PH response type multi-mode imaging diagnostic agent and high polymer material aging monitoring method

Abstract

The invention discloses a pH response type multi-mode imaging diagnostic agent and an aging monitoring method of a high polymer material. The diagnostic agent comprises a carrier, a fluorescent probe and a free radical trapping agent, the carrier is a Fe3O4 nano particle (PEI-coated Fe3O4) modified by polyethyleneimine (PEI); the fluorescent probe is a pH acid response BODIPY (boron dipyrromethene) fluorescent probe HGBDP; the free radical trapping agent is 4-oxygen-TEMPO (tetramethylpiperidinooxy); the aging monitoring method of the high polymer material comprises the following steps: mixing the pH response type multi-mode imaging diagnostic agent with a high polymer base material to prepare a sample to obtain a high polymer composite material, and then monitoring the aging state of the high polymer composite material in real time in a multi-mode manner; the diagnostic agent disclosed by the invention can respond to aging markers such as free radicals and acid degradation products generated in the service process of the material, so that lossless, real-time and visual evaluation and multi-mode cooperative monitoring of the aging degree of the material are realized, the defect of a single monitoring mode is overcome, and aging information is comprehensively obtained.

Description

Technical Field

[0001] This invention belongs to the field of materials technology, specifically relating to an imaging diagnostic agent and a method for monitoring the aging of polymer materials. Background Technology

[0002] Polymer materials are widely used in transportation, power equipment, aerospace, and infrastructure, and their long-term performance directly affects the stability and safety of system operation. However, polymer materials are prone to aging under long-term exposure to light, heat and oxygen, humidity fluctuations, and mechanical stress, leading to performance degradation, structural embrittlement, and decreased insulation properties, which can cause equipment failures or even serious safety accidents. As the operating environment becomes increasingly complex, the need for polymer material aging monitoring is becoming more prominent.

[0003] Currently, methods for detecting the aging of polymer materials mainly include destructive mechanical testing, thermal analysis, or chemical titration. These methods typically require sampling or damaging the material's structure, making continuous monitoring under actual service conditions impossible. Furthermore, some detection techniques based on surface spectroscopy or external signals can only obtain information from the material's surface, failing to reflect the internal aging process. In many engineering applications, due to the lack of effective real-time monitoring methods, material aging is often only detected after reaching a critical stage or failure, failing to provide early warning and posing significant safety hazards. Overall, there is still a lack of effective, non-destructive, sensitive, and real-time monitoring methods for aging markers such as trace free radicals and acidic degradation products within materials. The lag and inaccuracy of monitoring methods have become key issues limiting the safe use of polymer materials. Summary of the Invention

[0004] To address the shortcomings of existing polymer material aging detection technologies, such as reliance on destructive testing, inability to monitor the internal aging process of materials, and inability to identify early chemical changes during aging, this invention provides a diagnostic agent for monitoring the aging process of polymer materials. This diagnostic agent can respond to aging markers such as free radicals and acidic degradation products generated during the service of materials, thereby achieving non-destructive, real-time, and visual assessment of the degree of material aging. Multimodal collaborative monitoring comprehensively acquires aging information, making up for the shortcomings of single monitoring methods.

[0005] To achieve the above objectives, the following technical solution is adopted: A pH-responsive multimodal imaging diagnostic agent includes a carrier, a fluorescent probe, and a free radical scavenger; the carrier is polyethyleneimine (PEI) modified Fe3O4 nanoparticles PEI@Fe3O4; the fluorescent probe is a pH-responsive fluoroboron dipyrrole fluorescent probe HGBDP; and the free radical scavenger is 4-oxy-TEMPO. The pH-responsive fluoroboron dipyrrole fluorescent probe and 4-oxygen-TEMPO are sequentially bonded to the surface of PEI@Fe3O4 via a Schiff base reaction to form the HGBDP-PEI@Fe3O4-TEMPO aging probe.

[0006] The present invention also provides a polymer composite material formed by blending the above-mentioned pH-responsive multimode imaging diagnostic agent with a polymer matrix.

[0007] This invention also provides a method for monitoring the aging of polymer materials, comprising the following steps: (1) The above-mentioned pH-responsive multi-mode imaging diagnostic agent was mixed with a polymer substrate to prepare a polymer composite material; (2) Use multimodal real-time monitoring of the aging state of polymer composite materials.

[0008] According to the above scheme, the amount of imaging diagnostic agent added in step (1) is 0.1% to 10.0% by mass percentage.

