Double-coating-film lantern-shaped side-throwing PCF refractive index sensor for cancer cell detection and preparation method

Abstract

The invention provides a double-coated lantern-shaped side-cast PCF refractive index sensor for cancer cell detection and a preparation method, and relates to the field of optical fiber sensing, the sensor comprises a photonic crystal fiber body, the photonic crystal fiber body comprises a substrate material, the substrate material is quartz, the structure is a cylinder, the cylinder comprises a smooth upper tangent plane, and the smooth upper tangent plane is provided with a lower tangent plane. The smooth upper section silver-plated film is used for exciting the SPR effect, and a titanium dioxide layer is deposited on the basis of the silver film to inhibit the silver film from being oxidized and serves as a detection channel for enhancing the mode coupling efficiency; and cladding air holes are formed in the substrate structure. The refractive index is measured in the range of 1.35-1.42, the highest refractive index sensitivity can reach-83100 nm / RIU, and the quality factor can reach-83100 nm / RIU. Meanwhile, biological functionalization modification is carried out on the surface of the titanium dioxide layer by utilizing a light functionalization method, high-sensitivity specific detection on cancer cells can be realized at the same time, and the sensor is particularly suitable for diagnosis and early monitoring of breast cancer.

Description

Technical Field

[0001] This invention relates to the field of fiber optic sensing, specifically to a double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection and its fabrication method. Background Technology

[0002] Cancer, as one of the leading causes of death worldwide, poses a significant threat to human life and health, making early diagnosis crucial. Currently, traditional methods such as biopsy, X-ray imaging, and magnetic resonance imaging are widely used for cancer identification and have demonstrated good accuracy in detecting various types of cancer. However, these technologies still face limitations such as high cost, reliance on markers, and insufficient sensitivity in early stages, which can easily lead to diagnostic delays, affecting treatment timing and patient survival rates. To address these challenges and meet the growing demand in modern biomedical detection for highly sensitive, non-invasive, and remotely operable sensing systems, researchers have introduced surface plasmon resonance (SPR) technology based on photonic crystal fiber (PCF) into this field, aiming to advance the development of early cancer diagnosis technologies.

[0003] SPR (Surface Plasma Resonance) is a physical-optical phenomenon occurring at the metal-dielectric interface, manifested as resonant coupling between surface plasmon waves and evanescent waves. Traditional SPR detection systems are mainly based on prism or fiber coupling methods. Prism structures are typically large and costly, limiting their practicality. The fiber optic SPR sensor, first reported in 1993, provided a new approach to overcome these limitations, particularly suitable for remote sensing and real-time monitoring scenarios. To improve SPR sensing performance, researchers have focused on exploring three types of fiber structures: geometrically modified fibers (such as tapered, bent, and side-projected fibers), grating-assisted fibers, and special fibers (including polarization-preserving fibers, hollow fibers, and PCF). Among these, PCF exhibits significant advantages due to its structural design flexibility, ease of miniaturization, large mode area, and controllable birefringence. By optimizing the geometric parameters of PCF, the phase matching between the core mode and the surface plasmon mode can be effectively controlled, thereby efficiently exciting the SPR effect. PCF-based SPR sensors (PCF-SPR) combine multiple advantages such as high sensitivity, compact structure, resistance to electromagnetic interference, fast response speed, and strong field confinement, and have shown significant application potential in the field of biomedical diagnostics in recent years.

[0004] PCF-SPR sensors distinguish between healthy and cancerous cells by detecting changes in refractive index (RI). Current research primarily focuses on two sensing mechanisms: internal and external sensing. Internal sensing achieves this by monitoring changes in RI or molecular interactions within the microporous structure of the optical fiber. For example, integrating microfluidic cavities into PCFs can detect cells such as cervical cancer cells, achieving a maximum sensitivity of 10625 nm / RIU. While this method is advantageous for achieving high sensitivity and multi-component detection, its fabrication process is complex, and achieving uniform metal plating and nanocavity filling presents challenges in practical manufacturing. In contrast, external sensing mechanisms capture external analyte signals by depositing functional material coatings on the outer surface of the PCF. This process is simpler and more suitable for experimental and fabrication purposes. However, this approach typically yields lower sensitivity and resolution, thus necessitating a detection sensor with higher sensitivity and resolution. Summary of the Invention

[0005] To address the shortcomings of the prior art, the present invention aims to provide a double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection and its preparation method. This sensor not only inhibits the oxidation of the silver film and improves the adhesion of the metal layer, but also effectively enhances the interaction between the core mode and the surface plasmon mode, thereby achieving high-sensitivity detection capability for cancer cells.

