Temperature-adaptive continuous glucose detection system working electrode and preparation method and application thereof

By forming nanochannels on the CGMS working electrode and depositing temperature-adaptive particles, the diffusion rate of glucose molecules is automatically adjusted, solving the problem of unstable sensitivity of CGMS at different temperatures, achieving more accurate glucose detection and reducing the risk of equipment failure.

CN120629301APending Publication Date: 2025-09-12HUZHOU MEIQI MEDICAL EQUIP CO LTD
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Patent Information

Application Number
CN202510940961.9
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-07-09
Publication Date
2025-09-12

AI Technical Summary

Technical Problem

The existing continuous glucose monitoring system (CGMS) has unstable sensitivity at different temperatures and is greatly affected by temperature, resulting in inaccurate measurement data. Existing devices also increase the risk of equipment failure.

Method used

The temperature-adaptive continuous glucose detection system working electrode automatically adjusts the diffusion rate of glucose molecules by forming nanochannels on the substrate layer and depositing temperature-adaptive particles to offset the impact of temperature increase on the detection results.

Benefits of technology

It effectively reduces the impact of temperature on glucose detection, improves the stability and accuracy of the detection system, and reduces the risk of equipment failure.

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Abstract

The invention relates to the technical field of intelligent glucose monitoring materials, in particular to a temperature-adaptive continuous glucose monitoring system working electrode and a preparation method and application thereof. The metal catalyst layer covers the surface of the conductive substrate; the glucose oxidase layer covers the surface of the metal catalyst layer; the substrate layer covers the surface of the glucose oxidase layer; the nano-channel layer covers the surface of the substrate layer and is provided with a nano-channel; temperature self-adaptive particles are deposited in the nano-channel, and the volume of the temperature self-adaptive particles is expanded when the temperature rises, so that the effective aperture of the nano-channel is reduced, and the increase of the diffusion rate of glucose is inhibited. The polymer layer with the nano-channel is formed on the substrate layer through polycondensation, the temperature self-adaptive particles are deposited in the nano-channel, and when the temperature of the particles rises, the size of the particles is increased, the particles occupy the nano-channel, and the diffusion rate is reduced, so that the phenomenon that the diffusion rate is increased due to temperature rise is counteracted.
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Description

Technical Field

[0001] The present invention relates to the technical field of intelligent glucose monitoring materials, and in particular to a temperature-adaptive continuous glucose detection system working electrode, a preparation method and an application thereof. Background Art

[0002] According to the "Global Diabetes Atlas" released by the International Diabetes Federation (IDF), the number of adults with diabetes worldwide reached 537 million in 2021, with a compound annual growth rate of approximately 3.91% from 2011 to 2021. This proportion accounts for approximately 10% of the global population and is projected to reach 643 million by 2030. Among these, the number of adults with diabetes in China reached 141 million in 2021, and is projected to reach 164 million in 2030 and 174 million in 2045. According to IDF estimates, approximately 51.7% of adults with diabetes in China were undiagnosed in 2021, primarily due to a lack of self-diabetes monitoring devices and the invasiveness and inconvenience of existing devices, which discourage their use. In recent years, continuous glucose monitoring systems (CGMS) have gradually gained recognition in both domestic and international markets, and blood glucose fluctuation parameters based on CGMS data have been widely used in clinical practice. Unlike single-point blood glucose measurement, typically achieved through blood glucose test strips, the CGMS system effectively reflects the relationship between daily activities and blood glucose fluctuations in diabetic patients, facilitating rational medication use by doctors and patients. The working electrodes of existing CGMS systems typically consist of a substrate, a metal electrochemical layer, a glucose oxidase layer, and a diffusion-limiting layer. The principle is that glucose oxidase catalyzes the decomposition of glucose into hydrogen peroxide. The electrode captures the electrochemical signal from this reaction, which exhibits a linear relationship between signal strength and glucose concentration. The glucose concentration can be calculated by converting the signal strength into the desired value, thereby achieving glucose concentration monitoring.

