Glassy carbon microneedle, preparation method therefor and use thereof

Abstract

The present invention relates to the field of glassy carbon preparation, and specifically to a glassy carbon microneedle, a preparation method therefor, and a use thereof. The glassy carbon microneedle is prepared using a centralized heat preservation method, and the preparation method comprises the steps of: preparing a precursor, the precursor having a microneedle structure to be formed; placing the precursor in a heating chamber, and performing critical gradient heat preservation on the precursor in a low temperature range; and completing the final conversion to glassy carbon material by using a rapid heating process. The centralized heat preservation method provided by the present invention can effectively prevent defects such as foaming, deformation, and breakage of glassy carbon micro-needle patches, thereby optimizing the performance of glassy carbon products.

Description

Glassy carbon microneedle and its preparation method and application

[0001] Priority application

[0002] This application claims priority to Chinese invention patent application [CN2023117246296] "[A roller microneedle and its preparation method]" filed on December 14, 2023, which is incorporated by reference in its entirety. Technical Field

[0003] The present invention relates to the field of glassy carbon preparation, in particular to a glassy carbon microneedle and a preparation method and application thereof. Background Art

[0004] Microneedle products, such as microneedle patches, are composed of multiple tiny needle tips connected to a base in an array, and have a wide range of applications in disease prevention, diagnosis, rehabilitation, medical aesthetics and other fields.

[0005] Glassy carbon (also known as glassy carbon) is a type of amorphous carbon with good mechanical properties, electrical conductivity, biocompatibility, and chemical stability. Compared with commonly used polymers, metals, ceramics and other materials for preparing microneedle patches, it has some unique properties. Microneedle patches based on glassy carbon have unique applications in medicine, electronics, chemical industry and other fields. The development of products such as microneedle patches based on glassy carbon is of great significance.

[0006] Glassy carbon is usually prepared by gradient pyrolysis of a polymer precursor. The process is complicated, and the pyrolysis process will result in a large volume shrinkage, causing large product defects, such as: denaturation, foaming, cracking, breakage, etc., and it is very difficult to develop high-quality glassy carbon microneedle patches. For example, CN109627003A discloses a method for preparing a new glassy carbon material using furfural furfuryl alcohol modified resin. For another example, CN105819859A discloses a method for preparing a glassy carbon material based on a polymer prepolymer precursor. However, this process is relatively complex in terms of heating procedures, especially the need to perform several insulation treatments relatively frequently at various temperature points (which will also involve multi-stage temperature control, and the process implementation cost and monitoring difficulty are relatively large), and the process is relatively time-consuming; secondly, when preparing glassy carbon microneedle products with tiny morphology, it is extremely difficult to avoid large product defects, which will also seriously affect the morphology and performance of the glassy carbon.

[0007] Currently, research has achieved the preparation of glassy carbon microneedles; however, microneedles often need to be made into microneedle patches for convenient use and effectiveness. In particular, the conductivity and other functions of glassy carbon microneedles are highly dependent on the performance of the microneedle base. However, due to the delicate and complex structure of microneedle patches, the pyrolysis process used in glassy carbon preparation can cause severe deformation defects in conventional microneedle patches, making the development of high-quality glassy carbon microneedle patches a huge challenge.

[0008] Therefore, the development of new glassy carbon microneedle patches and efficient preparation methods has important scientific significance and significant application value. Currently, there is an urgent need for a preparation method that can improve the morphology, performance and other properties of glassy carbon microneedle patches and can control the implementation cost. Summary of the Invention

[0009] The purpose of the present invention is to provide a method for preparing glassy carbon microneedles, which partially solves or alleviates the above-mentioned deficiencies in the prior art, can improve the preparation quality of microneedles, and reduce the preparation cost. In order to solve the above-mentioned technical problems, the present invention specifically adopts the following technical solutions: On the one hand, the present invention provides a method for preparing glassy carbon microneedles, which comprises the steps of:

[0010] A precursor is prepared by using a carbon-based polymer raw material, wherein the precursor has a microneedle or microneedle-like structure;

[0011] The precursor is placed in a heating box and a centralized heat preservation method is started; and the step of starting the centralized heat preservation method includes: selecting a stress relief temperature to heat-treat the precursor in a first heating stage to relieve stress in the precursor; wherein the stress relief temperature is selected according to a first selection rule; and the first selection rule is: selecting the stress relief temperature from the weight loss rate fluctuation temperature; and the weight loss rate fluctuation temperature corresponds to the temperature value corresponding to the data point with the largest curvature change in the range less than the pyrolysis carbonization temperature in the thermogravimetric differential curve;

[0012] The temperature is raised to enter a second heating stage, and in the second heating stage, the precursor is again kept warm at the pyrolysis carbonization temperature to cause the precursor to undergo pyrolysis carbonization. At this time, the microneedles or the microneedle-like structure shrinks during the pyrolysis carbonization process; wherein the pyrolysis carbonization temperature is selected according to a second selection rule; wherein the second selection rule is: selecting the pyrolysis carbonization temperature from the weight loss fluctuation temperature; wherein the weight loss fluctuation temperature corresponds to the temperature value corresponding to the curve segment with the largest curvature change within the interval where the slope of the thermogravimetric analysis curve gradually decreases;

[0013] In the subsequent third heating stage, the temperature is continuously raised from the pyrolysis carbonization temperature to the target heating temperature, and finally the precursor prepared from the carbon-based polymer is converted into glassy carbon microneedles.

[0014] Furthermore, the present invention provides a glassy carbon microneedle patch, comprising: a main body, and a hollow area that may be provided in the main body; the main body comprises: a gridded substrate, a plurality of grid holes are arranged at intervals on the gridded substrate, and a plurality of microneedles or microneedle-like structures are arranged on the edges of the grid holes; wherein, the glassy carbon microneedle patch is prepared by subjecting a gridded precursor to centralized heat-insulating pyrolysis treatment, and the gridded precursor is prepared from a carbon-based polymer.

[0015] In some embodiments, the mesh pores in the meshed precursor have a line width L1 less than or equal to 2 mm, and the body has a radius L2 less than or equal to 100 mm. In some embodiments, the body can have one or more of the following shapes: circular, annular, elliptical, rounded rectangular, or regular polygonal. In some embodiments, the base of the microneedle-like structure can have one or more of the following shapes: circular, rectangular, cross-shaped, or 'P'-shaped.

[0016] The present invention also provides a method for preparing a glassy carbon microneedle patch, wherein the centralized heat preservation step comprises: S20 placing the gridded precursor in a heating box and starting the centralized heat preservation method; and S20 includes:

[0017] S21 selects a stress relief temperature to perform insulation treatment on the gridded precursor in the first heating stage to relieve stress on the gridded precursor; wherein, the stress relief temperature is selected by a first selection rule; and the first selection rule is: select the stress relief temperature from the weight loss rate fluctuation temperature; and the weight loss rate fluctuation temperature corresponds to the temperature value corresponding to the data point with the largest curvature change in the thermogravimetric differential curve within the range less than the pyrolysis carbonization temperature.

[0018] In some embodiments, S20 also includes: S22 heating to enter the second heating stage, and selecting the pyrolysis carbonization temperature to keep the grid precursor insulated again in the second heating stage to make the grid precursor undergo pyrolysis carbonization. At this time, the microneedles or microneedle-like structures to be formed on the grid precursor and the grid holes shrink proportionally during the pyrolysis carbonization process, and the impurities generated can be evenly discharged outward using the grid arrangement; wherein, the pyrolysis carbonization temperature is selected by the second selection rule; the second selection rule is: selecting the pyrolysis carbonization temperature from the weight loss fluctuation temperature; wherein, the weight loss fluctuation temperature corresponds to the temperature value corresponding to the curve segment with the largest curvature change in the interval where the slope of the thermogravimetric analysis curve gradually decreases.

[0019] That is to say, in some embodiments of the present invention, only one heat preservation treatment can be used for the low temperature range, for example, only one pyrolysis carbonization treatment is performed. Moreover, it has been verified through experiments that only one low temperature heat preservation treatment is performed, and the microneedles finally prepared also have good morphology. For example, in some embodiments, the preparation method of glassy carbon microneedles provided by the present invention includes: heating to enter the second heating stage, and selecting the pyrolysis carbonization temperature to perform heat preservation treatment on the precursor again in the second heating stage, so that the precursor is pyrolyzed and carbonized. At this time, the microneedles or microneedle-like structures to be formed shrink proportionally during the pyrolysis carbonization process, and the impurities generated can be discharged evenly to the outside; wherein, the pyrolysis carbonization temperature is selected by the second selection rule; the second selection rule is: selecting the pyrolysis carbonization temperature from the weight loss fluctuation temperature; wherein, the weight loss fluctuation temperature corresponds to the temperature value corresponding to the curve segment with the largest curvature change in the interval where the slope of the thermogravimetric analysis curve gradually decreases.

[0020] In some embodiments, it also includes: S30 in the subsequent third heating stage, continuously heating from the pyrolysis carbonization temperature to the target heating temperature; and finally converting the precursor prepared from the carbon-based polymer into glassy carbon microneedles (such as converting the gridded precursor into a microneedle patch).

[0021] In some embodiments, the method further includes: in the third heating stage, selecting a target heating temperature to perform heat preservation treatment on the precursor again.

[0022] In some embodiments, it also includes: during the heating stage of the (gridized) precursor, an inert gas is introduced into the heating box to protect the precursor, and impurities generated during the heating stage can be discharged; and the concentration index of the impurities is collected by a gas monitoring device.

[0023] In some embodiments, it also includes: in the third heating stage, when the concentration index of the impurity is monitored to be lower than the set concentration range, a conversion moment is selected according to the current moment, wherein the difference between the conversion moment and the current moment is less than the set difference range; at the conversion moment, the current first heating rate is increased to the second heating rate, and the temperature is continued to rise to the target heating temperature.

[0024] In some embodiments, the carbon-based polymer includes: a carbon-rich polymer, and the carbon-rich polymer includes one or more of the following: polyurethane, epoxy resin, phenolic resin, polyacrylonitrile, polyimide, polystyrene, polytetrafluoroethylene, polyethylene, polyaniline, or a product obtained by further modification of the carbon-rich polymer; and / or, the preparation method of the gridded precursor includes: mold molding, and / or 3D printing.

[0025] On the other hand, the present invention also provides a method for preparing glassy carbon microneedles, wherein the glassy carbon is prepared by a centralized heat preservation method based on a gridded precursor. Accordingly, the method comprises the steps of: S10 preparing a precursor using a carbon polymer raw material, for example, it can be a gridded precursor, and the gridded precursor includes a plurality of grid holes arranged at intervals, the grid holes intersecting each other to form a grid arrangement, and microneedles or microneedle-like structures to be formed are provided at the edges of the grid holes; S20 placing the gridded precursor in a heating box and starting the centralized heat preservation method, S20 including:

[0026] S21: In the first heating stage, a stress relief temperature is selected to perform heat preservation treatment on the grid precursor to relieve stress on the grid precursor; wherein, the stress relief temperature is selected by the first selection rule; S22: The temperature is raised to enter the second heating stage, and in the second heating stage, a pyrolysis carbonization temperature is selected to perform heat preservation treatment on the grid precursor again to pyrolysis carbonize the grid precursor. At this time, the target to be formed on the grid precursor and the grid holes shrink in proportion during the pyrolysis carbonization process, and the impurities generated can be evenly discharged outwards by using the grid arrangement; wherein, the pyrolysis carbonization temperature is selected by the second selection rule. The method is to select the temperature by taking the rule; S30 in the subsequent third heating stage, continuously raise the temperature from the pyrolysis carbonization temperature to the target heating temperature; finally, the carbon polymer is converted into glassy carbon; wherein, the first selection rule is: select the stress relief temperature from the weight loss rate fluctuation temperature; and the weight loss rate fluctuation temperature corresponds to the temperature value corresponding to the data point with the largest curvature change in the interval less than the pyrolysis carbonization temperature in the thermogravimetric differential curve; the second selection rule is: select the pyrolysis carbonization temperature from the weight loss fluctuation temperature; wherein, the weight loss fluctuation temperature corresponds to the temperature value corresponding to the curve segment with the largest curvature change in the interval where the slope of the thermogravimetric analysis curve gradually decreases.

