In-vivo blood glucose monitoring method and system based on microgel sensor

Abstract

The invention discloses an in-vivo blood glucose monitoring system based on microgel response characteristics, which is characterized by improving a microgel synthesis process, accurately characterizing physical properties and response characteristics of a material, optimizing the design of an implanted microgel sensor and constructing an electromagnetic detection module based on dielectric constant measurement. Accurate, real-time and continuous monitoring of the in-vivo blood glucose level is achieved. The system overcomes the problems of large trauma, discontinuous data, insufficient long-term stability, high cost and the like of a traditional blood drawing method by utilizing the remarkable volume and dielectric constant change of microgel under the conditions of low blood sugar and high blood sugar, and has the remarkable advantages of high sensitivity, quick response and long-term stability; a brand new technical scheme is provided for precise management of metabolic diseases such as diabetes, and the technical scheme also has a wide application prospect in other biomedical monitoring fields.

Description

Technical Field

[0001] The present invention relates to the field of continuous blood glucose monitoring for the human body, and provides a method and system for in-vivo blood glucose monitoring based on a microgel sensor. Background Art

[0002] In recent years, wireless implantable sensors have attracted extensive attention in the biomedical field due to their ability to achieve real-time in-vivo monitoring. Especially in disease management and continuous monitoring of physiological parameters, accurate, real-time, and long-term stable data collection is particularly crucial. Microgel, as a multifunctional gel material composed of highly dispersed polymer particles at the nanoscale, has a fine network structure and excellent water absorption. When faced with external environmental stimuli, it can rapidly undergo physical or chemical property changes. For example, under the influence of factors such as temperature, pH value, or blood glucose concentration, the microgel can exhibit volume expansion or contraction. This controllability makes microgel very suitable for sensor design, especially in applications that require high sensitivity and high specificity.

[0003] Blood glucose monitoring, as an important means for the management of diabetes and other metabolic diseases, plays an irreplaceable role in maintaining the health of patients. Currently, the main method for blood glucose monitoring clinically is intermittent blood sampling for detection. Although this method has high detection accuracy, its operation process has obvious trauma, and repeated blood sampling is prone to infection risks. In addition, the detection data is discontinuous and difficult to reflect the dynamic changes of blood glucose, which brings inconvenience to the daily management of patients. In order to reduce the pain of patients and achieve continuous monitoring, non-invasive and minimally invasive blood glucose monitoring technologies have emerged one after another in recent years. These technologies have made certain progress in reducing operation trauma and achieving real-time data collection; however, they still have deficiencies in detection accuracy, continuity, long-term stability, and cost control. Although some new continuous blood glucose monitoring systems can provide relatively detailed dynamic data, due to the high cost of equipment, the need for regular replacement of sensors, and the high requirements for accurate analysis of continuous data, they face great economic and technical challenges in large-scale clinical promotion.

[0004] In addition, existing sensors often have difficulty maintaining high response speed and sensitivity in the complex and dynamically changing physiological environment in the body, and are easily interfered by temperature, humidity, and other substances, resulting in large fluctuations or long-term instability of monitoring data. This not only affects the reliability of the continuous monitoring system, but also increases the uncertainty of data analysis and subsequent clinical decision-making. Therefore, there is an urgent need to develop a quasi-non-invasive, highly sensitive, and continuously stable operating continuous blood glucose monitoring method to meet the needs of modern clinical real-time accurate monitoring. Summary of the Invention

[0005] In view of the deficiencies of the prior art, the present invention proposes an in-vivo blood glucose monitoring method and system based on a microgel sensor, aiming to overcome the problems of large trauma, discontinuous data, insufficient long-term stability, and high cost existing in traditional blood glucose monitoring methods, so as to achieve accurate, real-time, and continuous monitoring of in-vivo blood glucose levels. The present invention constructs an in-vivo blood glucose monitoring system based on the response characteristics of microgels by synthesizing microgel nanomaterials, designing the structure of an implantable microgel sensor, and adopting electromagnetic detection and signal processing technologies.

