A temperature-spectral coupled response material based on hydrogel microstructure regulation and its preparation method

Abstract

This application relates to the field of ultrasound therapy phantoms, and more particularly to a temperature-spectral coupling response material based on hydrogel microstructure regulation and its preparation method. The material comprises: 70-80% degassed deionized water, 8-12% polyvinyl alcohol, 5-10% thiamine, 0.4-0.6% chitosan, 1-5% CdSe / ZnS quantum dots, and 2-11% cellulose. The preparation process combines high-temperature dissolution with low-temperature doping, followed by five freeze-thaw cycles for cross-linking and molding. This application utilizes the linear temperature-dependent fluorescence peak wavelength of quantum dots to achieve real-time reversible quantitative temperature measurement with a resolution of 0.1℃ within a range of 30-160℃. Furthermore, the material's acoustic parameters are tissue-compatible, and it is safe and non-toxic, solving the technical problems of irreversible temperature measurement, low accuracy, and toxic raw materials in traditional phantoms. Its fast response speed and high stability provide a reliable experimental platform for focal zone monitoring and efficacy evaluation in high-intensity focused ultrasound therapy.

Description

Technical Field

[0001] This invention belongs to the field of functional materials and biomedical engineering technology. Background Technology

[0002] The use of high-intensity focused ultrasound (HIFU) in hyperthermia research and clinical applications is gradually increasing, and its therapeutic effect is highly dependent on the temperature distribution characteristics within the focal zone. Therefore, constructing experimental models that can reflect spatial changes in the temperature field has become an important foundation for related research. To study the tissue temperature distribution during hyperthermia, researchers often use phantom materials to simulate biological tissues and incorporate temperature-sensitive substances into them. Currently, most phantoms commonly used in research both domestically and internationally use acrylamide and protein as the main raw materials, using protein denaturation due to heat to cause an appearance of turbidity or whitening to represent the focal zone. However, the response mechanism of these protein-based phantoms is based on thermal denaturation coagulation, and their temperature response is irreversible, meaning that a single phantom can only be used once, failing to meet the requirements for reproducible experiments.

[0003] To improve reusability, existing technologies have developed tissue-mimicking phantoms based on isopropylacrylamide polymer hydrogels. While these materials can change color upon heating and return to their original state after the heat dissipates, the acrylamide monomers required in their preparation have significant neurotoxicity and potential carcinogenicity, posing safety hazards to operators and the environment. Furthermore, some methods monitor temperature by adding thermochromic inks to polyacrylamide gels or coating the absorber surface with thermochromic liquid crystals; however, the color-changing range of these materials is typically narrow, failing to cover the full range of needs from low-temperature hyperthermia to high-temperature ablation therapy. More importantly, existing temperature-spectral coupled response materials based on hydrogel microstructure regulation generally rely on visual observation or image analysis to assess temperature changes. This semi-quantitative analytical method is highly susceptible to ambient light, shooting angle, and equipment parameters, resulting in low temperature measurement accuracy and difficulty in achieving precise temperature quantification.

[0004] Although quantum dot-based thermometry technologies have been publicly disclosed, utilizing the temperature-dependent properties of quantum dot fluorescence peak wavelengths, these technologies are typically used in the fabrication of flexible transparent films. These films involve complex structures and lack acoustic, thermal, and mechanical properties similar to biological tissues, making them unsuitable for direct use as biomimetic materials in ultrasound therapy. In summary, existing thermosensitive biomimetic materials still have significant shortcomings in real-time reversible monitoring, material safety, temperature measurement accuracy, measurement range, and tissue simulation characteristics, failing to meet the high standards of online monitoring and automated quantitative analysis required in modern dynamic hyperthermia research. Therefore, developing a novel temperature-spectral coupling response material based on hydrogel microstructure regulation that possesses excellent tissue simulation properties, high-precision quantitative temperature measurement capabilities, and is safe and non-toxic has significant academic and practical value. Summary of the Invention

[0005] This invention addresses the technical shortcomings of existing thermosensitive phantom materials, including irreversible temperature response, neurotoxicity and carcinogenic risks of raw materials, narrow temperature measurement range, and reliance on visual observation leading to limitations in high-precision quantitative monitoring. It provides a temperature-spectral coupled-response material based on hydrogel microstructure regulation and its preparation method. By precisely proportioning a biocompatible matrix, plasticizer, acoustic scattering agent, and high-efficiency fluorescent probe, combined with a specific physical cross-linking process, this invention yields a novel temperature-spectral coupled-response material based on hydrogel microstructure regulation. This material possesses excellent tissue simulation properties, real-time reversible response capability, wide measurement range, and high-precision quantitative monitoring capabilities.

