Closed-loop control system

Abstract

The utility model belongs to the technical field of biosensors, and provides a closed-loop control system, which comprises a graphene electrode microneedle sensor, an ultrasonic pump and a control module, the graphene electrode micro-needle sensor comprises a polystyrene micro-needle array, a working electrode and a reference electrode / counter electrode cover the convex surface of a micro-needle body of the polystyrene micro-needle array, and the electrodes comprise the working electrode and the reference electrode / counter electrode which are formed by printing graphene composite ink on the surface of the micro-needle array. The graphene-PB electrode can improve the sensitivity of the microneedle without changing the structural shape of the microneedle, the ultrasonic pump and the microneedle sensor are further integrated, medicine is conveyed through a hollow channel of the microneedle, and the microneedle has the advantages 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 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 drug delivery and control module, which can calculate drug infusion dose according to blood glucose level, to realize automatic blood glucose management.Biological sensor is usually made of microneedle sensor, with the characteristics of minimally invasive, painless, miniature, portable and relatively safe.The existing microneedle sensor can be based on physical vapor deposition technology to prepare working sensing electrode, reference electrode and counter electrode on the side wall of 3D printed microneedle, but the process of manufacturing electrode by these methods is complex and expensive, so that the closed-loop control system cannot be widely used.Ultrasonic pump closed-loop system is a treatment method that can continuously subcutaneously inject drugs, which is composed of computer control circuit, sensor and ultrasonic pump.The ultrasonic pump monitors the concentration of index substance of patient by sensor, analyzes the detected index substance concentration information by computer control circuit, and controls the opening and closing of ultrasonic pump switch by analysis result, without the need for patients to inject themselves, greatly reducing the pain and trouble of multiple subcutaneous injection of drugs for diabetic patients, while it can flexibly adjust the drug dose and reduce the mistakes caused by improper operation when diabetic patients inject drugs themselves.But the cost of existing closed-loop system is high. SUMMARY

[0003] To solve the technical problems of high cost, not easy to manufacture of existing ultrasonic pump closed-loop system, and large capacity of drug infusion closed-loop control system device, not easy to wear, so that it is more easily used in daily life, the utility model provides a kind of closed-loop control system, enhances the wearability, quick manufacturing and stability of closed-loop system, delivers drugs by microneedle, detects gap index substance by microneedle biological sensing device, and the ultrasonic pump is automatically started when the index substance is higher than normal concentration to deliver drugs.

[0004] The specific scheme is as follows:

[0005] A kind of closed-loop control system, including: graphene electrode microneedle sensor, ultrasonic pump and control module.

[0006] The graphene electrode microneedle sensor comprises a substrate, a polystyrene microneedle array arranged at one end of the substrate and integrated with the substrate, and an electrode made of a composite graphene material covering the substrate and the microneedle array; the electrode is composed of a working electrode and a reference electrode / counter electrode, the electrode covers the convex surface of the microneedle array composed of microneedle bodies, the polystyrene microneedle array is composed of at least one microneedle body, the bottom end and the top end of the microneedle body respectively comprise a bottom end square or circular hole and a top end square or circular injection hole, a hollow channel is connected between the bottom end square or circular hole and the top end square or circular injection hole, and the inside of the substrate comprises a containing cavity, the top end of the containing cavity is connected with the bottom end square or circular hole;

[0007] The ultrasonic pump comprises a pump body for storing drugs, a film with a tapered hole arranged in the pump body, and a piezoelectric ring arranged on the film, the film and the piezoelectric ring are connected with an external alternating current power supply through wires, and the bottom end of the containing cavity is connected with the film.

[0008] 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 ultrasonic 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 ultrasonic pump through a gate circuit.

[0009] By adopting the above technical scheme, the ultrasonic pump and the graphene electrode microneedle sensor are integrated together, a closed loop is formed by connection and control of the control module, the electrode on the graphene electrode microneedle sensor is used to collect and detect the concentration of the index substance in the patient's tissue fluid, so as to control the working of the ultrasonic pump.

[0010] Further, the film is a hard film material or a flexible film material.

[0011] By adopting the above technical scheme, the film is made of a hard or flexible film material, which can be stretched and bent under vibration

[0012] Preferably, each microneedle body is in the shape of a pyramid or a cone, the diameter of the bottom of the microneedle body is 50-1000 microns, and the height is 300-2000 microns.

[0013] Preferably, the size of the bottom end square or circular hole of the microneedle body is 30-900 microns, the size of the top end square or circular hole is 10-100 microns, and the thickness of the sidewall of the microneedle body is 10-100 microns.

