Closed-loop control system

Abstract

The utility model belongs to the field of biosensors, and provides a closed-loop control system which comprises a graphene electrode microneedle sensor, an electrochemical pump and a control module, the graphene electrode micro-needle sensor comprises a polystyrene micro-needle array, the polystyrene micro-needle array comprises a plurality of micro-needle bodies, the convex surfaces of the micro-needle bodies of the polystyrene micro-needle array are covered with electrodes, the electrodes comprise a working electrode and a reference electrode / counter electrode, and the working electrode and the reference electrode / counter electrode are arranged on the polystyrene micro-needle array. The working electrode and the reference electrode / counter electrode are formed by depositing and printing graphene composite ink on the surface of the microneedle. Graphene is an attractive nano material with high specific surface area, mechanical strength, conductivity and biocompatibility, and the graphene electrode microneedle sensor and the electrochemical pump are intelligently controlled by a printed circuit board, so that a closed loop function is realized, and the graphene electrode microneedle sensor has the characteristics of being stable, wearable, miniaturized, painless, accurate, high in cost benefit, easy to manufacture and the like.

Description

TECHNICAL FIELD

[0001] The utility model relates to biological sensor technical field, especially in a kind of closed loop control system. BACKGROUND

[0002] Closed loop control system is usually composed of biological sensor monitoring tissue fluid physiological index, subcutaneous pump and control module.For example, drug closed loop control system includes: interstitial subcutaneous biological sensor, subcutaneous pump for delivering drug and control module, can calculate drug infusion dose according to blood glucose level, realize automatic blood glucose management.Electrochemical pump as a kind of small volume, portable subcutaneous pump, can be used to deliver drug.Biological sensor is usually made of microneedle sensor, with minimally invasive, painless, miniature, portable and relatively safe characteristics.The existing microneedle sensor can be based on physical vapor deposition technology, working sensing electrode, reference electrode and counter electrode and reference electrode are prepared on the sidewall of 3D printing microneedle., But these methods are complex and expensive in the process of manufacturing electrode;Make closed loop control system unable to be widely used. SUMMARY

[0003] In order to solve the problem of high cost of sensing electrode and microneedle biological sensor manufacturing material in existing closed loop control system, not easy to manufacture, the utility model provides a kind of closed loop control system, reaction enzyme is coated on sensor and reacts with the index material of corresponding disease, when index material reaches a certain concentration, control module controls subcutaneous pump to open automatically, and delivers as therapeutic drug solution.

[0004] The specific scheme is as follows:

[0005] A kind of closed loop control system, including graphene electrode microneedle sensor, electrochemical pump and control module;The graphene electrode microneedle sensor includes: base, polystyrene microneedle array placed in base one end, and electrode made of composite graphene material covering base and microneedle array;The electrode is composed of working electrode and reference electrode / counter electrode, the electrode covers the convex surface of microneedle array composed of microneedle body, the polystyrene microneedle array includes microneedle body, the bottom end and top end of the microneedle body include bottom end square or circular hole and top end square or circular injection hole respectively, hollow channel is connected between the bottom end square or circular hole and top end square or circular injection hole, the base inside includes containing cavity, the containing cavity top end is connected with the bottom end square hole;

[0006] The electrochemical pump includes pump body, the pump body has containing area, the containing area has medium solution and electrode layer connected with the inner wall of the pump body in it, and the pump body is provided with expansion film covering the containing area, and the containing cavity bottom end is connected with the expansion film;

[0007] The input end of the control module is connected with the output end of the graphene electrode microneedle sensor, and the output end of the control module is connected with the input end of the electrochemical pump; the control module is used for receiving the electrical signal output by the graphene electrode microneedle sensor and controlling the opening or closing of the electrochemical pump through a gate circuit.

[0008] Each microneedle body is in a pyramidal or conical shape, the bottom diameter of the microneedle body is 50-1000 μm, and the height is 300-2000 μm.

[0009] The size of the square or circular hole at the bottom end of the microneedle body is 30-900 μm, the size of the square hole at the top end is 10-100 μm, and the thickness of the sidewall of the microneedle body is 10-100 μm.

