricalcium phosphate fluorescent nanoparticle provided by the second aspect of the present invention.
The third aspect of the invention provides an application of europium-doped beta-tricalcium phosphate fluorescent nanoparticles, wherein the europium-doped beta-tricalcium phosphate fluorescent nanoparticles are applied to cell fluorescent labeling as a fluorescent developing agent; the europium-doped beta-tricalcium phosphate fluorescent nano-particle is obtained by the preparation method of the europium-doped beta-tricalcium phosphate fluorescent nano-particle provided by the first aspect of the invention.
Compared with the prior art, the invention has the following beneficial effects:
the invention utilizes the ultrasonic cavitation effect to remove Ca 2+ 、Eu 3+ The ion mixed solution is converted into mist-shaped liquid drops, so that the specific surface area of the solution is increased, and the mixing uniformity of the ion mixed solution and the phosphate radical ion solution is improved; meanwhile, polyacrylic acid containing a large amount of carboxylate radicals is adsorbed on the surface of calcium phosphate (europium) particles through electrostatic interaction, and the particles can be prevented from agglomerating and growing up by virtue of a steric effect; in addition, in the high-temperature calcination process, polyacrylic acid chain segments existing on the surfaces of calcium phosphate (europium) particles can play a role in blocking, the agglomeration degree of the particles in the calcination process is reduced, and the growth of the particles is inhibited.
The fluorescent nano-particles prepared by the method are in a nano-scale size, low in agglomeration degree, spherical and good in fluorescence property, and can be used as a fluorescent developer for cell marking.
Drawings
FIG. 1 shows Eu in example 1 3+ X-ray diffraction pattern of doped β -TCP particles;
FIG. 2 shows Eu in example 1 3+ A transmission electron microscope picture of the doped beta-TCP particles;
FIG. 3 shows Eu in example 1 3+ Scanning electron microscope pictures of the doped beta-TCP particles;
FIG. 4 shows Eu in example 1 3+ Fluorescence microscopy pictures of doped beta-TCP particles;
FIG. 5 shows Eu in example 2 3+ X-ray diffraction pattern of doped β -TCP particles;
FIG. 6 shows Eu in example 3 3+ X-ray diffraction pattern of doped β -TCP particles;
FIG. 7 shows Eu in comparative example 1 3+ Scanning electron microscope pictures of the doped beta-TCP particles;
FIG. 8 shows Eu in comparative example 2 3+ Scanning electron microscope pictures of the doped beta-TCP particles;
FIG. 9 is an X-ray diffraction pattern of the product of comparative example 3;
FIG. 10 shows Eu as an application example 1 3+ Fluorescence microscopy pictures of doped beta-TCP granular cell markers.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be described in further detail below with reference to the accompanying drawings and examples. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The first aspect of the invention provides a preparation method of europium-doped beta-tricalcium phosphate fluorescent nanoparticles, which comprises the following steps:
s1, preparing a mixed solution of polyacrylic acid and phosphate ions, and adjusting the pH value to 11-12 by using ammonia water; in the process, polyacrylic acid and diammonium hydrogen phosphate are used as raw materials to prepare a mixed solution of polyacrylic acid and phosphate radical ions; in the mixed solution of polyacrylic acid and phosphate radical ions, the concentration of the phosphate radical ions is 0.06-0.1 mol/L, and the concentration of the polyacrylic acid is 1.0-2.0 mg/ml;
s2 preparation of Ca 2+ 、Eu 3+ An ion mixed solution; in the process, soluble calcium salt and soluble europium salt are used as raw materials to prepare Ca 2+ 、Eu 3+ An ionic mixed solution; further, the soluble calcium salt is one or two of calcium acetate and calcium nitrate, preferably calcium nitrate; the soluble europium salt is one or more of europium acetate and europium nitrate, and is preferably europium nitrate; ca 2+ 、Eu 3+ In ionic mixed solution, ca 2+ 、Eu 3+ The total concentration of ions is 0.09-0.15 mol/L, and the molar ratio of Eu/(Ca + Eu) is (0.001-0.01): 1;
s3 reacting the Ca with 2+ 、Eu 3+ Mixing the ion mixed solution into the mixed solution of the polyacrylic acid and the phosphate radical ions through ultrasonic spraying, simultaneously stirring the solution by magnetic force to obtain milky white suspension, freeze-drying the milky white suspension to obtain powder, and calcining the powder at high temperature to obtain europium-doped beta-tricalcium phosphate fluorescent nano particles; in the process, the ultrasonic spray flow is 1.0 x 10 -6 m 3 /s～2.0×10 -6 m 3 The ultrasonic power is 300-500W, the magnetic stirring speed is 1000-1500 r/min, the molar ratio of (Ca + Eu)/P is 1.5 after the final mixing is finished, the calcining temperature is 800 ℃, and the heat preservation time is 1-3 h. In the process, in order to improve the mixing uniformity, the spraying process and the magnetic stirring process are carried out simultaneously, and after the spraying is finished, powder can be obtained through freeze drying.
