A liver pathological slice detection structure based on spatial Goos-Hansen shift and its preparation method

By combining liver slices with multi-layer dielectrics, using spatial Gus-Hansen displacement detection technology, the problems of long detection cycle, large misjudgment rate and high cost in the existing technology are solved, and lossless, fast and high-sensitivity liver pathological slice detection is achieved.

CN115144370BActive Publication Date: 2025-05-16HUBEI UNIV OF SCI & TECH
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Patent Information

Application Number
CN202210783199.4
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2022-07-05
Publication Date
2025-05-16
Estimated Expiration
2042-07-05

AI Technical Summary

Technical Problem

The prior art has problems such as long detection cycle, large misjudgment rate and high cost in organ tissue pathological section detection, and most of them are destructive detection.

Method used

A liver pathological section detection structure based on spatial Gus-Hansen displacement was designed. By compounding the liver section with a multilayer dielectric layer, an asymmetric multilayer structure was formed, and quantitative detection of the refractive index of the liver pathological section was achieved by changing the incidence angle with a fixed wavelength.

Benefits of technology

Non-destructive testing is realized, pathological sections can be reused, simple operation, fast detection speed, ultra-high sensitivity, and the overall preparation method is versatile, which is convenient for large-scale production.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention relates to a liver pathological section detection structure based on the spatial Goos-Hänchen shift, which can be expressed as DE(AB)<supgt;N< / supgt;C(BA)<supgt;N< / supgt>, where N is the number of periods of the photonic crystal, A, B, and C are dielectric thin films with different refractive indexes respectively, D is a hemispherical dielectric optical waveguide, E is a liver pathological section, and C is a defect layer for generating a defect mode. The present invention also provides a preparation method of the above-mentioned liver pathological section detection structure. The liver pathological section detection structure designed by the present invention is a non-destructive detection for liver pathological sections. The pathological sections can be used repeatedly, and the operation is simple, the detection speed is fast, and it has ultra-high sensitivity. In addition, the overall preparation method has universality, strong operability, and is convenient for large-scale production.
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Description

Technical Field

[0001] The invention belongs to the field of medical detection and optical technology, and in particular relates to a liver pathological slice detection structure based on spatial Goos-Hansen shift and a preparation method thereof. Background Art

[0002] Since the existing detection methods for organ tissue pathological sections mostly use microscope observation, laboratory testing and X-ray irradiation, most of these detection methods have the disadvantages of long detection cycle, high misjudgment rate and high cost, and most of them are destructive detection. In addition, different organ tissue sections correspond to different refractive indices, and the pathological changes of organ tissues will cause the refractive index of pathological sections to change (reduced or increased relative to the normal value).

[0003] When a light wave is incident on the interface between two different media, an evanescent wave will form near the interface, which is equivalent to a virtual reflection surface on the lower or upper side of the interface. The reflected light beam will be laterally displaced relative to the position predicted by the geometric light. This displacement is called the spatial Goos-Hansen shift. The spatial Goos-Hansen shift is very sensitive to the refraction of dielectrics, so the Goos-Hansen shift effect can be used as a refractive index sensor. At the same time, a lossy asymmetric dielectric multilayer structure will cause a huge spatial Goos-Hansen shift, which can be used to measure the refractive index of the medium, and its sensitivity can be greatly improved compared to a symmetric multilayer structure. Therefore, it is considered to combine organ tissue pathological sections with dielectric multilayers to form an asymmetric multilayer structure. For example, pathological sections have large optical losses, and liver sections and dielectric multilayers are combined to form an asymmetric structure to achieve a huge spatial Goos-Hansen shift, thereby quantitatively measuring the refractive index of liver pathological sections.

