CN217359718U - Flexible micro-needle patch and flexible wearable sensor - Google Patents
Flexible micro-needle patch and flexible wearable sensor Download PDFInfo
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Abstract
The utility model provides a flexible micro-needle patch and a flexible wearable sensor, wherein the flexible micro-needle patch comprises a polyimide substrate, and a polyimide micro-needle array and metal pins are arranged on the surface of the polyimide substrate; the polyimide microneedle array is divided into a counter electrode, a working electrode and a reference electrode; the counter electrode is sequentially provided with a titanium metal bottom layer and a platinum metal layer; the working electrode comprises a glucose working electrode and/or an alcohol working electrode; the glucose working electrode is sequentially provided with a titanium metal bottom layer, a platinum metal layer, a Prussian blue layer, a glucose oxidase layer, a chitosan layer and a Nafion layer; the alcohol working electrode is sequentially provided with a titanium metal bottom layer, a platinum metal layer, a Prussian blue layer, an alcohol oxidase layer, a bovine serum albumin layer, a chitosan layer and a Nafion layer; the reference electrode is sequentially provided with a titanium metal bottom layer, a platinum metal layer and a silver chloride layer; the metal pin comprises a titanium metal bottom layer and a platinum metal layer.
Description
Technical Field
The utility model relates to a non-invasive analysis and detection technical field especially relates to a flexible micropin paster and flexible wearable sensor.
Background
Diabetes mellitus is a chronic metabolic disease, and is often accompanied by changes in the structure and function of multiple tissues and organs. And various related examinations are made in time, and the method has extremely important significance for treating and preventing complications. The diabetes patient can ensure the healthy life of the diabetes patient by constantly monitoring the glucose content in the body of the diabetes patient and matching with a proper treatment method. Alcohol consumption is very common in society, millions of people drink regularly, and the number of people who drink alcohol in a special time period is increased sharply, such as traditional holidays. Such use has a wide range of adverse effects on personal health, social safety and economic factors, severely affecting social stability and personal safety. Therefore, monitoring of alcoholism and effective real-time alcohol detection is a substantial social problem, and has extremely important practical and potential applications in personal and traffic safety as well as in clinical medicine (excessive drinking can cause various disease complications including fetal alcohol spectrum disorders, various types of cancer, cardiovascular disease, stroke, cirrhosis, various psychiatric complications, pancreatitis, etc.).
Currently, the most prominent glucose and alcohol concentration measurement methods are direct measurements of both the blood levels in humans. This detection method relies on invasive blood sampling, is not suitable for continuous monitoring applications, and is inconvenient and costly to operate. Thus, reliable and convenient determination of blood glucose and alcohol concentrations by non-invasive or minimally invasive means (i.e., without the need to collect blood) is of great significance for clinical, safety and forensic applications, as well as for safe recreational consumption and basic research.
Due to the need for non-invasive analysis, the measurement of glucose and ethanol in body fluids for clinical and safety purposes has become important. In this case, sweat is an attractive option because it is easier to obtain personal consent for sampling, and in some cases, such as monitoring a driver or an individual engaged in safety-related tasks, sweat detection is easier to collect than urine and blood. There have been a lot of published data showing the correlation between glucose in sweat and blood glucose concentration in human body, and simultaneously, the human body can realize ethanol degradation by enzyme of human body after drinking alcohol, and in addition, oral ethanol can also be eliminated by skin perspiration. In fact, some publications have suggested using human sweat rather than blood to estimate glucose and ethanol concentrations or other clinically relevant analytes, such as lactic acid, in humans. There is also a relevant literature demonstrating a clear correlation between sweat and blood alcohol concentrations when a person consumes alcohol.
However, the problems of weak sensing signal, poor sensitivity and unstable result are easy to occur by adopting non-invasive analysis, and how to improve the sensing signal strength and sensitivity of the non-invasive analysis is a problem which needs to be solved at present.