[0003] Since the current CGMS uses electrical signals through electrochemical methods, the electrochemical reaction will be greatly affected by temperature. Therefore, the sensitivity of CGMS is different at different temperatures. For every 1°C increase, the sensitivity increases by about 8-10%. When the user's body temperature changes, or when the CGMS is testing its performance in vitro, if the CGMS continues to use the original sensitivity to convert the electrical signal, it will lead to inaccurate measurement data. In addition, the CGMS is implanted in the human epidermis for use, and its operating temperature is easily affected by the external ambient temperature. Therefore, it is very necessary to develop a CGMS that can reduce the impact of temperature. Existing technologies mostly use temperature or other temperature-related indicators for monitoring, and re-convert the electrical signal based on the monitoring results. Using this method will increase the number of devices that the CGMS needs to carry, and the risk of equipment failure will increase. Summary of the Invention

[0004] The purpose of the present invention is to solve the above-mentioned problems existing in the current CGMS at different temperatures and to provide a temperature-adaptive continuous glucose monitoring system working electrode and its preparation method and application.

[0005] In a first aspect, the present invention provides a temperature-adaptive continuous glucose monitoring system working electrode, which realizes automatic temperature calibration through the adaptive function of the material, making the CGMS less susceptible to temperature interference.

[0006] The following technical solutions are adopted:

[0007] A temperature-adaptive continuous glucose monitoring system working electrode, comprising:

[0008] Conductive substrate;

[0009] A metal catalyst layer covering the surface of the conductive substrate;

[0010] a glucose oxidase layer covering the surface of the metal catalytic layer;

[0011] The basal layer covers the surface of the glucose oxidase layer;

[0012] a nanochannel layer covering the surface of the substrate layer, the nanochannel layer comprising nanochannels;

[0013] Temperature-adaptive particles are deposited in the nanochannel. When the temperature rises, the volume of the temperature-adaptive particles expands, which reduces the effective pore size of the nanochannel and inhibits the increase of the glucose diffusion rate.

[0014] Preferably, the pore size of the nanochannel is 100-300 nm.

[0015] Preferably, the raw materials for forming the temperature-adaptive particles include the following components in parts by weight: 5-10 parts of inorganic metal salt, 6-8 parts of organic ligand, and 70-90 parts of solvent.

[0016] Preferably, the inorganic metal salt is one or more of zinc nitrate, zirconium chloride and titanium chloride.

[0017] Preferably, the organic ligand is one or more of phthalic acid, trimesic acid, and trimesic acid.

[0018] Preferably, the raw materials for forming the nanochannel layer include:

[0019] Composition 1: 10-20 parts of polymerizable monomer 1, 80-90 parts of solvent 1, wherein the polymerizable monomer 1 is one or more of ethylenediamine, 1,3-propylenediamine, and 1,4-butylenediamine;

[0020] Composition 2: 15-25 parts of polymerizable monomer 2 and 75-85 parts of solvent 1, wherein the polymerizable monomer 2 is one or more of isophthaloyl chloride, terephthaloyl chloride, and trimesoyl chloride.

[0021] A second aspect of the present invention provides a method for preparing the working electrode, comprising the following steps:

[0022] S1 provides a conductive substrate having a metal catalyst layer and a glucose oxidase layer sequentially formed on the surface;

[0023] S2. Immersing the conductive substrate in a basement membrane solution to form a base layer on the conductive substrate;

[0024] S3. The conductive substrate in S2 is sequentially immersed in a monomer solution, dried, immersed in a monomer solution II, dried, and washed to form a nanochannel layer on the conductive substrate;

[0025] S4. The conductive substrate in S3 is placed in a suspension containing temperature-adaptive nanoparticles to obtain a working electrode for a temperature-adaptive continuous glucose monitoring system.

