A fiber optic SPR sensing device for detecting multiple tumor markers

By designing optical fiber SPR sensing devices, using multi-core optical fiber and SPR sensing components, combined with tumor marker receptors, the rapid and efficient detection of various tumor markers is achieved, solving the problems of low sample destruction and detection efficiency in the prior art, and improving detection accuracy and speed.

CN113295624BActive Publication Date: 2025-03-25SHANGHAI UNIV OF ENG SCI
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Patent Information

Application Number
CN202110450370.5
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2021-04-25
Publication Date
2025-03-25
Estimated Expiration
2041-04-25

AI Technical Summary

Technical Problem

The prior art has problems such as sample damage, low contact efficiency, easy cell blockage, and difficult maintenance when detecting tumor markers. In addition, traditional microfluidic chips and prism-coupled SPR sensors cannot detect multiple tumor markers efficiently in real time.

Method used

Design a fiber SPR sensing device, using multi-core optical fiber and SPR sensing components, SPR phenomenon occurs through the fiber core and the surface of the metal film, and combines the tumor marker receptor to achieve rapid and efficient detection of various tumor markers.

Benefits of technology

It realizes rapid, highly sensitive and real-time detection of various tumor markers in the liquid to be tested, avoids sample damage, improves detection accuracy and speed, and reduces maintenance costs.

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Abstract

The present invention relates to an optical fiber SPR sensing device for detecting multiple tumor markers, comprising a spectrum emission component, a multi-core optical fiber, an SPR sensing component, a spectrum receiving component and a processor. The two ends of the multi-core optical fiber are respectively connected to the spectrum emission component and the spectrum receiving component. A cavity is provided in the SPR sensing component for containing a liquid to be tested. In the multi-core optical fiber, a sensing area is provided in the middle of each core optical fiber, and each sensing area is respectively used to detect a different tumor marker. The sensing area is provided in the cavity of the SPR sensing component and contacts with the liquid to be tested. The processor is connected to the spectrum receiving component. Compared with the prior art, the present invention has the advantages of high detection efficiency, high sensitivity and the like.
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Description

Technical Field

[0001] The invention relates to the field of optical fiber sensing, and in particular to an optical fiber SPR sensing device for detecting multiple tumor markers. Background Art

[0002] The detection of tumor markers plays an important guiding role in the prognosis, efficacy evaluation and individualized treatment of cancer patients. Common tumor markers include:

[0003] Carcinoembryonic antigen (CEA) is a tumor-associated antigen first extracted from colon cancer and embryonic tissue by Gold and Freedman in 1965. It is an acidic glycoprotein with human embryonic antigen characteristics. It exists on the surface of cancer cells differentiated from endoderm cells and is a structural protein of the cell membrane. It is formed in the cytoplasm, secreted outside the cell through the cell membrane, and then enters the surrounding body fluids. Therefore, it can be detected from serum, cerebrospinal fluid, breast milk, gastric juice, pleural effusion, urine, feces and other body fluids and excretions.

[0004] Squamous cell carcinoma antigen SCC is the preferred tumor marker for cervical squamous cell carcinoma. Its cutoff value is generally 2.5μg / L. SCC participates in the regulation of protein degradation in normal and malignant conditions, but it cannot be diagnosed as cervical squamous cell carcinoma simply based on the increase of this indicator. It needs to be closely combined with clinical and other examination methods for comprehensive judgment. In addition, this indicator will also increase in some patients with lung cancer, gastric cancer, and ovarian cancer.

[0005] The molecular weight of tissue polypeptide antigen (TPA) is 17,000-43,000. TPA is mainly present in the placenta and most tumor tissues. The detection rate of serum TPA in patients with various malignant tumors (ovarian cancer, colon cancer, rectal cancer, hepatocellular carcinoma, pancreatic cancer, lung cancer, breast cancer, endometrial cancer, testicular tumors, etc.) (>130U / L serum is positive) can range from 20% to 90%, and some people believe that it can be as high as 80%-100%.

