A programmable self-assembling hydrogel optical fiber for decoupling multiple physiological signals and its preparation method and use

Abstract

The application discloses a programmable self-assembled hydrogel optical fiber for decoupling multiple physiological signals and a preparation method and application thereof, and the method comprises the following steps: blending an amino-containing fiber-forming polymer, an aldehyde polymer containing a carbonyl group and polyethylene glycol diacrylate to obtain a prepolymer solution by taking deionized water as a solvent; and injecting the prepolymer solution into a tubular mold by adopting a template molding method, and after polymerization molding, the tubular mold is removed to obtain the programmable self-assembled hydrogel optical fiber. The application is based on the template molding method, the proportion among the fiber-forming polymer, a crosslinking agent and a linear polymer is adjusted, the crosslinking rate of the prepolymer solution is adjusted, and the injection fiber-forming process is ensured to be smooth. The hydrogel optical fiber with a uniform structure, uniform size and self-healing performance is obtained through Schiff base reaction in the tube. The method has the advantages of simple process, controllable diameter and adjustable mechanical property.

Description

Technical Field

[0001] The present invention relates to the technical field of fiber material design and preparation, and in particular to a programmable self-assembly hydrogel optical fiber for decoupling multiple physiological signals, and a preparation method and application thereof. Background Art

[0002] Diagnostic methods based on biosignal recognition and analysis enable doctors to diagnose diseases and initiate interventions as early as possible, significantly improving patient survival rates. For example, for diseases such as cancer and diabetes that are prone to recurrence and require lengthy treatment cycles, the detection, analysis, and diagnosis of biosignals are crucial for developing subsequent treatment plans. However, when it comes to detecting physiological signals in the body, the mismatch between implantable physiological signal sensors based on traditional materials and the natural tissue interface can cause tissue damage and signal loss. Furthermore, the detection of physiological signals such as blood glucose and pH is often affected by the complex physiological environment within the body, and signals can interfere with each other, leading to signal offsets. To address the issue of multi-signal acquisition interference, researchers have successfully achieved independent acquisition of multiple signals from the human body by integrating multi-signal acquisition platforms and constructing multi-signal transmission channels. However, currently developed multi-signal sensors still rely on traditional materials, and the mismatch between them and the tissue interface remains unresolved, significantly limiting the feasibility of long-term sensor implantation. Summary of the Invention

[0003] To address these technical challenges, the present invention provides a programmable self-assembling hydrogel fiber for decoupling multiple physiological signals and its preparation method. This hydrogel fiber combines excellent light-guiding properties with interfacial compatibility with biological soft tissues. Furthermore, the functional splicing achieved through self-healing properties enables the material to decouple multiple physiological signals.

[0004] To achieve the above object, the present invention provides a programmable self-assembling hydrogel optical fiber for decoupling multiple physiological signals, which comprises the following steps:

[0005] S1. Using deionized water as a solvent, blending an amino-containing fiber-forming polymer, a carbonyl-containing aldehyde polymer, and polyethylene glycol diacrylate in a mass ratio of 6:2:(2-4) to obtain a prepolymer solution; wherein the amino-containing fiber-forming polymer is at least one of carboxymethyl chitosan, sodium alginate, and polyvinyl alcohol having a molecular weight Mw of 4000 to 4000000 Da, and the carbonyl-containing aldehyde polymer is at least one of oxidized hyaluronic acid, oxidized sodium alginate, and oxidized dextran;

[0006] S2: Using a template molding method, a prepolymer solution is injected into a tubular mold. After polymerization and molding, the mold is removed to produce a programmable self-assembling hydrogel optical fiber. The prepolymer solution forms a gel network structure with dynamic covalent bonds through Schiff base reactions within the tube. A semi-interpenetrating network based on hydrogen bonds further enhances the system's self-healing properties.

[0007] As a further preferred technical solution of the present invention, step S1 specifically includes the following steps:

[0008] A fiber-forming polymer containing amino groups is mixed with deionized water to form a polymer solution A having a mass fraction of 4% to 10%. A carbonyl-containing aldehyde polymer is mixed with deionized water to form a polymer solution B having a mass fraction of 5% to 10%. Polymer solution A, polymer solution B, and polyethylene glycol diacrylate are blended to obtain a prepolymer solution. Preferably, the polyethylene glycol diacrylate accounts for 2% to 4% by weight of the prepolymer solution.

[0009] As a further preferred technical solution of the present invention, steps S1 and S2 are both performed at room temperature.

[0010] As a further preferred technical solution of the present invention, after the prepolymer solution in step S1 is mixed, the prepolymer solution is completely injected into the tubular mold within 1-3 minutes.

[0011] As a further preferred technical solution of the present invention, the tubular mold is a tubular Teflon template.

