X-ray scintillation rare earth element-doped perovskite quantum dot with stable aqueous phase and biological friendliness and preparation method of X-ray scintillation rare earth element-doped perovskite quantum dot

Abstract

The invention discloses a water-phase-stable and bio-friendly X-ray scintillation rare earth element doped perovskite quantum dot and a preparation method thereof, and belongs to the field of quantum dots. Comprising the following steps: preparing an oil phase precursor solution from CsX, PbX2 OLA and 4-X butyric acid, and carrying out anti-solvent doping and wrapping on the oil phase precursor solution, a CeX3 solution and Brij C10 to obtain the X-ray scintillation CsPbX3: Ce < 3 + > quantum dot. The advantages of higher luminous efficiency, higher water stability, low biotoxicity and the like under X-ray excitation are realized.

Description

Technical Field

[0001] This invention belongs to the field of nanoluminescent materials, specifically relating to a rare earth element Ce that exhibits water-phase bio-friendly X-ray scintillation. 3+ Doped CsPbX3 quantum dots and their preparation methods Background Technology

[0002] The luminescence principle of X-ray scintillators can be divided into three steps: conversion, transport, and luminescence. [1] As shown in Figure 1, during the conversion process, when the photon energy is less than 1 MeV, the interaction between the high-energy photon and the scintillator material lattice is mainly the photoelectric effect and Compton scattering effect; when the photon energy is less than 1 keV, the photoelectric effect plays a major role. Under the action of high-energy photons, electron-hole pairs are generated in the conduction band and valence band, respectively, and the electron-hole pairs are thermalized. [2,3] The conversion process lasts less than 1 ps. Afterwards, during transport, the electrons and holes that ultimately generate excitons migrate within the material. During this migration, electrons and holes may continuously experience energy loss due to defect trapping and non-radiative recombination. This recapture of charge carriers at the bandgap trap levels introduces a significant time delay during the migration phase. This phase is the most difficult to predict because the introduced bandgap levels are primarily caused by point defects, flaws, interfaces, and surfaces in the material. These phenomena are mainly due to insufficient manufacturing processes and have a significant impact on the material's luminescence properties. In the final luminescence stage, luminescence is due to the continuous trapping of electrons and holes at the luminescence center and their radiative recombination.

[0003] Scintillator materials can be classified into internal systems, where the luminescent center is generated by inherent defects in the structural units or the bulk, or external systems, where the luminescent center is provided by doping with ions. Halide perovskites are an excellent choice for luminescent materials due to their high photoluminescence quantum efficiency, wide color gamma coverage, and simple fabrication process. Because the constituent elements of halide perovskites, such as lead, bromine, and iodine, have high atomic numbers and elemental masses, and because the cross-sectional area of ​​the material is approximately proportional to the fourth power of the atomic number, they exhibit high absorption capacity for ionizing radiation.

[0004] Halide perovskite quantum dots possess a unique electronic structure that allows them to exist in a highly radiative triplet state in their excited state, resulting in extremely fast emission. Furthermore, due to the effects of quantum confinement and the increased overlap of electron and hole wave functions, the spatial distribution of the luminescent centers and X-ray-generated excitons can be confined within the Bohr radius of the quantum dot. [24,25]X-ray incident photons interact with heavy atoms (such as Pb, Tl, or Ce) through the photoelectric effect, generating a large number of hot electrons. Simultaneously, these charge carriers rapidly heat from low-energy excitons and can then be transported to defect centers or the working matter to produce radiation. In perovskite quantum dots (QDs), incident X-ray photons with energies below several hundred keV interact primarily with the lattice atoms of the QDs through the photoelectric effect during the initial conversion phase. This process generates a large number of high-energy electrons and holes, and electron transport occurs. Then, the hot electrons and holes are rapidly heated at the edges of the conduction band (CB) and valence band (VB). Finally, the trapping and radiative recombination of electron-hole pairs can be tuned to produce the desired visible light color by adjusting the bandgap energy. Therefore, high-energy X-ray photons can be converted into a large number of low-energy visible photons through direct bandgap radiation in lead halide perovskite QDs.

[0005] However, the stability of perovskite materials in air containing water and oxygen has been a significant challenge, severely limiting their application and commercialization. The low formation energy and ionic properties of perovskites determine their high decomposability and instability in the face of oxygen, light, heat, and especially water. [8-10] To date, several encapsulation methods have demonstrated the ability to improve the water resistance of perovskite quantum dots by forming a surface hydrophobic layer, primarily including oxides. [11-14] Organic polymers [15-17] Inorganic salts [18-21] and metal-organic framework [22，23] It's easy to understand that these additional organic and inorganic materials contribute to the water resistance of perovskite quantum dots by the absence of hydrophilic groups and high decomposition functions, respectively. However, achieving long-term effective water resistance of calcium ion quantum dots solely through organic ligands remains a significant challenge because the binding between organic ligands and quantum dot surface sites is typically weak.

[24] The lack of theoretical research and the unclear mechanism of water resistance have also hindered the further development of water-stable perovskite quantum dots. Recently, Bi et al. reported a method to prevent water molecule penetration by adding a tight ligand barrier around the quantum dots, achieved by partially replacing the original long-chain ligands octanoic acid and OLA with the short-chain ligand 2-aminoethyl sulfide. However, the calcium ion quantum dots could only survive in water for 1 hour.

[25] .

[0006] The main difficulties are:

[0007] 1. The low formation energy and ionic properties of perovskite quantum dots (QDs) determine their high decomposability and instability in the face of oxygen, light, heat, and especially water, limiting their application in the biological field. To address this issue, current methods for improving the water stability of QDs mostly involve encapsulation to form an insulating layer, preventing direct contact between water and the QDs, thereby enhancing their stability in water. This encapsulation method typically involves dissolving a readily soluble polymer in a low-polarity organic solvent, then evaporating the solvent (e.g., using an antisolvent) to encapsulate the QDs, or reacting to generate metal oxides on the QD surface. These two encapsulation methods mean that some water-soluble and biocompatible polymers cannot be directly used for encapsulating perovskite QDs. Instead, they must first be encapsulated in a low-polarity organic solvent to give the QDs water resistance, and then a second encapsulation with a water-soluble and biocompatible polymer in water is required for their application in the biological field. This multi-encapsulation method involves complex reaction processes and cumbersome steps, significantly increasing the size of the encapsulated QDs and limiting their application in the biological field due to their small size. Furthermore, the repeated encapsulation and solvent conversion processes increase the loss of quantum dots.

