Multi-parameter optical fiber health monitoring device

Abstract

The invention provides a multi-parameter optical fiber health monitoring device. The device comprises a light source system, a light source conduction system, a sensing system, a sensing light conduction system and a spectrum processing system, the light source system can emit light signals of a single wavelength or a plurality of different wavelengths; the light source conduction system can transmit light signals, provide multi-channel light signal channels and realize random switching of the light signal channels; the sensing system comprises at least one optical fiber sensor, and one end of the optical fiber sensor acts under the action of a marker to cause the change of an optical signal; the sensing light conduction system can pass back a changed light signal and gate of a path; and the spectrum processing system can collect and process the returned optical signals to obtain spectrum data. According to the invention, multi-channel synchronous monitoring can be realized, a plurality of physiological and biochemical markers can be detected at the same time, and the detection efficiency is greatly improved; the method has high sensitivity and stability; the invention has a wide clinical application prospect.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biomedical engineering and optical sensing technology, in particular to a multi-parameter optical fiber health monitoring device. BACKGROUND

[0002] In the diagnosis and treatment of traumatic brain injury, stroke and other nervous system diseases, real-time monitoring of multiple key physiological and biochemical parameters is of great significance. The existing monitoring methods are mostly single-parameter, highly invasive, low sensitivity or lack of multi-channel integration capability, which is difficult to meet the needs of clinical dynamic monitoring. Therefore, there is an urgent need for an optical fiber health monitoring system that can realize multi-parameter simultaneous monitoring, has good flexibility and biocompatibility.

[0003] In the field of implantable sensing, quartz glass optical fibers have been tried for intracranial monitoring due to their small size and resistance to electromagnetic interference, but their technical route has inherent shortcomings. Traditional commercial optical fibers use quartz glass as the matrix, and their preparation techniques can be roughly divided into two categories: 1) surface modification type: the surface of the quartz optical fiber is first treated with hydroxylation and silanization, and then functional materials such as fluorescent molecules, quantum dots, gold / silver nanoparticles are fixed on the surface of the cladding layer through physical adsorption or chemical grafting. This method has many process steps, the functional layer is easy to peel off, the probe is difficult to reuse, and the sensing signal must rely on external analysis equipment such as spectrometer and photodetector, which makes the system complex and costly. 2) Microstructure type: one-dimensional periodic microstructures such as fiber Bragg gratings (FBG) are written inside the quartz optical fiber using femtosecond laser etching or photolithography, and sensing is achieved through the wavelength-selective reflection / transmission of the microstructure. This scheme avoids the problem of surface functional material peeling off, but the microstructure processing precision requirement is extremely high, the yield is low, and the cost is relatively high. Most importantly, the quartz glass fiber has strong rigidity and cannot be bent at a large angle, which can easily cause secondary damage to tissues and organs during intracranial monitoring.

[0004] In addition, in recent years, hydrogel materials are considered as ideal candidates to replace quartz due to high water content, adjustable modulus (1-100 kPa), excellent light transmittance (>95%, visible light band) and good biocompatibility. The existing hydrogel optical fibers mostly adopt a single-layer uniform structure, which cannot form a stable "core refractive index > cladding refractive index" total reflection condition, resulting in large transmission loss and serious signal attenuation; some studies try to introduce a "core-cladding" double-layer structure, and embed functional materials in the core or use the deformation of hydrogel to realize sensing. The existence of the optical fiber cladding not only makes the refractive index difference between the core and the cladding fixed, and the light transmits stably to produce total reflection. Moreover, the cladding can effectively protect the surface of the optical fiber from being polluted by humid gas and stains and being scratched by external force, and reduce the additional loss of optical fiber micro-bending. Therefore, it has important technical value and application prospect to develop a double-layer hydrogel optical fiber with stable total reflection condition (refractive index is precisely controlled through structure design) and excellent light transmission performance (low loss). SUMMARY

[0005] The present application aims to solve at least one of the above-mentioned problems in the prior art.

[0006] To achieve the above-mentioned purpose, the present application provides a multi-parameter optical fiber health monitoring device.

[0007] The multi-parameter optical fiber health monitoring device comprises a light source system, a light source transmission system, a sensing system, a sensing light transmission system and a spectrum processing system. The light source system can emit single-wavelength or multiple different wavelength light signals. The light source transmission system can transmit the light signals emitted by the light source system, and in the case of multiple different wavelengths emitted by the light source system, the light source transmission system can provide a multi-channel light signal path and realize arbitrary switching of the light signal path. The sensing system comprises at least one optical fiber sensor. The optical fiber sensor can receive the light signals transmitted by the light source transmission system. One end of the optical fiber sensor can be affected by a marker to cause an effect, thereby causing a change in the light signal. In the case of multiple optical fiber sensors, the optical fibers of the optical fiber sensors are independent of each other. The sensing light transmission system can return the changed light signals and can also switch the light signal path. The spectrum processing system can collect and process the returned light signals to obtain spectrum data.

[0008] Optionally, the light source system comprises a multi-wavelength laser, an LED, an ultra-continuous light source or a halogen lamp array. The multi-wavelength laser comprises a plurality of single-wavelength lasers.

[0009] Optionally, the light source transmission system is equipped with an M*N program-controlled optical switch, which is connected to the light source system through an optical and physical interface to complete the transmission of optical signals, wherein M and N are positive integers. The light source system is connected with the light source conducting system through M optical fibers, and connected with the sensing system through N optical fibers.

[0010] Optionally, the sensing system comprises at least one of a pH optical fiber sensor, a glucose optical fiber sensor, an intracranial pressure optical fiber sensor, a lactate sensing module, a dissolved oxygen sensing module, a temperature sensing module, a sodium ion sensing module, and a calcium ion sensing module.

[0011] Optionally, the pH optical fiber sensor comprises an optical fiber, and a hydrogel sensing layer polymerized on the end face of the optical fiber; wherein the hydrogel sensing layer comprises a functionalized hydrogel containing a pH fluorescent probe, and the pH fluorescent probe comprises a naphthalimide pH fluorescent probe with a structural formula of: ; or, The pH optical fiber sensor comprises a hydrogel optical fiber including an inner layer core and an outer layer cladding, and a pH fluorescent probe dispersed in the inner layer core; wherein The inner layer core is cured from a core monomer A, a core monomer B, a core monomer C, and a photoinitiator; the core monomer A comprises acrylamide, N-vinylpyrrolidone, or 2-hydroxyethyl methacrylamide, the core monomer B comprises polyethylene glycol diacrylate, and the core monomer C comprises hydroxyethyl methacrylate or comprises hydroxyethyl methacrylate and methyl methacrylate; the outer layer cladding is cured from a low refractive index PEGDA hydrogel and a photoinitiator, and has a refractive index lower than that of the inner layer core.

[0012] Optionally, the glucose optical fiber sensor comprises an optical fiber, and a glucose fluorescent sensing module immobilized on the end face of the optical fiber, wherein the glucose fluorescent sensing module is fixed in a hydrogel network by covalent reaction between a glucose fluorescent probe and epoxy groups in the hydrogel network through amino groups at the ends of the glucose fluorescent probe; the glucose fluorescent probe contains a boronic acid group and terminal amino groups, and has a structural formula of: .

[0013] Optionally, the intracranial pressure optical fiber sensor comprises a flexible optical pressure sensitive film, a sleeve, and an optical fiber; wherein the flexible optical pressure sensitive film is immobilized at one end of the sleeve, the other end of the sleeve is sleeved on the end of the optical fiber, and a closed cavity is formed among the three; the material of the flexible optical pressure sensitive film comprises a fluorescent dye and an elastomer material; the fluorescent dye comprises N, N-di (octadecyl) -pyrene-3, 4, 9, 10-tetracarboxylic acid bisimide.

[0014] Optionally, the optical fiber of the optical fiber sensor comprises a quartz optical fiber, a plastic optical fiber, a PDMS optical fiber, a hydrogel optical fiber, or a composite material thereof.

[0015] Optionally, the optical fiber is a double-layer hydrogel optical fiber, comprising an inner layer core and an outer layer cladding, wherein the inner layer core is cured by a core monomer A, a core monomer B, a core monomer C and a photoinitiator; the core monomer A comprises acrylamide, N-vinyl pyrrolidone or 2-hydroxyethyl methacrylamide, the core monomer B comprises polyethylene glycol diacrylate; the core monomer C comprises hydroxyethyl methacrylate or comprises hydroxyethyl methacrylate and methyl methacrylate; the outer layer cladding is cured by a low refractive index PEGDA hydrogel and a photoinitiator, and the refractive index is lower than that of the inner layer core.

[0016] Optionally, the device further comprises a data analysis system, and the control system can at least one of analyze, process and display data of the spectral data.

[0017] Compared with the prior art, the beneficial effects of the present application include at least one of the following: (1) The multi-channel synchronous monitoring of the present application can simultaneously detect multiple physiological and biochemical markers, greatly improving the detection efficiency.

[0018] (2) The present application has high sensitivity and stability. Through precise spectral analysis and light filtering technology, the system can maintain high accuracy under various environmental changes.

[0019] (3) The present application can perform real-time data processing and diagnosis. Through the cooperative work of advanced algorithms and hardware, reliable diagnosis results can be generated in real time, which has a wide clinical application prospect. Finally, the modular design makes the system have strong flexibility and scalability, which is convenient for later upgrading and individual customization.

[0020] (4) The pH hydrogel optical fiber sensor of the present application has excellent performance, high sensitivity, high stability and good biocompatibility. The sensing layer uses functionalized hydrogel containing pH fluorescent probes, which can realize fast, reversible and high-resolution fluorescence response in the physiological pH range (6.8-7.8); at the same time, the close combination of hydrogel and optical fiber structure ensures the stability and repeatability of signal transmission. The sensor is flexible and suitable for long-term implantation and dynamic monitoring in the body environment, is not affected by electromagnetic interference, and can be integrated with other fluorescent modules to realize multi-parameter synchronous detection, which has a wide application prospect.

[0021] (5) The glucose hydrogel optical fiber sensor of the present application has excellent performance, high sensitivity and good selectivity, and can realize stable and real-time detection of glucose concentration in complex physiological environment. The sensor structure is flexible and has good biocompatibility, does not depend on enzyme reaction, avoids the signal drift problem caused by enzyme inactivation; at the same time, it has good repeatability and can be integrated with other optical sensing modules to realize multi-parameter synchronous monitoring, which is suitable for long-term dynamic monitoring application in the body.

[0022] (6) The intracranial pressure sensor of this invention is a novel structure with excellent stability. Compared with traditional fiber optic pressure sensors that rely on micro-nano fabrication, this invention has a simple structure and a mild fabrication process. It does not require grating etching, vacuum coating, or precision microcavity fabrication. It can be fabricated simply by assembling ordinary multimode optical fiber and flexible fluorescent / reflective film, resulting in low manufacturing cost and high process repeatability. The probe diameter is less than 3 mm, and the flexible encapsulation material (such as PDMS, Ecoflex, or SEBS) has excellent biocompatibility and mechanical compliance, which can adapt to micro-deformation of brain tissue and reduce implantation trauma. The sensing signal is based on changes in light intensity or interference, and has high sensitivity, fast response, and anti-electromagnetic interference capabilities. The signal drift is small, and the stability is excellent. The device adopts a modular fiber bundle design, which can achieve reliable optical coupling and long-term monitoring. It also has the potential for mass production and single-use, providing a low-cost, flexible, and clinically applicable practical solution for dynamic intracranial pressure monitoring.

[0023] (7) This invention, by designing a double-layer structure with a core refractive index greater than that of the cladding, ensures that total internal reflection is met when light propagates in the optical fiber, effectively reducing light transmission loss and improving light transmission efficiency. The preparation method is simple and easy to implement, with mild process conditions, facilitating large-scale production. Furthermore, the selected hydrogel material has good biocompatibility and flexibility, making the double-layer hydrogel optical fiber biocompatible, flexible, and not easily brittle. Even if it breaks, it will not cause harm to organisms, making it suitable for sensitive detection of various parameters and long-term monitoring of the brain tissue microenvironment.

