A conductive hydrogel neural probe and its preparation method

Abstract

This invention discloses a conductive hydrogel neural probe and its preparation method. The conductive hydrogel neural probe includes: a light guide core, which is a hydrogel formed by a photoinitiator, a water-soluble double-bonded olefin monomer, and a first crosslinking agent; a light guide shell, which wraps around the surface of the light guide core; the light guide shell is a transparent plastic tube or silicone tube; a conductive layer, which is solidified on the surface of the light guide shell; the conductive layer is a hydrogel formed by a photoinitiator, a conductive polymer, and a second crosslinking agent; and an insulating layer, which is solidified on the surface of the conductive layer. It features excellent light guiding performance (light transmission loss <0.5dB / cm); good conductivity based on the conductive polymer hydrogel, and long-term stability of conductivity; and matched tissue mechanical properties (flexural stiffness <10N / m within the physiological activity frequency range of 0.1-10Hz) ensuring long-term stability of light guiding and conductivity after implantation into brain tissue.

Description

Technical Field

[0001] This invention relates to the field of neural probe technology, and in particular to a conductive hydrogel neural probe and its preparation method. Background Technology

[0002] Research into the brain's neural circuits has spurred exploration of future brain-computer interfaces (BCIs), enabling direct communication between the brain and external devices by capturing neuronal activity. Embedded optical fibers and electrode probes are the most common invasive devices in this field. However, long-term implantation of these devices often leads to foreign body reactions. The implanted probes gradually become encased in glial scarring, subsequently losing their recording and stimulation capabilities, resulting in device malfunction. Studies indicate that these adverse reactions stem from chronic tissue damage, largely due to the mismatch between the mechanical properties of rigid materials and biological tissues. During long-term implantation, micromovements occur, causing neural tissue damage and accompanying foreign body reactions. Essentially, this is because traditional implantable probes are primarily made of inorganic materials. Commonly used tungsten and silicon metal electrodes have Young's moduli greater than 100 GPa, while existing optical fiber materials, such as polycarbonate (2-2.4 GPa) and quartz (50-85 GPa), also have Young's moduli far greater than those of brain tissue (1-10 kPa).

[0003] While existing research has effectively improved foreign body response during long-term implantation by modifying the surface of rigid probes with soft materials, several challenges remain to be overcome in practical applications. First, the assembly of optical fibers and electrodes is not only difficult to manufacture but also often causes additional tissue damage. Second, due to the small band gaps of metals (such as iridium, gold, and platinum), metal-based neural electrodes are highly susceptible to interference light-induced artifacts, thereby increasing signal noise and erroneous results.

[0004] Therefore, existing technologies still need further improvement and development. Summary of the Invention

[0005] In view of the shortcomings of the prior art, the purpose of this invention is to provide a conductive hydrogel neural probe and its preparation method. This invention prepares the light-guiding layer and conductive layer of the probe from hydrogel, which has a three-dimensional network structure with high water content, giving the hydrogel mechanical properties that are highly similar to biological tissue. This can effectively reduce foreign body reaction during long-term testing after implantation into brain tissue, thereby effectively improving the compliance and service life of the neural probe and the fidelity of the recorded signal.

[0006] To achieve this objective, the present invention adopts the following technical solution:

[0007] In a first aspect, a conductive hydrogel neural probe includes:

[0008] The light guide core is a hydrogel formed by crosslinking a photoinitiator, a water-soluble double-bonded olefin monomer, and a first crosslinking agent;

[0009] A light-guiding shell is provided, which encloses the light-guiding core. The light-guiding shell is a transparent tube, such as a plastic tube or a silicone tube. The refractive index of the tube is less than that of the light-guiding core, which avoids light scattering during transmission and achieves efficient light guiding of the probe.

[0010] A conductive layer is solidified on the surface of the light guide shell layer; the conductive layer is a hydrogel layer formed by crosslinking a photoinitiator, a conductive polymer, and a second crosslinking agent.

[0011] An insulating layer, which is cured on the surface of the conductive layer.

[0012] The conductive hydrogel neural probe provided by this invention has good biocompatibility and tissue mechanical adaptability because it uses hydrogel as the guiding core and conductive layer, and has long-term stability under physiological conditions.