[0004] However, the investigation found that the patent "A photonic crystal for pathological slice detection (202110705260.9)" inserts the pathological slice into the middle of the photonic crystal, finds the functional correspondence between the Goos-Hansen shift and the wavelength near the defect mode, and detects the pathological slice; while the patent "A multilayer dielectric structure for liver pathological slice detection (202110740167.1)" uses an asymmetric photonic multilayer structure to obtain the direction-dependent Goos-Hansen shift, and compares the peak Goos-Hansen shift of the left and right incident light to achieve pathological analysis of the liver. The common feature of these two patents is "fixed incident angle, changing wavelength", and in actual operation, in general, once the light source is fixed, its wavelength is basically fixed, and it is difficult to adjust its wavelength within a certain range. Summary of the invention

[0005] In order to find a more experimentally operable solution, the present invention designs a liver pathology slice detection structure and a preparation method thereof from the perspective of "fixing the wavelength and changing the incident angle", which uses the Goos-Hansen shift to detect the refractive index of the liver pathology slice. That is, when the incident wavelength is fixed, the size and position of the peak Goos-Hansen shift of the reflected light beam are functions of the incident angle, and the size and position of the peak Goos-Hansen shift are also functions of the refractive index of the liver pathology slice. Therefore, the refractive index of the liver pathology slice can be compared by scanning the size of the peak Goos-Hansen shift and the position of the incident angle, thereby quantitatively analyzing the liver pathology slice.

[0006] The technical solution of the present invention to solve the above technical problems is as follows:

[0007] A liver pathological slice detection structure based on spatial Goos-Hansen shift, the detection structure can be expressed as DE(AB) N C(BA) N , where N is the period number of the photonic crystal, A, B and C are dielectric sheets with different refractive indices, D is a hemispherical dielectric optical waveguide, E is a liver pathological section, and C is a defect layer for generating defect modes; that is, the main body of the entire structure is two photonic multilayer structures (AB) N and(BA) N Symmetrical distribution about defect layer C forms defect photonic crystal (AB) N C(BA) N , liver pathological section E is located in the defective photonic crystal (AB) N C(BA) N Either end, that is, E(AB) N C(BA) N , the optical waveguide D is located at the other end of the liver pathological section E, and finally forms the structure DE(AB) N C(BA) N .

[0008] Based on the above technical solution, the present invention can also be improved as follows.

[0009] Furthermore, the material of the dielectric sheet A is titanium dioxide, and its refractive index is n a =2.5086; the material of dielectric sheet B is zirconium dioxide, and its refractive index is n b =2.132; the material of the dielectric sheet C is silicon, and its refractive index is n c =3.636; the material of the optical waveguide D is silicon dioxide, and its refractive index is n d =1.4525.

[0010] Furthermore, the thicknesses of the dielectric sheets A and B are 1 / 4 of the optical wavelength corresponding to their respective refractive indices; the lengths and widths of the dielectric sheets A, B, C and the liver pathological slice E are more than two orders of magnitude larger than the incident wavelength.

[0011] Furthermore, the thickness of the dielectric sheet A is d a =λ / 4 / n a = 0.0847 μm, the thickness of dielectric sheet B is d b =λ / 4 / n b =0.0997 μm, where the incident wavelength λ = 0.85 μm; the thickness of the dielectric sheet C is d c =0.145 μm; the thickness of the liver pathological section E is d e =0.2μm; the length and width of the dielectric sheets A, B, C and the liver pathological section E are all 100μm, and the radius of the optical waveguide D is 50μm.

[0012] Furthermore, the period number N of the photonic crystal is 2 or 4.

[0013] Another object of the present invention is to provide a method for preparing the above-mentioned liver pathological section detection structure.

[0014] The specific technical solutions are as follows:

[0015] A method for preparing a liver pathological section detection structure comprises the following steps:

[0016] 1) Prepare dielectric sheets A, B, C and liver pathological slice E, and arrange dielectric sheets A and B alternately to form a multilayer dielectric structure E (AB) with liver pathological slice E and defect layer C. N C(BA) N ;

[0017] 2) Make a hemispherical dielectric optical waveguide D and place it in the above structure E (AB) N C(BA) N The end of the liver pathology section E is close to form the liver pathology section detection structure DE (AB) N C(BA) N .

[0018] Furthermore, in the step 1), the dielectric sheets A, B, and C are all made according to the following process: directional sectioning → grinding → polishing; the liver pathological section E is made according to the following process: sampling → fixation → dehydration → transparent treatment → wax dipping → wax melting → embedding → cooling → wax repair → sectioning → sticking → spreading → baking → staining → air drying and sealing.