[0006] To achieve high-precision reversible monitoring of the temperature field, this invention constructs a temperature-spectral coupling response material based on hydrogel microstructure regulation. By adjusting the interaction between the matrix network structure and the fluorescent probe, a stable mapping of the temperature signal is achieved. Its components, by weight percentage, include: 70wt%~80wt% degassed water, 8wt%~12wt% polyvinyl alcohol, 5wt%~10wt% thiamine, 0.4wt%~0.6wt% chitosan, 1wt%~5wt% CdSe / ZnS water-soluble quantum dots, and 2wt%~11wt% cellulose. The degassed water serves as the solvent, undergoing vacuum degassing to remove internal air bubbles, providing the basic acoustic propagation medium for the material. The polyvinyl alcohol serves as the matrix material, preferably with a degree of polymerization of 1700 and a degree of alcoholysis of 99%. It forms a stable three-dimensional hydrogel framework through hydrogen bonding between molecular chains, mimicking the mechanical support structure of biological tissues. The thiamine, through its polyhydroxy structure, participates in hydrogen bond network reconstruction and, during freezing, regulates the nucleation and growth behavior of ice crystals through steric hindrance, thereby affecting the size distribution of the polyvinyl alcohol microcrystalline region. This microstructure regulation further stabilizes the spatial distribution of quantum dots in the gel and its local dielectric environment. Chitosan, as a natural preservative, utilizes the antibacterial activity of its amino groups to extend the material's storage life at room temperature. The CdSe / ZnS water-soluble quantum dots, as temperature-sensitive fluorescent probes, have a core diameter controlled at 9 nm and are encapsulated with a ZnS shell to passivate defect states on the core surface, improving fluorescence quantum yield. Their fluorescence peak wavelength exhibits a linear redshift characteristic with increasing temperature in the range of 30℃ to 160℃. Cellulose, as a scattering agent, has a particle size distribution between 10 μm and 50 μm. By forming an acoustic impedance difference interface in the gel matrix, it adjusts the ultrasonic attenuation coefficient of the material, matching its acoustic characteristics to those of human soft tissue.

[0007] Furthermore, when the mass percentage of polyvinyl alcohol is selected as 10 wt%, the Young's modulus of the material is in the range of 15 kPa to 30 kPa, simulating the hardness characteristics of human liver tissue. The mass ratio of thiamine to polyvinyl alcohol is controlled between 0.5:1 and 0.8:1 to ensure that the material does not experience crack propagation after multiple deformations. The CdSe / ZnS water-soluble quantum dots are modified with carboxyl or hydroxyl functional groups, giving them excellent dispersibility in the aqueous matrix and preventing fluorescence quenching caused by aggregation during gelation. The cellulose content is adjusted according to the acoustic attenuation requirements of the target tissue; when its content is 5 wt%, the acoustic attenuation coefficient of the material at a frequency of 1 MHz is maintained between 0.5 dB / cm and 0.7 dB / cm.

[0008] This invention also provides a method for preparing the above-mentioned temperature-spectral coupling response material based on hydrogel microstructure regulation. This method combines high-temperature dissolution with low-temperature doping to maintain the fluorescence activity of quantum dots while ensuring matrix homogeneity. The preparation method specifically includes the following steps: First, the matrix solution is prepared by weighing polyvinyl alcohol, thiamine, chitosan, and cellulose according to a preset ratio, and then adding them sequentially to degassed deionized water. The mixture is placed in a constant temperature water bath or heating jacket, and the heating temperature is controlled at 95℃±1℃. Simultaneously, a stirring device is started, and the mixture is continuously stirred at a speed of 700 to 800 rpm. This high-temperature environment is maintained for at least 30 minutes, allowing the polyvinyl alcohol particles to absorb water, swell, and completely dissolve, forming a transparent, homogeneous mixed solution with a certain viscosity. During this process, thiamine and chitosan are uniformly distributed between the long chains of polyvinyl alcohol under thermodynamic drive, while cellulose achieves physical dispersion under high-speed shear force.

[0009] Following this, a low-temperature doping process is performed. The previously high-temperature mixed solution is removed from the heating environment and allowed to cool naturally in a cleanroom. Once the solution temperature has decreased to room temperature (25℃±2℃), a predetermined mass of CdSe / ZnS water-soluble quantum dot solution is slowly added dropwise. At this point, the stirring speed is reduced to 50-100 rpm for low-speed, light-protected stirring. This low-speed stirring process effectively prevents microbubbles generated by high-speed shearing from being entrained in the high-viscosity solution, ensuring the acoustic uniformity of the final material. The quantum dots are thoroughly mixed with the polyvinyl alcohol segments at room temperature. Because the high-temperature stage is avoided, the surface ligands of the quantum dots remain stable, and the fluorescence efficiency loss rate is less than 5%.

[0010] Finally, physical cross-linking and molding processes are performed. The uniformly mixed liquid material is injected into a pre-shaped mold, and the mold edges are sealed to prevent moisture evaporation. The mold is placed in a low-temperature freezing environment of -20℃±2℃ for 24 hours, causing the moisture to freeze and displace the polyvinyl alcohol (PVA) segments, promoting the PVA segments to move closer together in local high-concentration areas. Subsequently, the mold is moved to a room temperature environment of 25℃±2℃ for natural thawing for 24 hours. This freeze-thaw process constitutes a complete physical cross-linking cycle. By repeating the above freeze-thaw cycle five times, the growth and melting of ice crystals induce the formation of stable microcrystalline cross-linking points in the PVA molecular chains. The process parameters of the five cycles ensure that the material has an optical transmittance of not less than 85%, while maintaining the fluorescence activity of the quantum dots at over 95%, and finally, the finished product is obtained by demolding.

