CN112842333A - Visual glucose concentration detection microneedle patch, preparation method and application - Google Patents

Abstract

The invention discloses a visual glucose concentration detection microneedle patch, a preparation method and application. The microneedle patch comprises a substrate and a needle point, wherein the needle point comprises a polymer matrix and nano particles or cavities periodically distributed in the polymer matrix, and the polymer matrix can perform a dehydration condensation reaction with glucose, so that a polymer matrix network shrinks or expands, the space between the nano particles or the cavities is changed, and the color of the microneedle needle point is changed. The method can be used for visualizing the glucose concentration detection and can be applied to the glucose concentration detection. Under different glucose concentrations, the microneedle tips have different colors, and the glucose concentration can be simply and efficiently determined by a colorimetric method. The detection is simple and quick, the anti-interference capability is strong, continuous and instant detection can be realized, and the problems of complex and fussy detection process and strong blood taking pain sense in the traditional means are solved.

Description

Visual glucose concentration detection microneedle patch, preparation method and application

Technical Field

The invention belongs to the technical field of microneedles, and particularly relates to a visual glucose concentration detection microneedle patch, a preparation method and application.

Background

In recent years, more and more people suffer from diabetes. Therefore, there is a great need for a device that can continuously and instantly monitor the glucose concentration of a human body. The most widely used household blood glucose monitors can detect the concentration of glucose in blood according to an electrochemical method or a photochemical technology. However, the wide use of the detection instrument is limited by the problems of large blood taking amount, strong blood taking pain, large detection deviation, high cost and the like of the detection instrument. The micro-needle is a micron-scale array structure which is made of metal, silicon, polymer and other materials, has the length of 25-2000 mu m and has a needle point in a symmetrical conical shape or an asymmetrical inclined plane shape. As an effective tool for transdermal detection, microneedles with tiny sharp protrusions can penetrate the stratum corneum and thus painlessly enter the dermis. The proper length of the microneedles can avoid stimulation of dermal nerve fibers or damage to dermal blood vessels, and the resulting small and shallow wounds can heal within 30 minutes, which humanized functions reduce fear for the user and improve patient compliance. In addition, microneedles are a new type of point-of-care device that allows painless transdermal sampling, sensing and drug delivery without the need for trained personnel. And the combination of the biosensor and the micro-needle greatly expands the application of the micro-needle in the aspect of biological detection. However, no glucose detection technique or method by microneedles exists in the current art.

Disclosure of Invention

Aiming at the defects or improvement requirements of the prior art, the invention provides a visual glucose concentration detection microneedle patch, a preparation method and application, and aims to change the color of a microneedle by carrying out dehydration condensation reaction on glucose and a polymer matrix modified with a glucose response group in the microneedle to change periodically arranged nano particles or cavities in the microneedle, thereby solving the technical problems of large blood taking amount, strong blood taking pain, large detection deviation and the like of a glucose concentration detection instrument.

In order to achieve the above object, according to one aspect of the present invention, there is provided a visual glucose concentration detection microneedle patch, including a substrate and a needle tip, where the needle tip includes a polymer matrix, nanoparticles or cavities periodically distributed in the polymer matrix, and the polymer matrix is capable of undergoing a dehydration condensation reaction with glucose, so that a network of the polymer matrix shrinks or swells, and a distance between the nanoparticles or the cavities is changed, thereby changing a color of the needle tip of the microneedle.

Preferably, the polymer matrix contains a glucose-responsive group that is a boronic acid group or a phenylboronic acid group. The boronic acid group or phenylboronic acid group is illustratively derived from a borate, a phenylboronic acid, respectively.

The dehydration condensation reaction process of the glucose response group and glucose is exemplarily shown as follows, and it can be seen that after the dehydration condensation reaction of the phenylboronic acid group and glucose, the reaction product is negatively charged, the Tangnan potential of the whole polymer is changed, so that the needle point polymer is more hydrophilic, and after the needle point polymer is contacted with tissue fluid, the needle point polymer is swelled to be larger, the distance between the nano particles or the cavities is enlarged, and the color change of the microneedle patch is obvious.