[0008] 2. The doping process is complex. Current synthesis methods can be broadly classified into two types: hot injection and antisolvent methods. For the hot injection method, taking the synthesis of CsPbBr3 as an example, it typically involves adding a solution to dissolve the dopant ions to a lead precursor solution after preparing the cesium precursor solution, followed by injection into the cesium precursor solution to complete the quantum dot preparation. The preparation process of the dopant ion solution is complex, similar to that of the lead precursor solution. It requires the use of organic ligands (such as oleic acid and oleylamine) to assist in the dissolution of the dopant ion compound, and involves multiple high-temperature stages in a vacuum and nitrogen atmosphere to complete the preparation. Improper handling of the ligands in this environment can easily lead to oxidation and deterioration, resulting in uneven doping or phase separation.

[0009] 3. The luminescence brightness under X-ray excitation is relatively low. This is mainly attributed to energy loss of charge carriers during transport and recombination. After X-rays are absorbed and generate a large number of high-energy electron-hole pairs, these charge carriers are easily captured by defects in the material during the "transport" stage as they migrate towards the luminescence center. These defects mainly originate from point defects, surface or interface flaws in the material itself. Charge carriers captured by defects lose energy through non-radiative recombination and cannot effectively participate in subsequent radiative recombination luminescence.

[0010] To address the aforementioned bottlenecks, this invention focuses on designing a high-brightness, water-phase-doped X-ray scintillation quantum dot and proposing an in-situ synthesis method for bio-friendly quantum dots. Utilizing the bio-friendly, high-brightness, and X-ray scintillation properties of water-phase-doped CsPbX3 perovskite quantum dots, high-brightness cell tracing under X-ray excitation is achieved, providing a foundation for X-ray-based diagnostic and therapeutic systems.

[0011] References

[0012] [1] Nikl M. Scintillation detectors for x-rays[J / OL]. MeasurementScience and Technology, 2006, 17(4): R37-R54. DOI:10.1088 / 0957-0233 / 17 / 4 / R01.

[0013] [2]Rodnyi PA, Dorenbos P, Van Eijk CW E. Energy Loss in InorganicScintillators[J / OL]. physica status solidi (b), 1995, 187(1): 15-29. DOI:10.1002 / pssb.2221870102.

[0014] [3]Vasil'ev A N. Polarization approximation for electron cascade ininsulators after high-energy excitation[J / OL]. Nuclear Instruments andMethods in Physics Research Section B: Beam Interactions with Materials andAtoms, 1996, 107(1-4): 165-171. DOI:10.1016 / 0168-583X(95)01023-8.

[0015] [4]Physical Processes in Inorganic Scintillators | Piotr A. Rodnyi |Tayl[EB / OL]. [2024-04-08]. https: / / www.taylorfrancis.com / books / mono / 10.1201 / 9780138743352 / physical-processes-inorganic-scintillators-piotr-rodnyi.

[0016] [5]Problems related to p-n junctions in silicon | Semantic Scholar[EB / OL]. [2024-04-08]. https: / / www.semanticscholar.org / paper / Problems-related-to-p-n-junctions-in-silicon-Shockley / 2d486106b2750aad676500dac33f66473c9d69e0.

[0017] [6]Robbins D J. On Predicting the Maximum Efficiency of PhosphorSystems Excited by Ionizing Radiation[J / OL]. Journal of The ElectrochemicalSociety, 1980, 127(12): 2694-2702. DOI:10.1149 / 1.2129574.

[0018] [7]Understanding and designing magnetoelectric heterostructuresguided by computation: progresses, remaining questions, and perspectives |npj Computational Materials[EB / OL]. [2024-04-08]. https: / / www.nature.com / articles / s41524-017-0020-4.

[0019] [8]Murty R C. Effective Atomic Numbers of Heterogeneous Materials[J / OL]. Nature, 1965, 207(4995): 398-399. DOI:10.1038 / 207398a0.

[0020] [9]Wide Band Gap Scintillation Materials: Progress in the Technologyand Material Understanding - Nikl - 2000 - physica status solidi (a) - WileyOnline Library[EB / OL]. [2024-04-08]. https: / / onlinelibrary.wiley.com / doi / abs / 10.1002 / 1521-396X%28200004%29178%3A2%3C595%3A%3AAID-PSSA595%3E3.0.CO%3B2-X.

[0021]

[10] Degradation of field emission display phosphors | SemanticScholar[EB / OL]. [2024-04-08]. https: / / www.semanticscholar.org / paper / Degradation-of-field-emission-display-phosphors-Holloway-Trottier / f5261ff98335becd0d0c5ec4b1e1b627cec96ca5.

[0022]

[11] Weber M J. Scintillation: mechanisms and new crystals[J / OL].Nuclear Instruments and Methods in Physics Research Section A: Accelerators,Spectrometers, Detectors and Associated Equipment, 2004, 527(1): 9-14. DOI:10.1016 / j.nima.2004.03.009.

[0023]

[12] Non-proportionality in the scintillation response and the energyresolution obtainable with scintillation crystals | IEEE Journals & Magazine| IEEE Xplore[EB / OL]. [2024-04-09]. https: / / ieeexplore.ieee.org / document / 489415.

[0024]

[13] Gleaming Uranium: An Emerging Emitter for Building X‐rayScintillators - Wang - 2020 - Chemistry – A European Journal - Wiley OnlineLibrary[EB / OL]. [2024-04-09]. https: / / chemistry-europe.onlinelibrary.wiley.com / doi / 10.1002 / chem.201904409.

[0025]

[14] Tyagi M, Rawat S, Kumar G A, et al. A novel versatile phoswichdetector consisting of single crystal scintillators[J / OL]. NuclearInstruments and Methods in Physics Research Section A: Accelerators,Spectrometers, Detectors and Associated Equipment, 2020, 951: 162982. DOI:10.1016 / j.nima.2019.162982.