[0009] According to the above scheme, the polymer substrate in step (1) is one of polylactic acid, polycaprolactone, and polycarbonate.

[0010] According to the above scheme, the multimodal real-time monitoring in step (2) includes the use of one or more of the following methods for coordinated monitoring: fluorescence imaging (FI), magnetic resonance imaging (MRI), and paramagnetic resonance spectroscopy (EPR).

[0011] According to the above scheme, the fluorescence imaging (FI) includes detecting the change in fluorescence intensity during the aging process of the composite material using 440nm as the excitation wavelength and 535nm as the filter wavelength.

[0012] According to the above scheme, the magnetic resonance imaging (MRI) includes coronal scanning imaging of polymer composite materials using an Express Head Neck Array-Cspine Array coil and an OSagT2FlexFRFSE-DNE sequence, with a slice thickness of 0.7 mm, a slice spacing of 0.0 mm, TR 2236.0, and TE 68.0.

[0013] According to the above scheme, the paramagnetic resonance spectroscopy (EPR) includes a magnetic field centered at 3510.00 G, a sweep width of 100 G, a scan time of 46 s, a microwave power of 19.71 GHz, a frequency of 9.852131 GHz, and the paramagnetic resonance spectrum of the detected material.

[0014] According to the above scheme, step (2) also includes the following steps: as the aging time increases, the fluorescence intensity of the polymer composite material shows a gradually increasing characteristic change. Keeping the magnetic resonance imaging signal unchanged, the aging process is fully tracked by combining the free radical evolution data obtained by paramagnetic resonance imaging.

[0015] This invention synthesizes a pH-responsive fluoroboron dipyrrole fluorescent probe (HGBDP) with near-infrared I region imaging capability by modifying the core structure of HGBDP. This probe, along with 4-oxy-TEMPO (which has free radical scavenging effect), is then chemically grafted onto an amino-modified magnetic magnetite (PEI@Fe3O4) surface, thereby producing a pH-responsive paramagnetic resonance / fluorescence dual-mode imaging diagnostic agent. This diagnostic agent can respond to aging markers such as free radicals and acidic degradation products generated during material service, enabling non-destructive, real-time, and visual assessment of the aging degree of materials. Through the synergistic effect of multimodal imaging, it achieves comprehensive monitoring of the aging process of polymer materials.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows: By integrating the advantages of fluorescence imaging, magnetic resonance imaging, and paramagnetic resonance imaging, multimodal collaborative monitoring can be achieved, making up for the shortcomings of single monitoring methods and comprehensively acquiring aging information.

[0017] It features real-time performance, non-destructive testing, and high sensitivity, and can track the aging process from 0 to 312 hours. Changes in fluorescence intensity directly reflect the aging stage.

[0018] By correlating free radical capture with signal response, we can provide molecular-level evidence for the study of aging mechanisms in polymer materials.

[0019] It is suitable for various polymer materials such as PLA, and can be adapted to different monitoring needs by adjusting the probe mass percentage. Attached Figure Description

[0020] Figure 1 Transmission electron microscopy image of HGBDP-PEI@Fe3O4-TEMPO nanoparticles.

[0021] Figure 2 EPR overlay images of 4-oxygen-TEMPO, PEI@Fe3O4-TEMPO and HGBDP-PEI@Fe3O4-TEMPO.

[0022] Figure 3 Fluorescence imaging of PLA discs doped with different mass percentages of diagnostic reagent over aging time (0~312h).

[0023] Figure 4Magnetic resonance imaging (MRI) images of PLA discs doped with different mass percentages of diagnostic reagent over aging time (0-312h). Detailed Implementation

[0024] The following embodiments further illustrate the technical solution of the present invention, but are not intended to limit the scope of protection of the present invention.

[0025] A specific embodiment provides a method for preparing a pH-responsive multimodal imaging diagnostic agent, comprising the following steps: Preparation of S1 and PEI@Fe3O4: Accurately weigh 6.49 g FeCl3·6H2O and dissolve it in 100 mL of water in a three-necked flask. Slowly add 50 mL of 0.16 mol / L sodium sulfite solution and stir for 30 min. Then add 1.0 mL of 10% PEI solution and 10 mL of ammonia water in sequence. Stir at 60℃ for 30 min and then stop the reaction. Magnetically separate and wash the solid with water 5 times. Then ultrasonically disperse the solid in water to obtain PEI@Fe3O4.

