pH hydrogel optical fiber sensor and method of making the same

Abstract

This invention provides a pH hydrogel fiber optic sensor and its fabrication method. The fiber optic sensor comprises a bilayer hydrogel fiber and a hydrogel sensing layer polymerized on the end face of the hydrogel fiber; the hydrogel sensing layer includes a functionalized hydrogel containing a pH fluorescent probe. Alternatively, the fiber optic sensor comprises: a hydrogel fiber including an inner core and an outer cladding; and a pH fluorescent probe dispersed in the inner core. The pH hydrogel fiber optic sensor of this invention exhibits high sensitivity, high stability, and good biocompatibility, achieving rapid, reversible, and high-resolution fluorescence response within the physiological pH range; simultaneously, it is suitable for long-term implantation and dynamic monitoring of the in vivo environment, and can be integrated with other fluorescence modules to achieve simultaneous detection of multiple parameters.

Description

Technical Field

[0001] This invention relates to the fields of biomedical engineering and optical sensing technology, specifically to a pH hydrogel fiber optic sensor and its preparation method. Background Technology

[0002] pH is often an important physiological and biochemical parameter in various medical diagnoses. Accurate and timely acquisition of pH values ​​is of great significance in the diagnosis and treatment of neurological diseases such as traumatic brain injury and stroke, as well as diseases such as tumors, diabetes, and gastrointestinal diseases.

[0003] Currently, existing pH fluorescence sensors still have many limitations in physiological applications. Most reported fluorescent probes have response ranges biased towards strongly acidic or strongly alkaline regions, making it difficult to accurately reflect minute pH changes of 6.8–7.8 in physiological systems. Furthermore, some probes suffer from poor photostability, susceptibility to fluorescence quenching, and poor repeatability, leading to signal drift and detection errors. In addition, traditional sensors often employ rigid carrier structures, which have limited biocompatibility and flexibility, hindering long-term stable monitoring in vivo. Summary of the Invention

[0004] The purpose of this invention is to address at least one of the aforementioned deficiencies in the prior art.

[0005] To achieve the above objectives, the first aspect of the present invention provides a pH hydrogel fiber optic sensor.

[0006] The pH hydrogel fiber optic sensor includes: a hydrogel fiber and a hydrogel sensing layer polymerized on the end face of the hydrogel fiber; wherein the hydrogel sensing layer includes a functionalized hydrogel containing a pH fluorescent probe.

[0007] Optionally, the hydrogel 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 a photoinitiator, with a refractive index lower than that of the inner core.

[0008] Furthermore, the inner fiber core has a diameter of 50~600 μm and a refractive index of 1.46~1.48; the outer cladding has a thickness of 20~100 µm and a refractive index of 1.38~1.40.

[0009] The second aspect of the present invention provides a method for preparing a pH hydrogel fiber optic sensor as described in the first aspect.

[0010] The method includes: using a pre-gel solution based on a pH fluorescent probe to attach a uniform liquid film to one end of the hydrogel optical fiber by dip-coating; then using ultraviolet light to irradiate the end face to polymerize the liquid film into the hydrogel sensing layer; subsequently placing it in deionized water and washing it with water changes multiple times to obtain a pH hydrogel optical fiber sensor.

[0011] Optionally, the method further includes: vertically immersing one end of the hydrogel optical fiber in a pregel solution of a pH fluorescent probe, and uniformly pulling the optical fiber to coat its end with a uniform liquid film. Immediately irradiating the end face with ultraviolet light causes the liquid film to polymerize into a hydrogel. Then, placing the end of the hydrogel optical fiber in deionized water and changing the water multiple times to remove unreacted monomers and unfixed probe molecules, thus obtaining an optical fiber pH sensor.

[0012] Furthermore, the ultraviolet light wavelength is 200~400 nm, for example 365 nm. The ultraviolet light irradiation time is 30~60 s. The fiber pulling speed is 0.1~5 mm / s.

[0013] The third aspect of the present invention provides another method for preparing a pH hydrogel fiber optic sensor as described in the first aspect.

[0014] The method includes: directly drop-coating a pre-gel solution of a pH fluorescent probe onto a clean end face of the hydrogel optical fiber; then irradiating the end face with ultraviolet light to polymerize the liquid film on the end face into the hydrogel sensing layer; subsequently placing it in deionized water and rinsing it with water changes multiple times to obtain a pH hydrogel optical fiber sensor.

[0015] Optionally, the method further includes: fixing the hydrogel optical fiber, taking 0.5 ~ 20 µL of pregel solution, and directly drop-coating this pregel solution onto a clean optical fiber end face; immediately irradiating the end face with 200 ~ 400 nm ultraviolet light to polymerize the droplet into a hydrogel film, with the interface bonded by free radical-free radical covalent bonding.

