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 electroosmotic pump and a signal conversion module, the graphene electrode microneedle sensor comprises a substrate, a polystyrene microneedle array and an electrode, wherein the polystyrene microneedle array is arranged at one end of the substrate, the polystyrene microneedle array and the substrate are integrally formed, the electrode covers the substrate and the microneedle array and is made of a composite graphene material, and the electrode is formed by printing graphene-Prussian blue composite ink on the surface of the microneedle array. Compared with a micro / nano manufacturing method, the manufacturing process of the electrode prepared from the graphene-Prussian blue composite ink is simple, rapid, economical and easy to operate. The graphene electrode microneedle biosensor and the electroosmotic pump are intelligently controlled by a printed circuit board, so that the closed-loop function is realized, and the characteristics of wearing, miniaturization, no pain, accuracy, high cost benefit, easiness in manufacturing and the like are realized.

Description

Technical Field

[0001] This utility model relates to the field of biosensor technology, and in particular to a closed-loop control system. Background Technology

[0002] Closed-loop control systems typically consist of biosensors that monitor blood parameters, subcutaneous pumps, and control modules. For example, an insulin closed-loop control system includes a subcutaneous biosensor for interstitial markers, a subcutaneous pump for drug delivery, and a control module. It calculates the insulin infusion dose based on blood glucose levels, enabling automated blood glucose management. Biosensors are often fabricated using microneedle sensors, which are minimally invasive, painless, miniaturized, portable, and relatively safe. Existing microneedle sensors can be fabricated using physical vapor deposition (PVD) technology, where working sensing electrodes, reference electrodes, counter electrodes, and reference electrodes are prepared on the sidewalls of 3D-printed microneedles. However, the electrode fabrication process is complex and expensive.

[0003] The pump devices currently in use are large in size, making them inconvenient to wear and carry in daily life, which causes inconvenience for diabetic patients. Utility Model Content

[0004] To address the technical challenges of high cost, difficulty in manufacturing, and large capacity of existing closed-loop control systems for drug infusion, making them less wearable and easier for daily use, this invention proposes a closed-loop control system that enhances wearability, rapid manufacturing, and stability. The system delivers drugs through the hollow channels of microneedles, and microneedle biosensors detect interstitial markers. When the marker concentration exceeds the normal level, the electroosmotic pump automatically activates to deliver the drug.

[0005] The specific plan is as follows:

[0006] A closed-loop control system includes: a graphene electrode microneedle sensor, an electroosmosis pump, and a signal conversion module;

[0007] 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 electrode / counter electrode, the electrode covering the protruding surface of the microneedle array composed of microneedle bodies, the polystyrene microneedle array including microneedle bodies, 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 containing a receiving cavity, the top end of the receiving cavity being connected to the bottom square or circular hole;

[0008] The electroosmotic pump is provided with a first electrode layer, a second electrode layer and an intermediate membrane layer. The intermediate membrane layer is disposed between the first electrode layer and the second electrode layer. The intermediate membrane layer is provided with at least one through hole. The bottom end of the receiving cavity is connected to the second electrode layer.

[0009] The input terminal of the signal conversion module is connected to the output terminal of the graphene electrode microneedle sensor, and the output terminal of the signal conversion module is connected to the input terminal of the electroosmotic pump. The signal conversion module is used to receive the electrical signal output by the graphene electrode microneedle sensor and then output a command to the electroosmotic pump to control the opening or closing of the electroosmotic pump.

[0010] Preferably, each microneedle is pyramidal or conical in shape, with a bottom diameter of 50-1000 micrometers and a height of 300-2000 micrometers.

[0011] Preferably, the size of the square or circular hole at the bottom of the microneedle is 30-900 micrometers, the size of the square or circular hole at the top is 10-100 micrometers, and the thickness of the sidewall of the microneedle is 10-100 micrometers.

[0012] Preferably, the polystyrene microneedle array is an m×n microneedle array, and the working electrode and the reference electrode / counter electrode occupy several rows and several columns of microneedles, respectively.

[0013] Preferably, the working electrode is smooth and covered with a uniformly shaped multilayer structure. The working electrode is a graphene-Prussian blue composite ink layer, and the multilayer structure includes an indicator reactive enzyme layer and a biocompatible polymer layer.

[0014] Preferably, the materials of the composite graphene-Prussian blue ink layer include: graphene, Prussian blue, and polyvinylidene fluoride; the thickness of the composite graphene-Prussian blue ink layer is 0.1-40 micrometers, and the length of the composite graphene-Prussian blue electrode is 50-100 micrometers, and the width is 10-50 micrometers.

