A blood glucose monitoring apparatus and method capable of continuous blood glucose monitoring and control

Abstract

The application discloses a blood glucose monitoring device and method capable of realizing continuous blood glucose monitoring and control. The monitoring method comprises the following steps: regulating the subcutaneous penetration state of insulin by changing the direction of an electric field applied to an insulin gel composition; wherein the insulin gel composition is communicated with a microneedle array composed of hollow microneedles, and the insulin gel composition comprises insulin, hyaluronic acid and a hydrogel. The application can realize automatic and continuous blood glucose monitoring and dynamic insulin regulation, and can be designed in the form of a skin patch for application by a patient, and has the advantages of small volume, high comfort and low cost.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of blood glucose monitoring devices, in particular to the technical field of automated blood glucose monitoring devices. BACKGROUND

[0002] The monitoring and control of blood glucose is the core of the diagnosis and treatment of diabetes. In the prior art, blood glucose monitoring mainly includes four ways: non-invasive, semi-implantable, implantable and minimally invasive. Among them, non-invasive blood glucose monitoring mainly includes two technical routes. One is to analyze the glucose content in body fluids such as sweat, tears, and urine to infer blood glucose content, but due to the low correlation between the glucose concentration in body fluids and blood glucose, and many interferences, the accuracy is low, and it is difficult to be used for clinical diagnosis. The second is to calculate the blood glucose value by infrared, metabolism, impedance and other methods, including infrared detection method, counter-ion electroosmosis method and wireless resistance method. Although this method can achieve 80% accuracy under ideal conditions, it cannot be widely used in actual application due to serious interference, low signal-to-noise ratio and other defects; the semi-implantable blood glucose monitoring method is to measure the blood glucose content by inserting a long needle (0.5 cm) into the subcutaneous capillary. This method has relatively high accuracy, but has the disadvantages of needle pain and short service life of the testing tool; the implantable blood glucose monitoring method is to implant a sensor into the subcutaneous tissue to measure the glucose content in the interstitial fluid. Since the correlation between glucose in interstitial fluid and blood is high, the measurement accuracy is high, but this method requires professional medical personnel to operate, is not convenient for patients to use, and the equipment is expensive; the minimally invasive blood glucose monitoring method is to use a microneedle to penetrate the skin epidermis layer, and then measure the glucose content in the interstitial fluid to correlate the blood glucose content. Since the length of the microneedle is only a few hundred microns, it will not contact the nerve to produce pain, so this method has the characteristics of non-invasive, high precision and good stability, and is currently considered the most ideal continuous blood glucose monitoring method. However, the existing minimally invasive blood glucose monitoring method still has problems such as low accuracy of the sensor used and feedback lag, and further technical improvement is needed.

[0003] On the other hand, in terms of blood glucose control, the prior art is mainly achieved by injecting insulin. Common insulin injection methods include needle subcutaneous injection, insulin pump injection and minimally invasive injection. Among them, the needle subcutaneous injection is to inject a certain amount of insulin into the subcutaneous tissue by a syringe for medical personnel or patients with certain operation ability. This method has low cost, but poor comfort, and it is difficult to achieve blood glucose control in patients without active consciousness (such as sleeping). The insulin pump injection is to inject insulin into the subcutaneous tissue to achieve blood glucose control by controlling the system through long-term penetration of the needle into the subcutaneous tissue. This method can achieve blood glucose control in patients without active consciousness, but has high cost and poor comfort. The minimally invasive injection mainly includes two ways. One is to inject insulin into the subcutaneous tissue through a high-speed and extremely fine water column. This method has strong comfort, but has high cost and needs self-injection of patients. The other is to inject insulin into the patient's body through a microneedle, which has higher comfort and lower cost, but usually needs to rely on the self-injection of patients and is difficult to achieve continuous insulin control. It can be seen that the existing insulin injection scheme needs to be further improved.

[0004] In addition, in the prior art, blood glucose monitoring and insulin injection are usually completed by different instruments and equipment, and it is difficult to achieve rapid and efficient unified regulation and control between them, and it is also easy to cause multiple trauma to patients. SUMMARY

[0005] In view of the defects of the prior art, the purpose of the present application is to provide a novel blood glucose monitoring device and method. The microneedle in the blood glucose monitoring device can be used as a carrier and electrode of a high-accuracy blood glucose sensor and an insulin permeation channel, and can automatically achieve blood glucose monitoring and insulin injection. The blood glucose monitoring device can also dynamically regulate the penetration of insulin into the subcutaneous tissue based on the principle of iontophoresis, and can be designed as a skin patch, which has small volume, high comfort and low cost.