[0019] Furthermore, in step 1), the dielectric sheet A is made of a material having a refractive index of na =2.5086 titanium dioxide crystal preform rod, made into a thickness of d a =λ / 4 / n a =0.0847μm dielectric sheet A; dielectric sheet B is made of a dielectric sheet with a refractive index of n b =2.132 zirconium dioxide crystal preform, made into a thickness of d b =λ / 4 / n b =0.0997μm dielectric sheet B, where the incident wavelength λ = 0.85μm; the dielectric sheet C is made of a dielectric sheet with a refractive index of n c =3.636 silicon crystal preform, made into a thickness of d c =0.145μm dielectric sheet C; liver pathological slice E is made from a diseased body sample within 30min of in vitro ex vivo, and is made into a thickness of d e =0.2μm liver pathological section E.

[0020] Further, the preparation of the hemispherical dielectric optical waveguide D in step 2) includes the following specific steps: d =1.4525 silicon dioxide crystal preform rod is directional sliced ​​→ ground → polished to make a hemispherical shape.

[0021] Furthermore, the length and width of the dielectric sheets A, B, C and the liver pathological section E in step 1) are both 100 μm, and the radius of the hemispherical dielectric optical waveguide D in step 2) is 50 μm.

[0022] The beneficial effects of the present invention are as follows: the liver pathology section detection structure designed by the present invention based on spatial Goos-Hansen shift is a non-destructive detection of liver pathology sections, the pathology sections can be used repeatedly, and the operation is simple, the detection speed is fast, and it has ultra-high sensitivity. In addition, the overall preparation method is universal, highly operable, and convenient for large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 Schematic diagram of liver pathological slice detection based on spatial Goos-Hansen shift according to Example 1 of the present invention (N=2);

[0024] Figure 2 This is a flow chart of manufacturing liver pathological sections, dielectric sheets and optical waveguides according to Example 1 of the present invention;

[0025] Figure 3 This is a schematic diagram of the steps for making a liver pathology slice detection structure based on spatial Goos-Hansen shift in Example 1 of the present invention;

[0026] Figure 4(a) is the relationship between the phase of the light wave reflection coefficient and the incident angle in Example 2 of the present invention, Figure 4 (b) is the relationship between the reflectivity and the incident angle in Example 2 of the present invention, Figure 4 (c) is the relationship between the valley reflectivity of the reflectivity curve and the refractive index of the liver in Example 2 of the present invention, Figure 4 (d) is the relationship between the incident angle corresponding to the valley point of the reflectivity curve and the refractive index of the liver in Example 2 of the present invention, where the period number N of the photonic crystal is 4;

[0027] Figure 5 (a) is the relationship between the spatial Goos-Hansen displacement and the incident angle in Example 2 of the present invention, Figure 5 (b) is the relationship between the peak Goos-Hansen shift and the liver refractive index in Example 2 of the present invention, Figure 5 (c) is the relationship between the incident angle corresponding to the peak Goos-Hansen shift and the liver refractive index in Example 2 of the present invention. DETAILED DESCRIPTION

[0028] The principles and features of the present invention are described below. The examples given are only used to explain the present invention and are not used to limit the scope of the present invention.

[0029] Unless otherwise specified, the raw materials and equipment used in the present invention are conventional raw materials and equipment (conventional commercial products) in the art and can be purchased on the market.

[0030] When light is incident on the interface between two materials with different refractive indices at an incident angle θ, the reflected light will undergo a certain lateral displacement relative to the position predicted by geometric optics, namely the spatial Goos-Hansen displacement. shift: GH displacement).

[0031] For TM (transverse magnetic) waves, the reflection coefficient r

[0032]

[0033] Where n1 and n2 are the refractive indices of dielectric 1 and dielectric 2 respectively, and θ1 and θ2 are the incident angle and the exit angle at the interface between dielectric 1 and dielectric 2 respectively.

[0034] Further, according to Fresnel's law, the above formula can be rewritten as

[0035]

[0036] When n2<n1, From formula (2), we can see that the reflection coefficient r is a complex number, that is, the reflected light will move laterally relative to the incident point.