[0010] The polystyrene microneedle array is an m×n microneedle array, and the working electrode and the reference electrode / counter electrode respectively occupy a plurality of rows and a plurality of columns of microneedle bodies.

[0011] The working electrode is a composite graphene-Prussian blue ink layer, the upper surface of the working electrode is covered with a uniform multi-layer structure, and the multi-layer structure comprises a reaction enzyme layer containing an index reaction enzyme and a biocompatible polymer layer.

[0012] The material of the composite graphene-Prussian blue ink layer comprises graphene, Prussian blue and polyvinylidene fluoride; the thickness of the composite graphene-Prussian blue ink layer is 0.1-40 microns, and the length of each composite graphene-Prussian blue electrode in the microneedle array biosensor is 50-100 microns and the width is 10-50 microns.

[0013] The material of the biocompatible polymer layer comprises chitosan film and perfluorosulfonic acid film.

[0014] The material of the polystyrene microneedle array comprises 10-50% polystyrene solution.

[0015] The material of the expansion film comprises at least one of the following: polytetrafluoroethylene, polydimethylsiloxane, polyacrylate, silica gel, rubber, latex, polyurethane, parylene and polyimide.

[0016] The control module comprises a first conversion unit, a control unit and a second conversion unit; the first conversion unit is used for receiving and converting the electrical signal output by the graphene electrode microneedle sensor, the control unit is used for receiving the electrical signal converted by the first conversion unit, outputting a command signal to the second signal conversion unit through a gate circuit, and the second signal conversion unit is used for receiving and converting the command signal output by the control unit and transmitting the command signal to the electrochemical pump to control the opening and closing of the electrochemical pump.

[0017] The utility model has the advantages of the following beneficial effects:

[0018] The utility model provides a kind of closed loop control system, comprising: graphene electrode microneedle sensor, electrochemical pump, control module;The graphene electrode microneedle sensor includes polystyrene microneedle array, the polystyrene microneedle array includes multiple microneedle body, the microneedle body convex surface of the polystyrene microneedle array is covered with electrode, the electrode includes working electrode and reference electrode / counter electrode, the polystyrene microneedle array is provided with containing cavity on the side away from the electrode, and the containing cavity is used to store therapeutic drug solution;The microneedle body top end includes square injection micropore, and the square injection micropore is used to transmit therapeutic drug solution from the containing cavity to the side where electrode is located;First, the microneedle array in the graphene electrode microneedle sensor of the closed loop control system used polystyrene hollow microneedle array, and the polystyrene hollow microneedle array has the characteristics of low cost, good biocompatibility, high mechanical strength and stable chemical properties, and compared with long needle, polystyrene microneedle biosensor can alleviate patient pain, and the polystyrene microneedle is easy to manufacture using soft lithography technology;Second, the working electrode and reference / counter electrode used in the closed loop control system are all graphene-prussian blue electrode, that is, formed by printing graphene composite ink on the surface of microneedle.Meanwhile, graphene is an attractive nanomaterial with high specific surface area, mechanical strength, electrical conductivity and biocompatibility.In addition, it can be simply combined with other materials to form composite ink.Due to its simplicity and low cost, graphene is the best choice for manufacturing sensing electrode, and compared with micro / nano manufacturing method, the whole manufacturing process of graphene-prussian blue electrode is simple, fast, economical and easy to operate. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 The overall structure diagram of a kind of closed loop control system.

[0020] Figure 2 The overall structure diagram of closed loop system.

[0021] Figure 3 The side view of graphene electrode microneedle sensor.

[0022] Figure 4 The distribution diagram of polystyrene microneedle array.

[0023] Figure 5 The side view of microneedle body covered with working electrode.

[0024] Figure 6 The structure diagram of electrochemical pump.

[0025] The graphene electrode microneedle sensor 1, the electrochemical pump 2, the control module 3, the substrate 11, the containing cavity 111, the polystyrene microneedle array 12, the electrode 13, the working electrode 131, the reference electrode / counter electrode 132, the microneedle body 14, the bottom square hole 141, the top square hole 142, the hollow channel 143, the pump body 21, the electrode element 22, the anode 221, the cathode 222, the expansion film 23, the first conversion unit 31, the control unit 32, the second conversion unit 33, the graphene-prussian blue composite ink layer 1311, the reaction enzyme layer 1312, the biocompatible polymer layer 1313, the drug solution A, and the electrolyte solution B. DETAILED DESCRIPTION

[0026] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are some of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the protection scope of the present application.

