Intestinal disease detection device based on tapering multimode fiber ring laser

Abstract

The invention discloses an intestinal disease detection device based on a tapering multimode fiber ring laser. According to the device, a tapering multimode fiber is prepared through a tapering multimode fiber preparation module by adopting a fused biconical taper method; functional modification is performed on the surface of an optical fiber taper region of the tapering multimode optical fiber through a tapering multimode optical fiber functional module, and a specific antibody of an intestinal disease marker is fixed; an intestinal disease marker detection module is integrated in an optical fiber ring laser system by utilizing a functionalized sensing probe, the laser wavelength drift distance is detected through the optical fiber ring laser system, an intestinal disease marker is detected according to the laser wavelength drift distance, and an intestinal disease detection result is obtained. The spectral line width can be effectively compressed, and the signal-to-noise ratio is improved, so that high-precision, high-sensitivity and rapid label-free detection of the intestinal disease marker is realized.

Description

Technical Field

[0001] This invention relates to the field of fiber optic biosensing technology, and in particular to an intestinal disease detection device based on a tapered multimode fiber ring laser. Background Technology

[0002] Intestinal diseases, including inflammatory bowel diseases (such as Crohn's disease and ulcerative colitis), colorectal cancer, and other infectious bowel diseases and nonspecific enteritis, have become increasingly prominent public health problems worldwide. Colorectal cancer ranks among the top malignant tumors in terms of incidence and mortality globally, while inflammatory bowel disease, as a chronic and relapsing disease, imposes a long-term burden and economic pressure on patients. Early detection, accurate diagnosis, disease activity assessment, and efficacy monitoring are of great significance for improving patient prognosis and achieving precision medicine.

[0003] Currently, clinical diagnosis and monitoring of intestinal diseases are mainly achieved through the detection of specific biomarkers. In the field of inflammatory bowel disease (IBD), fecal calprotectin, as a non-invasive indicator reflecting the level of intestinal mucosal inflammation, can be used to differentiate between inflammatory and functional bowel diseases and assess disease activity. Serum C-reactive protein, as a systemic inflammatory marker, is used for auxiliary screening. Autoantibodies such as anti-acid yeast antibodies and perinuclear anti-neutrophil cytoplasmic antibodies are helpful for the subtyping diagnosis of IBD. In colorectal cancer screening, fecal immunochemical testing has become the preferred primary screening method due to its high specificity and convenience. Carcinoembryonic antigen (CEA), as a classic serum tumor marker, plays a key role in postoperative efficacy evaluation and recurrence monitoring.

[0004] Currently, commonly used clinical methods for biomarker detection mainly include enzyme-linked immunosorbent assay (ELISA) and immunofluorescence chromatography; although these methods are widely used, they generally have the following limitations: Traditional methods require complex sample pretreatment processes, rely on labeling operations, have limited detection limits, involve cumbersome procedures, have high equipment costs, and have long detection cycles. Fiber optic sensing technology, as an emerging detection method, theoretically possesses advantages such as high sensitivity, ease of integration, and low cost, and is expected to overcome the limitations of traditional methods. However, existing fiber optic sensors, including fiber grating sensors, surface plasmon resonance sensors, and fiber optic interferometer sensors, still face many challenges in practical applications. In particular, traditional tapered fiber interferometers, due to their wide full width at half maximum (FWHM) of the interference spectrum, result in insufficient system signal-to-noise ratio, making it difficult to meet the requirements for low-concentration, high-precision detection of intestinal disease biomarkers in complex biological samples. Summary of the Invention

[0005] The main objective of this invention is to provide an intestinal disease detection device based on a tapered multimode fiber ring laser, which aims to solve the technical problems of insufficient sensitivity, complex operation and reliance on invasive sampling in existing intestinal disease detection technologies, which result in the inability to reliably detect early intestinal disease biomarkers, leading to high clinical missed diagnosis rates and low diagnostic efficiency.

[0006] This invention provides a device for detecting intestinal diseases based on a tapered multimode fiber ring laser. The device comprises: a tapered multimode fiber fabrication module, a tapered multimode fiber functionalization module, and an intestinal disease biomarker detection module; wherein... The tapered multimode fiber fabrication module is used to fabricate tapered multimode fibers using the fused taper method; The tapered multimode fiber functionalization module is used to functionalize the surface of the tapered region of the tapered multimode fiber to fix specific antibodies for intestinal disease biomarkers. The intestinal disease biomarker detection module is used to integrate a functionalized sensing probe into a fiber optic ring laser system, detect the laser wavelength drift through the fiber optic ring laser system, and detect intestinal disease biomarkers based on the laser wavelength drift to obtain intestinal disease detection results.

[0007] Optionally, the tapered multimode fiber fabrication module is also used to fusion splice multimode fiber between two single-mode fibers to construct an optical fiber assembly; The coating layer of the multimode fiber midsegment of the optical fiber assembly is stripped and cleaned to generate a standard multimode fiber. The standard multimode optical fiber is fixed to the displacement stage of the tapered machine.

[0008] Optionally, the tapered multimode fiber fabrication module is also used to control the temperature and stretching rate of the fiber heating zone, stretch the standard multimode fiber into a tapered structure, and ensure that the waist diameter of the tapered multimode fiber is stable within a preset diameter range.

