Closed-loop insulin micropump based on microneedle array and its control system

Abstract

This invention belongs to the field of medical device technology and provides a closed-loop insulin micropump based on a microneedle array and its control system. A closed-loop insulin micropump based on a microneedle array includes: a drug reservoir, a piezoelectric pump, and a microneedle array. This invention solves the technical problems of inconvenience in using existing insulin pumps and the lack of closed-loop treatment; it uses biodegradable chitosan to prepare the microneedles, avoiding material toxicity, and the micron-scale microneedle array reduces the depth of skin penetration, avoiding nerve damage.

Description

Technical Field

[0001] This invention relates to the field of medical device technology, and in particular to a closed-loop insulin micropump based on a microneedle array and its control system. Background Technology

[0002] As of 2023, there were approximately 537 million people with diabetes worldwide, and this number is projected to rise to 643 million by 2030 and 783 million by 2045. Millions of people die each year directly from diabetes or indirectly from complications caused by diabetes. Therefore, how to treat diabetes efficiently and conveniently has become a hot research topic, and many research groups around the world have conducted research in this field.

[0003] While there has been some progress in insulin pump research, most of these pumps are bulky, cannot form a closed-loop treatment, and their high price increases the financial burden on patients. Some insulin pumps are also implantable, which can increase patient pain and have a certain impact on the patient's nerves.

[0004] This invention addresses the technical problems of existing insulin infusion pumps, such as inconvenience in use, inability to form a closed-loop treatment, and the potential for inflammation during use. It provides a closed-loop insulin micropump based on a microneedle array and its control system. Summary of the Invention

[0005] This invention provides a closed-loop insulin micropump based on a microneedle array and its control system, which solves the technical problems of inconvenience in using insulin pumps, inability to form a closed-loop treatment, and inflammation caused during use in the prior art.

[0006] On the one hand, the present invention provides a closed-loop insulin microinjection pump based on a microneedle array, comprising: a drug reservoir, a piezoelectric pump, and a microneedle array;

[0007] The drug storage device is used to store insulin to be injected;

[0008] The piezoelectric pump is used to connect the drug reservoir and the microneedle array, and to directionally transport insulin from the drug reservoir to the microneedle array.

[0009] The microneedle array includes a working electrode microneedle array, a counter electrode microneedle array, a working electrode circuit, and a counter electrode circuit, and is used to monitor the glucose concentration in human tissue fluid.

[0010] The microneedle array is also used to release insulin into human tissue fluid;

[0011] The counter electrode is also used as a reference electrode.

[0012] According to the present invention, a closed-loop insulin micropump based on a microneedle array is provided, wherein the piezoelectric pump comprises: a shell, a piezoelectric material, a vibrating plate, a resonant plate, a diaphragm, and an electrode; the vibrating plate comprises an upper vibrating plate and a lower vibrating plate; and the electrode comprises an upper electrode and a lower electrode.

[0013] According to the present invention, a closed-loop insulin micropump based on a microneedle array is provided, wherein the upper vibrating plate is located above the piezoelectric material and the lower vibrating plate is located below the piezoelectric material; the resonant plate is fixed to the outer shell through three pins; the upper part of the diaphragm is connected to the lower vibrating plate and the lower part is connected to the resonant plate to form a cavity; the upper electrode is connected to the upper vibrating plate and the lower electrode is connected to the lower vibrating plate.

[0014] According to the present invention, a closed-loop insulin micropump based on a microneedle array is provided, wherein the piezoelectric material is a polyvinylidene fluoride film or a polychlorotrifluoroethylene film; the vibrating plate is aluminum or titanium; and the diaphragm is nitrile rubber.

[0015] On the other hand, the present invention also provides a method for preparing a closed-loop insulin micropump based on a microneedle array, comprising the following steps:

[0016] Chitosan solution was poured into a polydimethylsiloxane mold with a microneedle pattern, and after curing and peeling, the microneedle body was obtained.

