A transmission-type metasurface near-field focusing microwave hyperthermia system

By designing a transmissive metasurface near-field focused microwave hyperthermia system, and utilizing phase modulation of the 2.45 GHz band and subwavelength unit structure, high-energy-density precise focusing was achieved in a live tumor model. This solved the problem of existing systems being unable to achieve precise focusing in live tumor models, and achieved efficient tumor suppression and biosafety.

CN122376248APending Publication Date: 2026-07-14AIR FORCE UNIV PLA
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Patent Information

Application Number
CN202610836030.9
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2026-06-10
Publication Date
2026-07-14

AI Technical Summary

Technical Problem

Existing microwave hyperthermia systems struggle to achieve precise and efficient energy focusing in living tumor models, and the existing devices are bulky and expensive, failing to meet clinical treatment needs.

Method used

A transmissive metasurface near-field focused microwave hyperthermia system is designed, employing a 2.45 GHz microwave feed and a transmissive metasurface array. By adjusting the geometric parameters of the subwavelength unit structure, the spatial phase distribution of microwaves is achieved to form a high-energy-density focusing point in the near-field region. Combined with a fixation and positioning device for a tumor-bearing animal model, precise hyperthermia at the tumor site is ensured.

Benefits of technology

It achieves high-energy-density precise focusing in in vivo tumor models with a tumor inhibition rate of up to 96%, while ensuring that the temperature of the surrounding healthy tissue is maintained within a safe range. It provides a complete in vivo validation method to verify the system's bioeffectiveness and safety.

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Abstract

The application discloses a transmission type metasurface near-field focusing microwave hyperthermia system and relates to the technical field of biomedical engineering based on electromagnetic fields. The application is characterized in that a plurality of subwavelength unit structures arranged in an array are arranged on the outgoing path of a microwave feed source, the geometric structure parameters of a metal pattern layer in the subwavelength unit structures are adjusted, a preset spatial phase distribution is exerted on the transmitted microwaves by the transmission type metasurface array, a high-energy-density focusing focal point is formed to perform hyperthermia, the process is not simply frequency replacement, but according to the resonance condition of a Fabry-Perot resonant cavity, the medium thickness, the dielectric constant and the geometric parameters and spacing of the metal pattern layer in the subwavelength unit structures are redesigned, the resonance peak is accurately dropped on a preset working frequency, a deeper penetration depth that meets the requirement is achieved, the transmission efficiency and the accurate phase control ability at a specific frequency are extremely high, and thus the precise thermal ablation of a living tumor is realized.
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Description

Technical Field

[0001] This invention relates to the field of biomedical engineering technology based on electromagnetic fields, and in particular to a transmissive metasurface near-field focused microwave hyperthermia system. Background Technology

[0002] Microwave hyperthermia, a non-invasive physical therapy for tumors, selectively heats tumor tissue to an effective therapeutic temperature (typically 41-45°C) using microwave energy to induce tumor cell apoptosis or necrosis. It can also synergize with radiotherapy and chemotherapy, demonstrating significant clinical application potential. The core challenge of this technology lies in how to precisely and efficiently focus microwave energy on deep or specifically shaped tumor areas while minimizing collateral damage to surrounding healthy tissues.

[0003] In the early stages of microwave hyperthermia development, researchers mainly used systems based on traditional antenna arrays (such as phased arrays). By adjusting the feed phase and amplitude of each antenna element in the array, constructive interference could be formed in the target area, thereby achieving energy focusing. However, such systems are usually large in size and expensive, and require complex and costly phase shifters and feed networks for beam control. Therefore, in recent years, researchers have turned their attention to metasurface technology. Metasurfaces can arbitrarily shape the phase, amplitude and other parameters of electromagnetic waves by independently adjusting the geometric parameters of the unit structure at the subwavelength scale, thereby forming a high-energy-density focus in the near-field region.

[0004] Currently used near-field focused microwave hyperthermia devices typically employ higher frequency bands such as 5.8 GHz. The penetration depth of electromagnetic waves in biological tissues at this frequency is only a few millimeters. For ex vivo phantoms cut into thin slices, this does not pose an obstacle. However, in real subcutaneous tumor models, the treatment target area often needs to cover a deeper location. Even for mouse subcutaneous tumors, the thickness plus the coverage of skin and connective tissue often exceeds the effective penetration depth of 5.8 GHz electromagnetic waves. Therefore, existing devices cannot perform selective penetration therapy based on the frequency band required for clinical treatment. Summary of the Invention

[0005] This invention provides a transmissive metasurface near-field focused microwave hyperthermia system, which can solve the problems existing in the prior art.

