A self-calibrating multi-parameter microneedle monitoring system

Abstract

The present invention discloses a self-calibrating multi-parameter microneedle monitoring system, comprising a detection circuit module and a data processing module, a flexible circuit substrate, and a solid microneedle electrode array vertically fixed to the surface of the flexible circuit substrate; the solid microneedle electrode array includes a reference electrode, a calibration electrode, and a glucose electrode; the glucose electrode and calibration electrode serve as working electrodes, respectively, and together with the reference electrode, form a two-electrode system; the detection circuit module is used to apply a working voltage to the electrode system and read the impedance value of the calibration electrode and the response current of the glucose electrode; the data processing module is used to read the impedance value of the calibration electrode and the response current of the glucose electrode, and perform current correction and glucose concentration conversion processes. The present invention can calibrate sensor data based on the depth of microneedle penetration into the subcutaneous tissue, thereby improving the accuracy of the monitoring system.

Description

Technical Field

[0001] The invention belongs to the technical field of medical monitoring instruments and relates to a self-calibration multi-parameter microneedle monitoring system. Background Art

[0002] Biochemical indicators such as blood sugar and electrolytes accurately reflect a person's health and are crucial for disease diagnosis, treatment, and patient care. Currently, clinical testing of these biochemical indicators relies primarily on blood tests, which fail to provide timely feedback on a person's health and are costly. Continuous monitoring of these indicators can effectively monitor a person's physical condition, further preventing related diseases and optimizing treatment and management plans.

[0003] The content of markers in tissue fluid is closely related to that in blood. Compared with other methods, monitoring multiple markers in tissue fluid through microneedles can achieve continuous monitoring of markers, and only causes tiny wounds and little damage to the skin barrier. It is suitable for patients with chronic diseases who need frequent monitoring.

[0004] However, during the use of the sensor, due to skin conditions and insertion methods, the microneedle array sometimes cannot completely penetrate the subcutaneous tissue, resulting in inaccurate sensor data and inability to obtain the true health status of the human body. Therefore, the current microneedle sensors still need to be improved. Summary of the Invention

[0005] To address the aforementioned shortcomings of the existing technology, the present invention proposes a self-calibrating multi-parameter microneedle monitoring system. This system can simultaneously monitor multiple biomarkers in tissue fluid. It also measures the current microneedle penetration depth using calibration electrodes and self-calibrates the measured data based on a pre-derived calibration curve, thereby improving the accuracy of the monitoring system.

[0006] The technical solutions adopted by the present invention to solve the technical problems are as follows:

[0007] A self-calibrating multi-parameter microneedle monitoring system comprises a detection circuit module and a data processing module, a flexible circuit substrate, and a solid microneedle electrode array vertically fixed to the surface of the flexible circuit substrate; the solid microneedle electrode array comprises a reference electrode, a calibration electrode, and a glucose electrode; the glucose electrode and the calibration electrode serve as working electrodes, respectively, and together with the reference electrode, form a two-electrode system;

[0008] The detection circuit module is used to apply a working voltage to the electrode system and read the impedance value of the calibration electrode and the response current of the glucose electrode;

[0009] The data processing module is used to read the impedance value of the calibration electrode and the response current of the glucose electrode, and execute the current correction and glucose concentration conversion process. The procedure of this process is: first, call the first fitting equation obtained by fitting the measured data, and calculate the insertion depth of the glucose electrode according to the impedance value of the calibration electrode; then call the second fitting equation obtained by fitting the measured data, and calculate the first slope of the current-glucose concentration response curve corresponding to the current insertion depth according to the insertion depth of the glucose electrode; then, based on the second slope of the current-glucose concentration response curve corresponding to the full insertion depth obtained by measurement, the response current of the glucose electrode is corrected with the ratio of the second slope to the first slope as a correction factor; finally, call the current-glucose concentration response curve corresponding to the full insertion depth, and calculate the glucose concentration according to the corrected response current.

[0010] Preferably, the solid microneedle electrode array further includes a counter electrode, which forms a three-electrode system with the working electrode and the reference electrode.