[0006] The present application provides the following technical solutions:

[0007] A blood glucose monitoring method capable of achieving continuous blood glucose monitoring and control, comprising: controlling the penetration or non-penetration of insulin in the subcutaneous tissue by regulating the direction of the electric field applied to the insulin gel composition; wherein the insulin gel composition is in communication with a microneedle array composed of hollow microneedles of metal, and the insulin gel composition comprises insulin, hyaluronic acid and hydrogel.

[0008] According to some preferred embodiments of the present application, the blood glucose monitoring method further comprises: obtaining blood glucose data by a glucose sensor fixed at the needle tip of part of the microneedles in the microneedle array.

[0009] The application further provides a blood glucose monitoring device capable of continuous blood glucose monitoring and control, which comprises a substrate with load and fixing functions, a microneedle array fixed to the substrate and composed of hollow metal microneedles and a porous support plate in communication with the hollow metal microneedles, a gel layer attached to the porous support plate and composed of a mixture of insulin and gel material, an electrode plate located on the gel layer and capable of defining the gel layer therebetween after being attached to the porous support plate, a controller electrically connected to the electrode plate, a battery electrically connected to the electrode plate and the controller respectively for supplying power to the monitoring device, and a glucose sensor fixed to the tips of some metal microneedles; wherein the porous support plate is made of insulating material; the battery contains a cathode and an anode; the gel material is a hydrogel material containing hyaluronic acid; the electrode plate comprises a middle electrode plate located in the middle and a surrounding electrode plate surrounding the middle electrode plate, and the middle electrode plate and the surrounding electrode plate are electrically connected to the controller respectively; the porous support plate has a structure with a recessed middle part and a flat edge, and the recessed middle part is provided with an array of holes in communication with the metal microneedles, and the gel material is hyaluronic acid.

[0010] According to some preferred embodiments of the application, the microneedle array comprises three types of microneedles, namely working electrode microneedles, counter electrode microneedles and reference electrode microneedles, wherein the working electrode microneedles are fixed with the glucose sensor at their tips, and have openings on the side of the needle head of the working electrode microneedles above the glucose sensor for insulin penetration; the counter electrode microneedles form an electronic circuit with the working electrode microneedles; and the reference electrode microneedles provide a reference potential for the working electrode microneedles.

[0011] According to some preferred embodiments of the application, the working electrode microneedles are formed of gold material, the counter electrode microneedles are formed of platinum gold material, and the reference electrode microneedles are formed of silver and silver chloride material; the blood glucose monitoring device comprises 2 working electrode microneedles, 1 counter electrode microneedle and 1 reference electrode microneedle, and in the process of blood glucose testing, the 2 working electrode microneedles are directly connected by wires, the 2 working electrode microneedles and the counter electrode microneedle are connected by wires and then connected to the controller, and the reference electrode microneedle is directly connected to the controller.

[0012] According to some preferred embodiments of the application, the glucose sensor is fixed by the following method: the glucose sensor is sucked into the needle hole of the working electrode microneedle through air pressure difference, and then the sensor is fixed on the working electrode microneedle by hydraulic pump compression.

[0013] According to some preferred embodiments of the present application, the preparation of the gel layer comprises: mixing acrylamide, N,N'-methylene bisacrylamide and a photoinitiator, and then performing photoinitiated polymerization to obtain a hydrogel patch, and then immersing the hydrogel patch in a mixed solution of 400 U / ml of insulin and 0.1 wt% of hyaluronic acid to obtain the gel layer.

[0014] According to some preferred embodiments of the present application, the controller is implemented by an MCU, which contains a charging unit, a power supply unit, a processing unit, a display unit and a digital-to-analog conversion unit.

[0015] According to some preferred embodiments of the present application, the glucose sensor is a third-generation or improved third-generation glucose sensor based on glucose oxidase.

[0016] According to some preferred embodiments of the present application, the substrate and the porous support plate and the electrode plate are all flexible materials.

[0017] According to some preferred embodiments of the present application, the glucose sensor is a third-generation or improved third-generation glucose sensor based on glucose oxidase.

