Noninvasive blood glucose detection sensor and method based on CIOD

Abstract

The invention relates to the technical field of sensors, in particular to a CIOD-based noninvasive blood glucose detection sensor and method.The sensor comprises a multi-layer structure and comprises a first flexible polyimide substrate tightly attached to the skin, a temperature control assembly, a second flexible polyimide substrate and a glucose detection patch; the temperature control assembly comprises a temperature sensor and a heating wire and is used for thermally activating the skin; the glucose detection patch comprises three electrode areas filled with perfluorinated sulfonic acid resin, wherein the first electrode area comprises a first sodium ion working electrode, a shared electrode and a detection working electrode; the second electrode region contains a sodium ion reference electrode; the third electrode area comprises a second sodium ion working electrode and an auxiliary electrode; the electrodes are connected through insulating coating wires; the shared electrode and the auxiliary electrode form an interstitial fluid extraction electrode pair, and the detection working electrode and the shared electrode form a glucose detector to detect a hydrogen peroxide signal generated by glucose oxidation; the first sodium ion working electrode, the second sodium ion working electrode and the sodium ion reference electrode form a sodium ion differential detector to calibrate a glucose signal. According to the novel noninvasive blood glucose detection sensor provided by the invention, efficient, noninvasive and portable blood glucose monitoring can be realized by combining thermal activation and differential self-calibration.

Description

Technical Field

[0001] This invention relates to the field of sensor technology, and in particular to a non-invasive blood glucose detection sensor and method based on CIOD. Background Technology

[0002] Current blood glucose monitoring technologies primarily rely on invasive methods, such as finger-prick blood sampling or continuous glucose monitoring (CGM) systems. While accurate, these methods often cause pain, inconvenience, and infection risks for patients. Traditional non-invasive monitoring devices, such as optical or electrochemical sensors, typically suffer from insufficient sensitivity, significant individual variability, and interference from passive sweating, leading to unstable measurement results and an inability to achieve real-time, accurate monitoring. Furthermore, existing flexible wearable devices have limitations in interstitial fluid extraction efficiency, the extraction process is easily affected by the skin barrier, and it is difficult to effectively integrate thermal activation and differential calibration mechanisms, further limiting their clinical application.

[0003] To overcome these challenges, existing technologies attempt to develop sensors based on microfluidics and nanostructures. However, current solutions still have shortcomings in electrode design and signal calibration, such as the lack of an effective sodium ion internal reference calibration model and the inability to eliminate fluctuations in individual interstitial fluid extraction. Furthermore, the complex and costly manufacturing process also hinders large-scale deployment. Therefore, a novel non-invasive blood glucose monitoring sensor is needed that combines thermal activation, differential self-calibration, and multilayer flexible structures to achieve efficient and accurate blood glucose monitoring. Summary of the Invention

[0004] In view of the above technical problems, the present invention provides a non-invasive blood glucose detection sensor and method based on CIOD, so as to provide a novel non-invasive blood glucose detection sensor that can combine thermal activation and differential self-calibration to achieve efficient, non-invasive and portable blood glucose monitoring.

[0005] Other features and advantages of the invention will become apparent from the following detailed description, or may be learned in part by practice of the invention.