[0017] Parylene layers were deposited on the inner and outer surfaces of the microneedle body, and injection ports were formed by drilling.

[0018] A titanium layer is deposited on the surface of the microneedle body using a working electrode microneedle mask, and a gold layer is deposited on the surface of the titanium layer to obtain a gold electrode and a working electrode circuit.

[0019] The gold electrode is etched with an etching solution, cleaned, and dried to obtain the etched gold electrode.

[0020] Prussian blue solution was added to deposit a Prussian blue layer on the etched gold electrode surface;

[0021] Add an enzyme immobilization reagent to immobilize glucose oxidase on the surface of Prussian blue to obtain the working electrode;

[0022] A silver electrode and a counter electrode circuit are obtained by depositing a silver layer on the surface of the microneedle body using a counter electrode microneedle mask.

[0023] A chlorinating agent is added to react with the silver electrode to obtain an Ag / AgCl counter electrode.

[0024] According to the present invention, a method for preparing a closed-loop insulin micropump based on a microneedle array is provided, wherein the thickness of the titanium layer is 2-8 nm, the thickness of the gold layer is 100-300 nm, and the thickness of the silver layer is 50-150 nm.

[0025] The etching solution is an aqueous solution of I2 and KI, wherein the concentration of I2 is 0.5~1.5 g / L and the concentration of KI is 2~6 g / L;

[0026] The Prussian blue solution comprises FeCl3, K3Fe(CN)6, and chitosan solution, wherein the concentration of FeCl3 is 1-4 mmol / L, the concentration of K3Fe(CN)6 is 1-4 mmol / L, and the concentration of chitosan solution is 0.01-0.07%.

[0027] The Prussian blue solution also includes a KCl solution or an HCl solution, wherein the concentration of the KCl solution is 0.1 mol / L and the concentration of the HCl solution is 0.1 mol / L.

[0028] The enzyme immobilization reagent includes glutaraldehyde solution, chitosan solution and glucose oxidase solution, with a volume ratio of glutaraldehyde solution, chitosan solution and glucose oxidase solution of (0.5~2): (0.5~2): (0.5~2), a concentration of glutaraldehyde solution of 0.5~4%, a concentration of chitosan solution of 0.1~3%, and a concentration of glucose oxidase solution of 5~15 U / μL;

[0029] The chlorinating agent is a FeCl3 solution with a concentration of 0.03~0.07 mol / L.

[0030] On the other hand, the present invention also provides a control system for a closed-loop insulin micropump based on a microneedle array, the control system comprising:

[0031] The data acquisition module is used to acquire the detection current A between the working electrode microneedle and the counter electrode, and also to preset the target current I;

[0032] The data processing module is used to correct the driving voltage B between the upper and lower electrodes based on the detected current A and the target current I.

[0033] According to the present invention, a closed-loop insulin microinjection pump control system based on a microneedle array is provided, wherein the data acquisition module is further used to preset a preset difference matrix D and a driving voltage matrix B for the detection current A and the target current I;

[0034] The preset difference matrix D is defined as D(D1, D2, D3, D4), where D1 is the first preset difference, D2 is the second preset difference, D3 is the third preset difference, and D4 is the fourth preset difference, and 0 < D < D0. <D1<D2<D3<D4;

[0035] The driving voltage matrix B is set as B(B1, B2, B3, B4, B5), where B1 is the first preset driving voltage, B2 is the second preset driving voltage, B3 is the third preset driving voltage, B4 is the fourth preset driving voltage, B5 is the fifth preset driving voltage, and B1 < B2 < B3 < B4.