[0013] The following are preferred technical solutions of the present invention, but are not intended to limit the technical solutions provided by the present invention. The purpose and beneficial effects of the present invention can be better achieved and realized through the following preferred technical solutions.

[0014] As a preferred technical solution, the conductive hydrogel neural probe contains water-soluble double-bonded olefin monomers, including but not limited to acrylic acid or acrylamide compounds; the acrylamide compounds include methyl hydroxyethyl acrylate, acrylamide, and hydroxyethyl acrylamide.

[0015] As a preferred technical solution, the conductive hydrogel neural probe includes, but is not limited to, polyaniline, polypyrrole, poly(2,3-dihydrothieno-1,4-dioxin)-poly(styrene sulfonate) and poly(p-styrene).

[0016] As a preferred technical solution, the conductive hydrogel neural probe wherein the first crosslinking agent and the second crosslinking agent are independently selected from PEG(m)-DA, ethylene glycol dimethacrylate, triethylene glycol dimethacrylate, N,N-methylenediacrylamide, etc. Wherein, m represents a molecular weight of 700, 2000, 4000, 6000, etc.

[0017] Secondly, a method for preparing a conductive hydrogel neural probe as described above, comprising:

[0018] Provide the aforementioned transparent plastic or silicone tube;

[0019] A mixed solution containing a water-soluble double-bonded olefin monomer and a first crosslinking agent is injected into the transparent plastic or silicone tube, and after a first curing treatment, an optical fiber is obtained.

[0020] A mixed solution containing a conductive polymer compound and a second crosslinking agent is coated onto the surface of the optical fiber, and a second curing treatment is performed to obtain a conductive layer.

[0021] A solution containing an insulating polymer is coated onto the surface of the conductive layer, and the conductive hydrogel neural probe is obtained after drying.

[0022] The method for preparing the conductive hydrogel neural probe provided by the present invention involves injecting a water-soluble double-bonded olefin monomer and a crosslinking agent into a transparent plastic tube or silicone tube, and then curing it to obtain a light-guiding optical fiber (light-guiding core and light-guiding shell). The curing method can be photocuring, i.e., adding a photoinitiator to a mixed solution.

[0023] Transparent plastic tubes and silicone hoses can be selected, including soluble polytetrafluoroethylene (PFA), polyurethane (PU), polyvinyl chloride (PVC), and polydimethylsiloxane (PDMS), etc.

[0024] As a preferred technical solution, in the method for preparing the conductive hydrogel neural probe, the mass fraction of the water-soluble double-bonded olefin monomer in the mixed solution containing the water-soluble double-bonded olefin monomer and the first crosslinking agent is 70-90%.

[0025] As a preferred technical solution, the conductive hydrogel neural probe further contains a photoinitiator in the mixed solution containing a water-soluble double-bonded olefin monomer and a first crosslinking agent; the photoinitiator is selected from any one of 2-hydroxy-4-(2-hydroxyethoxy)-2-methylphenylacetone, α-ketoglutaric acid, phenyl-2,4,6-trimethylbenzoyl lithium phosphite, and 2-hydroxy-2-methylphenylacetone.

[0026] As a preferred technical solution, the conductive hydrogel neural probe further includes a photoinitiator in the mixed solution containing the conductive polymer compound and the second crosslinking agent; the photoinitiator is selected from any one of 2-hydroxy-4-(2-hydroxyethoxy)-2-methylphenylacetone, α-ketoglutaric acid, phenyl-2,4,6-trimethylbenzoyl lithium phosphite, and 2-hydroxy-2-methylphenylacetone.

[0027] As a preferred technical solution, in the method for preparing the conductive hydrogel neural probe, the mass fraction of the photoinitiator is 0.3-3%.

[0028] As a preferred technical solution, in the method for preparing the conductive hydrogel neural probe, the mass fraction of the insulating polymer in the solution containing the insulating polymer is 10-20%.