[0006] According to one aspect of the present invention, a non-invasive blood glucose detection sensor based on CIOD is provided. The sensor has multiple layers, comprising, from top to bottom, a first flexible polyimide substrate, a temperature control component, a second flexible polyimide substrate, and a glucose detection patch, wherein: The first flexible polyimide substrate and the second flexible polyimide substrate are 8-10 micrometer thick PI films with a surface that enhances hydrophilicity; The temperature control component is used to provide temperature control and includes a temperature sensor and a heating wire; The glucose detection patch includes a first electrode region, a second electrode region, and a third electrode region filled with ion-selective protective material. The first electrode region includes a first sodium ion working electrode, a shared electrode, and a detection working electrode. The first sodium ion working electrode and the detection working electrode are arc-shaped. The second electrode region includes a sodium ion reference electrode. The third electrode region includes a second sodium ion working electrode and an auxiliary electrode. Each electrode is led out by its corresponding wire. The shared electrode and the auxiliary electrode form an interstitial fluid extraction electrode pair. The detection working electrode and the shared electrode form a glucose detector. The detection working electrode is provided with a glucose oxidase layer. The first sodium ion working electrode, the sodium ion reference electrode, and the second sodium ion working electrode form a sodium ion differential detector. When the shared electrode is used in the interstitial fluid extraction electrode pair, it plays an extraction role. When it is used in the glucose detector, it plays a role in providing a reference potential. During blood glucose testing, the temperature control component applies thermal stimulation to improve interstitial fluid extraction efficiency; the sodium ion differential detector is used to detect sodium ion concentration and uses a pre-set calibration model to measure sodium ion concentration as an internal reference to calibrate the glucose signal, thereby eliminating interstitial fluid extraction fluctuations caused by individual differences; the glucose detector is used to achieve in-situ glucose measurement, wherein glucose oxidase catalyzes glucose oxidation to produce hydrogen peroxide, and hydrogen peroxide is reduced at a low potential to generate a current signal to form the glucose signal.

[0007] Furthermore, the conductor is coated with an insulating material coating.

[0008] Furthermore, the ion-selective protective material is a perfluorosulfonic acid resin, which encapsulates the electrodes in the first electrode region, the second electrode region, and the third electrode region.

[0009] Furthermore, the detection working electrode specifically includes: The glucose oxidase layer is used to catalyze the glucose oxidation reaction in the interstitial fluid to generate hydrogen peroxide, providing a measurable signal for electrochemical detection. The Prussian blue layer, located below the glucose oxidase layer, acts as an electrochemical mediator, reducing hydrogen peroxide at low potential to lower the detection potential of the detection electrode and reduce background interference. A platinum nanoparticle layer, located beneath the Prussian blue layer, exhibits a three-dimensional rolled structure and is formed by spraying platinum nanoparticle ink. This layer is used to increase the electrode surface area, thereby enhancing the electron transfer rate and catalytic efficiency. A graphene layer, located below the platinum nanoparticle layer, serves as a conductive substrate to support the adhesion of the platinum nanoparticle ink. A first gold layer, located beneath the graphene layer, serves as the bottom electrode.

[0010] Furthermore, both the first sodium ion working electrode and the second sodium ion working electrode include: Sodium ion selective membrane, which is composed of polyvinyl chloride-sodium ion carrier membrane, is used for selectively binding and transporting sodium ions; A poly(3,4-ethylenedioxythiophene) layer is located below the sodium ion selective membrane. As a conductive polymer, it is used to transmit the sensing signal of sodium ions. The second gold layer serves as the bottom electrode.

[0011] Furthermore, the sodium ion reference electrode includes: Sodium ion reference membrane, which is used to provide a stable sodium ion reference potential; The third gold layer is used as the bottom electrode.

[0012] According to another aspect of the present invention, a non-invasive blood glucose detection method based on CIOD is provided, the method being used in the aforementioned sensor, the method comprising: The temperature control component is activated to locally heat and maintain the temperature of the skin to achieve thermal activation, thereby promoting skin penetration and improving the efficiency of transdermal interstitial fluid extraction. A constant current is applied to the shared electrode pair, and interstitial fluid is extracted percutaneously from subcutaneous tissue through ion transport microchannels within the skin. The glucose concentration in the extracted interstitial fluid was detected in situ using the glucose detector, and the serum sodium concentration was detected in situ using the sodium ion differential detector. Based on the measured blood sodium concentration, the blood glucose value is calculated using the calibration model, wherein the calculation process involves linear regression analysis, using the ratio of the interstitial fluid glucose concentration to the blood sodium concentration as a variable, and fitting a standard curve to predict the blood glucose level. The method further includes using the auxiliary electrode to measure background noise and subtracting it from the signal received by the detection working electrode to eliminate the influence of passive sweating and improve the linear correlation and accuracy of blood glucose prediction.