[0011] The technical principle of this invention lies in utilizing the high temperature sensitivity of the semiconductor band structure of CdSe / ZnS quantum dots. As the ambient temperature increases, the quantum dot lattice undergoes thermal expansion, and the electron-phonon coupling strengthens, leading to a narrowing of its band gap. The quantum dots embedded in the gel network exhibit a stable spectral response during temperature changes, with their peak wavelength showing an approximately linear relationship with temperature. By confining the local environment of the quantum dots through the matrix structure, signal fluctuations caused by non-radiative transitions can be reduced, thereby improving the linearity of temperature measurement. The fluorescence signal inside the material is acquired through an external optical acquisition system, and combined with a pre-calibrated wavelength-temperature curve, achieving non-contact, real-time online temperature measurement with a spatial resolution of 0.1℃. Since this physical process does not involve the breaking of chemical bonds or the denaturation of proteins, when the temperature decreases, the quantum dot band structure returns to its original state, and the fluorescence spectral characteristics shift synchronously, thus endowing the material with completely reversible thermal response characteristics.

[0012] Furthermore, when the temperature-spectral coupling response material based on hydrogel microstructure regulation is irradiated with high-intensity focused ultrasound (HIFU), the internal cellulose particles generate acoustic scattering, simulating the absorption and scattering of sound energy by biological tissue. The acoustic energy is converted into heat energy, leading to a local temperature increase and exciting the quantum dots to produce a spectral shift. The polyvinyl alcohol backbone maintains stable physicochemical properties within the temperature range of 30℃ to 160℃, without melting or decomposition, supporting the continuous operation of the quantum dots in high-temperature ablation monitoring experiments.

[0013] Specifically, this invention modifies the micropore structure of polyvinyl alcohol hydrogel by introducing thiamine. The hydrogen bond network formed by the thiamine molecules and polyvinyl alcohol alters the nucleation rate and growth size of ice crystals during freezing, resulting in a finer microstructure in the cross-linked gel. This structure, on the one hand, improves the material's encapsulation force for quantum dots, preventing leakage during long-term experiments; on the other hand, it enhances the material's tear resistance, preventing mechanical fatigue failure when subjected to high-frequency ultrasonic vibration.

[0014] The synergistic effect of chitosan and thiamine is also reflected in improving the chemical stability of the material. The addition of chitosan not only inhibits microbial growth but also captures residual oxygen in the solution through its active groups on its molecular chain, slowing down the photo-oxidation rate of quantum dots during photoexcitation. The five freeze-thaw cycles used in the preparation method are crucial for achieving performance balance. Fewer than five cycles result in insufficient mechanical strength, making the material brittle under high-intensity ultrasonic treatment; more than five cycles lead to excessive polyvinyl alcohol crystallinity, reducing the material's optical transparency and hindering external acquisition of fluorescence signals.

[0015] The beneficial effects of this invention are reflected in the following aspects: Firstly, it achieves high-precision quantitative monitoring. This invention abandons the low-precision methods of traditional thermosensitive materials that rely on visual color identification or RGB image analysis. By precisely capturing the minute shifts in the peak wavelength of quantum dot fluorescence, a temperature inversion model based on spectroscopy is established. This approach improves the resolution of temperature monitoring to the order of 0.1℃, meeting the needs of precise temperature field distribution research in the focal domain of high-intensity focused ultrasound, and achieving a technological leap from "qualitative observation" to "quantitative measurement."

[0016] Secondly, it possesses excellent reversibility and real-time response capabilities. Since the band structure change of quantum dots is a physically reversible process, the material provided by this invention can rapidly recover its initial fluorescence characteristics after the heat source is removed. This characteristic allows a single phantom material to undergo hundreds or thousands of repeated experiments, significantly reducing research and testing costs. Simultaneously, the fluorescence response speed reaches the millisecond level, enabling real-time tracking of the dynamic rise and fall curves of the focal zone temperature during ultrasonic irradiation.

[0017] Third, it expands the measurement range of temperature-sensitive monitoring. Compared to traditional thermochromic inks or protein materials that typically only cover a narrow range of 20°C to 50°C, this invention utilizes the high-temperature stability of CdSe / ZnS quantum dots and the high melting point of polyvinyl alcohol to extend the effective temperature measurement range to 30°C to 160°C. This range not only covers the 42°C to 45°C range for tumor thermotherapy but also encompasses the 60°C to 100°C and above range for high-temperature ablation and tissue carbonization research.

[0018] Fourth, it significantly improves biocompatibility. The matrix material polyvinyl alcohol, the plasticizer thiamine (vitamin B1), and the preservative chitosan selected in this invention are all biocompatible or food-grade raw materials, completely replacing the acrylamide monomers in traditional processes, which have serious neurotoxicity and carcinogenic risks. The preparation process does not require complex chemical synthesis reactions, is friendly to the health of operators and the laboratory environment, and meets the requirements of green chemistry development.

