技术领域Technical Field
本发明涉及微纳机器人技术领域，具体涉及一种微纳机器人及其制备方法与应用。The present invention relates to the technical field of micro-nano robots, and in particular to a micro-nano robot and a preparation method and application thereof.
背景技术Background technique
近年来，微纳机器人因其体积小、可无线操控、及自主智能化运动等特点而受到广泛关注。其在传感检测、微纳尺度水平输送、疾病的诊断及治疗及微创手术等领域具有巨大的潜在应用价值。In recent years, micro-nano robots have attracted widespread attention due to their small size, wireless control, and autonomous intelligent movement. They have great potential application value in the fields of sensor detection, micro-nanoscale horizontal transportation, disease diagnosis and treatment, and minimally invasive surgery.
然而，因受到制备材料、界面效应及低雷诺数环境下的运动限制，微纳机器人的发展面临诸多挑战，其中最重要的一个方面是其功能比较单一，难以满足实际的工作要求。利用物理或化学改性的方法对制备微纳机器人的材料进行改性，赋予其特定的功能，是对微纳机器人进行功能化行之有效的方法。微纳机器人的功能化是使微纳机器人执行导航以外其它额外任务的关键步骤。对于生物应用，功能化过程不仅可以应用于靶向药物的运输，还可以应用于体外和体内微纳机器人的可视化和跟踪(即定位)。此外，功能化过程还可以改善生物相容性，并防止免疫系统将微纳机器人识别为异物并对其进行攻击，这会增加其在体内的保留时间。迄今为止，几种针对特殊生物医用的功能化策略和方法被探索，其中包括物理结合和化学键合，将药物、聚合物、蛋白质和QD分子结合或锚定在微纳机器人上。However, due to the limitations of the materials used, interface effects, and motion in low Reynolds number environments, the development of micro-nano robots faces many challenges, one of the most important of which is that their functions are relatively simple and difficult to meet actual work requirements. Modifying the materials used to prepare micro-nano robots by physical or chemical modification methods and giving them specific functions is an effective method for functionalizing micro-nano robots. The functionalization of micro-nano robots is a key step in enabling micro-nano robots to perform additional tasks other than navigation. For biological applications, the functionalization process can be applied not only to the transportation of targeted drugs, but also to the visualization and tracking (i.e., positioning) of micro-nano robots in vitro and in vivo. In addition, the functionalization process can also improve biocompatibility and prevent the immune system from identifying micro-nano robots as foreign bodies and attacking them, which will increase their retention time in the body. To date, several functionalization strategies and methods for special biomedical applications have been explored, including physical binding and chemical bonding to bind or anchor drugs, polymers, proteins, and QD molecules to micro-nano robots.
为得到特定功能且具有均匀稳定形状结构的微纳机器人，目前大多采用光刻或者3D打印等技术，利用光刻胶等材料制备微纳机器人。然而这些材料通常具有极大的生物毒性，且其生物相容性较差，另外目前所制得微纳机器人功能单一，这在很大程度上限制了微纳机器人在生物医学领域中的应用。In order to obtain micro-nano robots with specific functions and uniform and stable shapes and structures, most of the current technologies are photolithography or 3D printing, using materials such as photoresists to prepare micro-nano robots. However, these materials usually have great biotoxicity and poor biocompatibility. In addition, the functions of the micro-nano robots currently prepared are single, which greatly limits the application of micro-nano robots in the biomedical field.
发明内容Summary of the invention
为了克服上述现有技术存在的问题，本发明的目的之一在于提供一种微纳机器人。本发明的目的之二在于提供这种微纳机器人的制备方法。本发明的目的之三在于提供这种微纳机器人的应用。In order to overcome the problems existing in the above-mentioned prior art, one of the purposes of the present invention is to provide a micro-nano robot. The second purpose of the present invention is to provide a method for preparing such a micro-nano robot. The third purpose of the present invention is to provide an application of such a micro-nano robot.
本发明将海藻酸钠或壳聚糖为初始材料，通过物理或化学手段对其进行荧光化功能改性，以其为制备材料并利用光刻等技术手段制备具有特定形状结构特点的微纳机器人，推动微纳机器人在生物医学领域中的应用。The present invention uses sodium alginate or chitosan as the initial material, performs fluorescence functional modification on it by physical or chemical means, uses it as the preparation material and utilizes technical means such as photolithography to prepare a micro-nano robot with specific shape and structural characteristics, thereby promoting the application of micro-nano robots in the biomedical field.
