Application of CuUiO-66@TiO2 composite nanomaterial in detection of beta amyloid
By preparing CuUiO-66@TiO2 composite nanomaterials and utilizing the core-shell heterojunction structure to enhance the Raman signal, the problems of insufficient sensitivity and stability in traditional detection methods were solved, and high-sensitivity and stable β-amyloid protein detection was achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- NINGBO FIRST HOSPITAL
- Filing Date
- 2025-12-16
- Publication Date
- 2026-04-10
AI Technical Summary
Existing methods for detecting β-amyloid protein are insufficient in terms of sensitivity and stability, making it difficult to achieve rapid and accurate clinical testing.
CuUiO-66@TiO2 composite nanomaterials were used to prepare CuUiO-66 nanoparticles by solvothermal and sol-gel methods, and TiO2 shells were grown in situ on their surfaces to form core-shell heterojunctions. These heterojunctions synergistically modulate the electronic structure and interfacial electric field, thereby enhancing the Raman signal.
It achieves highly sensitive and stable detection of β-amyloid protein, with a detection limit as low as 10⁻⁹ mg/mL, and has excellent detection universality and chemical stability, making it suitable for clinical trace protein detection.
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Figure CN121347485B_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The application relates to a beta-amyloid detection material, in particular to application of a CuUiO-66@TiO2 composite nanomaterial in beta-amyloid detection. BACKGROUND
[0002] Alzheimer's disease (AD) is insidious in the course, and it is difficult to identify in the early stage. Early intervention is the key to diagnosis and treatment, so higher requirements are put forward for the early accurate diagnosis of AD. AD biomarkers refer to biomolecules closely related to the disease detected in body fluid samples, which are involved in the pathophysiological process of disease occurrence and development, including beta-amyloid protein (Aβ), tau protein, neurofilament light chain protein (NfL), etc. Among them, Aβ protein can be used for screening, diagnosis, staging, disease progression prediction and monitoring drug efficacy of AD. Therefore, developing a rapid, high-sensitivity, high-specificity, high-stability Aβ detection method has become an urgent need in the field of precision medicine.
[0003] Traditional Aβ detection methods mainly include enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence immunoassay (ECLIA), fluorescence-based biosensors, single molecule array (Simoa), etc. ELISA has high accuracy and specificity, but the instrument equipment is expensive, the sample processing process is complex, the reaction time is long, and professional operators are needed, so it is difficult to realize rapid on-site detection. Traditional immunodetection techniques have limited sensitivity for detecting low-concentration molecules, making it difficult to achieve accurate detection of complex body fluids such as blood. In summary, these methods have obvious limitations in clinical real-time monitoring, detection of complex samples and large-scale screening.
[0004] Surface-Enhanced Raman Spectroscopy (SERS) technology provides a new possibility for the identification of Aβ protein due to its fingerprint identification ability, high sensitivity, non-destructive detection and fast response. The enhancement effect of SERS signal is highly dependent on the performance of the substrate material. The development of SERS active substrate with high enhancement factor, good uniformity and stability is the key to realize the accurate detection of trace markers. In recent years, the composite system of metal-organic framework (MOF) and semiconductor material has attracted widespread attention in the design of SERS substrate due to its adjustable energy band structure and excellent charge separation ability. Through ion doping and heterojunction engineering to optimize the interface characteristics of the material, the SERS performance can be further improved, which provides a new technical path for the trace detection of Aβ protein in clinic. SUMMARY
[0005] The technical problem to be solved by the present application is to provide a CuUiO-66@TiO2 composite nanomaterial with high sensitivity and good stability for the detection of β amyloid protein.
[0006] The technical solution adopted by the present application to solve the above technical problem is: the application of CuUiO-66@TiO2 composite nanomaterial in the detection of β amyloid protein, which is not for the purpose of disease diagnosis, and the steps are as follows: adding CuUiO-66@TiO2 composite nanomaterial to 10-20 μL of β amyloid protein solution to be detected, and naturally drying in a dust-free environment, then detecting the SERS intensity by Raman spectroscopic instrument, and calculating the concentration of β amyloid protein in the solution to be detected according to the linear relationship between the concentration of β amyloid protein solution and the Raman intensity.