[0037] For TM waves, the movement Writing the reflection coefficient modulo the argument of the angle:

[0038]

[0039] where i represents the imaginary unit and the phase shift is

[0040]

[0041] When the incident light is totally reflected at the dielectric interface, part of the light will penetrate from the upper layer into the lower layer of the medium. The incident light beam is regarded as a wave packet composed of plane waves ky and ky+δky with slightly different wave vectors. Then the complex amplitude of the incident wave packet at the input port is

[0042]

[0043] The complex amplitude of the reflected beam is is the phase shift of the reflected light, further

[0044]

[0045] in,

[0046] The wavelength remains unchanged, but the incident angle of the light changes. Define Δ=Δ y cosθ, then

[0047]

[0048] The lateral displacement of this reflected beam, i.e., the spatial Goos-Hansen shift, is proportional to the derivative of the reflection coefficient phase with respect to the incident angle, i.e., the greater the rate of change of the reflection coefficient phase with respect to the incident angle, the greater the lateral movement of the reflected beam.

[0049] Based on this, the present invention designs a liver pathology section detection structure and a specific preparation method thereof, which not only has a fast detection speed and ultra-high sensitivity, but also is simple to operate and convenient for large-scale production. In addition, the detection of liver pathology sections is non-destructive detection, and the liver pathology sections can be reused.

[0050] Example 1

[0051] The liver pathological slice detection structure designed in this embodiment based on spatial Goos-Hansen shift can be expressed as DE(AB) 2 C(BA) 2 , that is, the period number of the photonic crystal is N = 2, Figure 1 The following is a schematic diagram of the detection. A, B and C are dielectric sheets with different refractive indices, D is a hemispherical dielectric optical waveguide, and E is a liver pathological section. θ is the incident angle, Ii is the incident light, I r1 Predicting reflected rays for geometric optics, I r2 is the actual reflected light, I r2 Relative to I r1 There is a certain lateral displacement, namely the spatial Guth-Hansen displacement.

[0052] In the liver pathological slice detection structure, C is a defect layer used to generate a defect mode. The loss of the pathological slice will cause an increase in the reflectivity of the defect mode and a drastic change in the phase of the reflection coefficient. The spatial Goos-Hansen shift is proportional to the rate of change of the reflection coefficient phase. Therefore, a reflected light beam with considerable reflectivity and spatial Goos-Hansen shift can be observed near the defect mode. When the refractive index of the pathological slice changes, the size of the spatial Goos-Hansen shift and the position of the peak Goos-Hansen shift will change, so that the liver pathological slice E can be quantitatively detected.

[0053] The hemispherical dielectric optical waveguide D is arranged at the incident end to ensure that no matter what value of the incident angle the incident light is incident at, the incident light always remains perpendicular to the outer surface of the hemispherical medium.

[0054] The incident wavelength is set to λ = 0.85μm, and it is a TM wave. Figure 1 It can be seen that the main body of the entire structure is two truncated photonic crystals (AB) 2 and(BA) 2 Symmetrical distribution about defect layer C forms defect photonic crystal (AB) 2 C(BA) 2 Liver pathological section E is located in the defective photonic crystal (AB) 2 C(BA) 2 Either end, that is, E(AB) 2 C(BA) 2 , the optical waveguide D is located at the other end of the liver pathological section E, and finally forms the structure DE(AB) 2 C(BA) 2 The number of periods of a photonic crystal is originally infinite, but in practical applications, it always takes a finite number of periods, so it is called a truncated photonic crystal. The truncated photonic crystal structure is also called a photonic multilayer structure.

[0055] The material of the dielectric sheet A in this embodiment is titanium dioxide (TiO2), and its refractive index is n a =2.5086; the material of dielectric sheet B is zirconium dioxide (ZrO2), and its refractive index is n b =2.132; the material of the dielectric sheet C is silicon (Si), and its refractive index is n c=3.636; the material of the optical waveguide D is silicon dioxide (SiO2), and its refractive index is n d =1.4525.

[0056] The thickness of the dielectric sheet A is d a =λ / 4 / n a = 0.0847 μm (micrometer); the thickness of the dielectric sheet B is d b =λ / 4 / n b =0.0997μm; the thickness of the dielectric sheet C is d c =0.145μm; the thickness of liver pathological section E is d e =0.2 μm. The length and width of the dielectric sheets A, B, C and the liver pathological slice E can be at least two orders of magnitude larger than the incident wavelength λ, which is 100 μm in this embodiment, and the radius of the optical waveguide D is 50 μm.