[0015] Preferably, the materials of the biocompatible polymer layer include: a chitosan membrane and a perfluorosulfonic acid membrane.

[0016] Preferably, the material of the polystyrene microneedle array comprises: 10-50% polystyrene solution.

[0017] Preferably, the material of the intermediate membrane layer is a PC membrane, i.e., a polycarbonate membrane, modified with a coating of polydopamine, polyethylene glycol, and bovine serum albumin, wherein the diameter of the PC membrane is 1-3 cm.

[0018] Preferably, the first electrode layer is an anode mesh, the second electrode layer is a cathode mesh, the anode mesh is made of aluminum, and the cathode mesh is made of stainless steel.

[0019] Preferably, the signal conversion module includes: a first signal conversion unit, a control unit, and a second signal conversion unit; the first signal 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 signal conversion unit and output a command signal to the second signal conversion unit through the gating circuit of the microcontroller; 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 electroosmotic pump to control the opening and closing of the electroosmotic pump.

[0020] This utility model has the following beneficial effects:

[0021] This invention proposes a closed-loop control system, comprising: a graphene electrode microneedle biosensor, an electroosmotic pump, and a signal conversion module. The graphene electrode microneedle biosensor includes: a substrate, a polystyrene microneedle array, and an electrode covering the substrate. The electrode includes a working electrode and a reference / counter electrode. The working electrode is smooth and covered with a uniformly shaped multilayer structure. The working electrode is a graphene-Prussian blue composite ink layer, and the multilayer structure includes an indicator reactive enzyme layer and a biocompatible polymer layer. First, the microneedle array in the graphene electrode microneedle biosensor used in this closed-loop control system is a hollow polystyrene microneedle array. The hollow polystyrene microneedle array has the characteristics of low cost, good biocompatibility, high mechanical strength, and stable chemical properties. At the same time, compared with long needles, the biosensor made of hollow polystyrene microneedles can alleviate patient pain. The hollow polystyrene microneedles are easy to manufacture using soft photolithography technology. Second, the working electrode and the reference / counter electrode used in this closed-loop control system are both graphene-Prussian blue electrodes, which are formed by printing graphene composite ink on the surface of the microneedles. Compared to micro / nano manufacturing methods, the entire manufacturing process of the graphene-Prussian blue electrode is simple, rapid, economical, and easy to operate. Finally, the closed-loop control system further integrates the electroosmotic pump with the polystyrene hollow microneedles, delivering drugs through the hollow channels of the polystyrene hollow microneedles. The graphene electrode microneedle biosensor device detects interstitial markers; when the marker concentration exceeds the normal range, the electroosmotic pump automatically activates to deliver the drug. Both the graphene electrode microneedle biosensor and the electroosmotic pump are intelligently controlled by a single printed circuit board, achieving a closed-loop function while also offering wearable, miniaturized, painless, precise, cost-effective, and easy-to-manufacture features. Attached Figure Description

[0022] Figure 1 A schematic diagram of the overall structure of a closed-loop control system.

[0023] Figure 2 Overall structure diagram of the closed-loop control system.

[0024] Figure 3 Diagram of an electroosmotic pump.

[0025] Figure 4 Side view of the graphene electrode microneedle sensor.

[0026] Figure 5 Side view of the microneedle covered with the working electrode.

[0027] The components include: a graphene electrode microneedle sensor 1, an electroosmotic pump 2, a signal conversion module 3, a substrate 11, a receiving cavity 111, a polystyrene microneedle array 12, an electrode 13, a working electrode 131, a reference electrode / counter electrode 132, a microneedle body 14, a square or round hole at the bottom 141, a square or round hole at the top 142, a hollow channel 143, an intermediate film layer 21, a first electrode layer 22, a second electrode layer 23, a first signal conversion unit 31, a control unit 32, a second signal conversion unit 33, a graphene-Prussian blue composite ink layer 1311, an indicator reactive enzyme layer 1312, a biocompatible polymer layer 1313, and drug A. Detailed Implementation

[0028] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0029] Reference Figure 1 and Figure 3 As shown, this application discloses a closed-loop control system, which includes a graphene electrode microneedle sensor 1, an electroosmotic pump 2, and a signal conversion module 3.

[0030] The electroosmotic pump 2 includes an intermediate membrane layer 21, a first electrode layer 22, and a second electrode layer 23. The intermediate membrane layer 21 is located between the first electrode layer 22 and the second electrode layer 23. The intermediate membrane layer 21 has multiple through-holes. The material of the intermediate membrane layer is a PC membrane (polycarbonate membrane) coated with polydopamine, polyethylene glycol, and bovine serum albumin, with a diameter of 1-3 cm. The first electrode layer 22 is an anode mesh, and the second electrode layer 23 is a cathode mesh. The anode mesh is made of aluminum, and the cathode mesh is made of stainless steel. Both the anode mesh and the cathode mesh have a width of 1.5 cm and a length of 2 cm.