[0006] Specifically, the present invention provides a double-coated lantern-shaped side-polished PCF refractive index sensor for cancer cell detection, which includes a photonic crystal fiber body, a analyte channel, and a perfect matching layer. The analyte channel is immersed in the side-polished portion of the photonic crystal fiber body, and the perfect matching layer is located on the outer layer of the photonic crystal fiber body. The photonic crystal fiber body includes a substrate material, which is cylindrical in structure. A smooth upper tangent is formed on the upper side of the cylinder. The outer surface of the upper tangent is coated with a silver film for exciting the SPR effect. A titanium dioxide layer is deposited on the surface of the silver film to suppress silver film oxidation and to serve as a detection channel for enhanced mode coupling efficiency. Cladding air holes are provided inside the cylinder, including internal air holes and air holes near the side surface. The internal air holes include eight first air holes, and the air holes near the side surface include three second air holes adjacent to the side surface, used to flexibly adjust the evanescent field leakage channel. The first and second air holes are integrally arranged in a [missing information - likely a specific configuration]. The lamp-shaped, asymmetrical arrangement, wider at the top and narrower at the bottom, has two of the eight first air holes located on the sides and below the second air holes. The remaining six first air holes are arranged in groups of three, away from the side surface. The titanium dioxide layer is biofunctionalized using photofunctionalization to immobilize antibodies that can specifically recognize cancer cell surface markers. The negatively charged carboxyl termini of the antibodies are adsorbed onto the positively charged titanium dioxide surface through electrostatic interactions, while the positively charged amino termini of the antibodies are fully exposed towards the analyte, thus achieving specific recognition and detection of cancer cell antigens.

[0007] Preferably, the diameter of the first air hole is The diameter of the second air hole is 4.2-4.8 μm, and the spacing between adjacent air holes is 6.0 μm.

[0008] Preferably, the thickness of the silver film coated on the smooth upper cut surface is 35-45 nm.

[0009] Preferably, the thickness of the titanium dioxide layer coated on the silver film is 35-45 nm.

[0010] Preferably, the thickness of the silver film coated on the smooth upper surface is 35 nm, and the thickness of the titanium dioxide layer coated on the silver film is 40 nm.

[0011] Preferably, the substrate structure is made of silicon dioxide.

[0012] Preferably, the arrangement of air holes with a wider top and narrower bottom in the shape of a lantern can compress the light field energy upward, allowing more energy to penetrate into the silver-titanium dioxide double-coated area on the upper surface, enhancing the interaction between light and the silver-titanium dioxide composite layer, thereby enhancing the coupling between the fiber core mode and the plasma mode and improving the surface plasma resonance intensity.

[0013] In a second aspect, the present invention provides a method for fabricating a double-coated lantern-shaped side-sprayed PCF refractive index sensor for cancer cell detection, which includes the following steps: S1, using stacking technology to obtain a photonic crystal fiber preform containing an arrangement of air holes, wherein the air holes are arranged in a hexagonal lattice. S2. The preform is placed in an optical fiber drawing tower for drawing to obtain a photonic crystal fiber. The diameter of the first internal air hole is [missing information]. Then, two of the five air holes in the original cladding were removed to obtain three second air holes close to the side surface. The diameter of the three second air holes is 4.2-4.8 μm and the distance between two adjacent air holes is 6.0 μm. S3. Polish the upper side of the photonic crystal fiber using a fiber polishing machine to obtain a smooth upper tangent. The smooth upper tangent is parallel to the center line of the three second air holes near the side polishing surface. The air holes are arranged in a lantern shape with a wider top and a narrower bottom, which can squeeze the light field energy upward and concentrate it on the upper tangent. S4. Deposit and solidify a silver thin film and a titanium dioxide layer on a smooth upper cross surface using magnetron sputtering technology. S5. Biofunctionalization modification of the titanium dioxide layer surface was performed using photofunctionalization to immobilize antibodies that can specifically recognize cancer cell surface markers. The sensor with the deposited titanium dioxide layer was then irradiated under ultraviolet light for a certain period of time, causing the titanium dioxide layer surface to generate a photogenerated positive charge and transform into a superhydrophilic state. The photofunctionalized sensor was immediately immersed in phosphate buffer containing antibodies at room temperature. During the immersion process, the negatively charged carboxyl terminus of the antibody was adsorbed onto the positively charged titanium dioxide layer surface through electrostatic interaction, while the positively charged amino terminus of the antibody was fully exposed towards the analyte of the cancer cells to be tested.

[0014] Preferably, the polishing depth formed by polishing the smooth upper cut surface is 7.0-7.4μm; the silver film thickness is 35-45nm; and the titanium dioxide layer thickness is 35-45nm.