[0057] like Figure 2 As shown, the production process of the liver pathological slice E, each dielectric sheet A, B, C and optical waveguide D in this embodiment is as follows:

[0058] 1) Preparation of dielectric sheet A: TiO2 crystal preform rod is oriented and sliced ​​→ ground → polished to a thickness of d a =0.0847 μm;

[0059] 2) Preparation of dielectric sheet B: Directional slicing of zirconium dioxide crystal preform → grinding → polishing to a thickness of d b =0.0997 μm;

[0060] 3) Preparation of dielectric sheet C: Orientation slice of silicon crystal preform → grinding → polishing to make it thicker than d c =0.145 μm;

[0061] 4) Preparation of liver pathological sections E: Take the diseased specimen within 30 minutes of ex vivo treatment → Fix the pathological specimen (Put it in a sealed container with 10% formaldehyde solution, the volume of the solution is 10 times the volume of the specimen, and the fixation time is 12-48 hours) → Take the specimen (Rinse and cut into pieces with a size of 100μm×100μm×100μm, and place in an embedding box) → Dehydrate (Treat with 50% ethanol reagent for 30 minutes, 60% ethanol reagent for 30 minutes, 70% ethanol reagent for 30 minutes, 80% ethanol reagent for 30 minutes in, 90% ethanol reagent treatment for 30min, 95% ethanol I reagent treatment for 30min, 95% ethanol II reagent treatment for 30min, anhydrous ethanol I reagent treatment for 20min, anhydrous ethanol II reagent treatment for 20min) → transparent (xylene I reagent and xylene I reagent treatment for 10min each, the treatment time can be determined according to the transparent effect) → wax immersion (paraffin I wax immersion for 10min, paraffin II wax immersion for 10min, open the water bath at 80℃ in advance, adjust to 60℃ after the paraffin is almost completely melted, and place in a constant temperature box 120min) → Melt wax (the embedding machine needs to be turned on in advance and preheated for half an hour to melt the paraffin) → Embed (Put the tissue in the middle of the iron embedding frame and drip the melted paraffin for embedding. During this period, pay attention to the relative position of the tissue and the wax block) → Cool (Put it in a -10 degree refrigerator) → Trim and slice (Put the embedded tissue on the slicer after trimming, adjust the position and set the slice thickness to 0.2um) → Spread (Take the slide that has been ultrasonically rinsed with 30% ethanol, spread it in 30% ethanol, take the slide after 5s and put it in a 40℃ water bath to spread it, and wait for slicing Completely and neatly taken out) → drying (60℃ constant temperature oven drying for 20-30min) → dewaxing and staining (hematoxylin staining for 4min, water washing for 2min, 1% hydrochloric acid alcohol differentiation for 20s (seconds), water washing for 2min, 1% dilute ammonia water blueing for 30s, water washing for 2min, distilled water washing for 1min, eosin staining for 90s, rinsed with running water) → drying and sealing (after the residual liquid around the slide tissue is dried, immediately drop a drop of neutral gum on the tissue, cover it with a cover slip to cover it naturally, and lay it flat), and the finished liver pathological section E is obtained;

[0062] 5) Fabrication of hemispherical dielectric optical waveguide D: Oriented slicing of silicon dioxide crystal preform → grinding → polishing to form a hemispherical shape with a radius of 50 μm.

[0063] like Figure 3 As shown, the method for preparing the liver pathology section detection structure of this embodiment using the dielectric sheets A, B, C, optical waveguide D and liver pathology section E prepared as above comprises the following steps:

[0064] 1) Alternately arrange dielectric sheets A and B, together with liver pathological slice E and defect layer C, to form a multilayer dielectric structure: E(AB) 2 C(BA) 2 ,like Figure 3 (a)

[0065] 2) Place the hemispherical dielectric optical waveguide D in the above structure E (AB) 2 C(BA) 2 The end of the liver pathology section E is close to form the liver pathology section detection structure DE (AB) 2 C(BA) 2 ,like Figure 3 (b) is shown. The lateral displacement of the reflected light, i.e., the spatial Goos-Hansen displacement, is controlled by the angle of the incident TM light from the outside. The present invention analyzes the pathology of the liver slice by the peak spatial Goos-Hansen displacement of the reflected light and the incident angle position corresponding to the peak Goos-Hansen displacement.

