WO2022111438A1 - Rocket-imitation microneedle micromotor and preparation method therefor - Google Patents

Rocket-imitation microneedle micromotor and preparation method therefor Download PDF

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WO2022111438A1
WO2022111438A1 PCT/CN2021/132264 CN2021132264W WO2022111438A1 WO 2022111438 A1 WO2022111438 A1 WO 2022111438A1 CN 2021132264 W CN2021132264 W CN 2021132264W WO 2022111438 A1 WO2022111438 A1 WO 2022111438A1
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microneedle
template
rocket
fuel
micromotor
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PCT/CN2021/132264
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French (fr)
Chinese (zh)
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赵远锦
蔡丽均
王月桐
商珞然
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南京鼓楼医院
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0023—Drug applicators using microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0046—Solid microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0053—Methods for producing microneedles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
    • A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
    • A61M2037/0061—Methods for using microneedles

Definitions

  • the invention relates to the field of biomedical materials, in particular to a rocket-imitation micro-needle micro-motor and a preparation method thereof.
  • Microneedles are microneedles with microscale lengths that penetrate the stratum corneum and reach the epidermis/dermis without touching pain neurons and blood vessels. Thus, microneedles can deliver a wide range of molecules into the skin in a minimally invasive manner. Over the past decade, researchers have invented a variety of microneedling platforms. These microneedle platforms have been widely explored for transdermal drug delivery to treat local and systemic diseases, they can be loaded with small molecule drugs, peptides and proteins (such as insulin, vaccines and antibodies), oligonucleotides and nanomedicines, etc. They are delivered to peripheral tissues such as the skin, eyes, mouth, blood vessel walls, etc. However, the current microneedles mainly rely on manual operations, such as manual pressing, tape adhesion, etc., in order to be able to intervene in the tissue to play a role. This limits the application of microneedles in the human body.
  • Micromotor is a device that can convert other forms of energy into kinetic energy to achieve autonomous propulsion. It has been widely used in sensing, biomedicine, surgery, imaging and other biological fields. In particular, the self-propelled nature of micromotors has propelled the development of in vivo diagnosis and treatment of diseases. With the continuous efforts of scientists, many micromotors with different propulsion mechanisms have been invented, including bubble propulsion, self-diffusion electrophoresis, self-acupoint electrophoresis, and self-electrophoresis. Feasibility, is the most widely used mechanism for micromotors in vivo. In addition to the propulsion mechanism, the morphology of the micromotor is also a research hotspot. However, to the best of our knowledge, no micromotors with microneedle morphology have been developed yet.
  • the purpose of the present invention is to provide a novel rocket-like microneedle micromotor and a preparation method thereof.
  • the microneedle micromotor prepared by the present invention has good motion performance. It can realize the autonomous movement of the microneedle, breaking the limitation of the traditional microneedle that relies on manual operation to intervene in the tissue.
  • the invention has the advantages of simple preparation, low cost and high versatility, and promotes the application of the microneedle in the field of biomedicine.
  • a preparation method of a rocket-like micro-needle micro-motor comprising the following steps:
  • Step 1 Preparation of the needle tip part: place a certain amount of hydrogel pre-solution in a female template with a conical needle tip part and a tail part, so that it fills the conical needle tip part of the female template; remove excess air and solidify the needle tip part. Hydrogel pre-solution to obtain hydrogel tip;
  • Step 2 Preparation of fuel load cavity: place a certain amount of hydrogel pre-solution in the female template containing the hydrogel tip obtained in step 1 to cover the tail part of the female template; remove excess air, and use a protruding structure.
  • the positive template covers the top of the negative template to cure the hydrogel pre-solution in the tail part; peel off the positive template to obtain a hydrogel fuel load cavity;
  • Step 3 Fuel loading: mix the fuel substance with the hydrogel pre-solution to form a mixed solution, pour it into the negative template containing the hydrogel fuel loading cavity obtained in the second step, solidify the mixed solution, complete the loading of the fuel, and obtain fuel-loaded microneedles;
  • Step 4 Obtaining the micro-needle and micro-motor: the prepared fuel-loaded micro-needle is completely peeled off the negative template to obtain a micro-needle micro motor with a rocket shape.
  • the negative template is a polydimethyloxane negative template.