[0006] To achieve the above technical objectives, the present invention adopts the following technical solutions:

[0007] An in-vivo blood glucose monitoring system based on a microgel sensor includes five major modules:

[0008] (1) Microgel material synthesis module;

[0009] (2) Particle size distribution characterization module;

[0010] (3) Time-domain characteristic characterization module;

[0011] (4) Implantable microgel sensor design module;

[0012] (5) Electromagnetic characteristic detection module.

[0013] Further, in the microgel material synthesis module, the microgel material is synthesized by precipitation polymerization of N-isopropylmethacrylamide, diacrylamide, and a blood glucose-sensitive monomer 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylacetic acid to form temperature-sensitive microgel particles with phenylboronic acid groups.

[0014] Further, the test conditions of the time-domain characteristic characterization module are as follows: 4 mg of microgel is dispersed in 2 mL of buffer solution, and after adding 10 μL of high-concentration glucose, the transmittance is continuously monitored at a concentration of 0 - 5 g / L.

[0015] Further, in the implantable microgel sensor design module, the sensor is formed by embedding the microgel particles in a polyvinyl alcohol matrix, and the polyvinyl alcohol matrix encapsulates the microgel particles through physical cross-linking.

[0016] Further, in the electromagnetic characteristic detection module, the module monitors the swelling state of the microgel sensor in real time through dielectric constant measurement, and the dielectric constant measurement is carried out in the frequency band of 0.5 - 6 GHz, and wireless data acquisition is realized through a vector network analyzer and a dielectric probe.

[0017] The present invention also provides an in-vivo blood glucose monitoring method based on a microgel sensor, including the following steps:

[0018] (1) Microgel synthesis: Feed materials according to the molar ratio of N-isopropylmethacrylamide, diacrylamide, and 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylacetic acid of 6.0:0.13:0.486, and generate microgels containing phenylboronic acid groups through precipitation polymerization reaction;

[0019] (2) Particle size and responsiveness characterization: Observe the dry particle size by SEM, measure the hydrated radius at different glucose concentrations by DLS, and establish a particle size-concentration calibration relationship;

[0020] (3) Dynamic response test: Verify the response speed of microgels to changes in glucose concentration within a certain time by ultraviolet spectrophotometer;

[0021] (4) Sensor preparation and implantation: Mix and crosslink microgels with PVA solution to form an implantable gel sensor and implant it subcutaneously;

[0022] (5) Electromagnetic signal detection: Real-time monitor the swelling state of the sensor through dielectric constant measurement, and convert the blood glucose concentration through the change of dielectric constant in a certain frequency band.

[0023] Further, in step (1), the argon pretreatment time of the polymerization reaction is ≥1 hour, and the reaction temperature is 70°C.

[0024] Further, in step (2), the concentration of the microgel dispersion for DLS test is 0.1 mg / mL, and the pH 7.4 buffer solution is phosphate buffered saline.

[0025] Further, in step (4), the sensor implantation position is subcutaneous in the upper arm, and the implantation depth is 2-5 mm.

[0026] Further, in step (5), the dielectric constant is 20.13-60.27.

[0027] The technical principle of the present invention:

[0028] 1. Synthesis method and property characterization of microgel materials

[0029] Microgel nanoparticles with high sensitivity to changes in blood glucose concentration were synthesized by using the precipitation polymerization process, using the copolymerization reaction of the monomer N-isopropylmethacrylamide and the monomer 4-(2-acrylamidoethylcarbamoyl)3-fluorophenylacetic acid, which is sensitive to blood glucose. By precisely controlling the feed amount of each component, the reaction temperature and time, the prepared microgel particles have a regular spherical structure, a narrow particle size distribution and excellent responsiveness. The microgel has a small volume under low blood glucose conditions, but under high blood glucose conditions, the hydrophilicity is enhanced due to the reaction of the phenylboronic acid groups in the microgel network with glucose, and the particles swell significantly, and the volume increases accordingly. This obvious change in physical parameters provides a reliable signal basis for blood glucose concentration detection. At the same time, in order to verify the response speed of the prepared microgel particles to changes in blood glucose concentration, the time domain characteristics of the microgel were characterized by ultraviolet spectrophotometry. The results showed that the microgel responded and reached expansion equilibrium within about 5 minutes, further verifying the nonlinear time domain response characteristics of the microgel in dynamic blood glucose monitoring, which provides strong support for the realization of highly sensitive and real-time blood glucose monitoring.

[0030] 2. Structural design of implantable microgel sensors

[0031] In order to achieve real-time monitoring in vivo, the present invention evenly disperses the synthesized microgel in a flexible matrix such as polyvinyl alcohol (PVA) to form a wireless implantable sensor with a compact overall structure and excellent mechanical flexibility. By forming crystal physical crosslinks in the PVA matrix, it can not only effectively encapsulate the microgel particles and ensure their long-term stability in the in vivo environment, but also have good biocompatibility, reducing tissue stimulation and rejection during implantation. The sensor design fully considers the influence of various factors such as temperature and humidity in the body, and ensures that the slight changes in the microgel response can be accurately captured in a dynamic physiological environment through structural optimization.

[0032] 3. Electromagnetic characteristics detection and signal processing technology

[0033] The present invention uses dielectric constant as a key detection parameter, and converts the size change of microgel in vivo caused by changes in blood glucose concentration into dielectric constant change through a wireless signal transmission module. The sensor is detected in real time using a vector network analyzer and a dedicated dielectric probe, and a quantitative relationship between dielectric constant and blood glucose concentration is established. Based on this relationship, we can quantitatively describe the changes of microgel sensors under different blood glucose concentrations, and achieve real-time estimation of blood glucose levels through the dielectric constant detected by an external sensor.

[0034] Compared with the prior art, the present invention has the following significant advantages:

[0035] 1. High sensitivity and fast response

[0036] Due to the extremely high sensitivity of the microgel material to changes in blood glucose concentration, fluctuations in blood glucose levels in the body can rapidly trigger changes in the volume and dielectric constant of the microgel, thus enabling real-time capture and accurate measurement of blood glucose levels. Experimental results show that there are significant differences of nearly two times and nearly three times in the diameter and dielectric constant of microgel particles under hypoglycemic and hyperglycemic conditions, respectively, ensuring the distinguishability of monitoring data.

[0037] 2. Continuous and real-time monitoring

[0038] The design of the implantable microgel sensor enables the entire system to work stably in the body for a long time, achieving continuous monitoring of blood glucose levels and avoiding the problem of discontinuous data collection in the traditional blood sampling method. At the same time, advanced data processing technology can analyze the monitoring signals in real time, providing continuous and accurate dynamic blood glucose curves for clinical use, which helps to optimize diabetes management programs.

[0039] 3. Quasi-noninvasive and long-term stability

[0040] The present invention uses an implantable sensor to replace frequent blood sampling, significantly reducing the operational trauma and infection risk; while the optimized microgel synthesis and encapsulation process ensure the long-term stability of the sensor in the body, reducing the sensor replacement frequency and maintenance cost, and improving the patient's compliance and quality of life.

[0041] 4. Cost-effectiveness and broad application prospects

[0042] By optimizing material preparation and system design, the overall cost of the sensor is expected to be significantly reduced, providing the possibility for large-scale clinical applications. In addition, the technical solution adopted in the present invention is not only applicable to blood glucose monitoring, but its basic principle and detection method can also be extended to other biomedical monitoring fields, such as the detection of in vivo pH value, temperature and other biological indicators, with high application promotion value and market prospects.