[0015] Preferably, step S5 specifically includes the following steps: S51. Perform sensor cleaning. Place the lamp-shaped side-polished PCF refractive index sensor with silver-titanium dioxide double coating in acetone, anhydrous ethanol and deionized water in sequence, and perform ultrasonic treatment to thoroughly remove residual organic impurities, dust and stains on the surface of the optical fiber. After cleaning, slowly blow dry the sensor surface with high-purity nitrogen gas for later use. S52. Conduct ultraviolet light functionalization and activation treatment. Place the dried sensor under a 365nm wavelength ultraviolet lamp, maintaining a vertical irradiation posture, and control the ultraviolet light intensity at 2-5mW / cm². 2 Within the range, continuous irradiation for more than 1 hour will generate a large number of photogenerated positive charges on the surface of the titanium dioxide layer through ultraviolet light excitation, and at the same time realize the transformation of the surface from hydrophobic to superhydrophilic state, laying the foundation for subsequent antibody targeted fixation. S53. Immediately after UV activation, perform rapid post-processing. Gently rinse the sensor surface three times with deionized water, then rinse once with anhydrous ethanol to remove residual impurities and unreacted active groups. Dry with high-purity nitrogen. The total post-processing time should be less than 10 minutes to avoid rapid decay of the positive charge and hydrophilic active sites generated on the titanium dioxide surface. S54. Perform electrostatic fixation of cancer cell antibodies. Immerse the photofunctionalized sensor completely in a 20 μg / mL cancer cell antibody solution prepared with phosphate buffer and incubate at 4°C in the dark for 12 h. Utilize the electrostatic interaction between the positive charge on the surface of titanium dioxide and the negative charge of the C-terminal carboxyl group of the antibody to achieve directional and stable binding of the antibody and retain the antibody's biological activity in recognizing cancer cells. S55. After incubation, the sensor surface was gently rinsed three times with PBS buffer to thoroughly wash away unbound free antibodies. Then, the sensor was immersed in a PBS solution of 1% bovine serum albumin and blocked at room temperature for 1 hour to block the unmodified non-specific adsorption sites on the titanium dioxide surface, reduce the non-specific adhesion of impurities to cells during subsequent detection, and improve detection specificity. S56. After sealing, the sensor surface is rinsed again with PBS buffer to remove residual bovine serum albumin solution, and then dried with high-purity nitrogen to obtain a double-coated lantern-shaped side-sprayed PCF refractive index sensor for cancer cell detection.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) The double-coated lantern-shaped side-sprayed PCF refractive index sensor for cancer cell detection provided by the present invention has a lantern-shaped asymmetrical arrangement of air holes with a wider top and narrower bottom, which can generate ultra-high birefringence, squeeze the light field energy upward, and allow more energy to penetrate into the silver-titanium dioxide double-coated area of ​​the upper section, enhance the interaction between light and silver-titanium dioxide composite film, significantly enhance the coupling between fiber core mode and plasma mode, and improve the surface plasma resonance intensity.

[0017] (2) The double-coated lamp-shaped side-displacement PCF refractive index sensor for cancer cell detection provided by this invention has higher sensitivity than existing PCF sensors. Compared with gold film, silver film has a sharper resonant absorption peak and a narrower half-width at half-maximum, which significantly improves the resolution of the sensor. It can simultaneously detect refractive index and cancer cells. In the refractive index range of 1.35~1.42, due to the anomalous blue shift of the resonant wavelength, its refractive index sensitivity can reach up to -83100nm / RIU, and its quality factor can reach [missing value]. .

[0018] (3) The double-coated lantern-shaped side-polished PCF refractive index sensor for cancer cell detection provided by the present invention, compared with the existing PCF sensor, uses a side polishing method to process the single-core PCF, so that the side-polished plane has extremely high surface flatness, so as to obtain a flat sensing area for SPR excitation, and ensure the thickness uniformity of the silver film and titanium dioxide layer at the nanoscale, thereby avoiding the broadening of the SPR resonance peak caused by uneven thickness.

[0019] (4) The double-coated lantern-shaped side-displacement PCF refractive index sensor for cancer cell detection provided by the present invention utilizes photofunctionalization to biofunctionalize the surface of the titanium dioxide layer in order to achieve specific recognition of antigens, thereby immobilizing antibodies that can specifically recognize cancer cell surface markers. This method does not require complex chemical reagents, can spontaneously immobilize antibodies in an "standing" manner, maximize antibody-antigen binding ability, and can significantly improve detection sensitivity.

[0020] (5) The double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection provided by this invention, through testing five types of cancer cells, shows that it has the best detection performance for MDA-MB-231, with a wavelength sensitivity of -46928.57 nm / RIU and a resolution of [missing information]. .

[0021] (6) The double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection provided by this invention establishes a two-dimensional modulation scheme of wavelength-amplitude sensitivity by synchronously monitoring the changes in resonance wavelength and amplitude, thereby providing a unique "fingerprint" feature and overcoming the problem of wavelength overlap response and detection confusion caused by blue shift of resonance peak. The amplitude sensitivity can reach The resolution is . Attached Figure Description