[0014] Preferably, 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.

[0015] By adopting the above scheme, the tip of the polystyrene microneedle body is convenient to pierce into the skin.

[0016] Further, the piezoelectric ring is integrally connected with the film.

[0017] By adopting the above technical scheme, the piezoelectric ring is integrally connected with the film, so that the vibration of the piezoelectric ring directly drives the vibration of the film, and energy loss is avoided.

[0018] Further, the working electrode is smooth, and a uniform multilayer structure is covered on the electrode, the working electrode is a graphene-prussian blue composite ink layer, and the multilayer structure above the graphene-prussian blue composite ink layer includes an index substance reaction enzyme layer and a biocompatible polymer layer.

[0019] Further, the material of the composite graphene-prussian blue ink layer includes graphene, prussian blue and polyvinylidene fluoride, the thickness of the composite graphene-prussian blue ink layer is 0.1-40 mu m, and the length of each graphene-prussian blue electrode in the microneedle array biosensor is 50-100 mu m, and the width is 10-50 mu m.

[0020] Further, the material of the biocompatible polymer layer includes chitosan film and perfluorosulfonic acid film.

[0021] Further, the material of the polystyrene microneedle array includes 10-50% polystyrene solution.

[0022] Further, the control unit is used for receiving the converted electric signal of the first signal unit, outputting a command signal to the second signal conversion unit through a gate circuit of a microcontroller, 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 an ultrasonic pump to control the opening and closing of the ultrasonic pump.

[0023] The utility model has the advantages of:

[0024] The utility model provides a kind of closed loop control system, comprising: graphene electrode microneedle biosensor, ultrasonic pump, control module, the graphene electrode microneedle biosensor includes: be placed in base one end, with the polystyrene microneedle array of integrally formed base and the electrode made of composite graphene material covered on the base and microneedle array;Electrode manufacturing process cost of composite graphene material is low, easy to operate, easy to realize, and the thickness range of composite graphene electrode is about 10-40 μm, relative to the thickness of ordinary carbon ink electrode 100-500 μm, so that graphene-PB electrode can improve the sensitivity of microneedle while not changing the shape of microneedle structure;Secondly, microneedle biosensor uses microneedle array as pyramidal polystyrene microneedle array, so that drug solution is easy to insert skin through the hollow passage of microneedle and reach interstitium quickly.Then sensor starts to detect interstitial index again.Third, deposit chitosan film and perfluorosulfonic acid film on working electrode, improve the stability of electrode, increase the biocompatibility of living body, resist the electrically active interference in interstitial fluid, finally, the utility model further integrates ultrasonic pump and microneedle sensor, and drug is transported through the hollow passage of microneedle.Microneedle biosensor detects interstitial index, when index is higher than normal concentration, micropump is automatically opened, and drug is transported.Sensor and ultrasonic pump are all controlled by a piece of printed circuit board, so as to realize closed loop function, with stable, wearable, miniaturization, painless, accurate, cost-effective and easy to manufacture etc. BRIEF DESCRIPTION OF DRAWINGS

[0025] Figure 1 A kind of closed loop control system overall structure diagram.

[0026] Figure 2 A kind of closed loop control system control structure diagram.

[0027] Figure 3 Ultrasonic pump structure diagram.

[0028] Figure 4 Graphene electrode microneedle sensor side view.

[0029] Figure 5 Microneedle body side view covered with working electrode.

[0030] The graphene electrode microneedle sensor 1, the ultrasonic pump 2, the control module 3, the base 11, the polystyrene microneedle array 12, the electrode 13, the working electrode 131, the reference electrode / counter electrode 132, the microneedle body 14, the square or circular hole at the bottom end 141, the square or circular hole at the top end 142, the hollow channel 143, the containing cavity 111, the pump body 21, the film 22, the tapered hole 23, the piezoelectric ring 24, the first signal conversion unit 31, the control unit 32, the second signal conversion unit 33, the graphene-Prussian blue composite ink layer 1311, the index substance reaction enzyme layer 1312, the biocompatible polymer layer 1313, and the drug solution A. DETAILED DESCRIPTION

[0031] The utility model will be further described below in combination with the drawings and examples.

[0032] The specific scheme is described as follows:

[0033] Reference Figure 1 As shown in the figure, the closed-loop control system disclosed by the embodiment of the application comprises a graphene electrode microneedle sensor 1, an ultrasonic pump 2 and a control module 3.

