Dual-wavelength confocal superlenses and their design methods, photoacoustic imaging methods and systems

By designing a dual-wavelength confocal superlens and controlling the geometry and material selection of the metasurface structure, the problems of tissue light absorption spectrum overlap and resolution limitation in single-wavelength photoacoustic imaging were solved, achieving high-contrast photoacoustic imaging and enhancing the effectiveness of cancer cell monitoring and treatment.

CN119937158BActive Publication Date: 2026-03-10QINGDAO UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2025-03-14
Publication Date
2026-03-10

AI Technical Summary

Technical Problem

Existing single-wavelength photoacoustic imaging technology suffers from overlapping tissue light absorption spectra, lack of multimodal information, and spatial resolution limitations, making it difficult to effectively monitor and treat cancer.

Method used

A dual-wavelength confocal superlens is designed to respond to different wavelengths of light by controlling the geometry and material selection of the metasurface structure. Combined with photoacoustic imaging methods, this enhances imaging contrast and resolution.

Benefits of technology

It provides comparison of multiple tissue features in the same imaging process, enhances the ability to detect lesions, improves the imaging signal-to-noise ratio, and improves the resolution of the imaging system, making it suitable for cancer cell monitoring and treatment.

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Abstract

This invention provides a dual-wavelength confocal superlens and its design method, as well as a photoacoustic imaging method and system, belonging to the field of optical lens technology. The invention provides a design method for a dual-wavelength confocal superlens that can use two different wavelengths of light to visualize cancer cells and normal tissues. Normal cells and cancer cells absorb energy from the two different wavelengths, causing them to heat up and expand. After cooling, they emit ultrasonic waves, which are then collected by an ultrasonic transducer. Finally, photoacoustic imaging is achieved through calculation. This invention aims to enhance photoacoustic imaging contrast while avoiding the risks of invasive procedures. The dual-wavelength design provides multiple contrast mechanisms, allowing for the comparison of various tissue features during the same imaging process, enhancing the detection capability of lesions, and effectively reducing the influence of noise in the photoacoustic signal. This invention can be applied to early cancer detection and can also be used to monitor tumor response during treatment and evaluate treatment effectiveness.
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Description

Technical Field

[0001] This invention relates to the field of optical lens technology, and in particular to a dual-wavelength confocal superlens and its design method, photoacoustic imaging method and system. Background Technology

[0002] Metamaterials have attracted widespread attention due to their ability to achieve electromagnetic responses that do not exist in nature. These materials are composed of subwavelength-scale nanounits, and by controlling the geometry, material selection, and lattice constant of these units, the polarization, phase, amplitude, and frequency of electromagnetic waves can be precisely controlled. Based on this principle, superlenses utilize artificially designed two-dimensional nanostructures to control the propagation path and focal point imaging of light, overcoming the physical limitations of traditional lenses. Superlenses offer advantages such as thinness, compactness, and high integration, and are particularly outstanding in terms of flexibility and tunability. They are compatible with various materials, suitable for different wavelengths, and can exhibit different optical properties at different optical wavelengths according to design requirements, achieving multi-wavelength confocal imaging capabilities.

[0003] Cancer is the second leading cause of death worldwide, after heart disease. Due to the complexity of different cancer types, there is currently no completely comprehensive treatment. Treatment methods mainly include chemotherapy, radiotherapy, and surgery. For cancer monitoring and post-operative rehabilitation, imaging techniques (such as X-rays and ultrasound), tumor markers, blood tests, and tissue biopsies are frequently used. Although these technologies are constantly being improved, they can still cause secondary harm to the human body, including radiation risks and potential bleeding and infection during surgery, which may damage normal healthy cells or increase the likelihood of secondary cancers. Photoacoustic technology integrates optics, acoustics, biology, and computer vision. Its basic principle is that laser irradiation of biological tissue causes local temperature rise through light energy absorption, leading to tissue expansion and the generation of ultrasound signals. By detecting these ultrasound signals, the spatial distribution of the tissue can be reconstructed, achieving high-resolution imaging and assisting in clinical diagnosis and treatment. As a non-invasive technology, photoacoustic imaging can acquire tumor information through surface or shallow optical signals, making it particularly valuable in the early diagnosis of cancer. Compared to traditional pathological examination, photoacoustic imaging avoids the risks of invasive procedures. By selecting specific wavelengths of laser light, biomarkers of cancer cells can be sensitively monitored, especially the vascular structure and oxyhemoglobin distribution in the tumor area, thereby improving the sensitivity and specificity of diagnosis.

[0004] The following defects exist in single-wavelength photoacoustic imaging in related technologies: 1. Overlapping tissue light absorption spectra limit the system's ability to distinguish different tissues or substances; 2. Lack of multimodal information, providing only single contrast information; 3. Limited spatial resolution, which may not be sufficient for imaging fine structures or tiny lesions. Summary of the Invention

[0005] In view of this, the purpose of this invention is to provide a dual-wavelength confocal superlens and its design method, photoacoustic imaging method, and system. The dual-wavelength confocal superlens design method of this invention enables high-contrast photoacoustic imaging for cancer cell monitoring and treatment. By enhancing imaging contrast, it allows for the comparison of multiple tissue features during the same imaging process, thereby enhancing the detection capability of lesions.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0007] This invention provides a design method for a dual-wavelength confocal superlens, comprising the following steps:

[0008] S1. Define the design objectives, determine the dual working wavelengths to be achieved for confocalization, clarify the optical functions that the metasurface should achieve, so that it can respond to two different wavelengths of light and achieve confocalization. The metasurface includes a focusing metasurface and a filtering metasurface.