[0006] Alpha-fetoprotein (AFP) is a glycoprotein that belongs to the albumin family and is mainly synthesized by fetal liver cells and yolk sac. AFP is closely related to the occurrence and development of liver cancer and various tumors. It can be found in high concentrations in many tumors and can be used as a positive detection indicator for many tumors. At present, it is mainly used as a serum marker for primary liver cancer in clinical practice, and is used for the diagnosis and efficacy monitoring of primary liver cancer.

[0007] There are many methods for detecting tumor markers, such as Flow cytometry, which uses fluorescently coded microspheres to specifically bind to cross-linked molecules on the surface of microspheres in suspension. There are also methods such as automated analyzers and membrane filtration based on immunomagnetic principles. All of the above methods require blood to be processed in advance, which will damage the sample and cause problems such as low separation purity in the later separation.

[0008] Surface Plasmon Resonance (SPR) technology is a new sensing technology that integrates physical optics, material chemistry and other disciplines. It can be used in biomedicine, food safety, environmental testing, chemical analysis and other fields. It can also be used for the detection of tumor markers. However, the traditional microfluidic chip plus prism coupled SPR sensor forces the sample to contact the bottom metal film through the mediating structure. The contact efficiency during the flow process is low, and cells are easily blocked by stacking, making it impossible to perform real-time data analysis efficiently. Under long-term operation, blood substances in the front pipe are prone to blockage due to gravity sedimentation, and it is difficult to maintain. Summary of the invention

[0009] The purpose of the present invention is to overcome the defects of the above-mentioned prior art and to provide a fiber optic SPR sensing device for detecting multiple tumor markers, which can quickly, efficiently and highly sensitively perform refractive index sensing of the sample to be tested and detect multiple tumor markers at the same time.

[0010] The purpose of the present invention can be achieved by the following technical solutions:

[0011] An optical fiber SPR sensing device for detecting multiple tumor markers, comprising a spectrum emission component, a multi-core optical fiber, an SPR sensing component, a spectrum receiving component and a processor, wherein two ends of the multi-core optical fiber are respectively connected to the spectrum emission component and the spectrum receiving component, a cavity is provided in the SPR sensing component for containing a liquid to be tested, a sensing area is provided in the middle of each core optical fiber in the multi-core optical fiber, each sensing area is respectively used to detect a different tumor marker, the sensing area is provided in the cavity of the SPR sensing component and contacts the liquid to be tested, and the processor is connected to the spectrum receiving component;

[0012] When the device is working, the liquid to be tested is contained in the cavity of the SPR sensing component, the spectrum emission component emits the light source spectrum to the multi-core optical fiber, each sensing area of ​​the multi-core optical fiber contacts the liquid to be tested and generates an SPR phenomenon to produce an SPR sensing spectrum, when one or more tumor markers are present in the liquid to be tested, the SPR sensing spectrum generated by the corresponding sensing area in the multi-core optical fiber changes, the spectrum receiving component receives the SPR sensing spectrum and sends it to the processor, and the processor processes the SPR spectrum to realize the detection of multiple tumor markers in the liquid to be tested.

[0013] Furthermore, in the multi-core optical fiber, each core optical fiber comprises an optical fiber cladding, a metal film, a tumor marker receptor and an optical fiber core, the optical fiber cladding is wrapped around the optical fiber core, at the sensing area, the optical fiber cladding is partially removed and the optical fiber core is exposed, the metal film is arranged on the exposed optical fiber core to form an SPR sensing structure, the tumor marker receptor is arranged on the metal film, and in the multi-core optical fiber, each core optical fiber corresponds to a tumor marker receptor of a different tumor marker;

[0014] The light source spectrum is transmitted by reflection in the optical fiber core, and an SPR phenomenon occurs between the optical fiber core and the metal film surface to produce an SPR sensing spectrum. When one or more tumor markers are present in the liquid to be tested, the tumor markers bind to and dissociate from the corresponding tumor marker receptors, causing the refractive index of the metal film surface to change, changing the intensity of the transmitted light, and changing the SPR sensing spectrum generated by the corresponding optical fiber core and the metal film.

[0015] Furthermore, the multi-core optical fiber is a four-core optical fiber, and the tumor marker receptors include a coupled carcinoembryonic antigen receptor, a coupled squamous cell carcinoma antigen SCC receptor, a coupled tissue polypeptide antigen receptor and a coupled alpha-fetoprotein receptor.