[0022] Figure 1 This is a schematic diagram of the detection system structure of the double-coated lantern-shaped side-sprayed PCF refractive index sensor for cancer cell detection according to the present invention. Figure 2 This is a schematic diagram of the fabrication process of the double-coated lantern-shaped side-sprayed PCF refractive index sensor for cancer cell detection according to the present invention. Figure 3 This invention relates to the photofunctionalization process of the titanium dioxide layer surface of the double-coated lantern-shaped side-polished PCF refractive index sensor for cancer cell detection. Figure 4 The Y-polarized core mode and SPP mode dispersion relationship and limit loss curves of the double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection of the present invention are shown. Figure 5The diagram shows the dispersion relationship and confinement loss curves of the core mode and SPP mode in the Y-polarization direction when the refractive index changes from 1.35 to 1.42. Figure 6 The spectrum of loss and dispersion of the double-coated lantern-shaped side-polished PCF refractive index sensor for cancer cell detection according to the present invention is shown as a function of the diameter of the internal air hole. Figure 7 The image shows the spectral diagram of the loss and dispersion of the double-coated lantern-shaped side-polished PCF refractive index sensor for cancer cell detection as a function of the diameter of the air hole near the side-polished surface. Figure 8 The spectrum of loss and dispersion as a function of polishing depth is shown for the double-coated lamp-shaped side-polished PCF refractive index sensor for cancer cell detection of the present invention. Figure 9 The spectrum of loss and dispersion of the double-coated lamp-shaped side-polished PCF refractive index sensor for cancer cell detection of the present invention is shown as a function of silver film thickness. Figure 10 The image shows the spectral diagram of the loss and dispersion of the double-coated lamp-shaped side-polished PCF refractive index sensor for cancer cell detection as a function of titanium dioxide layer thickness. Figure 11 This is a graph showing the loss of the double-coated lantern-shaped side-sprayed PCF refractive index sensor for cancer cell detection of the present invention as a function of normal cells and cancerous cells of the adrenal gland, blood, breast, and cervix. Figure 12 This is a comparison chart of the amplitude sensitivity of the double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection of the present invention for five types of cancer cells. Detailed Implementation

[0023] Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings.

[0024] In a first aspect, the present invention provides a double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection as a sensing probe of a detection system, such as... Figure 1 As shown, the entire detection system includes a broadband light source 10, a single-mode optical fiber 11, a polarization controller 12, a spectrometer 14, an ultrasonic cleaner 15, an Abbe refractometer 16, a cancer cell analyte 17, and a micro-injection pump 18, etc. Its sensing probe part, namely the double-coated lantern-shaped side-polished PCF refractive index sensor for cancer cell detection of the present invention, includes a PCF body 13, the side polished part of the PCF in which the analyte 2 is immersed, and a perfectly matched layer is located on the outer layer of the PCF, which is an absorption boundary added when simulating the performance of the optical fiber.

[0025] The PCF body includes a substrate material 3, which has a cylindrical structure. The cylinder has a smooth upper cross-section 9, and a silver film 7 is deposited on the upper cross-section to excite the SPR effect. A titanium dioxide layer 8 is then deposited on the silver film to suppress the oxidation of the silver layer and to serve as a detection channel to enhance the mode coupling efficiency. The substrate material 3 has cladding air holes 4, which include an internal first air hole 5 and a second air hole 6 near the side parabolic surface.

[0026] In a specific application embodiment, the diameter of the first air hole is The diameter of the second air hole is 4.2-4.8 μm, and the spacing between adjacent air holes is 6.0 μm. The thickness of the silver film coated on the smooth upper surface is 35-45 nm. The thickness of the titanium dioxide layer coated on the silver film is 35-45 nm.

[0027] In a preferred embodiment of the present invention, the diameter of the first internal air hole is 4.0 μm, and the distance between two adjacent air holes is 6.0 μm. By removing two of the five air holes in the original cladding, three second air holes are obtained near the side-surface. The diameter of the second air holes near the side-surface is... .

[0028] As a preferred embodiment of the present invention, a silver film 7 coated on the smooth upper cross-section 9 has a thickness of 35 nm and is used as an inducing material to support the SPR effect. The material of the silver film is silver. A titanium dioxide layer 8 coated on the surface of the silver film 7 has a thickness of 40 nm and is made of titanium dioxide.

[0029] In a preferred embodiment of the present invention, the substrate material 3 is silicon dioxide.

[0030] Secondly, the present invention provides a method for preparing a silver-titanium dioxide double-coated lantern-shaped side-polished PCF refractive index sensor for the above-mentioned cancer cell detection, such as... Figure 2 As shown, it includes the following steps: S1. Using stacking technology, a photonic crystal fiber preform containing air holes is obtained, with the air holes arranged in a hexagonal lattice.

[0031] S2. The preform is placed in an optical fiber drawing tower for drawing to obtain a photonic crystal fiber. The diameter of the first internal air hole is [missing information]. Then, two of the five air holes in the original cladding are removed to obtain three second air holes near the side surface. The diameter of the three second air holes is 4.2-4.8 μm and the distance between two adjacent air holes is 6.0 μm. More preferably, the diameter of the internal air holes is 4.0 μm and the distance between two adjacent air holes is 6.0 μm. By removing two of the five air holes in the original cladding, three air holes near the side surface are obtained. The diameter of the three air holes near the side surface is 4.4 μm.

[0032] S3. The upper side of the photonic crystal fiber is polished using a fiber polishing machine to obtain a smooth upper cut surface. The cut surface is parallel to the center line connecting the three air holes near the side polishing surface. The air holes are arranged in a lantern shape, wider at the top and narrower at the bottom, which can compress the light field energy upward and concentrate it on the upper cut surface. In a specific embodiment, the polishing depth is 7.0 μm.