[0006] This invention provides a transmissive metasurface near-field focusing microwave hyperthermia system, comprising a microwave feed source and a transmissive metasurface array; The microwave feed source is used to generate microwaves at a preset operating frequency and irradiate the transmissive metasurface array. The transmissive metasurface array includes multiple subwavelength unit structures arranged in an array and configured on the emission path of the microwave feed source. Each subwavelength unit structure includes two dielectric substrates and a metal pattern layer distributed therebetween, forming a Fabry-Perot resonant cavity. By adjusting the geometric parameters of the metal pattern layer within the subwavelength unit structure, the resonance conditions of the Fabry-Perot resonant cavity are changed, so that the transmissive metasurface array applies a preset spatial phase distribution to the transmitted microwaves, thereby forming a focusing point with a higher energy density than preset in the near-field region on the emission surface side of the transmissive metasurface array, to perform microwave thermotherapy on the target.

[0007] Preferably, it also includes a device for fixing and positioning tumor-bearing animal models; The tumor-bearing animal model fixation and positioning device is used to repeatedly align and attach the subcutaneous tumor site of the tumor-bearing live animal to the focal point formed by the transmissive metasurface array, so as to achieve continuous and spatially selective microwave focused thermotherapy on the tumor site.

[0008] Preferably, the microwaves generated by the microwave feed source operate at a frequency of 2.45 GHz, which is used to ensure tissue penetration depth while achieving wavefront phase modulation.

[0009] Preferably, the subwavelength unit structure includes a first metal layer, a first dielectric substrate, a second metal layer, a second dielectric substrate, and a third metal layer arranged sequentially from top to bottom; The first and third metal layers are both a set of parallel metal gratings, and the second metal layer is an umbrella-shaped metal resonant ring.

[0010] Preferably, the phase modulation of the subwavelength unit structure is achieved by changing the opening angle of the umbrella-shaped metal resonator. α and rotation angle β and the length of the metal grating l With width w 2. w 3. To achieve this.

[0011] Preferably, the transmissive metasurface array is configured to form a focusing point with a higher energy density than a preset energy density in the near-field region 310 mm from its exit surface.

[0012] This invention also provides a method for verifying the application of a tumor-bearing animal model, which is implemented using a transmissive metasurface near-field focused microwave hyperthermia system as described above, and includes the following steps: The tumor-bearing live animal is fixed on the tumor-bearing animal model fixation and positioning device, so that its subcutaneous tumor site is precisely aligned with and closely attached to the near-field focusing point of the transmissive metasurface array. The microwave feed source is activated to provide continuous, periodic microwave thermotherapy to the tumor site over several days. The efficacy of hyperthermia was comprehensively evaluated after the periodic hyperthermia period by real-time temperature distribution, changes in tumor volume and inhibition rate, and H&E staining pathological analysis based on tissue sections.

[0013] Preferably, in the periodic microwave hyperthermia, the power of the microwaves generated by the microwave feed source is controlled to bring the temperature of the tumor site to and maintain it within a treatment temperature window of 41.5°C to 43.5°C.

[0014] Preferably, the real-time temperature distribution data is compared with the theoretical calculation results based on the Pennes biothermal equation and incorporating the focused electric field distribution of the transmissive metasurface array as the electromagnetic thermal power density heat source term, so as to quantitatively verify the spatial selective heating capability and energy deposition mechanism of the transmissive metasurface array in the living physiological environment from the perspective of biothermal transfer mechanism.

[0015] Preferably, the determination of tumor volume change and inhibition rate is achieved by periodically measuring and recording the three-dimensional dimensions of the tumor to plot a tumor growth curve and obtain the tumor volume inhibition rate.