Preferably, the nanoparticles periodically distributed in the polymer matrix are of an opal structure, and the cavities periodically distributed in the polymer matrix are of an inverse opal structure.

Preferably, the nanoparticles are at least one of zinc oxide, titanium dioxide, silicon carbide, ferroferric oxide, aluminum oxide, monodisperse polysulfides, carbon, polystyrene, polymers composed of acrylic monomers, polymers composed of methacrylic monomers, a first copolymer, and polyurethane, wherein the first copolymer is composed of at least two of styrene monomers, acrylic monomers, and methacrylic monomers. The monodisperse polysulfides can illustratively be sodium polysulfides, such as Na₂S₄、Na₂S₅And the like. Polymers composed of polyacrylic monomers, e.g. isopropyl polyacrylate, n-butyl polyacrylate, poly(ii) acrylamide; polymers composed of polymethacrylic acid-based monomers such as polymethyl methacrylate, polyhydroxyethyl methacrylate; copolymers composed of at least two of styrene monomers, acrylic monomers, and methacrylic monomers, such as polystyrene-methyl methacrylate, polystyrene-acrylic acid, polystyrene-methyl methacrylate-acrylic acid, polymethyl methacrylate-hydroxyethyl methacrylate, and the like.

Preferably, the size of the nanoparticles or cavities is 100-300 nm.

Preferably, the cavity is obtained by etching periodically arranged nanoparticles in the needle tip.

Preferably, the polymer matrix is at least one of polyvinyl alcohol, polyacrylic acid, polyethylene glycol, polymethacrylic acid, polyvinylpyrrolidone, polylactic acid, polyglycolic acid, polyethylene oxide, polymaleic acid, and derivatives of the above polymers. Illustratively, the derivative of the above polymer may be isopropyl polyacrylate, polyacrylamide, poly-n-butyl acrylate, poly-hydroxyethyl methacrylate, poly-ethylene glycol methacrylate, or the like.

According to another aspect of the present invention, there is provided a method of manufacturing the microneedle patch described above, including the steps of:

(1) uniformly mixing nano particles, a polymer monomer and a polymer monomer modified with a glucose response group, filling the mixture into a microneedle mould, and initiating the polymer monomer to carry out polymerization reaction by light to obtain a needle point, wherein the needle point comprises a polymer matrix modified with the glucose response group and nano particles periodically arranged in the polymer matrix;

or, uniformly mixing the nano particles, the polymer monomer and the polymer monomer modified with the glucose response group, filling the mixture into a microneedle mould, initiating polymerization reaction of the polymer monomer by light, and removing the nano particles from a reaction product by an etching method to obtain a needle point, wherein the needle point comprises a polymer matrix containing the glucose response group and cavities periodically distributed in the polymer matrix;

wherein, the difference between the polymer monomer in step (1) and the polymer monomer containing a glucose-responsive group can be whether the glucose-responsive group is modified.

(2) And coating a base polymer at the bottom of the needle tip, drying and demolding to obtain the microneedle patch.

According to still another aspect of the present invention, there is provided a method of manufacturing the microneedle patch described above, including the steps of:

uniformly mixing nano particles and a polymer monomer, filling the mixture into a microneedle mould, initiating the polymer monomer to carry out polymerization reaction by light to obtain a to-be-modified needle point, coating a base polymer on the bottom of the needle point, drying, demoulding to obtain a to-be-modified microneedle patch, and soaking the to-be-modified microneedle patch in a solution with a glucose response group to obtain the microneedle patch, wherein the needle point of the microneedle patch is a polymer matrix containing the glucose response group and nano particles periodically distributed in the polymer matrix;

or uniformly mixing the nano particles and the polymer monomer, filling the mixture into a microneedle mould, carrying out polymerization reaction on the polymer monomer through light initiation to obtain a to-be-modified needle point, coating a base polymer on the bottom of the needle point, drying, demoulding to obtain a to-be-modified microneedle patch, putting the to-be-modified microneedle patch into a solution with a glucose response group for soaking, and then removing the nano particles through an etching method to obtain the microneedle patch, wherein the needle point of the microneedle patch is a polymer matrix containing the glucose response group and a cavity periodically distributed in the polymer matrix.