[0009] Optionally, the tapered multimode fiber functionalization module is further used to sequentially perform surface cleaning, surface activation, coupling agent modification, antibody immobilization and blocking treatment on the surface of the fiber tapered region of the tapered multimode fiber, thereby immobilizing specific antibodies of intestinal disease biomarkers on the surface of the fiber tapered region and constructing a biosensor interface.

[0010] Optionally, the tapered multimode fiber functionalization module is further used to remove impurities from the surface of the tapered region of the tapered multimode fiber by cleaning with chemical reagents. Activating functional groups are introduced by activating reagents and then modified by coupling agents to form functionalized interfaces that can immobilize biomolecules. Specific antibodies for intestinal disease biomarkers were covalently immobilized on the surface of the fiber cone region, and non-specific sites were blocked with bovine serum albumin solution to complete the construction of the biosensor interface.

[0011] Optionally, the intestinal disease biomarker detection module is further used to integrate the sensing probe of the functionalized tapered multimode fiber into the fiber ring laser system, the fiber ring laser system including an erbium-doped fiber amplifier, an optical isolator, a polarization controller, an optical coupler, and a spectrometer. The laser wavelength drift is monitored in real time by the fiber ring laser system, and the laser wavelength drift is converted into the concentration of biomarkers for intestinal diseases. Intestinal disease detection results are generated based on the biomarker concentration.

[0012] Optionally, the intestinal disease biomarker detection module is also used to connect the sensing probe of the functionalized tapered multimode fiber to the fiber ring laser system, start the erbium-doped fiber amplifier and spectrometer in the fiber ring laser system, adjust the spectrometer to the predetermined observation range, until the spectrometer displays a stable laser oscillation peak. The sensing probe is immersed in a solution containing intestinal disease biomarkers, and the laser spectrum is continuously monitored. When the laser wavelength stabilizes due to the complete antigen-antibody binding reaction, the current laser spectrum is recorded. The concentration of the solution is changed to obtain the laser wavelength values ​​corresponding to different concentrations. The wavelength shift of the laser wavelength is measured to be quantifiable, and the wavelength shift is converted into a marker concentration based on a preset calibration curve. The intestinal disease detection result is generated based on the marker concentration.

[0013] Optionally, the intestinal disease biomarker detection module is further configured to monitor in real time the quantifiable wavelength shift of the laser wavelength in the fiber ring laser system using the spectrometer, and to obtain the preset calibration curve by mathematically fitting the known concentration of the standard sample with the corresponding wavelength shift. The wavelength drift is converted into a marker concentration based on the preset calibration curve. The intestinal disease status is determined based on the comparison between the marker concentration and a preset concentration threshold, and the intestinal disease detection result is output.

[0014] Optionally, the intestinal disease biomarker detection module is further configured to linearly fit the wavelength drift and the environmental refractive index of the solution to obtain the preset calibration curve corresponding to the mapping relationship between the wavelength drift and the environmental refractive index; The detection limit of the intestinal disease detection device based on the tapered multimode fiber ring laser is obtained according to the preset calibration curve.

[0015] Optionally, the intestinal disease biomarker detection module is further configured to obtain the detection limit using the following formula:

[0016]

[0017]

[0018]

[0019] in, To explore the limits, For quantitative resolution, For the refractive index sensitivity of the sensor, The standard deviations related to each noise factor, To amplify the noise, For spectral resolution, Temperature-induced drift To experimentally measure the full width at half maximum (FWHM) of the spectrum, For signal-to-noise ratio, This represents the resolution of the spectrometer.

[0020] This invention proposes an intestinal disease detection device based on a tapered multimode fiber ring laser. The device fabricates tapered multimode fibers using a fused taper method via a tapered multimode fiber fabrication module. A tapered multimode fiber functionalization module functionalizes the surface of the tapered region of the fiber, immobilizing specific antibodies for intestinal disease biomarkers. An intestinal disease biomarker detection module integrates functionalized sensing probes into a fiber ring laser system. The system detects the laser wavelength shift and uses this shift to detect intestinal disease biomarkers, obtaining detection results. This device effectively compresses spectral linewidth and improves the signal-to-noise ratio, thereby achieving high-precision detection of intestinal disease biomarkers. High sensitivity and rapid label-free detection: By rationally setting the diameter of the tapered plate, high-sensitivity dual-mode interferometric sensing is achieved, effectively overcoming the inherent defects of traditional immunoassay processes such as complexity, label dependence, and long processing time. It provides a new technical path for the early screening and rapid diagnosis of intestinal diseases, effectively stimulating and enhancing higher-order modes to generate a stronger evanescent field, enhancing the interaction with the analyte, and obtaining higher refractive index sensitivity. This lays the physical foundation for high-sensitivity biosensing, significantly compressing the full width at half maximum (FWHM) of the spectrum, fundamentally solving the problem of limited detection accuracy caused by wide spectral lines and low signal-to-noise ratio in direct spectral detection, and achieving biomolecular detection performance with a lower detection limit and higher detection accuracy. Attached Figure Description

[0021] Figure 1This is a functional block diagram of the first embodiment of the intestinal disease detection device based on a tapered multimode fiber ring laser of the present invention; Figure 2 This is a schematic diagram of the structure of a tapered multimode optical fiber; Figure 3 A schematic diagram illustrating the simulation results of the refractive index sensitivity of tapered multimode fiber; Figure 4 A schematic diagram of a tapered multimode fiber ring laser sensor system; Figure 5 A schematic diagram of the output spectrum of a tapered multimode fiber ring laser; Figure 6 This is a schematic diagram of the output spectrum of a tapered multimode fiber ring laser under different refractive indices. Figure 7 This is a schematic diagram showing the linear fitting results between the peak wavelength of the output laser from a tapered multimode fiber ring laser and the refractive index of the environment. Figure 8 This is a schematic diagram illustrating the process of functionalizing tapered multimode optical fibers using calprotectin antibodies.