In the present invention, it should be noted that the above steps S1 and S2 are not limited in sequence. Steps S1 and S2 may be performed sequentially or simultaneously.
The invention utilizes the ultrasonic cavitation effect to remove Ca 2+ 、Eu 3 The + ion mixed solution is converted into mist-shaped liquid drops, so that the specific surface area of the solution is increased, and the mixing uniformity of the solution and the phosphate radical ion solution is improved; meanwhile, polyacrylic acid containing a large amount of carboxylate radicals is adsorbed on the surface of calcium phosphate (europium) particles through electrostatic interaction, and the particles can be prevented from agglomerating and growing up by virtue of a steric effect; in addition, during the high-temperature calcination, the calcium phosphate (europium) exists on the surface of the calcium phosphate particlesThe polyacrylic acid chain segment can play a role in blocking, so that the agglomeration degree of particles in the calcining process is reduced, and the growth of the particles is inhibited; by adopting higher pH, on one hand, the invention can ensure that liquid drops can be rapidly and completely precipitated when meeting a mixed solution of polyacrylic acid and phosphate radical ions; on the other hand, PAA molecules can be fully protonated, carboxylate radicals in the molecules are exposed, the PAA is guaranteed to have a dispersing effect on precipitate particles, the protonated carboxylate radicals can be combined with the surfaces of the precipitate particles through electrostatic interaction on the surfaces of the particles, and the agglomeration of the particles is prevented through a steric hindrance effect.
The second aspect of the present invention provides a europium-doped β -tricalcium phosphate fluorescent nanoparticle, which is obtained by the preparation method of the europium-doped β -tricalcium phosphate fluorescent nanoparticle provided by the second aspect of the present invention.
The third aspect of the invention provides an application of europium-doped beta-tricalcium phosphate fluorescent nanoparticles, wherein the europium-doped beta-tricalcium phosphate fluorescent nanoparticles are applied to cell fluorescent labeling as a fluorescent developing agent; the europium-doped beta-tricalcium phosphate fluorescent nano-particles are obtained by the preparation method of the europium-doped beta-tricalcium phosphate fluorescent nano-particles provided by the first aspect of the invention.
Example 1
Preparing 100ml of a mixed solution of polyacrylic acid and diammonium hydrogen phosphate, and adjusting the pH value to 11-12 by using ammonia water; wherein the concentration of phosphate ions is 0.06mol/L, and the concentration of polyacrylic acid is 1.0mg/ml;
preparing 100ml of a calcium nitrate and europium nitrate mixed aqueous solution; wherein, ca 2+ 、Eu 3+ The total concentration of ions is 0.09m, the molar ratio Eu/(Ca + Eu) is 0.005;
mixing 100ml of calcium nitrate and europium nitrate mixed aqueous solution into 100ml of polyacrylic acid and diammonium hydrogen phosphate mixed solution through ultrasonic spraying, simultaneously stirring by magnetic force to obtain milky white suspension, freeze-drying to obtain powder, and calcining at high temperature to obtain Eu 3+ Doped beta-TCP particles; wherein the ultrasonic spray flow rate is 1.0 × 10 -6 m 3 The ultrasonic power is 300W, the magnetic stirring speed is 1000r/min, the calcining temperature is 800 ℃, and the temperature is keptThe warm time is 1h.
As shown in fig. 1, the main crystal phase of the product is beta-TCP; as shown in FIG. 2 and Table 1, the particle size obtained by TEM is less than 100nm, the morphology is spherical, the particle is monodisperse and has low agglomeration, and the average particle size obtained by a laser particle sizer is 251nm; as shown in fig. 3, the particle size of the product observed by a scanning electron microscope is less than 100nm, the product is approximately spherical, and the particles are in a dispersed state; as shown in FIG. 4, eu obtained 3+ The doped beta-TCP particles emit strong red fluorescence under the excitation of ultraviolet light.