[0007] Further, the preparation method of the CuUiO-66@TiO2 composite nanomaterial comprises the following steps:
[0008] Step 1: synthesizing CuUiO-66 nanoparticles doped with copper ions by solvothermal method;
[0009] Step 2: growing TiO2 shell on the surface of CuUiO-66 core in situ based on sol-gel method to obtain CuUiO-66@TiO2 composite nanomaterial.
[0010] Further, step 1 is specifically as follows:
[0011] Dissolve 200-260 mg of terephthalic acid powder in 10-20 mL of dimethylformamide, and slowly add 2-4 mL of glacial acetic acid; at the same time, mix and dissolve 140-252 mg of zirconium chloride and 17-81 mg of copper chloride powder in 10-20 mL of dimethylformamide, then mix the two prepared solutions, and stir vigorously for 30-50 minutes to fully mix, then transfer the obtained light blue solution to an autoclave, keep at 120-140 DEG C for 22-26 hours, then wash with anhydrous ethanol and dry to obtain CuUiO-66 nanoparticles.
[0012] Further, step 2 is specifically as follows:
[0013] Take 30 mg of CuUiO-66 nanoparticles and add them to 20-30 mL of 0.1 M hydrochloric acid aqueous solution and ultrasonically disperse for 15-17 minutes (to achieve full negative charging of the CuUiO-66 nanoparticle surface, the negative charge enriched on the surface can adsorb positively charged titanium ions through electrostatic interaction, providing anchoring sites for the subsequent directional deposition of the TiO2 film on the CuUiO-66 core surface), collect the product by centrifugation, and wash repeatedly with deionized water; then add the treated CuUiO-66 nanoparticles, 100-140 μL of NH3·H2O, and 4-6 mL of butyl titanate to a mixed solution composed of 6-8 mL of acetonitrile and 18-22 mL of ethanol, and continue to stir for 2-4 hours, after the reaction is completed, collect the obtained white precipitate, and wash thoroughly with distilled water and ethanol, then dry the product in a vacuum oven at 30-50 DEG C for 12-14 hours to obtain a CuUiO-66@TiO2 composite nanosensor.
[0014] Further, the beta amyloid protein includes Aβ-40, Aβ-42, etc.
[0015] Compared with the prior art, the advantages of the present application are:
[0016] 1. Synergistically enhanced charge transfer mechanism: through Cu 2+ Doping of ions in the UiO-66 core and the formation of a core-shell heterojunction of TiO2 shell realize dual regulation, Cu 2+ Doping in the UiO-66 lattice introduces defect energy levels, effectively regulating its Fermi energy level and electronic structure; while the interface built-in electric field formed by the core-shell heterojunction significantly promotes the directional migration of photo-generated electrons from CuUiO-66 to TiO2. This synergistic effect greatly reduces the probability of charge recombination, thereby realizing a SERS enhancement factor (≥10 6 ).
[0017] 2、Controllable preparation and excellent structural reproducibility: Unlike many composite substrates prepared by physical adsorption or simple mixing, the present application uses a step-by-step solvothermal / hydrothermal method to achieve in-situ and uniform growth of the TiO2 shell on the surface of the CuUiO-66 core. This process ensures a tight interface between the core and shell, controllable shell thickness, and the formation of a well-defined heterojunction. This highly uniform and reproducible structure is the basis for obtaining stable and reliable SERS signals, effectively avoiding the signal fluctuation problem caused by the randomness of "hot spots" distribution in traditional SERS substrates, and providing the possibility for quantitative analysis.
[0018] 3、Excellent detection sensitivity and wide applicability: Experimental results show that the detection limit of the composite nano-sensor for Aβ-40 is as low as 10 -9 mg / mL, with a sensitivity that is even better than some LC-MS methods and far higher than conventional ELISA methods. At the same time, since its enhancement mechanism mainly relies on the high-efficiency chemical enhancement (CM) effect rather than being limited to specific "hot spots", it shows excellent universal detection ability for various Raman-active Aβ protein molecules, with detection limits reaching the nanomolar to picomolar level, fully meeting the dual requirements of high sensitivity and wide spectrum for clinical trace protein detection.
[0019] 4、Good stability and application potential: The TiO2 shell not only participates in charge separation as a functional component, but also provides physical protection for the internal CuUiO-66 core, enhancing the chemical stability and service life of the composite material in complex detection environments. In addition, the preparation process has low raw material cost and simple steps, and has the potential for large-scale production, laying a solid foundation for its practical application in clinical rapid screening.