[0016] This invention provides a transmissive metasurface near-field focused microwave hyperthermia system, which has the following advantages compared with the prior art: This invention utilizes a transmissive metasurface array positioned along the emission path of microwaves at a preset operating frequency generated by a microwave feed. This array comprises multiple subwavelength unit structures arranged in an array. By adjusting the geometric parameters of the metal patterned layers within the subwavelength unit structures, the transmissive metasurface array applies a preset spatial phase distribution to the transmitted microwaves, thereby forming a high-energy-density focusing point in the near-field region of the transmissive metasurface array's emission surface for thermotherapy. This process is not simply a change of frequency; rather, based on the resonance conditions of the Fabry-Perot resonator, the dielectric thickness, dielectric constant, and geometric parameters and spacing of the metal patterned layers within the subwavelength unit structures are redesigned. This ensures that the resonance peak precisely falls at the preset operating frequency, achieving a deeper penetration depth as required. This results in extreme transmission efficiency at a specific frequency while maintaining a near 360° phase modulation capability and a transmission amplitude exceeding -2dB, enabling precise thermal ablation of living tumors. Essentially, it functions as a "microwave energy scalpel" for precise thermotherapy at a preset depth, allowing for selective penetration therapy based on the frequency band required for clinical treatment. Attached Figure Description

[0017] Figure 1 This is a schematic diagram of the overall experimental setup and in vivo application scenario provided in the embodiments of the present invention; Figure 2This is a schematic diagram illustrating the structural design and focusing performance of a transmissive metasurface provided in an embodiment of the present invention; Figure 3 This is a schematic diagram illustrating the verification results of the thermotherapy effect and long-term efficacy in a tumor-bearing live mouse model provided in this embodiment of the invention; wherein: (a) is an infrared comparison image before and after treatment; (b) is a temperature change image of the tumor site before and after treatment; (c) is a diagram of the treatment process; (d) is a diagram of tumor volume change; (e) is a diagram of tumor length and width change; and (f) is a diagram of tumor weight after treatment. Figure 4 The following is a schematic diagram of the simulation verification results of the near-field focusing performance provided in the embodiments of the present invention; wherein: (a) is a temperature distribution diagram of the Comsol simulated tumor model; (b) is a temperature curve along the dashed line in (a); (c) is a temperature distribution diagram of the multi-layer biological tissue model at different focusing distances; and (d) is a temperature curve along the tissue depth direction. Detailed Implementation

[0018] To make the above-mentioned objects, features, and advantages of the present invention more apparent and understandable, specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings. Many specific details are set forth in the following description to provide a thorough understanding of the present invention. However, the present invention can be practiced in many other ways different from those described herein, and those skilled in the art can make similar modifications without departing from the spirit of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0019] In the early stages of microwave hyperthermia development, researchers mainly used systems based on traditional antenna arrays (such as phased arrays). By adjusting the feed phase and amplitude of each antenna element in the array, constructive interference can be formed in the target area, thereby achieving energy focusing. However, such traditional systems are usually large in size and expensive, and require complex and expensive phase shifters and feed networks for beam control. More importantly, due to the diffraction limit and strong coupling effect between elements, it is difficult to achieve subwavelength-level fine focusing in the near field region, and energy utilization efficiency and spatial selectivity need to be improved.

[0020] To overcome the aforementioned bottlenecks of traditional antenna arrays, researchers have recently turned their attention to metasurface technology. Metasurfaces, as two-dimensional metamaterials, can arbitrarily manipulate the wavefront of electromagnetic waves with extremely low profile and cost. Their basic principle lies in the fact that metasurfaces are composed of a large number of subwavelength unit cells arranged periodically or aperiodically. By independently designing the geometry, size, or orientation of each unit cell, specific phase abrupt changes in transmitted or reflected electromagnetic waves can be achieved. Through careful design of the metasurface unit cells, precise focusing of microwaves can be realized, providing the possibility for developing a new generation of low-cost, high-precision microwave hyperthermia systems. Preliminary studies have verified the feasibility of using metasurfaces for near-field focused heating, for example, successfully achieving localized temperature rise on ex vivo biological tissue phantoms (such as pork). However, these proof-of-concept works have also exposed a deeper and more critical technical bottleneck: the research level is severely detached from the real biological environment. Existing validation efforts are generally limited to the level of in vitro phantoms. This static and homogeneous medium cannot simulate the complex blood perfusion, metabolism, and dynamic heat exchange processes within living biological tissues. Therefore, the effectiveness and safety of the ideal heating effect obtained on phantoms in vivo are completely unknown, and the research conclusions lack direct clinical guidance.

[0021] Based on the current state of research, there is a significant gap between "physical feasibility" and "bioeffectiveness" in applying metasurfaces to microwave hyperthermia. Simply proving that metasurfaces "can be heated" is far from sufficient. The industry urgently needs a complete technical solution that not only includes a hyperthermia system that can work stably in vivo, but more importantly, establishes a scientific and comprehensive in vivo validation method to assess its long-term tumor suppression effect, biosafety, and consistency with theoretical models.