[0026] Preparation of S2 and HGBDP-PEI@Fe3O4-TEMPO aging probes: 150 mg of dried PEI@Fe3O4, 134 mg of HGBDP, and 222 mg of 4-oxo-TEMPO were weighed and dissolved in 25 mL of dichloromethane. 56.28 mg of EDC and 33.75 mg of NHS were added. The reaction was carried out at room temperature for 24 h under N2 protection. After the reaction, the supernatant was discarded by centrifugation, and the supernatant was washed with dichloromethane and centrifuged until it became colorless. HGBDP-PEI@Fe3O4-TEMPO nanoparticles were obtained by vacuum drying.

[0027] The transmission electron microscope (TEM) image of the obtained HGBDP-PEI@Fe3O4-TEMPO nanoparticles is attached. Figure 1 As shown. EPR overlay images of 4-oxygen-TEMPO, PEI@Fe3O4-TEMPO, and HGBDP-PEI@Fe3O4-TEMPO are attached. Figure 2 As shown.

[0028] A specific embodiment also provides a polymer composite material containing the above-mentioned diagnostic agent: HGBDP-PEI@Fe3O4-TEMPO nanoparticles and polymer substrate are weighed at a mass percentage of 0.1%-10.0%, and an appropriate amount of dichloromethane is added and thoroughly shaken to dissolve, thus preparing a composite material sample solution; the composite material disc or other molded product is prepared by compression molding. In one feasible embodiment, the polymer substrate is polylactic acid (PLA), and the mass ratio of the diagnostic agent to PLA is as follows: 0.8 mg: 7992.0 mg, 8 mg: 7992.0 mg, 40.0 mg: 7960.0 mg, 80.0 mg: 7920.0 mg, 400.0 mg: 7600.0 mg, 800.0 mg: 7200.0 mg, with the diagnostic agent corresponding to mass percentages of 0.01%, 0.1%, 0.5%, 1.0%, 5.0%, and 10.0%, respectively.

[0029] Example 1 Weigh 50 mg of dried PEI@Fe3O4-TEMPO and 44 mg of HGBDP, dissolve them in 8 mL of dichloromethane, add 18 mg of EDC and 11 mg of NHS, and react at room temperature for 24 h under N2 protection. After the reaction is complete, centrifuge, discard the supernatant, wash with dichloromethane and centrifuge until the supernatant is colorless. Vacuum dry to obtain HGBDP-PEI@Fe3O4-TEMPO nanoparticles.

[0030] Example 2 Weigh the raw materials according to the following mass ratios: 0.01% mass percentage: 0.8 mg aging probe + 7992.0 mg PLA; 0.1% mass percentage: 8.0 mg aging probe + 7992.0 mg PLA; 0.5% mass percentage: 40.0 mg aging probe + 7960.0 mg PLA; 1.0% mass percentage: 80.0 mg aging probe + 7920.0 mg PLA; 5.0% mass percentage: 400.0 mg aging probe + 7600.0 mg PLA; 10.0% mass percentage: 800.0 mg aging probe + 7200.0 mg PLA. Add each set of raw materials to a glass bottle, add an appropriate amount of dichloromethane, and shake thoroughly to completely dissolve the raw materials, preparing a homogeneous composite material sample solution. Use the tablet compression method (pressure 10 MPa, holding pressure for 5 min) to prepare composite material discs from the sample solution for later use.

[0031] Example 3 This embodiment provides a multimodal monitoring method for the aging process of the above-mentioned polylactic acid composite material: Fluorescence imaging experiment: The FusionFX7Edge chemiluminescence imager from VIBER Bioimaging was used to detect the fluorescence intensity of composite discs with different aging times (0h, 8h, 16h, 24h, 48h, 72h, 120h, 168h, 240h, 312h) using 440nm as the excitation wavelength and 535nm as the filter wavelength, and the changes in fluorescence signal were recorded.

[0032] Magnetic resonance imaging experiment: The Optima MR360 magnetic resonance imaging system from General Electric (GE) was used, equipped with an ExpressHeadNeckArray-CspineArray coil. The OSagT2FlexFRFSE-DNE sequence was used to scan the coronal position of the composite disc. The scanning parameters were set as follows: slice thickness 0.7 mm, slice spacing 0.0 mm, TR 2236.0, TE 68.0. The changes in magnetic resonance imaging signals at different aging stages were recorded.

[0033] Fluorescence imaging images (0–312 h) of PLA discs doped with different mass percentages of diagnostic reagent as aging time are attached. Figure 3 As shown in the attached image. Magnetic resonance imaging (MRI) images of PLA discs doped with different mass percentages of diagnostic reagent over aging time (0–312 h) are also shown. Figure 4 As shown.