[0022] The realization of the objective, functional features and advantages of the present invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0023] It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

[0024] The solution of this invention mainly involves: fabricating tapered multimode fibers using a fused taper method via a tapered multimode fiber fabrication module; functionalizing the surface of the tapered region of the fiber using a tapered multimode fiber functionalization module to immobilize specific antibodies for intestinal disease biomarkers; and integrating the functionalized sensing probes into a fiber ring laser system using an intestinal disease biomarker detection module to detect the laser wavelength shift and detect intestinal disease biomarkers based on the laser wavelength shift, thereby obtaining intestinal disease detection results. This approach effectively compresses spectral linewidth and improves the signal-to-noise ratio, achieving high-precision, high-sensitivity, and rapid label-free detection of intestinal disease biomarkers. By rationally setting the tapered diameter, high-sensitivity two-mode interferometric sensing is achieved, effectively overcoming... Overcoming the inherent drawbacks of traditional immunoassay procedures, such as complexity, label dependence, and long processing times, this technology provides a novel approach for the early screening and rapid diagnosis of intestinal diseases. It effectively excites and enhances higher-order modes, thereby generating a stronger evanescent field, enhancing the interaction with the analyte, and achieving higher refractive index sensitivity. This lays the physical foundation for high-sensitivity biosensing and significantly compresses the full width at half maximum (FWHM) of the spectrum. It fundamentally solves the problem of limited detection accuracy caused by wide spectral lines and low signal-to-noise ratio in direct spectral detection. This technology achieves biomolecular detection performance with a lower detection limit and higher detection accuracy. It also addresses the technical problems of insufficient sensitivity, complex operation, and reliance on invasive sampling in existing intestinal disease detection technologies, which lead to unreliable detection of early intestinal disease biomarkers, resulting in high clinical missed diagnosis rates and low diagnostic efficiency.

[0025] Reference Figure 1 , Figure 1 This is a functional block diagram of the first embodiment of the intestinal disease detection device based on a tapered multimode fiber ring laser of the present invention.

[0026] In a first embodiment of the intestinal disease detection device based on a tapered multimode fiber ring laser of the present invention, the intestinal disease detection device based on a tapered multimode fiber ring laser includes: a tapered multimode fiber fabrication module 10, a tapered multimode fiber functionalization module 20, and an intestinal disease biomarker detection module 30; wherein... The tapered multimode fiber fabrication module 10 is used to fabricate tapered multimode fibers using the fused taper method.

[0027] The tapered multimode fiber functionalization module 20 is used to functionalize the surface of the tapered region of the tapered multimode fiber to fix specific antibodies for intestinal disease markers.

[0028] The intestinal disease biomarker detection module 30 is used to integrate a functionalized sensing probe into a fiber optic ring laser system, detect the laser wavelength drift through the fiber optic ring laser system, and detect intestinal disease biomarkers based on the laser wavelength drift to obtain intestinal disease detection results.

[0029] It should be noted that the tapered multimode fiber fabrication module can produce tapered multimode fibers with high surface curvature and optical field coupling efficiency through fused taper technology, providing core optical sensing elements for subsequent functionalization and integration of fiber ring laser systems.

[0030] Understandably, the tapered multimode fiber functionalization module can functionally modify the surface of the tapered region of the tapered multimode fiber, fix specific antibodies for intestinal disease biomarkers, provide a precise biorecognition layer for the fiber ring laser system, and ensure high sensitivity and specificity for subsequent laser wavelength drift detection.

[0031] It should be understood that the intestinal disease biomarker detection module integrates a functionalized tapered multimode fiber sensing probe into a fiber ring laser system. By monitoring the laser wavelength drift in real time, it detects intestinal disease biomarkers based on the laser wavelength drift and finally outputs highly sensitive intestinal disease detection results, achieving non-invasive and rapid clinical diagnosis.

[0032] Furthermore, the tapered multimode fiber fabrication module 10 is also used to fusion splice multimode fiber between two single-mode fibers to construct an optical fiber assembly. The coating layer of the multimode fiber midsegment of the optical fiber assembly is stripped and cleaned to generate a standard multimode fiber. The standard multimode optical fiber is fixed to the displacement stage of the tapered machine.

[0033] Understandably, the process of fabricating the core sensing unit using fused taper technology involves first fusing multimode optical fibers between two single-mode optical fibers to construct an optical fiber assembly, then stripping and cleaning the coating layer from the middle section of the multimode optical fiber, and finally fixing it to the taper machine's displacement stage.

[0034] Furthermore, the tapered multimode fiber preparation module 10 is also used to control the temperature and stretching rate of the fiber heating zone, stretch the standard multimode fiber into a tapered structure, and ensure that the waist diameter of the tapered multimode fiber is stable within a preset diameter range.