[0022] Based on this, the present invention provides a transmissive metasurface near-field focusing microwave hyperthermia system and its application verification in tumor-bearing animal models. The core of this system lies in constructing a transmissive metasurface array composed of subwavelength units and precisely designing its spatial phase distribution to achieve near-field precise focusing of 2.45 GHz microwaves; including: This invention designs a transmissive metasurface system specifically for in vivo hyperthermia, comprising: ① Microwave Feed and Metasurface Array: Utilizing the clinically compatible 2.45GHz operating frequency band, a suitable transmissive metasurface array is designed. This metasurface array consists of multiple subwavelength unit structures. By adjusting the geometric parameters of each unit structure on the array plane, the array generates a preset spatial phase distribution for the transmitted microwaves, enabling precise subwavelength focusing on the target area while maintaining tissue penetration depth. This metasurface can be implemented using a Fabry-Perot resonant cavity structure to achieve precise subwavelength focusing on the target area while maintaining tissue penetration depth.

[0023] ② Tumor-bearing animal model fixation and positioning device: Design a repeatable and high-precision animal fixation device to ensure that the tumor site of the tumor-bearing live animal can be stably and closely attached to the preset focal area of ​​the metasurface during continuous treatment for several days.

[0024] This invention establishes a complete method for verifying the application of tumor-bearing animal models, which includes the following steps: ① Model construction and localization: A subcutaneous tumor-bearing mouse model was constructed and fixed to a localization device to ensure that the tumor was precisely aligned with the metasurface focal point.

[0025] ② Long-term, periodic hyperthermia: Tumor-bearing mice are subjected to periodic microwave hyperthermia for several consecutive days, and the temperature at the center of the tumor is monitored in real time to ensure that it is maintained within the effective treatment window (e.g., 42-43℃).

[0026] ③ Multidimensional effect evaluation: During and after the treatment cycle, the effect of hyperthermia is comprehensively evaluated. The evaluation dimensions include at least: (a) real-time temperature distribution; (b) tumor volume change and inhibition rate; (c) H&E staining pathological analysis of major organs and tumor tissues.

[0027] ④ Verification by combining theory and practice: The measured temperature distribution data in living organisms are compared with the theoretical calculation results based on the Penns biothermal equation to quantitatively verify the precise energy deposition capability of metasurfaces in complex living environments from the perspective of biothermal transfer mechanism.

[0028] More specifically: like Figure 1The diagram shows the overall experimental setup and in vivo application scenario of the thermotherapy system of this invention. The entire experiment was conducted in a microwave anechoic chamber to eliminate environmental electromagnetic interference. A horn-shaped transmitting antenna served as a microwave feed source, transmitting microwaves at a working frequency of 2.45 GHz. A specially designed transmissive metasurface (left side) was placed vertically on the exit path of the microwave feed source. The key to this invention lies in the precise design of each unit structure on the metasurface (left side), enabling phase modulation of the transmitted microwaves, thereby achieving phase modulation in the near-field region on the exit surface side of the metasurface (z = 310 in this invention). A high-energy-density focusing point is formed at a distance of mm. In the experiment, a nude mouse with a successfully constructed subcutaneous tumor was used as a tumor-bearing animal model. After anesthetizing the mouse, it was placed on a fixation and positioning device (right side) with a low dielectric constant, such as foam plastic. By adjusting the position of the device, the subcutaneous tumor on the mouse's back was precisely aligned with and closely attached to the preset focus area of ​​the metasurface. The setup of this device is the first time that metasurface thermotherapy technology has been applied from static ex vivo biomimetic bodies to real, dynamic living biological models, which is the basis for the live verification of this invention.

[0029] like Figure 2 The diagram shows the structural design and focusing performance of the transmissive metasurface used in this invention. Figure 2 (a) shows the three-dimensional layered structure of the metasurface, which is composed of three layers of metal (yellow part in the figure) and two layers of dielectric substrate (blue part in the figure). The bottom layer is a parallel metal grating, the middle layer is an umbrella-shaped structure, and the top layer is a set of parallel metal gratings. This multi-layer structure achieves efficient control of transmitted electromagnetic waves through interlayer coupling.