[0036] According to a control system of a closed-loop insulin micro-injection pump based on a microneedle array provided by the present invention, the data processing module is further configured to calculate the difference X between the detected current A and the target current I, and the difference X = I - A;

[0037] The data processing module is further configured to select a corresponding preset driving voltage as the driving voltage between the upper electrode and the lower electrode according to the relationship between X and the preset difference matrix D;

[0038] When X < D1, the first preset driving voltage B1 is selected as the driving voltage between the upper electrode and the lower electrode;

[0039] When D1 < X < D2, the second preset driving voltage B2 is selected as the driving voltage between the upper electrode and the lower electrode;

[0040] When D2 < X < D3, the third preset driving voltage B3 is selected as the driving voltage between the upper electrode and the lower electrode;

[0041] When D3 < X < D4, the fourth preset driving voltage B4 is selected as the driving voltage between the upper electrode and the lower electrode;

[0042] When D4 < X, the fifth preset driving voltage B5 is selected as the driving voltage between the upper electrode and the lower electrode.

[0043] According to a control system of a closed-loop insulin micro-injection pump based on a microneedle array provided by the present invention, when X < 0, the driving voltage B = 0; when X = 0, the driving voltage B = 0.

[0044] The closed-loop insulin micro-injection pump based on a microneedle array and its control system provided by the present invention integrate a drug reservoir, a piezoelectric pump and a microneedle array, solve the technical problem of inconvenient use of insulin injection pumps in the prior art, and achieve the technical effect of convenient use. The closed-loop insulin micro-injection pump based on a microneedle array and its control system provided by the present invention sense blood glucose through microneedles and automatically drive the piezoelectric pump to inject insulin, solve the technical problem of the lack of closed-loop treatment of diabetes in the prior art, and achieve the technical effect of closed-loop treatment of diabetes. The closed-loop insulin micro-injection pump based on a microneedle array and its control system provided by the present invention use chitosan to prepare microneedles, which are safe, non-toxic and harmless when broken, and the micron-scale design reduces the penetration depth, effectively avoiding nerve damage and achieving safe and efficient closed-loop insulin injection. Attached Figure Description

[0045] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0046] Figure 1 This is a schematic diagram of the structure of a closed-loop insulin microinjection pump based on a microneedle array provided in an embodiment of the present invention;

[0047] Figure 2 This is a schematic diagram of the internal structure of a closed-loop insulin microinjection pump based on a microneedle array provided in an embodiment of the present invention;

[0048] Figure 3 This is a schematic diagram of the resonant plate structure of a closed-loop insulin microinjection pump based on a microneedle array provided in an embodiment of the present invention;

[0049] Figure 4 This is a schematic diagram of the microneedle array structure of the closed-loop insulin microinjection pump based on a microneedle array provided in an embodiment of the present invention;

[0050] Figure 5 This is a schematic diagram of the working electrode microneedle structure of the closed-loop insulin microinjection pump based on a microneedle array provided in an embodiment of the present invention;

[0051] Figure 6 This is a schematic diagram of the counter electrode microneedle structure of the closed-loop insulin microinjection pump based on a microneedle array provided in an embodiment of the present invention;

[0052] Figure 7 This is a functional structure block diagram of the control system for a closed-loop insulin microinjection pump based on a microneedle array provided in an embodiment of the present invention.

[0053] Figure label:

[0054] 1. Drug reservoir; 2. Piezoelectric pump; 3. Microneedle array; 21. Housing; 22. Piezoelectric material; 23. Upper vibrating plate; 24. Lower vibrating plate; 25. Resonant plate; 26. Diaphragm; 27. Upper electrode; 28. Lower electrode; 31. Working electrode microneedle array; 32. Counter electrode microneedle array; 33. Circuit. Detailed Implementation

[0055] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention.

[0056] This invention provides a closed-loop insulin microinjection pump based on a microneedle array, comprising: a drug reservoir, a piezoelectric pump, and a microneedle array;

[0057] The drug storage device is used to store insulin to be injected;

[0058] The piezoelectric pump is used to connect the drug reservoir and the microneedle array, and to directionally transport insulin from the drug reservoir to the microneedle array.

[0059] The microneedle array includes a working electrode microneedle array, a counter electrode microneedle array, a working electrode circuit, and a counter electrode circuit, and is used to monitor the glucose concentration in human tissue fluid.