[0043] In summary, the present invention provides an in vivo blood glucose monitoring system based on the response characteristics of microgels. By synthesizing microgel particles, designing the structure of the implantable microgel sensor, and using dielectric constant detection and signal processing technology, it effectively solves the problems of large trauma, discontinuous data, insufficient long-term stability and high cost existing in traditional blood glucose monitoring methods. This system not only realizes highly sensitive, real-time and continuous blood glucose monitoring, but also has good biocompatibility and long-term stability, providing a new technical path for the precise management of diabetes and other metabolic diseases. Brief description of the drawings

[0044] Figure 1 is a synthetic route diagram of microgel particles;

[0045] Figure 2 is an electron microscope scanning image of dried microgel particles;

[0046] Figure 3 is a graph showing the response of microgel particle size to different blood glucose concentrations;

[0047] Figure 4 This is the image of the dispersion change of microgel particles' transmittance induced by the change of glucose concentration;

[0048] Figure 5 is a curve diagram of the change in transmittance of the microgel dispersion as the glucose concentration increases;

[0049] Figure 6 is a diagram of the synthesized implantable microgel sensor;

[0050] Figure 7 Figure 2 is a diagram of the device for detecting the electromagnetic properties of the microgel sensor. DETAILED DESCRIPTION

[0051] In order to make the purpose, technical solution and advantages of the present invention clearer, the present invention - an in vivo blood glucose monitoring system based on microgel response characteristics is described in detail below in conjunction with specific embodiments. The in vivo blood glucose monitoring system of the present invention mainly consists of the following parts:

[0052] 1. Microgel material synthesis module

[0053] In order to realize microgel materials that are highly responsive to changes in blood glucose concentration under physiological conditions, this example uses precipitation polymerization to synthesize microgel particles. The specific steps are as follows:

[0054] 1) Raw material preparation and solution preparation

[0055] The main chemical reagents used and their suppliers are as follows:

[0056] N -isopropyl methacrylamide (NIPMAAM), acryloyl chloride, and diacrylamide (MBA) were purchased from Beijing Bailingwei Technology Co., Ltd.;

[0057] Ammonium persulfate (APS) and sodium dodecyl sulfate (SDS) were purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.;

[0058] Dimethyl sulfoxide (DMSO) was purchased from Sinopharm Group;

[0059] The blood glucose-sensitive monomer 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylacetic acid (AmECFPBA) was purchased from Shanghai Baide Pharmaceutical Technology Co., Ltd.

[0060] First, accurately weigh NIPMAAM (765 mg, 6.0 mmol), MBA (20 mg, 0.13 mmol), and SDS (2.4 mg, 0.008 mmol) and dissolve them in 76 mL of ultrapure water to form a homogeneous reaction solution. Meanwhile, pre-dissolve AmECFPBA (136.4 mg, 0.486 mmol) in 2 mL of methanol to ensure that the sensitive monomer is fully dissolved and ready for use.

[0061] 2) Polymerization reaction process

[0062] Mix the pre-prepared AmECFPBA solution with the above aqueous phase to form a homogeneous reaction mixture. To ensure that the oxygen in the reaction system is fully removed, the mixture is purged with argon at 70 °C for at least 1 hour. Subsequently, add 2 mL of 0.08 M degassed APS solution as an initiator to initiate the polymerization reaction. The reaction is carried out at 70 °C for 8 hours to ensure that the polymerization reaction proceeds fully and the target microgel particles are generated. The synthesis process of the microgel particles can be referred to the attached figure ( Figure 1 ).

[0063] 3) Post-treatment and passivation

[0064] After the polymerization reaction is completed, the resulting solution is dialyzed. The specific method is as follows: Place the reaction solution in a dialysis bag with an appropriate molecular weight cut-off, use deionized water as the dialysis medium, and the dialysis time is 7 days to remove unreacted monomers, initiator residues, and other low-molecular-weight impurities. After dialysis, the dialysis solution is freeze-dried to obtain dry microgel particles. The morphology and particle size distribution of the obtained product can be characterized by referring to the attached figure ( Figure 2 ).