[0012] As a further preferred technical solution of the present invention, the inner diameter of the tubular mold is 400 μm-1000 μm.

[0013] As a further preferred technical solution of the present invention, in step S2, the prepolymer solution is injected into the tubular mold using a syringe.

[0014] As a further preferred technical solution of the present invention, the prepolymer solution in step S1 is further doped with 0.01-0.03 wt % of rhodamine B and / or methylene blue.

[0015] According to another aspect of the present invention, the present invention also provides a programmable self-assembling hydrogel optical fiber, which is prepared by the above method.

[0016] According to another aspect of the present invention, a programmable self-assembling hydrogel fiber is used in the preparation of a biosensor. This biosensor is an implantable physiological signal sensor that transmits signals through the programmable self-assembling hydrogel fiber. By incorporating a semi-interpenetrating structure, the modulus and mechanical strength of the hydrogel fiber are modulated to closely match the mechanical properties of biological tissue. This reduces unnecessary tissue damage while collecting optical physiological signals and improves the biosensor's interfacial stability.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] (1) In order to solve the problems of tissue damage and sensor signal loss caused by the mismatch between the mechanical properties of the interface between the current implantable physiological signal sensor and the biological tissue, the present invention is based on the template molding method. By regulating the ratio between the three components of the fiber-forming polymer, the crosslinking agent and the linear polymer, the crosslinking rate of the prepolymer liquid is regulated to ensure the smooth injection fiber-forming process. After the Schiff base reaction in the tube, a hydrogel optical fiber with uniform structure, uniform size and self-healing properties is obtained. This method has the advantages of simple process, controllable diameter and adjustable mechanical properties.

[0019] (2) The present invention introduces a linear polymer containing polar groups, PEGDA, as a third component to construct a hydrogen-bonded semi-interpenetrating network structure, thereby achieving control over the material's mechanical properties without affecting its optical conductivity. Generally, the modulus of human soft tissue ranges from 0.1 MPa to 1.0 MPa. Controlling the PEGDA content in the system is key to achieving mechanical matching at the interface between the material and the tissue. The modulus of the optical fiber prepared by regulating PEGDA in the present invention is adjustable within the range of 0.2-0.6 MPa, meeting the requirement for matching the modulus of human tissue.

[0020] (3) The hydrogel optical fiber prepared by the present invention realizes assembly programming based on self-healing properties, and achieves simultaneous decoupling of multiple physiological signals in the body by splicing different functional segments, and the simple material preparation process meets the needs of large-scale preparation and testing. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0022] Figure 1 Schematic diagram of the preparation of programmable self-assembled hydrogel optical fibers for decoupling multiple signals according to Examples 1 to 4 of the present invention.

[0023] Figure 2 Light-guiding properties of hydrogel optical fibers with different polyethylene glycol diacrylate contents prepared in Examples 1, 2, and 3 of the present invention before and after splicing

[0024] Figure 3 Mechanical properties of hydrogel optical fibers with different polyethylene glycol diacrylate contents prepared in Examples 1, 2, and 3 of the present invention before (a) and after (b) splicing

[0025] Figure 4 This is a schematic diagram of two functional modules doped with different dyes according to Examples 4 and 5 of the present invention being spliced ​​and assembled into a complete optical fiber.

[0026] Figure 5 The specific responses of the hydrogel optical fiber for decoupling different signals prepared in the present invention to different stimulation signals, a is a segment stimulated by rhodamine B staining; b is a segment stimulated by methylene blue staining.

[0027] The purpose, features and advantages of the present invention will be further described with reference to the accompanying drawings and in conjunction with the embodiments. DETAILED DESCRIPTION

[0028] The following describes the specific embodiments of the present invention in detail with reference to the accompanying drawings. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention and are not intended to limit the present invention.

[0029] Unless otherwise defined, the technical terms used in the following examples have the same meanings as commonly understood by those skilled in the art to which this invention belongs. The experimental reagents used in the following examples, unless otherwise specified, are conventional biochemical reagents; the experimental methods described, unless otherwise specified, are conventional methods.

[0030] The raw materials used in the following examples are all commercially available. Oxidized sodium alginate can be obtained by oxidizing alginic acid with sodium periodate, followed by filtration, washing, and vacuum drying. Polyethylene glycol diacrylate with Mn=700 is selected. Deionized water is used as the solvent.

[0031] Example 1

[0032] This embodiment provides a preparation process for a self-assembled programmable hydrogel optical fiber for decoupling multiple biological signals, which specifically includes the following steps:

[0033] 1) Preparation of prepolymer solution:

[0034] First, 10 g of a 6 wt.% carboxymethyl chitosan aqueous solution was used as the matrix material solution, 2 g of a 10 wt.% sodium alginate aqueous solution was used as the crosslinker solution, and 0.3 g of polyethylene glycol diacrylate (Mn=700) was used as the third component to construct a hydrogen bond-based semi-interpenetrating network structure to achieve the purpose of regulating the material modulus to match the tissue modulus; the above three components were blended and dispersed by a homogenizer to obtain a prepolymer solution.

