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CN-122016719-A - Double-coated horselight type side-throwing PCF refractive index sensor for cancer cell detection and preparation method thereof

CN122016719ACN 122016719 ACN122016719 ACN 122016719ACN-122016719-A

Abstract

The invention provides a double-coated horselight-shaped side-polished PCF refractive index sensor for cancer cell detection and a preparation method thereof, and relates to the field of optical fiber sensing, wherein the sensor comprises a photonic crystal optical fiber body, the photonic crystal optical fiber body comprises a substrate material, the substrate material is quartz, the structure is a cylinder, the cylinder comprises a smooth upper tangential surface, a silver coating film on the smooth upper tangential surface is used for exciting an SPR effect, and a titanium dioxide layer is deposited on the basis of the silver coating film to inhibit the oxidation of the silver coating film and is used as a detection channel for enhancing the mode coupling efficiency; cladding air holes are formed in the base structure. The invention measures the refractive index in the range of 1.35-1.42, the sensitivity of the refractive index can reach-83100 nm/RIU, and the quality factor can reach . Meanwhile, the biological functionalization modification is carried out on the surface of the titanium dioxide layer by utilizing a photo-functionalization method, so that the high-sensitivity specific detection of cancer cells can be realized at the same time, and the method is particularly suitable for diagnosing and early monitoring breast cancer.

Inventors

  • WANG XINYU
  • HAN QICHANG

Assignees

  • 东北大学秦皇岛分校

Dates

Publication Date
20260512
Application Date
20260326

Claims (10)