SUMMERY OF THE UTILITY MODEL
In view of this, the to-be-solved technical problem of the present invention is to provide a flexible microneedle patch and a flexible wearable sensor, which can realize non-invasive detection and accurate detection result.
The utility model provides a flexible micro-needle patch, which comprises a polyimide substrate, wherein a polyimide micro-needle array and metal pins are arranged on the surface of the polyimide substrate;
the polyimide microneedle array is divided into a counter electrode, a working electrode and a reference electrode;
the counter electrode is sequentially provided with a titanium metal bottom layer and a platinum metal layer;
the working electrode comprises a glucose working electrode and/or an alcohol working electrode;
the glucose working electrode is sequentially provided with a titanium metal bottom layer, a platinum metal layer, a Prussian blue layer, a glucose oxidase layer, a chitosan layer and a Nafion layer;
the alcohol working electrode is sequentially provided with a titanium metal bottom layer, a platinum metal layer, a Prussian blue layer, an alcohol oxidase layer, a bovine serum albumin layer, a chitosan layer and a Nafion layer;
the reference electrode is sequentially provided with a titanium metal bottom layer, a platinum metal layer and a silver chloride layer;
the metal pin comprises a titanium metal bottom layer and a platinum metal layer.
Preferably, the polyimide microneedles are quadrangular pyramid shaped.
Preferably, the height of the polyimide microneedle is 1-300 mu m; more preferably 220 μm.
Because of the anisotropy of silicon under alkaline conditions, the side length of a square at the bottom of the microneedle determines the height of the microneedle, and the height of the microneedle is higher as the side length is longer, so that the height of the polyimide microneedle can be correspondingly changed according to the side length of the square at the bottom of the microneedle.
Preferably, the bottom surface of the polyimide microneedle connected with the polyimide substrate is square, and the side length of the square is preferably 10-500 μm, and more preferably 350 μm. The outer spacing is preferably 100-300 mu m; more preferably 200 μm.
Preferably, the bottom surface of the polyimide microneedle connected with the polyimide substrate is square, and the array of the square is 5 × 5.
Preferably, the thickness of the polyimide substrate is 20 to 100 μm.
The utility model provides a flexible wearable sensor, including above-mentioned flexible micropin paster, flexible micropin paster passes through metal pin and is connected with test platform.
Compared with the prior art, the utility model provides a flexible microneedle patch, which comprises a polyimide substrate, wherein a polyimide microneedle array and metal pins are arranged on the surface of the polyimide substrate; the polyimide microneedle array is divided into a counter electrode, a working electrode and a reference electrode; the counter electrode is sequentially provided with a titanium metal bottom layer and a platinum metal layer; the working electrode comprises a glucose working electrode and/or an alcohol working electrode; the glucose working electrode is sequentially provided with a titanium metal bottom layer, a platinum metal layer, a Prussian blue layer, a glucose oxidase layer, a chitosan layer and a Nafion layer; the alcohol working electrode is sequentially provided with a titanium metal bottom layer, a platinum metal layer, a Prussian blue layer, an alcohol oxidase layer, a bovine serum albumin layer, a chitosan layer and a Nafion layer; the reference electrode is sequentially provided with a titanium metal bottom layer, a platinum metal layer and a silver chloride layer; the metal pin comprises a titanium metal bottom layer and a platinum metal layer.
The utility model provides a flexible micropin paster belongs to and does not have wound sensor, uses flexible material can better laminate human skin, and simultaneously for traditional planar film sensor, it adopts three-dimensional micropin structure increase working electrode area surface, has bigger contact surface area to the sensing signal and the sensitivity in reinforcing later stage can accurate detection glucose and ethanol content in the human sweat. Meanwhile, a traditional electrochemical three-electrode system or four-electrode system is integrated into a miniature patch, so that the cost is reduced, and meanwhile, the wearing detection is facilitated.