[0016] Furthermore, liquid can be taken using a micropipette. The ultraviolet light wavelength is 365 nm.

[0017] Alternatively, the pregel solution of the pH fluorescent probe in the second and third aspects above is prepared from the following raw materials: the pH fluorescent probe, acrylamide, N,N-dimethylacrylamide, polyethylene glycol diacrylate and photoinitiator.

[0018] A fourth aspect of the present invention provides a pH hydrogel fiber optic sensor.

[0019] The pH hydrogel fiber optic sensor comprises: a hydrogel fiber, including an inner core and an outer cladding; a pH fluorescent probe dispersed in the inner core; 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, with a refractive index lower than that of the inner core.

[0020] Alternatively, the pH fluorescent probes in the first, second, third, and fourth aspects mentioned above include naphthalimide pH fluorescent probes with the following structural formula: .

[0021] Further, the preparation method of the naphthalimide pH fluorescent probe includes: dissolving 4-bromo-1,8-naphthalenedicarboxylic anhydride in a solvent, adding 4-aminobutyric acid, and stirring the reaction under an inert gas atmosphere. After the reaction is complete, the solvent is removed, and the residue is purified by silica gel column chromatography to obtain a solid compound; dissolving the solid compound in a solvent, adding N-methylpiperazine, and stirring the reaction under an inert gas atmosphere. After the reaction is complete, the reaction solution is poured into ice water, generating a yellow precipitate; filtering, washing, and drying to obtain the product NBD-COOH; dissolving NBD-COOH in anhydrous DMF. In a mixture, N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride or N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)hexafluorophosphate urea are added sequentially, stirred, and then an organic base and N-(3-aminopropyl)methacrylamide hydrochloride are added. The reaction is continued until the reaction is complete. The reaction solution is then poured into ice water, where a yellow precipitate is formed. The precipitate is purified by silica gel column chromatography to obtain the naphthalimide pH fluorescent probe.

[0022] The fifth aspect of the present invention provides a method for preparing a pH hydrogel fiber optic sensor as described in the fourth aspect.

[0023] The method includes: S1, preparing a core prepolymer solution by mixing core monomer A, core monomer B, core monomer C and a photoinitiator; S2, adding the pH fluorescent probe to the core prepolymer solution, mixing evenly, injecting into a capillary mold, curing by ultraviolet light irradiation, and removing it from the mold after photocrosslinking curing to form a core; S3, placing the obtained hydrogel core in a hydrogel precursor solution, treating its surface using an immersion pulling process, straightening the hydrogel core and hanging it after the pulling process, and irradiating it again under an ultraviolet lamp to solidify the hydrogel precursor solution on the surface of the hydrogel core to form a cladding layer, thereby obtaining the pH hydrogel fiber optic sensor.

[0024] The sixth aspect of this invention provides a naphthalimide pH fluorescent probe.

[0025] It can be the same as the above-mentioned naphthalimide pH fluorescent probe.

[0026] Compared with the prior art, the beneficial effects of the present invention include at least one of the following: (1) The pH hydrogel fiber optic sensor of the present invention exhibits excellent performance, with high sensitivity, high stability, and good biocompatibility. The sensing layer uses a functionalized hydrogel containing a pH fluorescent probe, which can achieve rapid, reversible, and high-resolution fluorescence response within the physiological pH range (6.8–7.8). At the same time, the tight integration of the hydrogel and the fiber optic structure ensures the stability and repeatability of signal transmission. The sensor is flexible and suitable for long-term implantation and dynamic monitoring of the in vivo environment. It is not affected by electromagnetic interference and can be integrated with other fluorescent modules to achieve simultaneous detection of multiple parameters, showing broad application prospects.

[0027] (2) 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 parameters such as pH and long-term monitoring of the brain tissue microenvironment. Attached Figure Description

[0028] 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 synthesis route of the naphthalimide pH fluorescent probe of the present invention is shown.

[0029] Figure 2A schematic diagram of the detection mechanism of the pH fiber optic sensor of the present invention is shown.

[0030] Figure 3 The performance test diagram of the pH fiber optic sensor of the present invention is shown. Detailed Implementation

[0031] The pH hydrogel fiber optic sensor and its preparation method of the present invention will be described in detail below with reference to exemplary embodiments.

[0032] Exemplary Example 1 This exemplary embodiment provides a pH fluorescent probe.