[0024] (8) The double-layer hydrogel optical fiber of the present invention has good compatibility and scalability, and can work stably in multi-channel systems. In addition, compared with traditional quartz optical fiber, the double-layer hydrogel optical fiber used in the present invention has the following significant advantages in multi-channel monitoring systems: good biocompatibility and flexibility, matching the mechanical properties of soft tissue, significantly reducing the risk of mechanical damage to sensitive areas such as brain tissue; it can realize the integration of light guiding and sensing functions: the hydrogel material can be directly doped with a variety of fluorescent probes (such as pH, glucose, ion probes, etc.) to realize the integration of sensing and transmission, which is conducive to integrating different functional modules in multi-channel structures and improving the system integration; the refractive index is adjustable and the transmission loss is low. By adjusting the refractive index difference between the core and cladding materials, the hydrogel optical fiber can achieve stable total internal reflection in the visible light band, supporting low-loss transmission under multi-wavelength excitation (such as 405 nm, 450 nm, 488 nm, etc.), meeting the needs of multi-wavelength parallel excitation in multi-channel systems; it is easy to couple with quartz optical fiber, etc.: the hydrogel optical fiber can be connected to the existing quartz optical fiber system through insertion, which is convenient for building a multi-channel, distributed optical fiber sensing network, taking into account both flexibility and system compatibility. Attached Figure Description

[0025] The above and other objects and / or features of the present invention will become clearer from the following description taken in conjunction with the accompanying drawings, in which: Figure 1 A schematic diagram of the multi-parameter fiber optic health monitoring device of the present invention is shown.

[0026] Figure 2 A schematic diagram of the fiber optic bundle inserted into the skull according to the present invention is shown.

[0027] Figure 3 A schematic diagram of the synthesis route of the naphthalimide pH fluorescent probe of the present invention is shown.

[0028] Figure 4 A schematic diagram of the detection mechanism of the pH fiber optic sensor of the present invention is shown.

[0029] Figure 5 The performance test diagram of the pH fiber optic sensor of the present invention is shown.

[0030] Figure 6 A schematic diagram of the synthesis route of the glucose fluorescent probe of the present invention is shown.

[0031] Figure 7 A schematic diagram of the detection mechanism of the glucose fiber optic sensor of the present invention is shown.

[0032] Figure 8 The performance test diagram of the glucose fiber optic sensor of the present invention is shown.

[0033] Figure 9 A schematic diagram of the synthesis route of the intracranial pressure fluorescent dye of the present invention is shown.

[0034] Figure 10 A schematic diagram of the intracranial pressure fiber optic sensor of the present invention is shown.

[0035] Figure 11 The performance test diagram of the intracranial pressure fiber optic sensor of the present invention is shown.

[0036] Figure 12 The monitoring mechanism and performance test results of the dissolved oxygen fiber optic sensor of the present invention are shown.

[0037] Figure 13 The monitoring mechanism and performance test results of the temperature sensor of the present invention are shown.

[0038] Explanation of key figure labels: 1-Light source system; 2-Light source conduction system; 3-Sensing system; 31-Flexible optical pressure-sensitive membrane; 32-Sheath; 33-Fiber optic cable; 34-Cavity; F-Intracranial pressure; 4-Sensing light transmission system; 5-Spectral processing system; 61-Data analysis unit, 62-Interaction unit, 63-Automation control unit. Detailed Implementation

[0039] The present invention will be described in detail below with reference to exemplary embodiments.

[0040] Exemplary Example 1 This exemplary embodiment provides a multi-parameter fiber optic health monitoring device. The health monitoring device of this invention can be a single-channel or multi-channel fiber optic monitoring system, and can be widely used for intraoperative and postoperative monitoring of neurological diseases such as traumatic brain injury, stroke, and epilepsy. It can also be applied to intensive care, personalized treatment, and drug screening research.

[0041] The device includes: a light source system, a light source conduction system, a sensing system, a sensing light conduction system, and a spectral processing system connected in sequence.

[0042] The light source system can emit light signals of a single wavelength or multiple different wavelengths.

[0043] When the light source system emits multiple different wavelengths, the light source transmission system can switch between multiple optical signal paths at will to isolate multiple optical signal paths of different wavelengths, making the optical signal paths independent of each other.

[0044] The sensing system includes at least one fiber optic sensor, which can change due to the action of a marker, such as pressure or specific physical or biochemical interaction with target molecules, thereby causing a change in the optical signal; when there are multiple fiber optic sensors, the optical fibers of the fiber optic sensors are independent of each other.

[0045] The sensing optical transmission system can transmit the changed optical signal back and also has the function of optical path switching control, that is, it can select the channel and select the optical path to be sensed to the spectrometer for acquisition.

[0046] The spectral processing system can collect and process the transmitted optical signals to obtain spectral data.

[0047] In this embodiment, the light source system may be a multi-wavelength laser, LED, supercontinuum light source, or halogen lamp array. As an example, the light source system can emit wavelengths in the range of 405–800 nm, but the invention is not limited to this, and the wavelength can be selected according to actual conditions.

[0048] This invention can achieve free switching, start / stop, and energy regulation of different wavelengths of the light source system through serial port, pulse, and other control methods.

[0049] Furthermore, the light source system may include a combination of multiple single-wavelength lasers, such as at least one of a 405nm laser, a 450nm laser, a 488nm laser, a 520nm laser, a 561nm laser, and a 637nm laser. However, the present invention is not limited thereto, and the specific wavelength and corresponding laser can be selected according to actual needs.

[0050] The laser of this invention can provide precise emission based on the response characteristics of different markers. The laser's frequency stability ensures the continuity and consistency of the output signal, with a spectral width typically within ±5nm, ensuring no spectral errors occur during measurement. Phase stability maintains the high coherence of the laser source, avoiding crosstalk between multi-channel signals and improving measurement accuracy. All laser sources undergo rigorous temperature control and feedback regulation to ensure stable wavelength and intensity within the operating temperature range (approximately 10℃–40℃), minimizing the impact of external environmental changes on signal output, thereby guaranteeing the accuracy and reliability of physiological and biochemical indicator detection.

[0051] The correspondence between some different markers and excitation wavelengths is as follows: Glucose: excitation wavelength 405 nm; maximum emission wavelength 490 nm; fluorescence amplitude is positively correlated with glucose concentration, increasing with increasing glucose concentration; pH: Excitation light 405 nm; Maximum emission wavelength 530 nm; Fluorescence amplitude is negatively correlated with pH, ​​decreasing as pH increases; Dissolved oxygen: excitation light 405 nm; maximum emission wavelength 645 nm; fluorescence amplitude is negatively correlated with oxygen concentration, decreasing as oxygen concentration increases; Temperature: Excitation wavelength 450 nm; Maximum emission wavelength 610 nm; Fluorescence amplitude is negatively correlated with temperature, decreasing as temperature increases; Intracranial pressure: excitation light 450 nm; maximum emission wavelength 635 nm; fluorescence amplitude is positively correlated with intracranial pressure, and the amplitude increases with increasing pressure concentration.

[0052] Lactic acid: excitation wavelength 405 nm; maximum emission wavelength 645 nm; fluorescence amplitude is positively correlated with lactic acid concentration, and the amplitude increases with increasing lactic acid concentration.

[0053] In this embodiment, the light source conduction system is equipped with an M*N programmable optical switch, which connects to the light source system via an optical physical interface to complete the conduction of optical signals. It can receive control signals from the automated control system via communication protocols such as serial ports, and uses time-division multiplexing technology to achieve arbitrary switching of multiple optical paths. The isolation of multiple optical signal paths of different wavelengths in the light source system ensures that the sensing excitation light source paths are independent of each other.

[0054] In this embodiment, the sensing system can also be called a fiber optic bundle sensing system, which is connected to the light source conduction system through N optical fibers.

[0055] The fiber optic bundle sensing system includes multiple different fiber optic sensors, with different sensing modules fixed at the end of each fiber. The fiber optic bundle sensing system can be used to monitor parameters such as pH, glucose, lactic acid, dissolved oxygen, temperature, intracranial pressure, sodium ions, and calcium ions.

[0056] The optical fibers in an optical fiber bundle sensing system can include silica optical fibers, plastic optical fibers, PDMS optical fibers, or composite materials thereof. Composite materials refer to optical fibers that are combined with other materials, such as silica-nanomaterial composites, PDMS-inorganic material composites, etc. The diameter of the optical fiber can range from 0.1 to 0.6 mm.

[0057] In this embodiment, the sensing system can also be called a fiber optic bundle sensing system, which is connected to the light source conduction system through multiple optical fibers.

[0058] The sensing system includes several independent fiber optic sensors that can be used to monitor parameters such as pH, glucose, lactic acid, dissolved oxygen, temperature, intracranial pressure, sodium ions, and calcium ions. As an example, different sensing modules can be mounted on the ends of the fiber optic sensors. Of course, the fiber optic sensors can also incorporate sensing probes, such as the pH sensor in Exemplary Example 4 where a pH fluorescent probe is dispersed within the inner fiber core.

[0059] The types of fiber optic sensors can include pH fiber optic sensors, glucose fiber optic sensors, intracranial pressure fiber optic sensors, lactate fiber optic sensors, dissolved oxygen fiber optic sensors, temperature fiber optic sensors, sodium ion fiber optic sensors, calcium ion fiber optic sensors, etc. Some or all of the fiber optic sensors of this invention can be commercially available sensors. The fiber optic sensors of this invention can be inserted into different locations according to actual needs. Taking TBI (traumatic brain injury) as an example, during intraoperative monitoring, they can be inserted into the lateral ventricle for monitoring to avoid affecting the surgical field. During postoperative monitoring, they can be inserted into the lesion site to monitor the dynamic changes in local microenvironment physiological and biochemical parameters.

[0060] It should be noted that the single optical fiber in the sensing system of this invention is itself the excitation fiber and the receiving fiber, and there is no need to add an additional receiving fiber, so the size of the end face can be reduced.

[0061] The measured physical and biochemical indicators are transmitted through an optical (chemical) sensing unit (i.e., a sensing module) mounted on the sensing end, acting on the optical fiber to transmit light waves, thereby modulating the characteristic parameters of the light waves. The modulation methods include: 1) Intensity modulation (intensity parameter): The fluorescence / colorimetric probe generates emission intensity changes under specific wavelength excitation, and the amplitude of these changes is quantitatively related to the concentration of the target indicator. The system directly extracts and analyzes the intensity changes through a spectrometer.

[0062] 2) Wavelength modulation (spectral drift): Holographic grating-type or refractive index-sensitive hydrogels undergo structural expansion / contraction under changes in ion concentration or pH, resulting in a shift in Bragg diffraction peaks or absorption peaks. The system extracts this shift amount through peak detection and algorithm decoupling.

[0063] 3) Frequency / phase modulation: For physiological parameters that require long-term high-precision monitoring, the phase of the light wave or the frequency of the interference fringes can be modulated by an interferometric fiber optic sensing structure, and the system can extract the signal through demodulation algorithms (Fourier transform or phase unwrapping).

[0064] 4) Polarization state modulation: If polarization-maintaining fiber or liquid-core fiber is used, some sensitive materials may cause changes in the polarization direction of light waves due to stress or refractive index anisotropy. The system can extract this parameter through a polarization demodulation unit (such as a polarization beam splitter or photodetector array).

[0065] This invention primarily utilizes intensity modulation and wavelength drift modulation, achieving highly sensitive collaborative monitoring of multiple parameters through fluorescence signals and holographic peak shifts. For example, it can simultaneously employ light intensity and wavelength modulation for three sensors: glucose, pH, and calcium ions. Furthermore, the system architecture is compatible and can be extended to modulation and demodulation of parameters such as frequency, phase, or polarization according to clinical needs, thus providing a technical foundation for future high-precision extended applications.