Wherein, the bottom of the needle tip refers to the position with the largest diameter of the needle tip, and the solution with the glucose response group can be a borate solution or a phenylboronic acid solution.

According to still another aspect of the present invention, there is provided use of the microneedle patch described above, characterized by constituting a device for visualizing glucose concentration measurement.

Referring to fig. 2, when the microneedle patch provided by the invention is used for visual glucose concentration detection, when a microneedle contacts interstitial fluid in skin, glucose in the interstitial fluid diffuses into the needle tip of the microneedle and reacts with a glucose response group on a polymer substrate, so that the chain distance is changed, the distance between nanoparticles is changed, and the color of the microneedle patch is changed.

In general, at least the following advantages can be obtained by the above technical solution contemplated by the present invention compared to the prior art.

(1) The invention provides a visual glucose concentration detection microneedle patch which can be used for visual glucose concentration detection. The microneedle tips carry nanoparticles or cavities arranged periodically, for example, the nanoparticles are arranged in an opal structure and the cavities are arranged in an inverse opal structure. And the polymer network is modified with groups which can generate dehydration condensation reaction with glucose, when the microneedle is contacted with tissue fluid in skin, the glucose in the tissue fluid is diffused into the needle point of the microneedle and reacts with the glucose response groups on the polymer substrate, and the chain distance is changed, so that the distance between the nano particles is changed, and the effect of changing the structural color of the microneedle patch is achieved. Compared with the traditional method, the means for detecting the glucose is simple and quick, has strong anti-interference capability, can continuously and instantly detect, and solves the problems of complex and fussy detection process and strong blood taking pain sense of the traditional means.

(2) The microneedle patch can be applied to glucose concentration detection, and after glucose in tissue fluid enters the microneedle tips and reacts with the modifying groups on the polymer chains, the polymer network is contracted or expanded, the distance between nano particles is changed, and the color of the microneedle tips is adjusted. Under different glucose concentrations, the microneedle tips have different colors, and the glucose concentration can be simply and efficiently determined by a colorimetric method.

(3) The invention introduces nano particles arranged into an opal structure or an inverse opal structure at the needle point of the micro needle, and the color of the micro needle structure is adjusted by utilizing the change of the distance between the nano particles, thereby indicating the concentration of glucose. The nano particles are arranged in a short-range order and a long-range disorder, and the color of the microneedle patch has no angle dependence. The initial color of the microneedle patch can be adjusted by controlling the size and type of the nanoparticles. The microneedle patch is simple to prepare, wide in raw material source, easy to process and suitable for large-scale production and manufacturing.

(4) According to the invention, the glucose response group is a boric acid group or a phenylboronic acid group, and after the boric acid group or the phenylboronic acid group and glucose are subjected to dehydration condensation reaction, the whole polymer is negatively charged, the Tangnan potential of the whole polymer is changed, so that the needle point polymer is more hydrophilic, and can swell more after contacting with tissue fluid, so that the distance between nano particles or cavities is enlarged, and the color change of the microneedle patch is obvious.

(5) The microneedle patch for detecting the concentration of the visual glucose is 25-2000 mu m in length, 50-250 mu m in diameter of the substrate and symmetrical or asymmetrical inclined plane-shaped in tip. The micro-needle can pierce the stratum corneum when penetrating into the skin of a human body, so that the micro-needle can enter the dermis layer painlessly, and the micro-needle with proper length can avoid stimulating dermal nerve fibers or damaging dermal blood vessels. Compared with other detection means, the method is milder, and can effectively reduce the fear of users and improve the compliance.

Drawings

Fig. 1 is a schematic view of an internal structure of a visualized glucose concentration detection microneedle patch provided in example 1 of the present invention;

fig. 2 is a schematic view of an internal structure of a microneedle after the microneedle is contacted with glucose when the visualized glucose concentration detection microneedle patch provided by the embodiment of the invention is used for visualized glucose concentration detection;

fig. 3 is an SEM image of a visualized glucose concentration detection microneedle patch provided in example 1 of the present invention;

fig. 4 is a diffraction wavelength chart of a visualized glucose concentration detection microneedle patch provided in example 1 of the present invention in different concentrations of glucose;

fig. 5 is an SEM image of a visualized glucose concentration detection microneedle patch provided in example 2 of the present invention;

fig. 6 is an SEM image of a visualized glucose concentration detection microneedle patch provided in example 3 of the present invention;

fig. 7 is an SEM image of a visualized glucose concentration detection microneedle patch provided in example 4 of the present invention.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.