[0019] Fifth, it achieves precise tissue simulation. By adjusting the proportion of cellulose added, the material of this invention closely matches human soft tissue in key acoustic parameters such as acoustic impedance, sound velocity, and sound attenuation coefficient. The acoustic impedance of the material is maintained between 1.5Mrayl and 1.7Mrayl, and the sound velocity is maintained between 1540m / s and 1580m / s. This ensures that the propagation behavior of ultrasound waves within the material is highly consistent with that in real tissue, guaranteeing the clinical reference value of the experimental data.

[0020] Sixth, it enhances the long-term stability and storage life of the material. The special process of "high-temperature dissolution and low-temperature doping" minimizes damage to the fluorescence performance of quantum dots during preparation. The addition of thiamine and chitosan not only improves mechanical properties but also constructs a multi-layered chemical protection system, enabling the material to maintain stable fluorescence performance for over 6 months under light-protected refrigerated conditions, solving the problems of traditional phantoms being prone to spoilage and water loss.

[0021] In summary, this invention, through specific component design and physical cross-linking processes, provides a safe, precise, reversible, and wide-range temperature-spectral coupling response material based on hydrogel microstructure regulation. This offers advanced technical means and a reliable experimental platform for equipment evaluation, parameter optimization, and clinical protocol development for high-intensity focused ultrasound and other thermotherapy technologies. The technical solution described in this invention is not limited to the field of ultrasound phantoms; it also has broad application prospects in microwave thermotherapy monitoring, laser ablation evaluation, and thermal management monitoring of precision electronic components. Those skilled in the art can obtain customized thermosensitive materials that meet different hardness, attenuation requirements, and temperature ranges by adjusting the component ratios and cycling process parameters. The implementation of this invention provides a high-performance standardized testing tool for the biomedical engineering field, with significant social and economic benefits. Attached Figure Description

[0022] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0023] Figure 1 A photograph of the actual material prepared according to the embodiment of the present invention, which is a temperature-spectral coupling response material based on hydrogel microstructure regulation. Figure 2 This is a schematic diagram of the structure of the HIFU transducer in this embodiment of the invention, showing that the focal region generated by the transducer is located inside the temperature-spectral coupling response material based on the hydrogel microstructure. Figure 3 The graph shows the fluorescence spectrum of the CdSe / ZnS quantum dots involved in this invention as a function of temperature. Figure 4 This is a linear fitting graph of the fluorescence peak wavelength of the CdSe / ZnS quantum dots involved in this invention as a function of temperature. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions in the embodiments of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are only some embodiments of this invention, not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0025] The present invention will be specifically described below through embodiments. It should be noted that the following embodiments are only used to further illustrate the present invention and should not be construed as limiting the scope of protection of the present invention. Those skilled in the art can make some non-essential improvements and adjustments to the present invention based on the above description.

[0026] The present invention will be further described below with reference to the accompanying drawings and specific embodiments. The present invention provides a temperature-spectral coupling response material based on hydrogel microstructure regulation, which, through specific component design and physical cross-linking process, deeply integrates the high-precision fluorescence temperature sensing characteristics of quantum dots with the biotissue simulation characteristics of polyvinyl alcohol hydrogel, thereby realizing real-time, reversible, and quantitative monitoring of the temperature field during hyperthermia such as high-intensity focused ultrasound.

[0027] This embodiment provides a temperature-spectral coupling response material based on hydrogel microstructure regulation. Its core components include degassed water, polyvinyl alcohol (PVA), thiamine, chitosan, CdSe / ZnS water-soluble quantum dots, and cellulose. In the material's microstructure, PVA forms a three-dimensional network hydrogel framework through physical cross-linking, with the degassed water filling the pores of the framework as a sound propagation medium. Thiamine molecules utilize their abundant hydroxyl groups to form competitive hydrogen bonds with the hydroxyl groups on the PVA chains, thereby inserting themselves between PVA molecular chains and weakening intermolecular forces, thus endowing the material with excellent flexibility. Chitosan is uniformly distributed in the system, utilizing its amino groups to perform antibacterial and preservative functions. CdSe / ZnS water-soluble quantum dots, as the core temperature-sensitive element, are uniformly dispersed within the hydrogel network, exhibiting... Figure 1 The transparent and uniform state shown ensures efficient transmission of excitation and emission light within the material. Cellulose particles act as acoustic scattering centers, simulating the ultrasonic attenuation characteristics of human tissue through the difference in acoustic impedance between them and the matrix.

[0028] The preparation process of the temperature-spectral coupling response material based on hydrogel microstructure regulation described in this embodiment strictly follows the following steps: S1: Preliminary preparation of the matrix solution. Weigh 75 wt% degassed deionized water into a sealed container. The degassed deionized water has been pre-degassed by a vacuum pump to remove tiny air bubbles that may interfere with ultrasonic propagation. Then, add 10 wt% polyvinyl alcohol, 7 wt% thiamine, 0.5 wt% chitosan, and 7.5 wt% cellulose sequentially to the water. Place the container on a magnetic stirring platform and seal the container opening with aluminum foil to prevent moisture evaporation and imbalance of component ratios. Start the stirring device, set the speed to 700 rpm, and slowly raise the temperature to 95°C. Maintain constant temperature stirring for 30 minutes at this temperature to ensure that the polyvinyl alcohol particles undergo sufficient swelling and dissolution, forming a homogeneous, transparent, and viscous matrix solution. 95°C serves as the critical temperature point, ensuring that the crystalline regions of the fully alcoholystolytic polyvinyl alcohol are completely destroyed, thus forming a stable molecular solution.

