CN107741409A - A cancer marker detection device and method based on tilted Bragg gratings - Google Patents

Abstract

The invention discloses a cancer marker detection device and method based on an inclined Bragg grating. The device includes sequentially connected light sources, polarizers, polarization controllers, sensing probes and spectrometers. The sensing probe is an inclined grating. A layer of nano film is coated on the surface of the inclined grating as a carrier of surface plasmon resonance. The surface of the nano film is provided with a chemical modification layer, and biological agents are immobilized on the chemical modification layer; the light emitted by the light source enters the Sensing probe, the sensing probe is placed in the object to be detected, and the biological agent on the surface of the sensing probe is used to combine with the object to be detected and undergo an immune reaction, which in turn causes the dielectric properties of the nano-film surface to change, resulting in resonance The wavelength shifts, and the conversion of the wavelength is analyzed by a spectrometer to obtain the concentration characteristics of the substance to be detected. The invention can obtain characteristics such as the concentration of the analyte to be tested, realize the detection of cancer factors and related applications in the fields of biomedicine and the like.

Description

A cancer marker detection device and method based on tilted Bragg gratings

technical field

The invention relates to the interdisciplinary fields of optical fiber sensing technology, material science, and early detection of cancer markers, in particular to a cancer marker detection device and method based on a tilted Bragg grating.

Background technique

With the improvement of people's living standards, people pay more and more attention to health issues. Cancer is still a major problem that plagues everyone. CD13 is a cancer cell expression factor, which has been found to exist in liver cancer cells and lung cancer cells, so it is of great significance to realize the early diagnosis and detection of cancer. In vitro detection and detection are the main means and important prerequisites for disease prevention, treatment and recovery tracking after treatment. In order to meet the needs of in vitro testing and diagnostic testing, it is necessary to develop specific and sensitive analytical methods. At present, the commonly used biological protein detection methods mainly include enzyme-linked immunosorbent assay, fluorescent immunoassay, electrochemical immunoassay, etc. These methods have some defects, such as inability to resist electromagnetic interference, high cost, and low sensitivity. If efficient detection methods can be developed for early detection and treatment of cancer, the survival rate of cancer patients will be greatly improved. Therefore, a small, fast, highly sensitive, highly stable, and low-cost sensor for early detection of cancer markers has become particularly important.

In recent years, there have been many reports on the research on fiber optic biosensors, and tilted gratings are one of the research hotspots. Since the inclined grating has a certain inclination angle, when the light emitted by the light source is transmitted to the inclined grating, part of the core light will be reflected by the grating region into the cladding, and the light leaked into the cladding is used for detection, effectively avoiding In order to process the cladding, the manufacturing process of the sensor is simplified, and by simply changing the wavelength of the light source, a variety of resonance modes can be generated, which enriches the detection objects and improves the detection sensitivity. Coating a layer of nano film on the surface of the tilted grating will form a tilted Bragg grating sensor based on surface plasmon resonance, which can realize sensing applications in biology and the environment.

Contents of the invention

The technical problem to be solved by the present invention is to provide a device and method for detecting cancer markers based on tilted Bragg gratings for the defect that it is difficult to detect the concentration of cancer cell expression factors in the prior art.

The technical solution adopted by the present invention to solve its technical problems is:

The invention provides a cancer marker detection device based on a tilted Bragg grating, which includes sequentially connected light sources, polarizers, polarization controllers, sensing probes and spectrometers, wherein the sensing probe is a tilted grating, and the tilted grating The surface is coated with a layer of nano-film, as the carrier of surface plasmon resonance, the surface of the nano-film is provided with a chemical modification layer, and biological agents are fixed on the chemical modification layer; the light emitted by the light source enters the sensing probe after passing through the polarizer and the polarization controller. The needle, the sensing probe is placed in the object to be detected, and the biological agent on the surface of the sensing probe is used to combine with the object to be detected and undergo an immune reaction, which in turn causes the dielectric properties of the nano-film surface to change, resulting in a shift in the resonance wavelength , and the conversion of the wavelength is analyzed by a spectrometer to obtain the concentration characteristics of the substance to be detected.

Further, the surface of the inclined grating of the present invention is plated with a nano film by magnetron sputtering or vacuum evaporation technology.