The utility model discloses only need adopt simple semiconductor processing technology to process out silicon-based mould and be used for polyimide micropin back mould, then realize the metal imaging with magnetron sputtering on the micropin film, form two essential electrochemistry three electrode system or four electrode system, rethread electrochemical deposition and biological modification gimmick accomplish the deposit of sensing dielectric layer and the decoration of oxidase, the required equipment of whole process flow is simple, and process steps is simple, and repeatability is good, and large-scale manufacturing becomes probably. The final effect can achieve good linear response to the detected glucose and ethanol concentration, the detection range is large, repeated measurement and continuous detection can be realized, and the flexible three-dimensional microneedle sensor is more suitable for clinical monitoring and diagnosis, and is also more suitable for the aspects of household practicality, traffic safety and the like.
Drawings
Fig. 1 is a schematic structural diagram of a flexible microneedle patch (four-electrode system) provided in the present invention;
fig. 2 is a 3D diagram of a metal-patterned microneedle patch provided by the present invention;
fig. 3 is a schematic view of a reverse-molded microneedle prepared in example 1;
fig. 4 is a schematic view of a microneedle structure in the modified microneedle patch;
FIG. 5 is a graph of an individual test alcohol response;
FIG. 6 is a graph of glucose response measured alone.
Detailed Description
The technical solution of the present invention will be examined and fully described below with reference to the following embodiments, and it should be understood that the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments in the present invention, all other embodiments obtained by a person skilled in the art without creative work belong to the protection scope of the present invention.
The utility model provides a flexible micro-needle patch, which comprises a polyimide substrate, wherein a polyimide micro-needle array and metal pins are arranged on the surface of the polyimide substrate;
the polyimide microneedle array is divided into a counter electrode, a working electrode and a reference electrode;
the counter electrode is sequentially provided with a titanium metal bottom layer and a platinum metal layer;
the working electrode comprises a glucose working electrode and/or an alcohol working electrode;
the glucose working electrode is sequentially provided with a titanium metal bottom layer, a platinum metal layer, a Prussian blue layer, a glucose oxidase layer, a chitosan layer and a Nafion layer;
the alcohol working electrode is sequentially provided with a titanium metal bottom layer, a platinum metal layer, a Prussian blue layer, an alcohol oxidase layer, a bovine serum albumin layer, a chitosan layer and a Nafion layer;
the reference electrode is sequentially provided with a titanium metal bottom layer, a platinum metal layer and a silver chloride layer;
the metal pin comprises a titanium metal bottom layer and a platinum metal layer.
Fig. 1 is a schematic structural diagram of a flexible microneedle patch (four-electrode system) provided by the present invention, wherein a circular region shown in fig. 1-1 is a silver chloride reference electrode, a circular region shown in fig. 1-2 is an alcohol working electrode, a circular region shown in fig. 1-3 is a counter electrode, a circular region shown in fig. 1-4 is a glucose working electrode, and a strip-shaped region shown in fig. 1-5 is a metal pin.
The utility model discloses in, flexible micropin paster can set up to three electrode systems, including counter electrode, working electrode and reference electrode, working electrode is glucose working electrode or alcohol working electrode.
The utility model discloses in, also can cut out through the flexible micropin paster to four electrode system, obtain three electrode system's flexible micropin paster.
The utility model discloses use polyimide as the raw materials, it has that insulating nature is good, mechanical properties is good, biocompatibility is good, the nature is stable and with low costs, processing convenient advantage.
In the present invention, the polyimide microneedles are preferably quadrangular pyramids, which can also be referred to as pyramids.
The quadrangular pyramid is made of polyimide, can not penetrate through the skin, and is used for monitoring the content of glucose and alcohol through sweat.
The height of the polyimide microneedle is preferably 1 to 300 μm, more preferably 200 to 220 μm, and still more preferably 220 μm.
The height of the polyimide microneedle refers to a linear distance between the top end of the microneedle and the polyimide substrate.