[0027] In some embodiments, when there is a first number of weight loss rate fluctuation temperatures, and the first number is greater than or equal to 2, the S21 includes the steps of:

[0028] A second number of weight loss rate fluctuation temperatures are intermittently selected from the first number of weight loss rate fluctuation temperatures, and a second number of stress relief temperatures are correspondingly obtained, the second number being less than or equal to the first number, and the stress relief temperatures at least including: a first stress relief temperature and a second stress relief temperature; in the first heating stage, the first stress relief temperature is used for heat preservation treatment, thereby performing the first stress relief on the gridded precursor; the temperature is continuously raised from the first stress relief temperature to the second stress relief temperature for heat preservation treatment, thereby performing the second stress relief on the gridded precursor.

[0029] In some embodiments, the steps are further included: during the heating stage of the gridded precursor, an inert gas is introduced into the heating box to discharge the impurities out of the heating box through an exhaust pipe; and the concentration index of the impurities is collected by a gas monitoring device connected to the exhaust pipe.

[0030] In some embodiments, the following steps are further included: in the third heating stage, when the concentration index of the impurity is monitored to be lower than the set concentration range, a conversion moment is selected according to the current moment, wherein the difference between the conversion moment and the current moment is less than the set difference range; at the conversion moment, the current first heating rate is increased to the second heating rate, and the temperature is continued to rise to the target heating temperature.

[0031] Furthermore, in some embodiments, S10 includes: providing a carbon-rich photopolymer material as a raw material, and obtaining process parameters for preparing the gridded precursor based on the photopolymer material, the process parameters including one or more of the following: the line width of the grid holes, the radius of the main body, the size of the target to be formed, and the thickness of the gridded precursor; inputting the process parameters into a 3D printing system based on photopolymerization, and discretizing and stacking the photopolymer material through the 3D printing system to obtain a corresponding gridded precursor.

[0032] In some embodiments, the carbon-based polymer includes: (1) a carbon-rich polymer, wherein the carbon-rich polymer includes one or more of the following: furan resin, furfuryl alcohol resin, furfuryl ketone resin, phenol, aldehyde resin, epoxy resin, polyurethane, polyimide, polyethylene glycol, acrylic resin, polylactic acid, polycaprolactone, polyethylene, polyetheretherketone, nylon, polycarbonate, polymethyl methacrylate, polyvinyl butyral, polyethylene terephthalate, polyacrylonitrile, polyvinylidene fluoride, polyvinylidene chloride, polystyrene, polytetrafluoroethylene, polybutadiene, polyphenylene oxide, polyphenylene sulfide, polybutene-1, polybenzimidazole, polyaryletherketone, polyarylsulfone, polynaphthalate Ethylene glycol ester, polyaniline, polyacetylene, poly(p-phenylene), polyphthalimide, poly(phenylene vinylene), polylactide, polychloroprene, cyanoacrylate, polynaphthylene vinylene, poly(p-xylene), polymethylphenylsiloxane, liquid crystal polymer, polythiophene, polyvinyl acetylene, polyoxadiazole, polybisphenol A, polyacrylonitrile-butadiene-styrene copolymer, polychlorotrifluoroethylene, polyepoxy-acrylate copolymer, polybenzoquinone, poly(p-phenylene sulfone), polyphenylene, polybenzoxazole, polypiperidine, polyvinyl acetal, polybenzothiazole and polyvinyl pyrrolidone; or (2) products obtained by further modification and / or modification of the carbon-rich polymer.

[0033] In some embodiments, the preparation method of the precursor includes: mold forming, and / or 3D printing. In some embodiments, the 3D printing method is: laser stereolithography, two-photon polymerization, digital light processing, liquid crystal display polymerization, continuous liquid interface manufacturing, fused deposition modeling, selective laser sintering, computer axial lithography, powder bonding molding, electric field direct writing, inkjet direct writing or static light projection printing. In some embodiments, the base of the microneedle or the microneedle-like structure can be in one or more of the following shapes: circular, rectangular, cross-shaped, M-shaped, hollow structure. In some embodiments, the precursor has a substrate, and the substrate is arranged with a plurality of microneedles or microneedle-like structures at intervals; or, the precursor is a microneedle particle. In some embodiments, the substrate includes a plurality of grid holes arranged at intervals, the grid holes intersect each other to form a grid arrangement, and the microneedles or the microneedle-like structures to be formed are arranged at the edges of the grid holes.

[0034] In some embodiments, the substrate comprises: a main body having a hollow area therein; a plurality of mesh holes spaced apart on the main body, wherein the main body can be in one or more of the following shapes: circular, annular, elliptical, or rounded rectangular. In some embodiments, the line width L1 of the mesh holes is less than or equal to 2 mm, and the radius L2 of the main body of the precursor is less than or equal to 100 mm. The present invention also provides a glassy carbon microneedle, which is prepared by the method described in any one of the present inventions.

[0035] Beneficial technical effects: Glassy carbon materials usually adopt a high-temperature sintering process with full-process gradient insulation (for example, it not only needs to be repeatedly insulated in the low-temperature range to reduce the heating rate, but it often needs to be heated to a high temperature of about a thousand degrees for insulation, such as a temperature of about 1000°C, etc.). On the contrary, the present invention proposes a centralized insulation treatment process that can complete the preparation of complex carbon microneedles (such as microneedle particles, or microneedle patches) only through a limited number of low-temperature insulations. And in the centralized treatment link, insulation treatment is directly guided by technical results. That is, directly with stress elimination or pyrolysis and carbonization as the goal, targeted insulation treatment is used to directly achieve the purpose of stress elimination or pyrolysis and carbonization. Thereby reducing the influence of the heating rate on the deformation of the precursor in the subsequent heating stage, so that the subsequent heating stage (such as the third heating stage) can be heated to the target heating temperature as soon as possible without relying on insulation treatment, thereby simplifying the heating process. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following is a brief introduction to the drawings required for the embodiments or the description of the prior art. In all drawings, similar elements or parts are generally identified by similar reference numerals. In the drawings, the various elements or parts are not necessarily drawn according to the actual scale. Obviously, the drawings described below are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can also be obtained based on these drawings without inventive work.

[0037] FIG1 is a schematic flow diagram of a centralized heat preservation method according to an exemplary embodiment of the present invention;

[0038] FIG2 a is a schematic diagram of temperature design of a centralized heat preservation method according to an exemplary embodiment of the present invention;

[0039] FIG2 b is a schematic diagram of temperature design of a centralized heat preservation method in another exemplary embodiment of the present invention;

[0040] FIG3 is a schematic diagram of a thermogravimetric curve of a precursor in an exemplary embodiment of the present invention;

[0041] FIG4 is a schematic diagram of the structure of a gridded microneedle in an exemplary embodiment of the present invention;

[0042] FIG5 is a schematic diagram of the surface morphology of a gridded precursor after pyrolysis treatment by a centralized heat preservation method in an exemplary embodiment of the present invention;

[0043] FIG6 is a schematic structural diagram of a gridded precursor in an exemplary embodiment of the present invention;

[0044] FIG7 is a schematic diagram showing the effect of different heating temperatures on the conductive properties of the meshed microneedles;

[0045] Figure 8 is a schematic diagram of a failed product;

[0046] FIG9 is a schematic diagram of modules of a monitoring system according to an exemplary embodiment of the present invention;

[0047] FIG10 is a schematic diagram of the structure of a microneedle in an exemplary embodiment of the present invention;

[0048] FIG11 is a first physical photograph of the sintered microneedle shown in FIG10 ;

[0049] FIG12 is a second physical photograph of the sintered microneedle shown in FIG10 ;

[0050] FIG13 is a schematic diagram of temperature design of a heat preservation method applicable to the microneedle shown in FIG10 ;

[0051] FIG14 is a schematic structural diagram of a needle roller precursor in an exemplary embodiment of the present invention;

[0052] FIG15 is a side view of the precursor shown in FIG14.

[0053] Figure numerals: 01 is the main body, 011 is the microneedle, 012 is the mesh hole, and 02 is the hollow area. DETAILED DESCRIPTION

[0054] To further clarify the objectives, technical solutions, and advantages of the embodiments of the present invention, the technical solutions of the embodiments of the present invention will be described in detail below, in conjunction with the accompanying drawings. It should be understood that the described embodiments represent only a portion of the embodiments of the present invention, and not all of them. All other embodiments derived by persons of ordinary skill in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention. The use of suffixes such as "module," "component," or "unit" to designate components herein is solely for the purpose of facilitating the description of the present invention and does not inherently have specific meanings. Therefore, "module," "component," or "unit" may be used interchangeably. Terms such as "upper," "lower," "inner," "outer," "front," "rear," "one end," and "the other end" herein, indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings and are intended solely to facilitate and simplify the description of the present invention. They are not intended to indicate or imply that the devices or components referred to must have, be constructed, or operate in a specific orientation, and are therefore not to be construed as limiting the present invention. Furthermore, the terms "first" and "second" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.

[0055] As used herein, unless otherwise expressly specified or limited, the terms "installed," "provided with," "connected," etc., should be understood broadly. For example, "connected" can mean fixed, removable, or integral; it can mean mechanical, direct, or indirect through an intermediary, or it can mean internal communication between two components. Those skilled in the art will understand the specific meanings of the above terms in the present invention on a case-by-case basis. As used herein, "and / or" includes any and all combinations of one or more of the listed items. As used herein, "plurality" means two or more, i.e., including two, three, four, five, etc. It should be noted that, as used herein, the terms "comprise," "include," or any other variations thereof are intended to encompass non-exclusive inclusion, such that a process, method, article, or apparatus comprising a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus. Without further limitation, an element specified by the phrase "comprises a..." does not preclude the presence of additional identical elements in the process, method, article, or apparatus comprising that element.

[0056] As used in this specification, the term "about" typically means + / - 5% of the stated value, more typically + / - 4% of the stated value, more typically + / - 3% of the stated value, more typically + / - 2% of the stated value, even more typically + / - 1% of the stated value, and even more typically + / - 0.5% of the stated value. In this specification, certain embodiments may be disclosed in a format that is within a range. It should be understood that such "within a range" description is merely for convenience and brevity and should not be interpreted as a rigid limitation on the disclosed range. Therefore, the description of a range should be considered to have specifically disclosed all possible subranges and individual numerical values ​​within that range. For example, the description of a range of 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as individual numbers within that range, such as 1, 2, 3, 4, 5, and 6. The above rules apply regardless of the breadth of the range. As used herein, a “data point” may refer to a segment of data corresponding to one or more temperature points.