[0033] S4. A silver thin film and a titanium dioxide layer are deposited on a smooth upper cross-section using magnetron sputtering technology and then cured. In one specific embodiment, the silver film thickness is 35 nm and the titanium dioxide layer thickness is 40 nm.

[0034] S5. A photofunctionalization method is used to biofunctionalize the surface of a titanium dioxide layer to immobilize antibodies that specifically recognize cancer cell surface markers. The sensor with the deposited titanium dioxide layer is irradiated under ultraviolet light for 1 hour, causing the titanium dioxide surface to generate a photogenerated positive charge and transform into a superhydrophilic state. The photofunctionalized sensor is then immediately immersed in a phosphate buffer containing antibodies, preferably at a concentration of 0.01-0.1 mg / mL, at room temperature for 5-15 minutes. During immersion, the negatively charged carboxyl termini of the antibody are adsorbed onto the positively charged titanium dioxide surface through electrostatic interactions, while the positively charged amino termini of the antibody, i.e., the antigen-binding sites, are fully exposed towards the analyte, the cancer cell target.

[0035] like Figure 3 As shown, step S5 specifically includes the following steps: S51. First, clean the sensor substrate. Place the lamp-shaped side-polished PCF refractive index sensor with silver-titanium dioxide double coating in acetone, anhydrous ethanol, and deionized water in sequence, and perform ultrasonic treatment for 15 minutes in each case to thoroughly remove residual organic impurities, dust, and stains on the fiber surface, ensuring uniform and stable surface activation and modification effects in the future. After cleaning, slowly dry the sensor surface with high-purity nitrogen gas for later use.

[0036] S52. Subsequently, ultraviolet (UV) functionalization activation treatment was carried out. The dried sensor was placed under a 365nm wavelength UV lamp, maintaining a vertical irradiation posture, and the UV light intensity was controlled at 2-5mW / cm². 2Within the range, continuous irradiation for 1 hour generates a large number of photogenerated positive charges on the surface of the titanium dioxide layer through ultraviolet light excitation, and at the same time realizes the transformation of the surface from hydrophobic to superhydrophilic state, laying the foundation for subsequent antibody-directed fixation.

[0037] S53. Immediately after UV activation, perform rapid post-processing by gently rinsing the sensor surface three times with deionized water, followed by rinsing once with anhydrous ethanol to quickly remove residual impurities and unreacted active groups. Then, immediately dry the surface with high-purity nitrogen gas. The entire process should be completed within 10 minutes to avoid rapid decay of the positive charge and hydrophilic active sites generated on the titanium dioxide surface, thus ensuring the efficiency of subsequent modification.

[0038] S54. Next, electrostatic fixation of cancer cell antibodies is performed. The photofunctionalized sensor is completely immersed in a 20 μg / mL cancer cell antibody solution prepared with phosphate-buffered saline (PBS) and incubated at 4°C in the dark for 12 hours. The electrostatic interaction between the positive charge on the surface of titanium dioxide and the negative charge of the C-terminal carboxyl group of the antibody is used to achieve directional and stable binding of the antibody, thus preserving the antibody's biological activity in recognizing cancer cells to the greatest extent.

[0039] S55. After incubation, the sensor surface was gently rinsed three times with PBS buffer to thoroughly wash away unbound free antibodies. Then, the sensor was immersed in a PBS solution containing 1% bovine serum albumin (BSA) and blocked at room temperature for 1 hour to block the unmodified non-specific adsorption sites on the titanium dioxide surface, reduce the non-specific adhesion of impurities to cells during subsequent detection, and improve detection specificity.

[0040] S56. After sealing, the sensor surface is rinsed again with PBS buffer to remove residual BSA solution, and then dried with high-purity nitrogen gas. Finally, a biofunctionalized fiber optic SPR sensor that can specifically identify cancer cell surface markers is obtained, which can be directly used for subsequent cancer cell capture and refractive index sensing detection.

[0041] Through the above operations, the double-coated lantern-shaped side-sprayed PCF refractive index sensor for cancer cell detection of the present invention can be obtained, namely, the silver-titanium dioxide double-coated lantern-shaped side-sprayed PCF refractive index sensor for cancer cell detection.

[0042] The refractive index of the quartz material required for this invention can be calculated using the Sellmeier equation: ; In the formula, n is the refractive index. Wavelength, in μm. , , , , , .

[0043] The dielectric constant of the silver film can be represented by the Drude-Lorentz model, and its expression is: ; in, For wavelength, , The Drude-Lorentz model can simulate the dielectric constant of silver very well.

[0044] The relationship between the refractive index of the titanium dioxide layer and the wavelength can be expressed as: .

[0045] In fiber optic sensing, the limiting loss (CL) of the fiber transmission mode refers to the degree of light field leakage from the fiber core to the sensing area near the polished surface. It is a key indicator for evaluating sensor performance, and its value can be calculated using the following formula: ; in, , representing the free space wavenumber, This represents the imaginary part of the effective refractive index, and the unit for limiting loss is dB / cm.

[0046] According to the transmission loss equation above, the larger the imaginary part of the effective refractive index, the more obvious the SPR phenomenon.