[0060] The microneedle array is also used to release insulin into human tissue fluid;

[0061] The counter electrode is also used as a reference electrode.

[0062] In this invention, the piezoelectric pump includes: a housing, a piezoelectric material, a vibrating plate, a resonant plate, a diaphragm, and electrodes; the vibrating plate includes an upper vibrating plate and a lower vibrating plate; the electrodes include an upper electrode and a lower electrode.

[0063] In this invention, the lower vibrating plate is located below the piezoelectric material; the resonant plate is fixed to the outer shell via three pins; the diaphragm is connected to the lower vibrating plate above and below, forming a cavity; the upper electrode is connected to the upper vibrating plate, and the lower electrode is connected to the lower vibrating plate.

[0064] In this invention, the piezoelectric material is a polyvinylidene fluoride film or a polychlorotrifluoroethylene film; the vibrating plate is aluminum or titanium; and the diaphragm is nitrile rubber.

[0065] This invention also provides a method for preparing a closed-loop insulin micropump based on a microneedle array, comprising the following steps:

[0066] Chitosan solution was poured into a polydimethylsiloxane mold with a microneedle pattern, and after curing and peeling, the microneedle body was obtained.

[0067] Parylene layers were deposited on the inner and outer surfaces of the microneedle body, and injection ports were formed by drilling.

[0068] A titanium layer is deposited on the surface of the microneedle body using a working electrode microneedle mask, and a gold layer is deposited on the surface of the titanium layer to obtain a gold electrode and a working electrode circuit.

[0069] The gold electrode is etched with an etching solution, cleaned, and dried to obtain the etched gold electrode.

[0070] Prussian blue solution was added to deposit a Prussian blue layer on the etched gold electrode surface;

[0071] Add an enzyme immobilization reagent to immobilize glucose oxidase on the surface of Prussian blue to obtain the working electrode;

[0072] A silver electrode and a counter electrode circuit are obtained by depositing a silver layer on the surface of the microneedle body using a counter electrode microneedle mask.

[0073] A chlorinating agent is added to react with the silver electrode to obtain an Ag / AgCl counter electrode.

[0074] In this invention, the thickness of the titanium layer is 2-8 nm, preferably 4-6 nm; the thickness of the gold layer is 100-300 nm, preferably 150-250 nm; and the thickness of the silver layer is 50-150 nm, preferably 80-120 nm.

[0075] The etching solution is an aqueous solution of I2 and KI, wherein the concentration of I2 is 0.5~1.5 g / L, preferably 0.8~1.2 g / L; and the concentration of KI is 2~6 g / L, preferably 3~5 g / L.

[0076] The Prussian blue solution comprises FeCl3, K3Fe(CN)6, and chitosan solution, wherein the concentration of FeCl3 is 1-4 mmol / L, preferably 2-3 mmol / L; the concentration of K3Fe(CN)6 is 1-4 mmol / L, preferably 2-3 mmol / L; and the concentration of chitosan solution is 0.01-0.07%, preferably 0.03-0.05%.

[0077] The Prussian blue solution further includes a KCl solution or an HCl solution, preferably an HCl solution; the concentration of the KCl solution is 0.1 mol / L, and the concentration of the HCl solution is 0.1 mol / L.

[0078] The enzyme immobilization reagent includes glutaraldehyde solution, chitosan solution, and glucose oxidase solution. The volume ratio of glutaraldehyde solution, chitosan solution, and glucose oxidase solution is (0.5~2):(0.5~2):(0.5~2), preferably 1:1:1. The concentration of glutaraldehyde solution is 0.5~4%, preferably 1~3%. The concentration of chitosan solution is 0.1~3%, preferably 0.5~2%. The concentration of glucose oxidase solution is 5~15 U / μL, preferably 8~12 U / μL.

[0079] The chlorinating agent is an FeCl3 solution, and the concentration of the FeCl3 solution is 0.03 to 0.07 mol / L, preferably 0.04 to 0.06 mol / L.