[0066] Example 2

[0067] Write the refractive index of a human liver pathological section as n e =n er +i*n ei , where n er represents the real part of the refractive index of the liver pathological section, n ei represents the imaginary part of the refractive index of the liver pathological section, and i represents the imaginary unit. When the incident light wavelength is λ = 0.85 μm, the real part of the refractive index of the normal human liver pathological section is n er =1.3694, the imaginary part of the refractive index is n ei =0.0031719. The imaginary part of the refractive index represents the gain and loss of light. A positive imaginary part indicates loss, and a negative imaginary part indicates gain. The imaginary part of the refractive index of a normal human liver pathological section is positive and small, indicating that the light loss is low and can be ignored. Therefore, when considering liver lesions later, only the real part of the refractive index changes, while the imaginary part remains unchanged.

[0068] Taking a liver pathological slice detection structure based on spatial Goos-Hansen shift designed in this embodiment as an example, its overall structure can be expressed as DE(AB) 4 C(BA) 4 The incident wavelength is λ=0.85 μm and is a TM excitation wave. The photon multilayer is incident from the optical waveguide D. The overall structure of this embodiment is different from that of embodiment 1 only in that the period number N of the photonic crystal is 4, and the rest of the structure is the same.

[0069] Figure 4(a) shows the relationship between the phase of the light wave reflection coefficient and the incident angle. When the human liver is diseased, its refractive index will change. It can be seen that different refractive indices correspond to different phase curves; as the incident angle changes, there is a 2π phase jump in each phase curve, which is meaningless; but at the phase jump, the phase curve change rate is the largest; as the refractive index increases, the phase jump point moves to the right, that is, moves to a larger incident angle. Because the spatial Goos-Hansen shift is proportional to the reflection coefficient phase change rate, there must be a large spatial Goos-Hansen shift near the phase jump point. The horizontal axis unit deg represents degrees, that is, "°"; the vertical axis unit rad represents radians.

[0070] Figure 4 (b) shows the relationship between the phase of the light wave reflectivity and the incident angle. It can be seen that different refractive indices correspond to different reflectivity curves; in each reflectivity curve, there is a valley; the lowest point of the valley is called the valley point. When the refractive index increases, the position of the valley point moves to the right, that is, moves to a larger incident angle; as the refractive index increases, the reflectivity of the valley point increases. The valley point of the reflectivity curve is recorded as (R v ,θ v ), where R v is the reflectivity corresponding to the valley point, θ v is the incident angle corresponding to the valley point. Normal liver (n er =1.3694) The corresponding reflectivity valley point is: R v = 0.0892 and θ v = 60.1°. When the liver refractive index decreases, for example, n er =1.2 The corresponding reflectivity valley point is: R v = 0.0517 and θ v =59.65°; when the liver refractive index increases, for example, n er =1.4 The corresponding reflectivity valley point is: R v = 0.1745 and θ v =60.55°.

[0071] Figure 4 (c) shows the relationship between the reflectivity of the valley point of the reflectivity curve and the refractive index of the liver. It can be seen that as the refractive index of the liver increases, the reflectivity R v The greater the reflectivity, the greater the reflected light intensity under the same incident light intensity, and the easier it is to observe the reflected light of the spatial Goos-Hansen shift.

[0072] Figure 4 (d) shows the relationship between the incident angle corresponding to the valley point of the reflectivity curve and the refractive index of the liver. It can be seen that as the refractive index of the liver increases, the incident angle θ corresponding to the valley pointv However, as the liver refractive index continues to increase, θ v The rate of increase gradually decreases.