[0026] Preferably, the operation of step S2 is:

[0027] S21. Mix 15-25 parts of a polymer with 75-85 parts of an organic solvent, heat to 45-60°C to dissolve, and form a uniform solution. Then, dropwise add 0-15 parts of ultrapure water and mix thoroughly. Finally, add 1-4 parts of polyethylene glycol and dissolve completely. Cool to room temperature to form a basement membrane solution. The polymer is one or more of polysulfone, polyethersulfone, polyacrylonitrile, and polyacrylamide.

[0028] S22. Take a conductive substrate with a metal catalytic layer and a glucose oxidase layer formed on the surface in sequence, immerse it in the above-mentioned basement membrane liquid, repeat 2-5 times, place it in room temperature air conditions for 10-30 minutes, and then put it into a vacuum drying oven. Store it at 25°C and -0.09MPa for 3-5 hours. The basement layer is completed.

[0029] Preferably, the operation of step S3 is:

[0030] S31 preparing a monomer solution and a monomer solution II;

[0031] S32. The conductive substrate obtained in step S2 is immersed in a monomer solution for 30-60s to fully absorb the solution, and the working electrode is slowly removed and dried at room temperature for 2-5min;

[0032] S33. The dried conductive substrate was immersed in the monomer solution II for 30-60 seconds to perform a polycondensation reaction, and the working electrode was slowly removed and dried at room temperature for 7-10min;

[0033] S34. Repeat steps S32- S33, repeating 1-4 times;

[0034] S35. Ultrasonic cleaning with one or more solutions of ethanol, ultrapure water, or acetone;

[0035] S36. The cleaned conductive substrate is stored at 25°C and -0.09 MPa for 3-5 hours to complete the fabrication of the nanochannel layer.

[0036] Preferably, in step S4, the preparation method of the suspension containing temperature-adaptive nanoparticles is as follows:

[0037] A. Take 5-10 parts of inorganic metal salt, 6-8 parts of organic ligand, and 70-90 parts of solvent, mix well, react at 100-150°C for 12-36 hours, and cool to obtain powder;

[0038] B. The powder is ultrasonically cleaned with ultrapure water for 4-6 times, each time for 5-10 minutes, and after drying, stored at 25°C and -0.09 MPa for 3-5 hours to obtain temperature-adaptive nanoparticles. The obtained particles have a porous and fluffy structure, which is more likely to expand after heating. The expansion of the porous structure also enhances the electrostatic adsorption capacity of glucose molecules, and can adjust the diffusion rate of glucose molecules as the temperature changes.

[0039] C. Mix 3-5 parts of temperature-adaptive nanoparticles, 0.02-0.05 parts of thickener, and 100 parts of solvent, and then ultrasonicate for 5-10 minutes to form a uniform suspension containing temperature-adaptive nanoparticles.

[0040] A third aspect of the present invention provides a continuous glucose monitoring system comprising the above-mentioned working electrode.

[0041] By implementing the above technical solution, compared with the prior art, the present invention has the following beneficial effects:

[0042] 1. The present invention forms a polymer layer with nanochannels on the base layer by polycondensation, which limits the speed at which glucose molecules pass through, changes the diffusion model of glucose molecules from free diffusion to spatial hindrance, and reduces the influence of temperature on the diffusion rate.

[0043] 2. Furthermore, the present invention deposits temperature-adaptive particles in the nanochannels. When the temperature rises, these particles will increase in volume, occupy the nanochannels, and increase the adsorption force on glucose molecules, thereby reducing the diffusion rate to offset the phenomenon of increased diffusion rate caused by temperature increase.

[0044] 3. According to the average pore size of the nanochannel (actually characterized by the basic sensitivity), the deposition time of the temperature-adaptive particles is adjusted so that the proportion of the pore volume occupied by the temperature-adaptive particles is basically consistent. DETAILED DESCRIPTION

[0045] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments will be clearly and completely described below in combination with the embodiments of the present invention. The following embodiments are used to illustrate the present invention but are not used to limit the scope of the present invention.