[0057] Herein, "carbon-based polymer" generally refers to a carbon-rich polymer. For example, it can be a light-curing polymer material such as polyurethane, epoxy resin, or a polymer such as acrylonitrile resin, phenolic resin or polyimide. For example, the carbon-rich polymer in the present invention can include one or more of the following polymers: furan resin, furfuryl alcohol resin, furfural resin, phenol, aldehyde resin, epoxy resin, polyurethane, polyimide, polyethylene glycol, acrylic resin, polylactic acid, polycaprolactone, polyethylene, polyetheretherketone, nylon, polycarbonate, polymethyl methacrylate, polyvinyl butyral, polyethylene terephthalate, polyacrylonitrile, polyvinylidene fluoride, polyvinylidene chloride, polystyrene, polytetrafluoroethylene, polybutadiene, polyphenylene ether, polyphenylene sulfide, polybutene-1, polybenzimidazole, polyaryletherketone ... Sulfone, polyethylene naphthalate, polyaniline, polyacetylene, poly(p-phenylene), polyphthalimide, polyphenylene acetylene, polylactide, polychloroprene, cyanopolyacrylate, polynaphthalene acetylene, poly(p-xylene), polymethylphenylsiloxane, liquid crystal polymer, polythiophene, polyvinyl acetylene, polyoxadiazole, polybisphenol A, polyacrylonitrile-butadiene-styrene copolymer, polychlorotrifluoroethylene, polyepoxy-acrylate copolymer, polybenzoquinone, poly(p-phenylene sulfone), polyphenylene, polybenzoxazole, polypiperidine, polyvinyl acetal, polybenzothiazole and polyvinyl pyrrolidone. Alternatively, the carbon-rich polymer can also refer to a product further modified based on one or more of the above polymers. For example, the modification method can be one or more of the following: blending modification, filling modification, reinforcement modification, physical / chemical crosslinking modification, graft copolymerization modification, nanocomposite modification, enzyme catalysis modification, and chemical modification. The precursor or the glassy carbon microneedles prepared from the precursor can also be modified. The modification methods used may include one or more of the following: chemical modification, physical vapor deposition, laser surface modification, chemical vapor deposition, spraying, sputtering, etching, surface roughness treatment, electrochemical treatment or plasma treatment. Modification methods can also be used to modify the glassy carbon microneedles.

[0058] As used herein, a "concentration index" refers to an indicator that can be used to characterize the quantity / concentration of a substance (e.g., an impurity). For example, in some embodiments, the concentration index can be characterized by the impurity flow rate per unit time; or, in other embodiments, by the amount of impurities discharged per unit time; or, in yet other embodiments, by the impurity concentration per unit gas.

[0059] In this article, "grid material" is also called "grid precursor", which refers to a material with multiple grid holes (or openings) distributed on the material plane, and a target to be formed (such as a microneedle) is provided at the edge of the grid hole. Such grid holes can be arranged on the material plane to form a regular grid distribution. Among them, the preparation method that can form grid holes on the precursor is called a grid preparation method, and the grid preparation method in this article is preferably a 3D printing method.

[0060] Glassy carbon materials usually adopt a high-temperature sintering process with full-process gradient insulation (for example, it is often necessary to heat to a high temperature of about a thousand degrees for insulation, such as a temperature of about 1000°C, etc.). In this article, the "centralized insulation process", also known as the low-temperature gradient insulation process, refers to the relatively concentrated insulation treatment of the key processes (such as stress relief and pyrolysis carbonization) of the microneedle structure (such as the grid precursor). And in the centralized treatment link, the insulation treatment is directly guided by the technical results. That is, with stress relief and pyrolysis carbonization as the goal, targeted insulation treatment is used to directly achieve the purpose of stress relief and pyrolysis carbonization. Thereby reducing the influence of the heating rate on the deformation of the precursor in the subsequent heating stage, so that the subsequent heating stage (such as the third heating stage) can be heated to the target heating temperature as soon as possible without relying on the insulation treatment, thereby simplifying the heating process.

[0061] In other words, the centralized heat preservation method based on the microneedle structure provided by the present invention is different from the procedure of setting the heat preservation treatment in a dispersed manner in the low temperature range and the high temperature range. It directly aims to eliminate stress or pyrolysis carbonization, and specifically achieves the treatment requirements in the low temperature range through a limited number of heat preservations (even being able to achieve the purpose under one, two or three heat preservation treatments). And this centralized heat preservation treatment design in the low temperature range also unexpectedly makes the glassy carbon preparation get rid of the dependence on high temperature heat preservation treatment. For example, when preparing a simpler microneedle particle structure, the preparation of microneedle particles can also be achieved under a limited number of low temperature insulations (such as one low temperature heat preservation treatment) to reduce the dependence on high temperature heat preservation treatment. As shown in Figures 11 to 13, even if only one low temperature insulation is performed, a microneedle structure with better morphology can still be prepared.

[0062] It should be understood that the centralized heat preservation treatment in the present invention has the following advantages: 1) It can reduce the dependence on high-temperature heat preservation treatment (for example, it can reduce the temperature of high-temperature heat preservation, or it can reduce the time of high-temperature heat preservation), but it does not limit the user to perform high-temperature heat preservation treatment. For example, according to the different forms of microneedle products, such as microneedle particles, users can still freely choose whether to add a high-temperature heat preservation process. 2) It can reduce the necessary number of low-temperature heat preservation treatments, but it can be understood that according to the process requirements of different microneedle products (such as strength requirements), users can still freely choose to use more times, such as two or three low-temperature heat preservation treatments, to complete the preparation of microneedle products.

[0063] Moreover, experiments have shown that glassy carbon products (such as microneedles or microneedle patches) obtained by centralized heat preservation methods can still achieve good quality (i.e., defects such as foaming, breakage, and deformation are effectively controlled).

[0064] Herein, "insulation treatment" refers to placing an object (such as a precursor) in an environment with a set insulation temperature and maintaining the insulation temperature for at least a period of time. For example, the insulation time can be at least about 5 minutes, at least about 10 minutes, at least about 30 minutes, at least about 60 minutes, or at least about 90 minutes. "Maintain" means that the degree of temperature fluctuation is less than a set proportional threshold, such as the proportional threshold can be set to about 1%, about 2%, about 3%, about 4%, about 5%, and so on. For example, the degree of fluctuation can be characterized by the fluctuation ratio (fluctuation ratio = the difference between the actual temperature and the set insulation temperature / the set insulation temperature). Of course, it is understandable that the actual insulation time and the set proportional threshold can be adaptively adjusted according to the type of material and the shape of the precursor.

[0065] As shown in Figure 2b, the "rapid heating process" herein refers to the third heating stage (i.e., after the pyrolysis carbonization heat preservation treatment), in which a continuous, rapid heating method (e.g., without the need for further heat preservation treatment at multiple high temperature intervals such as 600°C and 1000°C) can be used to achieve the final transformation of material properties and produce high-purity glassy carbon. For example, the rapid heating rate can be greater than or equal to about 0.5°C / min, and can even reach a heating rate of about 2°C / min after the speed change.

[0066] Microneedles (MN) are a new type of physical penetration-promoting technology. For example, it can be composed of a plurality of micron-sized tiny needle tips connected in an array on a base. For another example, as shown in Figure 10, it can also be an independent microneedle particle. Specifically, the shape of the "microneedle" on the microneedle patch is usually conical, and the top of the cone is the needle tip, and it can pierce the skin to a certain extent (for example, pierce the stratum corneum). The "microneedle-like structure" refers to other similar morphological designs that also have needle tips that can pierce the skin. For example, the bottom of the microneedle-like structure can be a variety of designs such as circular, square, cross-shaped, rice-shaped, hollow structure, and a needle tip is formed at its top. Among them, the microneedle can be a nano-sized microneedle or a micron-sized microneedle, etc.

[0067] Herein, a glassy carbon microneedle patch is provided, which includes: a main body, and a hollow area that may be provided in the main body; the main body includes: a gridded substrate, a plurality of grid holes are provided at intervals on the gridded substrate, and a plurality of microneedles or microneedle-like structures are provided at the edges of the grid holes; wherein, the glassy carbon microneedle patch is prepared by subjecting a gridded precursor to centralized heat-insulating pyrolysis treatment, and the gridded precursor is prepared from a carbon-based polymer.

[0068] Example 1

[0069] As shown in Figures 1 to 7, in order to reduce defects such as foaming caused by the sintering process of glassy carbon products (such as microneedle structures, microneedle particles as shown in Figure 10, or microneedle patches as shown in Figure 6), the present invention provides a method for preparing glassy carbon, which includes:

[0070] A precursor is prepared by using a carbon-based polymer raw material, wherein the precursor has a microneedle or microneedle-like structure;

[0071] The precursor is placed in a heating box and a centralized heat preservation method is started; and the step of starting the centralized heat preservation method includes: selecting a stress relief temperature to heat-treat the precursor in a first heating stage to relieve stress in the precursor; wherein the stress relief temperature is selected according to a first selection rule; and the first selection rule is: selecting the stress relief temperature from the weight loss rate fluctuation temperature; and the weight loss rate fluctuation temperature corresponds to the temperature value corresponding to the data point with the largest curvature change in the range less than the pyrolysis carbonization temperature in the thermogravimetric differential curve;

[0072] The temperature is raised to enter a second heating stage, and in the second heating stage, the precursor is again kept warm at the pyrolysis carbonization temperature to cause the precursor to undergo pyrolysis carbonization. At this time, the microneedles or the microneedle-like structure shrinks during the pyrolysis carbonization process; wherein the pyrolysis carbonization temperature is selected according to a second selection rule; wherein the second selection rule is: selecting the pyrolysis carbonization temperature from the weight loss fluctuation temperature; wherein the weight loss fluctuation temperature corresponds to the temperature value corresponding to the curve segment with the largest curvature change within the interval where the slope of the thermogravimetric analysis curve gradually decreases;

[0073] In the subsequent third heating stage, the temperature is continuously raised from the pyrolysis carbonization temperature to the target heating temperature, and finally the precursor prepared from the carbon-based polymer is converted into glassy carbon microneedles.

[0074] The preparation method is exemplified below by taking a gridded precursor as an example: the glassy carbon is prepared by a centralized heat preservation method based on the gridded precursor. Accordingly, the method comprises the steps of:

[0075] S10: A gridded precursor is prepared using a carbon-based polymer raw material, wherein the gridded precursor includes a plurality of grid holes arranged at intervals, wherein the grid holes form a grid arrangement, wherein a plurality of objects to be formed are arranged at the edges of the grid holes.

[0076] For example, in some embodiments, targets to be formed are provided at the intersections of the grid holes.

[0077] For another example, in some embodiments, the objects to be formed may be arranged at intervals along the edges of the grid holes.

[0078] S20 places the gridded precursor in a heating box and starts the centralized heat preservation method. S20 includes:

[0079] S21: performing a heat preservation treatment on the meshed precursor at a stress relief temperature in the first heating stage to relieve stress in the meshed precursor; wherein the stress relief temperature is selected according to a first selection rule;

[0080] S22: The temperature is raised to enter the second heating stage, and the gridded precursor is again kept warm at a pyrolysis carbonization temperature in the second heating stage to allow the gridded precursor to be pyrolyzed and carbonized. At this time, the target to be formed on the gridded precursor and the grid holes shrink and deform during the pyrolysis and carbonization process, and impurities generated during the process can be uniformly discharged outwards by utilizing the grid arrangement; the temperature of the second heating stage is higher than the temperature of the first heating stage; wherein the pyrolysis and carbonization temperature is selected according to the second selection rule;

[0081] In the subsequent third heating stage, S30 , the temperature is continuously raised from the pyrolysis temperature to the target heating temperature; and finally the carbon polymer is converted into glassy carbon.

[0082] In some embodiments, the first selection rule is: selecting the stress relief temperature from the weight loss rate fluctuation temperature (equivalent to the recommended temperature); wherein the weight loss rate fluctuation temperature corresponds to one or more temperature values ​​corresponding to at least one curve segment (or data point) with the largest curvature change in a thermogravimetric differential curve (e.g., a DTG curve, as shown in the second curve of FIG3 ); and the weight loss rate fluctuation temperature is often lower than the pyrolysis temperature. The thermogravimetric differential curve represents a curve showing how the rate of weight change changes with temperature.