[0034] Fluorescence imaging of HGBDP-PEI@Fe3O4-TEMPO / PLA wafers with different doping ratios revealed that the 0.1% and 0.5% doped samples exhibited the best fluorescence imaging performance. The fluorescence signal of these samples increased with aging time, indicating that the constructed probe has good stability in the material, and that the free radicals and acidic substances generated during the aging process contribute to the enhanced fluorescence signal. Meanwhile, magnetic resonance imaging results showed that the MRI signal of the samples remained unchanged with increasing HGBDP-PEI@Fe3O4-TEMPO doping ratio.

[0035] Paramagnetic resonance spectroscopy (EPR): A central magnetic field of 3510.00 G was used, with a scan width of 100 G, a scan time of 46 s, a microwave power of 19.71 GHz, and a frequency of 9.852131 GHz to detect the paramagnetic resonance spectrum of the material. With prolonged aging time, the fluorescence intensity of the composite material exhibited a gradually increasing characteristic change, while the magnetic resonance imaging signal remained unchanged. Combined with free radical evolution data obtained from paramagnetic resonance imaging, the aging process could be comprehensively tracked, and the aging mechanism clarified.

[0036] The above description is merely a preferred embodiment of the present invention and does not constitute any limitation on the technical scope of the present invention. Therefore, any minor modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention shall still fall within the scope of the technical solution of the present invention.

Claims

1. A pH-responsive multimodal imaging diagnostic agent, characterized in that... The system comprises a support, a fluorescent probe, and a free radical scavenger; the support is polyethyleneimine-modified Fe3O4 nanoparticles (PEI@Fe3O4); the fluorescent probe is a pH-responsive fluoroboron dipyrrole fluorescent probe (HGBDP); and the free radical scavenger is 4-oxy-TEMPO. The pH-responsive fluoroboron dipyrrole fluorescent probe and 4-oxygen-TEMPO are sequentially bonded to the surface of PEI@Fe3O4 via a Schiff base reaction to form the HGBDP-PEI@Fe3O4-TEMPO aging probe.

2. A polymer composite material, characterized in that... The pH-responsive multi-mode imaging diagnostic agent of claim 1 is formed by blending it with a polymer substrate.

3. A method for monitoring the aging of polymer materials, characterized in that... Includes the following steps: (1) A polymer composite material is obtained by mixing the pH-responsive multimode imaging diagnostic agent of claim 1 with a polymer substrate; (2) Use multimodal real-time monitoring of the aging state of polymer composite materials.

4. The aging monitoring method for polymer materials as described in claim 3, characterized in that... The amount of imaging diagnostic agent added in step (1) is 0.1% to 10.0% by mass percentage.

5. The aging monitoring method for polymer materials as described in claim 3, characterized in that... The polymer substrate in step (1) is one of polylactic acid, polycaprolactone, or polycarbonate.

6. The aging monitoring method for polymer materials as described in claim 3, characterized in that... Step (2) The multimodal real-time monitoring includes the use of one or more of the following methods in synergistic monitoring: fluorescence imaging, magnetic resonance imaging, and paramagnetic resonance spectroscopy.

7. The aging monitoring method for polymer materials as described in claim 6, characterized in that... The fluorescence imaging includes detecting changes in fluorescence intensity during the aging process of the composite material using an excitation wavelength of 440 nm and a filter wavelength of 535 nm.

8. The aging monitoring method for polymer materials as described in claim 6, characterized in that... The magnetic resonance imaging includes coronal scanning imaging of polymer composite materials using an Express Head Neck Array-Cspine Array coil and an OSagT2FlexFRFSE-DNE sequence, with a slice thickness of 0.7 mm, a slice spacing of 0.0 mm, a TR of 2236.0, and a TE of 68.

0.

9. The aging monitoring method for polymer materials as described in claim 6, characterized in that... The paramagnetic resonance spectrum includes the paramagnetic resonance spectrum of the detected material with a central magnetic field of 3510.00 G, a sweep width of 100 G, a sweep time of 46 s, a microwave power of 19.71 GHz, and a frequency of 9.852131 GHz.

10. The aging monitoring method for polymer materials as described in claim 3, characterized in that... Step (2) also includes the characteristic change that the fluorescence intensity of the polymer composite material gradually increases with the extension of aging time. Keeping the magnetic resonance imaging signal unchanged, the aging process is fully tracked by combining the free radical evolution data obtained by paramagnetic resonance imaging.

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