[0013] The technical solution of the present invention has the following beneficial effects: The non-invasive blood glucose sensor based on CIOD (reverse ionization) provided by this invention achieves highly efficient interstitial fluid extraction under thermal activation through the integration of a multilayer flexible polyimide substrate and a temperature control component, significantly improving extraction efficiency and reducing skin irritation. This design employs a sodium ion differential detector as an internal reference for calibration, eliminating individual differences and the influence of passive sweating, ensuring the accuracy and stability of the glucose signal, thereby providing reliable real-time monitoring for diabetic patients and improving overall diagnostic accuracy and user comfort.

[0014] Furthermore, the detection method of this invention utilizes linear regression analysis and background noise subtraction mechanisms to further optimize the linear correlation of blood glucose prediction and reduce measurement errors. This sensor is compact, low-cost, and easy to mass-produce and wearable, possessing broad clinical prospects. It can effectively overcome the limitations of existing non-invasive monitoring technologies and promote innovative development in the field of blood glucose management. Attached Figure Description

[0015] Figure 1 This is a structural diagram of a non-invasive blood glucose detection sensor based on CIOD, as described in the embodiments of this specification. Figure 2 This is a structural diagram of the glucose detection patch in the embodiments of this specification; Figure 3 This is a structural diagram of the detection working electrode in the embodiments of this specification.

[0016] Explanation of reference numerals in the attached figures: 1. First flexible polyimide substrate; 2. Temperature control component; 21. Temperature sensor; 22. Heating wire; 3. Second flexible polyimide substrate; 4. Glucose detection patch; 41. First electrode region; 411. First sodium ion working electrode; 412. Shared electrode; 413. Detection working electrode; 4131. Glucose oxidase layer; 4132. Prussian blue layer; 4133. Platinum nanoparticle layer; 4134. Graphene layer; 4135. First gold layer; 42. Second electrode region; 421. Sodium ion reference electrode; 43. Third electrode region; 431. Second sodium ion working electrode; 432. Auxiliary electrode; 44. Ion-selective protective material; 5. Skin. Detailed Implementation

[0017] Exemplary embodiments will now be described more fully with reference to the accompanying drawings. However, these exemplary embodiments can be implemented in many forms and should not be construed as limited to the examples set forth herein; rather, these embodiments are provided to make the invention more comprehensive and complete, and to fully convey the concept of the exemplary embodiments to those skilled in the art. The described features, structures, or characteristics can be combined in any suitable manner in one or more embodiments. In the following description, numerous specific details are provided to give a full understanding of embodiments of the invention. However, those skilled in the art will recognize that the technical solutions of the invention may be practiced with one or more of these specific details omitted, or other methods, components, apparatus, steps, etc., may be employed. In other instances, well-known technical solutions are not shown or described in detail to avoid obscuring various aspects of the invention.