[0011] Preferably, the flexible circuit substrate has a copper disk array that cooperates with the solid microneedle electrode array, the solid microneedles are mounted on the copper disks, and the two are electrically connected through conductive silver paste, and the conductive silver paste is covered with ultraviolet glue for circuit insulation.

[0012] Preferably, the copper disk array is electrically connected to a multi-channel interface via a wire, and the detection circuit module controls and collects signals from the solid microneedle electrode array on the flexible circuit substrate via the multi-channel interface.

[0013] Preferably, the first fitting equation is an exponential equation in the form of Z=m·H n , where m and n are fitting coefficients, H is the penetration depth of the calibration electrode and glucose electrode, and Z is the impedance value of the calibration electrode.

[0014] Preferably, the second fitting equation is a linear equation in the form of A′=a·H′+b, where a and b are fitting coefficients, H′ is the actual penetration depth of the glucose electrode, and A′ is the slope of the current-glucose concentration response curve corresponding to the actual penetration depth of the glucose electrode.

[0015] Preferably, the first fitting equation is obtained by fitting the measured data obtained by inserting the calibration electrode into different depths on agarose gels with different glucose concentrations; the second fitting equation is obtained by fitting the measured data obtained by inserting the glucose electrode into different depths on agarose gels with different glucose concentrations.

[0016] Preferably, the main body of the reference electrode is a first metal microneedle, and the surface of the first metal microneedle is modified with a silver / silver chloride layer;

[0017] The main body of the counter electrode is a second metal microneedle, and the surface of the second metal microneedle is modified with a platinum layer;

[0018] The main body of the calibration electrode is a third metal microneedle, and the surface of the third metal microneedle is modified with a gold layer;

[0019] The main body of the glucose electrode is a fourth metal microneedle, and the surface of the fourth metal microneedle is modified with a platinum layer, a poly-o-phenylenediamine layer, a glucose oxidase layer and a biocompatible layer in sequence from the inside to the outside.

[0020] Preferably, the first metal microneedle is a silver-plated needle or a silver needle with a diameter of 0.25 to 0.35 mm and a length of 0.5 to 1.5 mm;

[0021] The second metal microneedle, the third metal microneedle and the fourth metal microneedle are steel needles with a diameter of 0.25 to 0.35 mm and a length of 0.5 to 1.5 mm.

[0022] Preferably, the solid microneedle electrode array also includes an ion sensing electrode for detecting ion concentration. The main body of the ion sensing electrode is a fifth metal microneedle, and the surface of the fifth metal microneedle is modified with a gold layer, a polystyrene sulfonate-doped poly (3,4-ethylenedioxythiophene) layer, and an ion selective membrane layer from the inside to the outside.

[0023] Compared with the existing technology, the present invention includes the following beneficial effects: The present invention provides a self-calibrating microneedle monitoring system that can monitor multiple biochemical indicators such as glucose and ions in the human body in real time. The system adopts an innovative calibration method to pre-test the response curve of the working electrode to different concentrations of biomarkers at different insertion depths. In actual use, the system can automatically calibrate the sensor data according to the insertion depth of the microneedle, thereby providing more accurate and reliable biochemical monitoring results. This self-calibration function significantly improves the accuracy of monitoring, reduces the measurement error caused by inconsistent insertion depth, and makes the system more suitable for personalized medicine and long-term health monitoring. By providing real-time monitoring of multiple parameters, the present invention provides strong technical support for chronic disease management, health assessment and individualized treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 It is a schematic diagram of the overall structure of the present invention;

[0025] Figure 2 Schematic diagram of the structure of the reference electrode, calibration electrode, glucose electrode and ion sensing electrode of the present invention;

[0026] Figure 3 It is a schematic diagram of the array assembly process of the present invention;

[0027] Figure 41 is the response curve of the glucose electrode to different concentrations of the analyte at different depths obtained in the embodiment;

[0028] Figure 5 is the impedance of the calibration electrode at different depths obtained in the embodiment of the present invention;

[0029] Figure 6 It is the calibration principle in the embodiment of the present invention;

[0030] Figure 7 It is the relationship between the insertion depth and the slope of the response curve corresponding to the insertion depth in the embodiment of the present invention.