[0026]

[15] Rutstrom D, Stand L, Koschan M, et al. Europium concentrationeffects on the scintillation properties of Cs4SrI6:Eu and Cs4CaI6:Eu singlecrystals for use in gamma spectroscopy[J / OL]. Journal of Luminescence, 2019,216: 116740. DOI:10.1016 / j.jlumin.2019.116740.

[0027]

[16] Li Y, Shao W, Ouyang X, et al. Scintillation Properties ofPerovskite Single Crystals[J / OL]. The Journal of Physical Chemistry C, 2019,123(28): 17449-17453. DOI:10.1021 / acs.jpcc.9b05269.

[0028]

[17] Xu Q, Shao W, Liu J, et al. Bulk Organic–InorganicMethylammonium Lead Halide Perovskite Single Crystals for Indirect Gamma RayDetection[J / OL]. ACS Applied Materials & Interfaces, 2019, 11(50): 47485-47490. DOI:10.1021 / acsami.9b10367.

[0029]

[18] Song J, Ran P, Liu X, et al. Universal Wet-Chemistry-MethodsSynthesized Novel Halide-Intercalated Perovskites with Reduced ExcitonConfinement for Low-Dose X-ray Scintillation Imaging[J / OL]. Advanced OpticalMaterials, 2024, 12(6): 2302159. DOI:10.1002 / adom.202302159.

[0030]

[19] Quantum confinement for large light output from puresemiconducting scintillators | Applied Physics Letters | AIP Publishing[EB / OL]. [2024-04-09]. https: / / pubs.aip.org / aip / apl / article-abstract / 84 / 22 / 4370 / 116594 / Quantum-confinement-for-large-light-output-from?redirectedFrom=fulltext.

[0031]

[20] X-ray scintillation in lead-free double perovskite crystals |Science China Chemistry[EB / OL]. [2024-04-10]. https: / / link.springer.com / article / 10.1007 / s11426-018-9308-2.

[0032]

[21] Wang C, Yan Z G, Wang Y, et al. All-Inorganic Ruddlesden–PopperPerovskite Cs2CdCl4:Mn for Low-Dose and Flexible X-ray Imaging[J / OL]. ACSMaterials Letters, 2024, 6(4): 1429-1438. DOI:10.1021 / acsmaterialslett.3c01665.

[0033]

[22] Xu H, Liang W, Zhang Z, et al. 2D Perovskite Mn2+-DopedCs2CdBr2Cl2 Scintillator for Low-Dose High-Resolution X-ray Imaging[J / OL].Advanced Materials, 2023, 35(26): 2300136. DOI:10.1002 / adma.202300136.

[0034]

[23] Liu R, Liu Z, Lin C, et al. Indium-doped perovskite-relatedcesium copper halide scintillator films for high-performance X-ray imaging[J / OL]. Photonics Research, 2024, 12(2): 369-376. DOI:10.1364 / PRJ.501477.

[0035]

[24] Excitons in nanoscale systems | Nature Materials[EB / OL]. [2024-04-10]. https: / / www.nature.com / articles / nmat1710.

[0036]

[25] Wang Y, Li M, Chai Z, et al. Perovskite Scintillators for Improved X-ray Detection and Imaging[J / OL]. Angewandte Chemie International Edition, 2023, 62(38): e202304638. DOI:10.1002 / anie.202304638.

[0037]

[26] All-inorganic perovskite nanocrystal scintillators | Nature[EB / OL]. [2024-04-10]. https: / / www.nature.com / articles / s41586-018-0451-1. Summary of the Invention

[0038] The purpose of this invention is to develop and design an aqueous, bio-friendly X-ray scintillation rare earth element-doped CsPbX3:Ce 3+ Quantum dots and their preparation methods.

[0039] A method for preparing water-stable, bio-friendly X-ray scintillation rare-earth element-doped perovskite quantum dots, characterized in that the rare-earth element-doped perovskite quantum dots are rare-earth element-doped CsPbX3:Ce. 3+ Quantum dots, involving the formulation and preparation method of raw materials for precursor solutions, the ratio of dopant elements to precursor solutions and the ratio of encapsulating materials to antisolvents in the synergistic preparation of X-ray scintillation CsPbX3:Ce 3+ Quantum dots specifically include the following:

[0040] (1) Preparation of oil phase precursor liquid: Under natural conditions, according to the molar ratio (1-1.3):1, weigh cesium halide CsX and lead halide PbX2 separately, where X = chlorine, bromine, and iodine, and Pb... 2+ Amount of substance: Measure OLA in a molar ratio of 1:(3-7), then measure 4-X butyric acid in a molar ratio of (1-2):1, where X = chlorine, bromine, iodine; control Pb. 2+Under conditions where the molar concentration is 0.02-0.06 mol / L, the above-mentioned reagent is added to dimethylacetamide (DMA) solvent and stirred while maintaining the liquid temperature in the range of 50-70°C for 5-15 hours in an open environment. After that, a liquid containing white suspension is obtained, which indicates that the preparation of the oil phase precursor is complete. This process requires open insulation to allow a certain amount of solvent to evaporate during the long-term insulation process; otherwise, the precursor will not produce white suspension. This is an important step for the success of this invention.

[0041] In the preparation of the precursor solution, sufficient heating time and open conditions are crucial. If a precursor solution without white suspended matter is used for injection, the luminescence intensity of the generated quantum dots will be significantly affected.

[0042] (2) Bio-friendly Ce of X-ray scintillation 3+ Preparation of doped quantum dots:

[0043] (a) Take deionized water and add CeX3 powder to the deionized water to obtain CeX3 solution;

[0044] (b) Add Brij C10 to the CeX3 solution obtained in step (a) to obtain a mixed solution containing both CeX3 and Brij C10; under natural conditions, stir the mixed solution until homogeneous, and while maintaining stirring, heat the mixed solution to raise the temperature from room temperature to 40-80℃; X = chlorine, bromine or iodine;

[0045] (d) Shake the precursor solution prepared in step (1) until well mixed, and quickly inject it into the mixed solution heated in step (b). Under natural light, it can be seen that after the precursor solution is injected, the transparent mixed solution quickly turns yellow and forms Ce. 3+ Quantum doped solution.