[0020] In summary, the present application first proposes the application of a Cu ion-doped UiO-66 nanoparticle and TiO2 heterojunction coated CuUiO-66@TiO2 composite nano-sensor in Aβ protein detection. The composite nano-sensor has uniformly sized CuUiO-66 nanoparticles and uniformly grown TiO2 films, and the TiO2 film layer has an energy level that is compatible with the CuUiO-66 core, significantly reducing the excitation barrier and promoting the interface charge transfer efficiency, with a Raman signal enhancement factor ≥10 6 , and good reproducibility and uniformity, enabling large-area SERS imaging and quantitative detection, providing a more competitive solution for high-sensitivity detection of Aβ protein in clinical applications. BRIEF DESCRIPTION OF DRAWINGS
[0021] Figure 1 Scanning electron microscope photograph of the CuUiO-66 nanoparticles prepared in Example 1;
[0022] Figure 2 Scanning electron microscope photo of CuUiO-66@TiO2 composite nanomaterial prepared in Example 1;
[0023] Figure 3 Transmission electron microscope photo of CuUiO-66@TiO2 composite nanomaterial prepared in Example 1;
[0024] Figure 4 Raman spectrum of CuUiO-66@TiO2 composite nanomaterial prepared in Example 1 for detecting different concentrations of Aβ-40 solution;
[0025] Figure 5 Linear relationship between Aβ-40 solution and Raman intensity of CuUiO-66@TiO2 composite nanomaterial prepared in Example 1;
[0026] Figure 6 Scanning electron microscope photo of CuUiO-66@TiO2 composite nanomaterial prepared in Example 2;
[0027] Figure 7 Transmission electron microscope photo of CuUiO-66@TiO2 composite nanomaterial prepared in Example 2;
[0028] Figure 8 Raman spectrum of CuUiO-66@TiO2 composite nanomaterial prepared in Example 2 for detecting Aβ-40 solution with concentration of 10 -5 mg / ml;
[0029] Figure 9 Scanning electron microscope photo of CuUiO-66@TiO2 composite nanomaterial prepared in Example 3;
[0030] Figure 10 Transmission electron microscope photo of CuUiO-66@TiO2 composite nanomaterial prepared in Example 3;
[0031] Figure 11 Raman spectrum of CuUiO-66@TiO2 composite nanomaterial prepared in Example 3 for detecting Aβ-40 solution with concentration of 10 -5 mg / ml. DETAILED DESCRIPTION
[0032] The application will be further described in the following examples with reference to the accompanying drawings.
[0033] The following examples are intended to illustrate the present application but not to limit the scope of the present application. If not specifically mentioned, the technical means used in the examples are the conventional means well known to those skilled in the art, and the raw materials used are commercially available. The Raman spectrometer BWS415 used in the examples is purchased from B&W Tek Inc., USA.
[0034] Example 1, a preparation method of CuUiO-66@TiO2 composite nanomaterial, comprising the following steps:
[0035] Step 1, preparation of CuUiO-66 nanoparticles
[0036] The CuUiO-66 nanoparticles were synthesized by a typical hydrothermal method: first, 200 mg of terephthalic acid (abbreviated as PTA) powder was dissolved in 10 mL of dimethylformamide (abbreviated as DMF) and slowly added into 2 mL of glacial acetic acid; at the same time, 140 mg of zirconium chloride (ZrCl4) and 17 mg of copper chloride (CuCl2) powder were mixed and dissolved in 10 mL of DMF, then the two prepared solutions were mixed in a beaker and stirred vigorously for 30 minutes to ensure complete mixing, then the obtained light blue solution was transferred to a polytetrafluoroethylene-lined autoclave and kept in a preheated oven at 120 ℃ for 24 hours, then washed with anhydrous ethanol and dried to obtain CuUiO-66 nanoparticles;
[0037] Step 2, preparation of CuUiO-66@TiO2 composite nanosensor
[0038] A modified solvothermal method was used to deposit a layer of TiO2 film on the CuUiO-66 core. First, 30 mg of CuUiO-66 nanoparticles synthesized in step 1 were added to 20 mL of 0.1 M (moles per liter) hydrochloric acid aqueous solution and ultrasonically dispersed for 15 minutes to achieve full negative charging of the CuUiO-66 nanoparticle surface, which can adsorb positively charged titanium ions through electrostatic interaction, providing anchoring sites for the subsequent directional deposition of the TiO2 film on the surface of the CuUiO-66 core; then, the product was collected by centrifugation and washed repeatedly with deionized water; then, the treated CuUiO-66 nanoparticles, 100 μL of NH3·H2O and 4 mL of tetrabutyl titanate (abbreviated as TBOT) were sequentially added to a mixed solution composed of 6 mL of acetonitrile and 18 mL of ethanol, and continuously stirred at room temperature for 2 hours, after the reaction was completed, the white precipitate was collected and washed thoroughly with distilled water and ethanol, then the product was dried in a vacuum oven at 30 ℃ for 12 hours to obtain the CuUiO-66@TiO2 composite nanosensor.