[0009] S2. Select materials and parameters, find the dual-working-wavelength superlens material and substrate respectively, and test the optical properties at different wavelengths, including refractive index and transmittance;

[0010] S3. Multiscale structure design of metasurfaces: By adjusting the size of the unit structure, its response to light of different wavelengths can be adjusted, and the geometric parameters of the unit structure can be optimized. The influence on the phase change of the outgoing light wavefront can be analyzed, and a database of quantitative relationship between unit structure parameters and wavefront phase can be established.

[0011] S4. Based on the quantitative relationship database, and through the propagation phase distribution formula derived from the designed wavefront phase formula, unit structures of different materials and sizes are placed at specific positions on two surfaces of the substrate to achieve filtering or focusing functions.

[0012] S5. Repeat S1 to S4 so that different materials are placed at specific positions on the substrate according to the propagation phase formula, to obtain the focusing metasurface and the filtering metasurface respectively, forming the dual-wavelength confocal superlens.

[0013] Preferably, the dual operating wavelengths include the visible light band and the near-infrared light band, and the optical functions that the metasurface should achieve include imaging, focusing, transmission, refraction and filtering.

[0014] Preferably, the substrate has an optical bandgap greater than 3.1 eV in the visible light range and an optical bandgap greater than 1.5 eV in the near-infrared light range; the unit structure has a refractive index of 2.0~4.0 and an optical bandgap greater than 3.1 eV in the visible light range, and a refractive index of 1.8~3.5 and an optical bandgap greater than 1.5 eV in the near-infrared light range.

[0015] Preferably, the unit structure is a centrally symmetric structure.

[0016] Preferably, the surface shape of the unit structure is circular, square, or regular hexagonal.

[0017] Preferably, the geometric parameters include one or more of lattice constant, cross-sectional radius, and height.

[0018] The present invention also provides a dual-wavelength confocal superlens fabricated by the design method described above, comprising a substrate, a focusing supersurface on one side of the substrate, and a filtering supersurface on the other side of the substrate.

[0019] Preferably, the focusing metasurface uses 532nm and 785nm as working wavelengths, uses TiO2 as the unit structure for focusing 532nm light, and uses Si as the unit structure for focusing 785nm light; the filtering metasurface uses TiO2 as the unit structure.

[0020] The present invention also provides a photoacoustic imaging method, which utilizes the dual-wavelength confocal superlens described in the above technical solution.

[0021] The present invention also provides a photoacoustic imaging system, including the dual-wavelength confocal superlens and ultrasonic transducer described in the above technical solution.

[0022] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0023] This invention provides a design method for a dual-wavelength confocal superlens, enabling high-contrast photoacoustic imaging. This method is applied to cancer cell monitoring and treatment, enhancing imaging contrast and allowing for the comparison of multiple tissue features during the same imaging process, thus improving lesion detection capabilities. The combination of dual wavelengths also effectively reduces noise in the photoacoustic signal, improving the resolution of the imaging system. By controlling the geometry, material selection, and lattice constant of its subwavelength unit structure, precise control of the polarization, phase, amplitude, and frequency of electromagnetic waves through different mechanisms can be achieved. This allows for the expression of different optical properties at different optical wavelengths, thereby realizing multi-wavelength confocal imaging.

[0024] Specifically, the present invention has the following advantages:

[0025] 1. Enhanced imaging contrast: By utilizing two light sources of different wavelengths, different light absorption characteristics can be obtained simultaneously, providing more tissue information, which can significantly improve the imaging contrast.

[0026] 2. Multiple contrast mechanism: By modulating two different wavelengths of light, they act on different components of the tissue to obtain a comparison of multiple tissue characteristics, thereby enhancing the ability to detect lesions.

[0027] 3. Improve the signal-to-noise ratio and effectively reduce the impact of noise in photoacoustic signals. Attached Figure Description

[0028] Figure 1 This is a flowchart illustrating the design process of the dual-wavelength confocal superlens of the present invention.

[0029] Figure 2 This is a flowchart illustrating the photoacoustic imaging design of the present invention;

[0030] Figure 3 This is a schematic diagram of the dual-wavelength confocal superlens unit structure of the present invention;

[0031] Figure 4 This is a scan data diagram of the focused metasurface unit structure with a wavelength of 532nm according to the present invention;

[0032] Figure 5 This is a scanned image of the focused metasurface unit structure at a wavelength of 785nm, as shown in this invention.

[0033] Figure 6 This is a schematic diagram of the dual-wavelength confocal superlens structure of the present invention;

[0034] Figure 7 This is a dual-wavelength confocal superlens focusing pattern of the present invention.