[0065] 2. Particle size distribution characterization module of microgel

[0066] To verify the response characteristics of the prepared microgel material to changes in blood glucose concentration, the size and particle size distribution of the microgel are characterized in this example. First, use a scanning electron microscope (SEM) to observe the shape and diameter of the prepared microgel particles. The results are as Figure 2 shown, indicating that the microgel presents a regular spherical structure and the particle size distribution is relatively concentrated. After accurately measuring the SEM image using Nano Measurer software, it is determined that the average diameter of the microgel in the dry state is about 170 nm, and at a 92% confidence level, the confidence interval of its size distribution is from 163.27 nm to 178.12 nm, proving that the prepared microgel has uniformity and good dispersibility.

[0067] To further explore the effect of blood glucose concentration on the size of microgel particles, in this example, the dynamic light scattering method (DLS) was used to measure the hydrodynamic radius of microgels at different glucose concentrations. The specific steps were as follows: 1 mg of microgel was uniformly dispersed in 10 mL of pH 7.4 buffer solution, and the hydrodynamic radius of the microgel was measured using a nanoparticle size analyzer under different glucose concentrations (0 g / L, 1 g / L, 2 g / L, 3 g / L, 4 g / L, and 5 g / L). The test results showed that, as Figure 3 shown, the hydrodynamic radius of the microgel without glucose was approximately 180 nm, while under the condition of 4 g / L glucose, the hydrodynamic radius increased to 369 nm. This significant change was mainly attributed to the specific reaction between the phenylboronic acid groups in the microgel network and glucose, which enhanced the hydrophilicity of the polymer chains, resulting in an obvious swelling of the microgel particles. Based on these experimental data, the diameter and volume changes of the microgel particles at different blood glucose concentrations could be further calculated, providing a reliable physical basis for subsequent sensor signal conversion.

[0068] 3. Characterization module for the time-domain characteristics of microgels

[0069] The blood glucose concentration in the in vivo microenvironment may change drastically within a short period, such as a sudden increase in postprandial blood glucose levels. To characterize the response speed of microgels to changes in blood glucose concentration and their dynamic response characteristics, this example used an ultraviolet spectrophotometer for testing. The specific testing steps were as follows:

[0070] 4 mg of microgel was dispersed in 2 mL of pH 7.4 buffer solution, placed in the thermostatic bath of the ultraviolet spectrophotometer, and the transmittance of the dispersion was measured at predetermined time points (1, 2, 5, 10 minutes).

[0071] After completing a set of baseline measurements, 10 μL of high-concentration glucose buffer solution was added to the sample to rapidly increase the glucose concentration in the solution. At the same time, a control group was set up, and 10 μL of glucose-free buffer solution was added to it to exclude the change in transmittance caused by the dilution effect. Subsequently, the transmittance of the sample was continuously measured under the conditions of 0, 1, 2, 3, 4, and 5 g / L glucose concentrations.

[0072] As Figure 4 shown, as the glucose concentration increased, the transmittance of the microgel dispersion increased significantly, indicating that the solution gradually became clearer. Figure 5Quantitative analysis of the transmittance change was provided: in the experimental group, the transmittance showed a significant upward trend with the increase of glucose concentration, while the transmittance in the control group remained basically unchanged. This phenomenon indicates that the change in transmittance is mainly attributed to the specific reaction between glucose and the microgel, resulting in the swelling of the microgel, an increase in water absorption, and the refractive index approaching that of water. At the same time, the test data show that after adding glucose, the transmittance of the dispersion increased rapidly within the first 5 minutes and then remained basically stable, proving that the microgel can respond to the change in blood glucose concentration and reach the swelling equilibrium within about 5 minutes.

[0073] The detection methods and experimental data in the above embodiments all show that the microgel material has significant physical parameter changes and fast response characteristics under low and high blood glucose conditions, which lay the foundation for using the microgel as a blood glucose sensing medium.