Example 1:

the embodiment provides a preparation method of a visual glucose concentration detection microneedle patch, which comprises the following steps:

1. and etching a 10 multiplied by 10 Polydimethylsiloxane (PDMS) negative template with the diameter of 300 mu m at the bottom edge, the height of 600 mu m and the center distance of 600 mu m between adjacent microneedles for later use by using a laser engraving machine.

2. Taking 5g of glycidyl methacrylate modified polyvinyl alcohol solution, adding 0.5 wt% of photoinitiator DEAP and 10 wt% of polystyrene nano particles, swirling, injecting the dispersion into the tip of a PDMS mold by a vacuum pumping method, removing redundant solution by scraping, and performing photopolymerization for 45 minutes under a 365nm mercury lamp. And after polymerization, paving a layer of pure 200mg/ml PVA solution on a PDMS mould, removing bubbles in vacuum, drying for 24 hours, then demoulding, putting the needle point of the microneedle into a sodium tetraborate-sodium chloride solution with a certain concentration, soaking for 4 hours, taking out and drying to obtain the glucose-responsive microneedle patch with a PVA (polyvinyl alcohol) network modified by borax and polystyrene as nano particles. Wherein the particle size of the polystyrene nano-particles is 220nm and is purchased from sigma-aldrich.

SEM test was performed on the microneedle patch prepared in this example, and referring to fig. 3, it can be seen that the microneedle patch prepared in this example has an opal structure arranged periodically.

After the microneedle patch prepared by the embodiment of the invention is contacted with glucose with different concentrations, the diffraction wavelength of the microneedle patch is tested, and the result is shown in fig. 4, so that the diffraction wavelength of the microneedle patch is changed after the glucose with different concentrations is contacted with the microneedle patch, which indicates that the color of the microneedle patch is changed along with the change of the glucose concentration, and the microneedle patch provided by the embodiment of the invention can be directly applied to the detection of the glucose concentration.

In the process of detecting the glucose concentration, the microneedle patch prepared by the embodiment can be seen blue by naked eyes, and is immersed in the glucose solution for detection, and the microneedle patch changes from blue to green along with the increase of the glucose concentration in the glucose solution.

Example 2:

the embodiment provides a preparation method of a visual glucose concentration detection microneedle patch, which comprises the following steps:

1. and etching a 12 x 12 Polydimethylsiloxane (PDMS) negative template with the diameter of 300 mu m at the bottom edge, the height of 800 mu m and the center-to-center distance of 750 mu m between adjacent microneedles by using a laser engraving machine for later use.

2. A monodisperse polystyrene latex with a diameter of 230nm was obtained from Sigma-Aldrich.

3. A10 wt% homogeneous polymer monomer solution was prepared by dissolving the modified PVA powder in dimethyl sulfoxide (DMSO) at 100 ℃ for 2 hours in an N2 atmosphere. Then, adding 4-formylphenylboronic acid (4-BBA) and HCl drops for reaction to obtain 4-BBA modified 4-BBA-PVA solution, adding a proper amount of photoinitiator DEAP and 20 wt% of PS latex, uniformly mixing, pouring a PDMS template, removing excess solution after centrifugal molding, and carrying out photo-initiated polymerization under a mercury lamp for 45min to obtain the microneedle tip. And (3) coating a layer of 31.25 wt% PVP-ethanol solution on the negative template, centrifuging to remove air bubbles, and drying to obtain the glucose response microneedle patch with the PVA network modified by diboronic acid and the nano particles of polystyrene.

SEM test was performed on the microneedle patch prepared in this example, and referring to fig. 5, it can be seen that the microneedle patch prepared in this example has an opal structure arranged periodically.

In the process of detecting the glucose concentration, the microneedle patch prepared by the embodiment can be seen blue by naked eyes, and is immersed in the glucose solution for detection, and the microneedle patch changes from blue to green along with the increase of the glucose concentration in the glucose solution.