[0030] Figure 2 (b) The unit structure and key geometric parameters of the transmissive metasurface core are shown. The phase modulation of this invention is mainly achieved by changing the rotation angle of the intermediate metal strip. β This is achieved through a method that generates phase abrupt changes based on rotating geometry, known as the "geometric phase" or "Pancharatnam-Berry phase" principle, which offers advantages such as wide bandwidth and high efficiency. Furthermore, the performance of the unit cell structure is also related to other geometric parameters, such as the opening angle of the split-ring resonator. α Length of the metal strip l and width w 2. w 3rd grade; Figure 2 (c) This visually demonstrates how the invention transforms the theoretical phase distribution into a physical structure. The left half is a snapshot of the physical layout of the metasurface array, clearly showing that the metal strips in each cell have different rotation angles depending on their position in the array. βThe right half of the diagram is a discretized phase distribution diagram corresponding to the physical layout, where red and blue represent the two extremes of phase delay. This direct correspondence from physical rotation to phase distribution demonstrates the ingenuity of the design of this invention. Figure 2 (d) is the final verification of the effectiveness of the metasurface design of the present invention, showing the simulated electric field intensity distribution on the focal plane. The results clearly show that the electric field intensity is significantly enhanced in the central region of the metasurface, forming a highly concentrated red focal point, while the energy decays rapidly in the region outside the focal point. This proves that the metasurface design of the present invention successfully converges the incident plane wave into a compact, high-energy near-field focal point, providing a solid physical guarantee for subsequent precise heating on living tumors.

[0031] like Figure 3 The figure shows the results of the thermotherapy effect and long-term efficacy verification of the present invention in tumor-bearing live mouse models. Figure 3 (a) and 3(b) demonstrate the system's precise and efficient in vivo heating capability. Infrared thermal imaging clearly shows that in the "Only Signal" control group, which only had a microwave source and no metasurface, the mouse surface temperature showed no significant change or even a slight decrease. However, in the "Signal+Metasurface" treatment group using the system of this invention, after 40 minutes of microwave irradiation, the temperature of the tumor area (white elliptical area) significantly increased from 37.7°C before treatment to 43.2°C, with a temperature rise (ΔT) of approximately 6.5°C, reaching the recognized effective thermotherapy temperature window. Importantly, the high-temperature area was strictly confined to the tumor site, with no significant change in the temperature of the surrounding healthy tissue, strongly demonstrating the high spatial selectivity of the invention in complex in vivo environments.

[0032] Figure 3 (c)-(f) demonstrate the system's long-term, sustained tumor suppression effect. This invention designs a continuous treatment cycle of up to 11 days. Figure 3 As shown in the tumor growth curves in (d), the tumor volume in both the "Control" and "Only Signal" groups increased exponentially and rapidly. In stark contrast, the tumor growth in the treatment group of this invention was greatly inhibited, especially in the 40-minute treatment group, where the tumor volume hardly increased throughout the entire treatment cycle, and the final measured tumor inhibition rate was as high as 96%. Figure 3 (f) The final tumor weight data is also highly consistent with this conclusion; these long-term efficacy data, for the first time, confirm the effectiveness of metasurface microwave thermotherapy from a fundamental biological level, solving the major deficiency of existing technologies that can only prove "can be heated" but cannot prove "can be cured".

[0033] like Figure 4The figure shows the simulation verification results of the near-field focusing performance of the system of the present invention, which are used to clarify its physical working mechanism and corroborate the results of in vivo experiments. Figure 4 (a) and 4(b) use COMSOL multiphysics simulation software to deeply analyze the precise heating mechanism of this invention. In this simulation model, this invention constructs a geometric model that is closer to the real biological environment, which includes not only the target tumor tissue but also the surrounding healthy muscle tissue, and crucially introduces the Pennes biothermal equation considering the blood perfusion effect. The simulation results clearly show that although the microwave energy focused by the metasurface covers the tumor and its surrounding area, the temperature rise effect exhibits extremely high physiological selectivity. Figure 4 As shown in (a), the center of the "hot spot" formed after energy deposition highly coincides with the location of the tumor; more importantly, as Figure 4 (b) shows the temperature curves along the dashed path, where the temperature in the tumor region is significantly higher than that in the surrounding healthy muscle tissue.