[0029] Beneficial Effects: Compared with existing technologies, the conductive hydrogel neural probe provided by this invention integrates light guiding and conductivity, unlike traditional invasive implanted metal electrodes and quartz optical fibers. A robust interface is formed between the light guiding and conductive layers through chemical interaction, ensuring long-term stability during operation. Furthermore, both the light guiding and conductive layers of this neural probe are prepared from hydrogel, possessing a high-water-content three-dimensional network structure that endows the hydrogel with mechanical properties highly similar to biological tissue. This effectively reduces foreign body reactions during long-term testing after implantation into brain tissue, thereby significantly improving the compliance, lifespan, and fidelity of the recorded signal. This hydrogel neural probe exhibits excellent comprehensive performance, good biocompatibility, tissue mechanical adaptability, and the integrated light guiding and conductivity enables closed-loop regulation of optogenetics or intervention in neurological diseases. Attached Figure Description

[0030] Figure 1 This is a schematic diagram of the conductive hydrogel neural probe structure provided by the present invention.

[0031] Figure 2 This invention provides a fabrication route for an integrated hydrogel neural probe that is both light-guiding and conductive.

[0032] Figure 3 The test curve for optimizing the transparency of the HEMA hydrogel in the light guide core layer provided by this invention.

[0033] Figure 4 The refractive index measurement curve of the HEMA hydrogel in the light guide core layer provided by this invention.

[0034] Figure 5 Different thicknesses of the conductive layer provided by this invention introduce impedance variations.

[0035] Figure 6 The test results of the impedance stability of the conductive layer provided by this invention.

[0036] Figure 7 The result of the PU encapsulation insulation treatment provided by the present invention.

[0037] Figure 8 The results of the single cantilever bending test of the hydrogel probe provided by the present invention.

[0038] Figure 9 The results of light conduction loss measurement for the hydrogel neural probe provided in this invention.

[0039] Figure 10This is a schematic diagram of an apparatus for measuring the impedance of a conductive layer using an electrochemical method.

[0040] Figure 11 This is a schematic diagram of a single cantilever bending test. Detailed Implementation

[0041] This invention provides a conductive hydrogel neural probe and its preparation method. To make the objectives, technical solutions, and effects of this invention clearer and more explicit, the invention is further described in detail below. It should be understood that the specific embodiments described herein are only for explaining the invention and are not intended to limit the invention.

[0042] Those skilled in the art will understand that, unless specifically stated otherwise, the singular forms “a,” “an,” “the,” and “the” used herein may also include the plural forms. It should be further understood that the word “comprising” as used in this specification means the presence of the stated features, integers, or steps, but does not exclude the presence or addition of one or more other features.

[0043] It will be understood by those skilled in the art that, unless otherwise defined, all terms used herein (including technical and scientific terms) have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. It should also be understood that terms such as those defined in general dictionaries should be understood to have the same meaning as in the context of the prior art, and should not be interpreted in an idealized or overly formal sense unless specifically defined as herein.

[0044] Light guiding efficiency measurement The light guiding efficiency of optical fibers is evaluated by fiber loss (optical transmission loss). In this invention, the light guiding efficiency depends on the design and fabrication of the light guiding layer. The light guiding efficiency of an optical fiber is related to fiber size, core layer transparency and refractive index, and the difference in refractive index between the core and shell materials. With a fixed shell material, the light guiding efficiency can also be adjusted by regulating the transparency and refractive index of the core layer hydrogel. The truncation rule is one of the basic measurement methods based on the definition of the attenuation coefficient. Without changing the intensity of the excitation source, the output power PL of a fiber of length L and the output power P0 of the fiber after severing are measured. The attenuation coefficient of the fiber at a wavelength of 470 nm is denoted as a (optical loss), which represents the optical power attenuation per unit length of fiber, expressed in dB / cm. It is calculated using the following formula: a = -10 / L x Log 10 (P L / P0) .

[0045] Impedance measurement The impedance of the conductive layer was measured by an electrochemical method, with a frequency range of 1-10. 5 Hz, its working components are as follows (device diagram as shown) Figure 9As shown): conductive optical fiber (working electrode), platinum sheet (counter electrode), Ag / AgCl (reference electrode), electrolyte: PBS solution. Impedance at 1000 Hz was used as the standard, which is the frequency at which neural signals are recorded.