  • the female template has a conical needle tip portion and a tail portion; the protruding structure of the male template is embedded in the tail portion of the female template, and the protruding structure is the same as the shape of the conical needle tip portion close to one end of the tail portion; the The male formwork can cover the tail portion of the female formwork.
  • the hydrogel pre-solution is one of polyethylene glycol diacrylate aqueous solution and methacrylic anhydride gelatin aqueous solution, and contains 1 wt % of photoinitiator.
  • the air in the hydrogel pre-solution in the negative template is removed by vacuum pumping or centrifugation.
  • the curing method of the hydrogel pre-solution is ultraviolet polymerization.
  • the fuel material in step 3 is one of magnesium particles, zinc particles or platinum particles.
  • the loading volume of the fuel substance is 4.0 ⁇ 10 ⁇ 4 cubic centimeters.
  • the invention provides a rocket-imitation micro-needle micromotor and a preparation method thereof.
  • the rocket-imitation micro-needle micromotor is obtained by a step-by-step template replication method using hydrogel as a raw material, integrating a chemical reaction of bubble generation as a power source .
  • the micro-needle micro-motor of the present invention has the characteristics of the needle tip of the micro-needle and the tail structure used to load fuel, and has the function of spontaneous movement.
  • the preparation method provided by the invention has the advantages of simple preparation process, good repeatability, low cost, convenient mass production, etc.
  • the prepared microneedle micromotor has the function of self-driving, which can overcome the need of manual operation for traditional microneedles to enter.
  • the limitations of the human body provide unlimited potential for microneedles in the field of biomedicine, especially the in vivo application of microneedles.
  • Figure 1 Schematic diagram of the negative template of microneedle and micromotor.
  • Figure 2 Schematic diagram of the positive template of the microneedle and micromotor.
  • Figure 3 is a flow chart of the preparation method of the microneedle micromotor.
  • FIG. 4 is a physical diagram of the microneedle and micromotor prepared by the present invention.
  • Fig. 5 is a diagram of spontaneous motion of the microneedle prepared by the present invention.
  • Step 1 Preparation of the needle tip: place the polyethylene glycol diacrylate aqueous solution containing 1% photoinitiator in the designed negative template of polydimethyloxane as shown in Figure 1 to fill the cone of the template For the needle tip part, the excess air in the hydrogel pre-solution is removed by vacuuming, and the hydrogel pre-solution is UV-cured to obtain the needle tip part.
  • Step 2 Preparation of fuel load chamber: put a certain amount of polyethylene glycol diacrylate aqueous solution containing 1% photoinitiator in the female template containing the needle tip part, cover the tail part of the female template, and remove excess by vacuuming The air is covered with a male template with a protruding structure, the protruding structure of the male template matches the shape of the needle tip end of the middle part of the tail of the female template, UV-cured hydrogel pre-solution, and the male template is peeled off to obtain a fuel load cavity.
  • Step 3 Fuel loading: The magnesium particles are mixed with an aqueous solution of polyethylene glycol diacrylate containing 1% photoinitiator, placed in a fuel loading chamber, and the mixed solution is cured by ultraviolet light to complete the fuel loading.
  • Step 4 Obtaining the micro-needle and micro-motor: peeling off the prepared negative template to obtain a micro-needle micro-motor with a rocket shape.
  • Step 1 Preparation of the needle tip: Place the methacrylic anhydride gelatin aqueous solution containing 1% photoinitiator in the designed negative polydimethyloxane template to fill the conical needle tip of the template, and remove water by centrifugation. Excess air in the gel pre-solution, UV-cured the hydrogel pre-solution to obtain the tip section.
  • Step 2 Preparation of the fuel load chamber: place a certain amount of methacrylic anhydride gelatin aqueous solution containing 1% photoinitiator in the negative template containing the tip part, cover the tail part of the negative template, and remove excess air by centrifugation , covered with a positive template with a protruding structure, UV-cured hydrogel pre-solution, and peeled off the positive template to obtain a fuel-loading cavity.
  • Step 3 Fuel loading: The magnesium particles are mixed with an aqueous solution of methacrylic anhydride gelatin containing 1% photoinitiator, placed in a fuel loading chamber, and the mixed solution is UV-cured to complete the fuel loading.