[0083] For example, taking the DTG curve as an example, the following exemplary selection rules for the stress relief temperature are described:

[0084] A DTG curve of the precursor is obtained, where the DTG curve is considered to be composed of multiple curve segments. At this point, the curvature change value of each curve segment before the pyrolysis temperature (for example, before approximately 350°C in this example) can be calculated (for example, when a curve segment involves multiple data points, the average curvature change value of each data point can be calculated), and the temperature value corresponding to the curve segment with the largest curvature change is selected as the weight loss rate fluctuation temperature.

[0085] Alternatively, in other embodiments, the user may pre-set a screening threshold, from which a finite number (e.g., 1, 2, etc.) of curve segments are screened out, and a finite number of optional weight loss rate fluctuation temperatures are correspondingly provided, wherein the curvature change value of the selected curve segment falls within the screening threshold.

[0086] In some embodiments, if multiple weight loss rate fluctuation temperatures are present, it is preferable to perform two heat treatments for stress relief. For example, if multiple weight loss rate fluctuation temperatures are present, two (or more) stress relief temperatures may be selected from the multiple weight loss rate fluctuation temperatures at intervals to avoid frequent heat treatments within a single temperature interval.

[0087] The second selection rule for selecting the pyrolysis temperature is to select the pyrolysis temperature from the weight loss fluctuation temperature (equivalent to the recommended temperature); wherein the weight loss fluctuation temperature corresponds to one or more temperature values ​​corresponding to the curve segment with the largest change in curvature within the range of gradually decreasing slope of a thermogravimetric analysis curve (e.g., a TGA curve). The thermogravimetric analysis curve represents the relationship between weight change and temperature and is also called a thermal gravimetric loss curve.

[0088] For example, taking the TGA curve (as shown in the first curve) as an example, the selection of the pyrolysis temperature is exemplified:

[0089] The TGA curve can also be considered as consisting of several curve segments. In the interval where its slope gradually decreases (for example, the interval before approximately 425°C), the curve segment with the largest slope change is selected, and the corresponding temperature is the weight loss fluctuation temperature. The pyrolysis temperature selected is approximately 350°C.

[0090] For example, in some embodiments, the temperature corresponding to a data point with the largest curvature change in the thermogravimetric analysis curve (i.e., the slope difference between the current data point and the previous data point is the largest compared to the slope difference between any two adjacent data points in the curve) can also be selected as the weight loss fluctuation temperature.

[0091] In this embodiment, only one insulation treatment for stress relief can be used in combination with one insulation treatment for pyrolysis and carbonization, so that the precursor can undergo relatively concentrated deformation at a relatively low pyrolysis and carbonization temperature (for example, in Verification Example 1, insulation treatment is only performed within 350°C), thereby reducing the influence of the heating rate in the third heating stage on the deformation of the precursor.

[0092] Of course, in other embodiments, in order to achieve more uniform stress relief and avoid improper deformation during stress relief, when there is a first number of weight loss rate fluctuation temperatures, and the first number is greater than or equal to 2, the S21 includes the steps of:

[0093] A second number of weight loss rate fluctuation temperatures are intermittently selected from the first number of weight loss rate fluctuation temperatures, and a second number of stress relief temperatures are correspondingly obtained (for example, a stress relief temperature is correspondingly set for each weight loss rate fluctuation temperature), the second number is less than or equal to the first number, and the stress relief temperatures at least include: a first stress relief temperature, a second stress relief temperature; in the first heating stage, the first stress relief temperature is used for heat preservation treatment, thereby performing the first stress relief on the gridded precursor; the temperature is continuously raised from the first stress relief temperature to the second stress relief temperature for heat preservation treatment, thereby performing the second stress relief on the gridded precursor.

[0094] Therefore, in this embodiment, in the case where stress elimination is difficult, multiple heat preservation treatments can also be used to eliminate stress.

[0095] Furthermore, it is understandable that the stress relief temperature (or pyrolysis carbonization) of the material is not a single temperature value, and as the material type or external processing conditions change, those skilled in the art can flexibly adjust the actual stress relief temperature or pyrolysis carbonization temperature according to the actual situation based on the weight loss rate fluctuation temperature or the weight loss fluctuation temperature.

[0096] For example, in some embodiments, the stress relief temperature has a certain deviation from the given weight loss rate fluctuation temperature (eg, the deviation is within ±1° C., ±5° C., ±10° C., ±15° C., etc.).

[0097] Of course, in actual application, the weight loss rate fluctuation temperature or weight loss fluctuation temperature can also be obtained from existing thermogravimetric analysis related data, as long as the purpose of stress elimination and pyrolysis and carbonization is achieved.

[0098] For example, in some embodiments, after heating to the target heating temperature, the heat preservation treatment may no longer be performed, so that the microneedles can cool down naturally in the heating box.

[0099] Alternatively, in other embodiments, after heating to the target temperature, the user may also selectively perform heat preservation treatment based on the actual product form or product strength requirements, and the present invention does not impose any restrictions on this.

[0100] In some embodiments, the precursor has a substrate, and the substrate is arranged with a plurality of microneedles or microneedle-like structures at intervals. For example, when the precursor is a grid precursor, it includes a plurality of grid holes arranged at intervals on the substrate (also referred to as: main body), the grid holes intersecting each other to form a grid arrangement, and the microneedles or microneedle-like structures to be formed are arranged at the edges of the grid holes. Alternatively, the precursor can also be microneedle particles.

[0101] In some embodiments, S30 includes the following steps: S31 obtaining conversion information for switching the heating rate, the conversion information including: a switching temperature C4 and / or a switching time; S32 when heating from the pyrolysis temperature C2 at the first set sub-rate VIII-1 to the switching temperature C4, or when the heating time is at the switching time, switching the heating rate from the first set sub-rate VIII-1 to the second set sub-rate VIII-2; S33 heating to the target heating temperature C5 at the second set sub-rate VIII-2; wherein the second set sub-rate VIII-2 is greater than the first set sub-rate VIII-1.

[0102] In some embodiments, the setting range of the first setting sub-speed VIII-1 is approximately 0.1-1°C / min, and the setting range of the second setting sub-speed VIII-2 is approximately 1-3°C / min.

[0103] To improve the quality of glassy carbon (e.g., reducing defect area and increasing strength), the present invention proposes a centralized heat preservation method based on a gridded precursor. Unlike existing full-process gradient heat preservation processes, the present invention designs the following preparation stages for glassy carbon production: (1) a gridded preparation stage; (2) a technically driven, centralized stress relief and pyrolysis carbonization directly at low temperatures; and (3) a continuous heating method to directly reach the target heating temperature.

[0104] The present invention adopts the mutual coordination of stages (1)-(3), which can not only effectively improve the uniformity of the stress relief process of the precursor during the heating stage (avoiding cracks or adverse deformation caused by stress), but also alleviate the surface damage that may be caused by major deformation processes such as pyrolysis and carbonization of the material and continuous heating.

[0105] Furthermore, the present invention, through a gridded design combined with a centralized heat preservation method, minimizes the effect of the heating method (e.g., speed) on the precursor's deformation during the high-temperature stage. This eliminates the reliance on high-temperature heat preservation treatment and reduces process costs. Furthermore, experimental verification, such as that shown in Figure 5, shows that defects such as blistering, deformation, or breakage on the microneedle patch surface are minimal.

[0106] Furthermore, in order to facilitate the industrial application of the centralized insulation method, the temperature of each insulation treatment for the low-temperature insulation of the gridded precursor can be directly obtained from the thermogravimetric analysis data to assist users in quickly exploring the preparation conditions for the low-temperature gradient insulation. It is understandable that in order to improve the accuracy and reliability of temperature selection, the head interval of the thermal decomposition curve (such as TGA or DTG) is usually discarded (for example, depending on the type of material or the difference in the thermal decomposition analysis instrument, the curve segment with a temperature below about 50°C may be discarded), and then the effective interval of the curve is analyzed.

[0107] In some embodiments, the set curve segment may be the length of one data point or multiple data points.

[0108] The following provides a verification example 1 to illustrate the exemplary preparation steps of the glassy carbon microneedle patch of the present invention:

[0109] Using photosensitive resin as the raw material, a grid-like precursor was prepared and printed using 3D printing technology based on the principle of photopolymerization. The grid-like precursor had a line width (i.e., the edge width of the grid hole, or the width L1 of the edge sidewall of the grid hole) of 0.6 mm, a grid hole size (equivalent to the line spacing) of 1 mm, and a main body radius (i.e., the radius of the precursor edge) of 10 mm.

[0110] The gridded precursor is heated in a heating box (e.g., a high-temperature furnace) to convert the photosensitive resin into glassy carbon. The heating process mainly consists of the following three stages:

[0111] First heating stage: Step 1) heating to a first stress relief temperature C1 at a first set speed VI (1.5°C / min), and maintaining the temperature at the first stress relief temperature C1 for a first time period T1 (30 min). At this time, the first stress relief temperature selected by the first selection rule is 150°C;

[0112] Second heating stage: Step 2) heating the precursor to a pyrolysis temperature C2 at a second set rate VII (1°C / min), and maintaining the temperature at the pyrolysis temperature C2 for a second time period T2 (120 min), wherein the pyrolysis temperature C2 obtained by the second selection rule is 350°C; the meshed precursor can shrink and deform relatively uniformly during this process;

[0113] The third heating stage: Step 3) After the two insulation treatments in the low temperature zone are completed, the third heating stage of continuous heating is entered; specifically, the temperature is directly increased to the target heating temperature C5 (1000°C) according to the third set speed VⅢ (0.5°C / min), so that the gridded precursor is converted from a carbon polymer to a glassy carbon material.

[0114] In this verification example 1, a grid design is adopted for the precursor, and only two key insulations are carried out in the low temperature range, which specifically achieves the purposes of stress relief, pyrolysis carbonization, etc., eliminating the high-temperature insulation process. And the defect area (or defect generation rate) of the prepared grid microneedle can also be effectively controlled within 1% (the product quality is excellent). That is, the surface of the grid microneedle has good continuity, without defects such as foaming, cracks, and deformation, and because it also has high strength, it is suitable for actual industrial application needs.

[0115] It should be noted that this experiment used defect area (i.e., the percentage of defect area to the total surface area of ​​the meshed microneedles) to evaluate the quality of the meshed microneedles. When the defect area is 0-5%, the product quality is excellent; when the defect area is 5-15%, the product quality is good; and when the defect area exceeds 15%, the product quality is poor.

[0116] For another example, in some embodiments, since the present invention reduces the dependence of the third heating stage on the heating rate, variable speed heating can also be performed in the third heating stage.

[0117] The recommended speed change point (equivalent to the recommended temperature) for switching the heating rate can be the temperature corresponding to the data point where the slope of the thermogravimetric analysis curve is 0 or approximately 0 (e.g., within approximately ±0.001) as the slope gradually increases. As shown in Figure 3, the recommended speed change point is approximately 600°C. Furthermore, the actual speed change point selected is preferably no lower than the recommended speed change point (or generally within 1°C, 5°C, 10°C, etc., below the recommended speed change point).

[0118] The variable speed heating effect was verified through Verification Example 2 and Comparative Example 1:

[0119] In this verification example 2, the same gridded precursor as in verification example 1 was selected for centralized heat preservation treatment. The centralized heat preservation treatment includes:

[0120] First heating stage: heating to the first stress relief temperature C1 (150°C) at a first set speed VI (1.5°C / min), and keeping at the first stress relief temperature for 30 minutes; heating to the second stress relief temperature C3 (250°C) at a fourth set speed VI (1°C / min), and keeping at the second stress relief temperature for 60 minutes;

[0121] Second heating stage: heating from 250°C to 350°C at a rate of 1°C / min and keeping warm for 120 minutes;

[0122] The third heating stage: the temperature is raised from 350°C at a rate of 0.5°C / min, and then raised from 600°C to 1000°C at a rate of 2°C / min.