[0016] Preferably, the metal film is a nano-metal film capable of stimulating the SPR phenomenon.

[0017] Further preferably, the metal film is a gold film or a silver film.

[0018] Furthermore, the SPR sensing component includes a shell, a liquid injection port and a liquid discharge valve. The cavity is opened in the shell, including a liquid cavity and a fiber cavity that are interconnected. The liquid cavity is arranged at the center of the shell to hold the liquid to be tested. The fiber cavities are evenly distributed around the liquid cavity, and the number is the same as the number of fiber cores in the multi-core optical fiber. The cross-section of the fiber cavities matches the cross-section of the sensing area of ​​each fiber core in the multi-core optical fiber. The sensing area of ​​each fiber core in the multi-core optical fiber is respectively arranged in each fiber cavity, and the metal film and the tumor marker receptor are facing the direction of the liquid cavity and in contact with the liquid to be tested. The liquid injection port and the liquid discharge valve are respectively connected to the liquid cavity.

[0019] Furthermore, the spectrum emission component includes a light source, a light source pigtail, a fiber optic splitter and a first fiber optic welding machine connected in sequence, the output end of the first fiber optic welding machine is connected to the input end of the multi-core optical fiber, the light source is used to generate excitation light that excites the SPR phenomenon, the light source pigtail is used to transmit the light source spectrum, the fiber optic splitter is used to divide the light transmitted by the light source pigtail into multiple beams of light corresponding to the multi-core optical fiber, and the first fiber optic welding machine is used to inject the multiple beams of light output by the fiber optic splitter into each core of the multi-core optical fiber.

[0020] Furthermore, the spectrum receiving component includes a second optical fiber welding machine, a receiving optical fiber and a spectrometer connected in sequence, the output end of the multi-core optical fiber is connected to the input end of the second optical fiber welding machine, the receiving optical fiber is used to receive the SPR sensing spectrum, and the spectrometer is used to receive, display and record the SPR sensing spectrum.

[0021] Preferably, the excitation light generated by the light source is a supercontinuum light source with a spectral width of 450nm-1100nm, the spectral width range of the spectrometer is 450nm-1100nm, the refractive index range of the liquid to be measured is 1.333-1.385, the light source pigtail is a single-mode optical fiber, and the receiving optical fiber is a gradient refractive index multimode optical fiber or a step-index multimode optical fiber.

[0022] Preferably, the thickness of the metal film is 25 nm.

[0023] Compared with the prior art, the present invention has the following advantages:

[0024] 1) The present invention utilizes the characteristics of high integration, real-time transmission, high sensitivity, etc. of the optical fiber SPR sensor, reasonably designs the structure, avoids the destruction of the original sample, uses a micro-injection pump for pressurization, breaks the inherent use form of the traditional microfluidic chip plus prism coupling type SPR sensor, and forms a distributed optical fiber SPR liquid refractive index sensing device in the flow channel, which can realize the sensing of the refractive index change of the liquid to be measured in real time, quickly and efficiently;

[0025] 2) The present invention uses multi-core optical fibers to avoid the defect that the traditional structure can only detect one tumor marker, and can detect multiple tumor markers at the same time. The detection probe is made into a symmetrical four-sided structure, and the spacing is reasonably designed to ensure that the sample can contact the sensing area through the flow tube;

[0026] 3) The present invention realizes an online transmission type SPR sensor, and the optical fiber conducts online in real time, which has high sensitivity and is more accurate than the micro-flow plus prism coupling type SPR sensor. The four-core parallel distributed SPR sensor can be integrated in a set of sensing devices and used in parallel, which broadens the use of the optical fiber SPR sensor, and can continuously and efficiently perform refractive index sensing detection. The tumor markers detected by the detection device are transmitted to the processor for real-time analysis and statistics, which can determine the type and concentration of the tumor marker, improve the detection speed and accuracy, and improve the detection quality to a certain extent;

[0027] 4) The manufacturing materials of the present invention are simple and easy to find, the operation process is simple, the cost is low, it can be reused many times, the cost is saved, and the reliability is strong. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 It is a schematic diagram of the overall structure of the device of the present invention;

[0029] Figure 2 Schematic diagram of the three-dimensional structure of the SPR sensor component;

[0030] Figure 3 It is a schematic diagram of the cross section of the SPR sensor component;

[0031] Figure 4 Schematic diagram of the structure of the sensing area of ​​each optical fiber in a multi-core optical fiber.