[0080] The present invention also provides a control system for a closed-loop insulin micro-injection pump based on a microneedle array. The control system includes:

[0081] A data acquisition module for acquiring the detection current A between the working electrode microneedle and the counter electrode, and also for presetting a target current I;

[0082] A data processing module for correcting the driving voltage B between the upper electrode and the lower electrode according to the detection current A and the target current I.

[0083] In the present invention, the data acquisition module is further used for presetting a preset difference matrix D and a driving voltage matrix B of the detection current A and the target current I;

[0084] For the preset difference matrix D, set D (D1, D2, D3, D4), where D1 is the first preset difference, D2 is the second preset difference, D3 is the third preset difference, D4 is the fourth preset difference, and 0 < D1 < D2 < D3 < D4;

[0085] For the driving voltage matrix B, set B (B1, B2, B3, B4, B5), where B1 is the first preset driving voltage, B2 is the second preset driving voltage, B3 is the third preset driving voltage, B4 is the fourth preset driving voltage, B5 is the fifth preset driving voltage, and B1 < B2 < B3 < B4.

[0086] In the present invention, the data processing module is further used for calculating the difference X between the detection current A and the target current I, and the difference X = I - A;

[0087] The data processing module is further used for selecting a corresponding preset driving voltage as the driving voltage between the upper electrode and the lower electrode according to the relationship between X and the preset difference matrix D;

[0088] When X < D1, select the first preset driving voltage B as the driving voltage between the upper electrode and the lower electrode;

[0089] When D1 < X < D2, select the second preset driving voltage B2 as the driving voltage between the upper electrode and the lower electrode;

[0090] When D2 < X < D3, select the third preset driving voltage B3 as the driving voltage between the upper electrode and the lower electrode;

[0091] When D3 < X < D4, select the fourth preset driving voltage B4 as the driving voltage between the upper electrode and the lower electrode;

[0092] When D4 < X, select the fifth preset driving voltage B5 as the driving voltage between the upper electrode and the lower electrode.

[0093] In the present invention, when X < 0, the driving voltage B = 0; when X = 0, the driving voltage B = 0.

[0094] The following combines Figures 1-7 to describe the closed-loop insulin micro-injection pump based on a microneedle array and its control system of the present invention.

[0095] Figure 1 is a schematic structural diagram of a closed-loop insulin micro-injection pump based on a microneedle array provided by an embodiment of the present invention.

[0096] As Figure 1 shown, the closed-loop insulin micro-injection pump based on a microneedle array provided by an embodiment of the present invention includes: a drug reservoir, a piezoelectric pump, and a microneedle array; the drug reservoir is used to store the insulin to be injected; the piezoelectric pump is used to connect the drug reservoir and the microneedle array, and to transport the insulin from the drug reservoir to the microneedle array in a directional manner; the microneedle array includes a working electrode microneedle array, a counter electrode microneedle array, a working electrode circuit, and a counter electrode circuit, and is used to monitor the glucose concentration in human tissue fluid; the microneedle array is also used to release the insulin into the human tissue fluid; the counter electrode is also used as a reference electrode.

[0097] Figure 2 is a schematic internal structure diagram of a closed-loop insulin micro-injection pump based on a microneedle array provided by an embodiment of the present invention.

[0098] As Figure 2 shown, for the closed-loop insulin micro-injection pump based on a microneedle array provided by an embodiment of the present invention, the piezoelectric pump includes: a housing, a piezoelectric material, a vibrating plate, a resonant plate, a diaphragm, and an electrode; the vibrating plate includes an upper vibrating plate and a lower vibrating plate; the electrode includes an upper electrode and a lower electrode. The upper vibrating plate is located above the piezoelectric material, and the lower vibrating plate is located below the piezoelectric material; the diaphragm is connected to the lower vibrating plate above and to the resonant plate below, forming a cavity; the upper electrode is connected to the upper vibrating plate, and the lower electrode is connected to the lower vibrating plate. The piezoelectric material is a polyvinylidene fluoride film or a polychlorotrifluoroethylene film; the vibrating plate is aluminum or titanium; the diaphragm is nitrile rubber.