  • Step 4 Obtaining the micro-needle and micro-motor: peeling off the prepared negative template to obtain a micro-needle micro-motor with a rocket shape.
  • Figure 1 shows the schematic diagram of the female template of the micro-needle micro-motor, which can be divided into two parts: the needle tip and the tail.
  • Figure 2 shows the schematic diagram of the male template of the micro-needle micromotor, and its convex part is centered on the female template.
  • Figure 3 shows the schematic diagram of the fabrication process of the microneedle micromotor.
  • the needle tip portion of the negative template is covered with the hydrogel pre-solution, then the air in the hydrogel pre-solution in the negative template is removed, and then the needle tip portion is cured.
  • the tail part of the female template was then covered with a hydrogel pre-solution, covered with a positive template before curing, and the dye-loading cavity was obtained by peeling off the positive template after curing.
  • the next step is to fill the dye-loading cavity with a mixture of fuel substance and hydrogel pre-solution and then solidify.
  • a rocket-like micro-needle micro-motor is obtained by demoulding.
  • Figure 4 shows the physical picture of the micro-needle micro-motor, which has the morphological characteristics of a rocket.
  • Fig. 5 is the spontaneous motion diagram of the microneedle prepared by the present invention.

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Abstract

A rocket-imitation microneedle micromotor and a preparation method therefor. The preparation thereof comprises the steps of preparing a needle tip portion, preparing a fuel load chamber, loading fuel and obtaining the microneedle micromotor, wherein the main method involves using a hydrogel as a raw material, an integrated bubble generation chemical reaction is used as a power source, the microneedle micromotor is obtained by a step-wise template replication method, and the microneedle micromotor is provided with a needle-tip morphological characteristic of a microneedle and a fin structure for loading the fuel. The prepared microneedle micromotor has good motion performance, can achieve the autonomous movement of the microneedle, and breaks through the limitation of a traditional microneedle relying on manual operation to intervene in a tissue. The microneedle micromotor is relatively easy to prepare and low cost, has high universality, and the application of a microneedle in field of biomedicine can be promoted.

Description

一种仿火箭的微针微马达及其制备方法Micro-needle micro-motor imitating rocket and preparation method thereof 技术领域technical field
本发明涉及生物医学材料领域，具体涉及一种仿火箭的微针微马达及其制备方法。The invention relates to the field of biomedical materials, in particular to a rocket-imitation micro-needle micro-motor and a preparation method thereof.
背景技术Background technique
微针是一种具有微尺度长度的微型针，它们能够穿透角质层，到达表皮/真皮层，而不触及痛觉神经元和血管。因此，微针可以以一种微创的方式将广泛的分子运输到皮肤中。在过去的十年里，研究人员已经发明了各种各样的微针平台。这些微针平台已经被广泛探索用于经皮给药治疗局部和全身疾病，它们可以负载小分子药物、多肽和蛋白质(如胰岛素、疫苗和抗体)、寡核苷酸和纳米药物等，并将它们输送到皮肤、眼睛、口腔、血管壁等外周组织。然而，目前的微针主要依赖于人为操作，如手动按压、胶带黏附等手段，才能够介入组织发挥作用。这限制了微针在人体内的应用。Microneedles are microneedles with microscale lengths that penetrate the stratum corneum and reach the epidermis/dermis without touching pain neurons and blood vessels. Thus, microneedles can deliver a wide range of molecules into the skin in a minimally invasive manner. Over the past decade, researchers have invented a variety of microneedling platforms. These microneedle platforms have been widely explored for transdermal drug delivery to treat local and systemic diseases, they can be loaded with small molecule drugs, peptides and proteins (such as insulin, vaccines and antibodies), oligonucleotides and nanomedicines, etc. They are delivered to peripheral tissues such as the skin, eyes, mouth, blood vessel walls, etc. However, the current microneedles mainly rely on manual operations, such as manual pressing, tape adhesion, etc., in order to be able to intervene in the tissue to play a role. This limits the application of microneedles in the human body.