[0031] When the electroosmotic pump 2 is turned on, that is, after the first electrode layer 22 and the second electrode layer 23 are energized, the first electrode layer 22 and the second electrode layer 23 apply an electric field to the intermediate membrane layer 21, so that a double electric layer is formed on the inner wall of the through hole on the intermediate membrane layer 21. Then, under the action of the electric field, the charges in the double electric layer will be driven towards the electrodes with opposite charges and drag the surrounding liquid flow, thereby providing continuous infusion.

[0032] Reference Figure 2As shown, the signal conversion module 3 includes a first signal conversion unit 31, a control unit 32, and a second signal conversion unit 33. Specifically, the first signal conversion unit 31 is used to receive and convert the electrical signal output by the graphene electrode microneedle sensor 1; the control unit 32 is used to receive the electrical signal converted by the first signal conversion unit 31 and output a command signal to the second signal conversion unit 32 through a gating circuit; the second signal conversion unit 32 is used to receive and convert the command signal output by the control unit 33 and transmit the command signal to the electroosmotic pump to control the opening and closing of the electroosmotic pump.

[0033] The input terminal of the first signal conversion unit 31 is connected to the output terminal of the graphene electrode microneedle sensor, the output terminal of the first signal conversion unit 31 is connected to the input terminal of the control unit 32, the input terminal of the second signal conversion unit 33 is connected to the output terminal of the control unit 32, and the output terminal of the second signal conversion unit 33 is connected to the input terminal of the electroosmotic pump 2. In one feasible embodiment, the first signal conversion unit 31 is a first signal converter, the control unit 31 is a microcontroller, and the second signal conversion unit 33 is a second signal converter.

[0034] Specifically, refer to Figure 4 and Figure 5 As shown, the graphene electrode microneedle sensor includes a substrate 11, a polystyrene microneedle array 12 integrally formed with the substrate and disposed at one end of the substrate, and an electrode 13 made of composite graphene material covering the substrate 11 and the polystyrene microneedle array 12. The electrode consists of a working electrode 131 and a reference electrode / counter electrode 132. The electrode 13 covers the protruding surface of the microneedle array 12, which is composed of microneedle bodies 14. The polystyrene microneedle array includes microneedle bodies 14, and the bottom and top ends of the microneedle bodies respectively include a square or circular hole 141 at the bottom end and a square or circular injection hole 141 at the top end. Hole 142, a hollow channel 143 connects the bottom square or circular hole 141 and the top square or circular injection hole 142, the substrate 11 contains a receiving cavity 111, the top of the receiving cavity 111 is connected to the bottom square or circular hole 141; each microneedle 14 is pyramidal in shape, with a base width of 400 micrometers and a height of 1.2 millimeters, the size of the bottom square or circular hole 141 of the microneedle 14 is 30-900 μm, the size of the top square or circular injection hole 142 is 10-100 μm, and the thickness of the sidewall of the microneedle is 10-100 μm.

[0035] The polystyrene microneedle array 12 is made of 20% polystyrene microneedles. The 10-50% polystyrene microneedles are obtained by completely dissolving solid polystyrene in dimethylformamide in an oven at 90°C to form a 5-50% polystyrene solution. The polystyrene solution is then coated onto a paraffin mold and dried on a hot plate at 45°C for 24-48 hours to obtain the polystyrene microneedle array.

[0036] The polystyrene microneedle array is an m×n microneedle array, and the number of microneedles in each row of microneedle bodies 14 can be set to 6; the spacing between each two adjacent microneedles is 2 mm, and the working electrode 131 and the reference electrode / counter electrode 132 each occupy several rows and columns of microneedle bodies 14.

[0037] refer to Figure 5 As shown, the working electrode 131 is smooth and covered with a uniformly shaped multilayer structure. The working electrode is a graphene-Prussian blue composite ink layer 1311, with the multilayer structure including an indicator reactive enzyme layer 1312 and a biocompatible polymer layer 1313. The material of the graphene-Prussian blue composite ink layer 1311 is a composite graphene-Prussian blue ink, which contains graphene, Prussian blue, and polyvinylidene fluoride. The graphene, Prussian blue, and polyvinylidene fluoride are uniformly mixed and distributed on the microneedles 14. In the graphene-Prussian blue composite ink layer, the graphene acts as a conductive electrode, the Prussian blue acts as an electronic mediator to reduce the sensing potential, and the polyvinylidene fluoride acts as a binder to maintain the stability of the electrode in the liquid. Furthermore, the thickness of the graphene-Prussian blue composite ink layer 1311 is 0.1-40 micrometers, the length of the graphene-Prussian blue electrode is 50-100 micrometers, and the width is 10-50 micrometers. Coating the graphene-PB electrode does not change the shape of the microneedle, indicating that coating the surface of the microneedle with composite graphene-Prussian blue ink does not affect the insertion performance of the microneedle.