[0033] The pH fluorescent probe is a naphthalimide pH fluorescent probe, and its structural formula is shown below:

[0034] 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.

[0035] Exemplary Example 2 This exemplary embodiment provides a method for preparing a naphthimide pH fluorescent probe. Figure 1 A synthetic route diagram for the naphthalimide pH fluorescent probe is shown.

[0036] The preparation method includes the following steps: S1, take Figure 1 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 1 Solid compound 2 is shown.

[0037] In this embodiment, the molar ratio of 4-bromo-1,8-naphthalenedicarboxylic anhydride and 4-aminobutyric acid is 1:1 to 1:3.

[0038] In this embodiment, anhydrous ethanol is used as a solvent, but isopropanol, DMF (N,N-dimethylformamide), DMSO (dimethyl sulfoxide), NMP (N-methylpyrrolidone), etc. can also be used.

[0039] The amount of anhydrous ethanol used is determined by dissolving the raw material; for example, 1g of raw material corresponds to 10~20ml of solvent.

[0040] 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.

[0041] In this embodiment, 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, 1g of the raw material can be dissolved in 10~400ml of solvent.

[0042] In this embodiment, N-methylpiperazine is used 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.

[0043] 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.

[0044] In this embodiment, 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).

[0045] 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.

[0046] In this embodiment, the organic base includes triethylamine or N,N-diisopropylethylamine.

[0047] In this embodiment, the molar ratio of the organic base and 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 organic base is used to release N-(3-aminopropyl)methacrylamide hydrochloride from the hydrochloride salt.

[0048] 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.

[0049] 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.

[0050] 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.

[0051] Exemplary Example 3 This exemplary embodiment relates to a bilayer hydrogel optical fiber.

[0052] The double-layer hydrogel optical fiber comprises an inner core and an outer cladding. The outer cladding is formed by curing a low-refractive-index PEGDA hydrogel and a photoinitiator, and its refractive index is lower than that of the inner core.

[0053] The inner core is formed by curing core monomers A, B, and C with a photoinitiator. Based on a total mass fraction of 100 parts, core monomer A comprises 20-50 parts, core monomer B 10-40 parts, and core monomer C 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 it is >1%, residual photoinitiator reduces cell viability.

[0054] In this embodiment, 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 < 80 kPa. When AAM > 50 parts, the brittleness increases and the elongation at break < 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 can maintain high hydrophilicity and biocompatibility.

[0055] In this embodiment, the core monomer B includes polyethylene glycol diacrylate (PEGDA). When Mn < 400, the crosslinking density is too high, resulting in an increased core refractive index but a modulus > 300 kPa and decreased flexibility; when Mn > 1000, the refractive index < 1.45, and Δn is insufficient. Mn is the number-average molecular weight, and raw materials within the range of 400-1000 can be used.

[0056] In this embodiment, the core monomer C includes hydroxyethyl methacrylate (HEMA), or includes both 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, the hydrophobicity increases, the water content is less than 40%, and this affects subsequent performance.

[0057] 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.

[0058] In this embodiment, the photoinitiator may include: 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone IRGACURE 2959 or water-soluble phenyl-2,4,6-trimethylbenzoyl lithium phosphinate LAP, etc.

[0059] In this embodiment, the outer cladding layer 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. The photoinitiator can be the same as those described above.

[0060] 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.

[0061] 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 of ≤0.2 dB·cm. -1 The core diameter can be 50~600 μm. 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.

[0062] 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.

[0063] 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.

[0064] 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.

[0065] 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.

[0066] 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.

[0067] 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 range of 80–300 mPa·s. The PEGDA hydrogel content in the outer prepolymer solution is 40% wt–60 wt%, which helps to form a network structure with high cross-linking density, restricts water molecule penetration, keeps the water content less than 15%, maintains a low refractive index, and provides good mechanical protection. The mass ratio of PEGDA hydrogel to photoinitiator is 400–100:1. The solvent in the solution is water, such as ultrapure water. Unless otherwise specifically mentioned, ultrapure water can be used as the solvent in hydrogel optical fibers.

[0068] Alternatively, the hydrogel core can be left to stand in the solution for 10 seconds before the lifting operation to aid wetting and degassing.

[0069] To better understand the fabrication method of the above-mentioned bilayer hydrogel optical fiber, a specific fabrication example is provided below.

[0070] (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. 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 the core.

[0071] (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.

[0072] Exemplary Example 4 This exemplary embodiment provides a pH hydrogel sensor.

[0073] The pH hydrogel sensor is an end-cap type sensor, comprising: a bilayer 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.