[0046] Example 1

[0047] This embodiment provides a working electrode for a continuous glucose detection system. The working electrode has a temperature adaptive function and can automatically adjust the diffusion rate of glucose molecules according to temperature changes, thereby correcting the influence of temperature on the detection results.

[0048] The working electrode was prepared by the following method:

[0049] S1. Provide a semi-finished working electrode: the semi-finished working electrode includes a 304 stainless steel conductive substrate and a metal electrochemical layer (metal gold), a metal catalytic layer (metal platinum), and a glucose oxidase layer sequentially arranged outside the conductive substrate.

[0050] S2. Basal layer preparation:

[0051] S21. Mix 20 parts by weight of polyacrylamide with 80 parts by weight of N-methylpyrrolidone, heat to 60°C to dissolve to form a uniform solution, then dropwise add 10 parts by weight of ultrapure water, mix evenly, and finally add 1 part by weight of polyethylene glycol, dissolve completely, and cool to room temperature to form a basement membrane fluid.

[0052] S22. Take the semi-finished working electrode in S1 and immerse it in the above-mentioned basement membrane solution (submerged), repeat 2-5 times, place it in room temperature air conditions for 30 minutes, and then place it in a vacuum drying oven and store it at 25°C and -0.09MPa for 3 hours. The basement layer is completed.

[0053] S3. Fabrication of Nanochannel Layer:

[0054] S31. Dissolve 20 parts of ethylenediamine in 80 parts of ultrapure water to form a 20% monomer solution 1.

[0055] S32. Dissolve 25 parts of trimesoyl chloride in 75 parts of n-hexane, and then add 0.04 parts of tetrabutylammonium bromide to form a 25% monomer solution 2.

[0056] S33. Immerse the working electrode containing the substrate layer in the monomer solution for 60 seconds to fully absorb the solution, slowly remove the working electrode, and dry it at room temperature for 5 minutes;

[0057] S34. The dried working electrode was immersed in monomer solution 2 for 60 seconds to perform polycondensation reaction, and the working electrode was slowly removed and dried at room temperature for 10 minutes;

[0058] S35. Repeat steps 33 and 34 a total of three times to form a nanochannel layer on the substrate layer;

[0059] S36. Ultrasonic clean the surface with ultrapure water for 5 minutes. Replace the cleaning solution and clean again. Clean the surface 3-6 times in total.

[0060] S37. The cleaned electrode is stored at 25°C and -0.09 MPa for 3 hours to complete the fabrication of the nanochannel layer.

[0061] S38. Test the sensitivity of the working electrode containing the nanochannel layer, the value is 12.5 nA / mM, and set aside.

[0062] S4. Deposition of temperature-adaptive nanoparticles:

[0063] S41. Take 5 parts of zinc nitrate, 6 parts of phthalic acid, and 89 parts of DMAC, mix them evenly, put them into an autoclave, and react at 100° C. for 12 hours.

[0064] S42. After cooling, filter the obtained powder and ultrasonically clean it with ultrapure water 4 times, each time for 5 minutes.

[0065] S43. Store at 25°C and -0.09 MPa for 3 h to obtain temperature-adaptive nanoparticles for later use.

[0066] S44. 5 parts of the above powder, 0.02 parts of carboxymethyl cellulose ether as a thickener, and 100 parts of ultrapure water were mixed, and then ultrasonicated for 10 minutes to form a uniform suspension of temperature-adaptive nanoparticles.

[0067] S45. Immerse the working electrode containing the nanochannel layer twice in an ethanol solution containing 10% KH560 silane coupling agent. Remove and dry at room temperature for 5 minutes. Then immerse it in the above suspension and sonicate for 7 minutes. (The sonication time is determined by the sensitivity measured above. The higher the sensitivity, the longer the sonication time. A working electrode with high sensitivity indicates larger nanochannels, allowing glucose to pass more easily. Therefore, it takes longer to deposit the temperature-adaptive nanoparticles, ensuring that the proportion of nanochannels occupied by the particles in each working electrode is roughly the same.)