[0035] Figure 8 This is a schematic diagram of the dual-wavelength focal plane optical field of the dual-wavelength confocal superlens of the present invention;

[0036] Figure 9 This is a photoacoustic imaging sound pressure reconstruction image of the present invention;

[0037] In the figure, 1 is the unit structure, 2 is the substrate, 3 is TiO2, and 4 is Si. Detailed Implementation

[0038] This invention provides a design method for a dual-wavelength confocal superlens, comprising the following steps:

[0039] S1. Define the design objectives, determine the dual working wavelengths to be achieved for confocalization, clarify the optical functions that the metasurface should achieve, so that it can respond to two different wavelengths of light and achieve confocalization. The metasurface includes a focusing metasurface and a filtering metasurface.

[0040] S2. Select materials and parameters, find the dual-working-wavelength superlens material and substrate respectively, and test the optical properties at different wavelengths, including refractive index and transmittance;

[0041] S3. Multiscale structure design of metasurfaces: By adjusting the size of the unit structure, its response to light of different wavelengths can be adjusted, and the geometric parameters of the unit structure can be optimized. The influence on the phase change of the outgoing light wavefront can be analyzed, and a database of quantitative relationship between unit structure parameters and wavefront phase can be established.

[0042] S4. Based on the quantitative relationship database, and through the propagation phase distribution formula derived from the designed wavefront phase formula, unit structures of different materials and sizes are placed at specific positions on two surfaces of the substrate to achieve filtering or focusing functions.

[0043] S5. Repeat S1 to S4 so that different materials are placed at specific positions on the substrate according to the propagation phase formula, to obtain the focusing metasurface and the filtering metasurface respectively, forming the dual-wavelength confocal superlens.

[0044] Figure 1 This is a flowchart illustrating the design process of the dual-wavelength confocal superlens of the present invention.

[0045] This invention defines the design goal, determines the dual working wavelengths to be achieved for confocalization, and clarifies the optical functions that the metasurface should achieve, enabling it to respond to two different wavelengths of light and achieve confocalization. The metasurface includes a focusing metasurface and a filtering metasurface.

[0046] In this invention, the dual working wavelengths preferably have significant differences in the absorption spectrum of the material or tissue, so as to obtain rich information from the photoacoustic signal.

[0047] In this invention, the dual operating wavelengths preferably include the visible light band and the near-infrared light band, and the optical functions that the metasurface should achieve preferably include imaging, focusing, transmission, refraction and filtering.

[0048] This invention preferably utilizes a thorough understanding of the light absorption characteristics of endogenous substances in the human body during photoacoustic imaging. Simultaneously, it selects appropriate targeting contrast agents to enhance the detection capabilities of photoacoustic imaging and strengthen the signals of cancer cells and tumor-specific molecules, thereby determining the working wavelength for confocal imaging. Furthermore, it clearly defines the optical functions that the metasurface should achieve, enabling it to respond to two different wavelengths of light and realize confocal imaging.

[0049] In a specific embodiment of the present invention, the working wavelength is preferably determined based on the light absorption characteristics of blood cells and contrast agents in the human body, specifically 532nm (green light) and 785nm (infrared light).

[0050] This invention selects materials and parameters to find the dual-working-wavelength superlens material and substrate, and tests the optical properties at different wavelengths, including refractive index and transmittance.

[0051] In this invention, the different wavelengths preferably include 532nm and 785nm.

[0052] In this invention, the optical properties preferably also include absorptivity, loss, and phase change.

[0053] In this invention, the substrate preferably has a wide optical bandgap, excellent transparency, and can effectively transmit light waves in these bands without significant absorption, exhibiting low optical loss.

[0054] In this invention, the optical bandgap of the substrate in the visible light range (preferably 400~700nm) is preferably greater than 3.1eV, and the optical bandgap in the near-infrared light range (preferably 700~2500nm) is preferably greater than 1.5eV.

[0055] In this invention, the substrate material is preferably including, but not limited to, metallic materials, dielectric materials, semiconductor materials, composite materials, two-dimensional materials, or photonic crystal materials; the metallic materials are more preferably including, but not limited to, silver, gold, copper, and aluminum; the dielectric materials are more preferably including, but not limited to, silicon, silicon nitride, silicon dioxide, calcium fluoride, and barium titanate; the semiconductor materials are more preferably including, but not limited to, gallium arsenide and indium phosphide; the composite materials are more preferably including, but not limited to, silicon-based composite materials; and the photonic crystal materials are more preferably including, but not limited to, silicon photonic crystals and silicon nitride photonic crystals. The photonic crystal materials are used in the visible to infrared band and have high refractive index and good optical performance.

[0056] In this invention, the two-dimensional material preferably includes graphene and transition metal dichalcogenides, and the transition metal dichalcogenides more preferably include MoS2. The graphene has tunable optical absorption and transmission properties over a wide spectral range, making it very suitable for designing new superlenses. The transition metal dichalcogenides exhibit excellent optical response in the visible to near-infrared band, making them suitable for superlens design.