Example 3:

the embodiment provides a preparation method of a visual microneedle patch for detecting glucose concentration, which comprises the following steps:

1. and etching a 12 × 12 Polydimethylsiloxane (PDMS) negative template with the diameter of 400 μm at the bottom edge, the height of 800-.

2. Silica nanoparticles having a particle size of 220nm, which were obtained from sigma-aldrich, were taken and added to absolute ethanol and shaken to prepare a suspension.

3. Mixing the suspension with a mixed solution of 3-Acrylamido Phenyl Boric Acid (APBA), DEAP and Ethylene Glycol Dimethacrylate (EGDMA), pouring into a prepared PDMS template, vacuumizing to remove bubbles, and removing excessive solution by scraping. And (2) carrying out photoinitiated polymerization for 4h under a 365nm ultraviolet lamp, coating a layer of 25 wt% PVP solution on a PDMS template, vacuumizing to remove bubbles, drying, demoulding, immersing the needle tip in a 5% HF solution for 6h to remove silicon dioxide in the solution, taking out, immersing in distilled water to remove impurities, and drying to obtain the glucose response microneedle patch with the PEGDMA network being APBA modified and the inverse opal structure.

SEM test was performed on the microneedle patch prepared in this example, and referring to fig. 6, it can be seen that the microneedle patch prepared in this example has an inverse opal structure arranged periodically.

In the process of detecting the glucose concentration, the microneedle patch prepared by the embodiment can be seen blue by naked eyes, and is immersed in the glucose solution for detection, and the microneedle patch changes from blue to green along with the increase of the glucose concentration in the glucose solution.

Example 4:

the embodiment provides a preparation method of a visual microneedle patch for detecting glucose concentration, which comprises the following steps:

1. and etching a 12 × 12 Polydimethylsiloxane (PDMS) negative template with the diameter of 250 micrometers at the bottom edge, the height of 900 micrometers and the center-to-center distance of 500 micrometers between adjacent microneedles by using a laser engraving machine for later use.

2. Polystyrene nanoparticles having a particle size of 210nm were obtained and purchased from sigma-aldrich.

3. Acrylamide (AA), N-methylene Bisacrylamide (BIS), 3-acrylamidophenylboronic acid (3-APBA), DEAP, and DMSO were mixed to prepare a monomer solution. Adding the polystyrene nano particles, stirring and mixing for 10 minutes at 24 ℃, pouring the polystyrene nano particles into a prepared PDMS template, vacuumizing to remove bubbles, and scraping redundant solution by a scraper. And after photo-initiated polymerization is carried out for 45min at 365nm, coating a layer of 25 wt% PVP solution on the surface of the PDMS template, vacuumizing to remove bubbles, drying, and demoulding to obtain the glucose response microneedle patch with the PAM network modified by APBA and the polystyrene as the nano particles.

SEM test was performed on the microneedle patch prepared in this example, and referring to fig. 7, it can be seen that the microneedle patch prepared in this example has an opal structure arranged periodically.

In the process of detecting the glucose concentration, the microneedle patch prepared by the embodiment can be seen blue by naked eyes, and is immersed in the glucose solution for detection, and the microneedle patch changes from blue to yellow-green along with the increase of the glucose concentration in the glucose solution.

Examples 5 to 16

Examples 5-16 visual glucose concentration detection microneedle patches were prepared using different nanoparticles, see table 1 for details.

Table 1 color change of microneedle patches provided in examples 5-16 during measurement of glucose concentration

In the process of measuring the glucose concentration, the microneedle patches prepared in examples 5 to 16 above, which were visually observed to have different colors, were immersed in the glucose solution for measurement, and the color of the microneedle patch was changed accordingly as the concentration of glucose in the glucose solution increased, and the change in color was visually observed. Therefore, the microneedle patch provided by the embodiment of the invention can be directly applied to the detection of the glucose concentration. The method is simple and quick, has strong anti-interference capability and can continuously and instantly detect.

It will be understood by those skilled in the art that the foregoing is only a preferred embodiment of the present invention, and is not intended to limit the invention, and that any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the scope of the present invention.