[0099] Through the piezoelectric effect of the piezoelectric material, the upper vibrating plate and the lower vibrating plate vibrate, and the resonant plate is driven to vibrate. A chamber of the piezoelectric pump is formed between the vibrating plate and the resonant plate. By applying an alternating voltage between the upper electrode and the lower electrode, the volume of the chamber can be repeatedly changed, so as to achieve the directional transport of insulin from the drug reservoir to the microneedles

[0100] Figure 3 This is a schematic diagram of the resonant plate structure of a closed-loop insulin microinjection pump based on a microneedle array provided in an embodiment of the present invention.

[0101] like Figure 3 As shown, the closed-loop insulin micro-injection pump based on a microneedle array provided in this embodiment of the invention has a resonant plate fixed to the outer casing via three pins.

[0102] Figure 4 This is a schematic diagram of the microneedle array structure of a closed-loop insulin microinjection pump based on a microneedle array, provided in an embodiment of the present invention.

[0103] like Figure 4 As shown in the embodiment of the present invention, a closed-loop insulin micropump based on a microneedle array is provided. The microneedle array includes a working electrode microneedle array, a counter electrode microneedle array, a working electrode circuit, and a counter electrode circuit, and is used to monitor the glucose concentration in human tissue fluid. Furthermore, the counter electrode also serves as a reference electrode.

[0104] Figure 5 This is a schematic diagram of the working electrode microneedle structure of a closed-loop insulin microinjection pump based on a microneedle array, provided in an embodiment of the present invention.

[0105] like Figure 5 As shown in the embodiment of the present invention, the closed-loop insulin micropump based on a microneedle array has working electrode microneedles consisting of, from the inside out, a parylene layer, a chitosan layer, a parylene layer, a titanium layer, a gold layer, a Prussian blue layer, and a glucose oxidase layer.

[0106] This invention involves pouring a chitosan solution into a polydimethylsiloxane mold with a microneedle pattern, curing and peeling it off to obtain a microneedle body; depositing parylene layers on the inner and outer surfaces of the microneedle body, and punching holes to form injection ports; depositing a titanium layer on the surface of the microneedle body using a working electrode microneedle mask, and then depositing a gold layer on the surface of the titanium layer to obtain a gold electrode and a working electrode circuit; etching the gold electrode with an etching solution, cleaning, and drying to obtain an etched gold electrode; adding Prussian blue solution to deposit a Prussian blue layer on the surface of the etched gold electrode; and adding an enzyme immobilization reagent to immobilize glucose oxidase on the surface of the Prussian blue layer to obtain the working electrode.

[0107] Figure 6 This is a schematic diagram of the counter electrode microneedle structure of a closed-loop insulin microinjection pump based on a microneedle array, provided in an embodiment of the present invention.

[0108] like Figure 6 As shown, the closed-loop insulin micropump based on microneedle array provided in this embodiment of the invention has, from the inside out, a parylene layer, a chitosan layer, a parylene layer, a silver layer, and a silver chloride layer for the electrode microneedles.

[0109] This invention involves pouring a chitosan solution into a polydimethylsiloxane mold with a microneedle pattern, curing and peeling it off to obtain a microneedle body; depositing parylene layers on the inner and outer surfaces of the microneedle body, and punching holes to form injection ports; depositing a silver layer on the surface of the microneedle body using a counter electrode microneedle mask to obtain a silver electrode and a counter electrode circuit; and adding a chlorinating agent to react with the silver electrode to obtain an Ag / AgCl counter electrode.

[0110] Figure 7 This is a functional structure block diagram of the control system for a closed-loop insulin microinjection pump based on a microneedle array provided in an embodiment of the present invention.