[0046] In further step (b), the volume ratio of Brij C10 to deionized water is 1:(115-140).

[0047] In further step (d), the volume ratio of the precursor solution to the deionized water in step (a) is 1:(5-25).

[0048] In further step (d), the precursor solution Pb 2+ Ce 3+ The molar ratio is 1:(0.05-0.20).

[0049] (3) Purification of quantum dots: The Ce obtained in step (2) is purified. 3+The quantum dot solution is transferred into a centrifuge tube and centrifuged. The centrifuge speed is set to 2,000-10,000 rpm and the centrifugation time is set to 1-10 minutes. After centrifugation, a green supernatant can be seen. Remove the supernatant. A yellow precipitate is found at the bottom of the centrifuge tube. The precipitate is redispersed in deionized water and centrifuged again. The same centrifugation and redispersion process is repeated multiple times according to the same parameters. After this, the quantum dots are purified.

[0050] Further optimization is to ensure that CsX, PbX2, and CeX3 have the same elements.

[0051] The purified quantum dots of this invention are water-stable, bio-friendly perovskite quantum dots, composed of Ce... 3+ CsPbX3 and CsPb2X5 doped and wrapped with Brij C10.

[0052] The perovskite quantum dots obtained in this invention can be used to trace cells under UV-band excitation light in a biological fluorescence microscope, and can also be used to trace deep tissues that cannot be penetrated by ultraviolet light under X-ray excitation.

[0053] High-intensity X-ray scintillation and bio-friendly quantum dots: Compared to oil-phase quantum dots doped with the same rare earth elements, the quantum dots synthesized by this method exhibit higher luminescence efficiency, stronger water stability, and lower biotoxicity when using X-rays as the excitation source, making them more suitable for applications in the biological field (e.g., the human body is largely water-based). Characterization tests and analyses, including spectral analysis, revealed a significant increase in fluorescence signal intensity under X-ray excitation. Utilizing the absorption characteristics of this material under X-rays, it can be used for biological tracing of deep tissues that cannot be penetrated by ultraviolet light. Simultaneously, the quantum dots of this invention can also be used to trace cells under UV-band excitation light in conjunction with a biological fluorescence microscope. Attached Figure Description

[0054] Figure 1 Schematic diagram of quantum dot preparation and cell tracing process.

[0055] Figure 2 Comparison of peak XRD values ​​and peak statistics of mixed-phase quantum dots and standard single-crystal crystals at various doping concentrations.

[0056] Figure 3Characterization of optical properties of aqueous CsPbBr3 quantum dots at various doping concentrations. A. Fluorescence spectra of aqueous CsPbBr3 quantum dots at various doping concentrations compared to oil-based CsPbBr3 quantum dots with similar doping under 405 nm UV excitation. B. Absorption spectra of aqueous CsPbBr3 quantum dots at various doping concentrations compared to oil-based CsPbBr3 quantum dots with similar doping under different doping concentrations. C. Fluorescence intensity curves of aqueous CsPbBr3 quantum dots at various doping concentrations stored in water under 405 nm UV excitation over time. D. Fluorescence spectra of aqueous CsPbBr3 quantum dots at various doping concentrations compared to oil-based CsPbBr3 quantum dots with similar doping under X-ray excitation.

[0057] Figure 4 Comparison of fluorescence lifetimes of CsPbBr3 quantum dots in aqueous phase and oil phase with the same doping concentration at various doping concentrations.

[0058] Figure 5 Cell fluorescence tracing applications using Brij C10-coated versus uncoated aqueous CsPbBr3 quantum dots at the same doping ratio. Detailed Implementation

[0059] The present invention will be further described below with reference to the embodiments, but the present invention is not limited to the following embodiments.

[0060] Example 1 (Ce in aqueous CsPbBr3) 3+ Doping and biological experiments)

[0061] The preparation process is as follows: Figure 1 As shown.

[0062] (1) Preparation of precursor solution

[0063] Under natural conditions, 0.2 mmol of cesium bromide (CsBr) and 0.2 mmol of lead bromide (PbBr2) were weighed out in a 1:1 molar ratio. According to Pb... 2+ The amount of substance: 1 mmol of oleylamine (OLA) was taken at a molar ratio of 1:5. 1 mmol of 4-bromobutyric acid (BBA) was taken at a molar ratio of oleylamine to 4-bromobutyric acid (BBA) of 1:1, to control Pb. 2+ The above-mentioned drug was added to 5 ml of dimethylacetamide (DMA) solvent at a molar concentration of 0.04 mol / L. While magnetically stirring, the liquid temperature was maintained at 60 degrees Celsius for 10 hours. Afterward, a liquid containing a white suspension was obtained, indicating that the precursor solution was complete. The key point is to prepare it in a natural environment, allowing a certain amount of solvent to evaporate during the temperature maintenance process; otherwise, the precursor solution would not produce a white suspension.

[0064] (2) Preparation of bio-friendly Ce for X-ray scintillation 3+ Doped quantum dots

[0065] In the preparation of the precursor solution, sufficient heating time and open conditions are crucial. If a precursor solution without white suspended matter is used for injection, the luminescence intensity of the generated quantum dots will be significantly affected.

[0066] (a) Take 12.5 ml of deionized water and add 0.002 mmol of CeBr3 powder to the deionized water to obtain CeBr3 solution;

[0067] (b) Add 100 μL of Brij C10 to the CeBr3 solution obtained in step (a) to obtain a mixed solution containing both CeBr3 and Brij C10;

[0068] (c) Under natural conditions, use magnetic stirring to stir the mixture obtained in step (b) until homogeneous, and while maintaining stirring, raise the temperature of the mixture from room temperature to 60 degrees Celsius;

[0069] (d) Shake the precursor solution prepared in step (1) until well mixed, and take 1 ml of the precursor solution;

[0070] (e) The precursor solution obtained in step (d) is rapidly injected into the mixed solution in the state of step (c). Under natural light, it can be seen that after the precursor solution is injected, the transparent mixed solution quickly turns yellow.