Claims (10)

Translated fromChinese

1.一种可视化葡萄糖浓度检测微针贴片，其特征在于，包括基底和针尖，所述针尖包括聚合物基质、周期性分布于所述聚合物基质内的纳米粒子或空穴，所述聚合物基质能够与葡萄糖发生脱水缩合反应，使得聚合物基质网络收缩或胀大，改变纳米粒子或空穴之间间距，从而改变微针针尖颜色。1. a visual glucose concentration detection microneedle patch is characterized in that, comprises a base and a needle tip, and the needle tip comprises a polymer matrix, nanoparticles or holes periodically distributed in the polymer matrix, and the polymerized The polymer matrix can undergo a dehydration condensation reaction with glucose, so that the polymer matrix network shrinks or expands, changing the spacing between nanoparticles or cavities, thereby changing the color of the microneedle tip.2.根据权利要求1所述的微针贴片，其特征在于，所述聚合物基质含有葡萄糖响应基团，所述葡萄糖响应基团为硼酸基团或苯硼酸基团。2 . The microneedle patch according to claim 1 , wherein the polymer matrix contains a glucose-responsive group, and the glucose-responsive group is a boronic acid group or a phenylboronic acid group. 3 .3.根据权利要求2所述的微针贴片，其特征在于，所述周期性分布于所述聚合物基质内的纳米粒子为蛋白石结构，所述周期性分布于所述聚合物基质内的空穴为反蛋白石结构。3. The microneedle patch according to claim 2, wherein the nanoparticles periodically distributed in the polymer matrix have an opal structure, and the nanoparticles periodically distributed in the polymer matrix The cavity is an inverse opal structure.4.根据权利要求1-3任一项所述的微针贴片，其特征在于，所述纳米粒子为氧化锌、二氧化钛、二氧化硅、碳化硅、四氧化三铁、三氧化二铝、单分散多硫化物、碳、聚苯乙烯、由丙烯酸类单体构成的聚合物、由甲基丙烯酸类单体构成的聚合物、第一共聚物、聚氨基甲酸酯中的至少一种,其中，所述第一共聚物由苯乙烯单体、丙烯酸类单体、甲基丙烯酸类单体中的至少两种构成。4. The microneedle patch according to any one of claims 1-3, wherein the nanoparticles are zinc oxide, titanium dioxide, silicon dioxide, silicon carbide, ferric oxide, aluminum oxide, At least one of monodisperse polysulfide, carbon, polystyrene, polymer composed of acrylic monomer, polymer composed of methacrylic monomer, first copolymer, polyurethane, Wherein, the first copolymer is composed of at least two of styrene monomer, acrylic monomer and methacrylic monomer.5.根据权利要求1-3任一项所述的微针贴片，其特征在于，所述纳米粒子或空穴的尺寸为100-300nm。5 . The microneedle patch according to claim 1 , wherein the size of the nanoparticles or holes is 100-300 nm. 6 .6.根据权利要求1所述的微针贴片，其特征在于，所述空穴通过对针尖中周期性排列的纳米粒子进行刻蚀得到。6 . The microneedle patch according to claim 1 , wherein the cavities are obtained by etching the periodically arranged nanoparticles in the needle tip. 7 .7.根据权利要求1所述的微针贴片，其特征在于，所述聚合物基质为聚乙烯醇、聚丙烯酸、聚丙烯酰胺、聚乙二醇、聚甲基丙烯酸、聚乙烯基吡咯烷酮、聚乳酸、聚乙醇酸、聚氧化乙烯、聚马来酸、以上聚合物的衍生物中的至少一种。7. The microneedle patch according to claim 1, wherein the polymer matrix is polyvinyl alcohol, polyacrylic acid, polyacrylamide, polyethylene glycol, polymethacrylic acid, polyvinylpyrrolidone, At least one of polylactic acid, polyglycolic acid, polyethylene oxide, polymaleic acid, derivatives of the above polymers.8.