[0034] This significant temperature difference stems from the fundamental differences in their physiological characteristics. Healthy muscle tissue has a high blood perfusion rate and strong heat dissipation capacity due to its rich vascular network; while tumor tissue has an abnormal vascular structure and poor blood flow, causing heat to easily accumulate and be difficult to dissipate. Therefore, the present invention cleverly utilizes this physiological difference to selectively raise the temperature of tumor tissue, achieving an effective therapeutic temperature to cause damage while ensuring that the temperature of surrounding healthy tissue with good heat dissipation capacity is maintained within a safe range. This simulation result theoretically reveals the intrinsic mechanism of the high safety of the present invention and is consistent with... Figure 3 The experimental results observed in vivo, including precise heating and high tumor inhibition rates, form a perfect theoretical and practical closed loop.

[0035] Figure 4 (c) and 4(d) demonstrate the penetration and focusing capabilities in a multilayer biological tissue model. The simulation subdivides the biological tissue into three layers: skin, fat, and muscle, and examines the focusing effect at different distances (z=200, 270, 310 mm). The results show that the metasurface of the present invention can achieve optimal focusing at a specific distance (z=310 mm) and deposit energy mainly in the target tissue layer. The simulation results are based on the Pennes biothermal equation considering the blood perfusion effect, and its high consistency with in vivo experiments not only theoretically verifies the correctness of the design of the present invention, but also proves the scientificity and reliability of the "theoretical simulation-in vivo verification" closed-loop evaluation method established by the present invention.

[0036] This invention employs an innovative system and method design: on the one hand, utilizing its unique metasurface phase modulation technology, it achieves continuous and stable microwave focused hyperthermia for the first time on a real live animal model, rather than in vitro, demonstrating its technical feasibility in complex biological environments; on the other hand, its first multi-dimensional, long-term in vivo validation method scientifically proves the biological effectiveness and safety of the technology through irrefutable long-term efficacy data and pathological evidence. This synergistic validation of "technical feasibility" and "biological effectiveness" successfully bridges the gap between laboratory physical demonstrations and future clinical applications.

[0037] This invention systematically integrates metasurfaces with tumor-bearing in vivo animal models and pioneering a multi-dimensional, long-term in vivo validation method encompassing real-time temperature measurement, long-term efficacy tracking, histopathological analysis, and theoretical verification of the Pennes biothermal equation. This deep integration of system and method has, for the first time, demonstrated the sustained and efficient tumor-suppressing ability of metasurface technology at the in vivo level (experimental inhibition rate up to 96%), and irrefutably verified its scientific validity in precisely focused heating within complex biological tissues from the perspective of biothermal transfer mechanisms. This invention fills the key technological gap from metasurface physical design to in vivo preclinical validation, providing a complete technical solution and scientific evaluation standards for a new generation of precise, non-invasive physical tumor treatment technologies, and has broad application prospects in the fields of oncology, bioelectromagnetics, and the development of high-end medical devices.

[0038] This invention establishes for the first time a validation protocol for periodic in vivo treatment lasting at least 12 consecutive days, and introduces tumor volume change as a core efficacy indicator. Experimental data show that after treatment with the system of this invention, the tumor inhibition rate is as high as 96%, and about 40% of mouse tumors completely regress, while the tumor volume of the control group increases exponentially. This comparison provides irrefutable biological evidence for the first time that metasurface microwave thermotherapy can achieve continuous and repeatable tumor inhibition, historically elevating metasurface technology from a "demonstration of heatable" physical device to a "proven therapeutic" biomedical system, filling the most critical preclinical validation gap in this field.

[0039] This invention establishes a multi-dimensional closed-loop evaluation method comprising five levels: The first level is real-time in vivo temperature distribution assessment to verify the accuracy and selectivity of heating; the second level is long-term tumor volume tracking assessment to quantify the biological efficacy of treatment; the third level is histopathological analysis (H&E staining) to verify the degree of tumor necrosis and the biosafety of major organs from a cellular morphology perspective; the fourth level is a theoretical-experimental closed-loop verification based on the Pennes biothermal equation. By comparing the measured temperature distribution with the theoretical calculation results that incorporate the metasurface focused electric field distribution as a heat source term, the method quantitatively confirms from a biothermal transfer mechanism perspective that focused electromagnetic energy deposition is the fundamental cause of selective high temperatures, ruling out the possibility of overall irradiation heating. These four layers of verification are interconnected, forming a complete evidence loop from "physical focusing" to "thermal effect" to "biological efficacy" and "mechanism of action."