[0018] like Figure 1As shown, this invention provides a non-invasive blood glucose detection sensor based on CIOD. The sensor has multiple layers, including, from top to bottom, a first flexible polyimide substrate 1, a temperature control component 2, a second flexible polyimide substrate 3, and a glucose detection patch 4. The first flexible polyimide substrate 1 and the second flexible polyimide substrate 3 are 8-10 micrometer-thick PI films with surfaces that enhance hydrophilicity. The temperature control component 2 provides temperature control and includes a temperature sensor 21 and a heating wire. like Figure 2 As shown, the glucose detection patch 4 includes a first electrode region 41, a second electrode region 42, and a third electrode region 43 filled with an ion-selective protective material 44. The first electrode region 41 includes a first sodium ion working electrode 411, a shared electrode 412, and a detection working electrode 413. The first sodium ion working electrode 411 and the detection working electrode 413 are arc-shaped. The second electrode region 42 includes a sodium ion reference electrode 421. The third electrode region 43 includes a second sodium ion working electrode 431 and an auxiliary electrode 432. Each electrode is led out by its corresponding wire. Electrode 412 and the auxiliary electrode 432 form an interstitial fluid extraction electrode pair. The detection working electrode 413 and the shared electrode 412 form a glucose detector. The detection working electrode 413 is provided with a glucose oxidase layer 4131. The first sodium ion working electrode 411, the sodium ion reference electrode 421, and the second sodium ion working electrode 431 form a sodium ion differential detector. When the shared electrode 412 is working in the interstitial fluid extraction electrode pair, it plays an extraction role. When it is working in the glucose detector, it plays a role in providing a reference potential. The temperature control component 2 applies thermal stimulation to improve the extraction efficiency of interstitial fluid; the sodium ion differential detector is used to detect sodium ion concentration and uses a pre-set calibration model to measure sodium ion concentration as an internal reference to calibrate the glucose signal, thereby eliminating fluctuations in interstitial fluid extraction caused by individual differences; the glucose detector is used to realize in-situ glucose measurement, wherein glucose oxidase catalyzes glucose oxidation to produce hydrogen peroxide, and hydrogen peroxide is reduced at a low potential to generate a current signal to form the glucose signal.

[0019] As a supplement, the wires are coated with an insulating material. The wires with the insulating material coating are used to connect the various electrodes; the coating may specifically employ nano-silicon insulating ink to prevent electrical interference and ensure safety.

[0020] The ion-selective protective material 44 is a perfluorosulfonic acid resin, which encapsulates the electrodes in the first electrode region 41, the second electrode region 42, and the third electrode region 43. The perfluorosulfonic acid resin, used in the detection working electrode 413 and other components, prevents glucose oxidase leakage, serves as a microcell for electrochemical reactions, and improves biocompatibility with the skin 5, reducing irritation. Simultaneously, on the auxiliary electrode 432, the first sodium ion working electrode 411, the sodium ion reference electrode 421, and the second sodium ion working electrode 431, the ion-selective protective material 44 improves electrical contact with the skin 5 and acts as a biocompatible layer.

[0021] like Figure 3 As shown, the detection working electrode 413 specifically includes: The glucose oxidase layer 4131 is used to catalyze the glucose oxidation reaction in the interstitial fluid to generate hydrogen peroxide, providing a measurable signal for electrochemical detection. The Prussian blue layer 4132, located below the glucose oxidase layer 4131, acts as an electrochemical mediator to reduce hydrogen peroxide at a low potential, thereby lowering the detection potential of the detection working electrode 413 and reducing background interference. The platinum nanoparticle layer 4133, located below the Prussian blue layer 4132, has a three-dimensional rolled structure and is formed by spraying platinum nanoparticle ink. It is used to increase the electrode surface area to enhance the electron transfer rate and catalytic efficiency. A graphene layer 4134 is located below the platinum nanoparticle layer 4133 to serve as a conductive substrate for receiving the platinum nanoparticle ink. A first gold layer 4135 is located below the graphene layer 4134 to serve as a bottom electrode.

[0022] Furthermore, both the first sodium ion working electrode 411 and the second sodium ion working electrode 431 include: Sodium ion selective membrane, composed of polyvinyl chloride-sodium ion carrier membrane, is used to selectively bind and transport sodium ions; it is used to accurately measure the sodium ion concentration in interstitial fluid and serve as an internal calibration reference to eliminate individual differences and the effects of passive sweating. A poly(3,4-ethylenedioxythiophene) layer is located below the sodium ion selective membrane. As a conductive polymer, it has high conductivity and stability, enhances the electrochemical performance of the electrode, and supports the transmission of sodium ion sensing signals. The second gold layer serves as the bottom electrode, providing excellent conductivity and forming the electrochemical basis for the sodium ion sensor, ensuring reliable signal transmission.