The bottom surface of the polyimide microneedle connected with the polyimide substrate is preferably square, and the side length of the square is preferably 10-500 micrometers, and more preferably 350 micrometers. The outer pitch is preferably 100 to 300 μm, and more preferably 200 μm.
The bottom surface of the polyimide microneedle connected with the polyimide substrate is square, and the square array is preferably 5 × 5, that is, the number of microneedles per electrode is 25.
The thickness of the polyimide substrate is preferably 20 to 100 μm.
The thickness of the titanium metal bottom layer in the counter electrode, the working electrode and the reference electrode is preferably 5-20 nm, and more preferably 10 nm.
The thickness of the platinum metal layer in the counter electrode, the working electrode and the reference electrode is preferably 50 to 200nm, and more preferably 100 nm.
The utility model discloses in, the thickness of preferred control titanium metal bottom: the thickness of the platinum metal layer is 1: 10.
the method for arranging the titanium metal bottom layer and the platinum metal layer is preferably magnetron sputtering.
The glucose working electrode is characterized in that a Prussian blue layer, a glucose oxidase layer, a chitosan layer and a Nafion layer are sequentially modified on the surface of a platinum metal layer.
The Prussian blue layer is preferably modified on the surface of the platinum metal layer by adopting an electrochemical deposition method, and can be used for improving the detection sensitivity and enhancing the anti-interference performance.
Then modifying a glucose oxidase layer, fixing the oxidase on the surface of the platinum electrode through chitosan, and then dripping a Nafion solution to improve the stability and the reproducibility of the sensor.
The working principle of the glucose working electrode is that glucose is catalyzed by the specificity of glucose oxidase to react with oxygen and water to generate hydrogen peroxide and gluconic acid, the generated hydrogen peroxide can generate an oxidation-reduction reaction with a Prussian blue layer to generate electron transfer, and finally the change of the glucose concentration can be reflected by detecting the current.
The alcohol working electrode is characterized in that a Prussian blue layer, an alcohol oxidase layer, a bovine serum albumin layer, a chitosan layer and a Nafion layer are sequentially modified on the surface of a platinum metal layer.
The Prussian blue layer is preferably modified on the surface of the platinum metal layer by adopting an electrochemical deposition method, and can be used for improving the detection sensitivity and enhancing the anti-interference performance.
Then modifying an alcohol oxidase layer and a bovine serum albumin layer, fixing the alcohol oxidase and the bovine serum albumin on the surface of a platinum electrode through chitosan, and then dripping a Nafion solution to improve the stability and the reproducibility of the sensor.
The working principle of the alcohol working electrode is that the alcohol is catalyzed by the specificity of alcohol oxidase to react with oxygen and water to generate hydrogen peroxide and acetaldehyde, the generated hydrogen peroxide can generate oxidation-reduction reaction with a Prussian blue layer to generate electron transfer, and finally the change of the glucose concentration can be reflected by detecting the current.
The utility model discloses preferred, the center of working electrode aligns with the center of metal pin broadside.
In some embodiments of the present invention, the length of the metal pin may be 1cm, and the width may be 1 mm.
In some embodiments of the present invention, the metal pins may have a length of 0.7cm and a width of 1 mm.
The utility model provides a be provided with polyimide microneedle array's polyimide substrate in flexible micropin paster adds the thermal curing shaping back drawing of patterns and forms through liquid polyimide in the silica-based mould of specific shape.
Specifically, a semiconductor process is used for patterning a silicon-based material to be etched, the position, density and height of a microneedle in a film to be subjected to mold inversion at a later stage are determined, then the anisotropic corrosion principle of silicon under an alkaline condition is utilized, a pyramid groove with the depth of hundreds of microns can be efficiently and rapidly etched in the process, the polyimide film microneedle can be completely demoulded to form through mold inversion, then a three-electrode or four-electrode structure is formed through magnetron sputtering, and the whole sensor is finally processed through a biological modification process.