微马达是一种能够将其他形式的能量转化为动能而实现自主推进的装置，目前已被广泛应用于传感、生物医学、外科、成像等多种生物领域。特别地，微马达的自驱动特性推动了疾病在体诊断和治疗领域的发展。在科学家的不断努力下，已经有许多不同推进机制的微马达被发明出来，包括气泡推进、自扩散泳透、自穴位泳透、自电泳等，其中气泡推进机制由于其在复杂生物环境下的可行性，是微型电机在体内应用最广泛的机制。除了推进机制外，微马达的形貌也是研究热点。然而，据我们所知，目前还未有微针形貌的微马达被开发出来。Micromotor is a device that can convert other forms of energy into kinetic energy to achieve autonomous propulsion. It has been widely used in sensing, biomedicine, surgery, imaging and other biological fields. In particular, the self-propelled nature of micromotors has propelled the development of in vivo diagnosis and treatment of diseases. With the continuous efforts of scientists, many micromotors with different propulsion mechanisms have been invented, including bubble propulsion, self-diffusion electrophoresis, self-acupoint electrophoresis, and self-electrophoresis. Feasibility, is the most widely used mechanism for micromotors in vivo. In addition to the propulsion mechanism, the morphology of the micromotor is also a research hotspot. However, to the best of our knowledge, no micromotors with microneedle morphology have been developed yet.
发明内容SUMMARY OF THE INVENTION
本发明目的在于提供一种新型仿火箭的微针微马达及其制备方法，本发明制备得的微针微马达具有良好的运动性能。可实现微针的自主运动，打破传统微针依赖人为操作介入组织的局限性。且本发明制备简单、成本低，通用性高，推进了微针在生物医学领域的应用。The purpose of the present invention is to provide a novel rocket-like microneedle micromotor and a preparation method thereof. The microneedle micromotor prepared by the present invention has good motion performance. It can realize the autonomous movement of the microneedle, breaking the limitation of the traditional microneedle that relies on manual operation to intervene in the tissue. In addition, the invention has the advantages of simple preparation, low cost and high versatility, and promotes the application of the microneedle in the field of biomedicine.
为实现上述目的，本发明提供的技术方案是：For achieving the above object, the technical scheme provided by the present invention is:
一种仿火箭微针微马达的制备方法，包括以下步骤：A preparation method of a rocket-like micro-needle micro-motor, comprising the following steps:
步骤一、针尖部分的制备：将一定量水凝胶预溶液置于具有圆锥形针尖部分和尾翼部分的阴模板中，使其充满阴模板的圆锥针尖部分；去除多余的空气，固化针尖部分的水凝胶预溶液，获得水凝胶针尖；Step 1. Preparation of the needle tip part: place a certain amount of hydrogel pre-solution in a female template with a conical needle tip part and a tail part, so that it fills the conical needle tip part of the female template; remove excess air and solidify the needle tip part. Hydrogel pre-solution to obtain hydrogel tip;
步骤二、燃料负载腔的制备：将一定量水凝胶预溶液置于步骤一获得的含有水凝胶针尖的阴模板中，覆盖阴模板的尾翼部分；去除多余的空气，采用一具有突起结构的阳模板覆盖阴模板顶部，固化尾翼部分的水凝胶预溶液；剥去阳模板，获得水凝胶燃料负载腔；Step 2: Preparation of fuel load cavity: place a certain amount of hydrogel pre-solution in the female template containing the hydrogel tip obtained in step 1 to cover the tail part of the female template; remove excess air, and use a protruding structure. The positive template covers the top of the negative template to cure the hydrogel pre-solution in the tail part; peel off the positive template to obtain a hydrogel fuel load cavity;
步骤三、燃料的负载：将燃料物质与水凝胶预溶液混合，形成混合溶液，倒入步骤二获得的含有水凝胶燃料负载腔的阴模板中，固化混合溶液，完成燃料的负载，得到燃料负载微针；Step 3. Fuel loading: mix the fuel substance with the hydrogel pre-solution to form a mixed solution, pour it into the negative template containing the hydrogel fuel loading cavity obtained in the second step, solidify the mixed solution, complete the loading of the fuel, and obtain fuel-loaded microneedles;
步骤四、微针微马达的获得：将制备好的燃料负载微针整体剥离阴模板，获得具有火箭形貌的微针微马达。Step 4: Obtaining the micro-needle and micro-motor: the prepared fuel-loaded micro-needle is completely peeled off the negative template to obtain a micro-needle micro motor with a rocket shape.