[0068] S46. After the deposited temperature-adaptive nanoparticles are washed with ultrapure water for 1-2 times, they are stored at 25°C and -0.09 MPa for 3 hours to obtain a working electrode with temperature-adaptive function.

[0069] Example 2

[0070] This embodiment provides a working electrode for use in a continuous glucose monitoring system to resist temperature interference.

[0071] The working electrode was prepared by the following method:

[0072] S1. Provide a semi-finished working electrode: the semi-finished working electrode includes a 304 stainless steel conductive substrate and a metal electrochemical layer (metal gold), a metal catalytic layer (metal platinum), and a glucose oxidase layer sequentially arranged outside the conductive substrate.

[0073] S2. Basal layer preparation:

[0074] S21. Mix 15 parts of polysulfone with 85 parts of organic solvent N-methylpyrrolidone, heat to 55°C to dissolve and form a uniform solution, then add 10 parts of ultrapure water dropwise and mix evenly, finally add 4 parts of polyethylene glycol and dissolve completely, cool to room temperature to form a basement membrane fluid.

[0075] S22. Take the semi-finished working electrode in S1 and immerse it in the above-mentioned basement membrane solution twice. Place it in room temperature and air conditions for 30 minutes, then place it in a vacuum drying oven and store it at 25°C and -0.09 MPa for 5 hours. The basement layer is then completed.

[0076] S3. Fabrication of Nanochannel Layer:

[0077] S31. Dissolve 10 parts of 1,4-diaminobutane in 90 parts of ethanol to form a 10% monomer solution 1.

[0078] S32. Dissolve 15 parts of isophthaloyl dichloride in 85 parts of n-hexane, and then add 0.01 parts of tributylamine as a phase transfer catalyst to form a 15% monomer solution 2.

[0079] S33. Immerse the working electrode containing the substrate layer in the monomer solution for 60 seconds to fully absorb the solution, slowly remove the working electrode, and dry it at room temperature for 5 minutes;

[0080] S34. The dried working electrode was immersed in monomer solution 2 for 30 seconds to perform polycondensation reaction, and the working electrode was slowly removed and dried at room temperature for 10 minutes;

[0081] S35. Repeat steps 33 and 34 a total of 4 times to form a nanochannel membrane on the polymer substrate;

[0082] S36. Ultrasonic clean the surface with ethanol solution for 5 minutes, then replace the cleaning solution and clean again. Clean the surface a total of 6 times.

[0083] S37. The cleaned electrode is stored at 25°C and -0.09 MPa for 5 hours to complete the fabrication of the nanochannel layer.

[0084] S38. Test the sensitivity of the working electrode containing the nanochannel layer, the value is 10.6 nA / mM, and set aside.

[0085] S4. Deposition of Temperature-Adaptive Nanoparticles

[0086] S41. Take 10 parts of inorganic metal salt zirconium chloride, 6 parts of trimellitic acid, and 84 parts of DMF, mix them evenly, put them into a high-pressure reactor, and react at 100°C for 20 hours.

[0087] S42. After cooling, filter the obtained powder and ultrasonically clean it with ultrapure water for 6 times, each time for 10 minutes.

[0088] S43. Store at 25°C and -0.09 MPa for 5 hours to obtain temperature-adaptive nanoparticles for later use.

[0089] S44. 3 parts of the above powder, 0.05 parts of sodium alginate as a thickener, and 100 parts of ethanol were mixed, and then ultrasonicated for 10 minutes to form a uniform suspension of temperature-adaptive nanoparticles.

[0090] S45. Immerse the working electrode containing the nanochannel layer twice in an ethanol solution containing 15% KH560 silane coupling agent. After taking it out, dry it at room temperature for 5 minutes, immerse it in the above suspension, and sonicate it for 5 minutes.