[0031] Figure 8 Schematic diagram of the structure of the reference electrode, counter electrode, calibration electrode, glucose electrode and ion sensing electrode of the present invention;

[0032] Figure 9 Schematic diagram of the structure of the counter electrode of the present invention. DETAILED DESCRIPTION

[0033] In order to make the above-mentioned objects, features and advantages of the present invention more clearly understood, the specific embodiments of the present invention are described in detail below with reference to the accompanying drawings. In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention can be implemented in many other ways than those described herein, and those skilled in the art can make similar improvements without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below. The technical features in the various embodiments of the present invention can be combined accordingly without conflicting with each other.

[0034] In the description of the present invention, it should be understood that when an element is considered to be "connected" to another element, it can be directly connected to the other element or indirectly connected, that is, there are intermediate elements. On the contrary, when an element is said to be "directly" connected to another element, there are no intermediate elements.

[0035] In the description of the present invention, it should be understood that the terms "first" and "second" are used solely for descriptive purposes and are not to be construed as indicating or implying relative importance or implicitly specifying the number of technical features being described. Therefore, features defined as "first" or "second" may explicitly or implicitly include at least one of such features.

[0036] like Figure 1As shown, in a preferred embodiment of the present invention, a self-calibrating multi-parameter microneedle monitoring system is provided, which includes a detection circuit module and a data processing module, a flexible circuit substrate 1, and a solid microneedle electrode array vertically fixed to the surface of the flexible circuit substrate 1. The flexible circuit substrate 1 provides a mounting base for the solid microneedle electrode array and corresponding wires. The solid microneedle electrode array includes a reference electrode 2, a calibration electrode 4, and a glucose electrode 5. The glucose electrode 5 and the calibration electrode 4 serve as working electrodes, respectively, and together with the reference electrode 2, form a two-electrode system.

[0037] In addition to the two-electrode system, the solid microneedle electrode array of the present invention can further include a counter electrode 3 to form a three-electrode system with the working electrode and the reference electrode 2. In the embodiment of the present invention, a three-electrode system is preferably used to maximize the detection accuracy.

[0038] There are a series of existing technical implementations for the reference electrode 2, calibration electrode 4 and glucose electrode 5, and theoretically any commercially available product can be used to implement them. Figure 2 The figure shows the specific structures of the reference electrode 2, calibration electrode 4, and glucose electrode 5 in an embodiment of the present invention. The reference electrode 2 comprises a first metal microneedle 2.1, which is surface-modified with a silver / silver chloride layer 2.2. The counter electrode 3 comprises a second metal microneedle 3.1, which is surface-modified with a platinum layer 3.2. The calibration electrode 4 comprises a third metal microneedle 4.1, which is surface-modified with a gold layer 4.2. The glucose electrode 5 comprises a fourth metal microneedle 5.1, which is surface-modified, from the inside out, with a platinum layer 5.2, a poly(o-phenylenediamine) layer 5.3, a glucose oxidase layer 5.4, and a biocompatible layer 5.5. The first metal microneedle 2.1 is a silver-plated or silver-plated needle with a diameter of 0.25-0.35 mm and a length of 0.5-1.5 mm. The second metal microneedles 3.1, the third metal microneedles 4.1 and the fourth metal microneedles 5.1 are steel needles with a diameter of 0.25 to 0.35 mm and a length of 0.5 to 1.5 mm. The biocompatible layer 5.5 is a polyurethane (PU) layer.

[0039] In an embodiment of the present invention, the solid microneedle electrode array can be assembled onto a flexible circuit substrate 1 via a copper disc array. A copper disc array can be provided on the flexible circuit substrate 1 to complement the solid microneedle electrode array. Each solid microneedle is mounted on a corresponding copper disc, and the solid microneedles and the copper discs are electrically connected via a conductive silver paste, which is then covered with UV adhesive for circuit insulation. Furthermore, the copper disc array is electrically connected to a multi-channel interface via wires, and a detection circuit module controls and collects signals from the solid microneedle electrode array on the flexible circuit substrate 1 via the multi-channel interface.