[0074] 4. Implantable Microgel Sensor Design Module

[0075] To achieve real-time and continuous in-vivo blood glucose monitoring, in this example, a method of embedding glucose-sensitive microgel particles into a flexible monolithic gel matrix is adopted to prepare a wireless implantable microgel sensor (MBS), which can be directly implanted subcutaneously to collect real-time blood glucose data. Its preparation process and design scheme are as follows:

[0076] Polyvinyl alcohol (PVA) is selected as the carrier matrix because of its excellent biocompatibility and flexibility. During the preparation process, PVA is dissolved in deionized water at 95 °C until a uniform transparent solution is formed. This step ensures that the matrix has sufficient fluidity and uniformity, facilitating subsequent full mixing with the microgel.

[0077] The previously synthesized glucose-sensitive microgel particles are added to the prepared PVA solution, and the two are uniformly mixed by sufficient stirring. During the mixing process, it is required that the microgel particles are uniformly dispersed in the PVA solution to ensure that the microgel elements in the subsequent prepared sensor can be evenly distributed, thereby maximizing their response characteristics to the change in blood glucose concentration. After mixing, the mixture is left standing overnight to fully remove the possible bubbles in the solution and further ensure the uniformity of the microgel in the matrix.

[0078] The fully mixed microgel and PVA solution are poured into a pre-designed mold, and the mold should meet the requirements of the desired sensor size and shape. Subsequently, the mold is placed at 60 °C and dried for 24 hours. During the drying process, PVA undergoes a crystal physical cross-linking reaction to form a firm three-dimensional network structure, firmly encapsulating the microgel particles inside. The dried sensor is in a solid state, forming an elastic and flexible gel block, as Figure 6As shown in Figure 2, the sensor is not only compact in structure and mechanically flexible, but also can maintain long-term stable operation in the in vivo environment, providing a reliable physical platform for real-time continuous blood glucose monitoring.

[0079] 5. Electromagnetic characteristics detection module

[0080] In order to achieve real-time and continuous detection of the response of implantable microgel sensors to changes in blood glucose concentration, this example constructs an electromagnetic detection module based on dielectric constant measurement. This module uses the property that the dielectric constant of microgels changes due to water absorption and swelling under different blood glucose environments to convert physical changes into detectable electrical signals, and realizes continuous monitoring of blood glucose levels in the body through wireless data transmission. The specific implementation steps are as follows:

[0081] like Figure 7 As shown in Figure 1, this system uses a vector network analyzer (Keysight PNA N5222B) and a dielectric probe kit (Keysight 85070D) to form a measurement device. The working environment is set to room temperature 25°C and relative humidity 60%, and a total of 801 data points are recorded in the 0.5 to 6 GHz frequency band to ensure sufficient data resolution to capture small dielectric constant changes.

[0082] Before the formal measurement, the vector network analyzer and dielectric probe were calibrated according to the mature "open circuit-short circuit-distilled water" calibration steps to ensure the accuracy and repeatability of the subsequent measurement data. In order to reduce the data deviation caused by instrument error, each measurement sample was tested 10 times at different positions on its surface, and the average value was taken as the final data.

[0083] In the 2GHZ frequency band, the test results show that in the state of hypoglycemia, the dielectric constant of the microgel sensor is measured to be 20.13; in the state of hyperglycemia, the dielectric constant rises to 60.27. This result is consistent with the characterization results of the aforementioned microgel material: under hypoglycemia conditions, the diameter of the microgel particles is about 170nm; while under hyperglycemia conditions, the microgel particles absorb water and swell to about 360nm, and the diameter nearly doubles. The significant water absorption of the microgel under the hyperglycemia environment leads to an increase in its internal moisture content, which causes a significant change in the dielectric constant. The degree of change in the dielectric constant is not only related to the change in the diameter of the microgel particles, but also affected by factors such as particle concentration. This example realizes the real-time and accurate measurement of the implantable microgel sensor in response to changes in blood glucose concentration by constructing an electromagnetic property detection module based on dielectric constant detection. It not only verifies the significant physical property changes of the microgel material under different blood glucose environments, but also provides a reliable data basis for subsequent data processing and wireless transmission, thereby realizing accurate and continuous blood glucose monitoring.