Further, the material of the nano film of the present invention includes gold film, silver film, palladium film, copper mold or alloy film, or nano film is: the composite of the sensitive material of graphene/molybdenum disulfide/ITO combined with metal film membrane.

Further, the thickness of the nano film of the present invention is 40-100nm.

Furthermore, the inclined grating of the present invention has an inclination angle of 5°-20° and a length of 1-2cm.

Further, the output spectrum of the light source of the present invention is 1300-1700nm, and the output spectrum range matches the spectrum range of the inclined grating.

The invention provides a cancer marker detection method based on a tilted Bragg grating, comprising the following steps:

S1. Coating a nano film on the surface of the inclined grating;

S2. Adding a tilted grating as a sensing probe into the optical path, the optical path includes sequentially connected light sources, polarizers, polarization controllers, sensing probes and spectrometers;

S3. Surface pretreatment of inclined grating: Inject mercaptoundecanoic acid solution into the liquid tank, perform online chemical modification on the surface of the coated inclined grating, record the change of surface plasmon resonance shift by spectrometer, and monitor the process of mercaptoundecanoic acid fixation , when the resonance wavelength is no longer red-shifted, the immobilization process of mercaptoundecanoic acid is over, and then inject buffer to wash, wash off unbound mercaptoundecanoic acid and blow dry;

S4. Sensing probe preparation: Inject a buffer solution containing biopharmaceuticals into the liquid tank, perform online chemical modification on the pretreated inclined grating surface, record the change of surface plasmon resonance shift with a spectrometer, and monitor the process of biopharmaceutical immobilization , when the resonance wavelength is no longer red-shifted, the immobilization process of the biological agent is over, and then the buffer solution is injected to wash away the unbound biological agent, and after drying, the surface plasmon resonance immunosensing probe of the inclined grating is obtained;

S5. Calibration: Select a sample buffer with a known concentration, and take the buffer as a reference. The sample buffer with a known concentration passes through the liquid tank where the surface plasmon resonance immunosensing probe of the inclined grating is located and measures it. The spectrometer detects the size of the resonance wavelength shift, and calibrates and records the relationship between the different concentrations of the sample buffer and the detected physical quantity;

S6. Detection of unknown samples: use the cancer marker detection device based on tilted Bragg gratings to detect the buffer solution of unknown samples in real time, and compare the magnitude of the resonance wavelength shift with the numerical relationship in the calibration record to obtain the molecular concentration of the sample.

Further, the biopharmaceutical in the method of the present invention is a related protein of a cancer marker recognition object, and the biopharmaceutical can be directly combined with the nano-film with plasmon resonance effect, or can be combined by using the mercaptoundecanoic acid molecular group as a transition substance .

Furthermore, the detection sample in the method of the present invention includes biological proteins, nucleic acids, and polypeptides capable of immunoreacting with the probes.

Further, the biological agent in the method of the present invention is CNGRC, and the detection sample is the cancer cell expression factor CD13.

The beneficial effects produced by the present invention are: the cancer marker detection device and method based on the tilted Bragg grating of the present invention, by immobilizing the receptor on the surface of the sensing probe, when the analyte flows through the sensing probe, the analyte If there is a substance that binds to the receptor, it will cause a change in the dielectric properties of the nanofilm surface, resulting in a shift in the resonance wavelength. By analyzing the change in wavelength, the characteristics such as the concentration of the analyte to be measured can be obtained, and the realization of cancer Factor detection and related applications in biomedicine and other fields.

Description of drawings

The present invention will be further described below in conjunction with accompanying drawing and embodiment, in the accompanying drawing:

Fig. 1 is the device structure schematic diagram of the embodiment of the present invention;

Fig. 2 is the schematic diagram of the sensing probe of the embodiment of the present invention;

In the figure: 1-light source, 2-polarizer, 3-polarization controller, 4-sensing probe, 5-spectrometer.

detailed description

In order to make the object, technical solution and advantages of the present invention clearer, the present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described here are only used to explain the present invention, not to limit the present invention.