[0035] It should be noted that by controlling the heating temperature and stretching parameters, a tapered multimode fiber structure with a waist diameter of approximately 10 μm is formed during the molten tapering process, providing a highly sensitive evanescent field interaction region for subsequent sensing applications.

[0036] In practice, the tapered multimode fiber fabrication module employs fused taper technology. By precisely controlling the temperature (approximately 1500°C) and stretching rate (0.5-2 mm / s) of the fiber heating zone, standard multimode fibers are stretched into a tapered structure, ensuring that the waist diameter remains stable within the range of 5-15 μm. This process produces tapered multimode fibers with high surface curvature and optical field coupling efficiency, providing core optical components for subsequent functionalization and integration into fiber ring laser systems.

[0037] Furthermore, the tapered multimode fiber functionalization module 20 is also used to sequentially perform surface cleaning, surface activation, coupling agent modification, antibody fixation and blocking treatment on the surface of the tapered region of the tapered multimode fiber, fix the specific antibodies of intestinal disease biomarkers on the surface of the tapered region, and construct a biosensor interface.

[0038] Understandably, the functional module for tapered multimode fiber chemically modifies the tapered surface of the fiber to immobilize specific biorecognition molecules and construct a biosensing interface. This process includes sequential surface cleaning, activation, coupling agent modification, antibody immobilization, and blocking treatment.

[0039] Furthermore, the tapered multimode fiber functionalization module 20 is also used to remove impurities from the surface of the tapered region of the tapered multimode fiber by cleaning with chemical reagents. Activating functional groups are introduced by activating reagents and then modified by coupling agents to form functionalized interfaces that can immobilize biomolecules. Specific antibodies for intestinal disease biomarkers were covalently immobilized on the surface of the fiber cone region, and non-specific sites were blocked with bovine serum albumin solution to complete the construction of the biosensor interface.

[0040] It should be understood that, firstly, chemical reagents are used to clean and remove impurities from the surface of the cone region. Then, active functional groups are introduced through activating reagents, and then a functionalized interface capable of immobilizing biomolecules is formed by modification with a coupling agent. Subsequently, intestinal disease biomarker antibodies are immobilized on the surface of the cone region through covalent bonding. Finally, bovine serum albumin solution is used to block non-specific sites, thereby completing the construction of a biosensing interface with high specificity and stability.

[0041] In a specific implementation, surface cleaning can be achieved by treating with KOH solution for 1 hour, surface activation can be achieved by treating with silanized ethanol reagent for 4 hours, and then specific antibody fixation can be achieved by activating with a mixed solution of EDC and NHSS and then coupling with antibody solution for 4 hours. Finally, it can be blocked with bovine serum albumin solution. This process can efficiently and stably fix specific antibodies for intestinal disease markers on the surface of the fiber optic cone region, providing a reliable biometric interface for high-precision detection by the subsequent fiber optic ring laser system. Of course, other solutions or processing times can also be used, and this embodiment does not limit this.

[0042] Furthermore, the intestinal disease biomarker detection module 30 is also used to integrate the sensing probe of the functionalized tapered multimode fiber into the fiber ring laser system, which includes an erbium-doped fiber amplifier, an optical isolator, a polarization controller, an optical coupler, and a spectrometer. The laser wavelength drift is monitored in real time by the fiber ring laser system, and the laser wavelength drift is converted into the concentration of biomarkers for intestinal diseases. Intestinal disease detection results are generated based on the biomarker concentration.

[0043] It should be noted that the intestinal disease biomarker detection module integrates a functionalized tapered multimode fiber sensing probe into a fiber ring laser system (including an erbium-doped fiber amplifier, optical isolator, polarization controller, optical coupler, and high-precision spectrometer). It detects intestinal diseases by monitoring the laser wavelength drift in real time. Specifically, the fiber ring laser system monitors the laser wavelength drift in real time, converts the laser wavelength drift into biomarker concentrations, and generates intestinal disease detection results based on the biomarker concentrations.

[0044] Furthermore, the intestinal disease biomarker detection module 30 is also used to connect the sensing probe of the functionalized tapered multimode fiber to the fiber ring laser system, start the erbium-doped fiber amplifier and spectrometer in the fiber ring laser system, adjust the spectrometer to the predetermined observation range, until the spectrometer displays a stable laser oscillation peak. The sensing probe is immersed in a solution containing intestinal disease biomarkers, and the laser spectrum is continuously monitored. When the laser wavelength stabilizes due to the complete antigen-antibody binding reaction, the current laser spectrum is recorded. The concentration of the solution is changed to obtain the laser wavelength values ​​corresponding to different concentrations. The wavelength shift of the laser wavelength is measured to be quantifiable, and the wavelength shift is converted into a marker concentration based on a preset calibration curve. The intestinal disease detection result is generated based on the marker concentration.

[0045] Understandably, a fiber optic ring laser system is constructed using functionalized sensing probes for quantitative detection. First, the sensing fiber is connected to the fiber optic ring laser system, and the erbium-doped fiber amplifier and spectrometer are activated. The spectrometer is adjusted to a predetermined observation range until a stable laser oscillation peak is displayed. Then, the probe is immersed in a solution containing the target biomarker, and the laser spectrum is continuously monitored. When the laser wavelength stabilizes due to the complete antigen-antibody binding reaction, the spectrum is recorded. Next, the concentration of the target detection solution is changed to obtain the laser wavelength values ​​corresponding to different concentrations. The quantifiable wavelength shift of the laser wavelength is measured, and based on a preset calibration curve, the wavelength shift is converted into biomarker concentration. Finally, intestinal disease detection results are generated based on the biomarker concentration.