进一步的，所述的阴模板为聚二甲基氧烷阴模板。Further, the negative template is a polydimethyloxane negative template.
进一步的，所述的阴模板具有圆锥形针尖部分和尾翼部分；所述的阳模板的突起结构嵌入阴模板尾翼中，其突起结构与圆锥形针尖部分靠近尾翼部分一端的形状相同；所述的阳模板能够覆盖阴模板的尾翼部分。Further, the female template has a conical needle tip portion and a tail portion; the protruding structure of the male template is embedded in the tail portion of the female template, and the protruding structure is the same as the shape of the conical needle tip portion close to one end of the tail portion; the The male formwork can cover the tail portion of the female formwork.
进一步的，所述的水凝胶预溶液为聚乙二醇二丙烯酸酯水溶液、甲基丙烯酸酐化明胶水溶液中的一种，且其中含有1wt％的光引发剂。Further, the hydrogel pre-solution is one of polyethylene glycol diacrylate aqueous solution and methacrylic anhydride gelatin aqueous solution, and contains 1 wt % of photoinitiator.
进一步的，通过真空抽气或离心法去除阴模板内水凝胶预溶液中的空气。Further, the air in the hydrogel pre-solution in the negative template is removed by vacuum pumping or centrifugation.
进一步的，水凝胶预溶液的固化方式为紫外聚合。Further, the curing method of the hydrogel pre-solution is ultraviolet polymerization.
进一步的，步骤三中所述燃料物质为镁颗粒、锌颗粒或铂颗粒中的一种。Further, the fuel material in step 3 is one of magnesium particles, zinc particles or platinum particles.
进一步的，燃料物质的负载体积为4.0×10 -4立方厘米。 Further, the loading volume of the fuel substance is 4.0×10 −4 cubic centimeters.
与现有技术相比，本发明的有益效果是：Compared with the prior art, the beneficial effects of the present invention are:
本发明提供了一种仿火箭的微针微马达及其制备方法，该仿火箭微针微马达是以水凝胶为原材料，集成气泡生成化学反应为动力来源，通过分步模板复制法得到的。本发明的微针微马达具有微针的针尖形貌特征以及用来负载燃料的尾翼结构，具有自发运动的功能。The invention provides a rocket-imitation micro-needle micromotor and a preparation method thereof. The rocket-imitation micro-needle micromotor is obtained by a step-by-step template replication method using hydrogel as a raw material, integrating a chemical reaction of bubble generation as a power source . The micro-needle micro-motor of the present invention has the characteristics of the needle tip of the micro-needle and the tail structure used to load fuel, and has the function of spontaneous movement.
本发明提供的制备方法具有制备过程简单，重复性良好，成本低廉，便于大规模生产等优点，所制备的微针微马达具有自驱动的功能，可克服传统微针必须借助人为操作才可进入人体发挥作用的限制，为微针在生物医学领域，尤其是微针的体内应用，提供无限潜能。The preparation method provided by the invention has the advantages of simple preparation process, good repeatability, low cost, convenient mass production, etc. The prepared microneedle micromotor has the function of self-driving, which can overcome the need of manual operation for traditional microneedles to enter. The limitations of the human body provide unlimited potential for microneedles in the field of biomedicine, especially the in vivo application of microneedles.
附图说明Description of drawings
图1微针微马达阴模板示意图。Figure 1. Schematic diagram of the negative template of microneedle and micromotor.
图2微针微马达阳模板示意图。Figure 2. Schematic diagram of the positive template of the microneedle and micromotor.
图3微针微马达的制备方法流程图。Figure 3 is a flow chart of the preparation method of the microneedle micromotor.
图4本发明制备的微针微马达实物图。FIG. 4 is a physical diagram of the microneedle and micromotor prepared by the present invention.
图5本发明制备的微针的自发运动图。Fig. 5 is a diagram of spontaneous motion of the microneedle prepared by the present invention.
具体实施方式Detailed ways
下面结合具体实施例对本发明作进一步详细的说明。以下实施例仅用于说明本发明而不用 于限制本发明的范围。The present invention will be described in further detail below with reference to specific embodiments. The following examples are only intended to illustrate the present invention and not to limit the scope of the present invention.