  1. 1. The double-coated horselight-shaped side-polished PCF refractive index sensor for cancer cell detection is characterized by comprising a photonic crystal fiber body, an analyte channel to be detected and a perfect matching layer, wherein the analyte channel to be detected submerges a side polishing part of the photonic crystal fiber body, and the perfect matching layer is positioned on the outer layer of the photonic crystal fiber body; The photonic crystal fiber body comprises a base material, wherein the base material is of a cylinder, a smooth upper tangential surface is arranged on the upper side of the cylinder, a silver film for exciting an SPR effect is plated on the outer surface of the upper tangential surface, a titanium dioxide layer for inhibiting silver film oxidation and serving as a detection channel for enhancing mode coupling efficiency is deposited on the surface of the silver film, a cladding air hole is arranged in the cylinder, the cladding air hole comprises an inner air hole and an air hole close to a side polished surface, the inner air hole comprises eight first air holes, the air hole close to the side polished surface comprises three second air holes close to the side polished surface and used for flexibly adjusting an evanescent field leakage channel, two of the eight first air holes are respectively arranged on two sides and below the second air holes, the remaining six of the eight first air holes are arranged in a group mode of each three, the three first air holes are far away from the side polished surface, the surface of the titanium dioxide layer is subjected to biological functionalization by utilizing a light functionalization method so as to fix antibodies capable of specifically recognizing cancer cell surface markers, the carboxyl ends of the antibodies are closely adjacent to the side polished surface, the carboxyl ends of the antibodies are fully arranged in a lamp-shaped upper width and lower-width mode, the whole body is arranged in a lamp-shaped upper-width mode, the upper part is narrow-width mode, two first air holes are respectively arranged at two sides are arranged below the second air holes are arranged at two sides, the lower than the second air holes are far away from the side polished surface, and are far away from the side polished, and each side surface, and each side is fully, and can be fully modified by the side.
  2. 2. The double-coated horselight-shaped side-polished PCF refractive index sensor for detecting cancer cells according to claim 1, wherein the diameter of the first air hole is The second air holes have a diameter of 4.2-4.8 μm and the spacing between adjacent air holes is 6.0 μm.
  3. 3. The double-coated horselight-shaped side-polished PCF refractive index sensor for cancer cell detection according to claim 1, wherein the silver film coated on the smooth upper section has a thickness of 35-45nm.
  4. 4. The double-coated horselight-shaped side-polished PCF refractive index sensor for cancer cell detection according to claim 1, wherein the titanium dioxide layer coated on the silver film has a thickness of 35-45nm.
  5. 5. The double-coated horselight-shaped side-polished PCF refractive index sensor for cancer cell detection according to claim 1, wherein the silver film coated on the smooth upper section has a thickness of 35nm, and the titanium dioxide layer coated on the silver film has a thickness of 40nm.
  6. 6. The double-coated horselight-shaped side-polished PCF refractive index sensor for cancer cell detection as in claim 1, wherein the substrate structure is made of silica.
  7. 7. The double-coated horselight-shaped side-polished PCF refractive index sensor for cancer cell detection according to claim 1, wherein the horselight-shaped side-polished PCF refractive index sensor is characterized in that air holes with wide upper parts and narrow lower parts are arranged, so that light field energy can be upwards extruded, more energy can permeate into a silver-titanium dioxide double-coated area with a top section, interaction of light and a silver-titanium dioxide composite layer is enhanced, coupling of a fiber core die and a plasma die is enhanced, and surface plasma resonance intensity is enhanced.
  8. 8. A method for preparing the double-coated horselight-shaped side-polished PCF refractive index sensor for cancer cell detection, which is characterized by comprising the following steps: s1, adopting a stacking technology to obtain a photonic crystal optical fiber preform with air holes arranged in a hexagonal lattice; S2, placing the prefabricated rod in an optical fiber drawing tower to draw to obtain the photonic crystal fiber, wherein the diameter of the first air hole is Then removing two of the five air holes in the original cladding to obtain three second air holes close to the side polished surface, wherein the diameters of the three second air holes are 4.2-4.8 mu m, and the distance between every two adjacent air holes is 6.0 mu m; S3, polishing the upper side of the photonic crystal fiber by utilizing a fiber polishing machine to obtain a smooth upper tangent plane, wherein the smooth upper tangent plane is parallel to the central connecting line of three second air holes close to the side polishing surface, and the air holes are integrally arranged in a shape of a horse-shoe with wide upper part and narrow lower part, so that the energy of a light field can be extruded upwards, and the upper tangent plane is concentrated; s4, respectively depositing a silver film and a titanium dioxide layer on the smooth upper section by utilizing a magnetron sputtering technology and solidifying; S5, performing biological functionalization modification on the surface of the titanium dioxide layer by utilizing a photo-functionalization method, fixing an antibody capable of specifically recognizing a cancer cell surface marker, placing the sensor deposited with the titanium dioxide layer under ultraviolet light for irradiation for a certain time to enable the surface of the titanium dioxide layer to generate photo positive charges and convert the photo positive charges into a super-hydrophilic state, immediately immersing the sensor subjected to photo-functionalization treatment in phosphate buffer solution containing the antibody at room temperature, wherein in the immersing process, the carboxyl terminal of the antibody with negative charges is adsorbed on the surface of the titanium dioxide layer with positive charges through electrostatic interaction, and the amino terminal of the antibody with positive charges is fully exposed towards the direction of an analyte of a cancer cell to be detected.
  9. 9. The method for preparing a double-coated horselight-shaped side-polished PCF refractive index sensor for cancer cell detection according to claim 8, wherein the polishing depth of the smooth upper section formed by polishing is 7.0-7.4 μm, the silver film thickness is 35-45nm, and the titanium dioxide layer thickness is 35-45nm.
  10. 10. The method for preparing the double-coated horselight-shaped side-polished PCF refractive index sensor for cancer cell detection according to claim 8, wherein the step S5 comprises the following steps: S51, cleaning the sensor, sequentially putting the horse-shaped side-polished PCF refractive index sensor deposited with the silver-titanium dioxide double-coated film into acetone, absolute ethyl alcohol and deionized water, respectively performing ultrasonic treatment, thoroughly removing organic impurities, dust and stains remained on the surface of the optical fiber; S52, performing ultraviolet light functional activation treatment, placing the dried sensor under an ultraviolet lamp with the wavelength of 365nm, keeping a vertical irradiation posture, controlling the ultraviolet light intensity to be in the range of 2-5mW/cm 2 , continuously irradiating for more than 1 hour, exciting the surface of the titanium dioxide layer by ultraviolet light to generate a large amount of photo-generated positive charges, and simultaneously realizing the transition from hydrophobic to super-hydrophilic state of the surface, so as to lay a foundation for the directional fixation of the subsequent antibody; S53, immediately performing quick aftertreatment after ultraviolet activation is finished, gently flushing the surface of the sensor with deionized water for 3 times, rinsing with absolute ethyl alcohol for 1 time, removing residual impurities and unreacted active groups on the surface, drying with high-purity nitrogen, and ensuring that the total aftertreatment time is less than 10 minutes, so that positive charges generated on the surface of titanium dioxide and hydrophilic active sites are prevented from being attenuated quickly; s54, carrying out electrostatic fixation on the cancer cell antibody, completely immersing the sensor subjected to the photo-functionalization treatment in a 20 mug/mL cancer cell antibody solution prepared by using a phosphate buffer solution, placing the sensor in a low-temperature environment, and incubating for 12 hours in a dark place, wherein the directional stable combination of the antibody is realized by utilizing the electrostatic interaction between positive charges on the surface of titanium dioxide and negative charges on the carboxyl at the C end of the antibody, and the biological activity of the antibody for identifying the cancer cell is reserved; S55, after incubation, the surface of the sensor is gently washed for 3 times by using PBS buffer solution to thoroughly wash away unbound free antibody, then the sensor is immersed into PBS solution of 1% bovine serum albumin, and is blocked for 1h at room temperature, so that non-specific adsorption sites on the surface of titanium dioxide which are not modified are blocked, non-specific adhesion of impurities and cells in the subsequent detection process is reduced, and the detection specificity is improved; And S56, after the sealing is finished, flushing the surface of the sensor by using PBS buffer solution again, removing residual bovine serum albumin solution, and drying by using high-purity nitrogen to obtain the double-coated horselight-shaped side-polished PCF refractive index sensor for detecting cancer cells.