[0046] Furthermore, the intestinal disease biomarker detection module 30 is also used to monitor the quantifiable wavelength shift of the laser wavelength in the fiber ring laser system in real time through the spectrometer, and to obtain the preset calibration curve by mathematical fitting based on the known concentration of the standard sample and the corresponding wavelength shift. The wavelength drift is converted into a marker concentration based on the preset calibration curve. The intestinal disease status is determined based on the comparison between the marker concentration and a preset concentration threshold, and the intestinal disease detection result is output.

[0047] It should be understood that the intestinal disease biomarker detection module monitors the wavelength shift of the laser in the fiber ring laser system in real time using a high-precision spectrometer (e.g., range 0.1-10 nm). During the system development phase, mathematical fitting is performed based on the known concentration of standard samples and the corresponding wavelength shift. The relationship between biomarker concentration and wavelength shift is generally logarithmic, and a preset calibration curve is established in advance. In the actual detection process, the measured wavelength shift is substituted into this calibration curve to accurately convert it into biomarker concentration (e.g., calprotectin or carcinoembryonic antigen concentration), and the intestinal disease status (e.g., "low risk," "moderate risk," or "high risk") is automatically determined based on a preset concentration threshold (e.g., a positive cutoff of 50 ng / mL). Finally, a high-sensitivity output (detection limit 2.454 × 10⁻⁶) is provided. -5 The quantitative detection results of RIU enable non-invasive and rapid clinical diagnosis.

[0048] Furthermore, the intestinal disease biomarker detection module 30 is also used to linearly fit the wavelength drift and the environmental refractive index of the solution to obtain the preset calibration curve corresponding to the mapping relationship between the wavelength drift and the environmental refractive index; The detection limit of the intestinal disease detection device based on the tapered multimode fiber ring laser is obtained according to the preset calibration curve.

[0049] Understandably, a preset calibration curve can be established by linearly fitting the environmental refractive index change of the standard solution (e.g., the refractive index of solutions with different concentrations of intestinal disease biomarkers) to the measured laser wavelength drift. Subsequently, based on the slope of the calibration curve and the system noise level, the detection limit of the device is calculated. This value characterizes the minimum refractive index change that the system can reliably detect, and is used to verify whether the detection sensitivity meets the requirements for early clinical diagnosis.

[0050] Furthermore, the intestinal disease biomarker detection module 30 is also used for The detection limit is obtained by the following formula:

[0051]

[0052]

[0053]

[0054] in, To explore the limits, For quantitative resolution, For the refractive index sensitivity of the sensor, The standard deviations related to each noise factor, To amplify the noise, For spectral resolution, Temperature-induced drift To experimentally measure the full width at half maximum (FWHM) of the spectrum, For signal-to-noise ratio, This represents the resolution of the spectrometer.

[0055] It should be noted that the sensing principle of this embodiment is based on the two-mode interference refractive index sensing mechanism of tapered multimode optical fiber, and the refractive index change caused by the specific binding of antigens and antibodies on the optical fiber surface.

[0056] See Figure 2 , Figure 2 This is a schematic diagram of the structure of a tapered multimode optical fiber, as shown below. Figure 2 As shown, the diameter of its waist is typically between a few micrometers and tens of micrometers. When light is transmitted to the waist region, higher-order modes are excited due to core diameter mismatch, resulting in intermodal interference when the fiber exits the tapered region. During the tapering process of multimode fiber, the transmission mode in the tapered region evolves from core multimode to core single-mode, then to cladding multimode, and finally to cladding single-mode. By reasonably controlling the tapering diameter, the transmission mode in the tapered region can be maintained in the cladding dual-mode state, thereby realizing dual-mode interferometric sensing.

[0057] For tapered multimode fibers with two-mode interference, the position of the interference spectrum trough is determined by the following conditions:

[0058] in, The phase difference corresponding to the Nth interference valley. This represents the difference in propagation constants between the HE11 and HE12 modes. The length of the two-mode interference region. This is the difference in effective refractive index between the two modes. It refers to the wavelength corresponding to the position of the Nth trough in the interference spectrum.

[0059] Through derivation, the expression for the refractive index sensitivity of tapered multimode fiber can be obtained:

[0060]

[0061] in, To determine the refractive index sensitivity of tapered multimode fiber, It refers to the wavelength corresponding to the position of the Nth trough in the interference spectrum. For environmental refractive index, The group refractive index of the HE11 mode. For the HE12 mode group refractive index, For effective refractive index difference, The group refractive index.

[0062] The specific steps for fabricating tapered multimode optical fibers using the fused taper method are as follows: Step 1: Strip the bare fiber portions of the two single-mode fiber pigtails and the coatings at both ends of the multimode fiber, and clean the fiber cladding with alcohol; cut the end face with a fiber cleaver and fused the multimode fiber between the two single-mode fiber pigtails.