[0071] In step (a), the volume of deionized water is proportional to the volume of Brij C10 added in step (b). In this example, the ratio of deionized water to Brij C10 is 125:1.

[0072] In step (a), the volume of deionized water is proportional to the volume of precursor solution in step (d). In this example, the ratio of precursor solution to deionized water is 1:12.5.

[0073] In step (a), CeBr3 powder contains Ce 3+ The amount of ionic substances and the amount of Pb in the precursor solution in step (d) 2+ The amounts of ionic substances are proportional; in this example, it is Pb. 2+ Ce 3+ =1:0.05, corresponding to a 5% doping ratio.

[0074] Similarly, according to the Pb in the precursor solution 2+ Amount of ionic substance: Ce 3+ Different Ce ratios were prepared using molar ratios of 1:0.08, 1:0.10, 1:0.15, and 1:0.20. 3+ Quantum dots with doping levels (corresponding to 8%, 10%, 15%, and 20% doping, respectively).

[0075] (3) Purification of quantum dots

[0076] Under natural conditions, once the yellow liquid obtained in step two has cooled to room temperature, take several centrifuge tubes and evenly transfer the yellow liquid into 5ml centrifuge tubes. Set the centrifuge speed to 5,000 rpm and the centrifugation time to 10 minutes. After centrifugation using the above parameters, a green supernatant will be visible, and a yellow precipitate will be present at the bottom of the centrifuge tube. Remove the supernatant and redisperse the precipitate in 1ml of deionized water. During dispersion, an ultrasonic shaker should be used to assist in the dispersion process. Then, following step three and using the same parameters, perform two additional centrifugation and redisperation processes, thus achieving the purification of quantum dots.

[0077] After preparing quantum dots with different doping concentrations, the quantum dots doped with 0% CeBr3, 5%, 8%, 10%, 15%, and 20% CeBr3 were characterized.

[0078] Figure 2 The images show the characterization of quantum dot structures with different doping concentrations using X-ray diffraction. The images reveal a two-dimensional structure of CsPb₂Br₅ at approximately 12 degrees, and three-dimensional structures of CsPbBr₃ at approximately 21.5 and 30.5 degrees. This indicates that the product structure is a composite of two-dimensional (2D) and three-dimensional (3D) structures, including both CsPbBr₃ and CsPb₂Br₅.

[0079] Figure 3 The fluorescence intensity of aqueous quantum dots with different doping ratios and oil-phase quantum dots with an 8% doping ratio was compared under UV excitation. The results show that the oil-phase doped quantum dots emit stronger light under UV excitation than the aqueous quantum dots of this invention. However, the luminescence of the aqueous quantum dots of this invention is not weak either, and among all aqueous quantum dots, those doped with 5% Ce are the most luminescent. 3+ The quantum dots have the highest luminescence intensity; Figure 3 Figure B shows a comparison of the absorption curves of aqueous quantum dots with different doping ratios and oil-phase quantum dots with an 8% doping ratio. It shows that the absorption peak characteristics of both oil-phase quantum dots and aqueous quantum dots synthesized in this invention are consistent with the absorption characteristics of cesium lead bromine quantum dots, further proving that the quantum dots synthesized in this invention are perovskite quantum dots composed of cesium lead bromine. Figure 3 The figure compares the luminescence intensity of aqueous quantum dots with different doping ratios and oil quantum dots with an 8% doping ratio when stored in water. As can be seen from the figure, the aqueous quantum dots synthesized by the present invention have a significantly longer stable luminescence time in water than the oil quantum dots synthesized by the hot injection method, which proves the water stability of the quantum dots of the present invention. Figure 3The fluorescence intensity of aqueous quantum dots with different doping ratios and oil quantum dots with an 8% doping ratio under X-ray excitation was compared in Figure D. As can be seen from the figure, the fluorescence intensity of aqueous quantum dots synthesized by the present invention under X-ray excitation is much higher than that of oil quantum dots with an 8% doping ratio under X-ray excitation, and the optimal X-ray fluorescence intensity can be achieved under the condition of 5% doping concentration.

[0080] Figure 4 A comparison of the fluorescence lifetime of CsPbBr3 quantum dots in aqueous phase and oil phase with similar doping concentrations. This figure shows that the synthesis and doping methods of this invention significantly increase the fluorescence lifetime of the quantum dots, which means that the quantum dots have fewer surface defects.

[0081] (4) Select RAW264.7 cells in the logarithmic growth phase and seed them in glass-bottomed cell culture dishes with a diameter of 15 mm. Place the cells in a constant temperature incubator at 37°C and 5% CO2 for 24 hours. When the cell confluence reaches about 70%, proceed with subsequent experiments.

[0082] The experiment was divided into two groups: the CsPbBr3@Brij C10 group (i.e., the aqueous stable quantum dots synthesized in this invention) and a control group without CsPbBr3 encapsulation (equivalent to not adding Brij C10, but adding the corresponding CeBr3 for doping). The quantum dot concentration of each experimental group was diluted to 100 μmol / L using complete culture medium (containing fetal bovine serum, penicillin-streptomycin solution, and Gibco's DMEM aqueous medium). The culture medium for RAW264.7 cells was aspirated, and the cells were washed twice with PBS buffer (pre-warmed to 37°C, containing aqueous solutions of Na₂HPO₄, KH₂PO₄, NaCl, and KCl). Then, 1 ml of prepared quantum dot solution was added to each group of cells (four culture dishes per experimental group). Cells underwent phagocytosis experiments in the quantum dot solution, and samples were collected at 1 hour, 2 hours, 4 hours, and 24 hours. The culture medium was aspirated, and the cells were washed twice again with pre-warmed PBS to remove unphagocytosed quantum dots to the maximum extent. Background fluorescence was reduced, and then 1 ml of fresh complete culture medium was added. The samples were placed on the stage of a confocal microscope, the excitation wavelength was set to 336 nm, and the phagocytosis of quantum dots by cells in each group was observed and recorded under a 40X microscope.

[0083] Figure 5This study demonstrates the application of CsPbBr3@Brij C10 in cell fluorescence tracing and compares the fluorescence loss at different time points. The figures show that while fluorescence was observed in the uncoated quantum dots, the overall fluorescence was weak at different time points. In contrast, the coated quantum dots exhibited stronger overall fluorescence intensity, and their fluorescence decay was not significant over the 24-hour period. This further demonstrates the necessity and effectiveness of coating with Brij C10.