[0023] The sodium ion reference electrode 421 includes: A sodium ion reference membrane, used to provide a stable sodium ion reference potential, can be composed of a polyvinyl chloride (PVC)-polyvinylpyrrolidone (PVP) membrane. It provides a stable sodium ion reference potential as a reference standard for sodium ion sensors, ensuring potential stability during the measurement process. The third gold layer serves as the bottom electrode, providing excellent conductivity and acting as the electrochemical basis for the sodium ion reference electrode, ensuring reliable signal transmission.

[0024] Explanation of the principle: The sensor is attached to the surface of the target skin 5, and the second flexible polyimide substrate 3 (an 8-10 micrometer thick PI film with an enhanced hydrophilic surface) adheres tightly to the skin 5, ensuring good contact between the glucose detection patch 4 and the skin 5. The first flexible polyimide substrate 1 serves as a structural support and is integrated with the temperature control component 2. The temperature sensor 21 and heating wire in the temperature control component 2 are activated and preheated to the target temperature (e.g., 42°C) in preparation for thermal activation.

[0025] Temperature control component 2 applies thermal stimulation, locally heating the skin 5 via a heating wire, and combined with reverse iontophoresis, enhances the permeability of the skin 5. A constant current (e.g., 0.3 mA / cm²) is applied to the interstitial fluid extraction electrode pair (shared electrode 412 and auxiliary electrode 432), non-invasively extracting interstitial fluid from subcutaneous tissue through ion transport microchannels within the skin 5. Thermal activation enhances the efficiency of interstitial fluid extraction and reduces skin irritation.

[0026] The extracted interstitial fluid enters the glucose detection patch 4, and the first electrode region 41 (including the first sodium ion working electrode 411, the shared electrode 412, and the detection working electrode 413), the second electrode region 42 (sodium ion reference electrode 421), and the third electrode region 43 (second sodium ion working electrode 431 and auxiliary electrode 432) begin operation. All electrodes are connected by wires coated with nano-silicon insulating ink to ensure safe and interference-free signal transmission. Each electrode is encapsulated with an ion-selective protective material 44 (perfluorosulfonic acid resin) to prevent glucose oxidase leakage and improve biocompatibility.

[0027] The detection electrode 413 catalyzes the oxidation of glucose in the interstitial fluid through the glucose oxidase layer 4131, generating hydrogen peroxide. The Prussian blue layer 4132 acts as an electrochemical mediator, reducing hydrogen peroxide at a low potential (e.g., -0.1 V) to generate a current signal. The platinum nanoparticle layer 4133 (increasing surface area), the graphene layer 4134, and the first gold layer 4135 serve as a conductive substrate, ensuring high electron transfer efficiency. The shared electrode 412 acts as a reference potential at this time, forming a glucose detector with the detection electrode 413 to complete in-situ glucose measurement.

[0028] The first sodium ion working electrode 411 and the second sodium ion working electrode 431 selectively bind and transport sodium ions through a sodium ion selective membrane (polyvinyl chloride-sodium ion carrier membrane), while the poly(3,4-ethylenedioxythiophene) layer transmits the sensing signal, and the second gold layer serves as the bottom electrode. The sodium ion reference electrode 421 (including a sodium ion reference membrane and a third gold layer) provides a stable reference potential. These three electrodes constitute a sodium ion differential detector, which measures the sodium ion concentration in the interstitial fluid as an internal calibration reference.

[0029] The sodium ion differential detector data is input into a preset calibration model. Through linear regression analysis, the ratio of interstitial fluid glucose concentration to serum sodium concentration is used as a variable to fit a standard curve, calibrating the glucose signal and eliminating individual differences and fluctuations in interstitial fluid extraction. The auxiliary electrode 432 measures background noise, which is subtracted from the signal of the working electrode 413 to eliminate the influence of passive sweating and improve the linear correlation and accuracy of blood glucose prediction.

[0030] The calibrated blood glucose value is displayed via an external electrochemical workstation or wearable device, completing one cycle of non-invasive blood glucose testing. The sensor is reusable and provides real-time monitoring of blood glucose levels, supporting diabetes management.

[0031] This workflow combines thermal activation, reverse ion electroosmosis, and differential calibration technologies, making full use of the properties of multilayer flexible structures and nanomaterials to achieve efficient and accurate non-invasive blood glucose monitoring.