[0040] See also Figure 3 As shown, the specific process of processing the above-mentioned solid microneedle electrode array on the flexible circuit substrate 1 in the embodiment of the present invention is demonstrated. The specific method is: the microneedle electrode is placed vertically in the copper disk hole of the flexible circuit substrate, and the metal part of the microneedle can be connected to the copper disk using conductive silver paste, and ultraviolet glue is coated on the outside of the conductive silver paste to fix the microneedle electrode and insulate the circuit from the outside world. The effective length of the microneedle is 1mm. After the preparation of the microneedle array is completed, since the circuit is arranged on the flexible circuit substrate, the microneedle electrode is connected to the circuit through the conductive silver paste, and a three-electrode or two-electrode system is formed under the control of the detection circuit to complete the detection of relevant biomarkers. At the same time, thanks to the characteristics of the flexible circuit substrate, the microneedle array can fit the human skin without causing discomfort.

[0041] In addition, the detection circuit module is used to apply an operating voltage to the electrode system and read the impedance value of the calibration electrode 4 and the response current of the glucose electrode 5. The specific circuit form of the detection circuit module can be implemented with reference to existing microneedle sensor technology, and the operating voltage of each electrode can be optimized and adjusted based on actual conditions. In an embodiment of the present invention, when the monitoring system is in operation, the glucose electrode 5, the reference electrode, and the counter electrode form a three-electrode system. The operating voltage between the glucose electrode and the reference electrode is 0.5V. At this operating voltage, glucose molecules in the tissue fluid are decomposed into hydrogen peroxide by glucose oxidase, which, after catalysis by the platinum layer, forms a current signal related to the glucose concentration.

[0042] The core of the present invention lies in the data processing module, which is used to read the impedance value of the calibration electrode 4 and the response current of the glucose electrode 5, and execute the current correction and glucose concentration conversion process. The following is a detailed description of the current correction and glucose concentration conversion process:

[0043] First, the first fitting equation obtained by fitting the measured data is called, and the insertion depth of the glucose electrode 5 is calculated according to the impedance value of the calibration electrode 4;

[0044] Then, the second fitting equation obtained by fitting the measured data is called to calculate the first slope of the current-glucose concentration response curve corresponding to the current insertion depth according to the insertion depth of the glucose electrode 5;

[0045] Based on the second slope of the current-glucose concentration response curve corresponding to the measured full penetration depth, the response current of the glucose electrode 5 is corrected using the ratio of the second slope to the first slope as a correction factor;

[0046] Finally, the current-glucose concentration response curve corresponding to the full penetration depth is called, and the glucose concentration is calculated based on the corrected response current.

[0047] The first fitting equation is an exponential equation, in the form of Z = m·H n , where m and n are fitting coefficients, H is the penetration depth of the calibration electrode 4 and the glucose electrode 5, and Z is the impedance value of the calibration electrode 4. It should be noted that in the present invention, the penetration depths of the calibration electrode 4 and the glucose electrode 5 are regarded as the same. The above-mentioned second fitting equation is a linear equation in the form of A′=a·H′+b, where a and b are fitting coefficients, H′ is the actual penetration depth of the glucose electrode 5, and A′ is the slope of the current-glucose concentration response curve corresponding to the actual penetration depth of the glucose electrode 5. The above-mentioned first fitting equation is obtained by fitting the measured data obtained by inserting the calibration electrode 4 into different depths on agarose gels with different glucose concentrations; and the second fitting equation is obtained by fitting the measured data obtained by inserting the glucose electrode 5 into different depths on agarose gels with different glucose concentrations.

[0048] The following is a specific example to illustrate the pre-fitting method and actual execution procedure of the current correction and glucose concentration conversion process in the monitoring system.