[0032] 1. light source, 2. light source pigtail, 3. optical fiber beam splitter, 41. first optical fiber welding machine, 42. second optical fiber welding machine, 5. SPR sensor assembly, 6. device table, 7. injection pump, 8. spectrometer, 9. processor, 10. waste liquid tank, 11. receiving optical fiber, 12. drain valve, 13. multi-core optical fiber, 131. optical fiber cladding, 132. metal film, 133. tumor marker receptor, 134. optical fiber core, 14. liquid injection port, 15. shell, 151. liquid cavity, 152. optical fiber cavity. DETAILED DESCRIPTION

[0033] The present invention is described in detail below in conjunction with the accompanying drawings and specific embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work should belong to the scope of protection of the present invention.

[0034] Example

[0035] The present invention discloses a fiber SPR sensor device for detecting multiple tumor markers. The fiber SPR sensor has the characteristics of high integration, real-time transmission, high sensitivity, etc., and the structure is reasonably designed to avoid damage to the original sample. A micro-injection pump is used to pressurize the device, and only a small amount of sample is needed for detection. The fiber conducts online in real time and is highly sensitive. Compared with the previous microfluidic chip plus prism coupling SPR sensor, it is more accurate. The detection probe is specially made into a pattern, and the spacing is reasonably designed to ensure that the sample can contact the outer surface of the sensor in the flow tube. Finally, the multiple tumor markers detected by the probe are transmitted to a computer for real-time analysis and statistics, which improves the detection speed and accuracy.

[0036] like Figure 1 As shown, the device includes a spectrum emission component, a multi-core optical fiber 13, an SPR sensing component 5, a spectrum receiving component and a processor 9. The SPR sensing component 5 is arranged on the device table 6. The two ends of the multi-core optical fiber 13 are respectively connected to the spectrum emission component and the spectrum receiving component. A cavity is provided in the SPR sensing component 5 for containing the liquid to be tested. In the multi-core optical fiber 13, a sensing area is provided in the middle of each core optical fiber, and each sensing area is used to detect different tumor markers. The sensing area is provided in the cavity of the SPR sensing component 5 and contacts with the liquid to be tested. The sensing area is used to sense the refractive index change of the liquid to be tested, stimulate the SPR phenomenon, and generate an SPR sensing spectrum.

[0037] The spectral emission component includes a light source 1, a light source pigtail 2, a fiber optic splitter 3 and a first fiber optic welder 41 connected in sequence. The output end of the first fiber optic welder 41 is connected to the input end of the multi-core optical fiber 13. The light source 1 is used to generate excitation light that excites the SPR phenomenon. The light source pigtail 2 is used to transmit the light source spectrum. The fiber optic splitter 3 is used to divide the light transmitted by the light source pigtail 2 into multiple beams of light corresponding to the multi-core optical fiber 13. The first fiber optic welder 41 is used to inject the multiple beams of light output by the fiber optic splitter 3 into each core of the multi-core optical fiber 13.

[0038] The spectrum receiving component includes a second optical fiber welding machine 42, a receiving optical fiber 11 and a spectrometer 8 which are connected in sequence. The output end of the multi-core optical fiber 13 is connected to the input end of the second optical fiber welding machine 42. The receiving optical fiber 11 is used to receive the SPR sensing spectrum. The spectrometer 8 is used to receive, display and record the SPR sensing spectrum. The processor 9 adopts a computer and is connected to the spectrometer 8 for recording integrated data.