[0032] In one embodiment, based on the same principle, a non-invasive blood glucose detection method based on CIOD is provided. This method is used in the aforementioned sensor and includes: The temperature control component 2 is activated to locally heat the skin 5 and maintain the temperature to achieve thermal activation, thereby promoting skin penetration and improving the efficiency of transdermal interstitial fluid extraction. A constant current is applied to the shared electrode 412, and interstitial fluid is extracted percutaneously from subcutaneous tissue through ion transport microchannels within the skin 5. The glucose concentration in the extracted interstitial fluid was detected in situ using the glucose detector, and the serum sodium concentration was detected in situ using the sodium ion differential detector. Based on the measured blood sodium concentration, the blood glucose value is calculated using the calibration model, wherein the calculation process involves linear regression analysis, using the ratio of the interstitial fluid glucose concentration to the blood sodium concentration as a variable, and fitting a standard curve to predict the blood glucose level. The method further includes using the auxiliary electrode 432 to measure background noise and subtracting it from the signal received by the detection working electrode 413 to eliminate the influence of passive sweating and improve the linear correlation and accuracy of blood glucose prediction.

[0033] The technical solution of the present invention has the following beneficial effects: The non-invasive blood glucose sensor based on CIOD (reverse ionization) provided by this invention achieves highly efficient interstitial fluid extraction under thermal activation through the integration of a multilayer flexible polyimide substrate and a temperature control component 2, significantly improving extraction efficiency and reducing skin irritation 5. This design uses a sodium ion differential detector as an internal reference for calibration, eliminating individual differences and the influence of passive sweating, ensuring the accuracy and stability of the glucose signal, thereby providing reliable real-time monitoring for diabetic patients and improving overall diagnostic accuracy and user comfort.

[0034] Furthermore, the detection method of this invention utilizes linear regression analysis and background noise subtraction mechanisms to further optimize the linear correlation of blood glucose prediction and reduce measurement errors. This sensor is compact, low-cost, and easy to mass-produce and wearable, possessing broad clinical prospects. It can effectively overcome the limitations of existing non-invasive monitoring technologies and promote innovative development in the field of blood glucose management.

[0035] Other embodiments of the invention will readily occur to those skilled in the art upon consideration of the specification and practice of the invention disclosed herein. This application is intended to cover any variations, uses, or adaptations of the invention that follow the general principles of the invention and include common knowledge or customary techniques in the art not disclosed herein. The specification and embodiments are to be considered exemplary only, and the true scope and spirit of the invention are indicated by the claims.

[0036] It should be understood that the present invention is not limited to the precise structure described above and shown in the accompanying drawings, and various modifications and changes can be made without departing from its scope. The scope of the invention is limited only by the appended claims.

Claims

1. A non-invasive blood glucose detection sensor based on CIOD, characterized in that, The sensor has multiple layers, including, from top to bottom, a first flexible polyimide substrate, a temperature control component, a second flexible polyimide substrate, and a glucose detection patch, wherein: The first flexible polyimide substrate and the second flexible polyimide substrate are 8-10 micrometer thick PI films with a surface that enhances hydrophilicity; The temperature control component is used to provide temperature control and includes a temperature sensor and a heating wire; The glucose detection patch includes a first electrode region, a second electrode region, and a third electrode region filled with ion-selective protective material. The first electrode region includes a first sodium ion working electrode, a shared electrode, and a detection working electrode. The first sodium ion working electrode and the detection working electrode are arc-shaped. The second electrode region includes a sodium ion reference electrode. The third electrode region includes a second sodium ion working electrode and an auxiliary electrode. Each electrode is led out by its corresponding wire. The shared electrode and the auxiliary electrode form an interstitial fluid extraction electrode pair. The detection working electrode and the shared electrode form a glucose detector. The detection working electrode is provided with a glucose oxidase layer. The first sodium ion working electrode, the sodium ion reference electrode, and the second sodium ion working electrode form a sodium ion differential detector. When the shared electrode is used in the interstitial fluid extraction electrode pair, it plays an extraction role. When it is used in the glucose detector, it plays a role in providing a reference potential. During blood glucose testing, the temperature control component applies thermal stimulation to improve interstitial fluid extraction efficiency; the sodium ion differential detector is used to detect sodium ion concentration and uses a pre-set calibration model to measure sodium ion concentration as an internal reference to calibrate the glucose signal, thereby eliminating interstitial fluid extraction fluctuations caused by individual differences; the glucose detector is used to achieve in-situ glucose measurement, wherein glucose oxidase catalyzes glucose oxidation to produce hydrogen peroxide, and hydrogen peroxide is reduced at a low potential to generate a current signal to form the glucose signal.