[0039] Figure 1Scanning electron microscope (SEM) image of CuUiO-66 nanoparticles prepared for this example. As shown in Figure 1 , the prepared particles have a uniform size distribution, and the material surface exhibits a clear rough cubic structure. This densified surface feature not only effectively improves light capture capability, but also helps to improve the stability of charge transport within the material.
[0040] Figure 2 Scanning electron microscope (SEM) image of CuUiO-66@TiO2 composite nanosensor prepared in this example. As shown in Figure 2 , the surface morphology features were observed, and it was found that a uniform smooth shell layer was formed on the surface of the CuUiO-66 core after TiO2 coating. This surface shell layer not only enhances the light scattering effect, but also provides more site areas for subsequent molecular anchoring. In addition, the efficient preparation of this composite system provides a guarantee for efficient interfacial charge transport.
[0041] Figure 3 Transmission electron microscope (TEM) image of CuUiO-66@TiO2 composite nanosensor prepared in this example. As shown in Figure 3 , the core-shell structure features are clearly revealed. The dark CuUiO-66 core is completely coated with a light gray TiO2 shell layer, and the shell layer has uniform thickness and tight interface bonding. The synergistic effect of this interface structure not only reduces the probability of charge recombination, but also accelerates the directional migration of photo-generated electrons through the built-in electric field of the heterojunction, further indicating that the TiO2 shell layer optimizes the energy band structure through the heterojunction coating process, ultimately significantly improving the charge transfer efficiency of the composite nanosensor.
[0042] Figure 4 Raman spectrum of CuUiO-66@TiO2 composite nanosensor. Figure 4 shows the Raman signal characteristic peak values of different concentrations of Aβ-40 solution on the composite nanosensor. As can be seen from Figure 4 , with the increase of the concentration of Aβ-40 molecules, the intensity of the Raman characteristic peak also increases, indicating that the sensor has good detection capability for Aβ-40 molecules. In addition, the clear characteristic peak in the Raman spectrum also proves that the sensor has a high Raman signal enhancement effect, which can effectively improve the detection sensitivity.
[0043] Figure 5 Detection limit test results of CuUiO-66@TiO2 composite nanosensor. Figure 5 shows the SERS signal response of CuUiO-66@TiO2 composite nanosensor under different concentrations of Aβ-40 solution. By analyzing the Raman characteristic peak 1269 cm -1The relationship between the intensity and the concentration of Aβ-40 further determines the detection limit of the composite nanosensor for Aβ-40. The experimental results show that the sensor can effectively identify the Aβ-40 concentration as low as 10 ⁻9 mg / mL, which exhibits excellent sensitivity and has the potential to be applied to the detection of trace Aβ protein.
[0044] Example 2, a preparation method of a CuUiO-66@TiO2 composite nanomaterial, comprising the following steps:
[0045] Step 1, preparation of CuUiO-66 nanoparticles
[0046] The CuUiO-66 nanoparticles were synthesized by a typical hydrothermal method: first, 230 mg of PTA powder was dissolved in 15 mL of DMF and slowly added to 3 mL of glacial acetic acid; at the same time, 196 mg of ZrCl4 and 49 mg of CuCl2 powder were mixed and dissolved in 15 mL of DMF, then the two prepared solutions were mixed in a beaker and stirred vigorously for 40 minutes to ensure complete mixing, then the resulting light blue solution was transferred to a polytetrafluoroethylene-lined autoclave and kept in a preheated oven at 130℃ for 22 hours, then washed with anhydrous ethanol and dried to obtain CuUiO-66 nanoparticles;
[0047] Step 2, preparation of CuUiO-66@TiO2 composite nanosensor
[0048] First, 30 mg of CuUiO-66 nanoparticles synthesized in step 1 were added to 25 mL of 0.1M hydrochloric acid aqueous solution and ultrasonically dispersed for 16 minutes, then the product was collected by centrifugation and washed repeatedly with deionized water; then, the treated CuUiO-66 nanoparticles, 120 μL of NH3·H2O and 5 mL of TBOT were sequentially added to a mixed solution composed of 7 mL of acetonitrile and 20 mL of ethanol, and continuously stirred at room temperature for 3 hours, after the reaction was completed, the white precipitate was collected and thoroughly washed with distilled water and ethanol, then the product was dried in a vacuum oven at 40℃ for 13 hours to obtain the CuUiO-66@TiO2 composite nanosensor.