[0039] In this embodiment, the excitation light generated by the light source 1 is a supercontinuum light source with a spectral width of 450nm-1100nm, and the resonance wavelength range of the optical fiber SPR sensor is 450nm-1100nm, so the spectral width of the light source 1 needs to include 450nm-1100nm, that is, at least 450nm-1100nm, and the spectral width range of the spectrometer 8 is 450nm-1100nm, and the spectral width of the spectrometer 8 at least includes the minimum spectral width of the light source 1 of 450nm-1100nm, to ensure that a complete sensing spectrum can be received, the refractive index range of the liquid to be measured is 1.333-1.385, the light source pigtail 2 is a single-mode optical fiber, and the receiving optical fiber 11 is a gradient refractive index multimode optical fiber or a step multimode optical fiber.

[0040] like Figure 1-Figure 3 As shown, the SPR sensor assembly 5 includes a housing 15, a liquid injection port 14 and a liquid discharge valve 12. The cavity is opened in the housing 15, including a liquid cavity 151 and an optical fiber cavity 152 that are interconnected. The liquid cavity 151 is arranged at the center of the housing 15 for containing the liquid to be tested, and is respectively connected to the liquid injection port 14 and the liquid discharge valve 12. The optical fiber cavity 152 is evenly and symmetrically distributed around the liquid cavity 151. The optical fiber cavity 152 is arranged in a symmetrical type to ensure reasonable and uniform distribution. The number of optical fiber cavities 152 is the same as the number of optical fiber cores in the multi-core optical fiber 13, and its cross section is the same as the multi-core optical fiber 13. The cross-sections of the sensing areas of each optical fiber in the optical fiber 13 cooperate with each other, and the sensing areas of each optical fiber in the multi-core optical fiber 13 are respectively arranged in each optical fiber cavity 152, the injection port 14 is connected to the injection pump 7, and the drain valve 12 is connected to the waste liquid pool 10. The drain valve 12 can control the flow rate and the closing state. In this embodiment, the cross-section of the sensing area is D-shaped, and the shell 15 can be made of glass. The drain valve 12 can be automatically opened after the detection is completed to release the sample after the detection. The SPR sensor component 5 after chemical cleaning can be reused.

[0041] like Figure 4 As shown, in the multi-core optical fiber 13, each core optical fiber includes an optical fiber cladding 131, a metal film 132, a tumor marker receptor 133 and an optical fiber core 134. The optical fiber cladding 131 is wrapped around the optical fiber core 134. At the sensing area, the optical fiber cladding 131 is partially removed to expose the optical fiber core 134. The metal film 132 is disposed on the exposed optical fiber core 134 to form an SPR sensing structure. The tumor marker receptor 133 is disposed on the metal film 132. In the multi-core optical fiber 13, each core optical fiber corresponds to a tumor marker receptor 133 of a different tumor marker. There is a high-affinity specific binding between each tumor marker receptor 133 and the corresponding tumor marker, which will give the metal film the ability to specifically capture the marker.

[0042] In this embodiment, the multi-core optical fiber 13 is a four-core optical fiber, which has an inner wall diameter of 100 μm and is a single-mode optical fiber. The tumor marker receptor 133 includes a coupled carcinoembryonic antigen receptor, a coupled squamous cell carcinoma antigen SCC receptor, a coupled tissue polypeptide antigen receptor and a coupled alpha-fetoprotein receptor. The metal film 132 is a nano-metal film that can stimulate the SPR phenomenon. The metal film 132 is preferably a gold film or a silver film, and the thickness of the metal film 132 is preferably 25 nm.

[0043] The output end of the light source 1 is connected to the input end of the light source pigtail 2, the output end of the light source pigtail 2 is connected to the input end of the optical fiber splitter 3, the four output ends of the optical fiber splitter 3 are respectively welded to the multiple cores of the input end of the multi-core optical fiber 13 through the first optical fiber welding machine 41, and each core of the output end of the multi-core optical fiber 13 is respectively welded to the core of the input end of the receiving optical fiber 11 through the second optical fiber welding machine 42, and finally the signal is sent to the spectrometer 8.