[0018] According to some preferred embodiments of the present application, the glucose sensor is a glucose sensor based on glucose oxidase and flavin adenine dinucleotide coenzyme.

[0019] The present application has the following advantages:

[0020] The monitoring method or device of the present application can place the gel containing insulin outside the body, and through the regulation of the electric field, the insulin is injected into the subcutaneous tissue through the hollow microneedle channel, which can realize strong comfort, low cost, automatic and controllable continuous administration of insulin.

[0021] In the monitoring method or device of the present application, the insulin can be delivered transdermally based on the principle of iontophoresis through the microneedle array and the electric field, and the principle is as follows: the insulin gel composition contains both insulin and hyaluronic acid, wherein the insulin is electrically neutral and cannot penetrate into the subcutaneous tissue under the action of the electric field, but the hyaluronic acid is negatively charged and can penetrate into the subcutaneous tissue under the action of the electric field. During the penetration of hyaluronic acid into the subcutaneous tissue, due to the impact between molecules, hyaluronic acid molecules will penetrate into the subcutaneous tissue together with insulin molecules. This overcomes the problem that the prior art cannot directly penetrate insulin into the subcutaneous tissue by the action of the electric field.

[0022] The micro-needle array of the monitoring device can be directly inserted into the subcutaneous tissue, the active center of the glucose sensor fixed at the needle tip and the electrode surface can be directly connected, the length of the electron transfer path is greatly shortened, the voltage required for electron transfer is reduced, the accuracy, stability and safety of the sensor are improved, and continuous monitoring of blood glucose can be realized.

[0023] In the monitoring device of the application, the micro-needle can exist in the subcutaneous tissue at all times, which can be used as a carrier of the blood glucose sensor and an electrode and a data transmission path while serving as an insulin permeation channel. After being matched with an electric field and a controller, the micro-needle can control the release of insulin through the principle of ion electrophoresis, especially the counter-ion permeation technology, without worrying about the continuous penetration of insulin into the skin due to concentration difference in the case of no need for drug administration, and can dynamically regulate the drug release through blood glucose data, so that the drug can be automatically injected without human action.

[0024] In the monitoring device of the application, the micro-needle can be used for blood glucose monitoring and control at the same time, effectively reducing the size and cost of the device, so that it can be designed as a small skin patch for application. Compared with the existing monitoring and control system based on blood glucose meter and insulin pump, the monitoring device of the application is smaller in size, more comfortable to wear, and lower in cost, and can provide convenient, comfortable, safe and stable blood glucose monitoring and control services for a large number of diabetic patients. BRIEF DESCRIPTION OF DRAWINGS

[0025] Figure 1 It is a schematic diagram of the overall structure of the blood glucose monitoring device in the specific embodiment.

[0026] Figure 2 It is a schematic diagram of the structure of the micro-needle array in the specific embodiment.

[0027] Figure 3 It is a schematic diagram of the structure of the working electrode micro-needle in the specific embodiment.

[0028] Figure 4 It is a schematic diagram of the electrode plate electric field direction regulation in the specific embodiment.

[0029] Figure 5 It is a schematic diagram of the insulin controlled release state in the specific embodiment.

[0030] Figure 6 It is a schematic diagram of the controller composition structure in the specific embodiment.

[0031] Figure 7 It is a schematic diagram of the controller MCU circuit in the specific embodiment.

[0032] Figure 8 It is a schematic diagram of the power supply unit circuit in the specific embodiment.

[0033] Figure 9 This is a circuit diagram of the charging unit in a specific implementation.

[0034] Figure 10 This is a circuit diagram of the display unit in a specific implementation.

[0035] Figure 11 This is a circuit diagram of the digital-to-analog converter unit in a specific implementation.

[0036] Figure 12 This is a logic flowchart of the controller in a specific implementation. Detailed Implementation

[0037] The present invention will now be described in detail with reference to embodiments and accompanying drawings. However, it should be understood that the embodiments and drawings are for illustrative purposes only and do not constitute any limitation on the scope of protection of the present invention. All reasonable modifications and combinations included within the inventive spirit of the present invention fall within the scope of protection of the present invention.