[0047] When the core mode and the surface plasmon mode are coupled, the optical energy continuously transfers from the core to the silver film-titanium dioxide layer, and reaches a peak at the phase matching point, i.e., the resonance wavelength, which is manifested as a sharp resonance peak in the loss spectrum. At this time, the SPR phenomenon is most significant.

[0048] Figure 4 This diagram shows the dispersion relationship and confinement loss curves of the Y-polarized core mode and SPP mode of the refractive index sensor for cancer cell detection according to the present invention. Since this sensor polishes the fiber sidewalls axially, disrupting the symmetry of the cylindrical fiber only in the axial direction, this application only considers the sensing characteristics in the Y-polarization direction.

[0049] At a specific wavelength, the loss in the Y-polarized core mode reaches its peak, corresponding to the intersection of the dispersion curves of the Y-polarized core mode and the SPP mode, thus satisfying the phase-matching condition. This loss resonance peak can serve as a sensing channel for detecting the resonance resonance (RI). At this point, the Y-polarized core mode and the SPP mode are strongly coupled, and a large portion of the light field leaks from the core to the silver-titanium dioxide layer and the analyte region, which helps improve sensing performance.

[0050] Figure 5The diagram shows the dispersion relationship and limitation loss curves of the Y-polarized core mode and SPP mode of the refractive index sensor used for cancer cell detection, with the refractive index changed from 1.35 to 1.42.

[0051] In the performance evaluation of biosensors, wavelength sensitivity (S) is one of the key indicators, defined as the ratio of the shift in the loss spectral peak due to changes in the refractive index of the analyte to the corresponding refractive index difference: ; in, The magnitude of the resonance peak displacement. The change in the refractive index of the analyte is given by the analyte. and The value can be determined by Figure 6 Acquisition. Detection accuracy is also a key factor in evaluating sensor performance, and the corresponding minimum resolution can be obtained from the following formula: ; in, The magnitude of the resonance peak displacement. The change in the refractive index of the analyte is given by the analyte. The minimum resolution of the spectrometer is 0.1 nm. When the refractive index of the analyte changes from 1.39 to 1.40, the loss resonance peak undergoes an anomalous blue shift, resulting in negative sensitivity, with a sensitivity reaching -34200 nm / RIU.

[0052] Figure 6 This is a spectrum showing the variation of loss of the refractive index sensor for cancer cell detection as a function of the diameter of the internal air hole.

[0053] The structural parameters of a sensor directly affect its performance and stability. This invention focuses on the refractive index range of 1.39-1.40 and analyzes the geometric parameters of PCF, including the diameter of the internal air holes (…). ), the diameter of the air hole near the side surface ( Polishing depth (h), silver film thickness ( ), Titanium dioxide layer thickness ( The study aims to investigate the impact of these effects on sensor performance, with the goal of obtaining ultra-high sensitivity biosensors to detect minute refractive index changes in cancer biomarkers and related analytes.

[0054] Under the condition that other parameters remain unchanged, discuss The impact on sensor performance. For example... Figure 6 As shown, with As the wavelength increases from 3.6 μm to 4.4 μm, the resonance peak shifts towards shorter wavelengths. This is because the increased air holes around the fiber core lead to a decrease in the effective refractive index of the core mode. To match the higher effective refractive index of the surface plasmon mode, the resonance wavelength shifts towards shorter wavelengths. The curves show a clear trade-off between sensitivity and full width at half maximum (FWHM), although... It achieved the highest sensitivity of -65600nm / RIU, but its full width at half maximum (FWHM) also reached a maximum of 345nm, resulting in a quality factor of only 190.14RIU. -1 This limits the sensing accuracy. Considering all the above factors, the selected... At this optimal value, the sensitivity is -54300 nm / RIU, and the quality factor is 262.32 RIU. -1 .

[0055] Figure 7 , Figure 8 , Figure 9 and Figure 10 The loss of the refractive index sensor for cancer cell detection in this invention varies with... h and The spectral changes.

[0056] Through system optimization h as well as The influence of these key structural parameters on the loss spectrum and sensing performance was obtained in , , , and In its optimal configuration, this sensor achieves a sensitivity of -83100 nm / RIU, corresponding to a quality factor of [missing value]. The side-projectile PCF and optimized geometric parameters maximize the field overlap between the Y-polarized core mode and the surface plasmon mode, effectively promoting resonance peak shift and thus improving the sensor's sensitivity and resolution.

[0057] Figure 11 This is a graph showing the loss of the refractive index sensor for cancer cell detection according to the present invention as a function of normal cells and cancerous cells of the adrenal gland, blood, breast, and cervix.