[0049] First, the response of the two working electrodes to the object to be measured at different penetration depths is tested. In this example, the response curve of the glucose electrode to glucose at different penetration depths is tested. Agarose gel containing different concentrations of glucose is prepared using 0.1M phosphate buffer (PBS), 400g of agarose powder is dissolved in 20mL0.1M PBS, heated to 90°C on a heating table, and stirred continuously until the agarose is completely dissolved and the solution is clear. The solution is transferred to a culture dish, and the solution is returned to room temperature to prepare an agarose gel with a glucose concentration of 0. Repeat the above steps, and add different volumes of glucose solution to the solution in turn to prepare agarose gels with 2M, 4M, 6M, 8M, and 10M concentrations of glucose. The surface of the prepared agarose gel is smooth and does not contain bubbles or impurities. The glucose electrode 5, the reference electrode 2, and the counter electrode 3 are assembled into a microneedle array, the microneedle array is fixed on an electric translation table, and the agarose gel is fixed on the opposite side of the microneedle array, with the gel surface perpendicular to the microneedle. Move the electric translation stage until the microneedle contacts the surface of the gel, and record the depth at this time as 0mm. Control the electric translation stage to move 0.2mm each time. After stabilizing for 30s, control the detection circuit to apply the working voltage and record the current value until the effective part of the microneedle completely penetrates the agarose gel, that is, the longest moving distance is 1mm. Replace the agarose gel with different concentrations and repeat the above steps. The response curve between the current and glucose at different penetration depths of the glucose electrode, that is, the current-glucose concentration response curve, can be measured, as shown in Figure 2. Figure 4 shown.

[0050] Afterwards, the calibration electrode 4 was tested. Agarose gel was prepared using 0.1M PBS solution, using the same method as above. The calibration electrode 4, reference electrode 2 and counter electrode 3 were assembled into a microneedle array and fixed on an electric translation stage. The agarose gel was fixed on the opposite side of the microneedle array, with the gel surface perpendicular to the microneedle. Similarly, the electric translation stage was moved until the microneedle was in contact with the gel surface, and the depth at this time was recorded as 0mm. The electric translation stage was controlled to move a distance of 0.2mm each time, and an electrochemical impedance test was performed after stabilization for 30s, and the impedance value was recorded until the effective part of the microneedle completely penetrated the agarose gel, that is, the longest moving distance was 1mm. The impedance value of the calibration electrode 4 at different penetration depths can be measured, as shown in the attached figure. Figure 5 As shown. The fitting equation of the insertion depth and impedance value of the calibration electrode 4 can be obtained by fitting, that is, the above-mentioned first fitting equation is:

[0051] Z=m·H n Formula 1

[0052] Where m and n are the fitting coefficients, and H is the penetration depth.

[0053] In the present invention, since the glucose electrode 5 and the calibration electrode 4 are assembled on the flexible circuit substrate 1 with the same posture and length, the insertion depths of the two can be considered the same. The insertion depth of the calibration electrode 4 is the insertion depth of the glucose electrode 5.

[0054] During the test, the test results of the glucose electrode 5 are compensated and calibrated by the impedance test results of the calibration electrode. The calibration principle is as follows Figure 6 As shown, under standard conditions, the microneedle completely penetrates the skin, the penetration depth is H = 1mm, and the current-glucose concentration response curve corresponds to curve A. When the glucose concentration is M0, the test current is I0. In actual application, due to the influence of skin surface factors, the microneedle cannot completely penetrate the skin, resulting in a decrease in the actual penetration depth H' and a decrease in the slope of the corresponding curve. When the glucose concentration is M0, the actual measured current value is I1. Therefore, the current value needs to be compensated and calibrated. When the penetration depth is H', assuming that the current value before compensation is I1 and the current value after compensation is I0, the compensation equation is:

[0055] I0=I1·(1+f(H′)) Formula 2 Where, after derivation, f(H′) is determined by the following formula

[0056]

[0057] Where A is the slope of the response curve corresponding to the full insertion depth, that is, the slope of the current-glucose concentration response curve when the insertion depth is 1 mm, and A′ is the slope of the current-glucose concentration response curve corresponding to the actual insertion depth H′. Tests have found that the slope of the current-glucose concentration response curve corresponding to the insertion depth is linearly related to the insertion depth, which can be calculated according to the second fitting equation A′=a·H′+b. Figure 4 The different penetration depths and response curve slopes in the were fitted, i.e. Figure 4 Each response curve has a corresponding curve slope and corresponding penetration depth, which can be used as fitting data to obtain the following linear equation: Figure 7 The linear fitting curve is shown. Substituting the fitting formula of the linear fitting curve into formula 3, we can get:

[0058]

[0059] Where a is Figure 7 The slope of the linear fitting curve shown, b, is Figure 7 The intercept of the linear fitting curve is shown, and H′ is the actual penetration depth calculated according to Formula 1.