[0111] like Figure 7 As shown in the embodiment of the present invention, a closed-loop insulin micropump control system based on a microneedle array includes: a data acquisition module for acquiring a detection current A between the working electrode microneedle and the counter electrode, and for presetting a target current I; and a data processing module for correcting the driving voltage B between the upper electrode and the lower electrode based on the detection current A and the target current I. The data acquisition module is also used to preset a preset difference matrix D between the detection current A and the target current I, and a driving voltage matrix B. The data processing module is also used to calculate the difference X between the detection current A and the target current I, where the difference X = IA; and to select a corresponding preset driving voltage as the driving voltage between the upper electrode and the lower electrode based on the relationship between X and the preset difference matrix D.

[0112] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A closed-loop insulin microinjection pump based on a microneedle array, characterized in that, include: Drug reservoir, piezoelectric pump, and microneedle array; The drug storage device is used to store insulin to be injected; The piezoelectric pump is used to connect the drug reservoir and the microneedle array, and to directionally transport insulin from the drug reservoir to the microneedle array. The piezoelectric pump includes: a housing, a piezoelectric material, a vibrating plate, a resonant plate, a diaphragm, and electrodes; The piezoelectric material is a polyvinylidene fluoride film or a polychlorotrifluoroethylene film; the vibrating plate is aluminum or titanium; the diaphragm is nitrile rubber; The driving voltage of the piezoelectric pump is adjusted as follows: the detection current A between the working electrode microneedle and the counter electrode is detected; the difference X between the detection current A and the preset target current value I is calculated; the corresponding difference is matched from the preset difference matrix D according to the difference X; and then the corresponding driving voltage is matched from the driving voltage matrix B, thereby controlling the output flow of the piezoelectric pump; wherein, when X < 0, the driving voltage B = 0; when X = 0, the driving voltage B = 0. The microneedle array includes a working electrode microneedle array, a counter electrode microneedle array, a working electrode circuit, and a counter electrode circuit, and is used to monitor the glucose concentration in human tissue fluid. The microneedle array is also used to release insulin into human tissue fluid; The counter electrode is also used as a reference electrode; The microneedle body of the microneedle array is made of chitosan, and a parylene film layer is deposited on both the inner and outer surfaces of the microneedle body. The surface of the working electrode microneedle is sequentially provided with a titanium layer, a gold layer, a Prussian blue layer and a glucose oxidase layer, wherein the thickness of the titanium layer is 2~8nm and the thickness of the gold layer is 100~300nm. The surface of the counter electrode microneedle is provided with a silver layer and a silver chloride layer, wherein the thickness of the silver layer is 50~150nm; The working electrode circuit is electrically connected to the conductive layer of the working electrode microneedle through a titanium-gold layer, and the counter electrode circuit is electrically connected to the reference layer of the counter electrode microneedle through a silver layer.

2. The closed-loop insulin micropump based on a microneedle array according to claim 1, characterized in that, The vibrating plate includes an upper vibrating plate and a lower vibrating plate; the electrode includes an upper electrode and a lower electrode.

3. The closed-loop insulin microinjection pump based on a microneedle array according to claim 2, characterized in that, The upper vibrating plate is located above the piezoelectric material, and the lower vibrating plate is located below the piezoelectric material; The resonant plate is fixed to the outer shell via three pins; the diaphragm is connected to the lower vibrating plate above and to the resonant plate below, forming a cavity; the upper electrode is connected to the upper vibrating plate, and the lower electrode is connected to the lower vibrating plate.

4. A method for fabricating a closed-loop insulin micropump based on a microneedle array as described in claim 1, characterized in that, Includes the following steps: Chitosan solution was poured into a polydimethylsiloxane mold with a microneedle pattern, and after curing and peeling, the microneedle body was obtained. Parylene layers were deposited on the inner and outer surfaces of the microneedle body, and injection ports were formed by drilling. A titanium layer is deposited on the surface of the microneedle body using a working electrode microneedle mask, and a gold layer is deposited on the surface of the titanium layer to obtain a gold electrode and a working electrode circuit. The gold electrode is etched with an etching solution, cleaned, and dried to obtain the etched gold electrode. Prussian blue solution was added to deposit a Prussian blue layer on the etched gold electrode surface; Add an enzyme immobilization reagent to immobilize glucose oxidase on the surface of Prussian blue to obtain the working electrode; A silver electrode and a counter electrode circuit are obtained by depositing a silver layer on the surface of the microneedle body using a counter electrode microneedle mask. Add a chlorinating agent to react with the silver electrode to obtain an Ag / AgCl counter electrode.