[0123] The surface morphology of the product prepared in Verification Example 2 can also be seen in Figure 5. It can be seen that the gridded microneedles prepared in the present invention still have a good surface morphology even at a microscopic angle.

[0124] Comparative Example 1

[0125] The differences in preparation process between Comparative Example 1 and Verification Example 2 are shown in Table 1:

[0126] Table 1

[0127] Furthermore, the present invention also provides Verification Example 3 to prove that the temperature selection method based on the carbonization pyrolysis can also meet the preparation requirements when applied to relatively simple microneedle structures (such as microneedle particles). For example, a precursor of microneedle particles is prepared using polyurethane acrylate as a raw material, and the simplified centralized heat preservation process shown in Figure 13 is used for preparation and heating. Specifically, the temperature of the first heat preservation is about 350°C (which is the pyrolysis carbonization temperature), and the heat preservation time is about 60 minutes. The temperature of the second heat preservation is about 800°C, and the heat preservation time is about 30 minutes.

[0128] The physical form of the final product is shown in Figures 11 and 12. Obviously, it can be proved that the centralized insulation process actually reduces the dependence on complex gradient insulation, that is, the formation of defects can be avoided through a simpler insulation process.

[0129] In some embodiments, the method further comprises the steps of:

[0130] S200: When the glassy carbon preparation enters the centralized heat preservation method stage (preferably the second heating stage or the third heating stage), the concentration index of impurities discharged through the exhaust duct of the heating box is monitored; wherein the impurities include: first-class impurities, and the first-class impurities include one or more of the following: carbon monoxide, carbon dioxide, nitric oxide, nitrogen dioxide, and nitrogen; S201: automatically adjusting the centralized heat preservation method according to the concentration index and the current state of the centralized heat preservation method; wherein the concentration index includes: a first concentration index for characterizing the concentration of the first-class impurities; accordingly, S201 includes the steps of:

[0131] S11: when the centralized heat preservation method enters the pyrolysis temperature and reaches the first set time but does not reach the second time period T2, and the first concentration index falls within the first concentration threshold range X1, sending a first time reduction signal to the gradient control module (or control unit) of the heating box, wherein the gradient control unit is capable of reducing the second time period T2 in response to the first time reduction signal;

[0132] S12 When the centralized insulation method enters the pyrolysis temperature and reaches or exceeds the second time length T2, and the first concentration index belongs to the corresponding second concentration threshold range X2, a first delay signal is sent to the control unit, wherein the control unit can extend the second time length T2 in response to the first delay signal.

[0133] As a preferred embodiment, the present invention selects the concentration of nitrogen (or a gas containing nitrogen) as the first concentration indicator.

[0134] In some embodiments, the second type of impurities includes: tar.

[0135] During the centralized heat preservation method, the second type of impurities discharged from the heating box can also be monitored to obtain a second concentration index of the second type of impurities. The second concentration index, the first concentration index, and the current process status can be used to monitor and adjust parameters. It is understood that the temperature of the heat preservation treatment can be directly obtained from the thermogravimetric analysis results of the gridded precursor (as shown in Figure 3) or can also be an empirical value collected by engineers after process debugging.

[0136] In this embodiment, it is preferred to use finite factors such as nitrogen and second-class impurities to monitor the status and automatically adjust the centralized insulation method. This automated adjustment process based on finite factors can also reduce the user's accuracy requirements for setting process parameters in the early stage to a certain extent. For example, at the beginning of preparation, only a rough insulation treatment temperature can be selected based on the pyrolysis data (or the insulation temperature can be preliminarily selected based on the engineer's experience), and then the insulation treatment temperature can be relatively accurately adjusted according to the actual processing status through the automated adjustment process, thereby assisting engineers to quickly explore the preparation conditions and reduce the process application cost to a certain extent.

[0137] In some embodiments, the method further comprises the following steps: during the heating stage of the gridded precursor, introducing an inert gas into the heating box to discharge the impurities out of the heating box through the exhaust pipe, wherein the introduction rate of the inert gas is about 10-60 cm 3 / min; collecting the impurity concentration index through a gas monitoring device connected to the exhaust pipe.

[0138] In order to reduce the influence of stress relief and rapid deformation of the gridded precursor during the pyrolysis and carbonization process during the centralized heat preservation method, the gridded precursor is symmetrically designed. For example, in some embodiments, the gridded precursor includes: a main body, and a hollow area arranged in the middle of the main body, and the main body is evenly arranged around the edge of the hollow area. Among them, the evenly arranged grid holes are matched with the hollow area arranged along the middle, thereby forming an impurity discharge space on the gridded precursor that is conducive to the uniform discharge of impurities.

[0139] For example, in some embodiments, the edge of the main body can be one or more of the following shapes: circular, oval, or rounded rectangle. For example, in some embodiments, the base of the object to be formed can be one or more of the following shapes: circular, square, cross, crisscross, or hollow structure (equivalent to a hollow structure).

[0140] In some embodiments, the steps are also included: providing a carbon-rich photopolymer material as a raw material, and obtaining process parameters for preparing the gridded precursor based on the photopolymer material, wherein the process parameters include one or more of the following: grid hole size, size of the target to be formed, and thickness of the gridded precursor; inputting the process parameters into a 3D printing system based on photopolymerization, and discretizing and stacking the photopolymer material through the 3D printing system to obtain a corresponding gridded precursor.

[0141] For example, 3D printing technology based on the principle of photopolymerization and photocuring technology based on micro-template technology can be used to prepare grid precursors. Among them, 3D printing technology based on photopolymerization is used to prepare microneedles, including one or more of laser stereolithography (SLA), two-photon polymerization (TPP), digital light processing (DLP), liquid crystal display (LCD) polymerization, continuous liquid interface fabrication (CLIP), static light projection printing (SOPL), etc. This type of technology is based on digital models and produces three-dimensional entities in a discrete and stacked manner by controlling the light source.

[0142] For another example, a polymer microneedle precursor can also be prepared based on the photocuring molding technology of the micro-template process (for example, microneedles with different bases as shown in Figure 10, such as a cross-shaped base, or a five-pointed star or polygonal star-shaped base, can be prepared using photocuring molding technology), and a mold can be pre-made by etching, 3D printing, etc., and then the microneedle structure is obtained by filling the photopolymer material, exposing and curing, and demolding. The microneedle product prepared by the 3D printing process, precursor optimization design and centralized heat preservation method in this application has good continuity on the product surface (almost no obvious defects, uniform mechanical properties), improved strength and conductivity, and improved reliability and service life in actual application.

[0143] In this embodiment, a 3D printing process is introduced for precursor preparation to facilitate customized production of microneedle products. Furthermore, experimental verification shows that the grid design used in this application, combined with the low-temperature gradient insulation process, can effectively alleviate or reduce the defects that may occur during the sintering process of the precursor obtained by 3D printing. Of course, in other embodiments, the mold method can also be used to manufacture the microneedle precursor.

[0144] Furthermore, to improve the synergy between the grid design and the low-temperature gradient insulation process, when the grid precursor adopts a circular ring or rounded corner design, the edge width L1 of the precursor's grid holes is less than or equal to approximately 2 mm, and the radius L2 of the main body is less than or equal to approximately 100 mm, the overall morphology of the grid precursor remains good after treatment with the low-temperature gradient insulation process, with no obvious defects. The verification results are shown in Table 2.

[0145] Table 2 Note: The other preparation processes of the gridded precursor in Table 2 are the same as those in Verification Example 1;

[0146] The experimental data in Table 2 further show that the gridding process design provided by the embodiment of the present invention can achieve uniform stress elimination and proportional shrinkage deformation (such as the shrinkage rate of each local area is about 25%), and the defect area of ​​the final product is significantly reduced.

[0147] On the contrary, as shown in Figure 8, a preparation process similar to that of Verification Example 1 was used to perform low-temperature gradient processing on a circle with a radius of 8 mm and a rectangle with a length of 8 mm (which did not adopt a grid design). The microneedles prepared were severely deformed and could not meet the actual application requirements.

[0148] Therefore, based on the grid process design proposed in this embodiment, when it is needed to be applied to different process applications, the user can also adjust the product shape and size relatively flexibly from aspects such as morphological design and grid distribution according to actual product requirements (such as when preparing components of different sizes and performances such as medical devices and sensors) to ensure the reliability of the final molded product. For example, in some embodiments, when it is necessary to prepare microneedle particles, the base of the microneedle can also be set to a cross-shaped base, or a five-pointed star or polygonal star-shaped base, or its shape can be adaptively adjusted in other ways according to application requirements to prepare an independent microneedle particle product.

[0149] Correspondingly, the present invention provides an application of a glassy carbon microneedle in the preparation of a signal transmission device, wherein the glassy carbon microneedle is used to connect or form the signal transmission device, and the signal transmission device is used to transmit one or more of the following signals: electrical signals, thermal signals. For example, in some embodiments, the glassy carbon microneedle (or the signal transmission device formed thereby) can be used in medical fields such as mediating electrostimulation therapy, photothermal therapy, and gene transfection, such as being able to transmit electrical signals during electrostimulation therapy. For another example, it can transmit thermal signals (i.e., heat) during photothermal therapy, such as when therapeutic light is irradiated on the microneedle, the microneedle can convert light into heat.

[0150] In some embodiments, one end of the signal transmission device (also referred to as a signal sensing device) is connected to biological tissue, and the other end is connected to a biosensor and / or a brain-computer interface.

[0151] In the present invention, the grid design is used to facilitate the formation of uniform stress distribution on the structure of the precursor and the formation of space for uniform impurity discharge; at the same time, the corresponding centralized thermal insulation treatment is coordinated with the uniform stress distribution and uniform impurity discharge space, which can realize the core processes such as uniform and stable stress elimination and pyrolysis carbonization in stages.

[0152] In addition, the present invention utilizes a spatial design for uniform impurity discharge in conjunction with centralized heat preservation treatment, which can concentrate the main stages of pyrolysis and carbonization (first, from the perspective of time and temperature range, and second, relatively centralized exhaust from the perspective of exhaust), so that users can more easily achieve centralized monitoring of the pyrolysis and carbonization process during the production process.

[0153] Of course, in other embodiments, when targeting different application scenarios or different process standards, the user can also adaptively set the form of the precursor, such as the precursor can be set to the form of a microneedle patch, that is, a plurality of microneedles (or microneedle-like structures) are arranged at intervals on a substrate. In some embodiments, the plurality of microneedle structures can be arranged radiating outward around a central point. In some embodiments, the microneedles can also be subjected to one or more post-treatments to optimize the application performance of the microneedles. For example, the post-treatment method can be one or more of the following: chemical group modification, chemical group etching, for example, the modification method can be: chemical modification, physical vapor deposition, laser surface modification, chemical vapor deposition, spraying, sputtering, etching, surface roughness treatment, electrochemical treatment or plasma treatment.

[0154] Example 2

[0155] The centralized heat preservation method of the present invention comprises, first, centralized gradient heat preservation in the low-temperature region, and second, rapid temperature increase in the subsequent high-temperature phase. Furthermore, to accelerate the process in the high-temperature phase, the present invention also provides a preparation method that incorporates a variable speed adjustment process, and the preparation method may include the same or similar steps as in Example 1.

[0156] In some embodiments, the preparation method further comprises the steps of:

[0157] Monitor and collect the concentration index of impurities; when the concentration index is lower than the set first threshold range A, send a first speed change signal to the heating box (having a gradient control unit); the heating box responds to the first speed change signal and converts the current first set sub-speed (i.e., the first heating speed) to the second set sub-speed (i.e., the second heating speed).