[0063] Step 2: Connect the connectors of the two single-mode fiber pigtails to the broadband light source and the spectrometer, respectively. Strip the coating layer from the middle section of the multimode fiber, clean it, and fix it between the two displacement stages of the tapered machine. Ignite the oxyhydrogen flame and cover it with a lid.

[0064] Step 3: Turn on the broadband light source and spectrometer, adjust the spectrometer parameters and mathematical calculation functions, and observe the fiber optic transmission spectrum.

[0065] Step 4: Start the tapering machine and tape the multimode fiber according to the preset parameters, while observing the changes in the transmission spectrum on the spectrometer. After tapering is completed, the spectrometer should display a series of interference peaks and valleys.

[0066] Step 5: Place the tapered area on the surface of the glass slide and fix the tapered area of ​​the optical fiber to the glass slide using UV-curing adhesive or other methods.

[0067] It should be noted that the above steps can all be implemented without relying on manual operation, through robots, robotic arms or various mobile intelligent devices, and this embodiment does not impose any restrictions on this.

[0068] See Figure 3 , Figure 3 A schematic diagram illustrating the simulation results of the refractive index sensitivity of a tapered multimode fiber, wherein... Figure 3 (a) is a simulation result of the effective refractive index difference between the two modes of a tapered multimode fiber and the tapered diameter, showing the relationship between the effective refractive index difference and the tapered diameter. Figure 3 (b) is a simulation result of the refractive index sensitivity of tapered multimode fiber near a refractive index of 1.33 and the tapered diameter, showing the relationship between refractive index sensitivity and tapered diameter. The refractive index sensitivity has an infinite discontinuity at G=0. When the tapered diameter is smaller than this value, the tapered region is cladding single-mode and cannot be used for refractive index sensing. When the tapered diameter is larger than this value, the refractive index sensitivity decreases with increasing diameter and may transition to cladding multimode. This embodiment achieves high-sensitivity dual-mode interferometric sensing by reasonably setting the tapered diameter.

[0069] See Figure 4 , Figure 4 This is a schematic diagram of a tapered multimode fiber ring laser sensor system, as shown below. Figure 4 As shown, the system includes: 1) Erbium-doped fiber amplifier (EDFA): Provides gain and excites laser light; 2) Optical isolator (ISO): Prevents back-propagation of light and suppresses reflection effects; 3) Polarization controller (PC): controls the direction of laser polarization; 4) Tapered multimode fiber probe: modulated by the external environment, making the laser wavelength dependent on the environment; 5) 10:90 Optical Coupler (OC): 10% of the energy is directed to the spectrometer, and 90% of the energy is retained in the resonant cavity; 6) OSA (Optical System Spectrometer): Observes and records laser spectra.

[0070] After the system was set up, PBS solution was added to the glass slide, the erbium-doped fiber amplifier and spectrometer were turned on, and the laser output spectrum was observed as follows. Figure 5 As shown, Figure 5 A schematic diagram of the output spectrum of a tapered multimode fiber ring laser is shown in the image. Figure 5 Compared with the interference peak of tapered multimode fiber, the full width at half maximum (FWHM) of the spectrum is significantly reduced after the introduction of fiber ring laser, which can achieve high-precision measurement.

[0071] This embodiment uses sucrose solutions of different concentrations for refractive index sensing tests. A series of sucrose solutions with varying concentrations were prepared, and their refractive indices were calibrated at room temperature using a high-precision refractometer. Subsequently, the aforementioned tapered multimode fiber ring laser system was used for testing. The specific steps are as follows: Step 1: Immerse the sensing probe in deionized water and record the initial laser wavelength; Step 2: Immerse the probe in sucrose solutions of different concentrations in sequence, and record the laser wavelength after stabilizing in each solution for 5 minutes; Step 3: Plot the laser wavelength shift and the solution refractive index on the same graph and perform linear fitting to obtain the relationship between the wavelength shift and the environmental refractive index.

[0072] Measurement results as follows Figure 6 As shown, Figure 6 The diagram shows the output spectrum of a tapered multimode fiber ring laser under different refractive indices. (See attached diagram) Figure 6 As the refractive index increases, the laser wavelength undergoes a redshift.

[0073] The linear fitting results are as follows Figure 7 As shown, Figure 7 This is a schematic diagram illustrating the linear fitting results between the peak wavelength of the output laser from a tapered multimode fiber ring laser and the ambient refractive index. (See attached diagram) Figure 7 The refractive index sensitivity was obtained as 706.4 nm / RIU, and the linear correlation coefficient R was [value missing]. 2 =0.999.

[0074] The detection limit (LoD) of a sensor can be expressed as:

[0075]

[0076]

[0077]

[0078] in, To explore the limits, For quantitative resolution, For the refractive index sensitivity of the sensor, The standard deviations related to each noise factor, To amplify the noise, For spectral resolution, Temperature-induced drift To experimentally measure the full width at half maximum (FWHM) of the spectrum, For signal-to-noise ratio, This represents the resolution of the spectrometer.

[0079] It should be noted that, For quantitative resolution, which is related to the system's noise level, the experimentally measured full width at half maximum (FWHM) of the spectrum was 0.02 nm, and the signal-to-noise ratio (SNR) was 52.4 dB. The spectrometer resolution was [not specified]. The drift due to temperature is 0.02 nm. It is approximately 10 -14 m, the detection limit can be calculated to be 2.454 × 10 m. -5 RIU.