[0066] The detection mode of this invention can be "cerebrospinal fluid contact monitoring," or it can be contact detection of other parts of the human body or other organisms. Taking "cerebrospinal fluid contact monitoring" as an example, an optical fiber bundle is inserted into the lateral ventricle through minimally invasive means to fully contact the cerebrospinal fluid. Utilizing the dynamic exchange characteristics of the cerebrospinal fluid in the ventricular circulation, pH and Ca²⁺ are captured in real time. Na Changes in multiple physiological and biochemical indicators, such as glucose, dissolved oxygen, lactate, temperature, and ICP, are monitored. Specifically, fluorescent probes, hydrogel holographic gratings, or ion recognition materials mounted on the sensing module interact specifically with target molecules in the cerebrospinal fluid (CSF), causing signal modulation such as changes in light intensity or spectral peak shifts. This signal is then transmitted back to the host computer via optical fiber for interpretation. Since CSF reflects the metabolic and pathological state of the entire brain environment, especially in cases of brain injury, ischemia-hypoxia, and abnormal intracranial pressure, its biomarker levels are highly correlated with pathological changes in the lesion area. Therefore, reliable lesion information can be obtained without directly inserting a probe into the lesion. Clearly, this method avoids direct damage to the lesion tissue and indirectly achieves dynamic tracking of the lesion's functional status through multi-channel, multi-parameter collaborative monitoring.

[0067] In this embodiment, the fiber optic bundle sensing system further includes a filter to filter out excitation background light and irrelevant spectral components, retaining only the excitation spectral signal corresponding to the target physiological and biochemical indicators. The filter ensures that only light signals of specific wavelengths can pass through, reducing interference and improving signal purity and signal-to-noise ratio.

[0068] In this embodiment, the sensing optical transmission system is equipped with an N*1 programmable optical switch, which connects to the sensing system via an optical physical interface to transmit optical signals. It can receive control signals from the automated control system via communication protocols such as serial ports, and uses time-division multiplexing technology to achieve arbitrary switching of multiple optical paths. The sensing optical transmission system physically isolates multiple different optical paths of the fiber optic bundle sensing system and can integrate multiple optical paths into a single optical signal output port for signal analysis by the spectral processing system.

[0069] It should be noted that: in this invention, one optical fiber is both the excitation fiber and the receiving fiber, and there is no need to add an additional receiving fiber, thus reducing the size of the end face.

[0070] During data acquisition, this invention can quickly poll eight channels through time-division multiplexing via an automated program, completing a full cycle in 2–3 seconds. No “sequential order” needs to be set. This unordered design ensures the system’s versatility and flexibility, enabling the acquisition of multi-parameter collaborative monitoring data at the same speed and stability in different clinical scenarios, thereby avoiding limitations caused by arrangement rules or priority settings.

[0071] In this embodiment, the fiber optic bundle sensing system further includes a filter to filter out excitation background light and irrelevant spectral components, retaining only the excitation spectral signal corresponding to the target physiological and biochemical indicators. The filter ensures that only light signals of specific wavelengths can pass through, reducing interference and improving signal purity and signal-to-noise ratio.

[0072] In this embodiment, the spectral processing system includes a dispersive element, which realizes the spectral splitting of the optical signal and can convert the optical signal into a quantifiable digital signal through a photoelectric conversion device. Furthermore, it can control the trigger time, integration time, and other data through serial port, pulse, and other control methods to acquire spectral data for subsequent data analysis.

[0073] Exemplary Example 2 Based on Exemplary Example 1, the apparatus further includes a data analysis system.

[0074] The data analysis system can receive spectral data acquired and filtered by a spectrometer in real time through a standard data interface (such as USB, serial port or Ethernet), and perform at least one of the following: analysis, diagnosis, interaction and processing.

[0075] As an alternative to this invention, the core computing components of the data analysis system can be controlled using a combination architecture of a microcontroller, CPU, and GPU or NPU. The CPU is responsible for system task scheduling, channel management, serial communication, and basic signal preprocessing; the GPU or NPU is used to accelerate the operation of large-scale spectral decoupling, feature extraction, and artificial intelligence diagnostic algorithms. With this architecture, the system can complete quasi-simultaneous analysis of eight channels of data within a complete acquisition cycle of 2–3 seconds, and output results for pH, Ca²⁺, and other parameters on a millisecond to second timescale. Na The system provides diagnostic and predictive results for multiple parameters, including glucose, dissolved oxygen, lactate, temperature, and ICP. The collaborative working mode of CPU+GPU / NPU not only ensures high parallel processing capabilities in complex computing scenarios but also allows for flexible access to data from different channels based on clinical needs, forming real-time diagnostic and treatment support through multi-indicator fusion. Optionally, the control system of this invention can run on existing general-purpose computing platforms.

[0076] The data analysis system may include a data analysis unit, an interaction unit, and an automation control unit.

[0077] The data analysis unit integrates artificial intelligence algorithms to achieve multi-parameter data fusion, pattern recognition, and clinical early warning. It includes a data parsing module, a neural network analysis module, and an analysis result output module. The data parsing module preprocesses the signal transmitted from the spectrometer using filtering and other methods, then calculates the biomarker content through peak finding and wavelength analysis. Specifically, the peak finding algorithm uses a traversal approach, scanning spectral data within a given wavelength range to directly find the maximum value as the peak. The user pre-sets a wavelength range, and the algorithm traverses each data point within that range to find the maximum signal intensity. The wavelength corresponding to this maximum value is the peak position in the spectrum. This method is simple and efficient, quickly identifying peak positions in spectral data and serving as the basis for subsequent physiological and biochemical indicator analysis. Through this traversal approach, the system can extract the peak values ​​of relevant biomarkers in real time, ensuring the speed and accuracy of the diagnostic process. The neural network analysis module performs multimodal data, trend prediction, and disease diagnosis, fusing multimodal data and using a trained neural network model for trend prediction and disease diagnosis.

[0078] The interactive unit allows for parameter setting and monitoring data display of the data acquisition system through a user-friendly interface. The interactive module may include a display module and a command input module.

[0079] The automation control unit can connect to the light source system, light transmission system, sensor light transmission system, and signal acquisition system via communication protocols such as serial port and pulse. Based on the settings for automatically starting and stopping the light source channel and intensity, the automation control unit can control the optical path via light switches and control signal acquisition, thereby controlling the overall system's control logic and synchronizing the data acquisition timing of the entire system.

[0080] The automated control unit may include an instruction parsing module, and laser control module, optical switch control module, and acquisition control module, all connected to this module. The instruction parsing module is connected to the instruction input module of the interaction unit and can parse the input instructions. The laser control module is connected to the control module of the light source unit. The optical switch control module is connected to the control submodules connected to the light source conduction unit and the sensing light conduction unit, respectively. The acquisition control module is connected to the acquisition control module of the signal processing system, thereby achieving control of different systems.

[0081] Exemplary Example 3 Based on exemplary embodiment 1 or 2, the optical fiber of the optical fiber sensor may be wholly or partially double-layer hydrogel optical fiber. Partially double-layer hydrogel optical fiber means that a conventional optical fiber (such as a quartz optical fiber) is connected to the double-layer hydrogel optical fiber. This connection can be achieved through a heat-shrink tubing, for example, by inserting a quartz optical fiber into the hydrogel optical fiber, and then using the heat-shrink tubing to shrink and wrap the connection between the two parts.

[0082] The double-layer hydrogel optical fiber includes an inner core and an outer cladding.

[0083] In this embodiment, the inner core is formed by curing core monomer A, core monomer B, core monomer C, and a photoinitiator. Based on a total mass fraction of 100 parts, core monomer A comprises 20-50 parts, core monomer B comprises 10-40 parts, and core monomer C comprises 10-60 parts. The photoinitiator accounts for 0.2%-1% of the total mass of core monomers A, B, and C. When the photoinitiator content is <0.2%, the double bond conversion rate is <85%, and the mechanical strength decreases; when the photoinitiator content is >1%, residual photoinitiator will reduce cell viability.

[0084] The core monomer A includes acrylamide (AAm), N-vinylpyrrolidone (NVP), or 2-hydroxyethylmethacrylamide (HEMAAm). When core monomer A is AAM, its mass fraction is 20-50 parts. When AAM < 20 parts, the polymerization rate decreases, and the core strength is < 80 kPa. When AAM > 50 parts, brittleness increases, and the elongation at break is < 150%. When core monomer A is NVP, its mass fraction is 30-50 parts. When core monomer A is HEMAAm, its mass fraction is 20-50 parts. NVP and HEMAAm maintain high hydrophilicity and biocompatibility.

[0085] The fiber core monomer B includes polyethylene glycol diacrylate (PEGDA). When Mn < 400, the crosslinking density is too high, leading to an increase in the fiber core refractive index but a modulus > 300 kPa and decreased flexibility; when Mn > 1000, the refractive index < 1.45, resulting in insufficient Δn. Mn is the number-average molecular weight, and raw materials within the range of 400-1000 can be used.

[0086] The core monomer C includes hydroxyethyl methacrylate (HEMA), or a mixture of hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA). When the core monomer C is HEMA, its mass fraction is 10-60 parts; when it is a mixture of HEMA and MMA, the mass fraction of MMA is 5-15 parts, with the remainder being HEMA. 5-15 parts of MMA can increase the refractive index, but it needs to be controlled to ≤15 parts to maintain hydrophilicity. If it exceeds 15 parts, hydrophobicity increases, and the water content becomes less than 40%, affecting subsequent performance.

[0087] Photoinitiators may include: 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone IRGACURE 2959 or water-soluble phenyl-2,4,6-trimethylbenzoyl lithium phosphinate LAP, etc.

[0088] In this embodiment, the water content of the inner fiber core is 40-55% to meet the total internal reflection requirements. The inner fiber core achieves a water content of 40%-55% through a combination of acrylamide and other hydrophilic monomers, satisfying both flexibility and hydrophilicity requirements.

[0089] In this embodiment, the outer cladding is formed by curing a low-refractive-index PEGDA hydrogel and a photoinitiator, with a refractive index lower than that of the inner fiber core. The mass ratio of PEGDA hydrogel to photoinitiator is 400~100:1. Unless otherwise specified, all solvents used in the hydrogel optical fiber are ultrapure water. The photoinitiator can be the same as those described above.

[0090] In this embodiment, the PEGDA in the outer cladding layer can form a network structure with high cross-linking density, which restricts water molecule penetration, maintains low refractive index and good mechanical protection.

[0091] In this embodiment, the inner fiber core (high refractive index layer) has a refractive index of 1.46~1.48, a water content of 40~55%, a tensile modulus of 80~300 kPa, and an optical loss ≤0.2 dB cm⁻¹. -1 The core diameter can be 50~600μm. If it is <50 µm, the probe loading is insufficient, resulting in a signal-to-background ratio <3. When it is >600 μm, the central oxygen inhibition is severe, resulting in an uncured soft core.

[0092] The outer cladding (low refractive index layer) has a refractive index of 1.38–1.40 and a swelling rate in water of <15%. The cladding thickness can be 20–100 µm. When it is <20 µm, mechanical protection is insufficient, the lateral tearing force is <0.1 N, and the protection of the core layer is lost. When it is >100 µm, the overall stiffness of the optical fiber increases, which can easily induce an increase in inflammatory response.

[0093] The core refractive index of the bilayer hydrogel fiber is greater than that of the cladding, satisfying the total internal reflection condition and making it suitable for high-sensitivity fluorescence sensing. The refractive index Δn is 0.06~0.10. If Δn < 0.06, the numerical aperture NA < 0.3 and the bending loss > 1 dB (bending radius 5 mm). If Δn > 0.10, the cladding water content < 25%, which will reduce the probe diffusion coefficient.