实施例1Example 1
一种新型仿火箭的微针微马达及其制备方法的实施例如下：Embodiments of a novel rocket-like micro-needle micro-motor and its preparation method are as follows:
步骤一、针尖部分的制备：将含有1％光引发剂的聚乙二醇二丙烯酸酯水溶液置于设计好的如图1所示的聚二甲基氧烷阴模板中使其充满模板的圆锥针尖部分，通过抽真空去除水凝胶预溶液中多余的空气，紫外固化水凝胶预溶液，获得针尖部分。Step 1. Preparation of the needle tip: place the polyethylene glycol diacrylate aqueous solution containing 1% photoinitiator in the designed negative template of polydimethyloxane as shown in Figure 1 to fill the cone of the template For the needle tip part, the excess air in the hydrogel pre-solution is removed by vacuuming, and the hydrogel pre-solution is UV-cured to obtain the needle tip part.
步骤二、燃料负载腔的制备：将一定量将含有1％光引发剂的聚乙二醇二丙烯酸酯水溶液置于含有针尖部分的阴模板中，覆盖阴模板的尾翼部分，通过抽真空去除多余的空气，使用具有突起结构的阳模板覆盖，阳模板的突起结构与阴模板尾翼的中间部分的针尖末端形状相匹配，紫外固化水凝胶预溶液，剥去阳模板，获得燃料负载腔。Step 2. Preparation of fuel load chamber: put a certain amount of polyethylene glycol diacrylate aqueous solution containing 1% photoinitiator in the female template containing the needle tip part, cover the tail part of the female template, and remove excess by vacuuming The air is covered with a male template with a protruding structure, the protruding structure of the male template matches the shape of the needle tip end of the middle part of the tail of the female template, UV-cured hydrogel pre-solution, and the male template is peeled off to obtain a fuel load cavity.
步骤三、燃料的负载：将镁颗粒与含有1％光引发剂的聚乙二醇二丙烯酸酯水溶液混合，置于燃料负载腔，紫外固化混合溶液，完成燃料负载。Step 3. Fuel loading: The magnesium particles are mixed with an aqueous solution of polyethylene glycol diacrylate containing 1% photoinitiator, placed in a fuel loading chamber, and the mixed solution is cured by ultraviolet light to complete the fuel loading.
步骤四、微针微马达的获得：将制备好的整体剥离阴模板，获得具有火箭形貌的微针微马达。Step 4: Obtaining the micro-needle and micro-motor: peeling off the prepared negative template to obtain a micro-needle micro-motor with a rocket shape.
实施例2Example 2
一种新型仿火箭的微针微马达及其制备方法的实施例如下：Embodiments of a novel rocket-like micro-needle micro-motor and its preparation method are as follows:
步骤一、针尖部分的制备：将含有1％光引发剂的甲基丙烯酸酐化明胶水溶液置于设计好的聚二甲基氧烷阴模板中使其充满模板的圆锥针尖部分，通过离心去除水凝胶预溶液中多余的空气，紫外固化水凝胶预溶液，获得针尖部分。Step 1. Preparation of the needle tip: Place the methacrylic anhydride gelatin aqueous solution containing 1% photoinitiator in the designed negative polydimethyloxane template to fill the conical needle tip of the template, and remove water by centrifugation. Excess air in the gel pre-solution, UV-cured the hydrogel pre-solution to obtain the tip section.
步骤二、燃料负载腔的制备：将一定量将含有1％光引发剂的甲基丙烯酸酐化明胶水溶液置于含有针尖部分的阴模板中，覆盖阴模板的尾翼部分，通过离心去除多余的空气，使用具有突起结构的阳模板覆盖，紫外固化水凝胶预溶液，剥去阳模板，获得燃料负载腔。Step 2. Preparation of the fuel load chamber: place a certain amount of methacrylic anhydride gelatin aqueous solution containing 1% photoinitiator in the negative template containing the tip part, cover the tail part of the negative template, and remove excess air by centrifugation , covered with a positive template with a protruding structure, UV-cured hydrogel pre-solution, and peeled off the positive template to obtain a fuel-loading cavity.
步骤三、燃料的负载：将镁颗粒与含有1％光引发剂的甲基丙烯酸酐化明胶水溶液混合，置于燃料负载腔，紫外固化混合溶液，完成燃料负载。Step 3. Fuel loading: The magnesium particles are mixed with an aqueous solution of methacrylic anhydride gelatin containing 1% photoinitiator, placed in a fuel loading chamber, and the mixed solution is UV-cured to complete the fuel loading.