[0073] Figure 5 (a) shows the relationship between the spatial Goos-Hansen shift and the incident angle. It can be seen that different refractive indices of liver pathological slices E correspond to different spatial Goos-Hansen shift curves; as the incident angle changes, there is a peak in each spatial Goos-Hansen shift curve, and the peak Goos-Hansen shift is the largest; as the refractive index of the liver changes, the peak position of the spatial Goos-Hansen shift changes. Specifically, when the refractive index increases, the peak value of the spatial Goos-Hansen shift decreases, and the corresponding incident angle position moves to the right. The peak position of the Goos-Hansen shift is recorded as (Δ p ,θ p ), where Δ p is the peak spatial Goos–Hansen shift, θ p is the angle of incidence corresponding to the peak Goos–Hansen shift.

[0074] Figure 5 (b) shows the relationship between the peak Goos-Hansen shift and the refractive index of the liver. It can be seen that as the refractive index increases, the peak Goos-Hansen shift decreases. The larger the Goos-Hansen shift, the easier it is to observe in the experiment. The decrease in Goos-Hansen shift means that it is more difficult to observe the displacement in the reflected beam. Normal liver slice n er = 1.3694 corresponding to the corresponding peak Goos-Hansen shift Δ p =5.055λ, at the position of ☆ in the figure.

[0075] Figure 5 (c) shows the relationship between the incident angle corresponding to the peak Goos-Hansen shift and the liver refractive index. It can be seen that as the liver refractive index increases, the incident angle θ corresponding to the peak Goos-Hansen shift p However, as the refractive index increases, θ p The rate of increase gradually decreases. Normal liver (n er =1.3694) corresponds to a peak Goos-Hansen shift corresponding to an incident angle of θ p =60.05°, at the position of ☆ in the figure.

[0076] When the liver is diseased, the refractive index decreases or increases, and the position of the corresponding peak Goos-Hansen shift changes. Therefore, the liver can be pathologically detected by measuring the incident angle position and Goos-Hansen shift size corresponding to the peak Goos-Hansen shift. The incident angle position of the peak Goos-Hansen shift corresponding to a normal liver is θ p= 60.05°, and the corresponding peak Goos-Hansen shift is Δ p =5.055λ; when the liver refractive index decreases, for example, n er = 1.2 The incident angle position of the peak Goos-Hansen shift is θ p =59.6°, and the corresponding peak Goos-Hansen shift is Δ p =6.939λ; when the liver refractive index increases, for example, n er = 1.4, the incident angle position of the peak Goos-Hansen shift is θ p = 60.04°, and the corresponding peak Goos-Hansen shift is Δ p =3.269λ.

[0077] In summary, the present invention takes liver pathological sections as an example. The liver sections are compounded with dielectric sheets to form a multilayer dielectric structure with an asymmetrical distribution of defects. Near the defect mode, the reflected light beam has a large spatial Goos-Hansen shift and a considerable reflectivity. The size of the spatial Goos-Hansen shift peak and the incident angle corresponding to the peak Goos-Hansen shift are extremely sensitive to the refractive index of the liver pathological sections. When the liver is diseased, its refractive index changes. Therefore, by scanning the incident angle and measuring the peak Goos-Hansen shift size of the reflected light beam and the position of the corresponding incident angle, quantitative analysis of the pathological sections can be achieved.

[0078] The invention discloses a liver pathological slice detection structure based on spatial Gus-Hansen shift and a preparation method thereof. The overall preparation method is versatile, highly operable, and convenient for large-scale production. The detection of liver pathological slices belongs to non-destructive detection. The pathological slices can be used repeatedly, and the operation is simple, the detection speed is fast, and the sensitivity is ultra-high. The organ tissue slices of the invention take the liver as an example. In practical applications, other organ tissue pathological slices can also be detected based on this method.

[0079] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A liver pathological slice detection structure based on spatial Goos-Hansen shift, characterized in that: The detection structure can be expressed as DE(AB) N C(BA) N , where N is the period number of the photonic crystal, and N = 2 or 4, A, B and C are dielectric sheets with different refractive indices, D is a hemispherical dielectric optical waveguide, E is a liver pathological section, and C is a defect layer for generating defect modes; that is, the main body of the entire structure is two photonic multilayer structures (AB) N and(BA) N Symmetrical distribution about defect layer C forms defect photonic crystal (AB) N C(BA) N , liver pathological section E is located in the defective photonic crystal (AB) N C(BA) N Either end, that is, E(AB) N C(BA) N , the optical waveguide D is located at the other end of the liver pathological section E, and finally forms the structure DE(AB) N C(BA) N The use process and steps of the detection structure are as follows: the incident light is incident perpendicular to the optical waveguide D, the incident wavelength is fixed, and the maximum Goos-Hansen shift is found by changing the incident angle.