[0046] Example 1

[0047] refer to Figure 2 The preparation process involves preparing 80% HEMA and 1% PEG by mass. (700) An aqueous solution of -DA and 1% I2959 (by mass) was prepared. Nitrogen gas was bubbled into the aqueous solution for 5 min to remove oxygen, followed by centrifugation (3000 rpm / min) to remove air bubbles. The aqueous solution was injected into hollow PFA tubes with inner and outer diameters of 300 and 400 μm, respectively, using a syringe. After sealing, the tubes were irradiated with a UV lamp (365 nm wavelength) for 60 min. After the solution in the tubes solidified, they were removed and immersed in pure water for 3 days to achieve purification (removal of residual small molecules), yielding the optical fiber.

[0048] The optical fiber was immersed in a conductive layer prepolymer solution containing 15 wt% PVA-AA, 1.3 wt% PEDOT:PSS, 2 wt% PEG(700)-DA, and 1.5 wt% I2959 for 3 minutes. After immersion, the fiber was removed, the surface was smoothed with a scraper, and then cured under a 365 nm UV lamp for 60 seconds (30 seconds for each side, UV lamp power 250 mW / cm²). 2 ).

[0049] The conductive treated optical fiber was immersed in a 15 wt% PU insulating polymer solution (using commercially available waterborne polyurethane 2300H-3 as an example, hereinafter referred to as PU) for 15 minutes. After immersion, the fiber was removed, and the surface was smoothed with a scraper. Finally, it was air-dried to form a PU film protective layer that wrapped around the optical fiber. Its structure is as follows: Figure 1 As shown.

[0050] Example 2

[0051] refer to Figure 2 The preparation process involves preparing 80% HEMA and 1% PEG by mass. (700)An aqueous solution of -DA and 1% I2959 (by mass) was prepared. Nitrogen gas was bubbled into the aqueous solution for 5 min to remove oxygen, followed by centrifugation (3000 rpm / min) to remove air bubbles. The aqueous solution was injected into hollow PFA tubes with inner and outer diameters of 300 and 400 μm, respectively, using a syringe. After sealing, the tubes were irradiated with a UV lamp (365 nm wavelength) for 60 min. After the solution in the tubes solidified, they were removed and immersed in pure water for 3 days to achieve purification (removal of residual small molecules), yielding the optical fiber.

[0052] The optical fiber was immersed in a 1 wt% KH-570 solution (the solvent being 98% ethanol + 1.5% water + 0.5% acetic acid), then removed and further immersed in a solution containing 15 wt% PVA-AA, 1.3 wt% PEDOT:PSS, and PEG. (700) The sample was immersed in a conductive layer prepolymer solution containing 2 wt% DA and 1.5 wt% I2959 for 3 minutes. After immersion, the sample was removed, the surface was smoothed with a scraper, and then cured under a 365 nm UV lamp for 60 seconds (30 seconds for each side, UV lamp power 250 mW / cm²). 2 ).

[0053] The conductive-treated optical fiber was immersed in a 15 wt% PU insulating polymer solution for 15 minutes. After immersion, it was removed, and the surface was smoothed with a scraper. Finally, it was air-dried to form a PU film protective layer that wrapped around the optical fiber. Its structure is as follows: Figure 1 As shown.

[0054] Example 3

[0055] refer to Figure 2 The preparation process involves preparing 75% HEMA and 1.5% PEG by mass. (700) An aqueous solution of -DA and 0.8% I2959 was prepared. Nitrogen gas was bubbled into the aqueous solution for 5 min to remove oxygen, followed by centrifugation (3000 rap / min) to remove air bubbles. The aqueous solution was injected into hollow PFA tubes with inner and outer diameters of 300 and 400 μm, respectively, using a syringe. After sealing, the tubes were irradiated with a UV lamp (365 nm wavelength) for 60 min. After the solution in the tubes solidified, they were removed and immersed in pure water for 3 days to achieve purification (removal of residual small molecules), yielding the optical fiber.

[0056] The optical fiber was immersed in a 1.2 wt% KH-570 solution (the solvent being 98% ethanol + 1.5% water + 0.5% acetic acid), then removed and immersed in a solution containing 15 wt% PVA-AA, 1.3 wt% PEDOT:PSS, and PEG. (700) The sample was immersed in a conductive layer prepolymer solution containing 2 wt% DA and 1.5 wt% I2959 for 3 minutes. After immersion, the sample was removed, the surface was smoothed with a scraper, and then cured under a 365 nm UV lamp for 60 seconds (30 seconds for each side, UV lamp power 250 mW / cm²). 2 ).