[0035] 2) Fiber molding:

[0036] like Figure 1 As shown, the prepared polymer solution is quickly loaded into a syringe and squeezed into a 600μm diameter Teflon tube (completed within 1-3 minutes). The inner diameter of the tube determines the size of the fiber. The tube ends are then sealed with sealing film. After waiting for 30 minutes, the polymer cross-linking network inside the tube is completed to form a hydrogel fiber. Finally, the outer Teflon tube is peeled off to obtain a uniformly sized programmable self-assembled hydrogel optical fiber (hereinafter referred to as hydrogel fiber) with a diameter of 600μm. The sample is named C 0.6 P 0.3 .

[0037] The prepared hydrogel optical fiber sample C 0.6 P 0.3 Perform the following test:

[0038] Light guide performance test: The prepared hydrogel optical fiber is cut with a scalpel to ensure the flatness of the cut surface. Then the two cut surfaces are aligned and brought together under a microscope. Based on the dynamic covalent bonds within the cross-linked network of the hydrogel, the two independent optical fiber modules can be reassembled into a complete optical fiber. Figure 2 As shown, by connecting the optical fiber before / after assembly to a white light source, the light-guiding performance of the hydrogel optical fiber and the effect of splicing assembly on the light attenuation performance are tested.

[0039] Mechanical properties test: Fiber slitting and splicing are the same as light guide testing, such as Figure 3 As shown, the mechanical properties of the hydrogel optical fiber before and after assembly were tested by a tensile testing machine.

[0040] The results of mechanical and optical tests show that the optical / mechanical properties of hydrogel optical fiber did not decrease significantly before and after splicing, proving the feasibility of realizing optical signal transmission based on splicing and assembly of different modules.

[0041] In addition, since the materials used in this experiment are all biomass materials, they have been widely used in fields such as promoting cell growth and tissue repair, and therefore meet the biocompatibility requirements.

[0042] Examples 2 and 3

[0043] This example adopts the same preparation method as Example 1, the only difference being that the amount of polyethylene glycol diacrylate (PEGDA) is changed, and the content of PEGDA in the system is controlled at 0.2g and 0.4g respectively. The obtained samples are named C 0.6 P 0.2 and C 0.6 P 0.4 .

[0044] The same test method as in Example 1 was used to test sample C. 0.6 P 0.2 、C 0.6 P 0.4 The light guide performance and mechanical performance tests were carried out, and the results were as follows Figure 2 、 Figure 3 As shown. A comparative analysis was conducted to explore the effect of changes in the content of PEGDA as a supporting structure of the semi-interpenetrating network inside the hydrogel optical fiber on the optical conductivity and mechanical properties of the programmable self-assembled hydrogel optical fiber. By regulating the proportion of PEGDA in the system, the regulation of the hydrogel network structure is achieved. When the content of PEGDA increases, its semi-interpenetrating network structure based on hydrogen bonds also increases, making the network in the system tend to be dense, which causes the hydrogel to become harder and more brittle at the macro level, and thus the modulus also increases; in addition, the increase in the semi-interpenetrating network structure will limit the dynamic cross-linking of the imine bond, thereby reducing the self-healing performance of the material, and an excellent optical channel cannot be constructed after the optical fibers are spliced, thereby limiting their optical conductivity. The present invention can construct an excellent self-healing system to achieve programmable self-assembly on the basis of satisfying the modulus matching tissue modulus by regulating the third component PEGDA.

[0045] In summary, the test results of mechanical properties show that the increase of PEGDA content will make the optical fiber material stronger and tougher to a certain extent, and the modulus will increase, but the corresponding self-healing ability will decrease. With the increase of PEGDA content (0.2-0.4g), the mechanical strength is difficult to recover after splicing (from recovery to 90% to recovery to 30%). The best content of PEGDA was judged through mechanical testing. When PEGDA is 0.3g, the hydrogel optical fiber meets both mechanical and modulus requirements as well as self-healing requirements. The optical performance test shows that the hydrogel optical fiber has the ability to transmit optical signals and that the optical path can still be completely constructed after splicing and assembly, proving the feasibility of transmitting optical signals by programmable self-assembled hydrogel optical fiber based on self-healing properties.

[0046] Examples 4 and 5

[0047] This example uses the same preparation method and formula as Example 1. The only difference is that during the blending process, 0.01g of rhodamine B and 0.01g of methylene blue are introduced to dye-dope the hydrogel optical fiber to construct two different functional modules.