[0029] S2: Perform cooling treatment. After heating is stopped, allow the matrix solution to cool naturally at room temperature. Monitor the solution temperature in real time until it reaches approximately 25°C. This cooling step is crucial for protecting the activity of the quantum dots, preventing potential damage to the surface ligands and core-shell structure of the quantum dots from high temperatures.

[0030] S3: Quantum doping and mixing. Add 5 wt% water-soluble CdSe / ZnS quantum dot solution to the cooled matrix solution. The average particle size of the quantum dots was selected to be 9 nm, which ensures significant quantum confinement effect and high fluorescence efficiency. Then, reduce the magnetic stirrer speed to 80 rpm and perform low-speed stirring for approximately 5 minutes. This low-speed stirring process effectively prevents air from being entrained into the high-viscosity system and forming bubbles, ensuring the monodispersity of the quantum dots in the polyvinyl alcohol network precursor, thereby avoiding concentration quenching.

[0031] S4: Perform physical cross-linking molding process. Inject the uniformly mixed material into a mold of a pre-designed shape. Place the mold in a -20°C freezer for 24 hours, then remove it and allow it to thaw naturally at 20°C for 24 hours. By repeating the above freeze-thaw cycle 5 times, the exclusion effect generated by ice crystal growth promotes the high aggregation of polyvinyl alcohol molecular chains in local areas, forming stable microcrystalline regions as physical cross-linking points through hydrogen bonding. After 5 cycles, the material possesses the mechanical strength required to simulate biological tissue while maintaining good optical transparency, and is finally demolded to obtain... Figure 1 The finished product shown is a temperature-spectral coupling response material based on hydrogel microstructure regulation.

[0032] In practical application scenarios, such as Figure 2 As shown, the prepared temperature-spectral coupling response material based on hydrogel microstructure regulation was placed in the water bath of an ultrasound therapy system. The HIFU transducer emitted high-intensity focused ultrasound waves, which passed through the phantom matrix and converged at its internal focal point. Due to the uniform distribution of cellulose scattering agent within the phantom, its acoustic parameters highly matched those of human tissue, resulting in intense absorption and conversion of acoustic energy in the focal region, forming a biological focal zone. As the temperature of the focal zone increased, the CdSe / ZnS quantum dots embedded in the hydrogel framework sensed changes in the localized thermal field.

[0033] The operating principle of this invention is highly dependent on the photoluminescence properties of quantum dots. For example... Figure 3 As shown, the emission spectrum of CdSe / ZnS quantum dots exhibits a highly regular change with increasing temperature. The physical mechanism lies in the semiconductor lattice expansion and enhanced electron-phonon coupling caused by increasing temperature, which in turn narrows the band gap of the quantum dots. In macroscopic observations, this manifests as a gradual decrease in fluorescence peak intensity and a redshift of the center wavelength of the fluorescence peak. Figure 4 As shown, within a wide temperature range of 30℃ to 160℃, the fluorescence peak wavelength of this material linearly shifts from 600nm to 620nm, and its linear fit is... The temperature resolution exceeds 0.98, achieving a resolution of 0.1℃.

[0034] When researchers irradiate a temperature-spectral coupling response material based on the hydrogel microstructure with 450nm excitation light emitted from an external laser, the quantum dots inside the material are excited and emit fluorescence signals. These fluorescence spectra are collected through an optical window or fiber optic probe and transmitted to a spectrometer for processing. Based on the real-time peak wavelength shift and a pre-calibrated linear regression equation, the system can instantly calculate the precise temperature value at the biological focal zone. Because this color-changing process is based on the physical evolution of the band structure rather than a chemical reaction, the fluorescence spectrum of the quantum dots completely returns to its initial state after the HIFU transducer stops working and heat dissipates, achieving a high degree of reversibility in temperature monitoring.

[0035] In this embodiment, the introduction of thiamine significantly improves the experimental performance of the material. Compared to traditional glycerol plasticizers, the hydrogen bond network formed by thiamine molecules and polyvinyl alcohol segments is more robust. This prevents the phantom from developing fatigue cracks when subjected to high-frequency, high-pressure ultrasonic vibration, ensuring the continuity of the experiment. Simultaneously, the addition of chitosan allows the phantom to maintain stability for over three months under sealed conditions at room temperature, without mold growth or performance degradation.

[0036] Furthermore, the unique "high-temperature dissolution followed by low-temperature doping" process employed in this embodiment solves the challenge of ensuring the long-term stability of quantum dots in a hydrogel matrix. In the high-temperature stage of step S1, polyvinyl alcohol fully opens its chain segments, while the addition of quantum dots in the room-temperature stage of step S3 protects the ZnS passivation shell on the quantum dot surface. This stepwise method ensures that the final material maintains an extremely high fluorescence signal-to-noise ratio in high-temperature ablation experiments ranging from 30°C to 160°C.