Example 2
Preparing 100ml of a mixed solution of polyacrylic acid and diammonium hydrogen phosphate, and adjusting the pH value to 11-12 by using ammonia water; wherein the concentration of phosphate ions is 0.08mol/L, and the concentration of polyacrylic acid is 1.5mg/ml;
preparing 100ml of mixed aqueous solution of calcium nitrate and europium nitrate; wherein, ca 2+ 、Eu 3+ The total concentration of ions is 0.12mol/L, and the molar ratio of Eu/(Ca + Eu) is 0.001;
mixing 100ml of calcium nitrate and europium nitrate mixed aqueous solution into 100ml of polyacrylic acid and diammonium hydrogen phosphate mixed solution through ultrasonic spraying, simultaneously stirring by magnetic force to obtain milky white suspension, freeze-drying to obtain powder, and calcining at high temperature to obtain Eu 3+ Doped beta-TCP particles; wherein the ultrasonic spray flow rate is 1.5 × 10 -6 m 3 The ultrasonic power is 400W, the magnetic stirring speed is 1200r/min, the calcining temperature is 800 ℃, and the heat preservation time is 2h.
As shown in fig. 5, the main crystal phase of the product is beta-TCP; as shown in Table 1, the particle size obtained by TEM was less than 100nm, and the average particle size obtained by laser particle sizer was 299nm.
Example 3
Preparing 100ml of a mixed solution of polyacrylic acid and diammonium hydrogen phosphate, and adjusting the pH value to 11-12 by using ammonia water; wherein the concentration of phosphate ions is 0.1mol/L, and the concentration of polyacrylic acid is 2.0mg/ml;
preparing 100ml of a calcium nitrate and europium nitrate mixed aqueous solution; wherein, ca 2+ 、Eu 3+ The total concentration of ions is 0.15mol/L, and the molar ratio of Eu/(Ca + Eu) is 0.01;
mixing 100ml of mixed aqueous solution of calcium nitrate and europium nitrate into 100m by ultrasonic sprayingl in a mixed solution of polyacrylic acid and diammonium hydrogen phosphate, magnetically stirring to obtain a milky white suspension, freeze-drying to obtain powder, and calcining at high temperature to obtain Eu 3+ Doped beta-TCP particles; wherein the ultrasonic spray flow rate is 2.0 × 10 -6 m 3 The ultrasonic power is 500W, the magnetic stirring speed is 1500r/min, the calcining temperature is 800 ℃, and the heat preservation time is 3h.
As shown in fig. 6, the main crystal phase of the product is beta-TCP; as shown in Table 1, the particle size obtained by TEM is about 100nm, and the average particle size obtained by laser particle size analyzer is 304nm.
Comparative example 1
Preparing 100ml of a mixed solution of polyacrylic acid and diammonium hydrogen phosphate, and adjusting the pH value to 11-12 by using ammonia water; wherein the concentration of phosphate ions is 0.06mol/L, and the concentration of polyacrylic acid is 1.0mg/ml;
preparing 100ml of mixed aqueous solution of calcium nitrate and europium nitrate; wherein, ca 2+ 、Eu 3+ The total concentration of ions is 0.09mol/L, and the molar ratio of Eu/(Ca + Eu) is 0.005;
rapidly mixing 100ml of calcium nitrate and europium nitrate mixed aqueous solution into 100ml of polyacrylic acid and diammonium hydrogen phosphate mixed solution, magnetically stirring to obtain milky white suspension, freeze-drying to obtain powder, and calcining at high temperature to obtain Eu 3+ Doped beta-TCP particles; wherein, the magnetic stirring speed is 1000r/min, the calcining temperature is 800 ℃, and the heat preservation time is 1h.
As shown in FIG. 7, the observation of a scanning electron microscope shows that most particles have the size of more than 100nm, are irregular in shape and are in an agglomerated state; as shown in Table 1, the particle size obtained by TEM was about 245nm, and the average particle size measured by laser particle sizer was 597nm.
Comparative example 2
Preparing 100ml of diammonium hydrogen phosphate aqueous solution, and adjusting the pH value to 11-12 by using ammonia water; wherein the concentration of phosphate ions is 0.06mol/L;
preparing 100ml of mixed aqueous solution of calcium nitrate and europium nitrate; wherein, ca 2+ 、Eu 3+ The total concentration of ions is 0.09mol/L, and the molar ratio of Eu/(Ca + Eu) is 0.005;
100ml of mixed aqueous solution of calcium nitrate and europium nitrate is sprayed by ultrasoundMixing with 100ml diammonium hydrogen phosphate solution, magnetically stirring to obtain milky white suspension, freeze drying to obtain powder, and calcining at high temperature to obtain Eu 3+ Doped beta-TCP particles; wherein the ultrasonic spray flow rate is 1.0 × 10 -6 m 3 The magnetic stirring speed is 1000r/min, the calcining temperature is 800 ℃, and the heat preservation time is 1h.