[0057] The conductive-treated optical fiber was immersed in a 10 wt% PU insulating polymer solution for 15 minutes. After immersion, the fiber was removed, and the surface was smoothed with a scraper. Finally, it was air-dried to form a PU film protective layer that encapsulated the optical fiber. Its structure is as follows: Figure 1 As shown.

[0058] Example 4

[0059] refer to Figure 2 The preparation process involves preparing 90% HEMA and 1% PEG by mass. (700) An aqueous solution of -DA and 1.5% I2959 was prepared. Nitrogen gas was bubbled into the aqueous solution for 5 min to remove oxygen, followed by centrifugation (3000 rpm / min) to remove air bubbles. The aqueous solution was injected into hollow PFA tubes with inner and outer diameters of 300 and 400 μm, respectively, using a syringe. After sealing, the tubes were irradiated with a UV lamp (365 nm wavelength) for 60 min. After the solution in the tubes solidified, they were removed and immersed in pure water for 3 days to achieve purification (removal of residual small molecules), yielding the optical fiber.

[0060] The optical fiber was immersed in a 1.2 wt% KH-570 solution (the solvent being 98% ethanol + 1.5% water + 0.5% acetic acid), then removed and immersed in a solution containing 15 wt% PVA-AA, 1.3 wt% PEDOT:PSS, and PEG. (700) The sample was immersed in a conductive layer prepolymer solution containing 2 wt% DA and 1.5 wt% I2959 for 3 minutes. After immersion, the sample was removed, the surface was smoothed with a scraper, and then cured under a 365 nm UV lamp for 60 seconds (30 seconds for each side, UV lamp power 250 mW / cm²). 2 ).

[0061] The conductive-treated optical fiber was immersed in a 20 wt% PU insulating polymer solution for 15 minutes. After immersion, it was removed, and the surface was smoothed using a scraper (a hollow mold of suitable size). Finally, it was air-dried to form a PU film protective layer that wrapped around the optical fiber. Its structure is as follows: Figure 1 As shown.

[0062] Example 5: Technical route for preparing HEMA hydrogel for the light guide core layer

[0063] The light-guiding performance of this hydrogel neural probe is one of its core properties; higher transparency and refractive index result in better light-guiding performance. The homogeneity of the hydrogel network determines its transparency and refractive index, which can be adjusted by changing the solid content of HEMA or the water content of the hydrogel. An example formulation for this solution is as follows: HEMA as the monomer, PED... (m) -DA was used as a crosslinking agent (m=700 is an example), and I2959 was used as a photoinitiator. Since HEMA molecules become opaque after polymerization due to the hydrophobic effect of the methyl group (once the phase separates), adjusting the molecular weight and the water content during the preparation process are two important control parameters. The optimized ratios are shown in Table 1. The transmittance and refractive index in the visible light range (400-800 nm) were measured as follows: Figure 3 and Figure 4 As shown; secondly, since the hydrogel is polymerized in a PFA tube with an inner diameter of only 300 μm, the reactivity may be significantly lower than that of a large container used as a mold. Simultaneously, photo-initiated polymerization often releases a large amount of heat, leading to localized liquid vaporization, potentially causing micro-defects and light leakage during light transmission. Therefore, controlling the intensity of the reaction is crucial, and this will be achieved by adjusting the dosage of I2959 and the reaction time. The optimized ratios are shown in Table 2. The final optimization factor is the content of the crosslinking agent, as the degree of crosslinking in the hydrogel network structure affects the strength and swelling rate of the HEMA hydrogel. The optimization results are shown in Table 3. The optimal preparation scheme is: HEMA solid content 80 wt%; I2959 dosage 1 wt%; optimal reaction time 60 min; crosslinking agent PEG(700)-DA dosage 1 wt%.

[0064] Table 1: Optimization scheme for solid content of HEMA

[0065]

[0066] Special note: The above measurement results and the experimental results involved in this invention are all average values ​​of three or more measurement data.