Claims

1. An in-vivo blood glucose monitoring system based on a microgel sensor, characterized in that, It includes five major modules: (1) Microgel material synthesis module; (2) Particle size distribution characterization module; (3) Time-domain characteristic characterization module; (4) Implantable microgel sensor design module; (5) Electromagnetic characteristic detection module.

2. The in-vivo blood glucose monitoring system based on a microgel sensor according to claim 1, wherein In the microgel material synthesis module, the microgel material is synthesized by precipitation polymerization from N-isopropylmethacrylamide, diacrylamide, and the glucose-sensitive monomer 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylacetic acid to form thermosensitive microgel particles with phenylboronic acid groups.

3. The in-vivo blood glucose monitoring system based on a microgel sensor according to claim 1, characterized in that, The test conditions of the time-domain characteristic characterization module are as follows: 4 mg of microgel is dispersed in 2 mL of buffer solution. After adding 10 μL of high-concentration glucose, the transmittance is continuously monitored at a concentration of 0 - 5 g / L.

4. The in-vivo blood glucose monitoring system based on a microgel sensor according to claim 1, wherein In the implantable microgel sensor design module, the sensor is formed by embedding the microgel particles into a polyvinyl alcohol matrix, and the polyvinyl alcohol matrix encapsulates the microgel particles through physical cross-linking.

5. The in-vivo blood glucose monitoring system based on a microgel sensor according to claim 1, characterized in that, In the electromagnetic characteristic detection module, the module monitors the swelling state of the microgel sensor in real time through dielectric constant measurement. The dielectric constant measurement is carried out in the frequency band of 0.5 - 6 GHz, and wireless data acquisition is realized through a vector network analyzer and a dielectric probe.

6. A method for in vivo blood glucose monitoring based on a microgel sensor according to any one of claims 1-5, characterized in that, It includes the following steps: (1) Microgel synthesis: Feed materials according to the molar ratio of N-isopropylmethacrylamide, diacrylamide, and 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylacetic acid of 6.0:0.13:0.486, and precipitate polymerization reaction generates microgel containing phenylboronic acid groups; (2) Particle size and responsiveness characterization: Observe the dry particle size by SEM, measure the hydrated radius at different glucose concentrations by DLS, and establish a particle size-concentration calibration relationship; (3) Dynamic response test: Use an ultraviolet spectrophotometer to verify the response speed of the microgel to changes in glucose concentration within a certain time; (4) Sensor preparation and implantation: Mix and cross-link the microgel with a PVA solution to form an implantable gel sensor and implant it subcutaneously; (5) Electromagnetic signal detection: Monitor the swelling state of the sensor in real time through dielectric constant measurement, and convert the blood glucose concentration through the change in dielectric constant in a certain frequency band.

7. The method for in vivo blood glucose monitoring based on a microgel sensor according to claim 6, characterized in that, In step (1), the argon pretreatment time of the polymerization reaction is ≥1 hour, and the reaction temperature is 70 °C.

8. The in-vivo blood glucose monitoring method based on a microgel sensor according to claim 6, wherein In step (2), the concentration of the microgel dispersion solution for DLS test is 0.1 mg / mL, and the pH 7.4 buffer solution is phosphate buffered saline.

9. The in-vivo blood glucose monitoring method based on a microgel sensor according to claim 6, characterized in that In step (4), the sensor implantation position is subcutaneous in the upper arm, and the implantation depth is 2 - 5 mm.

10. The method for in-vivo blood glucose monitoring based on a microgel sensor according to claim 6, wherein, In step (5), the dielectric constant is 20.13 - 60.27.

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