[0084] This invention improves the fluorescence intensity of quantum dots under X-rays by doping with the rare earth element Ce, and the effectiveness has been demonstrated through experimental comparison. Furthermore, to enable its application in the biological field, it is encapsulated with bio-friendly Brij C10, improving its compatibility in cellular environments (i.e., environments where water is used as a solvent and various substances necessary for cell survival and reproduction are dissolved). As shown in the attached figures, compared to unencapsulated quantum dots, encapsulated quantum dots exhibit enhanced luminescence intensity in cellular environments and maintain fluorescence for a longer period, thus demonstrating its potential for biotracking in deep tissues.

[0085] Example 2 (Ce in aqueous CsPbI3) 3+ Doping and biological experiments)

[0086] (1) Preparation of precursor solution

[0087] Under natural conditions, 0.2 mmol of cesium iodide (CsI) and 0.2 mmol of lead iodide (PbI₂) were weighed out in a 1:1 molar ratio. According to Pb... 2+ The amount of substance: 1 mmol of oleylamine (OLA) was taken at a molar ratio of 1:5. 1 mmol of 4-iodobutyric acid was taken at a molar ratio of oleylamine to 4-iodobutyric acid of 1:1, to control Pb. 2+ The above-mentioned drug was added to 5 ml of dimethylacetamide (DMA) solvent at a molar concentration of 0.04 mol / L. While magnetically stirring, the liquid temperature was maintained at 60 degrees Celsius for 10 hours. Afterward, a liquid containing a white suspension was obtained, indicating that the precursor solution was complete. The key point is to prepare it in a natural environment, allowing a certain amount of solvent to evaporate during the temperature maintenance process; otherwise, the precursor solution would not produce a white suspension.

[0088] (2) Preparation of bio-friendly Ce for X-ray scintillation 3+ Doped quantum dots

[0089] In the preparation of the precursor solution, sufficient heating time and open conditions are crucial. If a precursor solution without white suspended matter is used for injection, the luminescence intensity of the generated quantum dots will be significantly affected.

[0090] (a) Take 12.5 ml of deionized water and add 0.002 mmol of CeI3 powder to the deionized water to obtain a CeI3 solution;

[0091] (b) Add 100 μL of Brij C10 to the CeI3 solution obtained in step (a) to obtain a mixed solution containing both CeI3 and Brij C10;

[0092] (c) Under natural conditions, use magnetic stirring to stir the mixture obtained in step (b) until homogeneous, and while maintaining stirring, raise the temperature of the mixture from room temperature to 60 degrees Celsius;

[0093] (d) Shake the precursor solution prepared in step (1) until well mixed, and take 1 ml of the precursor solution;

[0094] (e) The precursor solution obtained in step (d) is rapidly injected into the mixed solution in the state of step (c). Under natural light, it can be seen that after the precursor solution is injected, the transparent mixed solution quickly turns yellow.

[0095] In step (a), the volume of deionized water is proportional to the volume of Brij C10 added in step (b). In this example, the ratio of deionized water to Brij C10 is 125:1.

[0096] In step (a), the volume of deionized water is proportional to the volume of precursor solution in step (d). In this example, the ratio of precursor solution to deionized water is 1:12.5.

[0097] In step (a), CeI3 powder contains Ce 3+ The amount of ionic substances and the amount of Pb in the precursor solution in step (d) 2+ The amounts of ionic substances are proportional; in this example, it is Pb. 2+ Ce 3+ =1:0.05, corresponding to a 5% doping ratio.

[0098] Similarly, according to the Pb in the precursor solution 2+ Amount of ionic substance: Ce 3+ Different Ce ratios were prepared using molar ratios of 1:0.08, 1:0.10, 1:0.15, and 1:0.20. 3+ Quantum dots with doping levels (corresponding to 8%, 10%, 15%, and 20% doping, respectively).

[0099] (3) Purification of quantum dots

[0100] Under natural conditions, once the yellow liquid obtained in step two has cooled to room temperature, take several centrifuge tubes and evenly transfer the yellow liquid into 5ml centrifuge tubes. Set the centrifuge speed to 5,000 rpm and the centrifugation time to 10 minutes. After centrifugation, remove the supernatant and redisperse the precipitate in 1ml of deionized water. During dispersion, an ultrasonic shaker should be used to assist in the dispersion process. Then, following step three, perform two more centrifugation and redispersion processes with the same parameters. After this, the quantum dots are purified.

[0101] (4) Select RAW264.7 cells in the logarithmic growth phase and seed them in glass-bottomed cell culture dishes with a diameter of 15 mm. Place the cells in a constant temperature incubator at 37°C and 5% CO2 for 24 hours. When the cell confluence reaches about 70%, proceed with subsequent experiments.

[0102] The experiment was divided into two groups: the CsPbI3@Brij C10 group (i.e., the aqueous stable quantum dots synthesized in this invention) and a control group without CsPbI3 encapsulation (equivalent to not adding Brij C10, but adding the corresponding CeI3 for doping). The quantum dot concentration of each experimental group was diluted to 100 μmol / L using complete culture medium (containing fetal bovine serum, penicillin-streptomycin solution, and Gibco's DMEM aqueous medium). The culture medium for RAW264.7 cells was aspirated, and the cells were washed twice with PBS buffer (pre-warmed to 37°C, containing aqueous solutions of Na₂HPO₄, KH₂PO₄, NaCl, and KCl). Then, 1 ml of prepared quantum dot solution was added to each group of cells (four culture dishes per experimental group). Cells underwent phagocytosis experiments in the quantum dot solution, and samples were collected at 1 hour, 2 hours, 4 hours, and 24 hours. The culture medium was aspirated, and the cells were washed twice again with pre-warmed PBS to remove unphagocytosed quantum dots to the maximum extent. Background fluorescence was reduced, and then 1 ml of fresh complete culture medium was added. The samples were placed on the stage of a confocal microscope, the excitation wavelength was set to 336 nm, and the phagocytosis of quantum dots by cells in each group was observed and recorded under a 40X microscope.