[0044] When the device is working, the sample is pressurized by the micro-injection pump 7 to uniformly flow into the liquid cavity 151 of the SPR sensor component 5, so that the liquid cavity 151 is filled with the liquid to be tested, and the spectrum emission component emits the light source spectrum to the multi-core optical fiber 13, and the light source spectrum is transmitted by reflection in each optical fiber core 134, and the SPR phenomenon occurs on the surface of the optical fiber core 134 and the metal film 132 to generate the SPR sensing spectrum;

[0045] When one or more tumor markers exist in the liquid to be tested, various tumor markers continuously contact the metal film 132 containing specific biological molecules, and are captured by the tumor marker receptors 133 on the surface of the metal film 132 that has been specifically biochemically treated. The tumor markers bind and dissociate with the corresponding tumor marker receptors 133, causing the refractive index of the surface of the metal film 132 to change, changing the intensity of the transmitted light, and changing the SPR sensing spectrum generated by the corresponding optical fiber core 134 and the metal film 132. The spectrum receiving component receives the SPR sensing spectrum and sends it to the processor 9, which processes the SPR spectrum to achieve the detection of multiple tumor markers in the liquid to be tested.

[0046] The SPR optical detection system simultaneously realizes the category analysis and concentration measurement of the markers. Since SPR is very sensitive to the refractive index of the dielectric on the surface of the metal film, different dielectrics have different surface plasma resonance angles. The same dielectric has different amounts attached to the surface of the metal film, so the SPR response intensity is also different. The displacement that can be observed through the SPR spectrum peak is also different. This information data is transmitted online to the computer in a timely manner. Through spectral analysis, high-sensitivity detection can be performed to obtain accurate data information, providing guidance for the diagnosis and treatment of patients.

[0047] The present invention utilizes the characteristics of high integration, real-time transmission, high sensitivity, etc. of the optical fiber SPR sensor, and reasonably designs the structure to avoid the destruction of the original sample. It utilizes a trace sample and pressurizes it with a micro-injection pump to avoid the lack of marker collection in the traditional structure tube sample. Moreover, the optical fiber is online and real-time, highly sensitive, and more accurate than the previous microfluidic chip plus prism coupling SPR sensor. The detection probe is made into a three-dimensional symmetrical structure to ensure that the marker can contact the sensing surface when passing through the tube. Finally, the information of various tumor markers detected by the probe is transmitted to the computer for real-time analysis and statistics, which improves the detection speed and accuracy, and improves the detection quality to a certain extent.

[0048] The above is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any person familiar with the technical field can easily think of various equivalent modifications or substitutions within the technical scope disclosed by the present invention, and these modifications or substitutions should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention shall be based on the protection scope of the claims.