2. A liver pathological section detection structure based on spatial Goos-Hansen shift according to claim 1, characterized in that: The material of the dielectric sheet A is titanium dioxide, and its refractive index is n a =2.5086; the material of dielectric sheet B is zirconium dioxide, and its refractive index is n b =2.132; the material of the dielectric sheet C is silicon, and its refractive index is n c =3.636; the material of the optical waveguide D is silicon dioxide, and its refractive index is n d =1.4525.

3. A liver pathological slice detection structure based on spatial Goos-Hansen shift according to claim 2, characterized in that: The thickness of the dielectric sheets A and B is 1 / 4 of the optical wavelength corresponding to their respective refractive indices; the length and width of the dielectric sheets A, B, C and the liver pathological section E are more than two orders of magnitude larger than the incident wavelength.

4. A liver pathological slice detection structure based on spatial Goos-Hansen shift according to claim 2 or 3, characterized in that: The thickness of the dielectric sheet A is d a =λ / 4 / n a = 0.0847 μm, the thickness of dielectric sheet B is d b =λ / 4 / n b =0.0997 μm, where the incident wavelength λ = 0.85 μm; the thickness of the dielectric sheet C is d c =0.145 μm; the thickness of the liver pathological section E is d e =0.2μm; the length and width of the dielectric sheets A, B, C and the liver pathological section E are all 100μm, and the radius of the optical waveguide D is 50μm.

5. A method for preparing a liver pathological section detection structure according to any one of claims 1 to 4, characterized in that: The following steps are involved: 1) Prepare dielectric sheets A, B, C and liver pathological slice E, and arrange dielectric sheets A and B alternately to form a multilayer dielectric structure E (AB) with liver pathological slice E and defect layer C. N C(BA) N ; 2) Make a hemispherical dielectric optical waveguide D and place it in the above structure E (AB) N C(BA) N The end of the liver pathology section E is close to form the liver pathology section detection structure DE (AB) N C(BA) N .

6. The method for preparing the liver pathological section detection structure according to claim 5, characterized in that: In the step 1), the dielectric slices A, B, and C are all made according to the following process: directional sectioning → grinding → polishing; the liver pathological section E is made according to the following process: sampling → fixation → dehydration → transparent treatment → wax dipping → wax melting → embedding → cooling → wax repair → sectioning → sticking → spreading → baking → staining → air drying and sealing.

7. The method for preparing the liver pathological section detection structure according to claim 6, characterized in that: In the step 1), the dielectric sheet A is prepared by using a dielectric sheet having a refractive index of n a =2.5086 titanium dioxide crystal preform rod, made into a thickness of d a =λ / 4 / n a =0.0847μm dielectric sheet A; dielectric sheet B is made of a dielectric sheet with a refractive index of n b =2.132 zirconium dioxide crystal preform, made into a thickness of d b =λ / 4 / n b =0.0997μm dielectric sheet B, where the incident wavelength λ = 0.85μm; the dielectric sheet C is made of a dielectric sheet with a refractive index of n c =3.636 silicon crystal preform, made into a thickness of d c =0.145μm dielectric sheet C; liver pathological slice E is made from a diseased body sample within 30min of in vitro ex vivo, and is made into a thickness of d e =0.2μm liver pathological section E.

8. The method for preparing the liver pathological section detection structure according to claim 5, characterized in that: The preparation of the hemispherical dielectric optical waveguide D in step 2) comprises the following specific steps: d =1.4525 silicon dioxide crystal preform rod is directional sliced ​​→ ground → polished to make a hemispherical shape.

9. The method for preparing the liver pathological section detection structure according to claim 7, characterized in that: The length and width of the dielectric sheets A, B, C and the liver pathological section E in step 1) are both 100 μm, and the radius of the hemispherical dielectric optical waveguide D in step 2) is 50 μm.

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