[0158] For example, in some embodiments, the first set sub-speed is approximately 0.5° C. / min, and the second set sub-speed is approximately 2° C. / min.

[0159] In this embodiment, the concentration index can be used to control the variable speed heating process in real time.

[0160] It is worth noting that, unlike the glassy carbon preparation process of the prior art, the present invention focuses on the glassy carbon preparation of microneedle-shaped products. For microneedle products with small sizes, they are prone to adverse deformation due to excessive shrinkage speed during the actual sintering process, which in turn affects the surface morphology and strength of the final microneedles, making them difficult to apply in practice.

[0161] However, the present invention, through the precursor grid design and centralized heat preservation treatment, reduces the impact of the heating rate on the third heating stage to a certain extent. Correspondingly, this also reduces the volatility of the impurity content discharged during the third heating stage to a certain extent. Therefore, by combining the monitoring of key impurity parameters during the third heating stage with centralized heat preservation, this embodiment can ensure the reliability and stability of the monitoring results, thereby effectively optimizing product quality.

[0162] Example 3

[0163] In order to improve the reliability of the centralized insulation method (i.e., the low-temperature gradient insulation process) and reduce the labor cost in the preparation process to a certain extent, the present invention also provides an automated monitoring system for glassy carbon preparation, as shown in FIG9 , comprising:

[0164] A gradient control module 10 (or control unit) for controlling the heating process of the heating box;

[0165] The low temperature gradient process monitoring subsystem (also known as the centralized insulation monitoring subsystem) includes:

[0166] An impurity monitoring module 20 is connected to the exhaust duct of the heating box and is configured to monitor the concentration index of impurities discharged through the exhaust duct; wherein the impurities include: first-class impurities, and the first-class impurities include one or more of the following: carbon monoxide, carbon dioxide, nitric oxide, nitrogen dioxide, and nitrogen;

[0167] The signal adjustment module 21 is configured to automatically adjust the centralized insulation method according to the concentration index and the current state of the centralized insulation method; wherein the concentration index includes: a first concentration index for representing the concentration of the first type of impurities; accordingly, the signal adjustment module 21 includes:

[0168] The first adjustment unit 11 is configured to send a first time reduction signal to the gradient control module of the heating box when the centralized heat preservation method enters the pyrolysis temperature and reaches the first set time but does not reach the second time length T2 (i.e., the preset pyrolysis heat preservation time length), and the first concentration index falls within the first concentration threshold range X1, wherein the control unit is capable of reducing the second time length T2 in response to the first time reduction signal;

[0169] And / or, the second adjustment unit 12 is configured to send a first delay signal to the control unit when the centralized insulation method enters the pyrolysis temperature and reaches or exceeds the second time length T2, and the first concentration index belongs to the corresponding second concentration threshold range X2, wherein the control unit can extend the second time length T2 in response to the first delay signal.

[0170] When the first concentration index enters the first concentration threshold range X1, the heat preservation is ended and the rapid temperature rise stage is entered.

[0171] In some embodiments, the signal conditioning module 21 also includes: a speed changing unit 13, which is configured to send a first speed regulation signal to the control unit when the centralized insulation method heats up from the pyrolysis temperature to the target heating temperature and monitors that the first concentration index belongs to the third concentration threshold range X3, wherein the control unit can speed up the third set speed VⅢ (i.e., the heating speed of the third heating stage) in response to the first speed regulation signal.

[0172] In some embodiments, the impurity monitoring module 20 is further configured to monitor the second type of impurities discharged from the heating box during the centralized heat preservation method stage.

[0173] In some embodiments, the signal adjustment module 21 also includes: a comprehensive adjustment unit 14, which is configured to send a first time reduction signal to the control unit of the heating box when the heating box enters the pyrolysis temperature and reaches the first set time but has not reached the second time length T2, and the first concentration index belongs to the first concentration threshold range X1, and the second concentration index belongs to the fourth concentration threshold range X4, wherein the control unit is capable of reducing the second time length T2 in response to the first time reduction signal.

[0174] The first, second and fifth concentration threshold ranges are sequentially set according to the concentration of the first type of impurities, and the fourth and sixth concentration threshold ranges are sequentially set according to the concentration of the second type of impurities.

[0175] In some embodiments, the signal adjustment module 21 also includes: a user adjustment unit 15, which is configured to send a first prompt signal to the user when the heating box enters the pyrolysis temperature and when the first concentration index belongs to the fifth concentration threshold range X5, or when the second concentration index belongs to the sixth concentration threshold range X6, to prompt the user to adjust the centralized insulation method of the gradient control module.

[0176] In this embodiment, the pyrolysis holding time can be dynamically controlled based on the ranges corresponding to the first and second concentration indicators. For example, when the concentration indicators are relatively low (i.e., the first concentration indicator is within the first concentration threshold range, and the second concentration indicator is within the fifth concentration threshold range), the pyrolysis holding time is automatically reduced.

[0177] When at least one concentration index is too high, for example, when the first concentration index belongs to the fifth concentration threshold range X5, or when the second concentration index belongs to the sixth concentration threshold range X6, emergency human intervention is introduced.

[0178] Alternatively, in some embodiments, the comprehensive adjustment unit 14 is also configured to send a first delay signal to the control unit in the same manner when the first concentration index belongs to the second concentration threshold range, or when the second concentration index is in the seventh concentration threshold range (i.e., between the fourth concentration threshold range and the sixth concentration threshold range). Correspondingly, the control unit can extend the second time length T2 in response to the first delay signal.

[0179] In the actual processing process, due to different processing environments, equipment models and product requirements, the preparation conditions may be frequently adjusted. The present invention adopts an automated adjustment process to adjust only key nodes (such as the pyrolysis and insulation time in the low-temperature area), that is, it can flexibly and dynamically control the preparation conditions, and can also use limited factors to perform multi-level adjustment, so as to perform more accurate automatic adjustment of the pyrolysis and insulation time without increasing the application cost, thereby reducing the necessity of manual user participation.

[0180] In some embodiments, the invention further includes a grid-based process monitoring subsystem, wherein the grid-based process monitoring subsystem includes:

[0181] The first image acquisition module 30 is configured to acquire morphological information of the gridded precursor, wherein the morphological information includes: a first image for displaying dimensional features of the gridded precursor;

[0182] The view analysis module 40 is configured to obtain characteristic indicators of the gridded precursor based on the morphological information; wherein the gridded precursor includes: a main body and a hollow area provided in the middle of the main body; the characteristic indicators include a first characteristic indicator for standardizing the size characteristics, and the first characteristic indicator includes: a line width of a grid hole;

[0183] The execution condition judgment module 50 is configured to judge whether the gridded precursor meets the preset execution conditions of the centralized insulation method (such as the execution condition being the standard line width of the grid holes) based on the characteristic index.

[0184] In some embodiments, the morphological information further includes: a second image for displaying the morphological features of the gridded precursor; accordingly, the characteristic index further includes: a second characteristic index obtained from the second image for indicating the number of defects.

[0185] For example, in some embodiments, an image dimension measuring instrument may be used to obtain corresponding dimension data.

[0186] In some embodiments, the execution condition determination module 50 includes:

[0187] The first judging unit 51 is configured to judge the monitoring level of the centralized insulation method according to the first characteristic index, and is divided into: first-level monitoring; second-level monitoring according to the difference between the first characteristic index and the standard size characteristic;

[0188] The second judgment unit 52 is configured to judge the monitoring level of the centralized heat preservation method according to the second characteristic index, and is divided into: first-level monitoring; second-level monitoring according to the difference between the second characteristic index and the standard morphological characteristics;

[0189] an execution risk analysis unit 53 configured to determine an execution risk level of the centralized heat preservation method according to the monitoring level and the monitoring level; wherein, when the monitoring level and the monitoring level are both level 1, the execution risk level is low, and a first start signal is sent to the gradient control module, and the gradient control module starts the centralized heat preservation method in response to the first start signal, and starts the signal adjustment module 21;

[0190] When the monitoring level is level 1 and the monitoring level is level 2, or when the monitoring level is level 2 and the monitoring level is level 1, and the execution risk level is medium, a second start signal is sent to the gradient control module, and the gradient control module is started in response to the second start signal and executes a centralized heat preservation method in response to a gradient control parameter input by a user;

[0191] When the monitoring level and the surveillance level are both level two, the execution risk level is high, a prompt signal is sent to the user, and a control signal input by the user in real time is received within a set time.

[0192] In some embodiments, when the difference between the first characteristic indicator (such as the line width of the grid hole) and the standard size characteristic (such as the preset standard line width) is less than or equal to the preset first difference, the first-level monitoring (mode) is selected; when the difference is greater than the first difference and less than the preset second difference, the second-level monitoring (mode) is selected.

[0193] In some embodiments, when the difference between the second characteristic indicator (such as the number of defects) and the standard morphological characteristic (standard number of defects) is less than or equal to a preset third difference, the first-level monitoring (mode) is selected, and when the corresponding difference is greater than the third difference and less than the preset fourth difference, the second-level monitoring (mode) is selected.

[0194] For example, in some embodiments, when facing batch process production, before using a batch of gridded precursors for a centralized insulation method, some gridded precursors can be selected as test samples, and the monitoring level (or surveillance level) under the low-temperature gradient insulation process can be determined through the gridded process monitoring subsystem, thereby improving the effectiveness of the entire preparation process.

[0195] Furthermore, this embodiment utilizes two clear indicators, line width and defect count, to quickly and standardizedly assess the quality of the test sample, thereby flexibly linking it with the subsequent low-temperature gradient process. For example, when the monitoring and surveillance levels of the test sample are both level one, it is preferred to activate the signal conditioning module 21 to dynamically adjust the low-temperature process.

[0196] In some embodiments, the defect quantity may also be represented by the defect area.

[0197] It should be noted that in this embodiment, "monitoring" and "monitoring" have the same meaning, and different expressions are used here only for the convenience of distinction.

[0198] In this embodiment, in order to improve the accuracy and reliability of automated monitoring, a monitoring scheme based on multi-level dynamic regulation of different types of parameters is proposed. In addition, in order to reduce the difficulty of the monitoring process, the present invention mainly monitors the key dimensional features in the grid technology (such as the width of the grid holes) and the key output impurities (such as nitrogen) in the centralized insulation method, thereby forming a multi-level monitoring mode using a limited combination of factors. Therefore, this multi-level dynamic adjustment monitoring scheme can not only use a limited combination of factors to reduce the possibility of process failure caused by monitoring errors (or failure of a single monitoring device); at the same time, it can also avoid the monitoring and analysis difficulties that may be brought about by multi-factor monitoring to a certain extent (on the contrary, the present invention uses limited, standardized factor comparisons to quickly discover difficult problems (such as when the risk level is high), and then notify the user in the first time, realizing the coordination of automated control and manual monitoring).

[0199] In some embodiments, the system further includes an evaluation subsystem comprising:

[0200] A second image acquisition module 60 is configured to acquire a third image of the gridded microneedle product prepared from the gridded precursor;

[0201] an image comparison module 70 configured to compare the third image with the first image to obtain shrinkage data and morphological difference data of the gridded microneedle product, wherein the morphological difference data is a difference in deformation ratio between the gridded precursor and the gridded microneedle product at at least two points;

[0202] The quality assessment module 80 is configured to perform product quality analysis on the gridded microneedle product according to the shrinkage data and the morphology difference data.

[0203] For example, in some embodiments, when the shrinkage data and the morphological difference data all fall within the preset standard range, it is considered that the product quality meets expectations and the current preparation process also meets the specifications.