As shown in Figure 1, the cancer marker detection device based on the tilted Bragg grating of the embodiment of the present invention includes a light source 1, a polarizer 2, a polarization controller 3, a sensing probe 4 and a spectrometer 5 connected in sequence, wherein, The sensing probe 4 is an inclined grating, and a layer of nano-film is coated on the surface of the inclined grating as a carrier of surface plasmon resonance. The surface of the nano-film is provided with a chemically modified layer, and biological agents are fixed on the chemically modified layer; the light emitted by the light source 1 After passing through the polarizer 2 and the polarization controller 3, it enters the sensing probe 4, the sensing probe 4 is placed in the object to be detected, and the biological agent on the surface of the sensing probe 4 is used to bind to the object to be detected and undergo an immune reaction , and then cause the dielectric properties of the surface of the nanometer film to change, resulting in a shift in the resonance wavelength, and the conversion of the wavelength is analyzed by the spectrometer 5 to obtain the concentration characteristics of the substance to be detected.

The surface of the inclined grating is coated with a nano film by magnetron sputtering or vacuum evaporation technology.

The material of the nano film includes gold film, silver film, palladium film, copper mold or alloy film, or the nano film is a composite film of graphene/molybdenum disulfide/ITO sensitive material combined with a metal film.

The thickness of the nano film is 40-100nm.

The inclined grating has an inclination angle of 5°-20° and a length of 1-2cm.

The output spectrum of the light source 1 is 1300-1700nm, and the output spectrum range matches the spectrum range of the inclined grating.

The cancer marker detection method based on the tilted Bragg grating of the embodiment of the present invention comprises the following steps:

S1. Coating a nano film on the surface of the inclined grating;

S2. Adding a tilted grating as a sensing probe into the optical path, the optical path includes sequentially connected light sources, polarizers, polarization controllers, sensing probes and spectrometers;

S3. Surface pretreatment of inclined grating: Inject mercaptoundecanoic acid solution into the liquid tank, perform online chemical modification on the surface of the coated inclined grating, record the change of surface plasmon resonance shift by spectrometer, and monitor the process of mercaptoundecanoic acid fixation , when the resonance wavelength is no longer red-shifted, the immobilization process of mercaptoundecanoic acid is over, and then inject buffer to wash, wash off unbound mercaptoundecanoic acid and blow dry;

S4. Sensing probe preparation: Inject a buffer solution containing biopharmaceuticals into the liquid tank, perform online chemical modification on the pretreated inclined grating surface, record the change of surface plasmon resonance shift with a spectrometer, and monitor the process of biopharmaceutical immobilization , when the resonance wavelength is no longer red-shifted, the immobilization process of the biological agent is over, and then the buffer solution is injected to wash away the unbound biological agent, and after drying, the surface plasmon resonance immunosensing probe of the inclined grating is obtained;

S5. Calibration: Select a sample buffer with a known concentration, and take the buffer as a reference. The sample buffer with a known concentration passes through the liquid tank where the surface plasmon resonance immunosensing probe of the inclined grating is located and measures it. The spectrometer detects the size of the resonance wavelength shift, and calibrates and records the relationship between the different concentrations of the sample buffer and the detected physical quantity;

S6. Detection of unknown samples: use the cancer marker detection device based on tilted Bragg gratings to detect the buffer solution of unknown samples in real time, and compare the magnitude of the resonance wavelength shift with the numerical relationship in the calibration record to obtain the molecular concentration of the sample.

The biopharmaceutical in the method is the related protein of the cancer marker recognition object, and the biopharmaceutical can be directly combined with the nano film having the plasma resonance effect, or can be combined by using the mercapto undecanoic acid molecular group as a transition substance.

The detection sample in the method includes biological protein, nucleic acid and polypeptide capable of immunoreacting with the probe. The biopharmaceutical in the method is CNGRC, and the detection sample is the expression factor CD13 of cancer cells.

Example 1:

A cancer marker detection device based on a tilted Bragg grating, including a light source, a polarizer, a polarization controller, a sensing probe, and a spectrometer. The light source is connected to the polarizer, the polarizer is connected to the polarization controller, and the sensing probe is connected Polarization controller and spectrometer. The sensing probe part is an inclined grating, and a layer of nano film is coated on the surface of the inclined grating as a carrier of surface plasmon resonance, and chemical modification and biomedicine are fixed on the surface of the nano film.