5. The method for fabricating a closed-loop insulin micropump based on a microneedle array according to claim 4, characterized in that, The thickness of the titanium layer is 2 - 8 nm, the thickness of the gold layer is 100 - 300 nm, and the thickness of the silver layer is 50 - 150 nm; The etching solution is an aqueous solution of I2 and KI, the concentration of I2 is 0.5 - 1.5 g / L, and the concentration of KI is 2 - 6 g / L; The Prussian blue solution includes FeCl3, K3Fe(CN)6, and chitosan. The concentration of FeCl3 is 1 - 4 mmol / L, the concentration of K3Fe(CN)6 is 1 - 4 mmol / L, and the concentration of chitosan is 0.01 - 0.07%; The Prussian blue solution further includes a KCl solution or an HCl solution. The concentration of the KCl solution is 0.1 mol / L, and the concentration of the HCl solution is 0.1 mol / L; The enzyme immobilization reagent includes a glutaraldehyde solution, chitosan, and a glucose oxidase solution. The volume ratio of the glutaraldehyde solution, chitosan, and glucose oxidase solution is (0.5 - 2):(0.5 - 2):(0.5 - 2). The concentration of the glutaraldehyde solution is 0.5 - 4%, the concentration of chitosan is 0.1 - 3%, and the concentration of the glucose oxidase solution is 5 - 15 U / μL; The chlorinating agent is an FeCl3 solution, and the concentration of the FeCl3 solution is 0.03 - 0.07 mol / L.

6. A control system for a closed-loop insulin micropump based on a microneedle array as described in claim 1, characterized in that, The control system includes: A data acquisition module for acquiring the detection current A between the working electrode micro needle and the counter electrode, and also for presetting the target current I; A data processing module for correcting the driving voltage B between the upper electrode and the lower electrode according to the detection current A and the target current I.

7. The control system for the closed-loop insulin microinjection pump based on a microneedle array according to claim 6, characterized in that, The data acquisition module is also used for presetting a preset difference matrix D and a driving voltage matrix B for the detection current A and the target current I; For the preset difference matrix D, set D(D1, D2, D3, D4), where D1 is the first preset difference, D2 is the second preset difference, D3 is the third preset difference, D4 is the fourth preset difference, and 0 < D1 < D2 < D3 < D4; For the driving voltage matrix B, set B(B1, B2, B3, B4, B5), where B1 is the first preset driving voltage, B2 is the second preset driving voltage, B3 is the third preset driving voltage, B4 is the fourth preset driving voltage, B5 is the fifth preset driving voltage, and B1 < B2 < B3 < B4; 8. The control system for the closed-loop insulin microinjection pump based on a microneedle array according to claim 7, characterized in that, The data processing module is also used for calculating the difference X between the detection current A and the target current I, and the difference X = I - A; The data processing module is also used for selecting a corresponding preset driving voltage as the driving voltage between the upper electrode and the lower electrode according to the relationship between X and the preset difference matrix D; When X < D1, select the first preset driving voltage B1 as the driving voltage between the upper electrode and the lower electrode; When D1 < X < D2, select the second preset driving voltage B2 as the driving voltage between the upper electrode and the lower electrode; When D2 < X < D3, select the third preset driving voltage B3 as the driving voltage between the upper electrode and the lower electrode; When D3 < X < D4, select the fourth preset driving voltage B4 as the driving voltage between the upper electrode and the lower electrode; When D4 < X, select the fifth preset driving voltage B5 as the driving voltage between the upper electrode and the lower electrode.

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