[0057] In this invention, the silicon-based composite material preferably includes one or more of silicon oxide composite materials, silicon nitride composite materials, and silicon carbide composite materials.

[0058] In a specific embodiment of the present invention, the substrate is preferably silicon dioxide (SiO2).

[0059] In this invention, the unit structure preferably has a high refractive index, which can effectively control the propagation of light, has a high nonlinear optical effect, or has a specific optical band gap.

[0060] In this invention, the refractive index of the unit structure in the visible light range (preferably 400~700nm) is preferably 2.0~4.0, and the optical band gap is preferably greater than 3.1eV. In the near-infrared light range (preferably 700~2500nm), the refractive index is preferably 1.8~3.5, and the optical band gap is preferably greater than 1.5eV.

[0061] In this invention, the materials of the unit structure are preferably including, but not limited to, metallic materials, dielectric materials, semiconductor materials, two-dimensional materials, or photonic crystal materials; the metallic materials are more preferably including, but not limited to, silver, gold, copper, and aluminum; the dielectric materials are more preferably including, but not limited to, silicon, silicon nitride, silicon dioxide, calcium fluoride, and barium titanate; the semiconductor materials are more preferably including, but not limited to, gallium arsenide and indium phosphide; and the photonic crystal materials are more preferably including, but not limited to, silicon photonic crystals and silicon nitride photonic crystals.

[0062] In this invention, the two-dimensional material preferably includes graphene and transition metal disulfides, and the transition metal disulfides more preferably include MoS2.

[0063] In this invention, the material of the unit structure preferably has a high refractive index at 532 nm and 785 nm, and also has a high transmittance, and is more preferably transparent.

[0064] In a specific embodiment of the present invention, the material of the unit structure is preferably TiO2 or Si, wherein TiO2 is suitable for use in the 532nm band and Si is suitable for use in the 785nm band, the refractive index of TiO2 is 2.66 (532nm) and the refractive index of Si is 3.70 (785nm).

[0065] In a specific embodiment of the present invention, the material of the focusing metasurface is preferably TiO2 or Si, and the material of the filtering metasurface is preferably TiO2.

[0066] This invention designs a multi-scale metasurface structure, adjusts the response of the unit structure to light of different wavelengths by controlling the size of the unit structure, optimizes the geometric parameters of the unit structure, analyzes the influence on the phase change of the emitted light wavefront, and establishes a database of quantitative relationships between unit structure parameters and wavefront phase.

[0067] In this invention, it is preferred to use numerical simulation methods to optimize the geometric parameters of the unit structure. The numerical simulation methods preferably include geometric optics, wave optics, finite difference time-domain method, finite element method, boundary element method, or discrete Fourier transform method.

[0068] In this invention, the optimized output light preferably covers the phase range of 0 to 2π, and preferably has a light transmittance greater than 85%.

[0069] In this invention, the unit structure is preferably a centrally symmetric structure.

[0070] In this invention, the surface shape of the unit structure is preferably circular, square, or regular hexagonal.

[0071] In this invention, the geometric parameters preferably include one or more of the following: lattice constant (P), cross-sectional radius (r), and height (H).

[0072] In this invention, the optimized preferred method includes the following steps: First, the height of the unit structure is fixed. Then, by performing nested scans with a fixed step size on the lattice constant and cross-sectional radius of the unit structure, the phase change of the incident light wavefront and the transmittance parameters can be obtained. Next, with the lattice constant unchanged, nested scans with a fixed step size are performed on the height and cross-sectional radius of the unit structure. This process is repeated several times until the phase change gradient of the emitted light covers 0~2π, while maintaining high light transmittance. To ensure superior optical performance, the lattice constant must conform to the Nyquist sampling law, thereby avoiding the generation of optical artifacts.

[0073] In a specific embodiment of the present invention, the geometric parameters of the unit structure of the focusing metasurface include: for the unit structure with a wavelength of 532 nm, the lattice constant P = 0.31 μm, the height H = 0.8 μm, and the cross-sectional radius r = 0.05~0.09 μm; for the unit structure with a wavelength of 785 nm, the lattice constant P = 0.3 μm, the height H = 1.2 μm, and the cross-sectional radius r = 0.01~0.08 μm; the geometric parameters of the unit structure of the filtering metasurface include: for the unit structure with a filtering wavelength of 532 nm, the lattice constant P = 0.5 μm, the height H = 1 μm, and the cross-sectional radius r = 0.08 μm; for the unit structure with a filtering wavelength of 785 nm, the lattice constant P = 0.7 μm, the height H = 1 μm, and the cross-sectional radius r = 0.18 μm.

[0074] After obtaining the quantitative relational database, this invention, based on the quantitative relational database and the propagation phase distribution formula derived from the designed wavefront phase formula, places unit structures of different materials and sizes at specific positions on two surfaces of the substrate to achieve filtering or focusing functions.

[0075] The present invention repeats S1 to S4, so that different materials are placed at specific positions on the substrate according to the propagation phase formula, respectively obtaining the focusing metasurface and the filtering metasurface, forming the dual-wavelength confocal superlens.