[0060] Furthermore, substituting Equation 4 into Equation 2 yields:

[0061]

[0062] In this example, the monitoring system obtains the electrochemical impedance of the current microneedle electrode by calibrating the electrochemical impedance test of the electrode. Furthermore, the penetration depth of the microneedle array is deduced as H' according to Formula 1. When the glucose microneedle electrode is working, the current before electrode compensation is measured as I1. Substituting H' and I1 into Formula 5, the current value after compensation calibration, I0, can be obtained. Based on the current value after compensation calibration, I0 and Figure 4 The glucose concentration was calculated based on the current-glucose concentration response curve when the insertion depth was 1 mm.

[0063] Thus, the present invention obtains an electrode calibration curve by controlling the electrode penetration depth. In the present invention, agarose gel is used to simulate skin. By fixing the position of the agarose gel, a motorized translation stage is used to control the electrode penetration depth to obtain the electrode calibration curve. This method of controlling the electrode penetration depth is not limited to this. In practical applications, the relevant control method can be determined based on the different microneedle morphologies.

[0064] In addition, in the above embodiment of the present invention, the self-calibrating multi-parameter microneedle monitoring system is mainly used to calibrate the glucose electrode to achieve accurate blood glucose monitoring. However, the specific detection function of the system can be expanded as needed, for example, see Figure 8As shown, the solid microneedle electrode array may further include an ion sensing electrode 6 for detecting ion concentration. Figure 9 As shown, the main body of the ion sensing electrode 6 is a fifth metal microneedle 6.1. The surface of the fifth metal microneedle 6.1 is sequentially modified with a gold layer 6.2, a polystyrenesulfonate-doped poly (3,4-ethylenedioxythiophene) layer 6.3, and an ion-selective membrane layer 6.4, from the inside out. The ion-selective membrane layer 6.4 can be selective for potassium, sodium, calcium, or other ions, depending on the needs. The ion sensing electrode 6, together with a reference electrode and a counter electrode, forms an electrode system, generating a voltage signal at the electrodes that is related to the analyte.

[0065] The present invention provides a microneedle electrode calibration method with wide applicability. This method is not only applicable to glucose microneedle electrodes, but can also be used for electrochemical microneedle electrodes prepared by other electrochemical methods. In this example, a three-electrode system is constructed and the calibration curve of the glucose electrode is obtained by the amperometric method, and the current signal is compensated and corrected. The correction method of the present invention can be extended to other electrode systems, such as a two-electrode system, and can be applied to other electrochemical detection methods, such as potentiometric method and cyclic voltammetry. By measuring the response signals of the microneedle electrodes at different insertion depths, the problems of the electrodes in practical applications can be effectively compensated and corrected.

[0066] The embodiments described above are merely some preferred implementations of the present invention and are not intended to limit the present invention. Persons skilled in the art may make various changes and modifications without departing from the spirit and scope of the present invention. Therefore, any technical solution obtained by equivalent substitution or equivalent transformation falls within the scope of protection of the present invention.

Claims

1. A self-calibrating multi-parameter microneedle monitoring system, characterized in that: The invention comprises a detection circuit module and a data processing module, a flexible circuit substrate (1), and a solid microneedle electrode array vertically fixed on the surface of the flexible circuit substrate (1); the solid microneedle electrode array comprises a reference electrode (2), a calibration electrode (4), and a glucose electrode (5); the glucose electrode (5) and the calibration electrode (4) serve as working electrodes, respectively, and form a two-electrode system with the reference electrode (2); The detection circuit module is used to apply a working voltage to the electrode system and read the impedance value of the calibration electrode (4) and the response current of the glucose electrode (5); The data processing module is used to read the impedance value of the calibration electrode (4) and the response current of the glucose electrode (5), and execute the current correction and glucose concentration conversion process. The procedure of the process is as follows: first, calling the first fitting equation obtained by fitting the measured data, and calculating the insertion depth of the glucose electrode (5) according to the impedance value of the calibration electrode (4); then calling the second fitting equation obtained by fitting the measured data, and calculating the first slope of the current-glucose concentration response curve corresponding to the current insertion depth according to the insertion depth of the glucose electrode (5); then, based on the second slope of the current-glucose concentration response curve corresponding to the measured full insertion depth, the response current of the glucose electrode (5) is corrected with the ratio of the second slope to the first slope as a correction factor; finally, calling the current-glucose concentration response curve corresponding to the full insertion depth, and calculating the glucose concentration according to the corrected response current.