[0074] Figure 2 A schematic diagram of the detection mechanism of the pH fiber optic sensor of the present invention is shown. Figure 3 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, with a maximum emission wavelength of 530 nm. The fluorescence intensity of the sensor decreases as pH increases. 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 2 and Figure 3 The results shown are those of a sensor prepared by dip-coating.

[0075] In this embodiment, the method for preparing the pH hydrogel sensor includes: (1) A pregel solution was prepared using a naphthalimide pH fluorescent probe, acrylamide, N,N-dimethylacrylamide, polyethylene glycol diacrylate and a photoinitiator.

[0076] 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.

[0077] 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.

[0078] 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.

[0079] 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.

[0080] (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.

[0081] 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.

[0082] Exemplary Example 5 This exemplary embodiment provides a pH hydrogel sensor.

[0083] The pH hydrogel sensor is an end-face thin-film type 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.

[0084] In this embodiment, the method for preparing the pH hydrogel sensor includes: (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.

[0085] (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.

[0086] 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.

[0087] Exemplary Example 6 This exemplary embodiment provides a pH hydrogel sensor.

[0088] The pH hydrogel sensor's entire fiber core is the sensing material; it is a bilayer hydrogel fiber, consisting of an inner core and an outer cladding. The bilayer hydrogel fiber can be largely the same as that in Exemplary Example 3, except that the pH fluorescent probe is dispersed within the inner core. The pH fluorescent probe can be the same as that in Exemplary Example 1.

[0089] 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.

[0090] 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.

[0091] 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.

[0092] (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.

[0093] 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".

[0094] 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 pH hydrogel optical fiber sensor, characterized by, For long-term implantation and dynamic monitoring of the in vivo environment, including: 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. The pH fluorescent probe includes a naphthimide pH fluorescent probe with the following structural formula: ； The hydrogel optical fiber is a double-layer hydrogel optical fiber, comprising an inner core and an outer cladding. 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; and core monomer C includes hydroxyethyl methacrylate, or a mixture of hydroxyethyl methacrylate and methyl methacrylate. The outer cladding is formed by curing low-refractive-index PEGDA hydrogel and a photoinitiator, with a refractive index lower than that of the inner core.

2. The method of claim 1, wherein the pH hydrogel optical fiber sensor is prepared by the steps of: The method includes: A pregel solution based on a pH fluorescent probe is used to attach a uniform liquid film to one end of a hydrogel optical fiber by dip-coating. Then, the end face is irradiated with ultraviolet light to polymerize the liquid film into the hydrogel sensing layer. Subsequently, the fiber is placed in deionized water and washed with water changes multiple times to obtain a pH hydrogel optical fiber sensor.

3. The method of claim 1, wherein the pH hydrogel optical fiber sensor is prepared by the steps of: The method includes: The pregel solution of the pH fluorescent probe was directly drop-coated onto the clean end face of the hydrogel fiber; then the end face was irradiated with ultraviolet light to polymerize the liquid film on the end face into the hydrogel sensing layer; subsequently, it was placed in deionized water and rinsed with water changes several times to obtain the pH hydrogel fiber sensor.

4. The method of claim 2 or 3, wherein the pH hydrogel optical fiber sensor is prepared by the steps of: The prepolymer solution of the pH fluorescent probe was prepared from the following raw materials: The pH fluorescent probe, acrylamide, N,N-dimethylacrylamide, polyethylene glycol diacrylate, and photoinitiator are described.

5. A pH hydrogel optical fiber sensor characterized in that, For long-term implantation and dynamic monitoring of the in vivo environment, including: Hydrogel optical fiber, consisting of an inner core and an outer cladding; pH fluorescent probes are dispersed in the inner fiber core; 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. The pH fluorescent probe includes a naphthimide pH fluorescent probe with the following structural formula: 。 6. The method for preparing the pH hydrogel fiber optic sensor according to claim 5, characterized in that, The method includes: S1. Prepare a fiber core prepolymer solution by mixing fiber core monomer A, fiber core monomer B, fiber core monomer C and photoinitiator; S2. Add the pH fluorescent probe to the fiber core prepolymer solution, mix evenly, inject into the capillary mold, cure by ultraviolet light, and after photo-crosslinking and curing, remove from the mold to form the fiber core. S3. The obtained hydrogel fiber core is placed in the hydrogel precursor solution, and its surface is treated by dip-coating process. After the coating process is completed, the hydrogel fiber core is straightened and hung up, and then placed under ultraviolet light for irradiation to solidify the hydrogel precursor solution on the surface of the hydrogel fiber core to form a cladding layer with a thickness of 20~100 µm, thus obtaining the pH hydrogel fiber sensor.

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