[0103] The effect is similar to that of Example 1, with fluorescence enhancement.

[0104] Example 3 (Ce in aqueous CsPbCl3) 3+ Doping and biological experiments)

[0105] (1) Preparation of precursor solution

[0106] Under natural conditions, 0.2 mmol of cesium chloride (CsCl) and 0.2 mmol of lead chloride (PbCl2) were weighed out in a 1:1 molar ratio. According to Pb... 2+ The amount of substance: 1 mmol of oleylamine (OLA) was taken at a molar ratio of 1:5. 1 mmol of 4-chlorobutyric acid was taken at a molar ratio of oleylamine to 4-chlorobutyric acid of 1:1, to control Pb. 2+ The above-mentioned drug was added to 5 ml of dimethylacetamide (DMA) solvent at a molar concentration of 0.04 mol / L. While magnetically stirring, the liquid temperature was maintained at 60 degrees Celsius for 10 hours. Afterward, a liquid containing a white suspension was obtained, indicating that the precursor solution was complete. The key point is to prepare it in a natural environment, allowing a certain amount of solvent to evaporate during the temperature maintenance process; otherwise, the precursor solution would not produce a white suspension.

[0107] (2) Preparation of bio-friendly Ce for X-ray scintillation 3+ Doped quantum dots

[0108] In the preparation of the precursor solution, sufficient heating time and open conditions are crucial. If a precursor solution without white suspended matter is used for injection, the luminescence intensity of the generated quantum dots will be significantly affected.

[0109] (a) Take 12.5 ml of deionized water and add 0.002 mmol of CeCl3 powder to the deionized water to obtain a CeCl3 solution;

[0110] (b) Add 100 μL of Brij C10 to the CeCl3 solution obtained in step (a) to obtain a mixed solution containing both CeCl3 and Brij C10;

[0111] (c) Under natural conditions, use magnetic stirring to stir the mixture obtained in step (b) until homogeneous, and while maintaining stirring, raise the temperature of the mixture from room temperature to 60 degrees Celsius;

[0112] (d) Shake the precursor solution prepared in step (1) until well mixed, and take 1 ml of the precursor solution;

[0113] (e) The precursor solution obtained in step (d) is rapidly injected into the mixed solution in the state of step (c). Under natural light, it can be seen that after the precursor solution is injected, the transparent mixed solution quickly turns yellow.

[0114] In step (a), the volume of deionized water is proportional to the volume of Brij C10 added in step (b). In this example, the ratio of deionized water to Brij C10 is 125:1.

[0115] In step (a), the volume of deionized water is proportional to the volume of precursor solution in step (d). In this example, the ratio of precursor solution to deionized water is 1:12.5.

[0116] In step (a), the CeCl3 powder contains Ce 3+ The amount of ionic substances and the amount of Pb in the precursor solution in step (d) 2+ The amounts of ionic substances are proportional; in this example, it is Pb. 2+ Ce 3+ =1:0.05, corresponding to a 5% doping ratio.

[0117] Similarly, according to the Pb in the precursor solution 2+ Amount of ionic substance: Ce 3+ Different Ce ratios were prepared using molar ratios of 1:0.08, 1:0.10, 1:0.15, and 1:0.20. 3+ Quantum dots with doping levels (corresponding to 8%, 10%, 15%, and 20% doping, respectively).

[0118] (3) Purification of quantum dots

[0119] Under natural conditions, once the yellow liquid obtained in step two has cooled to room temperature, take several centrifuge tubes and evenly transfer the yellow liquid into 5ml centrifuge tubes. Set the centrifuge speed to 5,000 rpm and the centrifugation time to 10 minutes. After centrifugation using the above parameters, remove the supernatant and redisperse the precipitate in 1ml of deionized water. During dispersion, an ultrasonic shaker should be used to assist in the dispersion process. Then, following step three, perform two more centrifugation and redispersion processes using the same parameters. After this, the quantum dots are purified.

[0120] (4) Select RAW264.7 cells in the logarithmic growth phase and seed them in glass-bottomed cell culture dishes with a diameter of 15 mm. Place the cells in a constant temperature incubator at 37°C and 5% CO2 for 24 hours. When the cell confluence reaches about 70%, proceed with subsequent experiments.

[0121] The experiment was divided into two groups: the CsPbCl3@Brij C10 group (i.e., the aqueous stable quantum dots synthesized in this invention) and a control group without CsPbCl3 encapsulation (equivalent to not adding Brij C10, but adding the corresponding CeCl3 for doping). The quantum dot concentration of each experimental group was diluted to 100 μmol / L using complete culture medium (containing fetal bovine serum, penicillin-streptomycin solution, and Gibco's DMEM aqueous medium). The culture medium for RAW264.7 cells was aspirated, and the cells were washed twice with PBS buffer (pre-warmed to 37°C, containing aqueous solutions of Na₂HPO₄, KH₂PO₄, NaCl, and KCl). Then, 1 ml of prepared quantum dot solution was added to each group of cells (four culture dishes per experimental group). Cells underwent phagocytosis experiments in the quantum dot solution, and samples were collected at 1 hour, 2 hours, 4 hours, and 24 hours. The culture medium was aspirated, and the cells were washed twice again with pre-warmed PBS to remove unphagocytosed quantum dots to the maximum extent. Background fluorescence was reduced, and then 1 ml of fresh complete culture medium was added. The samples were placed on the stage of a confocal microscope, the excitation wavelength was set to 336 nm, and the phagocytosis of quantum dots by cells in each group was observed and recorded under a 40X microscope.

[0122] The effect is similar to that of Example 1, with fluorescence enhancement.

[0123] Comparative Example 4 (Ce in oil phase CsPbBr3) 3+ Doping)

[0124] (1) Preparation of cesium oleate precursor solution

[0125] (a) Add 1.25 mmol of cesium carbonate and 1.5 mL of oleic acid to a three-necked flask containing 15 mL of octadecene;

[0126] (b) Under magnetic stirring and vacuum conditions, heat the mixture in the three-necked flask of step (a) to 100 degrees Celsius and maintain it for 1 hour;

[0127] (c) After completing step (b), the mixture is purged three times with argon gas, and then heated to 150 degrees Celsius under argon protection until the cesium carbonate is completely dissolved. This indicates that the cesium oleate precursor solution is ready. The cesium oleate precursor solution must be maintained at 150 degrees Celsius before synthesizing quantum dots.