[0027] Referring to Figure 1 As shown in the figure, the closed-loop control system disclosed in the embodiments of the present application includes a graphene electrode microneedle sensor 1, an electrochemical pump 2, and a control module 3.

[0028] Specifically, referring to Figure 2 As shown in the figure, the control module 3 includes a first conversion unit 31, a control unit 32, and a second conversion unit 33. Specifically, the input end of the first conversion unit 31 is connected with the output end of the graphene electrode microneedle sensor 1, the output end of the first conversion unit 31 is connected with the input end of the control unit 32, the input end of the second conversion unit 33 is connected with the output end of the control unit 32, and the output end of the second conversion unit 33 is connected with the input end of the electrochemical pump 1.

[0029] When the electrochemical pump closed-loop control system is used, one end of the graphene electrode microneedle sensor enters the patient's body and contacts the patient's subcutaneous tissue fluid to detect the index substance concentration of the patient's subcutaneous tissue fluid.

[0030] The second conversion unit 33 can provide a constant voltage to drive the electrochemical pump 2 and control the drug injection volume by controlling the magnitude and duration of the voltage. The voltage can be between 0.1 and 2V. Thus, after the graphene electrode microneedle sensor 1 detects the concentration of the indicator substance and generates an electrical signal, the first conversion unit 31 of the signal conversion module receives and converts the electrical signal, and then sends the converted electrical signal to the control unit 32. After receiving the electrical signal converted by the first conversion unit 31, the control unit 32 generates different command information according to the different electrical signals. For example, the control unit 32 can generate an on or off command. Simultaneously, the control unit 32 sends the generated command to the second conversion unit 33, which then converts the received command into a corresponding signal and controls the on or off of the electrochemical pump 2 according to the signal. This achieves control of the electrochemical pump 2 based on the patient's real-time indicator substance concentration.

[0031] In one feasible implementation, the first conversion unit 31 is a first signal converter, the control unit 32 is a microcontroller, and the second conversion unit 33 is a second signal converter.

[0032] For details, please refer to Figure 3 and Figure 4 As shown, the graphene electrode microneedle sensor includes: a substrate 11, a polystyrene microneedle array 12 integrally formed with the substrate 11 and disposed at one end of the substrate 11, and an electrode 13 made of composite graphene material covering the substrate 11 and the microneedle array 12; the electrode consists of a working electrode 131 and a reference electrode / counter electrode 132, and the electrode 13 covers the protruding surface of the microneedle array 12 composed of microneedle bodies 14. The polystyrene microneedle array 12 includes microneedle bodies 14, with the bottom and top ends of the microneedle bodies respectively. The microneedle 14 includes a square hole 141 at the bottom and a square injection hole 142 at the top, with a hollow channel 143 connecting the two holes. The substrate 11 contains a receiving cavity 111, the top of which is connected to the square hole 141 at the bottom. Each microneedle 14 is pyramidal in shape. The size of the square or circular hole at the bottom of the microneedle is 30-900 μm, the size of the square hole at the top is 10-100 μm, and the thickness of the sidewall of the microneedle is 10-100 μm.

[0033] The polystyrene microneedle array 12 is made of 20% polystyrene microneedles, which are dissolved in dimethylformamide in an oven at 90°C to form a 20% polystyrene solution. The polystyrene solution is then coated onto a paraffin wax mold and dried on a hot plate at 45°C for 24-48 hours to obtain the polystyrene microneedle array 12.

[0034] refer to Figure 4As shown, the polystyrene microneedle array 12 is a 6x6 microneedle array, i.e., the polystyrene microneedle array contains six rows of microneedle bodies, and the number of microneedle bodies in each row of microneedle bodies is 6; the spacing between each two microneedles is 2 mm. The working electrode 131 and the reference electrode / counter electrode 132 respectively occupy three rows of microneedle bodies 14.