[0094] In this embodiment, the method for preparing the bilayer hydrogel optical fiber includes: S1. Prepare a core prepolymer solution by mixing core monomers A, B, and C with a photoinitiator. Inject the core prepolymer solution into a capillary mold and cure it by irradiation with ultraviolet light (200~400 nm). After photocrosslinking and curing, remove the prepolymer from the mold to form the core. The curing time can be 1~8 min. For core diameters of 50~600 µm, simply change the capillary mold. When the diameter is >400 µm, add 0.05 wt% hydroquinone (HQ) to the prepolymer solution to inhibit oxygen inhibition and ensure sufficient central curing.

[0095] Alternatively, a certain amount of water (such as high-purity water) can be added during the preparation of the fiber core prepolymer solution, so that the fiber core prepolymer solution contains a certain amount of water, and ultimately the water content of the inner core of the hydrogel fiber is 40~55%, which satisfies the total internal reflection adjustment.

[0096] Alternatively, water may not be added during the preparation of the fiber core prepolymer solution. In the subsequent step S2, the hydrogel fiber core will absorb water, ultimately resulting in a water content of 40-55% in the inner core of the hydrogel optical fiber.

[0097] S2. The obtained hydrogel fiber core is placed in the hydrogel precursor solution (i.e., the outer prepolymer solution), and its surface is treated using an immersion pulling process. After the pulling process, the hydrogel fiber core is straightened and hung vertically, and then irradiated under a UV lamp again to solidify the hydrogel precursor solution on the surface of the hydrogel fiber core, forming a cladding layer with a thickness of 20~100 µm, thus obtaining a hydrogel optical fiber. The hydrogel optical fiber consists of a core and a cladding layer, has a double-layer structure, and is cylindrical. The pulling speed is 10~50 mm·min. -1 The viscosity is controlled in conjunction with the viscosity, which ranges from 80 to 300 mPa·s. The PEGDA content in the outer prepolymer solution is 40% wt% to 60 wt%, which helps to form a network structure with high cross-linking density, restricts water molecule penetration, keeps the water content below 15%, maintains a low refractive index, and provides good mechanical protection. The mass ratio of PEGDA hydrogel to photoinitiator is 400 to 100:1. The solvent in the solution is water, such as ultrapure water. Unless otherwise specified, ultrapure water can be used as the solvent in hydrogel optical fibers.

[0098] Alternatively, the hydrogel core can be left to stand in the solution before the lifting operation, for example, for 10 seconds, to aid wetting and degassing.

[0099] To better understand the above preparation method, a specific preparation example is provided below.

[0100] (1) Core preparation: The core prepolymer solution was prepared according to the following mass percentages: Aam: 40%, PEGDA (Mn = 700): 30%, HEMA: 30%, photoinitiator (Irgacure 2959): 0.5%. Among them, the 0.5% photoinitiator refers to 0.5 wt% of the total mass of the three monomers.

[0101] The above solution was injected into a capillary mold with an inner diameter of 0.2 mm, irradiated with 365 nm ultraviolet light for 3 min to cure, and then removed to form a fiber core.

[0102] (2) Cladding preparation: The fiber core is immersed in the outer prepolymer solution (PEGDA 1000, 50 wt%, containing 0.5% photoinitiator), and its surface is treated by dip-coating process. Then it is hung and irradiated with 365 nm ultraviolet light for 1 min 30 s to form a cladding layer with a thickness of about 0.03 mm.

[0103] Exemplary Example 4 Based on exemplary embodiment 1, the pH sensor includes a hydrogel optical fiber and a hydrogel sensing layer polymerized on the end face of the hydrogel optical fiber; wherein, the hydrogel sensing layer includes a functionalized hydrogel containing a pH fluorescent probe.

[0104] The pH fluorescent probe includes a naphthimide pH fluorescent probe with the following structural formula: .

[0105] The pH sensor will be explained further below.

[0106] I. pH fluorescent probe.

[0107] The pH fluorescent probe of this invention is based on a naphthalimide-containing fluorescent probe. After modification with an acrylyl group, the fluorescent probe can be copolymerized into an acrylamide hydrogel network and fixed to the tip of an optical fiber. This probe exhibits reversible fluorescence intensity changes under acidic and alkaline environments, enabling real-time dynamic monitoring of the pH of the brain tissue microenvironment.

[0108] In this embodiment, Figure 3 A synthetic route diagram for the naphthalimide pH fluorescent probe is shown.

[0109] The preparation method of the naphthimide pH fluorescent detector includes the following steps: S1, take Figure 3 Compound 1 (4-bromo-1,8-naphthalenedicarboxylic anhydride) was dissolved in anhydrous ethanol, and 4-aminobutyric acid was added. The reaction was carried out under inert gas protection with stirring. After the reaction was completed, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography to obtain the following... Figure 3 Solid compound 2 is shown.

[0110] Furthermore, the molar ratio of 4-bromo-1,8-naphthalenedicarboxylic anhydride to 4-aminobutyric acid is 1:1 to 1:3.

[0111] Furthermore, anhydrous ethanol is used as a solvent, but isopropanol, DMF (N,N-dimethylformamide), DMSO (dimethyl sulfoxide), NMP (N-methylpyrrolidone), etc., can also be used.

[0112] The amount of anhydrous ethanol used is determined by dissolving the raw material; for example, 1g of raw material corresponds to 10~20 mL of solvent.

[0113] S2. Dissolve solid compound 2 in ethylene glycol monomethyl ether, add N-methylpiperazine, and stir the reaction under the protection of an inert gas. After the reaction is complete, pour the reaction solution into ice water to form a yellow precipitate. Filter, wash and dry to obtain the product NBD-COOH.

[0114] Furthermore, ethylene glycol monomethyl ether is used as a solvent, but DMF, DMSO, NMP, etc., can also be used instead. The amount of solvent used is determined according to the raw material being dissolved; for example, 1 g of the raw material can correspond to 10-400 mL of solvent.

[0115] Furthermore, N-methylpiperazine acts as both a reactant and an acid-binding agent, and is at least twice the amount of solid compound 2, and may be in appropriate excess, such as 2.5 times, 3 times, etc.

[0116] S3. Dissolve NBD-COOH in anhydrous DMF, then add N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) sequentially, stirring to promote the reaction. Add organic bases (triethylamine, N,N-diisopropylethylamine) and N-(3-aminopropyl)methacrylamide hydrochloride, and continue the reaction. After the reaction is complete, pour the reaction solution into ice water to form a yellow precipitate. The precipitate is purified by silica gel column chromatography to obtain the product NBD-AC, which is a naphthalimide pH fluorescent probe.

[0117] Furthermore, N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) can be replaced with N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)hexafluorophosphate urea (HATU).

[0118] The dosage of NHS is 0.8–1.2 eq of the raw material NBD-COOH; the dosage of EDC·HCl is 1.0–1.5 eq, that is, the dosage of EDC·HCl is 1.0–1.5 eq of NBD-COOH. Furthermore, the ratio of NHS to EDC·HCl can be 1:1. When HATU is selected, its dosage is also 1.0–1.5 eq of NBD-COOH.

[0119] Furthermore, the organic base includes triethylamine or N,N-diisopropylethylamine.

[0120] Furthermore, the molar ratio of the organic base to N-(3-aminopropyl)methacrylamide hydrochloride is the same as that of the raw material NBD-COOH: 1–1.5 eq. That is, the amount of organic base used is 1–1.5 eq of NBD-COOH, and the amount of N-(3-aminopropyl)methacrylamide hydrochloride used is also 1–1.5 eq of NBD-COOH. The purpose of the organic base is to release N-(3-aminopropyl)methacrylamide hydrochloride from the hydrochloride.

[0121] As a specific example of the present invention, the pH fluorescent probe synthesis process may include: Compound 1 (1.0 g, 3.2 mmol, 4-bromo-1,8-naphthalenedicarboxylic anhydride) was dissolved in 30 mL of anhydrous ethanol, and 0.37 g, approximately 3.7 mmol, of 4-aminobutyric acid was added. The reaction was carried out under nitrogen protection and stirred at room temperature for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation, and the residue was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 20:1, v / v) to give compound 2 as a yellow solid, in approximately 70% yield.

[0122] Compound 2 (0.50 g, approximately 1.5 mmol) was dissolved in 20 mL of ethylene glycol monomethyl ether, and N-methylpiperazine (0.3 mL, approximately 3 mmol) was added. The mixture was stirred at room temperature for 6 hours under nitrogen protection, and the reaction was monitored by thin-layer chromatography (TLC). After the reaction was complete, the reaction solution was poured into 100 mL of ice water, resulting in a yellow precipitate. The precipitate was filtered, washed with water, and dried to give the product NBD-COOH, in approximately 82% yield.

[0123] NBD-COOH (0.30 g, 1.0 mmol) was dissolved in 15 mL of anhydrous DMF, and N-hydroxysuccinimide (NHS, 0.14 g, 1.2 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl, 0.23 g, 1.2 mmol) were added sequentially. After stirring at room temperature for 2 hours, triethylamine (0.11 g, approximately 1.1 mmol) and N-(3-aminopropyl)methacrylamide hydrochloride (0.18 g, approximately 1.1 mmol) were added, and the reaction was continued for 12 hours. After the reaction was completed, the reaction solution was poured into 100 mL of ice water, and a yellow precipitate was formed. The precipitate was purified by silica gel column chromatography (eluent: dichloromethane / methanol = 10:1, v / v) to obtain the target product NBD-AC in approximately 75% yield.

[0124] II. pH sensor.

[0125] In this embodiment, the pH sensor is also called a pH hydrogel sensor, and its optical fiber is the double-layer hydrogel optical fiber in exemplary embodiment 3.

[0126] In this embodiment, the pH hydrogel sensor is an end-cap type sensor, comprising: a double-layer hydrogel optical fiber as shown in Exemplary Example 3, and a hydrogel sensing layer polymerized on the end face of the hydrogel optical fiber; wherein, the hydrogel sensing layer is formed by copolymerizing a pH fluorescent probe into an acrylamide-based hydrogel network after modification with an acryloyl group. The hydrogel sensing layer includes a functionalized hydrogel containing a pH fluorescent probe.

[0127] Figure 4 A schematic diagram of the detection mechanism of the pH fiber optic sensor of the present invention is shown. Figure 5 The performance test graphs of the pH fiber optic sensor of the present invention are shown, wherein (a) the fluorescence change of the pH sensor in the pH range of 6-8; (b) the relationship between the fluorescence intensity of the pH sensor at 530 nm and pH; and (c) the reversibility of the pH sensor. The pH sensor of the present invention has an excitation wavelength of 405 nm, and its emitted fluorescence is in the range of 450-750 nm. The fluorescence intensity of the sensor at the maximum emission wavelength of 530 nm decreases with increasing pH. The fluorescence intensity at 530 nm shows a linear relationship with pH, ​​with a coefficient of 0.98, indicating that the sensor has good continuous monitoring capability for temperature display. Figure 4 and Figure 5 The results shown are those of a sensor prepared by dip-coating.

[0128] The fabrication methods for pH hydrogel sensors (end-cap type sensors) include: (1) A pregel solution was prepared using a naphthalimide pH fluorescent probe, acrylamide, N,N-dimethylacrylamide, polyethylene glycol diacrylate and a photoinitiator.

[0129] The mass ratio of acrylamide, N,N-dimethylacrylamide, and polyethylene glycol diacrylate is 15-40:5-15:0.5-2. Specifically, a pregel solution is prepared using acrylamide (15%-40%, w / v), N,N-dimethylacrylamide (5%-15%, w / v), and polyethylene glycol diacrylate (0.5%-2%, w / v), where w / v is mass / volume, and the corresponding unit is g / mL. For example, 1 mL of pregel solution contains 0.15-0.4 g of acrylamide (i.e., 150-400 mg). The solvent is water, such as high-purity water. The three components work synergistically through their mass-volume ratios to achieve the flexibility and cross-linking stability of the hydrogel. Polyethylene glycol diacrylate is the cross-linking agent and is used in the lowest amount, while acrylamide is the main monomer and is used in the highest amount.