Preferably, the silicon-based mold with the specific shape is prepared according to the following method:
depositing and growing silicon nitride on a silicon substrate, performing patterning treatment by using photoresist, removing the silicon nitride which is not protected by the photoresist, etching a pyramid groove by using the anisotropy of the silicon under the alkaline condition, and then dewatering the surface of a reverse mold, depositing and growing silicon oxide (200 nm silicon oxide in some examples) with a certain thickness on a mould to change the surface hydrophilicity and prevent the film from shrinking and wrinkling in the curing process, then spin-coating a polyimide solution on the mould according to a certain spin-coating process (the thickness of the cured polyimide film is controlled to be between 20um and 120um by controlling the spin-coating process), heating and curing, demoulding to prepare a microneedle film, then carrying out metal patterning on the microneedle sample by magnetron sputtering and a special silicon material graphic mask, and finally processing the polyimide flexible microneedle sample with the microneedle electrode area of the microneedle, wherein the thickness of the sputtered metal is 10nm titanium and 100nm platinum.
And then coating silver chloride ink on the surface of the reference electrode, and drying to form the reference electrode.
The Prussian blue layer, the glucose oxidase layer, the chitosan layer and the Nafion layer are sequentially modified on the surface of the glucose working electrode.
The surface of the alcohol working electrode is sequentially modified with a Prussian blue layer, an alcohol oxidase layer, a bovine serum albumin layer, a chitosan layer and a Nafion layer.
Before testing the concentration of glucose and/or alcohol solution, prussian blue needs to be activated in phosphate buffer (pH 6.5), preferably electrochemical time-current method is used for activating for 300S, the activation voltage is set to-0.05V, and then cyclic voltammetry is used for further activating, the maximum voltage of cyclic voltammetry is 0.35V, the minimum voltage is-0.05V, the cycle period is 20, and the sensitivity is 0.001. The activated sensor can start to detect glucose and/or ethanol, a reference electrode and a counter electrode are shared, an electrochemical four-electrode system of two separated working electrodes is adopted for time-sharing voltage-adding detection, a constant voltage method is adopted, the glucose detection starting voltage is 0.6V, the sampling interval is 0.1S, the alcohol detection starting voltage is 0.6V, and the sampling interval is 0.1S, the sensor can show good linear response to the glucose and/or the ethanol through a detection result, the response current is large, and the concentration change of a glucose and/or ethanol solution can be detected for a long time (not less than 3 days).
Based on this, the utility model provides a flexible wearable sensor, including above-mentioned flexible micropin paster, flexible micropin paster passes through metal pin and is connected with test platform.
In order to further explain the present invention, the following description will be made in detail with reference to the embodiments of the present invention, which provides a flexible microneedle patch for monitoring glucose and alcohol concentration in a human body by detecting tissue fluid or sweat.
Example 1
Selecting a clean and flat silicon wafer (100) crystal orientation silicon wafer, soaking and cleaning the silicon wafer for 5min by using acetone without requirements for doping, then washing the silicon wafer for 1min by using ultrapure water, and drying and cleaning by using nitrogen. Depositing and growing 300nm dense silicon nitride on the surface of the silicon wafer by LPCVD to form a protective layer which is used as a protective layer under the corrosion of potassium hydroxide at the later stage.