As shown in FIG. 8, the observation of a scanning electron microscope shows that most particles have a size of more than 100nm, are irregular in shape and are in an agglomerated state; as shown in Table 1, the particle size obtained by TEM was about 297nm and the average particle size measured by laser particle sizer was 696nm.
Comparative example 3
Preparing 100ml of a mixed solution of polyacrylic acid and diammonium hydrogen phosphate, and adjusting the pH value to 9-10 by using ammonia water; wherein the concentration of phosphate ions is 0.06M, and the concentration of polyacrylic acid is 1.0mg/ml;
preparing 100ml of a calcium nitrate and europium nitrate mixed aqueous solution; wherein, ca 2+ 、Eu 3+ The total concentration of ions is 0.09M, the molar ratio of Eu/(Ca + Eu) is 0.005;
mixing 100ml of calcium nitrate and europium nitrate mixed aqueous solution into 100ml of polyacrylic acid and diammonium hydrogen phosphate mixed solution through ultrasonic spraying, simultaneously stirring by magnetic force to obtain milky white suspension, freeze-drying to obtain powder, and calcining at high temperature to obtain Eu 3+ Doped beta-TCP particles; wherein the ultrasonic spray flow rate is 1.0 × 10 -6 m 3 The ultrasonic power is 300W, the magnetic stirring speed is 1000r/min, the calcining temperature is 800 ℃, and the heat preservation time is 1h.
As shown in FIG. 9, the main crystal phase of the product is calcium pyrophosphate, and the target product Eu having a higher purity cannot be obtained 3+ Doped beta-TCP particles.
TABLE 1 average particle size of samples measured by transmission electron microscope and laser particle sizer in examples 1 to 3 and comparative examples 1 to 2
(in the process of laser particle sizer testing, the dispersant is water, and the dispersibility is poor, so that the size of the laser particle sizer is larger, and tends to be the size of agglomerates; the effect of reducing the particle size and agglomeration can be illustrated by a transverse comparison between the sizes of the laser particle sizer).
As can be seen from Table 1 and FIGS. 1 to 6, the products obtained in examples 1 to 3 of the present invention are Eu 3+ Doped β -TCP particles with TEM particle size around 100nm illustrate that aspects of the invention can be beneficial in reducing product particle size.
Compared with example 1, comparative example 1 does not mix the mixed aqueous solution of calcium nitrate and europium nitrate into the mixed solution of polyacrylic acid and diammonium hydrogen phosphate by ultrasonic spraying, so that the product obtained in comparative example 1 has a higher particle size, which shows that the ultrasonic spraying is favorable for further reducing the particle size of the product.
Comparative example 2, in which no polyacrylic acid was added, resulted in a higher particle size of the product of comparative example 2 compared to example 1, indicating that the addition of polyacrylic acid facilitates a further reduction in the particle size of the product.
The pH in comparative example 3 was 9 to 10 as compared with example 1, resulting in that the product of comparative example 3 was calcium pyrophosphate as a main crystal phase, and Eu, the target product, having a higher purity, could not be obtained 3+ Doping beta-TCP particles shows that pH has an important influence on the formation of a target product, and if the pH is lower and the alkalinity is insufficient, a pure beta-TCP phase cannot be formed.
Application example 1
Eu synthesized in example 1 3+ Doped beta-TCP particles are used for tumor cell marking. Weighing 1mg of Eu 3+ Dispersing the doped beta-TCP particles in 10ml of deionized water, then adding 6mg of heparin sodium, and obtaining Eu stabilized by the heparin sodium through ultrasonic dispersion treatment 3+ Doping a beta-TCP particle suspension; liver cancer cells (HepG 2) according to 1X 10 5 Inoculating at a density of one well in a glass-bottom culture dish, adding 5% CO in RPMI-1640 medium (containing 10% calf serum and 1% penicillin-streptomycin) 2 Culturing for 24h (37 ℃), sucking out the original culture medium,adding Eu diluted 10 times with fresh culture medium 3+ Doping the beta-TCP particle suspension, continuously culturing for 24h, then sucking out the culture medium in a glass bottom culture dish, washing with PBS, staining cell nuclei by Hoechst33342, and then placing the culture dish under a fluorescence microscope for cell fluorescence imaging. As shown in fig. 10, red fluorescence signals were observed between cells and inside cells, indicating that the nanoparticles have potential as tumor cell markers.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention.