[0130] The pregel solution contains 0.01%–0.1% (w / v) of the naphthalimide pH fluorescent probe NBD-AC, for example, 0.1–1 mg of NBD-AC per 1 mL of pregel solution.

[0131] Photoinitiators may include IRGACURE 2959, LAP, etc., and the mass of the photoinitiator is 0.2% to 0.8% of the total mass of the monomer. For example, each 1 mL of pregel solution contains 0.4-4.6 mg of LAP or IRGACURE 2959.

[0132] The pregel solution contains acrylamide monomers such as acrylamide and N,N-dimethylacrylamide, while the pH fluorescent probe has been modified with acryloyl groups. It can form covalent bonds through free radical polymerization, thereby immobilizing the probe in the hydrogel network.

[0133] (2) Based on the pregel solution, the present invention can prepare a pH hydrogel fiber optic sensor using an immersion-pulling method. Specifically, it includes: vertically immersing the end of the hydrogel fiber into the pregel solution, and uniformly pulling the fiber at a speed of 0.1-5 mm / s to coat the end with a uniform liquid film. Immediately irradiate the end face with ultraviolet light for 30-60 s to polymerize the liquid film into a hydrogel. The ultraviolet light wavelength is 200-400 nm, for example, 365 nm ultraviolet light. Then, place the end of the hydrogel fiber in deionized water, changing the water multiple times to remove unreacted monomers and unfixed probe molecules, thus obtaining the fiber optic pH sensor.

[0134] This method enables the formation of a hydrogel sensing cap, with a thickness of tens to hundreds of micrometers, chemically bonded to the fiber optic cable at the fiber end face. The resulting sensing layer is relatively thick and exhibits good mechanical strength.

[0135] In this embodiment, the pH hydrogel sensor is an end-face thin-film sensor, which includes: a double-layer hydrogel optical fiber as in exemplary embodiment 3, and a hydrogel sensing layer polymerized on the end face of the hydrogel optical fiber; wherein, the hydrogel sensing layer includes a functionalized hydrogel containing a pH fluorescent probe.

[0136] The fabrication methods for pH hydrogel sensors (end-face thin-film type sensors) include: (1) A pregel solution is prepared using the naphthalimide pH fluorescent probe, acrylamide, N,N-dimethylacrylamide, polyethylene glycol diacrylate, and a photoinitiator. This step can be the same as step (1) of preparing the pregel in Exemplary Example 4.

[0137] (2) Based on the pregel solution, the present invention can prepare hydrogel fiber pH sensors using a drop-coating method. Specifically, the hydrogel fiber is horizontally fixed, and 0.5-20 µL of pregel solution is taken using a micropipette and directly drop-coated onto the clean end face of the fiber. The end face is immediately irradiated with 365 nm ultraviolet light (200~400 nm ultraviolet light is also acceptable) for 30-60 s, causing the droplet to polymerize into a hydrogel film. The interface is bonded by free radical-free radical covalent bonds, with an adhesion strength >200 kPa. Then, the end of the hydrogel fiber is placed in deionized water, and the water is changed several times to remove unreacted monomers and unfixed probe molecules. The present invention utilizes the characteristic that the hydrogel material itself contains unreacted double bonds or can be excited to generate free radicals, so that the newly added prepolymer solution can undergo an in-situ polymerization reaction with the fiber end face, thereby achieving high-strength chemical integration.

[0138] This method enables the formation of ultrathin sensing films with a thickness of 10–100 µm on the end face of optical fibers. The film formation is uniform, requires fewer reagents, and the thin film results in a faster sensor response.

[0139] Exemplary Example 5 Based on Exemplary Example 1, the entire core of the pH sensor is itself the sensing material, which is a bilayer hydrogel optical fiber, including an inner core and an outer cladding. The bilayer hydrogel optical fiber can be largely the same as that in Exemplary Example 3, except that the pH fluorescent probe is dispersed in the inner core. The pH fluorescent probe can be the same as that in Exemplary Example 4.

[0140] In this embodiment, a monolithic functional fiber optic sensor can be prepared by a blending method. The preparation process is largely the same as that for bilayer hydrogel fiber optics, but the key difference is that a certain amount of pH fluorescent probe (NBD-AC) is directly dispersed in the fiber core solution (0.1~0.5 mM). Specifically, the preparation method of the pH fiber optic sensor includes: (1) Core preparation This step is largely the same as step S1 in the bilayer hydrogel optical fiber preparation method of Exemplary Example 3, except that a naphthalimide pH fluorescent probe is added to the fiber core prepolymer solution. Specifically: A fiber core monomer A, fiber core monomer B, fiber core monomer C, and a photoinitiator were formulated into a fiber core prepolymer solution.

[0141] A 0.1–0.5 mM NBD-AC pregel solution was obtained by adding a naphthalimide pH fluorescent probe to the fiber core prepolymer solution and mixing it thoroughly. Alternatively, the naphthalimide pH fluorescent probe can be prepared into a NBD-AC solution of the target concentration using an aqueous solution of DMSO. For example, a 1 mM NBD-AC solution can be prepared with a 5% DMSO aqueous solution and then added to the fiber core prepolymer solution to obtain a 0.1–0.5 mM NBD-AC pregel solution.

[0142] The mixed solution is injected into a capillary mold and cured by ultraviolet light (200~400 nm), i.e., photocrosslinking and curing. After curing, the core is removed from the mold. The curing time can be 1~8 min. The core diameter can be adjusted within the range of 50~600 µm by changing the capillary mold; when the diameter is >400 µm, 0.05 wt% hydroquinone (HQ) needs to be added to the prepolymer solution to inhibit oxygen inhibition and ensure sufficient central curing.

[0143] (2) Preparation of the coating This step can be the same as step S2 in the bilayer hydrogel optical fiber preparation method in Exemplary Example 3.

[0144] This invention achieves uniform fixation of functional probes within the entire hydrogel fiber core through three steps: "bulk copolymerization - whole-segment probe loading - coaxial coating".

[0145] Exemplary Example 6 Based on Exemplary Example 1, the glucose sensor includes: an optical fiber, and a glucose fluorescence sensing module fixed on the end face of the optical fiber.

[0146] The glucose fluorescence sensing module can be formed by introducing a glucose fluorescent probe into the hydrogel network through a covalent reaction between the amino group at its end and the epoxy group in the hydrogel network.

[0147] The glucose fluorescent probe contains a boric acid group and a terminal amino group, and its structural formula is shown below: .

[0148] Figure 7 A schematic diagram of the detection mechanism of the glucose fiber optic sensor of the present invention is shown. Figure 8 The performance test graphs of the glucose fiber optic sensor of the present invention are shown, wherein (a) the fluorescence spectrum of the glucose sensor changes in the 0-10 mM glucose range; (b) the fitting relationship between the fluorescence intensity of the glucose sensor at 490 nm and the glucose concentration; (c) the reversibility of the glucose sensor; (d) the selectivity of the glucose sensor to different interfering substances; (e) the pH stability of the glucose sensor; and (f) the temperature stability of the glucose sensor. The glucose sensor of the present invention has an excitation wavelength of 405 nm, emits fluorescence in the range of 450-650 nm, and has a maximum emission wavelength of 490 nm. The fluorescence intensity of the sensor increases with increasing glucose concentration; the fluorescence intensity at 490 nm shows a linear relationship with glucose concentration, with a linearity coefficient of 0.99; the sensor exhibits good continuous monitoring capability for glucose, and its fluorescence is not affected by other substances in the cerebrospinal fluid, pH, or temperature.

[0149] The glucose sensor will be further explained below.

[0150] I. Glucose fluorescent probe.

[0151] The glucose fluorescent probe contains boric acid groups and terminal amino groups. The probe can specifically bind to the cis-diol structure on the glucose molecule, resulting in changes in fluorescence intensity or lifetime.

[0152] As an application example, this probe is introduced into the hydrogel network and fixed to the end face of an optical fiber after a covalent reaction between its terminal amino group and the epoxy group of the hydrogel layer, enabling real-time monitoring of glucose concentration in cerebrospinal fluid or interstitial fluid.

[0153] Methods for preparing glucose fluorescent probes include: (1) Dissolve 1-[9,10-bis(bromomethyl)-2-anthrayl]acetone in the first solvent, add N-Boc-butanediamine, and then stir the reaction under an inert gas atmosphere. After cooling the reaction solution, pour it into ice water to precipitate the solid. Filter, wash and purify by silica gel column chromatography to obtain the first intermediate compound. (2) Dissolve the first intermediate compound in the second solvent, add p-2-bromomethylphenylboronic acid ester, and then heat to the target temperature under an inert gas atmosphere and stir the reaction. After the reaction is completed, cool and remove the solvent by rotary evaporation. Separate the residue by column chromatography to obtain the second intermediate compound. (3) The second intermediate compound was dissolved in a tert-butyl protecting group hydrolysis solution and stirred at room temperature to remove the tert-butyl protecting group. The reaction solution was concentrated under reduced pressure and the residue was purified by column chromatography to obtain a glucose fluorescent probe.

[0154] Further, in step (1), the molar ratio of N-Boc-butanediamine to 1-[9,10-bis(bromomethyl)-2-anthrayl]acetone is greater than or equal to 2, for example 2.5, 3, etc.

[0155] Further, in step (1), the first solvent includes anhydrous DMF, tetrahydrofuran, dichloromethane, acetonitrile, dichloroethane, chloroform, or 1,4-dioxane.

[0156] Furthermore, in step (1), an acid-binding agent may be added to promote the reaction. The acid-binding agent includes at least one of potassium carbonate, sodium carbonate, triethylamine, and N,N-diisopropylethylamine.

[0157] Furthermore, the target temperature in step (2) is 50~70℃.

[0158] Further, in step (2), the second solvent includes anhydrous acetonitrile, tetrahydrofuran, DMF, dichloromethane, acetonitrile, dichloroethane, chloroform, or 1,4-dioxane.

[0159] Furthermore, in step (2), the molar ratio of 2-bromomethylphenylboronic acid ester to the first intermediate compound is greater than or equal to 2, for example, 2.5, 3, etc.

[0160] Furthermore, in step (3), an acid-binding agent may be added to promote the reaction. The acid-binding agent includes at least one of potassium carbonate, sodium carbonate, triethylamine, and N,N-diisopropylethylamine.

[0161] Further, in step (3), the tert-butyl protecting group hydrolysis solution includes: a dichloromethane solution of trifluoroacetic acid, a tetrahydrofuran solution of trifluoroacetic acid, or a hydrogen chloride-1,4-dioxane / ethyl acetate / methanol system.

[0162] Figure 6 The synthetic route for the glucose fluorescent probe is shown, specifically including: A1, as follows Figure 6 Raw material 1 (1-[9,10-bis(bromomethyl)-2-anthrayl]acetone) was dissolved in anhydrous DMF, and N-Boc-butanediamine (i.e., Figure 6The raw material 2) was reacted with potassium carbonate, and then stirred under an inert gas atmosphere. After cooling the reaction solution, it was poured into ice water to precipitate the solid. The solid was filtered, washed, and purified by silica gel column chromatography to obtain the first intermediate compound 3.

[0163] In step A1, anhydrous DMF is used as a solvent, but it can also be replaced by solvents such as tetrahydrofuran, dichloromethane, acetonitrile, dichloroethane, chloroform, and 1,4-dioxane.

[0164] In step A1, the molar ratio of N-Boc-butanediamine to raw material 1 is at least 2, for example, 2.5, 3, 3.5, etc.

[0165] In step A1, potassium carbonate acts as an acid-binding agent to promote the reaction. This step can also be performed without potassium carbonate, although it will take longer. Potassium carbonate can also be replaced by sodium carbonate, triethylamine, N,N-diisopropylethylamine, etc.