[0038] See attached document Figures 1-3 According to the technical solution of the present invention, in some specific embodiments, the blood glucose monitoring device capable of continuous blood glucose monitoring and control includes:

[0039] The system comprises: a substrate 1; a microneedle array 2 fixed to the substrate 1, consisting of hollow metal microneedles 21 and a porous support plate 20 communicating with the hollow metal microneedles; a gel layer 3 attached to the porous support plate, comprising a mixture of insulin and a gel material; an electrode plate 4 located on the gel layer 3, which can be bonded to the porous support plate to confine the gel layer 3 between the two; a controller 5 electrically connected to the electrode plate 4; and a battery 6 containing a cathode and an anode, connected to the controller 5 and supplying power to the monitoring device; wherein the gel material is a hydrogel material containing hyaluronic acid; the electrode plate 4 includes a central electrode plate located in the middle and peripheral electrode plates surrounding the central electrode plate, the central electrode plate and the peripheral electrode plates being electrically connected to the controller 5 respectively, and controlled by the controller 5. The controller 5 dynamically controls the electrical properties of the intermediate electrode plate and the surrounding electrode plates through a control program; the porous support plate 20 has a structure with a concave center and flat, convex edges, and the concave center has an array of holes communicating with the metal microneedles 21; the microneedle array 2 includes three types of microneedles, namely working electrode microneedles, counter electrode microneedles, and reference electrode microneedles, wherein the working electrode microneedle has a blood glucose sensor 201 fixed at the tip, and the blood glucose sensor 201 enters the dermis layer of the skin with the help of the microneedle to sense the glucose content in the tissue fluid. There is an opening 202 on the side of the needle tip of the working electrode microneedle and on the blood glucose sensor to realize the release of insulin; the counter electrode microneedle and the working electrode form an electronic circuit; the reference electrode microneedle can provide a reference potential for the working electrode.

[0040] In some preferred embodiments, to increase signal strength, eliminate common mode interference, and improve signal-to-noise ratio, the blood glucose monitoring device uses two identical working electrode microneedles, one counter electrode microneedle, and one reference electrode microneedle. During the blood glucose test, the two working electrode microneedles are directly connected by wires, and the two working electrode microneedles and the counter electrode microneedle are connected by wires and then connected to the controller 5. The reference electrode microneedle is directly connected to the controller 5. The electrical signals output by the working electrode microneedle and the reference electrode microneedle are input into the controller 5 as blood glucose test output signals.

[0041] In some preferred embodiments, the porous support plate 20 can be made by 3D printing technology. The material used is preferably a non-conductive polymer material such as polylactic acid, polycarbonate, etc. The porous support plate 20 and the hollow metal microneedle 21 are physically connected and can be reinforced with conductive glue.

[0042] The substrate 1 is the carrier of the entire monitoring device, responsible for carrying the microneedle array, blood glucose sensor, gel, electrode plate, controller, battery, and other components.

[0043] The middle electrode plate and the surrounding electrode plate of the electrode plate 4 can be made of stainless steel electrode sheets, which provide an electric field for the charged particles in the gel layer by outputting voltage. The direction of the electric field formed by the electrode plate 4 can be dynamically adjusted by the controller, forming an electric field direction of inside positive and outside negative or inside negative and outside positive, as shown in the accompanying Figure 4 .

[0044] The controller 5 can monitor blood glucose changes through the blood glucose sensor in electrical communication with the working electrode microneedle, and when the blood glucose data is abnormal, it can adjust the electric field direction of the electrode plate 4 to achieve controlled release of insulin molecules Y in the gel layer 3, stabilizing blood glucose.

[0045] As in a specific embodiment, referring to the accompanying Figure 5 , when high blood sugar is detected, the middle electrode plate in the electrode plate 4 is adjusted to be negatively charged, and the surrounding electrode plate is positively charged, with an electric field direction as shown in the accompanying Figure 4 middle right figure, at this time, the hyaluronic acid (negatively charged) in the gel layer 3 will enter the body from the outside due to the principle of same-sex repulsion, with insulin molecules Y mixed in; when the blood glucose level is normal, the middle electrode plate in the electrode plate 4 is adjusted to be positively charged, and the surrounding electrode plate is negatively charged, with an electric field direction as shown in the accompanying Figure 4 left figure, at this time, the hyaluronic acid (negatively charged) in the gel material will retain the insulin in the gel layer 3 and will not enter the body due to the principle of opposite sex attraction.