[0067] Table 2: Based on Table 1, the preferred HEMA solid content is 80%, and the optimized I2959 content is...

[0068]

[0069] Special note: wt% is calculated based on a total volume of 100 parts (e.g., 100 parts total volume contains 80 parts HEMA and 20 parts water).

[0070] Table 3: Based on the preferred HEMA solid content of 80 wt% in Table 1, the preferred I2959 feed amount of 1 wt% in Table 2, and the preferred reaction time of 60 min, PEG-DA was further optimized.

[0071]

[0072] Special note: wt% is calculated based on a total volume of 100 parts (e.g., 100 parts total volume contains 80 parts HEMA and 20 parts water).

[0073] Example 6: Optimized technical route for the preparation of conductive layer PEDOT:PSS hydrogel

[0074] To optimize the conductivity of the hydrogel probe, this invention focuses on optimizing the components and their proportions in the PEDOT:PSS hydrogel preparation formulation. Simultaneously, to achieve a robust interface formation of the conductive layer on the PFA tube surface, further optimization of the preparation method is necessary. This mainly includes PEDOT:PSS, PVA-AA, illumination time, hydrophilic modification conditions of the PFA tube, and parameters related to the dip-coating method. The PEDOT:PSS hydrogel preparation is shown in Table 4; the conductivity (impedance change) and conductive layer thickness under the most critical dip-coating operation optimization conditions are shown in Tables 5 and 6. Figure 5 As shown in Table 6; simultaneously, to characterize the long-term working stability of the conductive layer, the prepared conductive hydrogel neural probe was immersed in PBS for 30 days, and impedance changes were monitored. The results are shown in Table 6 and... Figure 6 As shown.

[0075] Table 4: Optimization of components in PEDOT:PSS formulation

[0076]

[0077] Special note: wt% is calculated with water as 100 parts of solvent in the system (for example, 1wt% = 1g of solute in 100g of water).

[0078] The five factors mentioned above are adjusted individually to optimize the overall performance of the final product of the photocurable bio-adhesive, with mechanical and adhesive properties being the primary considerations. Preferably, the amount of PEDOT:PSS used is 1.3 wt% (due to PEDOT:PSS solubility limitations); the amount of photoinitiator I2959 used is 2 wt% with a light exposure time of 60 s (30 s for each side); and the crosslinking agent is PEG. (700) - The amount of DA used is 2 wt%. The apparatus used for measuring the conductive layer impedance can be found in [reference needed]. Figure 9 .

[0079] Table 5: Changes in thickness and impedance corresponding to the number of dip-coating cycles during conductive layer fabrication

[0080]

[0081] Under the premise of ensuring an impedance of less than 300 KΩ (for recording electrophysiological signals with a higher signal-to-noise ratio), the smaller the probe size, the lower the invasive damage caused by implantation. Therefore, the preferred number of dipping and coating cycles is 3.

[0082] Table 6: Long-term stability test results of conductive layer

[0083]

[0084] Example 7: Optimization of Insulation Layer Preparation Scheme

[0085] The insulating layer consists of an aqueous polyurethane film. The hydrogel neural probe, after the conductive layer is introduced, is immersed in an aqueous polyurethane solution, preferably at a concentration of 15 wt% (the optimal dispersion ratio of the emulsion). Different thicknesses of insulating layers can be obtained by selecting the dip-coating operation parameters to meet application requirements. The changes in surface resistance and corresponding thicknesses after insulation are shown in Table 7. Figure 7 As shown. The following are the optimized preparation conditions:

[0086] Table 7: Optimization of Dip Coating Operation Parameters Introduced by PU Insulation Layer

[0087]

[0088] After PU insulation, the surface resistance increases significantly by 5-10 times to achieve the purpose of insulation. To ensure better insulation effect and its long-term working stability under physiological conditions, the preferred number of PU coatings is 2.

[0089] Example 8: Testing the Bending Stiffness of a Hydrogel Neural Probe

[0090] After implantation into brain tissue, the neural probe will deform under the micro-perturbation environment of the brain tissue. Its bending stiffness is used as an evaluation criterion to characterize the tissue mechanical adaptability of the neural probe. The lower the bending stiffness, the greater the deformation with brain tissue perturbation, and the smaller the stress concentration effect, thus exhibiting less brain tissue damage. The bending stiffness of the neural probe is characterized by a single cantilever bending test, with stainless steel and other materials used as controls for invasive neural probes. The test results are as follows: Figure 8 As shown. The single cantilever bending test can be referenced. Figure 11 .