[0166] A2. Dissolve the first intermediate compound 3 in anhydrous acetonitrile, and add p-2-bromomethylphenylboronic acid ester (i.e., Figure 6 The raw material 4) and potassium carbonate were reacted and heated to the target temperature under an inert gas atmosphere with stirring. After the reaction was completed, the mixture was cooled, the solvent was removed by rotary evaporation, and the residue was separated by column chromatography to obtain the second intermediate compound (i.e. Figure 6 (Substances labeled in 5).

[0167] In step A2, anhydrous acetonitrile is used as a solvent, but it can also be replaced by solvents such as tetrahydrofuran, DMF, dichloromethane, acetonitrile, dichloroethane, chloroform, and 1,4-dioxane.

[0168] In step A2, the molar ratio of 2-bromomethylphenylboronic acid ester to the first intermediate compound is at least 2, for example, 2.5, 3, 3.5, etc.

[0169] In step A2, potassium carbonate acts as an acid-binding agent to promote the reaction. This step can also be performed without potassium carbonate, although it will take longer. Potassium carbonate can also be replaced by sodium carbonate, triethylamine, N,N-diisopropylethylamine, etc.

[0170] A3, the second intermediate compound (i.e. Figure 6 The substance labeled in step 5 was dissolved in a solution of trifluoroacetic acid in dichloromethane or tetrahydrofuran. The mixture was stirred at room temperature to remove the tert-butyl protecting group. The reaction solution was concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the glucose fluorescent probe ACDBA. The reaction principle is that the tert-butyl protecting group hydrolyzes under acidic conditions. The volume ratio of trifluoroacetic acid to dichloromethane is 1:2 to 1:5, and the volume ratio of trifluoroacetic acid to tetrahydrofuran is 1:2 to 1:5.

[0171] In step A3, the protecting group can also be removed using the hydrogen chloride-1,4-dioxane / ethyl acetate / methanol system.

[0172] As a specific example of the present invention, the synthesis process may include: Starting material 1 (1-[9,10-bis(bromomethyl)-2-anthrayl]acetone) (1.0 g, 4 mmol) was dissolved in 40 mL of anhydrous DMF, and N-Boc-butanediamine (2 eq) and potassium carbonate (3 eq) were added. The reaction mixture was stirred at 80 °C for 12 hours under a nitrogen atmosphere. After cooling, the reaction solution was poured into 200 mL of ice water, and a solid precipitated. The solid was filtered, washed with water, and purified by silica gel column chromatography to give compound 3 in approximately 70% yield.

[0173] Compound 3 (0.50 g, 1 mmol) was dissolved in 30 mL of anhydrous acetonitrile, and 2-bromomethylphenylboronic acid ester (2.2 eq) and potassium carbonate (3 eq) were added. The mixture was heated to 60 °C under a nitrogen atmosphere and stirred for 24 hours. After the reaction was completed, the mixture was cooled, the solvent was removed by rotary evaporation, and the residue was separated by column chromatography to give compound 5 in approximately 55% yield.

[0174] Compound 5 was dissolved in 30 mL of a trifluoroacetic acid solution in dichloromethane (trifluoroacetic acid to dichloromethane volume ratio 1:3), and stirred at room temperature for 2 hours to remove the tert-butyl protecting group. The reaction solution was concentrated under reduced pressure, and the residue was purified by column chromatography to give the final product ACDBA in approximately 80% yield.

[0175] II. Glucose fluorescence sensing module.

[0176] The glucose fluorescence sensing module is formed by immobilizing the glucose fluorescence probe through a covalent reaction between the amino group at its end and the epoxy group in the hydrogel network.

[0177] Furthermore, the hydrogel network is equipped with epoxy groups by adding glycidyl methacrylate (GMA) during the preparation process.

[0178] The preparation method of the glucose fluorescence sensing module includes: dissolving the above-mentioned glucose fluorescence probe and triethylamine in dimethyl sulfoxide to obtain a precursor solution of the sensing material; immersing a hydrogel layer containing epoxy groups in the precursor solution to allow the amino groups of the glucose fluorescence probe to undergo a covalent grafting reaction with the epoxy groups of the hydrogel; then removing excess solution and washing with water to obtain the glucose fluorescence sensing module.

[0179] Furthermore, the hydrogel layer is prepared by the following method: A pregel solution was prepared using acrylamide, N,N-dimethylacrylamide, polyethylene glycol diacrylate, glycidyl methacrylate, and a photoinitiator. The mass ratio of acrylamide, N,N-dimethylacrylamide, and polyethylene glycol diacrylate was 15-40:5-15:0.5-2. Specifically, a pregel solution is prepared using acrylamide (15% - 40%, w / v), N,N-dimethylacrylamide (5% - 15%, w / v), polyethylene glycol diacrylate (0.5% - 2%, w / v), and a photoinitiator. The photoinitiator is 0.2% to 0.8% of the total mass of the hydrogel layer monomers (i.e., the four monomers mentioned above). w / v is mass / volume, and the corresponding unit is g / mL. For example, 1 mL of pregel solution contains 0.15-0.4 g of acrylamide (i.e., 150-400 mg). The solvent is water, such as high-purity water. The three components work synergistically through their mass-volume ratios to achieve the flexibility and cross-linking stability of the hydrogel. Polyethylene glycol diacrylate is the cross-linking agent and is used in the lowest amount. Acrylamide is the main monomer and is used in the highest amount. Photoinitiators may include IRGACURE 2959, LAP, etc., for example, 0.4 mg-4.6 mg LAP or IRGACURE 2959 per 1 mL of pregel solution.

[0180] A pregel solution was dropped onto the film, a glass slide was placed on it, and polymerization was carried out under ultraviolet light; then the polymerized hydrogel layer was washed and dried.

[0181] Furthermore, the film may include an aluminized polyester film. The glass slide may include a silanized glass slide.

[0182] As an example of the present invention, the preparation process of the glucose fluorescence sensing module includes: A pregel solution was prepared using acrylamide (15% - 40%, w / v), N,N-dimethylacrylamide (5% - 15%, w / v), polyethylene glycol diacrylate (0.5% - 2%, w / v), glycidyl methacrylate (0.5% - 5%, w / v), and a photoinitiator. The photoinitiator accounted for 0.2% to 0.8% of the total mass of the hydrogel layer monomers, and the solvent in the solution was water, such as ultrapure water.

[0183] A glucose fluorescent probe (ACDBA) was dissolved at 0.1–1 mg / mL, and triethylamine was dissolved at 1–2 molar amounts in dimethyl sulfoxide to obtain a precursor solution for the sensing material. Triethylamine acts as both a catalyst to activate the nucleophilicity of amino groups and an acid-binding agent to neutralize trace amounts of hydroxyl groups generated in the reaction. A 1–2 molar amount ensures sufficient covalent grafting of the probe while avoiding excessive residue that could affect biocompatibility. Specifically, a 1–2 molar amount of triethylamine (e.g., 1 molar amount) can completely neutralize the trace products generated in the reaction while activating most amino groups, ensuring a grafting efficiency ≥80% (meeting the fluorescence signal intensity requirements). If the amount of triethylamine exceeds 2 times, the excessive alkalinity may lead to non-specific hydrolysis of epoxy groups in the hydrogel (prematurely consuming epoxy groups, thus reducing probe grafting sites) or residual triethylamine may be difficult to completely remove by washing (excessive organic base can irritate in vivo tissues and is detrimental to biocompatibility).

[0184] A pre-gel solution was dropped onto an aluminized polyester film, a silanized glass slide was placed on it, and polymerization was carried out under ultraviolet light. The polymerized hydrogel layer was then washed and dried, and subsequently immersed in a precursor solution for 2 hours. During this process, the amino groups at the ends of the probe molecules underwent a ring-opening reaction with the epoxy groups in the hydrogel network, achieving covalent grafting of the probe. Excess solution was then wiped off, and the sample was placed in deionized water and washed repeatedly to remove any uncovalently fixed glucose sensing material, resulting in a glucose fluorescence photochemical sensing module, i.e., a glucose fluorescence sensing module.

[0185] By mounting the sensing module onto the tip of an optical fiber, a fiber optic photochemical glucose sensor can be obtained.

[0186] As another example of the present invention, the preparation process of the glucose fluorescence sensing module includes: the above-mentioned example of glucose fluorescence probe synthesis, and the above-mentioned example of glucose fluorescence sensing module preparation.

[0187] III. Glucose fiber optic sensor.

[0188] The glucose fiber optic sensor includes: an optical fiber and a glucose fluorescence sensing module fixed on the end face of the optical fiber.

[0189] (1) Optical fibers can be quartz optical fibers, plastic optical fibers, PDMS optical fibers or their composite materials. Among them, composite materials refer to optical fibers that are combined with other materials, such as quartz-nanomaterial composite materials, PDMS-inorganic material composite optical fibers, etc.

[0190] The glucose fluorescence sensing module can be mounted on conventional optical fibers using either physical bonding (e.g., using biocompatible adhesives) or chemical bonding. For example, a biocompatible medical adhesive (such as PEG-based UV-curable adhesive or silicone rubber sealant) can be used to tightly bond the glucose fluorescence sensing module to the fiber end face, followed by curing at room temperature for 1-2 hours, or irradiation with 365 nm ultraviolet light for 30-60 seconds (if using UV-curable adhesive) to achieve physical bonding. Alternatively, a silane coupling agent can be used to mediate the bonding. First, the conventional fiber end face is silanized (e.g., using 3-aminopropyltriethoxysilane) to introduce amino groups. Then, the epoxy groups on the sensing module surface react with the amino groups on the fiber end face in a ring-opening reaction, achieving chemical bonding. This method offers high bonding strength and is suitable for scenarios requiring extremely high stability (e.g., long-term implantation).

[0191] Using the above-mentioned fixation method, the bonding strength between the sensing module and the optical fiber can reach >150 kPa (conventional optical fiber-adhesive system), meeting the mechanical stability requirements for long-term implantation in vivo or in vitro testing.

[0192] (2) The optical fiber is the double-layer hydrogel optical fiber mentioned above, and the glucose optical fiber sensor is a double-layer hydrogel optical fiber sensor.

[0193] For bilayer hydrogel optical fibers, due to their similar materials, integrated integration is easier. This invention utilizes the similarity of hydrogel materials to directly contact the sensing module with the end face of the bilayer hydrogel optical fiber. Through the swelling-fusion effect of the hydrogel interface, under slight pressure (5~10 kPa) for 10~20 minutes, hydrogen bonds or physical entanglement are formed at the interface, achieving integrated integration. To further enhance stability, unreacted double bonds remaining in the hydrogel optical fiber and sensing module (such as the double bonds of acrylamide and polyethylene glycol diacrylate in the pre-gel) can be used. After bonding the end faces, irradiation with ultraviolet light (365 nm) for 30~60 seconds initiates free radical cross-linking, achieving chemical bonding. This method requires no additional reagents, is simple to operate, and has high bonding strength (the cross-linking effect can be optimized by adjusting the residual amount of photoinitiator).

[0194] Using the above-mentioned fixation method, the bonding strength between the sensing module and the optical fiber can reach >200 kPa (hydrogel optical fiber-swelling fusion system), which meets the mechanical stability requirements for long-term implantation in vivo or in vitro detection.

[0195] Exemplary Example 7 Based on Exemplary Example 1, the intracranial pressure sensor includes: a flexible optical pressure-sensitive membrane, a sheath, and an optical fiber; wherein, the flexible optical pressure-sensitive membrane is fixed to one end of the sheath, the other end of the sheath is sleeved on the end of the optical fiber, and a sealed cavity is formed between the three.

[0196] The intracranial pressure sensor will be explained further below.

[0197] I. Flexible optical pressure-sensitive membrane The flexible optical pressure-sensitive film includes an elastomer material and a fluorescent dye doped in the elastomer material.

[0198] In this embodiment, the mass ratio of the elastomer material to the fluorescent dye is 400:1 to 100:1, for example, 380:1, 300:1, 200:1, 150:1, 110:1, etc.

[0199] In this embodiment, the thickness of the flexible optical pressure-sensitive film is 100~200 μm, such as 110, 150, 180 μm, etc.