[0080] In the specific implementation, taking the detection of calprotectin as an example, the functionalization process of tapered multimode optical fibers is illustrated. All reagents used are those already available in our laboratory. In practical applications, other reagents with the same function can be used as substitutes. The process is as follows: Figure 8 As shown, Figure 8 For a flowchart illustrating the functionalization process of tapered multimode optical fibers using calprotectin antibodies, see [link / reference]. Figure 8 The specific steps are as follows: Step 1, Surface cleaning: Immerse the probe in KOH solution for 1 hour, then rinse with deionized water.

[0081] Step 2, surface activation: Immerse the probe in silanized ethanol reagent for 4 hours to introduce carboxyl functional groups, and then wash with PBS solution.

[0082] Step 3, antibody fixation: Immerse the probe in a mixed solution of EDC and NHSS for 1 hour, and then immediately immerse the probe in a calprotectin antibody solution for 4 hours to couple the calprotectin antibody to the sensor surface.

[0083] Step 4, Blocking: After washing the probe with PBS solution, immerse it in BSA solution to block the remaining unbound carboxyl sites. Wash again with PBS solution to complete the functionalization.

[0084] After immobilizing calprotectin antibodies on the surface of tapered multimode optical fibers, they can be used for calprotectin detection. Multiple tapered multimode optical fibers functionalized with calprotectin antibodies were prepared using the same parameters and immersed in calprotectin solutions of different concentrations. The wavelength shift was measured. A curve was plotted with calprotectin concentration on the x-axis and wavelength shift on the y-axis. A logarithmic function was used to fit the curve, yielding the relationship between calprotectin concentration and wavelength shift. Based on this relationship, the concentration of calprotectin can be calculated after measuring the wavelength shift in actual measurements, thus achieving high-sensitivity and high-precision detection of calprotectin.

[0085] Compared with existing technologies, the advantages and innovations of this solution are as follows: 1. This solution aims to address the problems of cumbersome operation, labeling requirements, limited sensitivity, and limited detection accuracy of existing intestinal disease biomarker detection technologies (such as enzyme-linked immunosorbent assay (ELISA), immunofluorescence chromatography, etc.). Compared with traditional intestinal disease biomarker detection methods such as ELISA, immunofluorescence chromatography, and chemiluminescent immunoassay (CLIA), this solution has higher detection sensitivity, lower detection limit, faster response speed, and requires no labeling. It effectively overcomes the inherent defects of traditional immunoassay procedures, such as complexity, labeling dependence, and long processing time, providing a new technical approach for the early screening and rapid diagnosis of intestinal diseases.

[0086] 2. Innovatively, multimode fiber is used as the tapered substrate; within the tapered region, higher-order modes can be effectively excited and enhanced, resulting in a stronger evanescent field. This enhances the interaction with the analyte, achieving higher refractive index sensitivity and laying the physical foundation for high-sensitivity biosensing. 3. By combining the high-sensitivity evanescent field sensing characteristics of tapered multimode fiber with the narrow linewidth and high signal-to-noise ratio spectral output advantages of fiber ring laser, and by converting the broadband interference signal into a single laser peak, the full width at half maximum (FWHM) of the spectrum is significantly compressed. This fundamentally solves the problem of limited detection accuracy caused by the low spectral linewidth and low signal-to-noise ratio in direct spectral detection, and achieves biomolecule detection performance with a lower detection limit and higher detection accuracy.

[0087] This approach combines the enhanced evanescent field characteristics of tapered multimode fiber with the narrow linewidth output advantage of fiber ring lasers. First, tapered multimode fiber is fabricated using the fused taper method. Its tapered structure enhances the interaction between the evanescent field and the external environment, significantly improving detection sensitivity. Then, the surface of the fiber's tapered region is functionalized to immobilize specific antibodies against intestinal disease biomarkers, achieving highly selective recognition of the target biomarkers. Finally, functionalized probes are integrated into the fiber ring laser system. By converting biorecognition events into high-precision laser wavelength signals, the interference spectral linewidth is effectively compressed and the signal-to-noise ratio is improved, thereby significantly reducing the detection limit. This effective compression of the spectral linewidth and improvement of the signal-to-noise ratio enable high-precision, high-sensitivity, and rapid label-free detection of intestinal disease biomarkers. Compared with traditional medical detection techniques, this approach offers advantages such as label-free operation, rapid response, and ease of operation, providing reliable technical support for early screening and disease assessment of intestinal diseases.

[0088] It should be noted that, in this document, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Unless otherwise specified, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes that element.

[0089] The sequence numbers of the above embodiments of the present invention are for descriptive purposes only and do not represent the superiority or inferiority of the embodiments.

[0090] The above are merely preferred embodiments of the present invention and do not limit the scope of the patent. Any equivalent structural or procedural transformations made based on the description and drawings of the present invention, or direct or indirect applications in other related technical fields, are similarly included within the scope of patent protection of the present invention.