Claims

1. A fiber SPR sensing device for detecting multiple tumor markers, characterized in that: The invention comprises a spectrum emission component, a multi-core optical fiber (13), an SPR sensing component (5), a spectrum receiving component and a processor (9), wherein two ends of the multi-core optical fiber (13) are respectively connected to the spectrum emission component and the spectrum receiving component, a cavity is provided in the SPR sensing component (5) for containing a liquid to be tested, a sensing area is provided in the middle of each core optical fiber in the multi-core optical fiber (13), each sensing area is respectively used to detect a different tumor marker, the sensing area is provided in the cavity of the SPR sensing component (5) and contacts with the liquid to be tested, and the processor (9) is connected to the spectrum receiving component; When the device is in operation, the cavity of the SPR sensing component (5) contains a liquid to be tested, the spectrum emission component emits a light source spectrum to the multi-core optical fiber (13), each sensing area of ​​the multi-core optical fiber (13) contacts the liquid to be tested and generates an SPR phenomenon to generate an SPR sensing spectrum; when one or more tumor markers are present in the liquid to be tested, the SPR sensing spectrum generated by the corresponding sensing area in the multi-core optical fiber (13) changes, the spectrum receiving component receives the SPR sensing spectrum and sends it to the processor (9), and the processor (9) performs data processing on the SPR spectrum to achieve detection of multiple tumor markers in the liquid to be tested; In the multi-core optical fiber (13), each core optical fiber comprises an optical fiber cladding (131), a metal film (132), a tumor marker receptor (133) and an optical fiber core (134); the optical fiber cladding (131) is wrapped around the optical fiber core (134); at the sensing area, the optical fiber cladding (131) is partially removed to expose the optical fiber core (134); the metal film (132) is disposed on the exposed optical fiber core (134) to form an SPR sensing structure; the tumor marker receptor (133) is disposed on the metal film (132); in the multi-core optical fiber (13), each core optical fiber corresponds to a tumor marker receptor (133) of a different tumor marker; The light source spectrum is transmitted through reflection in the optical fiber core (134), and an SPR phenomenon occurs on the surface of the optical fiber core (134) and the metal film (132) to generate an SPR sensing spectrum. When one or more tumor markers are present in the liquid to be tested, the tumor markers bind to and dissociate from the corresponding tumor marker receptors (133), causing the refractive index of the surface of the metal film (132) to change, changing the intensity of the transmitted light, and causing the SPR sensing spectrum generated by the corresponding optical fiber core (134) and the metal film (132) to change. The multi-core optical fiber (13) is a four-core optical fiber, and the tumor marker receptor (133) includes a coupled carcinoembryonic antigen receptor, a coupled squamous cell carcinoma antigen SCC receptor, a coupled tissue polypeptide antigen receptor and a coupled alpha-fetoprotein receptor; The SPR sensor assembly (5) comprises a housing (15), a liquid injection port (14) and a liquid discharge valve (12); the cavity is opened in the housing (15), and comprises a liquid cavity and a fiber cavity which are interconnected; the liquid cavity is arranged at the center of the housing (15) and is used to contain a liquid to be tested; the fiber cavities are evenly distributed around the liquid cavity, and the number of the fiber cavities is the same as the number of fiber cores in the multi-core optical fiber (13); the cross-section of the fiber cavities matches the cross-section of the sensing area of ​​each fiber core in the multi-core optical fiber (13); the sensing area of ​​each fiber core in the multi-core optical fiber (13) is respectively arranged in each fiber cavity, and the metal film (132) and the tumor marker receptor (133) face the direction of the liquid cavity and contact the liquid to be tested; the liquid injection port (14) and the liquid discharge valve (12) are respectively connected to the liquid cavity.

2. The optical fiber SPR sensing device for detecting multiple tumor markers according to claim 1, characterized in that: The metal film (132) is a nano metal film capable of stimulating the SPR phenomenon.

3. The optical fiber SPR sensing device for detecting multiple tumor markers according to claim 2, characterized in that: The metal film (132) is a gold film or a silver film.

4. The optical fiber SPR sensing device for detecting multiple tumor markers according to claim 1, characterized in that: The spectrum emission component comprises a light source (1), a light source pigtail (2), an optical fiber splitter (3) and a first optical fiber welder (41) which are connected in sequence. The output end of the first optical fiber welder (41) is connected to the input end of the multi-core optical fiber (13). The light source (1) is used to generate excitation light for exciting the SPR phenomenon. The light source pigtail (2) is used to transmit the light source spectrum. The optical fiber splitter (3) is used to split the light transmitted by the light source pigtail (2) into multiple beams of light corresponding to the multi-core optical fiber (13). The first optical fiber welder (41) is used to inject the multiple beams of light output by the optical fiber splitter (3) into each core of the multi-core optical fiber (13).

5. The optical fiber SPR sensing device for detecting multiple tumor markers according to claim 4, characterized in that: The spectrum receiving component comprises a second optical fiber welding machine (42), a receiving optical fiber (11) and a spectrometer (8) which are connected in sequence, the output end of the multi-core optical fiber (13) is connected to the input end of the second optical fiber welding machine (42), the receiving optical fiber (11) is used to receive the SPR sensing spectrum, and the spectrometer (8) is used to receive, display and record the SPR sensing spectrum.

6. The optical fiber SPR sensing device for detecting multiple tumor markers according to claim 5, characterized in that: The excitation light generated by the light source (1) is a supercontinuum light source with a spectrum width of 450nm-1100nm, the spectrum width range of the spectrometer (8) is 450nm-1100nm, the refractive index range of the liquid to be measured is 1.333-1.385, the light source pigtail (2) is a single-mode optical fiber, and the receiving optical fiber (11) is a gradient refractive index multimode optical fiber or a step-index multimode optical fiber.

7. The optical fiber SPR sensing device for detecting multiple tumor markers according to claim 1, characterized in that: The thickness of the metal film (132) is 25 nm.

Citation Information

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