[0200] In this embodiment, the fluorescent dye comprises N,N-bis(octadecyl)-perylene-3,4,9,10-tetracarboxylic acid diimine, with the following structural formula: .

[0201] In this embodiment, the elastomer material includes Ecoflex elastomer.

[0202] In this embodiment, the synthetic route for N,N-bis(octadecyl)-perylene-3,4,9,10-tetracarboxylic acid diimine is as follows: Figure 9 As shown, its specific preparation process includes: (1) Mix perylene-3,4,9,10-tetracarboxylic acid dianhydride, n-octadecylamine and imidazole, reflux, and cool to room temperature to obtain a reaction mixture.

[0203] (2) Disperse the reaction mixture in a polar solvent and add a solution that can form a salt with imidazole, stir, filter to obtain a solid, wash, dry, and obtain N,N-bis(octadecyl)-perylene-3,4,9,10-tetracarboxylic acid diimine (PDI).

[0204] Further, in step (1), the molar ratio of perylene-3,4,9,10-tetracarboxylic dianhydride to n-octadecylamine is at least 1:2 (n-octadecylamine can be in excess). It should be noted that at least 1:2 means that n-octadecylamine should be ≥2 in the ratio, such as 1:2.5, 1:3, etc. Imidazole is used as a solvent, and there is no specific requirement for the amount used; it only needs to be able to dissolve perylene-3,4,9,10-tetracarboxylic dianhydride and n-octadecylamine.

[0205] The reflux temperature is the boiling point of imidazole (°C), and the reflux time is sufficient for complete reaction. Alternatively, the reflux time can be determined by thin-layer chromatography to confirm the completeness of the reaction.

[0206] Furthermore, in step (2), the polar solvent may include polar solvents such as ethanol, methanol, acetonitrile, and isopropanol, for example, ethanol.

[0207] The solution that can form a salt with imidazole should be in excess to ensure that the imidazole is removed. Solutions that can form a salt with imidazole include: HCl solution, sodium bisulfate, trifluoroacetic acid, etc.

[0208] The drying process may include vacuum drying, for example, vacuum drying at room temperature to 110°C. Furthermore, in cases where the properties of the substance are uncertain, drying at temperatures below 60°C may be used to minimize the risk of deterioration.

[0209] As a specific example of the present invention, the preparation process may include: adding perylene-3,4,9,10-tetracarboxylic acid dianhydride (0.784 g, 2 mmol), n-octadecylamine (1.078 g, 4 mmol), and imidazole (4 g) to a 100 mL round-bottom flask, refluxing at 140 °C for 3 hours, cooling to room temperature, dispersing the reaction mixture in 100 mL of ethanol, adding 300 mL of 2M HCl, stirring overnight, filtering the resulting solid, thoroughly washing with distilled water, and drying the collected solid under vacuum at 100 °C to finally obtain N,N-bis(octadecyl)-perylene-3,4,9,10-tetracarboxylic acid diimine (PDI).

[0210] In this embodiment, the method for preparing the flexible optical pressure-sensitive film includes: A. Dissolve the fluorescent dye in a solvent, then mix it evenly with the elastomer material, remove the solvent and air bubbles, and obtain the intermediate product; B. Spin-coating and drying the intermediate product yields a flexible optical pressure sensing film with uniform thickness.

[0211] In this embodiment, in step A, the fluorescent dye and the elastomer material are used.

[0212] Solvents may include dichloromethane.

[0213] Methods for removing solvents and bubbles may include vacuuming.

[0214] In this embodiment, spin coating and drying in step B are conventional methods in the art, which are clear to those skilled in the art, and will not be described in detail here.

[0215] II. Intracranial pressure fiber optic sensor.

[0216] like Figure 10 As shown, the sensor may include a flexible optical pressure-sensitive membrane 31, a sleeve 32, and an optical fiber 33. Figure 10In this context, F represents intracranial pressure.

[0217] The membrane is encapsulated at the end of the sleeve 32 and coupled to the optical fiber 33. Specifically, a flexible optical pressure-sensitive membrane 31 is fixed to one end of the sleeve 32, and the other end of the sleeve 32 is fixed to the end of the optical fiber 33, forming a sealed cavity 34 between the three. Local pressure changes will cause the membrane to deform, thereby changing the fluorescence signal and realizing real-time monitoring of intracranial pressure.

[0218] In this embodiment, the flexible optical pressure-sensitive membrane 31 is the same as that in exemplary embodiment 1 or 2.

[0219] In this embodiment, the sleeve 32 includes polyethylene sleeve, polytetrafluoroethylene, polyimide, silicone rubber, PVC, polyurethane, etc. The inner diameter of the sleeve 32 is 1-3 mm.

[0220] In this embodiment, the fixation between the flexible optical pressure-sensitive membrane 31 and the sleeve 32 can be achieved through encapsulation. The fixation between the optical fiber 33 and the sleeve 32 can be achieved through biocompatible adhesive.

[0221] In this embodiment, the optical fiber can be a quartz optical fiber, a plastic optical fiber, a PDMS optical fiber, a hydrogel optical fiber, or a composite material thereof. Composite materials refer to optical fibers that are combined with other materials, such as quartz-nanomaterial composites, PDMS-inorganic material composites, etc.

[0222] In this embodiment, the optical fiber is the double-layer hydrogel optical fiber described in Exemplary Embodiment 3 above.

[0223] Figure 11 The performance test results of the intracranial pressure fiber optic sensor are shown in the following figures: (a) The fluorescence spectrum of the intracranial pressure sensor changes under different pressure environments; (b) The fitting relationship between the fluorescence intensity of the intracranial pressure sensor at 575 nm and temperature; (c) The reversibility of the intracranial pressure sensor; (d) The selectivity of the intracranial pressure sensor to different interfering substances; (e) The pH stability of the intracranial pressure sensor; and (f) The temperature stability of the intracranial pressure sensor. The intracranial pressure fiber optic sensor of this invention has an excitation wavelength of 450 nm, and its emitted fluorescence is in the range of 500-850 nm, with a maximum emission wavelength of 635 nm. The fluorescence intensity of the sensor increases with increasing external pressure. The fluorescence intensity at 635 nm exhibits a non-linear relationship with temperature, with a coefficient of 0.99. This sensor demonstrates excellent continuous monitoring capability for temperature display, and its fluorescence is unaffected by other substances in the cerebrospinal fluid or temperature interference.

[0224] In this embodiment, the height of the cavity 34 can be between 0.5 and 2 mm.

[0225] To better understand the above exemplary embodiments, the multi-parameter fiber optic health monitoring device will be further described below with reference to specific examples.

[0226] Figure 1 A schematic diagram of the structure of the multi-channel fiber optic monitoring device for intracranial physiological monitoring and the multi-parameter fiber optic health monitoring device of the present invention is shown.

[0227] The device is used for multi-parameter dynamic monitoring of intracranial brain tissue. Figure 2 The diagram illustrates the insertion of the optical fiber bundle into the cranium according to the present invention. The probe tip is preferably inserted into the ventricle, ventricular duct, or subarachnoid space, with an insertion depth ≤ 20 mm. In cortical injury monitoring scenarios, it can be inserted 3–10 mm deep into the cortical lesion area. For deep lesions (such as the basal ganglia, thalamus, and brainstem), the probe can be designed with a maximum insertion depth of less than 30 mm. A soft pad (such as a silicone gasket or cartilage sheet) is added between the probe and the skull to buffer pressure and limit probe displacement. The eight optical fibers of the present invention enter the lateral ventricle in a bundled manner, with their end faces entirely encased in a porous, flexible, biocompatible material. This structure ensures that cerebrospinal fluid can uniformly penetrate and fully contact the sensing modules at each fiber end face, enabling real-time monitoring of multiple indicators, while avoiding direct damage to brain tissue from the rigid ends of the optical fibers, ensuring the safety and long-term stability of the implantation.

[0228] like Figure 1 As shown, the device includes: a light source system 1, a light source transmission system 2, a sensing system 3, a sensing light transmission system 4, a spectral processing system 5, and a data analysis system connected in sequence.

[0229] like Figure 1 As shown, the light source system of this invention includes multiple lasers and adjustable laser intensity (0–100mW). Specifically, the light source system 1 includes six lasers: a 405nm laser, a 450nm laser, a 488nm laser, a 520nm laser, a 561nm laser, and a 637nm laser. These six wavelength lasers cover the excitation wavelengths of fluorescent materials in the vast majority of the visible light range, ensuring that project requirements and subsequent monitoring of other parameters are met. In actual use, the same wavelength may be reused, or some wavelengths may remain unused.

[0230] The light source system 1 and the light source transmission system 2 are connected by 6 quartz optical fibers.

[0231] The light source transmission system 2 can be equipped with a 6*8 programmable optical switch, which connects to the light source system 1 through an optical physical interface to complete the transmission of optical signals. It receives control signals from the automated control system through communication protocols such as serial ports, and uses time-division multiplexing technology to achieve arbitrary switching of multiple optical paths. The light source transmission system 2 isolates the six different wavelength optical signal paths of the light source system 1, making the sensing excitation light source paths independent of each other.

[0232] Sensing system 3 through, for example Figure 1 The eight quartz optical fibers shown are connected to the light source conduction system 2. The sensing system 3 includes eight fiber optic sensors for monitoring parameters such as pH, glucose, lactic acid, dissolved oxygen, temperature, intracranial pressure, sodium ions, and calcium ions. Figure 1 Both ends of the splitter section have SMA905 interfaces, which are also used in fiber optic patch cords, allowing for fiber optic cable connection. It should be noted that because the sensor is inserted into the brain, this part uses hydrogel fiber. The hydrogel fiber can be connected to the silica fiber using heat-shrink tubing. For example, the silica fiber is inserted into the hydrogel fiber, and the heat-shrink tubing shrinks and wraps around the connection point between the two parts.

[0233] like Figure 1 As shown, the sensing system also includes a filter to filter out the excitation background light and irrelevant spectral components, retaining only the excitation spectral signal corresponding to the target physiological and biochemical indicators.

[0234] The sensing optical transmission system 4 is equipped with an 8*1 programmable optical switch, which connects to the sensing system via an optical physical interface to transmit optical signals. The sensing optical transmission system 4 physically isolates the eight different optical paths of the fiber optic bundle sensing system and integrates them into a single optical signal output port for signal analysis by the spectral processing system 5. Each of the eight optical channels of the sensing optical transmission system 4 corresponds to a different fiber optic sensor, and each channel can independently collect pH and Ca²⁺ signals. Na The system can monitor signals from indicators such as glucose, dissolved oxygen, lactate, temperature, and ICP. Monitoring parameters can be flexibly set according to the doctor's clinical needs, such as enabling simultaneous monitoring of all eight indicators or selectively disabling certain channels to reduce data volume.

[0235] The spectral processing system 5 includes a spectrometer, which comprises modules such as a dispersive element, a photoelectric conversion element, and an analog-to-digital converter. The spectral signals output by the spectrometer correspond one-to-one with the 8-channel fiber optic bundle. Specifically, a 6×8 transmit optical switch selectively guides the laser excitation signal into a specific fiber optic channel. The optical response generated by the sensor after being acted upon by cerebrospinal fluid is then independently selected by a 1×8 return optical switch to the spectrometer input. Therefore, at any given time, only a single channel establishes an optical path connection with the spectrometer. This method utilizes time-division multiplexing to achieve rapid polling, ensuring that the acquisition of all 8 channels is completed within 2–3 seconds. This avoids optical crosstalk and superposition of signals from different channels, thus ensuring that each spectral data point can be accurately traced to its corresponding single fiber optic channel. This structure guarantees the independence and stability required for multi-parameter collaborative monitoring while facilitating subsequent channel allocation and data management in the software.

[0236] The data analysis system receives spectral data acquired and filtered by a spectrometer in real time through a standard data interface, and performs analysis, diagnosis, interaction, and processing. For example... Figure 1 As shown, the data analysis system includes a data analysis unit 61, an interaction unit 62, and an automation control unit 63.