[0058] The difference in refractive index between normal cells and cancerous cells directly causes a shift in the resonant wavelength, which provides a fundamental means for cancer detection. Figure 11This paper presents the loss spectrum of the silver-titanium dioxide double-coated lantern-shaped side-sprayed PCF refractive index sensor for cancer cell detection according to the present invention. By discussing the optical response characteristics of five common cancer cells (adrenal carcinoma, leukemia, type I breast cancer, type II breast cancer, and cervical cancer) and their normal cell samples, each cancer cell type exhibits a significant resonant wavelength shift relative to its normal counterpart. This essentially reflects the significant influence of refractive index changes on the phase matching point between the core mode and the surface plasmon mode. Wavelength demodulation analysis of the loss spectrum further yielded sensitivities of 4,357.14 nm / RIU, 19,785.71 nm / RIU, -46,928.57 nm / RIU, -46,142.86 nm / RIU, and 9916 nm / RIU for the five cancer cells. The present invention exhibits particularly high negative sensitivity for breast cancer cells (type I and type II), highlighting the superior performance of the silver-titanium dioxide double-coated lantern-shaped side-sprayed PCF refractive index sensor for breast cancer detection.

[0059] Figure 12 This is a comparison chart of the amplitude sensitivity of the refractive index sensor for cancer cell detection of the present invention for five types of cancer cells (adrenal cancer, leukemia, type I breast cancer, type II breast cancer, and cervical cancer).

[0060] The silver-titanium dioxide double-coated lantern-shaped side-polished PCF refractive index sensor for cancer cell detection of this invention has shown outstanding performance in breast cancer detection, achieving the highest detection sensitivity to date for both type I and type II breast cancer cells. However, anomalous negative sensitivity may lead to resonance wavelength overlap, thereby affecting the specificity and accuracy of the sensor. To overcome this limitation and improve detection accuracy, this invention proposes a resonance wavelength and amplitude synchronous demodulation scheme. Based on this, the sensor performance can be improved not only by the resonance wavelength shift but also by the amplitude sensitivity at a specific wavelength (…). A comprehensive evaluation is conducted, and the amplitude sensitivity is defined as the ratio of the relative change in the intensity of the loss spectrum to the change in the refractive index: ; in, The intensity of the loss spectrum represents the value of healthy cells, and Δn represents the difference in refractive index between healthy and cancer cells. This represents the corresponding change in the intensity of the loss spectrum. For example... Figure 12 As shown, the silver-titanium dioxide double-coated lantern-shaped side-polished PCF refractive index sensor for cancer cell detection of the present invention exhibits amplitude sensitivities of 60.28, -377.32, -1622.04, -2577.98, and -83.76 RIU for adrenal cancer, leukemia, type I breast cancer, type II breast cancer, and cervical cancer, respectively. -1 The minimum resolution is Even with resonance wavelength overlap due to anomalous negative sensitivity, the unique amplitude response still enables precise differentiation of different cancer cells. The wavelength-amplitude sensitivity dual-parameter modulation method significantly enhances the ability of this invention's silver-titanium dioxide double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection to identify and quantitatively detect target substances in complex biological samples. The sensor proposed in this invention has great potential for early cancer screening.

[0061] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A double-coated lantern-shaped side-projectile PCF refractive index sensor for cancer cell detection, characterized in that: It includes a photonic crystal fiber body, a channel for the analyte to be tested, and a perfect matching layer. The analyte channel is immersed in the side polished portion of the photonic crystal fiber body, and the perfect matching layer is located on the outer layer of the photonic crystal fiber body. The photonic crystal fiber body includes a substrate material, which is cylindrical in structure. A smooth upper tangent is formed on the upper side of the cylinder. The outer surface of the upper tangent is coated with a silver film for exciting the SPR effect. A titanium dioxide layer is deposited on the surface of the silver film to suppress silver film oxidation and to serve as a detection channel for enhanced mode coupling efficiency. Cladding air holes are provided inside the cylinder, including internal air holes and air holes near the side surface. The internal air holes include eight first air holes, and the air holes near the side surface include three second air holes adjacent to the side surface, used to flexibly adjust the evanescent field leakage channel. The first and second air holes are integrally arranged in a [missing information - likely a specific configuration]. The lamp-shaped, asymmetrical arrangement, wider at the top and narrower at the bottom, has two of the eight first air holes located on the sides and below the second air holes. The remaining six first air holes are arranged in groups of three, away from the side surface. The titanium dioxide layer is biofunctionalized using photofunctionalization to immobilize antibodies that can specifically recognize cancer cell surface markers. The negatively charged carboxyl termini of the antibodies are adsorbed onto the positively charged titanium dioxide surface through electrostatic interactions, while the positively charged amino termini of the antibodies are fully exposed towards the analyte, thus achieving specific recognition and detection of cancer cell antigens.

2. The double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection according to claim 1, characterized in that: The diameter of the first air hole is The diameter of the second air hole is 4.2-4.8 μm, and the spacing between adjacent air holes is 6.0 μm.

3. The double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection according to claim 1, characterized in that: The thickness of the silver film coated on the smooth upper surface is 35-45nm.

4. The double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection according to claim 1, characterized in that: The thickness of the titanium dioxide layer coated on the silver film is 35-45 nm.

5. The double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection according to claim 1, characterized in that: The thickness of the silver film coated on the smooth upper surface is 35nm, and the thickness of the titanium dioxide layer coated on the silver film is 40nm.