[0204] In this embodiment, the image comparison technology can also be used to quickly evaluate the final prepared product. If the product quality is significantly lower than the expected quality, the user can be notified in time to make process adjustments.

[0205] Example 4

[0206] The present invention also provides a corresponding semi-automatic monitoring method for glassy carbon preparation, comprising the steps of:

[0207] S200: When the glassy carbon preparation enters the centralized heat preservation method step, monitoring the concentration index of impurities discharged through the exhaust duct of the heating box; wherein the impurities include: first-class impurities, and the first-class impurities include one or more of the following: carbon monoxide, carbon dioxide, nitric oxide, nitrogen dioxide, and nitrogen;

[0208] S201 automatically adjusts the centralized insulation method according to the concentration index and the current state of the centralized insulation method; wherein the concentration index includes: a first concentration index for characterizing the concentration of the first type of impurities; accordingly, S201 includes the steps of:

[0209] S11: when the low-temperature gradient insulation process enters the pyrolysis temperature and reaches the first set time but does not reach the second time length T2 (i.e., the pyrolysis insulation time length), and the first concentration index falls within the first concentration threshold range X1, sending a first time reduction signal to the gradient control module of the heating box, wherein the control unit is capable of reducing the second time length T2 in response to the first time reduction signal;

[0210] S12 When the heating box enters the pyrolysis temperature and reaches or exceeds the second time length T2, and the first concentration index belongs to the corresponding second concentration threshold range X2, a first delay signal is sent to the control unit, wherein the control unit can extend the second time length T2 in response to the first delay signal.

[0211] In some embodiments, the S201 further includes the steps of:

[0212] S13 When the heating box is heated from the pyrolysis temperature to the heating temperature and it is monitored that the first concentration index belongs to the third concentration threshold range X3, a first speed regulation signal is sent to the control unit, wherein the control unit can speed up the third set speed VⅢ (i.e., the heating speed of the third heating stage) in response to the first speed regulation signal.

[0213] In some embodiments, S200 further includes the steps of:

[0214] During the centralized heat preservation method steps (such as the second heating stage and the third heating stage), the second type of impurities discharged from the heating box are monitored.

[0215] In some embodiments, the step S201 includes the following steps:

[0216] When the heating box enters the pyrolysis temperature and reaches the first set time but does not reach the second time length T2, and the first concentration index falls within the first concentration threshold range X1, and the second concentration index falls within the fourth concentration threshold range X4, a first time reduction signal is sent to the control unit of the heating box, wherein the control unit is capable of reducing the second time length T2 in response to the first time reduction signal;

[0217] And / or, after the heating box enters the pyrolysis temperature, and when the first concentration index belongs to the fifth concentration threshold range X5 and the second concentration index belongs to the sixth concentration threshold range X6, a first prompt signal is sent to the user to prompt the user to adjust the centralized insulation method of the gradient control module.

[0218] In some embodiments, before S200, the step further includes:

[0219] S203: collecting morphological information of the gridded precursor, the morphological information including: a first image for displaying the size characteristics of the gridded precursor;

[0220] S204 obtains characteristic indicators of the gridded precursor based on the morphological information; wherein the gridded precursor includes: a main body and a hollow area arranged in the middle of the main body; the characteristic indicators include a first characteristic indicator for standardizing the size characteristics, and the first characteristic indicator includes: an edge width of a grid hole on the main body and a radius of the main body;

[0221] S205 determines whether the gridded precursor meets the preset execution conditions of the low-temperature gradient insulation process based on the characteristic indicators.

[0222] In some embodiments, the morphological information further includes a second image for displaying morphological features of the meshed precursor; accordingly, the characteristic index further includes a second characteristic index for indicating the number of defects. The number of defects can be represented by the defect area. Defects may include foaming, breakage, deformation, etc.

[0223] The defect area can be calculated by image comparison. For example, the points with pixel differences between a test sample photograph (i.e., a surface photograph of the prepared glassy carbon product) and a standard sample photograph (a surface photograph of the glassy carbon product selected as the standard sample) can be used as the defect area to calculate the defect area. Alternatively, other automated defect detection equipment or automated defect detection technologies can be used to calculate the defect area (or number of defects).

[0224] In some embodiments, S205 includes the steps of:

[0225] S51 determines the monitoring level of the low-temperature gradient insulation process according to the first characteristic index, and classifies it into: first-level monitoring; second-level monitoring according to the difference between the first characteristic index and the standard size characteristic;

[0226] S52 determines the monitoring level of the low-temperature gradient insulation process according to the second characteristic index, and classifies it into: first-level monitoring; second-level monitoring according to the difference between the second characteristic index and the standard morphological characteristics;

[0227] S53: determining the execution risk level of the low-temperature gradient insulation process according to the monitoring level and the surveillance level;

[0228] When both the monitoring level and the surveillance level are level 1, a first start signal is sent to the gradient control module. The gradient control module starts the low-temperature gradient insulation process in response to the first start signal and executes S200.

[0229] When the monitoring level is level 1 and the monitoring level is level 2, or when the monitoring level is level 2 and the monitoring level is level 1, a second start signal is sent to the gradient control module, and the gradient control module is started in response to the second start signal and performs a low-temperature gradient holding process in response to the gradient control parameters input by the user (such as pyrolysis holding time and the heating rate of the third stage heating);

[0230] When the monitoring level and the surveillance level are both level two, a prompt signal is sent to the user, and a control signal input by the user in real time is received within a set time.

[0231] In some embodiments, the steps further include:

[0232] S206: collecting a third image of the gridded microneedle product prepared from the gridded precursor;

[0233] S207: Comparing the third image with the first image to obtain shrinkage data and morphological difference data of the gridded microneedle product, wherein the morphological difference data is a difference in deformation ratio between the gridded precursor and the gridded microneedle product at at least two points;

[0234] S208 performs product quality analysis on the gridded microneedle product according to the shrinkage data and the morphological difference data.

[0235] It should be noted that the set thresholds or ranges used in the present invention can be adjusted by the user in combination with actual process conditions.

[0236] It should be noted that the temperature value actually selected in the present invention may be the recommended temperature or a value close to the recommended temperature.

[0237] The microneedle products produced by the present invention using a gridded precursor and a heat-insulating temperature exhibit multiple advantages, including strong rigidity, good biocompatibility, heat resistance, chemical resistance, good conductivity, and high purity. These products can be applied not only to conventional solid and hollow microneedle arrays, but also to the preparation of components for precision devices such as electrospinning nozzles, extrusion printing nozzles, brain-computer interfaces, and biochemical sensors.

[0238] Correspondingly, the present invention provides an application of glassy carbon microneedles in the preparation of a delivery medium, wherein the delivery medium includes one or more of the following: a drug delivery medium, a biological sample delivery medium (or a biological sample extraction medium). The drug delivery medium can be connected to a pressure conduction system. In some embodiments, the glassy carbon microneedles are loaded with drugs and / or biological agents by at least one of coating, deposition, filling, wrapping, and chemical bonding. In some embodiments, in order to improve the drug loading performance of glassy carbon, the glassy carbon can be subjected to at least one post-treatment to facilitate loading of drugs and / or biological agents thereon by coating, deposition, filling, wrapping, and chemical bonding.

[0239] Example 5

[0240] It is worth noting that this centralized heat preservation method allows the needle roller products to maintain good morphology and strength properties even when producing larger needle rollers. For example, even when the needle roller precursor is expanded to 200mm in length and 100mm in width (equivalent to the radius), it can still maintain stable deformation during the heating process.

[0241] The present invention also provides a method for preparing a roller microneedle, comprising:

[0242] S401: Obtain a precursor prepared from a carbon-based polymer, as shown in FIG14 and FIG15 , wherein the precursor comprises: a plurality of first supports and a plurality of second supports arranged at intervals, the first and second supports intersecting to form a plurality of grid holes at intervals, and a plurality of microneedles or microneedle-like structures disposed on at least one of the supports;

[0243] S402 performs centralized heat preservation treatment on the precursor; wherein S402 includes the steps of:

[0244] In the first heating stage, the precursor is subjected to a heat preservation treatment at a stress relief temperature to relieve stress in the precursor; wherein the stress relief temperature is selected according to a first selection rule;

[0245] The temperature is raised to enter the second heating stage, and the precursor is again kept warm at a pyrolysis carbonization temperature in the second heating stage to allow the precursor to undergo pyrolysis carbonization. At this time, the precursor shrinks and deforms during the pyrolysis carbonization process; the pyrolysis carbonization temperature is selected according to the second selection rule;

[0246] Among them, the first selection rule is: selecting the stress relief temperature from the weight loss rate fluctuation temperature; wherein the weight loss rate fluctuation temperature corresponds to one or more temperature values ​​corresponding to at least one curve segment with the largest curvature change in the thermogravimetric differential curve, and the thermogravimetric differential curve is a curve representing the change in the rate of weight change with temperature; the second selection rule is: selecting the thermal decomposition temperature from the weight loss fluctuation temperature; wherein the weight loss fluctuation temperature corresponds to one or more temperature values ​​corresponding to the curve segment with the largest curvature change in the interval where the slope of the thermogravimetric analysis curve gradually decreases, and the thermogravimetric analysis curve is a curve representing the change in weight with temperature.

[0247] In some embodiments, the width (ie, line width) of the precursor support is less than or equal to 3 mm.

[0248] In some embodiments, the precursor can be prepared using photocuring 3D printing technology. Correspondingly, before S402, the step of soaking the precursor in a cleaning liquid (such as an alcohol liquid) for a first time is also included, and the alcohol liquid refers to an alcohol solution or an alcohol solvent.

[0249] In some embodiments, the alcohol solution may be ethanol, propanol, methanol, or the like in various concentrations.

[0250] The alcohol solution is preferably high-concentration ethanol, such as anhydrous ethanol.

[0251] In some embodiments, the first time period can be set by the user. For example, the first time period can be approximately 5 minutes, during which vibration and ultrasonic accelerated cleaning can be performed until the residual liquid on the surface of the precursor (which is the liquid raw material that adheres to the surface of the precursor and fails to form during the photopolymerization printing process) is washed away.

[0252] In some embodiments, after the immersion treatment and drying, secondary light curing is required to fully crosslink and cure the material (this step can also be performed by high-pressure air blowing or high-speed centrifugation to remove residual resin material in the bracket).

[0253] In some embodiments, the precursor may also be prepared by methods such as fused deposition modeling and mold forming.

[0254] In some embodiments, the precursor is of columnar design, wherein a plurality of the first supports are arranged at least in a circle, and a plurality of the second supports are arranged at intervals along the length direction of the first support and intersect with the plurality of the first supports to form a columnar frame in combination with the first support; the precursor also includes: a third support and a fourth support arranged on the inner side of the columnar frame, wherein the third support and the fourth support are cross-arranged in at least two directions, and the two ends of the third support and the fourth support are respectively connected to the first support or the second support to support the columnar frame; wherein a plurality of microneedles or microneedle-like structures are provided on the side of the first support and / or the second support.

[0255] In some embodiments, the length of the first support of the precursor is less than or equal to 200 mm, and the width of the columnar frame (for example, when the columnar frame is a cylindrical structure, the width may refer to the radius) is less than or equal to 100 mm.

[0256] It's worth noting that even small defects can severely impact the quality of microneedle products, and as the size of the precursor increases, processing becomes increasingly difficult (making it more susceptible to defects due to deformation). The centralized heat preservation method proposed in this invention can increase the size of the product while maintaining microneedle quality (i.e., limiting the number of defects generated).

[0257] It has been verified that even when the width of the precursor reaches 100mm and the length reaches 200mm, the needle roller product obtained by the final heat treatment can still maintain good shape and performance during the rapid heating process.