Selecting a photoetching mask plate, wherein the graph is a square array with the side length of 350um, the array is 5 multiplied by 5, the outer interval of the square is 200um, spin-coating photoresist on a silicon wafer with silicon nitride (S1813), the thickness is about 1.2um, the time of thermal baking at 115 ℃ is 1min, the ultraviolet exposure time is 7.5S, the developing time is 50S, the ultra-pure water cleaning time is 60S, and the film hardening temperature at 120 ℃ is 2 min. After the patterning treatment, the exposed position is not protected by photoresist to expose silicon nitride, the silicon nitride which is not protected by the photoresist is removed after the RIE treatment is carried out on the silicon wafer subjected to the patterning treatment by photoetching, the silicon wafer subjected to the RIE treatment is cleaned by NMP to remove residual photoresist and organic impurities on the surface, is cleaned by ultrapure water and is dried by nitrogen. After the steps are finished, the silicon wafer is placed into a potassium hydroxide solution with the mass fraction of 30%, the silicon wafer is corroded under the heating condition (70 ℃), and according to the anisotropy of silicon corrosion under the alkaline condition, the pyramid groove with the sharp end is a qualified corrosion sample as a final corrosion result, so that the pyramid microneedle which is reversely molded by the subsequent solution has an obvious sharp end. Finally, PECVD is used for depositing and growing silicon oxide with the thickness of about 200nm as a hydrophilic layer, so that later-stage demolding is facilitated. Therefore, the silicon substrate wafer die with the pyramid grooves is processed, the die can be repeatedly used for multiple times, and cost is saved, wherein the depth and distribution of the pyramid grooves corroded under the alkaline condition can be changed by changing the side length and array distribution of squares in the photoetching mask.
Spin-coating polyimide solution on a processed silicon-based mold, controlling the rotating speed and time of spin-coating to realize polyimide microneedle films with different thicknesses, taking quantitative polyimide solution to drip-coat on the silicon-based mold, uniformly opening at a certain rotating speed to realize a film with the thickness of 20-100um, then placing the film on a horizontal platform for standing for 1h to ensure that a pyramid groove on a silicon wafer is full of the solution, then placing the silicon wafer on a heating plate for heating and curing to form a film, wherein the heating process is as follows: heating at 80 deg.C for 30min, heating at 120 deg.C for 30min, heating at 150 deg.C for 30min, and heating at 200 deg.C for 15 min. After heating and curing, the polyimide film can be directly taken down from the silicon chip, the reverse molding and needling effects are good, compared with a plane electrode, the electrode containing the microneedle array has larger surface area, and can not cause any uncomfortable pain sensation to human skin while being fully contacted with the sweat of the human skin. Cutting the polyimide microneedle film into a proper size, processing a patterned silicon wafer by using laser to serve as a mask for magnetron sputtering metallization, wherein the silicon mask is required to be tightly attached to the microneedle film in the process so as to ensure that metal cannot fall off in the later testing process, depositing 10nm titanium on the film by magnetron sputtering to serve as an adhesion layer, then depositing 100nm platinum, and finally obtaining a complete sample after metal patterning as shown in figure 1.
Fig. 2 shows a 3D view of the metal-patterned microneedle patch. Wherein, 2-1 is a polyimide flexible substrate, 2-2 is a first working electrode (monitoring glucose), 2-3 is a silver chloride reference electrode, 2-4 is a titanium platinum metal lead (metal pin), 2-5 is a platinum metal auxiliary electrode (counter electrode), and 2-6 is a second working electrode (monitoring alcohol).
The reverse-molded microneedle schematic is shown in fig. 3, and it can be seen that it is about 220 microns in height.
Carrying out Prussian blue modification on the microneedle area by electrochemical deposition, wherein the Prussian blue deposition solution comprises the following components: 2.5mM ferric chloride, 2.5mM potassium ferricyanide, 0.05M hydrogen chloride and 0.1M potassium chloride, wherein the voltage of electrochemical deposition is 0.6V, the deposition time is 200S, and the sensitivity is set to be 0.001; then, the Prussian blue is stabilized in a mixed solution of 0.1M hydrogen chloride and 0.1M potassium chloride, the electrochemical cyclic voltammetry stability parameters are that the highest voltage is 0.35V, the lowest voltage is-0.05V, 40 cycles are carried out, and the sensitivity is 0.001; a post-deposition bake for 1 hour was then performed, and the process of depositing prussian blue and stabilizing was done directly using a commercial reference electrode. And after baking for 1h, smearing silver chloride ink on the circular area of the silver chloride reference electrode to roughly obtain a silver chloride ink layer with a certain uniform thickness, and baking for 1min at 121 ℃ to finish the modification of the silver chloride reference electrode.