2. The self-calibrating multi-parameter microneedle monitoring system according to claim 1, wherein: The solid microneedle electrode array further comprises a counter electrode (3), which forms a three-electrode system with the working electrode and the reference electrode (2).

3. The self-calibrating multi-parameter microneedle monitoring system according to claim 1, wherein: The flexible circuit substrate (1) has a copper disk array that matches the solid microneedle electrode array. The solid microneedles are mounted on the copper disks, and the two are electrically connected via conductive silver paste. The conductive silver paste is covered with ultraviolet glue for circuit insulation.

4. The self-calibrating multi-parameter microneedle monitoring system according to claim 3, wherein: The copper disk array is electrically connected to a multi-channel interface via a wire, and the detection circuit module controls and collects signals from the solid microneedle electrode array on the flexible circuit substrate (1) via the multi-channel interface.

5. The self-calibrating multi-parameter microneedle monitoring system according to claim 1, wherein: The first fitting equation is an exponential equation in the form of Z=m·H n , where m and n are fitting coefficients, H is the penetration depth of the calibration electrode (4) and the glucose electrode (5), and Z is the impedance value of the calibration electrode (4).

6. The self-calibrating multi-parameter microneedle monitoring system according to claim 1, wherein: The second fitting equation is a linear equation in the form of A′=a·H′+b, where a and b are fitting coefficients, H′ is the actual insertion depth of the glucose electrode (5), and A′ is the slope of the current-glucose concentration response curve corresponding to the actual insertion depth of the glucose electrode (5).

7. The self-calibrating multi-parameter microneedle monitoring system according to claim 1, wherein: The first fitting equation is obtained by fitting the measured data obtained by inserting the calibration electrode (4) into agarose gels with different glucose concentrations at different depths; the second fitting equation is obtained by fitting the measured data obtained by inserting the glucose electrode (5) into agarose gels with different glucose concentrations at different depths.

8. The self-calibrating multi-parameter microneedle monitoring system according to claim 1, wherein: The main body of the reference electrode (2) is a first metal microneedle (2.1), and the surface of the first metal microneedle (2.1) is modified with a silver / silver chloride layer (2.2); The main body of the counter electrode (3) is a second metal microneedle (3.1), and the surface of the second metal microneedle is modified with a platinum layer (3.2); The main body of the calibration electrode (4) is a third metal microneedle (4.1), and the surface of the third metal microneedle is modified with a gold layer (4.2); The main body of the glucose electrode (5) is a fourth metal microneedle (5.1), and the surface of the fourth metal microneedle is sequentially modified with a platinum layer (5.2), a poly-o-phenylenediamine layer (5.3), a glucose oxidase layer (5.4), and a biocompatible layer (5.5) from the inside to the outside.

9. The self-calibrating multi-parameter microneedle monitoring system according to claim 8, wherein: The first metal microneedle (2.1) is a silver-plated needle or a silver needle with a diameter of 0.25 to 0.35 mm and a length of 0.5 to 1.5 mm; The second metal microneedle (3.1), the third metal microneedle (4.1) and the fourth metal microneedle (5.1) are steel needles with a diameter of 0.25 to 0.35 mm and a length of 0.5 to 1.5 mm.

10. The self-calibrating multi-parameter microneedle monitoring system according to claim 1, wherein: The solid microneedle electrode array further comprises an ion sensing electrode (6) for detecting ion concentration. The main body of the ion sensing electrode (6) is a fifth metal microneedle (6.1). The surface of the fifth metal microneedle (6.1) is sequentially modified from the inside to the outside with a gold layer (6.2), a polystyrene sulfonate-doped poly (3,4-ethylenedioxythiophene) layer (6.3), and an ion selective membrane layer (6.4).

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