[0048] By splicing and assembling (see Example 1), the two modules doped with dyes are spliced ​​together to form a complete optical fiber, which is then introduced into an optical fiber system, such as Figure 4As shown, the two ends of the optical fiber are coupled to the ceramic coupling head, one end is connected to the white light source, and the other end is connected to the spectrometer, so that the white light source is transmitted through the hydrogel optical fiber into the spectrometer to generate characteristic peaks. In this test, a white light source covering the 200nm-1000nm band is used as the signal source, and the corresponding characteristic peaks are analyzed by the spectrometer. Then, a stress of 10Pa-30Pa is applied to different segments respectively, and a specific response is achieved based on the signal drift of the characteristic peak, and multiple signals are decoupled. Figure 5 As shown in Figure a, by applying stress to the Rhodamine B-doped fiber segment, the characteristic peak signal at 710 nm drifts; Figure 5 As shown in Figure (b), stress applied to a methylene blue-doped fiber segment causes a shift in the characteristic peak signal at 640 nm, demonstrating the programmable self-assembled fiber's ability to decouple different signals.

[0049] The above examples, through the exploration of the optical and mechanical properties before and after splicing, demonstrate the feasibility of using the hydrogel optical fiber prepared by the method of the present invention after programmed assembly. In addition, different functional segments can be constructed by dye doping, demonstrating its ability to decouple signals.

[0050] This invention uses a template-based method to fabricate structurally uniform hydrogel optical fibers. Using self-healing technology, different optical fibers can be spliced ​​and assembled programmatically, integrating multiple functional segments into a single fiber and successfully decoupling signals. Unlike traditional multi-signal transmission fibers, the fiber-optic sensor constructed with this invention eliminates the need for complex multi-signal channel design and exhibits excellent compatibility with tissue interfaces.

[0051] Although specific embodiments of the present invention are described above, those skilled in the art should understand that these are merely examples and that various changes or modifications may be made to the embodiments without departing from the principles and essence of the present invention. The scope of protection of the present invention is limited only by the appended claims.

Claims

1. A method for preparing a programmable self-assembled hydrogel optical fiber for decoupling multiple physiological signals, characterized in that: The following steps are involved: S1. Using deionized water as a solvent, a fiber-forming polymer containing an amino group, an aldehyde polymer containing a carbonyl group, and polyethylene glycol diacrylate are blended in a mass ratio of 6:2:(2-4) to obtain a prepolymer solution; Wherein, the fiber-forming polymer containing amino groups is carboxymethyl chitosan with a molecular weight Mw of 4000-4000000 Da, and the aldehyde polymer containing carbonyl groups is oxidized sodium alginate; S2. Using a template molding method, the prepolymer solution is injected into a tubular mold. After polymerization and molding, the tubular mold is removed to obtain a programmable self-assembled hydrogel optical fiber with a semi-interpenetrating network structure; Step S1 specifically includes the following steps: The amino-containing fiber-forming polymer and deionized water are mixed to form a polymer solution A with a mass fraction of 4%-10%. The carbonyl-containing aldehyde polymer is mixed with deionized water to prepare a polymer solution B with a mass fraction of 5%-10%; The polymer solution A, the polymer solution B and polyethylene glycol diacrylate are blended to obtain a prepolymer solution.

2. The method for preparing a programmable self-assembling hydrogel optical fiber for decoupling multiple physiological signals according to claim 1, characterized in that: Steps S1 and S2 are both performed at room temperature.

3. The method for preparing a programmable self-assembling hydrogel optical fiber for decoupling multiple physiological signals according to claim 1, characterized in that: After the prepolymer solution in step S1 is mixed, the prepolymer solution is completely injected into the tubular mold within 1-3 minutes.

4. The method for preparing a programmable self-assembling hydrogel optical fiber for decoupling multiple physiological signals according to claim 1, characterized in that: The tubular mold is a tubular Teflon template.

5. The method for preparing a programmable self-assembling hydrogel optical fiber for decoupling multiple physiological signals according to claim 1, characterized in that: The inner diameter of the tubular mold is 400 μm-1000 μm.

6. The method for preparing a programmable self-assembling hydrogel optical fiber for decoupling multiple physiological signals according to claim 1, characterized in that: In step S2, the prepolymer solution is injected into the tubular mold using a syringe.

7. The method for preparing a programmable self-assembling hydrogel optical fiber for decoupling multiple physiological signals according to any one of claims 1 to 6, characterized in that: The prepolymer solution in step S1 is also doped with 0.01-0.03 wt % of rhodamine B and / or methylene blue.

8. A programmable self-assembling hydrogel optical fiber, characterized in that: The method according to any one of claims 1 to 7 is used for preparation.

9. Use of the programmable self-assembling hydrogel optical fiber according to claim 8 in preparing a biosensor.

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