The main steps of the cancer marker detection method based on the tilted grating are:

(1) The gold-plated film of the inclined grating is used as the carrier of the sensing probe;

(2) Connect the inclined grating into the optical path, mainly including light source, polarizer, polarization controller, sensing probe, spectrometer, and liquid tank;

(3) Surface pretreatment of tilted gratings: First, inject mercaptoundecanoic acid solution into the liquid tank, carry out online chemical modification on the surface of tilted gratings after coating, use Au-S bonding characteristics, record the change of surface plasmon resonance displacement, monitor In the process of mercaptoundecanoic acid immobilization, when the resonance wavelength is no longer red-shifted, the mercaptoundecanoic acid immobilization process ends, and then buffer solution is injected to wash away unbound mercaptoundecanoic acid, and then blow dry.

(4) Sensing probe preparation: Inject a buffer solution containing CNGRC into the liquid tank, carry out online chemical modification on the surface of the inclined optical fiber after pretreatment, record the change of surface plasmon resonance displacement, and monitor the process of bioprobe immobilization. When the resonance wavelength is no longer red-shifted, the immobilization process of the biological probe is over, and then the buffer solution is injected to wash away the unbound biological agent, and after drying, the optical fiber surface plasmon resonance immunosensing probe is obtained.

(5) Calibration: select the buffer solution of the cancer marker CD13 of known concentration, and take the buffer solution as the reference, the CD13 buffer solution of known concentration respectively passes through the liquid tank where the inclined grating immunoprobe is located and measures it, by The spectrometer detects the magnitude of the resonance wavelength shift, and calibrates and records the relationship between the concentration of the cancer marker CD13 and the detected physical quantity.

(6) Unknown sample detection: use the tilted grating-based cancer marker early diagnosis device to measure the concentration of CD13 molecules in the liquid to be tested in real time, and measure the concentration of cancer marker CD13 molecules by detecting the size of the resonance wavelength shift. In the tilted grating sensing probe part, when a certain concentration of target CD13 molecules flow in, CNGRC and CD13 molecules specifically bind, resulting in a change in the effective refractive index on the surface of the metal film, which further causes a shift in the resonance wavelength. Different concentrations of CD13 Cancer markers induce varying degrees of resonance wavelength shift.

The inclined grating surface plasmon resonance sensor in the present invention uses the light reflected into the cladding for detection, avoiding the processing of the cladding of the optical fiber. First, the probe molecules are immobilized on the surface of the sensor, and the sample containing the analyte flows through the sensor surface. If the sample flowing through the surface of the sensing fiber contains a substance bound to it, the interaction between them will cause the sensing film to The dielectric properties of the surface change, which eventually leads to a red shift in the resonance wavelength. By detecting the wavelength change, information such as the concentration and specificity of the analyte can be obtained.

Example 2:

In the present embodiment, the nano film is a gold film, it can also be a silver film, a palladium film, a copper mold, an alloy film, or the nano film is: a composite film of the sensitive material of graphene/molybdenum disulfide/ITO combined with a metal film .

In this embodiment, the thickness of the nano film is 40-100 nm.

In this embodiment, the inclination angle of the inclined grating is 5°-20°, and the length is 1-2 cm.

In this embodiment, the output spectrum of the light source is 1300-1700 nm, and the output spectrum range matches the spectrum range of the inclined grating.

In this example, the biological reagents are all used in their respective required environmental solutions, such as prepared in PBS buffer.

The cancer marker detection method based on the tilted grating of the above-mentioned embodiment specifically comprises the following steps:

(1) The gold-plated film of the inclined grating is used as the carrier of the sensing probe;

(2) Connect the inclined grating into the optical path, mainly including light source, polarizer, polarization controller, sensing probe, spectrometer, and liquid tank;

(3) Surface pretreatment of tilted gratings: First, inject mercaptoundecanoic acid solution into the liquid tank, carry out online chemical modification on the surface of tilted gratings after coating, use Au-S bonding characteristics, record the change of surface plasmon resonance displacement, monitor In the process of mercaptoundecanoic acid immobilization, when the resonance wavelength is no longer red-shifted, the mercaptoundecanoic acid immobilization process ends, and then buffer solution is injected to wash away unbound mercaptoundecanoic acid, and then blow dry.

(4) Sensing probe preparation: Inject a buffer solution containing CNGRC into the liquid tank, carry out online chemical modification on the surface of the inclined optical fiber after pretreatment, record the change of surface plasmon resonance displacement, and monitor the process of bioprobe immobilization. When the resonance wavelength is no longer red-shifted, the immobilization process of the biological probe is over, and then the buffer solution is injected to wash away the unbound biological agent, and after drying, the optical fiber surface plasmon resonance immunosensing probe is obtained.