[0076] The present invention preferably divides the substrate into several grids with the substrate as the center and the lattice constant as the step size. By using the propagation phase distribution formula derived from the designed wavefront phase formula, unit structures of different materials and sizes are placed on specific grid points on two sides of the substrate, so that the incident light conforms to the propagation phase curve after passing through the superlens, thereby realizing the filtering or focusing function.

[0077] After obtaining the dual-wavelength confocal superlens, the present invention uses numerical simulation methods to perform far-field simulation to obtain light field data. Then, a three-layer skin model is designed, and numerical simulation methods are used to simulate light absorption and thermal effects, sound wave generation and propagation, sound wave detection, and image reconstruction and processing.

[0078] Figure 2 The photoacoustic imaging design flowchart of the present invention includes the following steps: first, define the computational grid properties, then define the medium properties, define the initial pressure distribution, define the sensor mask, then set the photoacoustic reconstruction method, and then perform photoacoustic reconstruction simulation.

[0079] In this invention, the three-layer skin model is preferably composed of the epidermis, dermis, and subcutaneous fat layer, with each layer assigned different optical and acoustic properties to reflect the heterogeneity of the skin.

[0080] In this invention, the design of the three-layer skin model preferably includes defining computational grid properties, defining medium properties, defining initial pressure distribution, and defining sensor mask.

[0081] In this invention, in order to reproduce the response of light as it passes through tissue as much as possible, the defined medium properties preferably include, but are not limited to, optical properties, acoustic properties, and thickness. The optical properties preferably include, but are not limited to, absorption coefficient, scattering coefficient, dispersion coefficient, and refractive index. The acoustic properties preferably include, but are not limited to, density, sound velocity, and impedance.

[0082] In this invention, the numerical simulation method for simulating light absorption and thermal effects preferably includes, but is not limited to, calculating the light absorption capacity of each tissue point based on the tissue's light absorption coefficient, scattering coefficient, and incident light intensity, and obtaining the initial pressure according to the photothermal conversion formula.

[0083] In this invention, the method for simulating the generation and propagation of sound waves preferably includes, but is not limited to, the wave equation method, the finite element method, or the boundary element method.

[0084] In this invention, the method for acoustic wave detection simulation and image reconstruction preferably includes, but is not limited to, an inversion reconstruction algorithm, a back projection algorithm, or an iterative reconstruction algorithm for acoustic wave signals. Preferably, this invention converts the detected acoustic wave signals into images and reconstructs the light absorption distribution within the tissue, thereby achieving photoacoustic imaging.

[0085] In a specific embodiment of the present invention, numerical simulation is preferably used to simulate the light absorption and thermal effects of the light field data to obtain the total light energy that passes through three layers of skin to reach the pathological tissue. Then, sound wave generation and propagation simulation is performed, and the corresponding sound pressure is obtained using the photothermal conversion formula. After that, the sound signals of normal and pathological tissues are detected by the set ultrasound sensor, and the image is reconstructed by the inversion algorithm using the sensor data.

[0086] The present invention also provides a dual-wavelength confocal superlens fabricated by the design method described above, comprising a substrate, a focusing supersurface on one side of the substrate and a filtering supersurface on the other side of the substrate, wherein light first passes through the filtering supersurface, then through the substrate, and then through the focusing supersurface.

[0087] This invention provides a dual-wavelength confocal superlens to achieve high-contrast photoacoustic imaging, which can be applied to cancer cell monitoring and treatment. The enhanced imaging contrast allows for the comparison of multiple tissue features during the same imaging process, improving the detection capability of lesions. The combination of dual wavelengths also effectively reduces the influence of noise in the photoacoustic signal, improving the resolution of the imaging system (down to the micrometer level). By controlling the geometry, material selection, and lattice constant of its subwavelength unit structure, the dual-wavelength confocal superlens achieves precise control of the polarization, phase, amplitude, and frequency of electromagnetic waves through different mechanisms, thus exhibiting different optical properties at different optical wavelengths and realizing multi-wavelength confocal imaging.

[0088] In this invention, the focusing metasurface preferably uses 532nm and 785nm as working wavelengths, preferably uses TiO2 as the unit structure for focusing 532nm light, and preferably uses Si as the unit structure for focusing 785nm light; the filtering metasurface preferably uses TiO2 as the unit structure.

[0089] In this invention, the geometric parameters of the unit structure are preferably consistent with the above-described scheme, and will not be repeated here.

[0090] The present invention also provides the application of the dual-wavelength confocal superlens described in the above technical solution in the field of photoacoustic imaging.

[0091] The present invention also provides a photoacoustic imaging method, which utilizes the dual-wavelength confocal superlens described in the above technical solution for photoacoustic imaging.

[0092] The present invention also provides a photoacoustic imaging system, including the dual-wavelength confocal superlens and ultrasonic transducer described in the above technical solution.

[0093] This invention addresses the limitations of single-wavelength photoacoustic imaging in terms of spatial resolution, overlapping tissue absorption spectra, and lack of multimodal information by providing a method for high-contrast photoacoustic imaging based on dual-wavelength confocal superlenses for cancer cell monitoring and treatment.