[0046] In some preferred embodiments, the substrate 1 is a flexible material that can be attached to the surface of the human body. The porous support plate 20 and the electrode plate 4 are both flexible materials that can bend with the substrate 1.

[0047] In some preferred embodiments, the working electrode microneedle is formed of gold material, the counter electrode microneedle is formed of platinum material, and the reference electrode microneedle is formed of silver and silver chloride material.

[0048] In some preferred embodiments, the metal microneedle 21 is in a conical structure with a conical height of 0.4-0.6 mm and a conical base diameter of 0.1-0.3 mm.

[0049] In some preferred embodiments, the blood glucose sensor 201 of the working electrode microneedle is installed at a height of 0-0.1 mm above the needle tip, and the side opening 202 has a diameter of 10-30 μm.

[0050] In some preferred embodiments, the blood glucose sensor is fixed by first sucking the blood glucose sensor 201 into the needle hole of the working electrode microneedle through air pressure difference, and then firmly fixing the sensor on the working electrode microneedle under a pressure of about 1000 N through hydraulic pump compression.

[0051] In some preferred embodiments, the blood glucose sensor 201 is a third generation or improved third generation glucose sensor based on glucose oxidase.

[0052] In some preferred embodiments, the blood glucose sensor 201 is a glucose sensor based on glucose oxidase and FAD (flavin adenine dinucleotide) coenzyme.

[0053] In some preferred embodiments, the preparation of the gel layer 3 includes mixing 5 wt% acrylamide, 0.24 wt% N,N'-methylene bisacrylamide, and 1 mg / ml photoinitiator 2959, and then irradiating under ultraviolet light for 120 min to form a 3 mm thick hydrogel patch. The hydrogel patch is soaked in a mixed solution of 400 U / ml insulin and 0.1% hyaluronic acid for 24 h to obtain the gel layer.

[0054] In some preferred embodiments, the controller is further provided with a display screen to display the current blood glucose condition and insulin administration condition.

[0055] In some preferred embodiments, as shown in FIG. 6, the controller uses an MCU containing a charging unit, a power supply unit, a processing unit, a display unit, and a digital-to-analog conversion unit. Figure 6 Further, as shown in FIG. 7, one realizable circuit structure of the power supply unit is as shown in FIG. 8.

[0056] Figure 8 Further, as shown in FIG. 9, one realizable circuit structure of the charging unit is as shown in FIG. 10. Figure 9 Further, as shown in FIG. 11, one realizable circuit structure of the display unit using a touch display screen is as shown in FIG. 12.​Figure 10 As shown in the figure, an implementable circuit structure of the digital-analog conversion unit is as shown in the figure Figure 11 As shown in the figure, an implementable circuit structure of the processing unit is as shown in the figure Figure 7 As shown in the figure.

[0057] Further, the controller further comprises a storage unit, which can save a voltage-blood glucose corresponding relationship truth table and a blood glucose signal processing algorithm.

[0058] The control process of the corresponding controller comprises: according to the input voltage value obtained from the digital-analog conversion unit, searching the voltage-blood glucose corresponding relationship truth table in the storage unit, according to the corresponding value in the truth table, performing blood glucose value calculation and comparison judgment with normal blood glucose value according to the preset blood glucose signal processing algorithm, and dynamically regulating the electric field direction of the electrode plate 4 according to the comparison judgment result, so as to achieve the purpose of retaining / releasing insulin.

[0059] Further, the controller further comprises a communication unit with remote communication function, which can further interact with remote devices such as handheld terminals and servers, and the interaction data can include blood glucose data, algorithm update data, etc.

[0060] In specific implementation, the monitoring device of the present application can further comprise other packaging structures, and form the shape of a skin patch as a whole, which can be circular, square, rectangular or other shapes and sizes convenient for patients to use.

[0061] In specific application, the skin patch can be attached to the skin surface and pressed with a pressure of 5MPa or more, so that the microneedle array penetrates the skin epidermis and enters the dermis layer to contact the interstitial fluid. The blood glucose sensor fixed at the microneedle tip is always in contact with the interstitial fluid, which can dynamically monitor the glucose concentration in the interstitial fluid and convert the glucose concentration signal into an electrical signal. The electrical signal is transmitted to the controller through the outer wall of the microneedle, and the controller judges whether the obtained glucose content data is normal according to the set algorithm logic. If normal, the polarity of the electrode plate is maintained as positive inside and negative outside, and the monitoring continues. If abnormal, the polarity of the electrode plate is adjusted to negative inside and positive outside, and insulin is released. During the release of insulin, the blood glucose sensor always monitors the glucose concentration in the interstitial fluid, and the insulin is continuously released until the blood glucose data received by the controller returns to normal, and the polarity of the electrode plate is adjusted to negative inside and positive outside, and the penetration of insulin into the skin stops.