权利要求1-7任一项所述的微针贴片的制备方法，其特征在于，所述方法包括下列步骤：8. the preparation method of the microneedle patch described in any one of claim 1-7, is characterized in that, described method comprises the following steps:(1)将纳米粒子、聚合物单体和修饰了葡萄糖响应基团的聚合物单体混合均匀后灌入微针模具，通过光引发所述聚合物单体发生聚合反应，得到针尖，该针尖包括含有葡萄糖响应基团的聚合物基质和周期性分布于所述聚合物基质中的纳米粒子；(1) Mix the nanoparticles, the polymer monomer, and the polymer monomer modified with the glucose-responsive group evenly, and then pour it into a microneedle mold, and trigger the polymer monomer to undergo a polymerization reaction by light to obtain a needle tip, and the needle tip includes a polymer matrix containing glucose-responsive groups and nanoparticles periodically distributed in the polymer matrix;或者，将纳米粒子、聚合物单体和修饰了葡萄糖响应基团的聚合物单体混合均匀后灌入微针模具，通过光引发所述聚合物单体发生聚合反应，将反应产物通过刻蚀的方法去除所述纳米粒子，得到针尖，该针尖包括含有葡萄糖响应基团的聚合物基质和周期性分布于所述聚合物基质中的空穴；Alternatively, the nanoparticles, the polymer monomer and the polymer monomer modified with the glucose-responsive group are mixed uniformly and then poured into the microneedle mold, and the polymer monomer is polymerized by light to initiate a polymerization reaction, and the reaction product is passed through the etching process. The method removes the nanoparticles to obtain a needle tip, the needle tip comprises a polymer matrix containing a glucose-responsive group and cavities periodically distributed in the polymer matrix;(2)在针尖底部涂覆基底聚合物，干燥后脱模得到所述微针贴片。(2) Coating a base polymer on the bottom of the needle tip, and demolding after drying to obtain the microneedle patch.9.权利要求1-7任一项所述的微针贴片的制备方法，其特征在于，所述方法包括下列步骤：9. the preparation method of the microneedle patch described in any one of claim 1-7, is characterized in that, described method comprises the following steps:将纳米粒子与聚合物单体混合均匀后灌入微针模具，通过光引发所述聚合物单体发生聚合反应，得到待修饰针尖，在针尖底部涂覆基底聚合物，干燥后脱模得到待修饰微针贴片，将该待修饰微针贴片放入有葡萄糖响应基团的溶液中浸泡，得到所述微针贴片，该微针贴片的针尖包括含有葡萄糖响应基团的聚合物基质和周期性分布于所述聚合物基质中的纳米粒子；Mix the nanoparticles and the polymer monomers evenly and pour them into the microneedle mold, trigger the polymerization of the polymer monomers by light to obtain the needle tip to be modified, coat the base polymer on the bottom of the needle tip, and demold it after drying to obtain the to-be-modified needle tip A microneedle patch, the microneedle patch to be modified is soaked in a solution with a glucose responsive group to obtain the microneedle patch, and the needle tip of the microneedle patch includes a polymer matrix containing a glucose responsive group and nanoparticles periodically distributed in the polymer matrix;或者，将纳米粒子与聚合物单体混合均匀后灌入微针模具，通过光引发所述聚合物单体发生聚合反应，得到待修饰针尖，在针尖底部涂覆基底聚合物，干燥后脱模得到待修饰微针贴片，将该待修饰微针贴片放入有葡萄糖响应基团的溶液中浸泡，然后通过刻蚀的方法去除所述纳米粒子，得到所述微针贴片，该微针贴片的针尖包括含有葡萄糖响应基团的聚合物基质和周期性分布于所述聚合物基质中的空穴。Alternatively, the nanoparticles and the polymer monomer are mixed uniformly and then poured into the microneedle mold, and the polymer monomer is polymerized by light to obtain the needle tip to be modified, the base polymer is coated on the bottom of the needle tip, and the mold is released after drying. The microneedle patch to be modified is soaked in a solution containing a glucose-responsive group, and then the nanoparticles are removed by etching to obtain the microneedle patch. The tip of the patch includes a polymer matrix containing glucose-responsive groups and cavities periodically distributed in the polymer matrix.10.权利要求1-7任一项所述的微针贴片的应用，其特征在于，用于构成可视化葡萄糖浓度检测的装置。10. The application of the microneedle patch according to any one of claims 1-7, characterized in that it is used to constitute a device for visualizing glucose concentration detection.

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