[0040] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the protection scope of the present invention. Therefore, the protection scope of this invention patent should be determined by the appended claims.

Claims

1. A transmissive metasurface near-field focused microwave hyperthermia system, characterized in that, include: Microwave feed and transmissive metasurface array; The microwave feed source is used to generate microwaves at a preset operating frequency and irradiate the transmissive metasurface array. The transmissive metasurface array includes multiple subwavelength unit structures arranged in an array and configured on the emission path of the microwave feed source. Each subwavelength unit structure includes two dielectric substrates and a metal pattern layer distributed therebetween, forming a Fabry-Perot resonant cavity. By adjusting the geometric parameters of the metal pattern layer within the subwavelength unit structure, the resonance conditions of the Fabry-Perot resonant cavity are changed, so that the transmissive metasurface array applies a preset spatial phase distribution to the transmitted microwaves, thereby forming a focusing point with a higher energy density than preset in the near-field region on the emission surface side of the transmissive metasurface array, to perform microwave thermotherapy on the target.

2. The transmissive metasurface near-field focused microwave hyperthermia system according to claim 1, characterized in that, It also includes devices for fixing and positioning tumor-bearing animal models; The tumor-bearing animal model fixation and positioning device is used to repeatedly align and attach the subcutaneous tumor site of the tumor-bearing live animal to the focal point formed by the transmissive metasurface array, so as to achieve continuous and spatially selective microwave focused thermotherapy on the tumor site.

3. The transmissive metasurface near-field focused microwave hyperthermia system according to claim 1, characterized in that, The microwaves generated by the microwave feed source operate at a frequency of 2.45 GHz, which is used to ensure tissue penetration depth while achieving wavefront phase modulation.

4. The transmissive metasurface near-field focused microwave hyperthermia system according to claim 1, characterized in that, The subwavelength unit structure includes a first metal layer, a first dielectric substrate, a second metal layer, a second dielectric substrate, and a third metal layer arranged sequentially from top to bottom; The first and third metal layers are both a set of parallel metal gratings, and the second metal layer is an umbrella-shaped metal resonant ring.

5. The transmissive metasurface near-field focused microwave hyperthermia system according to claim 4, characterized in that, Phase modulation of the subwavelength unit structure is achieved by changing the opening angle of the umbrella-shaped metal resonator. α and rotation angle β and the length of the metal grating l With width w 2. w 3. To achieve this.

6. The transmissive metasurface near-field focused microwave hyperthermia system according to claim 1, characterized in that, The transmissive metasurface array is configured to form a focusing point with a higher energy density than a preset value in the near-field region 310 mm from its exit surface.

7. A method for verifying the application of a tumor-bearing animal model, implemented using a transmissive metasurface near-field focused microwave hyperthermia system as described in any one of claims 1 to 6, characterized in that... Includes the following steps: The tumor-bearing live animal is fixed on the tumor-bearing animal model fixation and positioning device, so that its subcutaneous tumor site is precisely aligned with and closely attached to the near-field focusing point of the transmissive metasurface array. The microwave feed source is activated to provide continuous, periodic microwave thermotherapy to the tumor site over several days. The efficacy of hyperthermia was comprehensively evaluated after the periodic hyperthermia period by real-time temperature distribution, changes in tumor volume and inhibition rate, and H&E staining pathological analysis based on tissue sections.

8. The method for verifying the application of a tumor-bearing animal model according to claim 7, characterized in that, In the aforementioned periodic microwave hyperthermia, the power of the microwaves generated by the microwave feed source is controlled to bring the temperature of the tumor site up to and maintain it within a treatment temperature window of 41.5°C to 43.5°C.

9. The method for verifying the application of a tumor-bearing animal model according to claim 7, characterized in that, The real-time temperature distribution data was compared with the theoretical calculation results based on the Pennes biothermal equation and the introduction of the focused electric field distribution of the transmissive metasurface array as the electromagnetic thermal power density heat source term, so as to quantitatively verify the spatial selective heating capability and energy deposition mechanism of the transmissive metasurface array in the living physiological environment from the perspective of biothermal transfer mechanism.

10. The method for verifying the application of a tumor-bearing animal model according to claim 7, characterized in that, The determination of tumor volume change and inhibition rate is achieved by periodically measuring and recording the three-dimensional dimensions of the tumor to plot a tumor growth curve and obtain the tumor volume inhibition rate.