2. The non-invasive blood glucose detection sensor based on CIOD according to claim 1, characterized in that, The conductor is coated with an insulating material.

3. The non-invasive blood glucose detection sensor based on CIOD according to claim 1, characterized in that, The ion-selective protective material is perfluorosulfonic acid resin, which encapsulates the electrodes in the first electrode region, the second electrode region, and the third electrode region.

4. The non-invasive blood glucose detection sensor based on CIOD according to claim 1, characterized in that, The detection working electrode specifically includes: The glucose oxidase layer is used to catalyze the glucose oxidation reaction in the interstitial fluid to generate hydrogen peroxide, providing a measurable signal for electrochemical detection. The Prussian blue layer, located below the glucose oxidase layer, acts as an electrochemical mediator, reducing hydrogen peroxide at low potential to lower the detection potential of the detection electrode and reduce background interference. A platinum nanoparticle layer, located beneath the Prussian blue layer, exhibits a three-dimensional rolled structure and is formed by spraying platinum nanoparticle ink. This layer is used to increase the electrode surface area, thereby enhancing the electron transfer rate and catalytic efficiency. A graphene layer, located below the platinum nanoparticle layer, serves as a conductive substrate to support the adhesion of the platinum nanoparticle ink. A first gold layer, located beneath the graphene layer, serves as the bottom electrode.

5. The non-invasive blood glucose detection sensor based on CIOD according to claim 1, characterized in that, Both the first sodium ion working electrode and the second sodium ion working electrode include: Sodium ion selective membrane, which is composed of polyvinyl chloride-sodium ion carrier membrane, is used for selectively binding and transporting sodium ions; A poly(3,4-ethylenedioxythiophene) layer is located below the sodium ion selective membrane. As a conductive polymer, it is used to transmit the sensing signal of sodium ions. The second gold layer serves as the bottom electrode.

6. The non-invasive blood glucose detection sensor based on CIOD according to claim 1, characterized in that, The sodium ion reference electrode includes: Sodium ion reference membrane, which is used to provide a stable sodium ion reference potential; The third gold layer is used as the bottom electrode.

7. A non-invasive blood glucose detection method based on CIOD, characterized in that, The method is used in the sensor according to any one of claims 1-6, the method comprising: The temperature control component is activated to locally heat and maintain the temperature of the skin to achieve thermal activation, thereby promoting skin penetration and improving the efficiency of transdermal interstitial fluid extraction. A constant current is applied to the shared electrode pair, and interstitial fluid is extracted percutaneously from subcutaneous tissue through ion transport microchannels within the skin. The glucose concentration in the extracted interstitial fluid was detected in situ using the glucose detector, and the serum sodium concentration was detected in situ using the sodium ion differential detector. Based on the measured blood sodium concentration, the blood glucose value is calculated using the calibration model, wherein the calculation process involves linear regression analysis, using the ratio of the interstitial fluid glucose concentration to the blood sodium concentration as a variable, and fitting a standard curve to predict the blood glucose level. The method further includes using the auxiliary electrode to measure background noise and subtracting it from the signal received by the detection working electrode to eliminate the influence of passive sweating and improve the linear correlation and accuracy of blood glucose prediction.

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