步骤四、微针微马达的获得：将制备好的整体剥离阴模板，获得具有火箭形貌的微针微马达。Step 4: Obtaining the micro-needle and micro-motor: peeling off the prepared negative template to obtain a micro-needle micro-motor with a rocket shape.
图1给出了微针微马达的阴模板示意图，其可分为针尖和尾翼两个区块。Figure 1 shows the schematic diagram of the female template of the micro-needle micro-motor, which can be divided into two parts: the needle tip and the tail.
图2给出了微针微马达的阳模板示意图，其凸起部分与阴模板对中。Figure 2 shows the schematic diagram of the male template of the micro-needle micromotor, and its convex part is centered on the female template.
图3给出了微针微马达的制备过程示意图。首先利用水凝胶预溶液覆盖阴模板的针尖部分，接着去除阴模板内水凝胶预溶液中的空气，随后固化针尖部分。然后用水凝胶预溶液覆盖阴模板的尾翼部分，在固化前用阳模板覆盖，固化后剥去阳模板获得染料负载腔。下一步用燃料物质和水凝胶预溶液的混合液填满染料负载腔然后固化。最后，通过脱模获得仿火箭的微针微马达。Figure 3 shows the schematic diagram of the fabrication process of the microneedle micromotor. First, the needle tip portion of the negative template is covered with the hydrogel pre-solution, then the air in the hydrogel pre-solution in the negative template is removed, and then the needle tip portion is cured. The tail part of the female template was then covered with a hydrogel pre-solution, covered with a positive template before curing, and the dye-loading cavity was obtained by peeling off the positive template after curing. The next step is to fill the dye-loading cavity with a mixture of fuel substance and hydrogel pre-solution and then solidify. Finally, a rocket-like micro-needle micro-motor is obtained by demoulding.
图4给出了微针微马达的实物图，其具有仿火箭的形貌特征。Figure 4 shows the physical picture of the micro-needle micro-motor, which has the morphological characteristics of a rocket.
自发运动的功能：The function of spontaneous movement:
应用例1Application example 1
将实施例1制备得的微针微马达置于酸碱度为1的溶液中，记录其运动，得到图5。图5即为本发明制备的微针的自发运动图。The microneedle micromotor prepared in Example 1 was placed in a solution with a pH of 1, and its movement was recorded, and Figure 5 was obtained. Fig. 5 is the spontaneous motion diagram of the microneedle prepared by the present invention.
以上所述，仅是本发明的较佳实施例，并非对本发明作任何形式上的限制，任何熟悉本专业的技术人员，在不脱离本发明技术方案范围内，依据本发明的技术实质，对以上实施例所作的任何简单的修改、等同替换与改进等，均仍属于本发明技术方案的保护范围之内。The above are only preferred embodiments of the present invention, and do not limit the present invention in any form. Any person skilled in the art, without departing from the scope of the technical solution of the present invention, according to the technical essence of the present invention, Any simple modifications, equivalent replacements and improvements made in the above embodiments still fall within the protection scope of the technical solutions of the present invention.