Claims

1. A device for detecting intestinal diseases based on a tapered multimode fiber ring laser, characterized in that, The intestinal disease detection device based on a tapered multimode fiber ring laser includes: a tapered multimode fiber fabrication module, a tapered multimode fiber functionalization module, and an intestinal disease biomarker detection module; wherein... The tapered multimode fiber fabrication module is used to fabricate tapered multimode fibers using the fused taper method; The tapered multimode fiber functionalization module is used to functionalize the surface of the tapered region of the tapered multimode fiber to fix specific antibodies for intestinal disease biomarkers. The intestinal disease biomarker detection module is used to integrate a functionalized sensing probe into a fiber optic ring laser system, detect the laser wavelength drift through the fiber optic ring laser system, and detect intestinal disease biomarkers based on the laser wavelength drift to obtain intestinal disease detection results.

2. The intestinal disease detection device based on a tapered multimode fiber ring laser as described in claim 1, characterized in that, The tapered multimode fiber fabrication module is also used to fusion splice multimode fiber between two single-mode fibers to construct fiber optic components; The coating layer of the multimode fiber midsegment of the optical fiber assembly is stripped and cleaned to generate a standard multimode fiber. The standard multimode optical fiber is fixed to the displacement stage of the tapered machine.

3. The intestinal disease detection device based on a tapered multimode fiber ring laser as described in claim 2, characterized in that, The tapered multimode fiber fabrication module is also used to control the temperature and stretching rate of the fiber heating zone, stretching the standard multimode fiber into a tapered structure, and ensuring that the waist diameter of the tapered multimode fiber is stable within a preset diameter range.

4. The intestinal disease detection device based on a tapered multimode fiber ring laser as described in claim 1, characterized in that, The tapered multimode fiber functionalization module is also used to sequentially perform surface cleaning, surface activation, coupling agent modification, antibody fixation and blocking treatment on the surface of the tapered region of the tapered multimode fiber, fix the specific antibodies of intestinal disease biomarkers on the surface of the tapered region of the fiber, and construct a biosensor interface.

5. The intestinal disease detection device based on a tapered multimode fiber ring laser as described in claim 4, characterized in that, The tapered multimode fiber functionalization module is also used to remove impurities from the surface of the tapered region of the tapered multimode fiber by cleaning with chemical reagents. Activating functional groups are introduced by activating reagents and then modified by coupling agents to form functionalized interfaces that can immobilize biomolecules. Specific antibodies for intestinal disease biomarkers were covalently immobilized on the surface of the fiber cone region, and non-specific sites were blocked with bovine serum albumin solution to complete the construction of the biosensor interface.

6. The intestinal disease detection device based on a tapered multimode fiber ring laser as described in claim 1, characterized in that, The intestinal disease biomarker detection module is also used to integrate the sensing probe of the functionalized tapered multimode fiber into the fiber ring laser system, which includes an erbium-doped fiber amplifier, an optical isolator, a polarization controller, an optical coupler, and a spectrometer. The laser wavelength drift is monitored in real time by the fiber ring laser system, and the laser wavelength drift is converted into the concentration of biomarkers for intestinal diseases. Intestinal disease detection results are generated based on the biomarker concentration.

7. The intestinal disease detection device based on a tapered multimode fiber ring laser as described in claim 6, characterized in that, The intestinal disease biomarker detection module is also used to connect the sensing probe of the functionalized tapered multimode fiber to the fiber ring laser system, start the erbium-doped fiber amplifier and spectrometer in the fiber ring laser system, adjust the spectrometer to the predetermined observation range, until the spectrometer displays a stable laser oscillation peak. The sensing probe is immersed in a solution containing intestinal disease biomarkers, and the laser spectrum is continuously monitored. When the laser wavelength stabilizes due to the complete antigen-antibody binding reaction, the current laser spectrum is recorded. The concentration of the solution is changed to obtain the laser wavelength values ​​corresponding to different concentrations. The wavelength shift of the laser wavelength is measured to be quantifiable, and the wavelength shift is converted into a marker concentration based on a preset calibration curve. The intestinal disease detection result is generated based on the marker concentration.

8. The intestinal disease detection device based on a tapered multimode fiber ring laser as described in claim 7, characterized in that, The intestinal disease biomarker detection module is also used to monitor the quantifiable wavelength shift of the laser wavelength in the fiber ring laser system in real time through the spectrometer, and to obtain the preset calibration curve by mathematical fitting based on the known concentration of the standard sample and the corresponding wavelength shift. The wavelength drift is converted into a marker concentration based on the preset calibration curve. The intestinal disease status is determined based on the comparison between the marker concentration and a preset concentration threshold, and the intestinal disease detection result is output.

9. The intestinal disease detection device based on a tapered multimode fiber ring laser as described in claim 8, characterized in that, The intestinal disease biomarker detection module is also used to linearly fit the wavelength drift and the environmental refractive index of the solution to obtain the preset calibration curve corresponding to the mapping relationship between the wavelength drift and the environmental refractive index; The detection limit of the intestinal disease detection device based on the tapered multimode fiber ring laser is obtained according to the preset calibration curve.

10. The intestinal disease detection device based on a tapered multimode fiber ring laser as described in claim 9, characterized in that, The intestinal disease biomarker detection module is also used to obtain the detection limit by the following formula: in, To explore the limits, For quantitative resolution, For the refractive index sensitivity of the sensor, The standard deviations related to each noise factor, To amplify the noise, For spectral resolution, Temperature-induced drift To experimentally measure the full width at half maximum (FWHM) of the spectrum, For signal-to-noise ratio, This represents the resolution of the spectrometer.

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