[0035] Reference Figure 5 As shown, the working electrode 131 includes a graphene-prussian blue composite ink layer 1311, a reaction enzyme layer 1312, and a biocompatible polymer layer 1313; the material of the graphene-prussian blue composite ink layer 1311 is composite graphene-prussian blue ink, which contains graphene, prussian blue, and polyvinylidene fluoride, which are uniformly mixed and uniformly distributed on the microneedle body 14. In the graphene-prussian blue composite ink layer, the graphene plays the role of a conductive electrode, the prussian blue plays the role of an electronic mediator for reducing the sensing potential, and the polyvinylidene fluoride serves as an adhesive to maintain the stability of the electrode in the liquid. The thickness of the graphene-prussian blue composite ink layer is 40 μm, the length of each composite graphene-prussian blue electrode in the microneedle array biosensor is 50-100 μm, and the width is 10-50 μm. Coating the graphene-PB electrode does not change the shape of the microneedle body, which indicates that coating the composite graphene-prussian blue ink on the surface of the microneedle body does not affect the insertion performance of the microneedle.

[0036] The reaction enzyme layer 1312 coated on the working electrode 131 uses a material that is an indicator reaction enzyme, which can react with the corresponding analyte in the detected solution. When the working electrode 131 contacts the detected solution, the reaction enzyme reacts to produce a product, which undergoes oxidation or reduction reaction on the working electrode 131 to produce a change in the electrical signal.

[0037] The material used in the biocompatible polymer layer 1313 is a chitosan film and a perfluorosulfonic acid film. By covering the working electrode 131 with a liquid biocompatible polymer and then heating and drying the liquid biocompatible polymer, a biocompatible polymer layer 1313 is formed, which can improve the stability of the electrode, increase the biocompatibility of the living body, and resist the electrical activity interference in the interstitial fluid.

[0038] Reference Figure 6As shown, the electrochemical pump comprises a pump body 21, the pump body 21 has a containing area, the containing area is provided with an electrolyte solution B and an electrode element 22, wherein the electrode element 22 is located on the inner wall of the pump body, comprises at least one pair of electrodes, an anode 221 and a cathode 222, and the pump body is provided with an expansion film 23 covering the containing area. The electrode element 22 is preferably a platinum interdigital electrode, which comprises cross-ingredient platinum electrode sheets, as shown, the width of the platinum electrode sheet is 100 μm, and the distance between the platinum electrode sheets is also 100 μm. The platinum interdigital electrode is connected to the outside of the drug storage component by a wire for receiving current through the wire. The electrolyte solution B can be deionized water or a salt solution, and the expansion film 23 can be a polytetrafluoroethylene film. The expansion film 23 can also be selected from materials such as polydimethylsiloxane (PDMS), polyacrylate, silicone (such as Ecoflex, Dragon Skin), rubber (such as NBR, IIR), latex, polyurethane, parylene, polyimide, etc.

[0039] After the electrochemical pump 2 is powered on, the electrode element 22 will electrolyze water and generate hydrogen gas bubbles and oxygen gas bubbles, which will move towards the position where the expansion film 23 is located, and under the action of these bubbles, the expansion film 23 will deform and expand, and will generate a squeezing force on the drug A in the graphene electrode microneedle sensor containing cavity 111, so that the drug A flows out through the top square injection hole 142 and acts on the patient, and the drug can be injected into the patient's body. When the electrochemical pump 2 is not powered on, hydrogen and oxygen will recombine to water through the catalysis of the electrode layer, at this time the expansion film 23 will contract, so that the drug A no longer flows out from the top square injection hole 142.

[0040] Further, the input end of the control module 3 is connected with the output end of the graphene electrode microneedle sensor 1, and the output end is connected with the input end of the electrochemical pump 2. Therefore, the control module 3 can receive the electrical signal output by the graphene electrode microneedle sensor 1, because the microneedle body on the microneedle array enters the patient's body and contacts the patient's subcutaneous tissue fluid, so the concentration of the index substance in the patient's subcutaneous tissue fluid can be detected, and therefore the electrical signal output by the graphene electrode microneedle sensor can reflect the size of the blood glucose concentration. Exemplarily, the graphene electrode microneedle sensor 1 can detect the current under a constant voltage, and the size of the current signal is proportional to the size of the index substance concentration.