Claims (9)

  1. 一种仿火箭微针微马达的制备方法，其特征在于：包括以下步骤：A preparation method of a rocket-like micro-needle micro-motor is characterized in that: comprising the following steps:
    步骤一、针尖部分的制备：将一定量水凝胶预溶液置于具有圆锥形针尖部分和尾翼部分的阴模板中，使其充满阴模板的圆锥针尖部分；去除多余的空气，固化针尖部分的水凝胶预溶液，获得水凝胶针尖；Step 1. Preparation of the needle tip part: place a certain amount of hydrogel pre-solution in a female template with a conical needle tip part and a tail part, so that it fills the conical needle tip part of the female template; remove excess air and solidify the needle tip part. Hydrogel pre-solution to obtain hydrogel tip;
    步骤二、燃料负载腔的制备：将一定量水凝胶预溶液置于步骤一获得的含有水凝胶针尖的阴模板中，覆盖阴模板的尾翼部分；去除多余的空气，采用一具有突起结构的阳模板覆盖阴模板顶部，固化尾翼部分的水凝胶预溶液；剥去阳模板，获得水凝胶燃料负载腔；Step 2: Preparation of fuel load cavity: place a certain amount of hydrogel pre-solution in the female template containing the hydrogel tip obtained in step 1 to cover the tail part of the female template; remove excess air, and use a protruding structure. The positive template covers the top of the negative template to cure the hydrogel pre-solution in the tail part; peel off the positive template to obtain a hydrogel fuel load cavity;
    步骤三、燃料的负载：将燃料物质与水凝胶预溶液混合，形成混合溶液，倒入步骤二获得的含有水凝胶燃料负载腔的阴模板中，固化混合溶液，完成燃料的负载，得到燃料负载微针；Step 3. Fuel loading: mix the fuel substance with the hydrogel pre-solution to form a mixed solution, pour it into the negative template containing the hydrogel fuel loading cavity obtained in the second step, solidify the mixed solution, complete the loading of the fuel, and obtain fuel-loaded microneedles;
    步骤四、微针微马达的获得：将制备好的燃料负载微针整体剥离阴模板，获得具有火箭形貌的微针微马达。Step 4: Obtaining the micro-needle and micro-motor: the prepared fuel-loaded micro-needle is completely peeled off the negative template to obtain a micro-needle micro motor with a rocket shape.
  2. 根据权利要求1所述的仿火箭微针微马达的制备方法，其特征在于：所述的阴模板为聚二甲基氧烷阴模板。The method for preparing a rocket-like microneedle micromotor according to claim 1, wherein the negative template is a polydimethyloxane negative template.
  3. 根据权利要求1所述的仿火箭微针微马达的制备方法，其特征在于：所述的阴模板具有圆锥形针尖部分和尾翼部分；所述的阳模板的突起结构嵌入阴模板尾翼中，其突起结构与圆锥形针尖部分靠近尾翼部分一端的形状相同；所述的阳模板能够覆盖阴模板的尾翼部分。The method for preparing a rocket-like microneedle micromotor according to claim 1, characterized in that: the female template has a conical tip portion and a tail portion; the protruding structure of the male template is embedded in the tail of the female template, and the The protruding structure is the same as the shape of the conical needle tip part near the tail part; the male template can cover the tail part of the female template.
  4. 根据权利要求1所述的仿火箭微针微马达的制备方法，其特征在于：所述的水凝胶预溶液为聚乙二醇二丙烯酸酯水溶液、甲基丙烯酸酐化明胶水溶液中的一种，且其中含有1％的光引发剂。The preparation method of imitation rocket microneedle micromotor according to claim 1, is characterized in that: described hydrogel pre-solution is a kind of in polyethylene glycol diacrylate aqueous solution, methacrylic anhydride gelatin aqueous solution , and it contains 1% photoinitiator.
  5. 根据权利要求1所述的仿火箭微针微马达的制备方法，其特征在于：通过真空抽气或离心法去除阴模板内水凝胶预溶液中的空气。The method for preparing a rocket-like microneedle micromotor according to claim 1, wherein the air in the hydrogel pre-solution in the negative template is removed by vacuum pumping or centrifugation.
  6. 根据权利要求1所述的仿火箭微针微马达的制备方法，其特征在于：水凝胶预溶液的固化方式为紫外聚合。The method for preparing a rocket-like microneedle micromotor according to claim 1, wherein the curing method of the hydrogel pre-solution is ultraviolet polymerization.
  7. 根据权利要求1所述的仿火箭微针微马达的制备方法，其特征在于：步骤(3)中所述燃料物质为镁颗粒、锌颗粒或铂颗粒中的一种。The method for preparing a rocket-like microneedle micromotor according to claim 1, wherein the fuel material in step (3) is one of magnesium particles, zinc particles or platinum particles.
  8. 根据权利要求1所述的仿火箭微针微马达的制备方法，其特征在于：燃料物质的负载体积为4.0×10 -4立方厘米。 The method for preparing a rocket-like microneedle micromotor according to claim 1, wherein the load volume of the fuel material is 4.0× 10-4 cubic centimeters.
  9. 权利要求1-8任一项所述方法制备的仿火箭微针微马达。The rocket-like microneedle micromotor prepared by the method of any one of claims 1-8.
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