[0034] Reference Figure 2 As shown in the figure, the control module comprises a first signal conversion unit 31, a control unit 32 and a second signal conversion unit 33, the input end of the first signal conversion unit 31 is connected with the output end of the graphene electrode microneedle sensor 1, the output end of the first signal conversion unit 31 is connected with the input end of the control unit 32, the input end of the control unit 32 is connected with the input end of the second signal conversion unit 33, the output end of the second signal conversion unit 33 is connected with the input end of the ultrasonic pump 2, in a feasible implementation mode, 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.

[0035] Reference Figure 3As shown, the ultrasonic pump 2 comprises a pump body 21 for storing a drug, and a diaphragm 22 provided in the pump body. The diaphragm is made of a hard or flexible material, such as stainless steel, gold, copper, zinc, platinum, silver, tungsten, aluminum, aluminum alloy, natural rubber, isoprene rubber, polybutadiene rubber, styrene-butadiene rubber, butadiene rubber, chloroprene rubber, butyl rubber, halogenated butyl rubber, ethylene-propylene rubber, chloro-ether rubber, polyacrylate rubber, silicone rubber, fluorosilicone rubber, fluororubber, chlorosulfonated polyethylene, hydrogenated butadiene rubber, thermoplastic polyolefin elastomer, thermoplastic styrene-based elastomer, polyurethane-based thermoplastic elastomer, polyester-based thermoplastic elastomer, polyamide thermoplastic elastomer, halogen-containing thermoplastic elastomer, ionic thermoplastic elastomer, ethylene copolymer thermoplastic elastomer, 1,2-polybutadiene thermoplastic elastomer, trans-polyisoprene thermoplastic elastomer, melt processing thermoplastic elastomer, thermoplastic vulcanized rubber, polydimethylsiloxane, or the like.

[0036] A plurality of tapered holes 23 are formed in the diaphragm 22 by laser etching or ion selective etching. The large-diameter end of the tapered hole 23 is arranged at the side of the cavity for storing the drug, i.e., the large-diameter end of the tapered hole is the liquid inlet end, and the small-diameter end is the liquid outlet end. A piezoelectric ring 24 is further arranged on the diaphragm 22. The piezoelectric ring 24 is arranged at the side of the small-diameter end of the tapered hole 23. The piezoelectric ring 24 is made of a piezoelectric material such as a piezoelectric crystal, piezoelectric ceramic, or piezoelectric polymer. During manufacturing, a layer of piezoelectric material is deposited through a mask hole at the outer edge of the diaphragm to form the piezoelectric ring 24, so that the piezoelectric ring 24 is integrated with the diaphragm 22. The diaphragm 22 and the piezoelectric ring 24 are connected to an external AC power supply through wires. Specifically, the external AC power supply uses AC power with a voltage of 10V-100V. Alternatively, a 1-10V DC power supply can be used, which is converted to 10V-100V AC power through a circuit.

[0037] The first signal conversion unit 31 transmits the electrical signal detected by the graphene electrode microneedle sensor to the control unit. The control unit outputs a command signal to the second signal conversion unit through the gate circuit of the microcontroller. The second signal conversion unit controls the opening and closing of the ultrasonic pump according to the received command signal.

[0038] Specifically, referring to Figure 4As shown, the graphene electrode microneedle sensor comprises: a substrate 11, a polystyrene microneedle array 12 arranged at one end of the substrate and integrated with the substrate, and an electrode 13 made of composite graphene material covering the substrate and the microneedle array; the electrode is composed of a working electrode 131 and a reference electrode / counter electrode 132, the electrode 13 covers the convex surface of the microneedle array 12 composed of microneedle bodies 14, the polystyrene microneedle array 12 comprises microneedle bodies 14, the bottom end and the top end of the microneedle bodies 14 respectively contain a bottom end square or circular hole 141 and a top end square or circular injection hole 142, and a hollow channel 143 is connected between the bottom end square or circular hole 141 and the top end square or circular injection hole 142, the inside of the substrate 11 contains a containing cavity 111, the top end of the containing cavity 111 is connected with the bottom end square or circular hole 141; each microneedle body is in the shape of a pyramid, the bottom width is 400 μm, the height is 1.2 mm, the spacing between the microneedles is 2 mm, the size of the bottom end square or circular hole of the microneedle body is 30-900 μm, the size of the top end square or circular hole is 10-100 μm, and the thickness of the sidewall of the microneedle body is 10-100 μm.

[0039] The material of the polystyrene microneedle array 12 is 20% polystyrene microneedle, and the 10-50% polystyrene microneedle is formed by completely dissolving solid polystyrene into dimethylformamide to form a 5-50% polystyrene solution in an oven at 90°C. The polystyrene solution is coated on a paraffin mold and dried on a hot plate at 45°C for 24-48 hours to obtain the polystyrene microneedle array 12.