[0128] (2) Preparation of cerium oleate solution

[0129] (a) Add 1.8 mmol of cerium bromide to a three-necked flask containing 10 mL of methanol;

[0130] (b) Place the flask containing the mixture obtained in step (a) in an ultrasonic cleaner for 10 minutes to dissolve the CeBr3 powder with ultrasonic assistance.

[0131] (c) After adding 10 mL of oleic acid to the flask that completed step (b), heat the mixture to 80 degrees Celsius under argon protection. After the methanol has completely evaporated, cool the solution to room temperature to obtain a clear cerium oleate solution.

[0132] (3) Preparation of Ce in oil phase X-ray scintillation 3+ Doped quantum dots

[0133] (a) Take 1.656 mmol lead bromide, 5 ml oleylamine, 5 ml oleic acid and 800 μl cerium oleate solution obtained in step (2) and add them into a three-necked flask containing 50 ml octadecene;

[0134] (b) Heat the mixture from step (a) under vacuum to 100 degrees Celsius and hold for 60 minutes;

[0135] (c) The mixture from step (b) is purged three times with argon gas. Then, under argon protection, the mixture is heated to 160 degrees Celsius until the lead bromide powder is completely dissolved.

[0136] (d) Take 5 ml of the cesium oleate precursor solution obtained in step (1) and quickly inject it into the flask containing the mixture in step (c). After reacting for 10 seconds, place the flask in an ice water bath until the temperature of the solution in the flask drops to room temperature.

[0137] (4) Purification of quantum dots

[0138] Under natural conditions, the liquid obtained in step (3) was uniformly transferred into 5 ml centrifuge tubes. The centrifuge speed was set to 8,000 rpm and the centrifugation time was set to 10 minutes. After centrifugation according to the above centrifugation parameters, the supernatant was removed and the precipitate was redispersed in 10 ml of n-hexane. The same centrifugation parameters were then used to perform two more centrifugation and redispersion processes, after which the quantum dots were purified.

Claims

1. A method for preparing water-stable, bio-friendly X-ray scintillation rare-earth element-doped perovskite quantum dots, characterized in that, The rare earth element-doped perovskite quantum dots are rare earth element-doped CsPbX3:Ce 3+ Quantum dots, involving the formulation and preparation method of raw materials for precursor solutions, the ratio of dopant elements to precursor solutions and the ratio of encapsulating materials to antisolvents in the synergistic preparation of X-ray scintillation CsPbX3:Ce 3+ Quantum dots specifically include the following: (1) Preparation of oil phase precursor liquid: Under natural conditions, according to the molar ratio (1-1.3):1, weigh cesium halide CsX and lead halide PbX2 separately, where X = chlorine, bromine, and iodine, and Pb... 2+ Amount of substance: Measure OLA in a molar ratio of 1:(3-7), then measure 4-X butyric acid in a molar ratio of (1-2):1, where X = chlorine, bromine, iodine; control Pb. 2+ Under conditions where the molar concentration is 0.02-0.06 mol / L, the above-mentioned drug is added to dimethylacetamide (DMA) solvent and stirred while maintaining the liquid temperature in the range of 50-70℃, and the open reaction is maintained for 5-15 hours; after that, a liquid containing white suspension is obtained, which indicates that the preparation of the oil phase precursor is complete. (2) Bio-friendly Ce of X-ray scintillation 3+ Preparation of doped quantum dots: (a) Take deionized water and add CeX3 powder to the deionized water to obtain CeX3 solution; (b) Add Brij C10 to the CeX3 solution obtained in step (a) to obtain a mixed solution containing both CeX3 and Brij C10; under natural conditions, stir the mixed solution until homogeneous, and while maintaining stirring, heat the mixed solution to raise the temperature from room temperature to 40-80℃; X = chlorine, bromine or iodine; (d) Shake the precursor solution prepared in step (1) until well mixed, and quickly inject it into the mixed solution heated in step (b). Under natural light, it can be seen that after the precursor solution is injected, the transparent mixed solution quickly turns yellow and forms Ce. 3+ Quantum doped solution; (3) Purification of quantum dots: The Ce obtained in step (2) is purified. 3+ The quantum dot solution is transferred into a centrifuge tube and centrifuged. After centrifugation, a green supernatant can be seen. The supernatant is removed, and a yellow precipitate is found at the bottom of the centrifuge tube. The precipitate is redispersed in deionized water and centrifuged again. This process of centrifugation and redispersion is repeated multiple times to achieve the purification of quantum dots.

2. The method according to claim 1, characterized in that, In step (b), the volume ratio of Brij C10 to deionized water is 1:(115-140). In step (d), the volume ratio of the precursor solution to the deionized water in step (a) is 1:(5-25). In step (d), the precursor solution Pb 2+ Ce 3+ The molar ratio is 1:(0.05-0.20), preferably 1:0.

05.

3. The method according to claim 1, characterized in that, Step (3) Set the centrifuge speed to 2,000-10,000 rpm and the centrifugation time to 1-10 minutes.

4. The method according to claim 1, characterized in that, The X element is the same in CsX, PbX2, and CeX3.

5. The method according to claim 1, characterized in that, Quantum dots are composed of Ce 3+ CsPbX3 and CsPb2X5 doped and wrapped with Brij C10.

6. Aqueous-phase stable, bio-friendly X-ray scintillation rare-earth element-doped perovskite quantum dots prepared by the method according to any one of claims 1-5.

7. The application of the aqueous-phase stable, bio-friendly X-ray scintillation rare-earth element-doped perovskite quantum dots prepared according to any one of claims 1-5, for tracing cells under UV-band excitation light in conjunction with a biological fluorescence microscope; and the use of the quantum dots under X-ray excitation for biological tracing of deep tissues that cannot be penetrated by ultraviolet light.

8. The application according to claim 7, wherein the application is performed under aqueous conditions.

Images