6. The double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection according to claim 1, characterized in that: The substrate structure is made of silicon dioxide.

7. The double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection according to claim 1, characterized in that: The lantern-shaped air hole arrangement, wider at the top and narrower at the bottom, can compress the light field energy upwards, allowing more energy to penetrate into the silver-titanium dioxide double-coated area on the upper surface. This enhances the interaction between light and the silver-titanium dioxide composite layer, thereby strengthening the coupling between the core mode and the plasma mode and increasing the surface plasma resonance intensity.

8. A method for preparing a double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection as described in claim 1, characterized in that: It includes the following steps: S1. Using stacking technology, a photonic crystal fiber preform containing air holes is obtained, with the air holes arranged in a hexagonal lattice. S2. The preform is placed in an optical fiber drawing tower for drawing to obtain a photonic crystal fiber. The diameter of the first internal air hole is [missing information]. Then, two of the five air holes in the original cladding were removed to obtain three second air holes close to the side surface. The diameter of the three second air holes is 4.2-4.8 μm and the distance between two adjacent air holes is 6.0 μm. S3. Polish the upper side of the photonic crystal fiber using a fiber polishing machine to obtain a smooth upper tangent. The smooth upper tangent is parallel to the center line of the three second air holes near the side polishing surface. The air holes are arranged in a lantern shape with a wider top and a narrower bottom, which can squeeze the light field energy upward and concentrate it on the upper tangent. S4. Deposit and solidify a silver thin film and a titanium dioxide layer on a smooth upper cross surface using magnetron sputtering technology. S5. Biofunctionalization modification of the titanium dioxide layer surface was performed using photofunctionalization to immobilize antibodies that can specifically recognize cancer cell surface markers. The sensor with the deposited titanium dioxide layer was then irradiated under ultraviolet light for a certain period of time, causing the titanium dioxide layer surface to generate a photogenerated positive charge and transform into a superhydrophilic state. The photofunctionalized sensor was immediately immersed in phosphate buffer containing antibodies at room temperature. During the immersion process, the negatively charged carboxyl terminus of the antibody was adsorbed onto the positively charged titanium dioxide layer surface through electrostatic interaction, while the positively charged amino terminus of the antibody was fully exposed towards the analyte of the cancer cells to be tested.

9. The method for fabricating a double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection according to claim 8, characterized in that: The polishing depth formed by polishing the smooth upper cut surface is 7.0-7.4μm; the silver film thickness is 35-45nm, and the titanium dioxide layer thickness is 35-45nm.

10. The method for fabricating a double-coated lantern-shaped side-projected PCF refractive index sensor for cancer cell detection according to claim 8, characterized in that: Step S5 specifically includes the following steps: S51. Perform sensor cleaning. Place the lamp-shaped side-polished PCF refractive index sensor with silver-titanium dioxide double coating in acetone, anhydrous ethanol and deionized water in sequence, and perform ultrasonic treatment to thoroughly remove residual organic impurities, dust and stains on the surface of the optical fiber. After cleaning, slowly blow dry the sensor surface with high-purity nitrogen gas for later use. S52. Conduct ultraviolet light functionalization and activation treatment. Place the dried sensor under a 365nm wavelength ultraviolet lamp, maintaining a vertical irradiation posture, and control the ultraviolet light intensity at 2-5mW / cm². 2 Within the range, continuous irradiation for more than 1 hour will generate a large number of photogenerated positive charges on the surface of the titanium dioxide layer through ultraviolet light excitation, and at the same time realize the transformation of the surface from hydrophobic to superhydrophilic state, laying the foundation for subsequent antibody targeted fixation. S53. Immediately after UV activation, perform rapid post-processing. Gently rinse the sensor surface three times with deionized water, then rinse once with anhydrous ethanol to remove residual impurities and unreacted active groups. Dry with high-purity nitrogen. The total post-processing time should be less than 10 minutes to avoid rapid decay of the positive charge and hydrophilic active sites generated on the titanium dioxide surface. S54. Perform electrostatic fixation of cancer cell antibodies. Immerse the photofunctionalized sensor completely in a 20 μg / mL cancer cell antibody solution prepared with phosphate buffer and incubate it in the dark at low temperature for 12 hours. Utilize the electrostatic interaction between the positive charge on the surface of titanium dioxide and the negative charge of the C-terminal carboxyl group of the antibody to achieve directional and stable binding of the antibody and retain the antibody's biological activity in recognizing cancer cells. S55. After incubation, the sensor surface was gently rinsed three times with PBS buffer to thoroughly wash away unbound free antibodies. Then, the sensor was immersed in a PBS solution of 1% bovine serum albumin and blocked at room temperature for 1 hour to block the unmodified non-specific adsorption sites on the titanium dioxide surface, reduce the non-specific adhesion of impurities to cells during subsequent detection, and improve detection specificity. S56. After sealing, the sensor surface is rinsed again with PBS buffer to remove residual bovine serum albumin solution, and then dried with high-purity nitrogen to obtain a double-coated lantern-shaped side-sprayed PCF refractive index sensor for cancer cell detection.

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