After finishing the modification of the silver chloride reference electrode, respectively modifying two working electrode areas, firstly modifying a glucose working electrode, modifying glucose oxidase (from aspergillus niger), and selectively dripping 5ul of glucose oxidase according to the area of the electrode; after the modified oxidase is dried and solidified, 4ul of 1% chitosan solution (0.5g of chitosan, 1ml of glacial acetic acid and 49ml of ultrapure water) is modified, and the mixture is naturally dried for 5 hours at the temperature of 6 ℃; and after the chitosan modification layer is dried, modifying 4ul of 0.05 wt% Nafion solution, and naturally drying for 4h at 6 ℃ to finally form the glucose microneedle working electrode area of the glucose oxidase layer, the chitosan layer and the Nafion layer.
The modification process of the alcohol oxidase is similar, firstly 5ul of alcohol oxidase (from pichia pastoris) is dripped in a working electrode area, then 4ul of bovine serum albumin is dripped for protecting and stabilizing the alcohol oxidase, and the alcohol oxidase is naturally dried overnight at 6 ℃; after the modified oxidase and bovine serum albumin are dried and solidified, 4ul of 1% chitosan solution (0.5g of chitosan, 1ml of glacial acetic acid and 49ml of ultrapure water) is modified, and the mixture is naturally dried for 5 hours at the temperature of 6 ℃; and after the chitosan modification layer is dried, modifying 4ul of 0.05 wt% Nafion solution, and naturally drying for 4h at 6 ℃ to finally form the alcohol microneedle working electrode area of the alcohol oxidase layer, the bovine serum albumin layer, the chitosan layer and the Nafion layer. So far, the polyimide flexible integrated micro-needle patch for detecting the concentration of the corresponding substance in the human body by detecting the concentrations of glucose and alcohol in the human body sweat is processed.
The schematic diagram of the microneedle structure in the modified microneedle patch is shown in fig. 4, wherein a glucose working electrode, an alcohol working electrode and a silver chloride reference electrode are sequentially arranged from left to right. The glucose working electrode is sequentially layered from bottom to top: 6-polyimide flexible substrate, 5-titanium platinum layer, 4-Prussian blue layer, 3-glucose oxidase layer, 2-chitosan layer, 1-Nafion layer (perfluorinated resin layer); the alcohol working electrode is sequentially layered from bottom to top: 6-polyimide flexible substrate, 5-titanium platinum layer, 4-Prussian blue layer, 7-alcohol oxidase + bovine serum albumin layer, 2-chitosan layer and 1-Nafion layer; the layering of the silver chloride reference electrode is as follows from bottom to top in sequence: 6-polyimide flexible substrate, 5-titanium platinum layer and 8-silver chloride layer.
Example 2 detection test
Before testing the concentration of glucose and alcohol solution, prussian blue needs to be activated in phosphate buffer (pH 6.5), activated for 300S by electrochemical time-current method, the activation voltage is set to-0.05V, and then activated continuously by cyclic voltammetry, the maximum voltage of cyclic voltammetry is 0.35V, the minimum voltage is-0.05V, the cycle period is 20, and the sensitivity is 0.001. The activated sensor can start to detect glucose and ethanol, two separated electrochemical three-electrode systems are adopted for time-sharing detection, a reference electrode and a counter electrode are shared, a constant voltage method is adopted, a detected sample is human-like sweat, the components are mainly prepared according to the composition of the human sweat, the components are phosphate buffer solution + uric acid + ascorbic acid, the concentration of the uric acid is 500umol/L, the concentration of the ascorbic acid is 0.14mmol/L, a certain amount of glucose is added to enable the concentration of the glucose in the solution to be 5mmol/L when the anti-interference performance of the alcohol is tested, and similarly, the alcohol is added to enable the concentration of the alcohol in the solution to be 5mmol/L when the anti-interference performance of the glucose is tested.