[0037] Polyvinyl alcohol and cellulose were purchased from Sigma-Aldrich; thiamine was purchased from Sinopharm Chemical Reagent Co., Ltd.; chitosan was purchased from Nantong Lvshen Bioengineering Co., Ltd.; and CdSe / ZnS water-soluble quantum dots (8 μmol / L) were purchased from Aladdin.

[0038] Other experimental equipment included: a magnetic stirring heating table (IKAC-MAGHS7), a freezer (Haier DW-40L262), and a fluorescence spectrometer (Ocean Optics QEPro).

[0039] Example 1

[0040] This embodiment provides a temperature-spectral coupling response material based on hydrogel microstructure regulation. Its components, by weight percentage, are: 74 wt% degassed deionized water, 12 wt% polyvinyl alcohol, 6 wt% thiamine, 0.5 wt% chitosan, 5 wt% CdSe / ZnS water-soluble quantum dots, and 2.5 wt% cellulose. The polyvinyl alcohol has a degree of polymerization of 1700 and a degree of alcoholysis of 99%. The CdSe / ZnS quantum dot core has a diameter of 9 nm and is surface-modified with carboxyl groups. The cellulose particle size is 10 μm.

[0041] The preparation method includes the following steps: S1: Weigh each component according to the ratio, add polyvinyl alcohol, thiamine, chitosan and cellulose to deaerated deionized water in sequence, and stir continuously at 750 rpm for 30 minutes at 95℃±1℃ to form a matrix solution. S2: Allow the matrix solution to cool naturally to 25℃±2℃; S3: Slowly add CdSe / ZnS quantum dot solution dropwise to the cooled matrix solution, and stir at 80 rpm in the dark for 5 minutes to obtain a mixture; S4: Inject the mixture into a mold, seal it, and freeze it at -20°C for 24 hours. Then thaw it at 25°C for 24 hours. Repeat this freeze-thaw cycle 5 times to obtain a temperature-spectral coupling response material based on hydrogel microstructure regulation.

[0042] Performance testing: 1. Temperature measurement performance: Using a fluorescence spectrometer, within the temperature range of 30℃ to 160℃, the fluorescence peak wavelength linearly shifts from 600.2nm to 619.8nm, with a linear fitting coefficient R² = 0.986. The temperature measurement resolution reaches 0.1℃.

[0043] 2. Acoustic characteristics: At a frequency of 1MHz, the material's acoustic attenuation coefficient was measured to be 0.52dB / cm, the sound velocity was 1562m / s, and the acoustic impedance was 1.58Mrayl, which is close to that of human liver tissue.

[0044] 3. Mechanical properties and stability: The Young's modulus of the material is 22 kPa. After being stored in a light-protected environment at 4°C for 6 months, its fluorescence intensity decayed by less than 5%, and there was no obvious mold growth or dehydration.

[0045] Example 2

[0046] This embodiment is basically the same as Example 1, except that the weight percentage of the components is adjusted as follows: 70 wt% degassed deionized water, 10 wt% polyvinyl alcohol, 5 wt% thiamine, 0.6 wt% chitosan, 3.4 wt% CdSe / ZnS water-soluble quantum dots, and 11 wt% cellulose. The cellulose content is increased to 11 wt%, the particle size is 50 μm, and the quantum dots are surface-modified with hydroxyl groups. Stirring is performed in step S1 for 60 minutes.

[0047] Surface-modified hydroxyl groups.

[0048] Performance testing: This embodiment aims to verify the performance of hydroxyl-modified quantum dots in high acoustic attenuation scenarios. The test results are as follows: 1. Acoustic Characteristics: Due to the increased cellulose content, the acoustic attenuation coefficient is increased to 0.68 dB / cm at 1 MHz, simulating higher attenuation in human tissues (such as muscle or some glandular tissues). The sound velocity is 1545 m / s, and the acoustic impedance is 1.61 Mrayl.

[0049] 2. Temperature Measurement Performance: Despite increased acoustic attenuation, the fluorescence signal of the quantum dots can still be effectively acquired. Within the temperature range of 30-160℃, the peak wavelength redshift characteristic remains stable, with a linearity R² = 0.982 and a resolution of 0.1℃. Mechanical strength is improved, with a Young's modulus of 28 kPa.

[0050] 3. Mechanical properties: The matrix exhibits superior uniformity, and the polyvinyl alcohol is completely dissolved. The mechanical properties of the material are not significantly different from those in Example 1.

[0051] Example 3

[0052] This embodiment is basically the same as Example 1, except that the weight percentages of the components are adjusted as follows: 80 wt% degassed deionized water, 8 wt% polyvinyl alcohol, 6.4 wt% thiamine, 0.4 wt% chitosan, 1 wt% CdSe / ZnS water-soluble quantum dots, and 4.2 wt% cellulose. The number of freeze-thaw cycles in the preparation method is reduced to 4.

[0053] Performance testing: This example aims to verify the performance lower limit at lower PVA concentrations and fewer cycles. The test results are as follows: 1. Mechanical properties: The Young's modulus decreased to 20 kPa, making the material more flexible. After four freeze-thaw cycles, the material could still be molded, but its mechanical strength was lower than that of Example 1.