[0094] This invention can use a dual metasurface structure superlens to achieve dual-wavelength confocaling, thereby improving the spatial resolution of photoacoustic imaging, enhancing imaging contrast, and improving the imaging signal-to-noise ratio.

[0095] The technical solutions of this invention will be clearly and completely described below with reference to the embodiments thereof. Obviously, the described embodiments are only a part of the embodiments of this invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0096] Example 1

[0097] The dual-wavelength superlens employs a dual metasurface structure with three layers: a bottom filtering metasurface, a middle substrate, and an top focusing metasurface. The filtering metasurface allows only specific wavelengths of light to pass through, filtering out other wavelengths. The focusing metasurface focuses the incident light to the designed focal length. The design of the focusing metasurface is the most crucial aspect. In this embodiment, the focusing metasurface is composed of nanostructures with varying optical path lengths. The design method includes the following steps:

[0098] Step S1: Based on the light absorption characteristics of endogenous substances in human body photoacoustic imaging, and simultaneously selecting gold nanoparticles as a targeting contrast agent for tumor cells, 532nm and 785nm were determined as the working wavelengths. TiO2 was selected as the unit structure for focusing 532nm light, and Si was selected as the unit structure for focusing 785nm light. The lattice constant P range and shape of the unit structures were set according to the incident light wavelength.

[0099] In step S1:

[0100] To ensure that the unit cell structure produces the same response to different incident light polarization states, its cross-sectional shape needs to be centrosymmetric. A cylinder is used as the initial shape for the unit cell structure, as shown in the schematic diagram below. Figure 3 As shown.

[0101] The lattice constant P of a unit cell structure is defined as the minimum distance between adjacent units in that periodic structure. Its magnitude determines the optical properties of the material. To avoid the presence of multi-order diffraction light reducing optical efficiency and thus decreasing the effective transmission efficiency of the superlens for the target wavelength, its lattice constant needs to be smaller than the equivalent wavelength in the substrate. The equivalent wavelength can be calculated by dividing the incident wavelength by the refractive index of the substrate material. Simultaneously, the lattice constant should also satisfy the Nyquist sampling law, and its magnitude must be smaller than the ratio of the wavelength to twice the numerical aperture.

[0102] Numerical aperture = .

[0103] Step S2: Different geometric parameters will change the effective refractive index of the material, and according to Formula 1:

[0104] Formula 1,

[0105] In formula 1 The change in phase is represented by rad, λ represents wavelength by nm, and n eff H represents the effective refractive index, with a dimension of 1; H represents the optical path length, which is also the height of the unit cell, with the unit being nm.

[0106] Different effective refractive indices result in different optical path lengths for the emitted light, thus deflecting it at different angles. Based on the lattice constant range set by S1, the wavefront phase changes corresponding to different geometric parameters are calculated through parameter scanning and numerical simulation.

[0107] The parameter scanning method is as follows: First, the height of the unit structure is fixed, and nested scans with increasing step sizes are performed on the lattice constant and cross-sectional radius of the unit structure to obtain key optical parameters such as the phase change and transmittance of the incident light wavefront. Next, keeping the lattice constant P constant, nested scans with increasing step sizes are further performed on the height H and cross-sectional radius r of the unit structure, as follows: Figures 4-5 As shown. After repeating the aforementioned steps several times, the parameters for the two unit structures were finally determined as follows: for the unit structure with a wavelength of 532 nm, the lattice constant P = 0.31 μm, height H = 0.8 μm, and cross-sectional radius r = 0.05~0.09 μm; for the unit structure with a wavelength of 785 nm, the lattice constant P = 0.3 μm, height H = 1.2 μm, and cross-sectional radius r = 0.01~0.08 μm. This achieved a phase gradient coverage of 0~2π for the emitted light while maintaining high light transmittance, with a minimum transmittance exceeding 85%. A quantitative relationship database between structural geometric parameters and wavefront phase was established.

[0108] Step S3: Centered on the origin of the substrate, and using the lattice constant as the step size, divide the substrate into several grids. The propagation phase formula 2 can be derived from the generalized Snell's law.

[0109] Formula 2,

[0110] In formula 2 ψ(x, y) The phase magnitude of the point with coordinates (x, y) is expressed in rad, where x and y represent the distances from the origin, and f is the focal length. The units of x, y, and f are nm.

[0111] Unit structures of different materials and sizes are placed on specific lattice points of the substrate according to the propagation phase formula (the substrate is divided into several grids with the origin of the substrate as the center and the lattice constant as the step size. Each grid has lattice points, and each lattice point has its own coordinate value (x,y)). This ensures that the incident light conforms to the propagation phase curve after passing through the superlens, thereby achieving the focusing function.