[0091] S46. After the deposited temperature-adaptive nanoparticles are washed twice with ultrapure water, they are stored at 25° C. and -0.09 MPa for 3 hours to obtain a working electrode with temperature-adaptive function.

[0092] Example 3

[0093] The working electrode provided in this embodiment differs from that in embodiment 2 in S41. In this embodiment, S41 is to take 10 parts of titanium chloride, 6 parts of trimesic acid, and 84 parts of DMF, mix them evenly, put them into a high-pressure reactor, and react them at 110° C. for 20 hours.

[0094] Example 4

[0095] The working electrode provided in this embodiment differs from that in embodiment 2 in that S3 is as follows:

[0096] S31. Dissolve 15 parts of 1,3-propylenediamine in 85 parts of ethanol to form a 15% monomer solution 1.

[0097] S32. Dissolve 15 parts of isophthaloyl dichloride in 85 parts of n-hexane, and then add 0.01 parts of tributylamine as a phase transfer catalyst to form a 15% monomer solution 2.

[0098] S33. Immerse the working electrode containing the substrate layer in the monomer solution for 60 seconds to fully absorb the solution, slowly remove the working electrode, and dry it at room temperature for 2 minutes;

[0099] S34. The dried working electrode was immersed in monomer solution 2 for 30 seconds to perform polycondensation reaction, and the working electrode was slowly removed and dried at room temperature for 10 minutes;

[0100] S35. Repeat steps 33 and 34 a total of 4 times to form a nanochannel membrane on the polymer substrate;

[0101] S36. Ultrasonic clean the surface with ethanol solution for 5 minutes, then replace the cleaning solution and clean again. Clean the surface a total of 6 times.

[0102] S37. The cleaned electrode is stored at 25°C and -0.09 MPa for 5 hours to complete the fabrication of the nanochannel layer.

[0103] S38. Test the sensitivity of the working electrodes containing the nanochannel layer, and record the sensitivity of each working electrode for future use.

[0104] Example 5

[0105] The working electrode provided in this embodiment differs from that in embodiment 2 in that S3 is as follows:

[0106] S31. Dissolve 15 parts of ethylenediamine in 85 parts of ethanol to form a 15% monomer solution 1.

[0107] S32. Dissolve 15 parts of isophthaloyl dichloride in 85 parts of n-hexane, and then add 0.03 parts of tetrabutylammonium bromide as a phase transfer catalyst to form a 15% monomer solution 2.

[0108] S33. Immerse the working electrode containing the substrate layer in the monomer solution for 60 seconds to fully absorb the solution, slowly remove the working electrode, and dry it at room temperature for 2 minutes;

[0109] S34. The dried working electrode was immersed in monomer solution 2 for 30 seconds to perform polycondensation reaction, and the working electrode was slowly removed and dried at room temperature for 10 minutes;

[0110] S35. Repeat steps 33 and 34 a total of 4 times to form a nanochannel membrane on the polymer substrate;

[0111] S36. Ultrasonic clean the sample with ethanol for 5 minutes, then replace the cleaning solution and clean it again. This is a total of 6 cleaning cycles.

[0112] S37. The cleaned electrode is stored at 25°C and -0.09 MPa for 5 hours to complete the fabrication of the nanochannel layer.

[0113] S38. Test the sensitivity of the working electrodes containing the nanochannel layer, and record the sensitivity of each working electrode for future use.

[0114] Comparative Example 1

[0115] This comparative example provides a working electrode, which differs from Example 2 in that steps S3 and S4 are not performed, that is, the nanochannel layer and the deposition of temperature-adaptive nanoparticles are not provided.

[0116] Comparative Example 2

[0117] This comparative example provides a working electrode, which differs from Example 2 in that steps S3 and S4 are not performed, that is, the nanochannel layer and the deposition of temperature-adaptive nanoparticles are not provided, and the base layer adopts a traditional diffusion-limiting layer (polyvinyl chloride film).