[0054] 2. Temperature Measurement and Optical Performance: Optical transmittance is 88%. Temperature measurement performance remains stable, with a good linear relationship between peak wavelength shift and temperature (R²=0.975). However, under prolonged HIFU irradiation, its fatigue resistance is slightly inferior to that of Example 1.

[0055] Example 4

[0056] The components, by weight percentage, are: 73% degassed deionized water, 10% polyvinyl alcohol, 10% thiamine, 0.5% chitosan, 4.5% CdSe / ZnS water-soluble quantum dots, and 2% cellulose. The freeze-thaw cycle number of the preparation method was increased to 6 times.

[0057] Performance test results: Good flexibility and temperature resistance; 10% thiamine still maintains a stable plasticizing effect; 2% cellulose still provides sufficient acoustic scattering. Transparency is 82%; fluorescence is slightly reduced but still usable.

[0058] Comparative Example 1 This comparative example is basically the same as Example 1, except that thiamine is not added and the water content is 80% degassed.

[0059] Performance testing: 1. Mechanical properties: The material exhibits significantly increased brittleness, making it prone to cracking during demolding and exposure to ultrasonic vibration. Although the Young's modulus is 24 kPa, the elongation at break is reduced by more than 50%.

[0060] 2. Temperature measurement performance: The slightly poor uniformity of quantum dot distribution leads to poor spatial consistency of fluorescence signal and reduced temperature measurement repeatability.

[0061] Comparative Example 2 This comparative example is basically the same as Example 1, except that an equal amount of glycerol is used instead of thiamine as a plasticizer, and the mixture is stirred for 30 minutes in step S3.

[0062] Performance testing: 1. Stability: During storage, the material exhibits significant glycerol precipitation, leading to changes in the material's surface properties and unstable acoustic parameters.

[0063] 2. Quantum dot protection: During the freezing and thawing process, the fluorescence efficiency loss rate of quantum dots reaches 12%, which is higher than the 5% of the present invention, affecting the temperature measurement accuracy.

[0064] Comparative Example 3 This comparative example is basically the same as Example 1, except that in step S3 of the preparation method, the quantum dots are added at a high temperature (95°C).

[0065] Performance testing: Fluorescence performance: Due to the high temperature, the quantum dots are damaged, and the initial fluorescence efficiency decreases by 60%. In subsequent temperature measurement experiments, the fluorescence signal is extremely weak and the signal-to-noise ratio is poor, making it impossible to achieve accurate temperature measurement of 0.1℃.

[0066] Conclusion: This study verifies the necessity of the "high-temperature dissolution, low-temperature doping" process of the present invention.

[0067] Comparative Example 4 This comparative example is basically the same as Example 1, except that it contains 70% degassed deionized water, 12% thiamine, and 10% polyvinyl alcohol.

[0068] Performance test: White crystals precipitated, fluorescence was uneven, unusable.

[0069] Conclusion: Thiamine levels exceeding 10% will disrupt matrix stability.

[0070] Comparative Example 5 This comparative example is basically the same as Example 1, except that it contains 78% degassed deionized water, 10% polyvinyl alcohol, 4% thiamine, and only one freeze-thaw cycle.

[0071] Performance testing revealed that the material has extremely low strength and cannot be demolded.

[0072] Conclusion: When the thiamine / PVA mass ratio is less than 0.5:1, the performance deteriorates.

[0073] Comparative Example 6 This comparative example is basically the same as Example 1, except that in step S4 the freezing conditions are changed to -80°C for 6 hours, the thawing is still 25°C / 24h, and the freezing and thawing cycle is 7 times.

[0074] Performance testing: Uneven microstructure, transparency <70%.

[0075] Conclusion: Deviation from the parameters leads to uneven microstructure. Combined with Comparative Example 5, this shows that both excessive and insufficient freeze-thaw cycles cause performance degradation.

[0076] Based on specific experimental data, when the mass percentage of cellulose was adjusted to 5 wt%, the acoustic attenuation coefficient of the material at a frequency of 1 MHz was adjusted to 0.6 dB / cm, which is highly similar to the acoustic characteristics of human liver tissue. During HIFU irradiation experiments, a fluorescence monitoring system revealed that when the focal temperature reached 65℃, the fluorescence peak wavelength of the quantum dots inside the material red-shifted to 605.2 nm; when the temperature was further increased to 100℃, the wavelength red-shifted to 611.8 nm. This precise correlation allows researchers to overcome the limitations of traditional protein phantoms, which can only qualitatively determine the focal temperature by whitening, enabling a more refined evaluation of hyperthermia treatment protocols.

[0077] Another significant advantage of the material described in this invention lies in its multi-parameter temperature measurement capability. Besides utilizing... Figure 4In addition to the wavelength redshift characteristics shown, the system can also simultaneously extract the attenuation slope of fluorescence intensity and the extent of the full width at half maximum (FWHM) expansion as auxiliary criteria. Through a multi-parameter fusion algorithm, interference from excitation light fluctuations or ambient stray light on the temperature measurement results is further eliminated. This monitoring scheme based on deep spectroscopic features provides a standardized tool for in vitro simulation studies of various clinical treatment techniques such as ultrasound ablation, microwave hyperthermia, and laser interstitial hyperthermia.