[0112] The design of the filtering metasurface follows the steps described above, using TiO2 as the unit structure for both wavelengths of light. However, in step S2, a systematic scan of the geometric parameters of the unit structure aims to obtain a design result that allows a specific wavelength to pass through while effectively filtering out the other wavelength. Specifically, the unit structure filtering the 532nm wavelength should have a transmittance of nearly 0% for 532nm light, while its transmittance for 785nm light should exceed 80%, ideally approaching 100%. Similarly, the unit structure filtering the 785nm wavelength should have a transmittance of nearly 0% for 532nm light, ideally approaching 100%, while its transmittance for 785nm light should be close to 0%. By optimizing geometric parameters (first, fixing the height of the unit structure and performing nested scans with increasing step sizes on the lattice constant and cross-sectional radius of the unit structure to obtain key optical parameters such as the phase change and transmittance of the incident light wavefront; then, keeping the lattice constant P constant, further performing nested scans with increasing step sizes on the height H and cross-sectional radius r of the unit structure, repeating the above steps several times until parameters that satisfy the design result of "allowing a specific wavelength to pass through while effectively filtering out another wavelength" are found), the transmission characteristics of the metasurface to different wavelengths can be tuned, thereby achieving wavelength-selective filtering effects. The parameters of the two unit structures finally determined are: for the unit structure filtering a wavelength of 532nm, the lattice constant P=0.5μm, height H=1μm, and cross-sectional radius r=0.08μm; for the unit structure filtering a wavelength of 785nm, the lattice constant P=0.7μm, height H=1μm, and cross-sectional radius r=0.18μm.

[0113] The final realized superlens structure is shown in Figure 6 middle.

[0114] Example 2

[0115] Photoacoustic imaging also requires a skin model as a support to fit the light energy entering the tissue cells. This invention establishes a three-layer skin model, corresponding to the epidermis, dermis, and subcutaneous fat layer. The specific steps are as follows:

[0116] Step S1: Set the properties of the computational mesh. The properties of the computational mesh include the number of discrete points in 3D space, Nx, Ny, and Nz, which determine the spatial resolution of the simulation area. Increasing the number of mesh points improves the simulation resolution but also increases computational complexity and workload. Furthermore, the physical size of the mesh needs to be set, defined by the step size parameters dx, dy, and dz to define the spatial scale of each mesh cell. The reciprocals of these step sizes represent the spatial resolution, determining the spatial accuracy of each mesh in the simulation. A finer mesh and a smaller step size help to capture the details of sound wave propagation more accurately but also significantly increase the computational burden. Therefore, choosing an appropriate mesh resolution and step size is key to achieving a balance between accurate simulation and reasonable computational resource consumption.

[0117] In step S1, theoretically, the number of discrete points N and the step size parameter d can be set extremely precisely when computational resources are sufficient, i.e., N is extremely large and d is extremely small. Considering the limited actual computational resources, the actual number of computational grid points can be set between 10 and 1000. In this embodiment, the number of grid points is set to 450.

[0118] Step S2: Define medium properties. The characteristics of wave propagation in a medium are significantly affected by the medium's physical properties, mainly including sound velocity, density, and absorption coefficient. These physical parameters directly determine the propagation speed, attenuation process, and reflection characteristics of sound waves in the medium. Their acoustic properties are shown in Table 1.

[0119] Table 1. Acoustic properties of the skin model

[0120]

[0121] Step S3: Define the initial pressure distribution. In photoacoustic imaging, sound waves are generated due to physical expansion caused by temperature changes in local areas, which triggers the initial pressure distribution. For cancer cell detection, normal tissue cells and cancer cells are the initial pressure sources within the human body. Using the light intensity data obtained in Example 1, according to radiative transfer equation formula 3:

[0122] Formula 3,

[0123] In formula 3 It refers to position r and direction. The light intensity at time t, c is the speed of light, and μ t =μ a +μ8 is the total attenuation coefficient, μ aμ₈ is the absorption coefficient, and μₐ is the scattering coefficient. It is the scattering phase function, describing the direction of photon scattering. Scattered to direction The probability, It is a light source item;

[0124] The light energy that penetrates three layers of skin tissue to reach the cell interior can be obtained. Then, according to photothermal conversion formula 4, the initial value of the ultrasound emitted by the cell after absorbing the light energy, due to heating, expansion, and subsequent cooling and deformation, can be obtained.

[0125] Formula 4,

[0126] In Formula 4, p0(x) represents the initial pressure distribution, in Pa and μ. a (x) represents the light absorption coefficient distribution function, with units of m. -1 Γ(x) represents the Grunerson coefficient, which is dimensionless, and L(x) is the light distribution function, with units of joules;

[0127] Step S4: Define the sensor mask. In photoacoustic imaging, a sensor array is used to receive acoustic wave signals that propagate through the medium and are reflected back by the tissue. By acquiring these signals, imaging reconstruction can be performed to obtain information about the internal structure of the medium. For practical purposes, the sensor mask should be built outside the epidermal layer.