[0258] Table 3

[0259] The heating process parameters used in Table 3 are shown in Figure 2b.

[0260] In some embodiments, in some embodiments, S402 further includes the step of: continuously heating from the pyrolysis temperature to the target heating temperature in a subsequent third heating stage.

[0261] In some embodiments, in the third heating stage, the temperature is increased to the speed-changing temperature point using a first heating rate, and then the temperature is increased to the target heating temperature using a second heating rate, wherein the second heating rate is greater than the first heating rate, and the speed-changing temperature point is the temperature point corresponding to the numerical point where the slope of the thermogravimetric analysis curve is less than a preset slope threshold as the slope gradually increases.

[0262] In some embodiments, the method further includes: during the second heating stage, introducing gas into the heating box where the precursor is located.

[0263] In some embodiments, the gas introduction rate is 10-60 cm 3 / min.

[0264] In some embodiments, the method further comprises:

[0265] During the second heating stage, the concentration index of impurities in the precursor during the pyrolysis and carbonization process is collected through the gas; wherein the impurities include: first-class impurities, and the first-class impurities include one or more of the following: carbon monoxide, carbon dioxide, nitric oxide, nitrogen dioxide, and nitrogen;

[0266] When the pyrolysis temperature reaches the first set time and does not reach the second time length T2, and the first concentration index falls within the first concentration threshold range X1, a first time reduction signal is sent to the heating box;

[0267] Alternatively, when the centralized insulation method enters the pyrolysis temperature and reaches or exceeds the second time length T2, and the first concentration index belongs to the corresponding second concentration threshold range X2, a first delay signal is sent to the heating box; wherein, the second time length is a preset pyrolysis insulation treatment time length.

[0268] Example 6

[0269] The present invention also provides a roller microneedle preparation system corresponding to the fifth embodiment, comprising:

[0270] A centralized heat preservation module is configured to perform centralized heat preservation treatment on a precursor; wherein the precursor is prepared from a carbon-based polymer, and the precursor comprises: a plurality of first supports and a plurality of second supports arranged at intervals, the first and second supports intersecting to form a plurality of grid holes at intervals, and at least one support is provided with a plurality of microneedles or microneedle-like structures; and the centralized heat preservation module comprises:

[0271] A first heating unit is configured to perform a heat preservation treatment on the precursor at a stress relief temperature in a first heating stage to relieve stress on the precursor; wherein the stress relief temperature is selected according to a first selection rule;

[0272] The second heating unit is configured to increase the temperature to enter a second heating stage, and in the second heating stage, the precursor is again kept warm at a pyrolysis carbonization temperature to pyrolyze the precursor, wherein the precursor shrinks and deforms during the pyrolysis carbonization process; the pyrolysis carbonization temperature is selected according to a second selection rule;

[0273] Among them, the first selection rule is: selecting the stress relief temperature from the weight loss rate fluctuation temperature; wherein the weight loss rate fluctuation temperature corresponds to one or more temperature values ​​corresponding to at least one curve segment with the largest curvature change in the thermogravimetric differential curve, and the thermogravimetric differential curve is a curve representing the change in the rate of weight change with temperature; the second selection rule is: selecting the thermal decomposition temperature from the weight loss fluctuation temperature; wherein the weight loss fluctuation temperature corresponds to one or more temperature values ​​corresponding to the curve segment with the largest curvature change in the interval where the slope of the thermogravimetric analysis curve gradually decreases, and the thermogravimetric analysis curve is a curve representing the change in weight with temperature.

[0274] It can be understood that the centralized insulation method for preparing roller needles in the present invention can also adopt the same or similar steps as any of the above embodiments, so the methods and systems in Examples 5 and 6 can also include the steps or unit modules in any of the above embodiments.

[0275] It should be noted that the microneedles provided by the present invention can preferably be applied to the fields of drug delivery, biosensing, tissue repair, medical cosmetology, etc., by penetrating the skin or other biological barriers through the needle structure to achieve efficient substance transfer or signal acquisition: for example, in drug delivery, microneedles form microchannels to deliver drugs directly to the target, avoiding the first-pass effect and improving drug efficacy; in biosensing, microneedles can directly contact body fluids to achieve accurate signal detection; in tissue repair and medical cosmetology, the physical stimulation mediated by microneedles is combined with drugs to promote tissue regeneration and repair, improve skin quality, and treat skin diseases. Of course, the microneedles provided by the present invention can also be applied to other application scenarios, such as electronics, chemical industry and other fields, and the present invention does not limit this.

[0276] Through the description of the above embodiments, those skilled in the art can clearly understand that the above embodiment methods can be implemented by means of software plus the necessary general hardware platform, and of course can also be implemented by hardware, but in many cases the former is a better embodiment. Based on such an understanding, the technical solution of the present invention is essentially or the part that contributes to the prior art can be embodied in the form of a software product, which is stored in a storage medium (such as ROM / RAM, magnetic disk, optical disk), and includes several instructions for enabling a computer terminal (which can be a mobile phone, computer, server, or network device, etc.) to execute the methods described in each embodiment of the present invention. The embodiments of the present invention are described above in conjunction with the accompanying drawings, but the present invention is not limited to the above specific embodiments. The above specific embodiments are merely illustrative and not restrictive. Under the guidance of the present invention, those skilled in the art can also make many forms without departing from the scope of protection of the present invention and the claims, and these all fall within the protection of the present invention.

Claims

1. A method for preparing glassy carbon microneedles, characterized in that: include: A precursor is prepared by using a carbon-based polymer raw material, wherein the precursor has a microneedle or microneedle-like structure; Placing the precursor in a heating box and starting a centralized heat preservation method; The step of starting the centralized heat preservation method includes: selecting a stress relief temperature to perform heat preservation treatment on the precursor in the first heating stage to eliminate stress on the precursor; wherein the stress relief temperature is selected by a first selection rule; and the first selection rule is: selecting the stress relief temperature from the weight loss rate fluctuation temperature; and the weight loss rate fluctuation temperature corresponds to the temperature value corresponding to the data point with the largest curvature change in the thermogravimetric differential curve within the interval less than the pyrolysis carbonization temperature; The temperature is raised to enter the second heating stage, and in the second heating stage, the precursor is again kept warm at the pyrolysis carbonization temperature to pyrolyze the precursor. At this time, the microneedle or the microneedle-like structure shrinks during the pyrolysis carbonization process; wherein the pyrolysis carbonization temperature is selected by a second selection rule; the second selection rule is: the pyrolysis carbonization temperature is selected from the weight loss fluctuation temperature; wherein the weight loss fluctuation temperature corresponds to the temperature value corresponding to the curve segment with the largest curvature change in the interval where the slope of the thermogravimetric analysis curve gradually decreases; In the subsequent third heating stage, the temperature is continuously raised from the pyrolysis carbonization temperature to the target heating temperature, and finally the precursor prepared from the carbon-based polymer is converted into glassy carbon microneedles.

2. The preparation method according to claim 1, characterized in that: Also includes: During the heating stage of the precursor, an inert gas is introduced into the heating box to protect the precursor and to discharge impurities generated during the heating stage; The concentration index of the impurities is collected through a gas monitoring device.

3. The preparation method according to claim 2, characterized in that: Also includes: In the third heating stage, when the concentration index of the impurity is monitored to be lower than the set concentration range, a switching time is selected according to the current time, wherein the difference between the switching time and the current time is less than the set difference range; At the conversion moment, the current first heating rate is increased to a second heating rate, and the temperature is continuously increased to the target heating temperature.

4. The preparation method according to claim 1, characterized in that: The carbon-based polymer comprises: (1) A carbon-rich polymer, wherein the carbon-rich polymer comprises one or more of the following: furan resin, furfuryl alcohol resin, furfuryl ketone resin, phenol, aldehyde resin, epoxy resin, polyurethane, polyimide, polyethylene glycol, acrylic resin, polylactic acid, polycaprolactone, polyethylene, polyetheretherketone, nylon, polycarbonate, polymethyl methacrylate, polyvinyl butyral, polyethylene terephthalate, polyacrylonitrile, polyvinylidene fluoride, polyvinylidene chloride, polystyrene, polytetrafluoroethylene, polybutadiene, polyphenylene oxide, polyphenylene sulfide, polybutene-1, polybenzimidazole, polyaryletherketone, polyarylsulfone, polyethylene naphthalate, poly Aniline, polyacetylene, polyparaphenylene, polyphthalimide, polyphenylene vinylene, polylactide, polychloroprene, cyanoacrylate, polynaphthylene vinylene, polyparaxylene, polymethylphenylsiloxane, liquid crystal polymer, polythiophene, polyvinyl acetylene, polyoxadiazole, polybisphenol A, polyacrylonitrile-butadiene-styrene copolymer, polychlorotrifluoroethylene, polyepoxy resin-acrylate copolymer, polybenzoquinone, polyparaphenylene sulfone, polyphenylene, polybenzoxazole, polypiperidine, polyvinyl acetal, polybenzothiazole and polyvinyl pyrrolidone; or (2) products obtained by further modification of the carbon-rich polymer.

5. The preparation method according to claim 1, characterized in that: The preparation method of the precursor includes: mold forming, and / or 3D printing.

6. The preparation method according to claim 5, characterized in that: The 3D printing method is: laser stereolithography, two-photon polymerization, digital light processing, liquid crystal display polymerization, continuous liquid phase interface manufacturing, fused deposition modeling, selective laser sintering, computer axial lithography, powder bonding modeling, electric field direct writing, inkjet direct writing or static light projection printing.

7. The preparation method according to claim 1, characterized in that: The base of the microneedle or the microneedle-like structure can be in one or more of the following shapes: circular, rectangular, cross-shaped, criss-cross-shaped or hollow structure.

8. The preparation method according to claim 1, characterized in that: The precursor has a substrate, and a plurality of the microneedles or the microneedle-like structures are arranged at intervals on the substrate; Alternatively, the precursor is a microneedle particle.

9. The preparation method according to claim 8, characterized in that: The substrate includes a plurality of grid holes arranged at intervals, the grid holes intersect each other to form a grid arrangement, and the microneedles or microneedle-like structures to be formed are arranged at the edges of the grid holes.

10. The preparation method according to claim 9, characterized in that: The mesh holes are filled with a polymer film.

11. The preparation method according to claim 9, characterized in that: The substrate comprises: a main body, a hollow area is arranged in the main body; a plurality of grid holes are arranged on the main body at intervals, and the main body can be in one or more of the following shapes: circular, annular, elliptical, rounded rectangle, regular polygon.

12. The preparation method according to claim 11, characterized in that: The line width L1 of the grid holes is less than or equal to 2 mm, and the radius L2 of the main body of the precursor is less than or equal to 100 mm.

13. A glassy carbon microneedle, characterized in that: The glassy carbon microneedles are prepared by the method as described in any one of claims 1-12.

14. Use of the glassy carbon microneedle according to claim 13 in preparing a signal transmission device, wherein: The glassy carbon microneedles are used to connect or form the signal transmission device, and the signal transmission device is used to transmit one or more of the following signals: electrical signals, optical signals, and thermal signals.

15. The use according to claim 14, characterized in that: One end of the signal transmission device is connected to biological tissue, and the other end is connected to a signal processing device to form a biosensor and / or a brain-computer interface.

16. Use of the glassy carbon microneedle according to claim 13 in preparing a delivery medium, wherein: The delivery medium includes one or more of the following: a drug delivery medium, a biological sample delivery medium.

17. The use according to claim 16, characterized in that The drug delivery medium is connected to a pressure transmission system.

18. The use according to claim 15, characterized in that: The glassy carbon microneedles are loaded with drugs and / or biological agents by at least one of coating, deposition, filling, encapsulation, and chemical bonding.

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