[0237] The data analysis unit 61 includes a data parsing module, a neural network analysis module, and an analysis result output module.

[0238] The interactive unit 62 includes a display interaction module and a command input module.

[0239] The automation control unit 63 includes an instruction parsing module, as well as a laser control module, an optical switch control module, and an acquisition control module, all of which are connected to the instruction parsing module.

[0240] The device is designed with an SMA905 interface, which provides a robust and reliable connection with good shock resistance and interference resistance. It is suitable for long-term stable operation in implantable applications, and the interface material is high-strength stainless steel or alloy, offering corrosion and wear resistance. Of course, the invention is not limited to this; other suitable interfaces in the art can also be used.

[0241] The working process of the multi-parameter fiber optic health monitoring device is further explained below: The light source system 1 provides multi-wavelength excitation light, which is selected by the optical switch of the light source transmission system 2 and transmitted to the sensing module at the end face of the fiber bundle. This sensing module interacts with external environmental parameters (such as pH, ion concentration, dissolved oxygen, temperature, pressure, etc.) to modulate the physical properties of the light wave, including intensity, wavelength, phase, or polarization state. The modulated light signal is transmitted back through the optical fiber. A filter is used to filter out the excitation background light, and the optical switch of the sensing light transmission system 4 selectively directs the channel signal to the spectrometer, which performs spectral analysis. The data analysis system processes and analyzes the collected multi-channel data, extracts the characteristic information of physiological markers, and outputs the final diagnostic results. The interactive unit provides an interface between the user and the system, allowing the operator to select different monitoring indicators, adjust detection parameters, and view the analysis results in real time. The automated control unit is responsible for the real-time control of the entire system, including the coordination of light source excitation, optical switch switching, signal acquisition, and data processing. The modular design of the entire device ensures the efficient collaborative work of each functional module, improving the diagnostic accuracy and real-time performance of the system. At the same time, it provides a convenient and intuitive operating interface for clinicians, with high flexibility and scalability to adapt to different clinical needs.

[0242] Exemplary Example 8 Based on Exemplary Example 1, the sensing module of the dissolved oxygen sensor employs a fluorescent probe containing porphyrin or phthalocyanine metal complexes (such as PtOEP), embedded in a PDMS matrix, and fixed to the end of an optical fiber by dip-coating. The fluorescence lifetime of this probe quenches as the oxygen concentration increases, thereby achieving non-destructive, real-time monitoring of dissolved oxygen concentration.

[0243] As an example, the preparation process of the dissolved oxygen sensing module includes: when preparing the PDMS-PtOEP sensing membrane, 20 mg of prepolymer (Sylgard 184) and 2 mg of curing agent are mixed using a spatula. After thorough mixing, a transparent and homogeneous solution is formed. The indicator PtOEP is dissolved in THF at a concentration of 1 mmol·L⁻¹. 1 The total volume was 500 μL. The PDMS mixture was then added to the PdOEP / THF solution and stirred for several minutes until completely mixed. Gas was removed from the mixture under vacuum. The resulting solution was then used for dip coating. The film was dried and cured at room temperature for 4 days.

[0244] The dissolved oxygen sensor has an excitation wavelength of 405 nm, and its emitted fluorescence ranges from 600 to 750 nm, with a maximum emission wavelength of 645 nm. The fluorescence intensity of the sensor decreases with increasing oxygen content. The fluorescence intensity at 645 nm exhibits a non-linear relationship with oxygen content, with a coefficient of 0.99. This sensor demonstrates good continuous monitoring capability for dissolved oxygen, and its fluorescence is unaffected by other substances in the cerebrospinal fluid, pH, and temperature.

[0245] Figure 12 The monitoring mechanism and performance test results of the dissolved oxygen fiber optic sensor are shown. Among them, Figure 12 Figure (a) illustrates the monitoring mechanism of the dissolved oxygen sensor; (b) shows the variation of the fluorescence spectrum of the dissolved oxygen sensor in different oxygen content ranges; (c) shows the fitting relationship between the fluorescence intensity of the dissolved oxygen sensor at 645 nm and the oxygen content; (d) shows the reversibility of the dissolved oxygen sensor; (e) shows the selectivity of the dissolved oxygen sensor to different interfering substances; (f) shows the pH stability of the dissolved oxygen sensor; and (g) shows the temperature stability of the dissolved oxygen sensor.

[0246] Exemplary Example 9 Based on Exemplary Example 1, the sensing module of the temperature sensor can be based on a thermosensitive fluorescent probe (such as Ru(bpy)). This probe is embedded in epoxy resin or other inert polymers and fixed to the end of an optical fiber. Its fluorescence intensity and lifetime exhibit a reversible temperature response, enabling real-time dynamic detection of local tissue temperature.

[0247] Temperature sensors utilize Ru(bpy) Cl2 is prepared by encapsulating it in epoxy resin. The specific method is as follows: First, prepare 0.5 mL of 1 mmol·L⁻¹ solution. -1 Ru(bpy) Cl2 solution, i.e., 0.5 mmol Ru(bpy) Cl2 was dissolved in 0.5 mL of anhydrous ethanol and then thoroughly mixed with an equal volume of epoxy resin. The resulting mixture was heated on an 80 °C hot plate for 1 h to remove the ethanol. Then, epoxy curing agent was added at a ratio of 1 (curing agent): 2 (epoxy resin). Dip coating (1 cm / s) was then performed to coat the film onto the tip of the fiber optic coupler and cured at room temperature for 72 h. Before use, the fiber optic sensor should be rinsed with deionized water for several minutes.

[0248] The temperature sensor has an excitation wavelength of 450 nm, and its emitted fluorescence ranges from 550 to 800 nm, with a maximum emission wavelength of 610 nm. The fluorescence intensity of the sensor decreases with increasing temperature. The fluorescence intensity at 610 nm exhibits a linear relationship with temperature, with a coefficient of 0.97. This sensor demonstrates excellent continuous temperature monitoring capabilities, and its fluorescence is unaffected by other substances in the cerebrospinal fluid or pH levels.

[0249] Figure 13 The monitoring mechanism and performance test results of the temperature sensor are shown. Among them, Figure 13 Figure (a) shows a schematic diagram of the temperature sensor and the structure of the temperature probe; (b) shows the variation of the fluorescence spectrum of the temperature sensor in different temperature ranges; (c) shows the fitting relationship between the fluorescence intensity of the temperature sensor at 610 nm and temperature; (d) shows the reversibility of the temperature sensor; (e) shows the selectivity of the temperature sensor to different interfering substances; and (f) shows the pH stability of the temperature sensor.

[0250] Although the present invention has been described above in conjunction with exemplary embodiments and accompanying drawings, those skilled in the art should understand that various modifications can be made to the above embodiments without departing from the spirit and scope of the claims.

Claims

1. A multi-parameter fiber optic health monitoring device, characterized in that, include: The system comprises a light source system, a light source transmission system, a sensing system, a sensing light transmission system, and a spectral processing system. The light source system can emit light signals of a single wavelength or multiple different wavelengths; The light source transmission system can transmit the light signals emitted by the light source system, and when the light source system emits multiple different wavelengths, the light source transmission system can provide multiple optical signal paths and realize arbitrary switching of optical signal paths; The sensing system includes at least one fiber optic sensor, which can receive the light signal transmitted by the light source transmission system. One end of the fiber optic sensor can be activated by a marker, thereby causing a change in the light signal. In the case of multiple fiber optic sensors, the optical fibers of each fiber optic sensor are independent of each other. The sensing optical transmission system can transmit back the changed optical signal and can also switch the optical signal path; The spectral processing system can collect and process the returned optical signals to obtain spectral data.

2. The multi-parameter fiber optic health monitoring device according to claim 1, characterized in that, The light source system includes multi-wavelength lasers, LEDs, supercontinuum light sources, or halogen lamp arrays; The multi-wavelength laser includes multiple single-wavelength lasers.

3. The multi-parameter fiber optic health monitoring device according to claim 1, characterized in that, The light source transmission system is equipped with an M*N programmable optical switch, which is connected to the light source system through an optical physical interface to complete the transmission of optical signals, where M and N are both positive integers; The light source system is connected to the light source conduction system via M optical fibers, and to the sensing system via N optical fibers.

4. The multi-parameter fiber optic health monitoring device according to claim 1, characterized in that, The sensing system includes at least one of the following: pH fiber optic sensor, glucose fiber optic sensor, intracranial pressure fiber optic sensor, lactic acid sensing module, dissolved oxygen sensing module, temperature sensing module, sodium ion sensing module, and calcium ion sensing module.

5. The multi-parameter fiber optic health monitoring device according to claim 4, characterized in that, The pH fiber optic sensor comprises: an optical fiber, and a hydrogel sensing layer polymerized on the end face of the optical fiber; wherein... The hydrogel sensing layer includes a functionalized hydrogel containing a pH fluorescent probe, which is a naphthalimide pH fluorescent probe with the following structural formula: ； or, The pH fiber optic sensor comprises: a hydrogel optical fiber, including an inner core and an outer cladding; and a pH fluorescent probe dispersed in the inner core; wherein... The inner core is formed by curing core monomer A, core monomer B, core monomer C and a photoinitiator; core monomer A includes acrylamide, N-vinylpyrrolidone or 2-hydroxyethylmethacrylamide, core monomer B includes polyethylene glycol diacrylate; core monomer C includes hydroxyethyl methacrylate, or includes hydroxyethyl methacrylate and methyl methacrylate; the outer cladding is formed by curing low refractive index PEGDA hydrogel and a photoinitiator, and its refractive index is lower than that of the inner core.

6. The multi-parameter fiber optic health monitoring device according to claim 4, characterized in that, The glucose fiber optic sensor includes: an optical fiber, and a glucose fluorescence sensing module fixed on the end face of the optical fiber, wherein, The glucose fluorescence sensing module is formed by the covalent reaction between the amino group at the end of the glucose fluorescent probe and the epoxy group in the hydrogel network, thereby immobilizing the glucose fluorescent probe in the hydrogel network. The glucose fluorescent probe contains a boric acid group and a terminal amino group, and its structural formula is as follows: 。 7. The multi-parameter fiber optic health monitoring device according to claim 4, characterized in that, The intracranial pressure fiber optic sensor comprises: a flexible optical pressure-sensitive membrane, a sheath, and an optical fiber; wherein... A flexible optical pressure-sensitive membrane is fixed to one end of a sleeve, and the other end of the sleeve is fitted onto the end of an optical fiber, forming a sealed cavity between the three. The flexible optical pressure-sensitive membrane is made of fluorescent dyes and elastomer materials; the fluorescent dyes include N,N-di(octadecyl)-perylene-3,4,9,10-tetracarboxylic acid diimine.

8. The multi-parameter fiber optic health monitoring device according to claim 4, characterized in that, The optical fiber of the optical fiber sensor includes: quartz optical fiber, plastic optical fiber, PDMS optical fiber, hydrogel optical fiber, or composite materials thereof.

9. The multi-parameter fiber optic health monitoring device according to claim 4, characterized in that, The optical fiber is a double-layer hydrogel optical fiber, comprising an inner core and an outer cladding, wherein, The inner core is formed by curing core monomer A, core monomer B, core monomer C and a photoinitiator; core monomer A includes acrylamide, N-vinylpyrrolidone or 2-hydroxyethylmethacrylamide, core monomer B includes polyethylene glycol diacrylate; core monomer C includes hydroxyethyl methacrylate, or includes hydroxyethyl methacrylate and methyl methacrylate. The outer cladding is formed by curing low-refractive-index PEGDA hydrogel and photoinitiator, and its refractive index is lower than that of the inner fiber core.

10. The multi-parameter fiber optic health monitoring device according to claim 1, characterized in that, The device also includes a data analysis system, and the control system is capable of at least one of analyzing, processing, and displaying the spectral data.

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