Description

Double-coated horselight type side-throwing PCF refractive index sensor for cancer cell detection and preparation method thereof Technical Field The invention relates to the field of optical fiber sensing, in particular to a double-coated horselight-shaped side-polished PCF refractive index sensor for cancer cell detection and a preparation method thereof. Background Cancer is one of the highest global mortality diseases and constitutes a major threat to human life and health, so early diagnosis of cancer is particularly critical. At present, traditional methods such as biopsy, radiography, magnetic resonance imaging and the like are widely used for cancer identification, and exhibit better accuracy in detection of various types of cancers. However, these techniques still face the limitations of high cost, reliance on markers, insufficient sensitivity at early stages, etc., which can easily lead to delayed diagnosis, affecting treatment timing and patient survival. To address the above challenges and to accommodate the increasing demand for highly sensitive, non-invasive, remotely operable sensing systems in the field of modern biomedical detection, researchers have introduced Photonic Crystal Fiber (PCF) -based Surface Plasmon Resonance (SPR) technology into this field in an effort to drive the development of early diagnosis technology for cancer. SPR technology is a physical optical phenomenon that occurs at the metal-medium interface and is manifested as resonance coupling between surface plasmon waves and evanescent waves. Traditional SPR detecting system is based on prism or optical fiber coupling mode, and prism structure is usually bulky, with high costs, has restricted its sensing practicality. The optical fiber SPR sensor first reported in 1993 provides a new approach for solving the above limitations, and is particularly suitable for remote sensing and real-time monitoring scenes. To enhance SPR sensing performance, researchers have focused on exploring three types of fiber structures, including geometrically modified fibers (e.g., tapered, bent, and side-polished), grating-assisted fibers, and specialty fibers (including polarization maintaining fibers, hollow fibers, and PCF). Among them, PCF exhibits great advantages due to its structural design flexibility, easy miniaturization, large mode area, and controllable birefringence, etc. By optimizing the PCF geometric parameters, the phase matching between the fiber core mode and the surface plasma mode can be effectively regulated and controlled, so that the SPR effect is efficiently excited. PCF-based SPR sensors (PCF-SPR) combine multiple advantages of high sensitivity, compact structure, electromagnetic interference resistance, high response speed, strong field constraint and the like, and have shown remarkable application potential in the field of biomedical diagnosis in recent years. PCF-SPR sensors distinguish healthy cells from cancerous cells by detecting Refractive Index (RI) changes, and currently mainly deploy around two sensing mechanisms, internal sensing and external sensing. Internal sensing is achieved by monitoring RI changes or molecular interactions of the microporous structure inside the fiber, for example, a microfluidic cavity is integrated in the PCF to detect cells such as cervical cancer, and the highest sensitivity can reach 10625 nm/RIU. Although the method is favorable for realizing high-sensitivity and multi-component detection, the process is complex, and even metal coating and nano cavity filling are challenging in practical manufacturing. In contrast, the external sensing mechanism captures the external analyte signal by depositing a functional material coating on the external surface of the PCF, so that the process is simpler and more suitable for experiments and preparation. However, this approach generally achieves lower sensitivity and resolution, and thus a detection sensor with higher sensitivity and resolution is highly desirable. Disclosure of Invention In order to solve the defects in the prior art, the invention aims to provide the double-coated horselight-shaped side-polished PCF refractive index sensor for cancer cell detection and the preparation method thereof, which can inhibit oxidation of a silver film, improve the adhesive force of a metal layer and effectively improve the interaction between a fiber core mode and a surface plasma mode so as to realize high-sensitivity detection capability on cancer cells. Specifically, the invention provides a double-coated horselight-shaped side polishing PCF refractive index sensor for cancer cell detection, which comprises a photonic crystal fiber body, an analyte channel to be detected and a perfect matching layer, wherein the analyte channel to be detected submerges a side polishing part of the photonic crystal fiber body, and the perfect matching layer is positioned on the outer layer of the photonic crystal fiber body; The photonic crystal fiber body compri