[0049] Figure 6 The scanning electron microscope photo of the CuUiO-66@TiO2 composite nanosensor prepared in this embodiment presents its unique surface morphology characteristics. After being coated with TiO2, a continuous, uniform and dense shell structure is formed outside the CuUiO-66 core. This shell not only promotes the directional migration of charge carriers, but also effectively inhibits the probability of electron-hole recombination due to its ordered arrangement characteristics, in addition, the heterostructure formed contributes to the spatial separation of photo-generated electrons and holes.
[0050] Figure 7 The transmission electron microscope (TEM) photo of the CuUiO-66@TiO2 composite nanosensor prepared in this embodiment clearly presents its typical core-shell structure characteristics. The dark CuUiO-66 inner core is completely coated by a layer of thin light gray TiO2 shell with uniform thickness and continuity, and the core-shell interface is clear and closely combined, indicating that a stable heterojunction is formed. This structure significantly promotes the spatial separation of photo-generated electrons and holes by constructing an effective built-in electric field, effectively inhibiting the recombination of carriers. At the same time, the introduction of the TiO2 shell optimizes the overall band structure through heterojunction interface engineering, improving the directional migration ability of electrons under photoexcitation, thereby greatly enhancing the charge transfer efficiency of the sensor.
[0051] Figure 8 The Raman spectrum of the CuUiO-66@TiO2 composite nanosensor prepared in this embodiment is shown. Figure 8 The SERS signal of the Aβ-40 solution with a concentration of 10 ⁻5 mg / mL on the composite nanosensor is shown. The characteristic Raman peaks of Aβ-40 can be clearly observed in Figure 8 , indicating that the sensor has good detection performance for Aβ-40 protein. In addition, the Raman spectrum exhibits a high signal-to-noise ratio, further confirming that the sensor has significant Raman signal enhancement ability and can be used for effective detection of trace Aβ protein.
[0052] Embodiment 3, a preparation method of a CuUiO-66@TiO2 composite nanomaterial, comprising the following steps:
[0053] Step 1, preparation of CuUiO-66 nanoparticles
[0054] Dissolve 260 mg of PTA powder in 20 mL of DMF and slowly add 4 mL of glacial acetic acid; at the same time, dissolve 140 mg of ZrCl4 and 81 mg of CuCl2 powder in 20 mL of DMF, then mix the two prepared solutions in a beaker and stir vigorously for 50 minutes to fully mix, then transfer the obtained light blue solution to a polytetrafluoroethylene-lined autoclave, and keep it in a preheated oven at 140 ℃ for 26 hours, then wash with anhydrous ethanol and dry to obtain CuUiO-66 nanoparticles;
[0055] Step 2, preparation of CuUiO-66@TiO2 composite nanosensor
[0056] First, 30 mg of CuUiO-66 nanoparticles synthesized in step 1 were added to 30 mL of 0.1 M hydrochloric acid aqueous solution and ultrasonically dispersed for 17 minutes. The product was then collected by centrifugation and washed repeatedly with deionized water. Next, the treated CuUiO-66 nanoparticles, 140 μL of NH3·H2O, and 6 mL of TBOT were added sequentially to a mixed solution consisting of 8 mL of acetonitrile and 22 mL of ethanol. The mixture was stirred continuously at room temperature for 4 hours. After the reaction was completed, the resulting white precipitate was collected and thoroughly washed with distilled water and ethanol. The product was then dried in a vacuum oven at 50 °C for 14 hours to obtain the CuUiO-66@TiO2 composite nanosensor.