Claims (6)
1. A preparation method of europium-doped beta-tricalcium phosphate fluorescent nanoparticles is characterized by comprising the following steps of:
preparing a mixed solution of polyacrylic acid and phosphate ions, and adjusting the pH value to 11 to 12 by using ammonia water;
preparation of Ca 2+ 、Eu 3+ An ion mixed solution;
adding the Ca 2+ 、Eu 3+ And mixing the ion mixed solution into the mixed solution of polyacrylic acid and phosphate ions through ultrasonic spraying, simultaneously stirring by magnetic force to obtain milky white suspension, freeze-drying to obtain powder, and calcining at high temperature to obtain the europium-doped beta-tricalcium phosphate fluorescent nano-particles.
2. The method for preparing the europium-doped β -tricalcium phosphate fluorescent nanoparticle of claim 1, wherein the concentration of the phosphate ions in the mixed solution of polyacrylic acid and phosphate ions is 0.06 to 0.1mol/L, and the concentration of the polyacrylic acid is 1.0 to 2.0 mg/ml.
3. The method of claim 1, wherein the europium-doped β -tricalcium phosphate fluorescent nanoparticle is prepared, characterized in that the Ca is 2+ 、Eu 3+ In ionic mixed solution, ca 2+ 、Eu 3+ The total concentration of the ions is 0.09 to 0.15mol/L, and the molar ratio of Eu/(Ca + Eu) is (0.001 to 0.01): 1.
4. The method of claim 1, wherein the ultrasonic spray flow rate is 1.0 x 10 -6 m 3 /s~2.0×10 -6 m 3 And/s, the ultrasonic power is 300 to 500W.
5. The method of claim 1, wherein the molar ratio of (Ca + Eu)/P is 1.5 after the mixing.
6. The method for preparing europium-doped β -tricalcium phosphate fluorescent nanoparticles according to claim 1, wherein the calcination temperature is 800 ℃ and the holding time is 1 to 3 hours.
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| CN101343056A (en) * | 2008-07-30 | 2009-01-14 | 宁波大学 | Method for preparing hydroxyapatite nano-powder |
| KR20090112920A (en) * | 2008-04-25 | 2009-10-29 | 한국원자력연구원 | PREPARATION METHOD OF NANO SIZED beta-TRICALCIUM PHOSPHATE POWDERS IN HIGH PURITY USING ELECTRON BEAM IRRADIATION |
| CN105018086A (en) * | 2015-07-03 | 2015-11-04 | 武汉理工大学 | Rare-earth-doped calcium phosphate fluorescent nanoparticles, and preparation method and application thereof |
| CN110182778A (en) * | 2019-04-22 | 2019-08-30 | 武汉理工大学 | A kind of nano-grade hydroxy apatite raw powder's production technology |
| CN110182777A (en) * | 2019-04-22 | 2019-08-30 | 武汉理工大学 | A kind of beta-tricalcium phosphate raw powder's production technology |
| CN110240137A (en) * | 2019-04-22 | 2019-09-17 | 武汉理工大学 | A kind of preparation method of nano hydroxyapatite powder |
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| KR20090112920A (en) * | 2008-04-25 | 2009-10-29 | 한국원자력연구원 | PREPARATION METHOD OF NANO SIZED beta-TRICALCIUM PHOSPHATE POWDERS IN HIGH PURITY USING ELECTRON BEAM IRRADIATION |
| CN101343056A (en) * | 2008-07-30 | 2009-01-14 | 宁波大学 | Method for preparing hydroxyapatite nano-powder |
| CN105018086A (en) * | 2015-07-03 | 2015-11-04 | 武汉理工大学 | Rare-earth-doped calcium phosphate fluorescent nanoparticles, and preparation method and application thereof |
| CN110182778A (en) * | 2019-04-22 | 2019-08-30 | 武汉理工大学 | A kind of nano-grade hydroxy apatite raw powder's production technology |
| CN110182777A (en) * | 2019-04-22 | 2019-08-30 | 武汉理工大学 | A kind of beta-tricalcium phosphate raw powder's production technology |
| CN110240137A (en) * | 2019-04-22 | 2019-09-17 | 武汉理工大学 | A kind of preparation method of nano hydroxyapatite powder |
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