[0062] In some preferred embodiments, the algorithm logic of the controller can contain an alarm process, as shown in the figure Figure 12 As shown in the figure.

[0063] The above examples are only preferred embodiments of the present application, and the protection scope of the present application is not limited to the above examples. Any technical scheme falling within the concept of the present application belongs to the protection scope of the present application. It should be pointed out that improvements and refinements made by those of ordinary skill in the art without departing from the principles of the present application should also be considered as falling within the protection scope of the present application.

Claims

1. A blood glucose monitoring device capable of continuous blood glucose monitoring and control, characterized in that, It comprises: The blood glucose monitoring device comprises a substrate with load and fixing functions, a microneedle array composed of hollow metal microneedles and a porous support plate in communication with the hollow metal microneedles, a gel layer adhered to the porous support plate, the gel layer comprising a mixture composed of insulin and a gel material, an electrode plate located on the gel layer and capable of adhering to the porous support plate to define the gel layer therebetween, a controller electrically connected to the electrode plate, a battery for powering the monitoring device, and a glucose sensor fixed to the tips of some metal microneedles; wherein the porous support plate is made of insulating material; the battery comprises a cathode and an anode; the gel material is a hydrogel material containing hyaluronic acid; the electrode plate comprises a middle electrode plate located in the middle and a surrounding electrode plate surrounding the middle electrode plate, and the middle electrode plate and the surrounding electrode plate are respectively electrically connected to the controller; the porous support plate has a structure with a recessed middle part and a flat raised edge, and the recessed middle part is provided with an array of holes in communication with the metal microneedles.

2. The blood glucose monitoring device of claim 1, wherein, The microneedle array comprises three types of microneedles, namely working electrode microneedles, counter electrode microneedles and reference electrode microneedles, wherein the working electrode microneedles are fixed with the glucose sensor at their tips, and have openings on the side of the needle for insulin penetration above the glucose sensor; the counter electrode microneedles form an electronic circuit with the working electrode; the reference electrode microneedles provide a reference potential for the working electrode microneedles.

3. The blood glucose monitoring device of claim 2, wherein, The working electrode microneedles are formed of gold material, the counter electrode microneedles are formed of platinum gold material, and the reference electrode microneedles are formed of silver and silver chloride material; the blood glucose monitoring device comprises 2 working electrode microneedles, 1 counter electrode microneedle and 1 reference electrode microneedle, and in the process of blood glucose testing, the 2 working electrode microneedles are directly connected by wires, and the 2 working electrode microneedles and the counter electrode microneedle are connected by wires and then connected to the controller, and the reference electrode microneedle is directly connected to the controller.

4. The blood glucose monitoring device of claim 2, wherein, The fixing method of the glucose sensor is to suck the glucose sensor into the needle hole of the working electrode microneedle through air pressure difference, and then fix the sensor on the working electrode microneedle through hydraulic pump compression.

5. The blood glucose monitoring device of claim 1, wherein, The preparation of the gel layer includes: mixing acrylamide, N,N After mixing methylenebisacrylamide and a photoinitiator, light-induced polymerization is performed to obtain a hydrogel patch, and then the hydrogel patch is soaked in a mixed solution of 400 U / ml of insulin and 0.1 wt% of hyaluronic acid to obtain the gel layer.

6. The blood glucose monitoring device of claim 1, wherein, The controller is realized by MCU, which contains charging unit, power supply unit, processing unit, display unit and digital-analog conversion unit; and / or the substrate and the porous support plate, the electrode plate are flexible materials. The glucose sensor is the third generation or improved third generation glucose sensor based on glucose oxidase.

7. The blood glucose monitoring device according to any one of claims 1 to 6, characterized in that, The glucose sensor is a glucose sensor based on glucose oxidase and flavin adenine dinucleotide coenzyme.

8. The blood glucose monitoring device of claim 7, wherein, ​

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