[0057] Figure 9 This is a scanning electron microscope (SEM) image of the CuUiO-66@TiO2 composite nanosensor prepared in this embodiment. Figure 9 As shown, after TiO2 coating, a complete, uniform, and dense shell structure is formed outside the CuUiO-66 core. This shell not only facilitates the directional migration of photogenerated carriers, but its highly ordered microstructure also significantly suppresses the recombination process of electrons and holes. Furthermore, the constructed heterostructure effectively promotes the spatial separation of photogenerated electrons and holes, thereby further improving the charge separation performance of the material.
[0058] Figure 10 The transmission electron microscope (TEM) image of the CuUiO-66@TiO2 composite nanosensor prepared in this embodiment clearly shows its typical core-shell structure morphology. For example... Figure 10 As shown, the dark CuUiO-66 core is completely covered by a thick, continuous, and uniform light gray TiO2 shell. The interface between the core and shell is distinct and tightly bonded, indicating that this heterostructure possesses excellent structural integrity and interfacial compatibility. This core-shell heterojunction can effectively drive the spatial separation of photogenerated electrons and holes by constructing a built-in electric field, significantly suppressing carrier recombination. Simultaneously, through precise control of the interface characteristics between the TiO2 shell and the core, the band structure is rationally optimized, improving the directional migration rate of electrons and thus significantly enhancing the charge transport performance of the sensor.
[0059] Figure 11 The image shows the Raman spectrum of the CuUiO-66@TiO2 composite nanosensor prepared in this embodiment. Figure 11 This embodiment demonstrates the CuUiO-66@TiO2 composite nanosensor prepared in 10 -5The SERS spectrum of the Aβ-40 solution with 0.1 mg / mL. The characteristic Raman peaks of Aβ-40 are clearly shown in the spectrum, indicating that the sensor has good recognition performance for the target molecule. At the same time, the strong Raman signal response and the low background interference significantly improve the signal-to-noise ratio, further verifying the enhancement ability of the composite structure for the Raman signal, and showing its application potential in the detection of low-concentration Aβ protein.
[0060] The above description is not a limitation of the present application, and the present application is not limited to the above examples. Changes, modifications, additions or substitutions made by those skilled in the art within the spirit and scope of the present application should also be within the protection scope of the present application.
Claims
1. Application of CuUiO-66@TiO2 composite nanomaterial in detection of Aβ protein, which is not for the purpose of disease diagnosis, characterized in that The steps are as follows: the CuUiO-66@TiO2 composite nanomaterial is added to 10-20 muL of the A beta protein solution to be detected, and after natural drying in a dust-free environment, the SERS intensity is detected by a Raman spectrometer, and the concentration of the A beta protein in the solution to be detected is calculated according to the linear relationship between the A beta protein solution concentration and the Raman intensity, wherein the preparation method of the CuUiO-66@TiO2 composite nanomaterial comprises the following steps: Step 1: Synthesize CuUiO-66 nanoparticles doped with copper ions by a solvothermal method, specifically as follows: Dissolve 200-260 mg of terephthalic acid powder in 10-20 mL of dimethylformamide, and slowly add 2-4 mL of glacial acetic acid; at the same time, dissolve 140-252 mg of zirconium chloride and 17-81 mg of copper chloride powder in 10-20 mL of dimethylformamide, then mix the two prepared solutions, and stir vigorously for 30-50 minutes to fully mix them, then transfer the obtained light blue solution to an autoclave, keep it at 120-140 DEG C for 22-26 hours, then wash with anhydrous ethanol and dry to obtain CuUiO-66 nanoparticles; Step 2: Grow a TiO2 shell layer on the surface of the CuUiO-66 core in situ based on a sol-gel method to obtain CuUiO-66@TiO2 composite nanomaterial, specifically as follows: Take 30 mg of CuUiO-66 nanoparticles and add them to 20-30 mL of 0.1M hydrochloric acid aqueous solution, ultrasonically disperse for 15-17 minutes, then collect the product by centrifugation and wash repeatedly with deionized water; then add the treated CuUiO-66 nanoparticles, 100-140 muL of NH3·H2O and 4-6 mL of butyl titanate to a mixed solution composed of 6-8 mL of acetonitrile and 18-22 mL of ethanol, and continue to stir for 2-4 hours, after the reaction is completed, collect the obtained white precipitate, and wash it thoroughly with distilled water and ethanol, then dry the product in a vacuum oven at 30-50 DEG C for 12-14 hours to obtain a CuUiO-66@TiO2 composite nanosensor.
2. Use according to claim 1, characterized in that: The A beta protein includes A beta-40, A beta-42.
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