[0041] Then, the control module 3 can control the opening or closing of the electrochemical pump 2, that is, power on or power off the electrochemical pump 2, according to the electrical signal. Exemplarily, a preset value can be set in the control module 3, if the value of the electrical signal is greater than or equal to the preset value, the electrochemical pump 2 is powered on, if the value of the electrical signal is less than the preset value, the electrochemical pump 2 is not powered on. In this way, the electrochemical pump 2 can be controlled according to the real-time blood glucose concentration of the patient.

[0042] Specifically, the graphene electrode microneedle sensor can detect current under constant voltage, and the size of the current signal is proportional to the size of the index substance concentration. In addition to detecting the current signal, the first conversion unit also provides a constant voltage for the graphene electrode microneedle sensor. The constant voltage can be 0.1V, -0.1V, or 0.6V, etc.

[0043] And the graphene electrode microneedle sensor 1 is located outside the patient's body. The signal conversion module and the electrochemical pump are arranged in sequence at one end of the graphene electrode microneedle sensor 1, and the electrochemical pump is in close contact with the patient's skin to realize injection of medicine for the patient. And the graphene electrode microneedle sensor 1 with polystyrene microneedle array 12 can be deeply into the patient's dermis or fat layer, and for injecting medicine into the fat layer, the effect of injecting medicine is more significant.

[0044] The above are preferred embodiments of the present application, and are not intended to limit the protection scope of the present application, therefore: any equivalent changes made on the structure, shape, principle of the present application should be covered within the protection scope of the present application.

Claims

1. A closed-loop control system, characterized in that, This includes a graphene electrode microneedle sensor, an electrochemical pump, and a control module; The graphene electrode microneedle sensor includes: a substrate, a polystyrene microneedle array integrally formed with the substrate and disposed at one end of the substrate, and an electrode made of composite graphene material covering the substrate and the microneedle array; the electrode consists of a working electrode and a reference / counter electrode, the working electrode is a composite graphene-Prussian blue ink layer, the working electrode is smooth and covered with a uniformly shaped multilayer structure, the multilayer structure including: a reaction enzyme layer containing an indicator reaction enzyme and a biocompatible polymer layer; the electrode covers the raised surface of the microneedle array composed of microneedles, the polystyrene microneedle array including microneedles, the bottom end and the top end of the microneedle body respectively including a bottom square or circular hole and a top square or circular injection hole, a hollow channel connecting the bottom square or circular hole and the top square or circular injection hole, the substrate contains a receiving cavity, the top end of the receiving cavity is connected to the bottom square hole. The electrochemical pump includes a pump body with a receiving area containing a drug and an electrode layer connected to the inner wall of the pump body. An expansion membrane covering the receiving area is provided on the pump body, and the bottom end of the receiving cavity is connected to the expansion membrane. The input terminal of the control module is connected to the output terminal of the graphene electrode microneedle sensor, and the output terminal of the control module is connected to the input terminal of the electrochemical pump. The control module is used to receive the electrical signal output by the graphene electrode microneedle sensor and then control the electrochemical pump to turn on or off through a gating circuit.

2. The closed-loop control system according to claim 1, characterized in that, Each microneedle is pyramidal or conical in shape, with a bottom diameter of 50-1000 μm and a height of 300-2000 μm.

3. The closed-loop control system according to claim 1, characterized in that, The bottom square or circular hole of the microneedle has a size of 30-900μm, the top square hole has a size of 10-100μm, and the sidewall of the microneedle has a thickness of 10-100μm.

4. A closed-loop control system according to claim 1, characterized in that, The polystyrene microneedle array is an m×n microneedle array, with the working electrode and the reference electrode / counter electrode occupying several rows and several columns of microneedles, respectively.

5. A closed-loop control system according to claim 1, characterized in that, The control module includes: a first conversion unit, a control unit, and a second conversion unit; the first conversion unit is used to receive and convert the electrical signal output by the graphene electrode microneedle sensor; the control unit is used to receive the electrical signal converted by the first conversion unit and output a command signal to the second signal conversion unit through a gating circuit; the second signal conversion unit is used to receive and convert the command signal output by the control unit and transmit the command signal to the electrochemical pump to control the opening and closing of the electrochemical pump.

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