[0128] Example 3

[0129] Numerical simulation can be used to obtain the focusing optical path and focal plane light field data of the superlens, and the results are shown in the figure. Figure 7 and Figure 8 After obtaining the light field data and establishing the skin model, computational verification is needed to confirm whether high-contrast photoacoustic imaging of cancer cells can be achieved. Cancer cells in actual organisms are not arranged in a regular pattern, so the random distribution of cancer cell locations during the calculation process can more realistically reflect the diversity and complexity of tumors. Furthermore, the random distribution of cancer cells at different locations can simulate various challenges that may be encountered during photoacoustic imaging, such as non-uniform signal intensity and the complexity of the imaging area. The propagation of the acoustic signal follows the wave equation as shown in Equation 5:

[0130] Formula 5,

[0131] In Formula 5, p(x,t) represents the pressure distribution in Pa, p0(x) represents the initial pressure distribution in Pa, and v c The speed of sound is expressed in m / s, and δ(t) is a dimensionless impulse function.

[0132] The calculations were repeated multiple times, with the number and location of cancer cells and normal tissue being randomly distributed. The difference between the initial and reconstructed values ​​at the same location after each experiment was compared to assess image quality. The results are presented below:

[0133] Scenario 1: Initial quantity: 5 normal tissue cells, 15 cancer cells. Photoacoustic imaging reconstruction results showed 5 normal tissue cells and 15 cancer cells. The average sound pressure level of the reconstructed normal tissue cells was 21.70 Pa, and the average sound pressure level of the cancer cells was 207.15 Pa. Comparison of the initial and reconstructed sound pressure levels at random locations showed a high degree of fit between the reconstructed and initial sound pressure profiles.

[0134] Scenario 2: Initial quantity: 7 normal tissue cells, 18 cancer cells. Photoacoustic imaging reconstruction results showed 7 normal tissue cells and 18 cancer cells. The average sound pressure level of the reconstructed normal tissue cells was 14.17 Pa, and the average sound pressure level of the cancer cells was 299.83 Pa. Comparison of the initial and reconstructed sound pressure levels at random locations showed a high degree of fit between the reconstructed and initial sound pressure profiles.

[0135] Scenario 3: Initial quantity: 14 normal tissue cells and 11 cancer cells. Photoacoustic imaging reconstruction results showed 14 normal tissue cells and 11 cancer cells. The average sound pressure level of the reconstructed normal tissue cells was 10.31 Pa, and the average sound pressure level of the cancer cells was 196.64 Pa. Comparison of the initial and reconstructed sound pressure levels at random locations showed a high degree of fit between the reconstructed and initial sound pressure profiles.

[0136] The stress diagram of photoacoustic reconstruction is shown in Figure 9 middle.

[0137] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A design method of a dual-wavelength confocal superlens, characterized by, The method comprises the following steps: S1. defining design goals, determining to realize a double working wavelength of confocal, and making clear that the super surface should realize optical functions, so as to realize the response to two different wavelengths of light and realize confocal, wherein the super surface comprises a focusing super surface and a filtering super surface; S2. selecting materials and parameters, respectively finding a super lens material and a substrate for the double working wavelength, and testing optical properties under different wavelengths, wherein the optical properties comprise refractive index and transmittance; S3. super surface multi-scale structure design, adjusting the response to different wavelengths of light by regulating the size of the unit structure, optimizing the geometric parameters of the unit structure, analyzing the influence on the phase change of the outgoing light wave front, and establishing a quantitative relationship database between the unit structure parameters and the wave front phase; S4. according to the quantitative relationship database, placing unit structures of different materials and different sizes on specific positions of two surfaces of the substrate by using the propagation phase distribution formula derived by the designed wave front phase formula, to realize the filtering or focusing function; S5. repeating S1 to S4, so that different materials are placed at specific positions of the substrate according to the propagation phase formula, and the focusing super surface and the filtering super surface are obtained respectively, to form the double wavelength confocal super lens; The optical band gap of the substrate is greater than 3.1eV in the visible light range, and the optical band gap is greater than 1.5eV in the near infrared light range; the refractive index of the unit structure is 2.0~4.0 in the visible light range, and the optical band gap is greater than 3.1eV, the refractive index of the unit structure is 1.8~3.5 in the near infrared light range, and the optical band gap is greater than 1.5eV; The focusing super surface takes 532nm and 785nm as working wavelengths, takes TiO2 as the unit structure for focusing 532nm light, and takes Si as the unit structure for focusing 785nm light; the filtering super surface takes TiO2 as the unit structure.

2. The design method of claim 1, wherein The double working wavelength comprises a visible light band and a near infrared light band, and the optical functions that the super surface should realize comprise imaging, focusing, transmission, refraction and filtering.

3. The method of claim 1, wherein, The unit structure is a central symmetric structure.

4. The design method according to claim 1 or 3, characterized by, The surface shape of the unit structure is circular, square or regular hexagonal.

5. The method of claim 1, wherein, The geometric parameters comprise one or more of lattice constant, cross-sectional radius and height.

6. The dual-wavelength confocal superlens prepared by the design method of any one of claims 1-5, characterized in that, It comprises a substrate, a focusing super surface on one side surface of the substrate, and a filtering super surface on the other side surface of the substrate.

7. A photoacoustic imaging method, characterized by, The double wavelength confocal super lens of claim 6 is used for photoacoustic imaging.

8. A photoacoustic imaging system, characterized by, It comprises the double wavelength confocal super lens of claim 6 and an ultrasonic transducer.

Citation Information

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