(5) Calibration: select the buffer solution of the cancer marker CD13 of known concentration, and take the buffer solution as the reference, the CD13 buffer solution of known concentration respectively passes through the liquid tank where the inclined grating immunoprobe is located and measures it, by The spectrometer detects the magnitude of the resonance wavelength shift, and calibrates and records the relationship between the concentration of the cancer marker CD13 and the detected physical quantity.

(6) Unknown sample detection: use the tilted grating-based cancer marker early diagnosis device to measure the concentration of CD13 molecules in the liquid to be tested in real time, and measure the concentration of cancer marker CD13 molecules by detecting the size of the resonance wavelength shift. In the tilted grating sensing probe part, when a certain concentration of target CD13 molecules flow in, CNGRC and CD13 molecules specifically bind, resulting in a change in the effective refractive index on the surface of the metal film, which further causes a shift in the resonance wavelength. Different concentrations of CD13 Cancer markers induce varying degrees of resonance wavelength shift.

The biopharmaceutical CNGRC is a related protein of the cancer marker recognition, and the analyte CD13 is the cancer marker. Biopharmaceuticals include not only CNGRC, but also other biopharmaceuticals such as biological proteins, nucleic acids, and polypeptides that can be directly combined with nano-films with plasmon resonance effects or use mercaptoundecanoic acid as transition substances through the binding of molecular groups. The detection substances include not only CD13, but also other biological proteins, nucleic acids, polypeptides and other substances that can immunoreact with the probe.

The surface plasmon resonance immunosensor based on the tilted grating is not only used in the early detection of cancer markers, but also in other biomedical fields and environmental monitoring fields such as air pollution particles and heavy metal ions.

Accompanying drawing 2 is the schematic diagram of the surface plasmon resonance immunosensing probe of the inclined grating, in which the coating sensitive unit adopts a 1.5cm inclined grating, and the nano-film on the cladding surface of the inclined grating adopts a gold film, which is reflected to the cladding by using the inclined grating grid area. The photoexcitation of the layer generates an evanescent field, and then the surface of the gold film is modified with mercaptoundecanoic acid through the Au-S covalent bond, and then the molecular group combination of mercaptoundecanoic acid and CNGRC is used to realize the bilayer assembly of CNGRC. Preparation of biosensing probes, the sample containing the analyte flows through the sensor surface, if the sample flowing through the surface of the sensing fiber contains the cancer marker CD13 bound to it, the interaction between them will cause the sensing film to The dielectric properties of the surface change, which eventually leads to a red shift in the resonance wavelength. According to the standard curve, information such as the concentration and specificity of the analyte can be obtained.

CD13 was purchased from Merck, USA, and CNGRC was provided by Wuhan University. PBS buffer was purchased from Sinopharm Group Co., Ltd., the concentration was 0.01 mol/l, pH=7.4.

The cancer detection device method based on the inclined Bragg grating of the present invention, the core component is the sensing probe part, the sensing probe is composed of an inclined grating, a layer of nano-film is coated on the surface of the inclined grating, and the surface of the nano-film is chemically modified and the fixation of biological agents; the two ends of the sensing probe are respectively connected with a light source, a polarizer, a polarization controller, and a spectrometer. Since the inclined grating has a certain inclination angle, when the light emitted by the light source is transmitted to the inclined grating, part of the core light will be reflected by the grating region into the cladding, and the light leaked into the cladding is used for detection, effectively avoiding In order to process the cladding, the manufacturing process of the sensing probe is simplified. Immobilize the receptor on the surface of the sensing probe. When the analyte flows through the sensing probe, if there is a substance in the analyte that binds to the receptor, the dielectric properties of the nano-film surface will change, thereby This causes the resonance wavelength to shift, and by analyzing the change of the wavelength, the characteristics such as the concentration of the analyte to be measured can be obtained, and the detection of cancer factors and related applications in biomedicine and other fields can be realized.

It should be understood that those skilled in the art can make improvements or changes based on the above description, and all these improvements and changes should belong to the protection scope of the appended claims of the present invention.