[0091] Example 9: Measurement of Optical Transmission Loss of Hydrogel Neural Probe

[0092] In the optimization of the light guide core layer fabrication process in Case Study 1, the transparency and refractive index of the HEMA hydrogel were selected as the optimal parameters. These parameters ultimately manifest as light transmission loss in the probe performance. This loss was measured using the truncation method; for specific implementation details, please refer to the "Light Guide Efficiency Measurement" section for further information. Figure 10 The optical loss test results of the hydrogel neural probe obtained under the preferred preparation method are as follows: Figure 9 As shown.

[0093] It should be understood that the application of the present invention is not limited to the examples above. Those skilled in the art can make improvements or modifications based on the above description, and all such improvements and modifications should fall within the protection scope of the appended claims.

Claims

1. An electrically conductive hydrogel neural probe, comprising: The application relates to a conductive hydrogel nerve probe. The conductive hydrogel nerve probe comprises a light-guiding core, a light-guiding shell, a conductive layer and an insulating layer. The light-guiding core is a hydrogel formed by cross-linking of a photo initiator, a water-soluble double-bonded olefin monomer and a first cross-linking agent. The light-guiding shell is a transparent tube with a refractive index smaller than that of the hydrogel. The conductive layer is a hydrogel layer formed by cross-linking of a photo initiator, a conductive polymer and a second cross-linking agent. The insulating layer is formed on the surface of the conductive layer. The water-soluble double-bonded olefin monomer comprises acrylic acid or an acrylamide compound. The acrylamide compound comprises hydroxyethyl methacrylate, acrylamide and hydroxyethyl acrylamide.

2. A method of preparing the conductive hydrogel neural probe of claim 1, wherein, The conductive polymer comprises polyaniline, polypyrrole, poly (2,3-dihydrothiophene-1,4-dioxide) -poly (styrene sulfonate) and poly-p-phenylstyrene. The first cross-linking agent and the second cross-linking agent are independently selected from PEG (m)-DA, ethylene glycol dimethacrylate, triethylene glycol dimethacrylate and N, N-methylene bisacrylamide. The application also discloses a preparation method of the conductive hydrogel nerve probe. The transparent plastic tube or silica gel tube is provided. A mixed solution containing a water-soluble double-bonded olefin monomer and a first cross-linking agent is injected into the transparent plastic tube or silica gel tube to obtain a light-guiding optical fiber through a first curing treatment. A conductive layer pre-polymer solution containing a conductive polymer compound and a second cross-linking agent is coated on the surface of the light-guiding optical fiber to obtain a conductive layer through a second curing treatment. A solution containing an insulating polymer is coated on the surface of the conductive layer, and the conductive hydrogel nerve probe is obtained after drying.

3. The method of claim 2, wherein the conductive hydrogel neural probe is prepared by the steps of: The mixed solution containing the water-soluble double-bonded olefin monomer and the first cross-linking agent further contains a photo initiator.

4. The electrically conductive hydrogel neural probe of claim 2, wherein, The conductive layer pre-polymer solution containing the conductive polymer compound and the second cross-linking agent further contains a photo initiator.

5. The method for preparing the conductive hydrogel neural probe according to claim 2, characterized in that, The mass fraction of the water-soluble double-bonded olefin monomer in the mixed solution containing the water-soluble double-bonded olefin monomer and the first cross-linking agent is 70-90%.

6. The method of claim 5, wherein the conductive hydrogel neural probe is prepared by the steps of: The photo initiator is selected from any one of 2-hydroxy-4-(2-hydroxyethoxy)-2-methylpropiophenone, alpha-ketoglutaric acid, phenyl-2,4,6-trimethylbenzoyl lithium phosphite and 2-hydroxy-2-methylpropiophenone. The mass fraction of the photo initiator is 0.3-3%. The mass fraction of the insulating polymer in the solution containing the insulating polymer is 10-20%.

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