[0078] During the optimization of the preparation process, it was found that the number of freeze-thaw cycles has a significant impact on the material properties. If the number of cycles is less than 4, the physical strength of the material is insufficient, and it is prone to deformation during demolding. If the number of cycles exceeds 6, the high crystallinity of polyvinyl alcohol will cause the material to change from transparent to translucent or even opaque, significantly reducing the collection efficiency of fluorescence signals. Therefore, the 5-cycle scheme selected in the examples is the optimal process path that balances mechanical strength and optical transparency.

[0079] The preparation method provided in this embodiment also possesses extremely high tunability. By changing the core components or particle size of the quantum dots, the monitoring temperature range can be customized. For example, if monitoring of carbonization processes at higher temperatures is required, InP / ZnS quantum dots with higher stability can be selected; if operation in a strong scattering environment is required, the emission peak of CdSe / ZnS quantum dots can be adjusted to the near-infrared band. This flexibility makes the technical solution described in this invention highly adaptable to various industries.

[0080] In summary, this invention successfully constructed a novel tissue simulation material based on the microstructure regulation of hydrogels and its temperature-spectral coupling response by integrating high-performance CdSe / ZnS quantum dots into a modified polyvinyl alcohol hydrogel system. This material not only solves the problems of high toxicity, irreversibility, and low precision of traditional phantom materials, but also achieves digital and automated online monitoring of the hyperthermia process through spectral monitoring. It demonstrates extremely high application value in medical device development, hyperthermia dosimetry research, and clinical operation training.

[0081] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention can have various modifications and variations. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A temperature-spectral coupling response material based on hydrogel microstructure regulation, characterized in that, Its components, by weight percentage, include: 70 wt% to 80 wt% deaerated deionized water, 8 wt% to 12 wt% polyvinyl alcohol, 5 wt% to 10 wt% thiamine, 0.4 wt% to 0.6 wt% chitosan, 1 wt% to 5 wt% CdSe / ZnS water-soluble quantum dots, and 2 wt% to 11 wt% cellulose.

2. The temperature-spectral coupling response material based on hydrogel microstructure regulation according to claim 1, characterized in that, The polyvinyl alcohol has a degree of polymerization of 1700 and a degree of alcoholysis of 99%.

3. The temperature-spectral coupling response material based on hydrogel microstructure regulation according to claim 1, characterized in that, The core diameter of the CdSe / ZnS water-soluble quantum dots is 9 nm, and the surface of the CdSe / ZnS water-soluble quantum dots is modified with carboxyl functional groups or hydroxyl functional groups.

4. The temperature-spectral coupling response material based on hydrogel microstructure regulation according to claim 1, characterized in that, The cellulose has a particle size distribution between 10 μm and 50 μm.

5. The temperature-spectral coupling response material based on hydrogel microstructure regulation according to claim 1, characterized in that, The mass ratio of thiamine to polyvinyl alcohol is 0.5:1 to 0.8:

1.

6. A method for preparing a temperature-spectral coupling response material based on hydrogel microstructure regulation according to any one of claims 1 to 5, characterized in that, Includes the following steps: S1: Weigh polyvinyl alcohol, thiamine, chitosan and cellulose according to the preset ratio, add them to deaerated deionized water in sequence, and stir continuously for more than 30 minutes at a speed of 700 rpm to 800 rpm under the condition of 95℃±1℃ to form a matrix solution. S2: Remove the matrix solution from the heating environment and allow it to cool naturally to 25℃±2℃ at room temperature; S3: Slowly add CdSe / ZnS water-soluble quantum dot solution dropwise to the cooled matrix solution, and stir in the dark at a speed of 50 rpm to 100 rpm to obtain a mixture; S4: Inject the mixture into a mold and seal it, then perform freezing and thawing cycles to obtain a temperature-spectral coupling response material based on hydrogel microstructure regulation through physical cross-linking molding.

7. The preparation method according to claim 6, characterized in that, In step S1, intermolecular hydrogen bonds are formed between the hydroxyl groups in the thiamine molecule and the hydroxyl groups on the polyvinyl alcohol molecular chain.

8. The preparation method according to claim 6, characterized in that, In step S3, the low-speed stirring time is 5 minutes, and the fluorescence efficiency loss rate of the CdSe / ZnS water-soluble quantum dots is less than 5%.

9. The preparation method according to claim 6, characterized in that, The specific process parameters for the freezing and thawing cycle in step S4 are as follows: the mold is placed in an environment of -20℃±2℃ for 24 hours, and then moved to an environment of 25℃±2℃ for natural thawing for 24 hours.

10. The preparation method according to claim 9, characterized in that, The freezing and thawing cycles were repeated five times to form stable microcrystalline cross-linking points within the temperature-spectral coupling response material regulated by the hydrogel microstructure, thereby supporting the formation of a biological focal zone within the material when irradiated by a HIFU transducer.

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