Claims (10)

1. A cancer marker detection device based on a tilted Bragg grating, characterized in that it comprises sequentially connected light sources (1), polarizers (2), polarization controllers (3), sensing probes (4) and A spectrometer (5), wherein the sensing probe (4) is an inclined grating, and a layer of nano-film is coated on the surface of the inclined grating as a carrier of surface plasmon resonance, the surface of the nano-film is provided with a chemically modified layer, and the chemically modified layer is fixed There are biological agents; the light emitted by the light source (1) enters the sensing probe (4) after passing through the polarizer (2) and the polarization controller (3), and the sensing probe (4) is placed in the object to be detected, and the sensing probe (4) The biological agent on the surface of the sensing probe (4) is used to combine with the substance to be detected and undergo an immune reaction, which in turn causes a change in the dielectric properties of the nano-film surface, resulting in a shift in the resonance wavelength. The conversion of the wavelength is analyzed by the spectrometer (5). Obtain the concentration characteristics of the substance to be detected. 2 . The device for detecting cancer markers based on tilted Bragg gratings according to claim 1 , wherein the surface of the tilted grating is coated with a nano-film by magnetron sputtering or vacuum evaporation technology. 3. The cancer marker detection device based on the tilted Bragg grating according to claim 1, wherein the material of the nano-film comprises gold film, silver film, palladium film, copper mold or alloy film, or the nano-film is: with Composite film of graphene/molybdenum disulfide/ITO sensitive material combined with metal thin film. 4. The device for detecting cancer markers based on tilted Bragg gratings according to claim 1, wherein the thickness of the nano film is 40-100 nm. 5 . The device for detecting cancer markers based on tilted Bragg gratings according to claim 1 , wherein the tilt angle of the tilted grating is 5°-20°, and the length is 1-2 cm. 6 . The device for detecting cancer markers based on inclined Bragg gratings according to claim 1 , wherein the output spectrum of the light source ( 1 ) is 1300-1700 nm, and the output spectrum range matches the spectral range of the inclined grating. 7. A cancer marker detection method based on an inclined Bragg grating, characterized in that, comprising the following steps: S1. Coating a nano film on the surface of the inclined grating; S2. Adding a tilted grating as a sensing probe into the optical path, the optical path includes sequentially connected light sources, polarizers, polarization controllers, sensing probes and spectrometers; S3. Surface pretreatment of inclined grating: Inject mercaptoundecanoic acid solution into the liquid tank, perform online chemical modification on the surface of the coated inclined grating, record the change of surface plasmon resonance shift by spectrometer, and monitor the process of mercaptoundecanoic acid fixation , when the resonance wavelength is no longer red-shifted, the immobilization process of mercaptoundecanoic acid is over, and then inject buffer to wash, wash off unbound mercaptoundecanoic acid and blow dry; S4. Sensing probe preparation: Inject a buffer solution containing biopharmaceuticals into the liquid tank, perform online chemical modification on the pretreated inclined grating surface, record the change of surface plasmon resonance shift with a spectrometer, and monitor the process of biopharmaceutical immobilization , when the resonance wavelength is no longer red-shifted, the immobilization process of the biological agent is over, and then the buffer solution is injected to wash away the unbound biological agent, and after drying, the surface plasmon resonance immunosensing probe of the inclined grating is obtained; S5. Calibration: Select a sample buffer with a known concentration, and take the buffer as a reference. The sample buffer with a known concentration passes through the liquid tank where the surface plasmon resonance immunosensing probe of the inclined grating is located and measures it. The spectrometer detects the size of the resonance wavelength shift, and calibrates and records the relationship between the different concentrations of the sample buffer and the detected physical quantity; S6. Detection of unknown samples: use the cancer marker detection device based on tilted Bragg gratings to detect the buffer solution of unknown samples in real time, and compare the magnitude of the resonance wavelength shift with the numerical relationship in the calibration record to obtain the molecular concentration of the sample. 8. The method for detecting cancer markers based on tilted Bragg gratings according to claim 7, wherein the biopharmaceutical in the method is a related protein of the cancer marker recognition object, and the biopharmaceutical can interact with the nanometer with plasmon resonance effect. The films are bound directly, or using the molecular group of mercaptoundecanoic acid as a transition substance for binding. 9 . The method for detecting cancer markers based on inclined Bragg gratings according to claim 7 , wherein the detection samples in the method include biological proteins, nucleic acids, and polypeptides that can immunoreact with the probes. 10. The method for detecting cancer markers based on tilted Bragg gratings according to claim 7, wherein the biological agent in the method is CNGRC, and the detection sample is cancer cell expression factor CD13.