[0038] The material used for the indicator reaction enzyme layer 1312 coated on the working electrode 131 is an indicator reaction enzyme. The indicator reaction enzyme can react with the corresponding analyte in the test solution. When the working electrode 131 comes into contact with the test solution, the indicator reaction enzyme produces a product. The product will undergo oxidation or reduction reactions on the working electrode to generate changes in electrical signals.

[0039] The biocompatible polymer layer 1313 is made of chitosan membrane and perfluorosulfonic acid membrane. By covering the working electrode 131 with liquid biocompatible polymer and then heating and drying the liquid biocompatible polymer, a biocompatible polymer layer is formed, which can improve the stability of the electrode, increase biocompatibility, and resist electroactive interference in the interstitial fluid.

[0040] When using this closed-loop control system, one end of the graphene electrode microneedle sensor 1 enters the patient's body and contacts the patient's subcutaneous tissue fluid to detect the concentration of indicator substances in the subcutaneous tissue fluid. The graphene electrode microneedle sensor 1 can detect current under a constant voltage, and the magnitude of the current signal is proportional to the magnitude of the indicator substance concentration. In addition to detecting the current signal, the first signal conversion unit 31 also provides a constant voltage to the graphene electrode microneedle sensor 1. The constant voltage can be different voltages such as 0.1V, -0.1V, or 0.6V. The second signal conversion unit 33 can provide a constant voltage to drive the electroosmotic pump and control the drug injection volume by controlling the magnitude and duration of the voltage. The voltage magnitude can be from 0.1V to 20V.

[0041] After the graphene electrode microneedle sensor detects the concentration of the indicator substance and generates an electrical signal, the first signal conversion unit 31 of the signal conversion module 3 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 signal 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 command or an off command. At the same time, the control unit 32 sends the generated command to the second signal conversion module 33. The second signal conversion module 33 then converts the received command into a corresponding signal and controls the electroosmotic pump 2 to turn on or off according to the signal. In this way, the electroosmotic pump 2 can be controlled according to the concentration of the reactants monitored by the patient in real time.

[0042] In one feasible implementation, the closed-loop system further includes a cloud server, with the control unit 32 electrically connected to the cloud server. The cloud server receives and stores information sent by the control unit 32, which may include the concentration of markers in the patient's body. The closed-loop system also includes a display module, electrically connected to the signal conversion module 3, and also connected to the cloud server. The display module receives and displays the information sent by the control unit 32. In specific applications, the display module can be a computer, monitor, tablet computer, etc.

[0043] The above are all preferred embodiments of this application and are not intended to limit the scope of protection of this application. Therefore, all equivalent changes made in accordance with the structure, shape and principle of this application should be covered within the scope of protection of this application.

Claims

1. A closed-loop control system, characterized in that, include: Graphene electrode microneedle sensor, electroosmosis pump, and signal conversion 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 electrode / counter electrode, the electrode covering the protruding surface of the microneedle array composed of microneedle bodies, the polystyrene microneedle array including microneedle bodies, 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 containing a drug receiving cavity, the top end of the drug receiving cavity being connected to the bottom square or circular hole; The electroosmotic pump includes a pump body, in which a first electrode layer, a second electrode layer and an intermediate membrane layer are disposed. The intermediate membrane layer is disposed between the first electrode layer and the second electrode layer, and the intermediate membrane layer is provided with at least one through hole. The bottom end of the receiving cavity is connected to the second electrode layer. The input terminal of the signal conversion module is connected to the output terminal of the graphene electrode microneedle sensor, and the output terminal of the signal conversion module is connected to the input terminal of the electroosmotic pump; the signal conversion module controls the opening or closing of the electroosmotic pump 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 base diameter of 50-1000 micrometers and a height of 300-2000 micrometers.

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

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 working electrode is smooth and covered with a uniformly shaped multilayer structure. The working electrode is a graphene-Prussian blue composite ink layer, and the multilayer structure on it includes an indicator reaction enzyme layer and a biocompatible polymer layer.

6. A closed-loop control system according to claim 1, characterized in that, The signal conversion module includes: a first signal conversion unit, a control unit, and a second signal conversion unit; the first signal 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 signal 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 electroosmotic pump to control the opening and closing of the electroosmotic pump.

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