[0118] Comparative Example 3

[0119] This comparative example provides a working electrode, which differs from Example 2 in that step S4 is not performed, that is, the deposition of temperature-adaptive nanoparticles is not performed.

[0120] Comparative Example 4

[0121] This comparative example provides a working electrode. Unlike Example 2, this one does not determine the deposition time based on baseline sensitivity; instead, the deposition time in step S45 is set to 15 minutes. The adaptive particles occupy too many nanochannels, causing them to expand excessively when the temperature rises. This significantly hinders glucose diffusion and reduces sensitivity.

[0122] Application Examples

[0123] Reference electrode preparation:

[0124] 1. Plate a layer of silver on the stainless steel needle blank;

[0125] 2. Through electrochemical reaction, a layer of silver chloride is deposited on the silver layer to form an Ag / AgCl electrode;

[0126] 3. Apply a diffusion-restricting layer (polyvinyl chloride film) on the outside of the electrode to form a reference electrode.

[0127] The working electrodes obtained in each embodiment and comparative example and the aforementioned reference electrode were assembled into sensors and fully polarized (for more than 60 minutes) with a PBS solution. The sensors were then placed in glucose solutions of varying concentrations and tested for their response currents under different temperatures. Linear regression was performed based on the response currents and glucose solution concentrations to obtain sensitivity data (i.e., linear regression slopes) at different temperatures. The results are shown in Table 1.

[0128] Table 1

[0129] 25℃ sensitivity 37℃ sensitivity 37℃ / 25℃ 40℃ sensitivity 40℃ / 25℃ Example 1 8.5 8.8 1.035 9.0 1.059 Example 2 7.8 8.0 1.026 8.1 1.038 Example 3 7.0 7.3 1.040 7.4 1.060 Example 4 7.5 7.7 1.027 7.9 1.053 Example 5 8.0 8.3 1.038 8.4 1.050 Comparative Example 1 13.7 30.8 2.248 32.7 2.387 Comparative Example 2 6.7 17.2 2.567 18.6 2.776 Comparative Example 3 10.9 14.7 1.349 15.2 1.394 Comparative Example 4 5.9 4.5 0.763 4.3 0.729

[0130] The results show:

[0131] Compared with Example 2, the working electrodes of Comparative Examples 1 and 2 have no nanochannels and temperature-adaptive particles, and only use a diffusion-restricted layer. The sensitivity deviations measured under high and low temperature environments are huge.

[0132] Compared with Example 2, Comparative Example 3 contains only a base layer and a nanochannel layer on the working electrode, and no temperature-adaptive particle deposition is performed. Although the influence of temperature on sensitivity can be reduced, the effect is not as good as that of Example 2.

[0133] Compared with Example 2, in Comparative Example 4, the working electrode does not determine the deposition time based on the basic sensitivity. The deposition time is too long, and the adaptive particles occupy too many nanochannels, resulting in too much particle expansion volume when the temperature rises, excessive glucose diffusion hindrance, and reduced sensitivity.

Claims

1. A working electrode for a temperature-adaptive continuous glucose monitoring system, characterized in that: include: Conductive substrate; A metal catalyst layer covering the surface of the conductive substrate; a glucose oxidase layer covering the surface of the metal catalytic layer; The basal layer covers the surface of the glucose oxidase layer; a nanochannel layer covering the surface of the substrate layer, which has nanochannels with a pore size of 100-300 nm; Temperature-adaptive particles are deposited in the nanochannel. When the temperature rises, the volume of the temperature-adaptive particles expands, which reduces the effective pore size of the nanochannel and inhibits the increase of the glucose diffusion rate.

2. The working electrode according to claim 1, characterized in that The raw materials for forming the temperature-adaptive particles include the following components in parts by weight: 5-10 parts of inorganic metal salt, 6-8 parts of organic ligand, and 70-90 parts of solvent.

3. The working electrode according to claim 2, characterized in that The inorganic metal salt is one or more of zinc nitrate, zirconium chloride and titanium chloride.