The glucose detection starting voltage is 0.05V, the sampling interval is 0.1S, the alcohol detection starting voltage is 0.6V, and the sampling interval is 0.1S, so that the sensor shows good linear response to glucose and ethanol according to the detection result, the response current is large, and the concentration change of the glucose and ethanol solution can be detected for a long time (not less than 4 hours).
The results of the detection are shown in fig. 5 and 6.
Fig. 5 is a response curve of alcohol alone, fig. 6 is a response curve of glucose alone, and the linear fitting of the alcohol test data of fig. 5 in ORIGIN can obtain a linear fitting equation of the sensor to alcohol, wherein Y is 0.49X +8.18, the correction coefficient R2 is 0.918, the zero position of the sensor is 8.18uA, the sensitivity (S) is 0.49uA/(mmol/L), the linear range is about 32mmol/L, and the detection Limit (LOD) is 4.016 mmol/L; linear fitting of the glucose test data in fig. 6 can obtain a linear fitting equation of the sensor to glucose, where Y is 3.27X +2.88, the correction coefficient R2 is 0.996, the zero position of the sensor is 2.88uA, the sensitivity (S) is 3.27uA/(mmol/L), the linear range is about 24mmol/L, and the detection Limit (LOD) is 0.134 mmol/L. The integrated sensor has good linear response and linear range to two substances to be detected.
The above description of the embodiments is only intended to help understand the method of the present invention and its core ideas. It should be noted that, for those skilled in the art, without departing from the principle of the present invention, the present invention can be further modified and modified, and such modifications and modifications also fall within the protection scope of the appended claims.
Claims (8)
1. A flexible microneedle patch comprises a polyimide substrate, wherein a polyimide microneedle array and metal pins are arranged on the surface of the polyimide substrate;
the polyimide microneedle array is divided into a counter electrode, a working electrode and a reference electrode;
the counter electrode is sequentially provided with a titanium metal bottom layer and a platinum metal layer;
the working electrode comprises a glucose working electrode and/or an alcohol working electrode;
the glucose working electrode is sequentially provided with a titanium metal bottom layer, a platinum metal layer, a Prussian blue layer, a glucose oxidase layer, a chitosan layer and a Nafion layer;
the alcohol working electrode is sequentially provided with a titanium metal bottom layer, a platinum metal layer, a Prussian blue layer, an alcohol oxidase layer, a bovine serum albumin layer, a chitosan layer and a Nafion layer;
the reference electrode is sequentially provided with a titanium metal bottom layer, a platinum metal layer and a silver chloride layer;
the metal pin comprises a titanium metal bottom layer and a platinum metal layer.
2. The flexible microneedle patch according to claim 1, wherein said polyimide microneedles are in the shape of a quadrangular pyramid.
3. A flexible microneedle patch according to claim 1, wherein said polyimide microneedles are 1-300 μm in height.
4. The flexible microneedle patch according to claim 1, wherein the bottom surface of the polyimide microneedle to which the polyimide substrate is attached is a square, and the side length of the square is 10 to 500 μm.
5. The flexible microneedle patch according to claim 4, wherein the outer pitch of the square shape is 100 to 300 μm.
6. A flexible microneedle patch according to claim 1, wherein the bottom surface of the polyimide microneedle to which the polyimide substrate is attached is square, and the array of the squares is 5 x 5.
7. The flexible microneedle patch according to claim 1, wherein the polyimide substrate has a thickness of 20 to 100 μm.
8. A flexible wearable sensor comprising the flexible microneedle patch of any one of claims 1-7, connected to a test platform by metal pins.
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| CN117405748A (en) * | 2023-12-14 | 2024-01-16 | 北京大学 | Flexible stretchable biosensor and preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117405748A (en) * | 2023-12-14 | 2024-01-16 | 北京大学 | Flexible stretchable biosensor and preparation method and application thereof |
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