[0040] The polystyrene microneedle array 12 is an m×n microneedle array; the spacing between each two microneedles is 2 mm. The working electrode 131 and the reference electrode / counter electrode 132 respectively occupy a plurality of rows and a plurality of columns of microneedle bodies 14.

[0041] Reference Figure 5As shown, the working electrode 131 is composed of a graphene-Prussian blue composite ink layer 1311, on which a marker reaction enzyme layer 1312 and a biocompatible polymer layer 1313 are uniformly coated; 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. 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 0.1-40 μm, the length of each graphene-Prussian blue electrode in the microneedle array biosensor is 50-100 μm, and the width is 10-50 μm. The coating of the graphene-PB electrode does not change the shape of the microneedle body, which indicates that the coating of the composite graphene-Prussian blue ink on the surface of the microneedle body does not affect the insertion performance of the microneedle.

[0042] The material used for the marker reaction enzyme layer 1312 coated on the working electrode 131 is a marker reaction enzyme, which can react with the corresponding analyte in the detected solution. When the working electrode contacts the detected solution, the product is produced by the reaction of the marker reaction enzyme, and the product undergoes oxidation or reduction reaction on the working electrode to produce a change in the electric signal.

[0043] The material used for the biocompatible polymer layer 1313 is chitosan film and perfluorosulfonic acid film. By covering the working electrode with liquid biocompatible polymer and then drying the liquid biocompatible polymer, a biocompatible polymer layer 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.

[0044] In specific operation, the thin film 22 is powered on with the piezoelectric ring 24, and the piezoelectric ring 24 generates vibration after being powered on with alternating current, which drives the thin film to stretch or bend. The tapered hole 23 continuously expands and contracts under the stretching or bending action of the thin film 22, and the caliber alternately changes, thereby extruding the drug stored in the pump body.

[0045] The use principle of the closed-loop control system in the embodiment is as follows: after the polystyrene microneedle array 12 pierces the skin, an electrochemical reaction occurs on the working electrode 131, the change of the electric signal is transmitted to the first signal conversion unit 31, the first signal conversion unit 31 transmits the electric signal to the control unit 32, the control unit 32 analyzes the index substance concentration in the interstitial fluid, so as to judge whether the drug needs to be injected; if the index substance concentration in the interstitial fluid increases, the control unit sends an injection instruction to the second signal conversion unit through the gate circuit in the microcontroller, the ultrasonic pump is controlled to be powered on by the second signal conversion unit, the piezoelectric ring 24 generates radial vibration to drive the thin film to vibrate synchronously in the radial direction, so that the tapered hole 23 on the thin film 22 repeatedly extends and bends to continuously feed the drug into the graphene electrode microneedle sensor 1 on the thin film 22, and then into the subcutaneous tissue, so that the monitoring of different index substances can be realized, for example, the detection of the blood glucose concentration of a diabetic patient and the automatic supply of the drug, in the use process, no manual intervention is needed, the use is convenient, the functions of measurement and treatment are realized, and the integration is higher. Moreover, the ultrasonic pump and the graphene electrode microneedle sensor are small in size, convenient to carry and low in cost.

[0046] The above are preferred embodiments of the utility model, and do not limit the protection scope of the application, so that: equivalent changes made according to the structure, shape and principle of the application should be covered in the protection scope of the application.

Claims

1. A closed-loop control system, characterized in that, include: Graphene electrode microneedle sensor, ultrasonic pump and 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 smooth and covered with a uniformly shaped multilayer structure, the working electrode is a graphene-Prussian blue composite ink layer, the multilayer structure includes an indicator reactive enzyme layer and a biocompatible polymer layer; the electrode covers the raised surface of the microneedle array composed of microneedles, the polystyrene microneedle array includes microneedles, the bottom end and the top end of the microneedle body respectively include a bottom square or circular hole and a top square or circular injection hole, a hollow channel is connected between 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 or circular hole. The ultrasonic pump includes a pump body for storing drugs. The pump body is provided with a diaphragm with a tapered hole. A piezoelectric ring is provided on the diaphragm. The diaphragm and the piezoelectric ring are connected to an external AC power supply through wires. The bottom end of the receiving cavity is connected to the diaphragm. 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 ultrasonic pump. The control module is used to receive the electrical signal output by the graphene electrode microneedle sensor and then control the ultrasonic 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 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 film is a rigid or flexible film material, and the piezoelectric ring is integrally linked to the film.

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

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