4. The working electrode according to claim 2, characterized in that The organic ligand is one or more of phthalic acid, trimesic acid, and trimesic acid.

5. The working electrode according to claim 1, characterized in that The raw materials for forming the nanochannel layer include: Composition 1: 10-20 parts of polymerization monomer 1, 80-90 parts of solvent 1, wherein the polymerization monomer 1 is one or more of ethylenediamine, 1,3-propylenediamine, and 1,4-butylenediamine; Composition 2: 15-25 parts of polymerizable monomer 2 and 75-85 parts of solvent 1, wherein the polymerizable monomer 2 is one or more of isophthaloyl chloride, terephthaloyl chloride, and trimesoyl chloride.

6. The method for preparing a working electrode according to any one of claims 1 to 5, wherein: The steps include: S1 provides a conductive substrate having a metal catalyst layer and a glucose oxidase layer sequentially formed on the surface; S2. Immersing the conductive substrate in a basement membrane solution to form a base layer on the conductive substrate; S3. The conductive substrate in S2 is sequentially immersed in a monomer solution, dried, immersed in a monomer solution II, dried, and washed to form a nanochannel layer on the conductive substrate; S4. The conductive substrate in S3 is placed in a suspension containing temperature-adaptive nanoparticles to obtain a working electrode for a temperature-adaptive continuous glucose monitoring system.

7. The preparation method according to claim 6, characterized in that The operation of step S2 is: S21. Mix 15-25 parts of a polymer with 75-85 parts of an organic solvent, heat to 45-60°C to dissolve, and form a uniform solution. Then, dropwise add 0-15 parts of ultrapure water and mix thoroughly. Finally, add 1-4 parts of polyethylene glycol and dissolve completely. Cool to room temperature to form a basement membrane solution. The polymer is one or more of polysulfone, polyethersulfone, polyacrylonitrile, and polyacrylamide. S22. Take a conductive substrate with a metal catalytic layer and a glucose oxidase layer formed on the surface in sequence, immerse it in the above-mentioned basement membrane liquid, repeat 2-5 times, place it in room temperature air conditions for 10-30 minutes, and then put it into a vacuum drying oven. Store it at 25°C and -0.09MPa for 3-5 hours. The basement layer is completed.

8. The preparation method according to claim 6, characterized in that The operation of step S3 is: S31 preparing a monomer solution and a monomer solution II; S32. The conductive substrate obtained in step S2 is immersed in a monomer solution for 30-60s to fully absorb the solution, and the working electrode is slowly removed and dried at room temperature for 2-5min; S33. The dried conductive substrate was immersed in the monomer solution II for 30-60 seconds to perform a polycondensation reaction, and the working electrode was slowly removed and dried at room temperature for 7-10min; S34. Repeat steps S32- S33, repeating 1-4 times; S35. Ultrasonic cleaning with one or more solutions of ethanol, ultrapure water, or acetone; S36. The cleaned conductive substrate is stored at 25°C and -0.09 MPa for 3-5 hours to complete the fabrication of the nanochannel layer.

9. The preparation method according to claim 6, characterized in that In step S4, the preparation method of the suspension containing temperature-adaptive nanoparticles is as follows: A. Take 5-10 parts of inorganic metal salt, 6-8 parts of organic ligand, and 70-90 parts of solvent, mix well, react at 100-150°C for 12-36 hours, and cool to obtain powder; B. ultrasonically cleaning the powder with ultrapure water for 4-6 times, each time for 5-10 minutes, drying it, and storing it at 25° C. and −0.09 MPa for 3-5 hours to obtain temperature-adaptive nanoparticles; C. Mix 3-5 parts of temperature-adaptive nanoparticles, 0.02-0.05 parts of thickener, and 100 parts of solvent, and then ultrasonicate for 5-10 minutes to form a uniform suspension containing temperature-adaptive nanoparticles.

10. A continuous glucose monitoring system, characterized in that: The method comprises the working electrode according to any one of claims 1 to 5.