为了实现上述目的，本发明所采取的技术方案是：In order to achieve the above object, the technical solution adopted by the present invention is:
本发明第一方面提供了一种微纳机器人，包括层叠设置的功能层和磁性层；所述功能层包括功能性物质和光交联聚合物；所述功能性物质设置在光交联聚合物的内部；所述功能性物质为荧光分子修饰的海藻酸钠或荧光分子修饰的壳聚糖；所述磁性层包括磁性材料。The first aspect of the present invention provides a micro-nano robot, comprising a functional layer and a magnetic layer stacked in layers; the functional layer comprises a functional substance and a photo-cross-linked polymer; the functional substance is arranged inside the photo-cross-linked polymer; the functional substance is sodium alginate modified with fluorescent molecules or chitosan modified with fluorescent molecules; the magnetic layer comprises a magnetic material.
优选地，所述荧光分子修饰的海藻酸钠为四苯乙烯荧光分子修饰的海藻酸钠。Preferably, the sodium alginate modified with fluorescent molecules is sodium alginate modified with tetraphenylethylene fluorescent molecules.
所述四苯乙烯荧光分子为带有氨基的四苯乙烯。进一步地，所述带有氨基的四苯乙烯的氨基数量为1-4个。更进一步地，所述带氨基的四苯乙烯的氨基可为短链/长链/支链的氨基，且氨基为端基。The tetraphenylethylene fluorescent molecule is a tetraphenylethylene with amino groups. Further, the number of amino groups of the tetraphenylethylene with amino groups is 1-4. Furthermore, the amino groups of the tetraphenylethylene with amino groups can be short-chain/long-chain/branched amino groups, and the amino groups are terminal groups.
优选地，所述荧光分子修饰的壳聚糖为四苯乙烯荧光分子修饰的壳聚糖。Preferably, the chitosan modified with fluorescent molecules is chitosan modified with tetraphenylethylene fluorescent molecules.
更优选地，所述四苯乙烯荧光分子为带有羧基的四苯乙烯。进一步地，所述带有羧基的四苯乙烯的羧基数量为1-4个。更进一步地，所述带羧基的四苯乙烯的羧基可为短链/长链/支链的羧基，且羧基为端基。More preferably, the tetraphenylethylene fluorescent molecule is a tetraphenylethylene with a carboxyl group. Further, the number of carboxyl groups of the tetraphenylethylene with a carboxyl group is 1-4. Furthermore, the carboxyl group of the tetraphenylethylene with a carboxyl group can be a short-chain/long-chain/branched carboxyl group, and the carboxyl group is a terminal group.
更优选地，所述功能性物质设置在光交联聚合物的内部具体为：所述功能性物质锁定在聚乙二醇二丙烯酸酯聚合所形成的网络结构中。More preferably, the functional substance is disposed inside the photo-crosslinked polymer, specifically: the functional substance is locked in a network structure formed by polymerization of polyethylene glycol diacrylate.
优选地，所述磁性材料选自铁、钴、镍及其合金或磁性化合物中的至少一种。Preferably, the magnetic material is selected from at least one of iron, cobalt, nickel and alloys or magnetic compounds thereof.
更优选地，所述磁性材料选自括Fe3O4、铁酸钴、铁酸镍、铁铬钴合金、铝镍钴合金中的至少一种。More preferably, the magnetic material is selected from at least one of Fe3 O4 , cobalt ferrite, nickel ferrite, iron-chromium-cobalt alloy, and aluminum-nickel-cobalt alloy.
优选地，所述微纳机器人的尺寸小于1000μm。Preferably, the size of the micro-nano robot is less than 1000 μm.
优选地，所述微纳机器人为弧形结构；所述弧形结构的圆周角为91°-179°。Preferably, the micro-nano robot is an arc-shaped structure; the circumferential angle of the arc-shaped structure is 91°-179°.
优选地，所述功能性物质与光交联聚合物的质量比为1：(1-2)。Preferably, the mass ratio of the functional substance to the photo-crosslinked polymer is 1:(1-2).
更优选地，所述荧光分子修饰的海藻酸钠与光交联聚合物的质量比为1：(1-1.5)。More preferably, the mass ratio of the fluorescent molecule-modified sodium alginate to the photo-crosslinked polymer is 1:(1-1.5).
更优选地，所述荧光分子修饰的壳聚糖与光交联聚合物的质量比为1：(1.5-2)。More preferably, the mass ratio of the fluorescent molecule-modified chitosan to the photo-crosslinked polymer is 1:(1.5-2).
本发明第二方面提供了第一方面所述的微纳机器人的制备方法，包括如下步骤：The second aspect of the present invention provides a method for preparing the micro-nano robot according to the first aspect, comprising the following steps:
S1.1、将海藻酸钠与荧光分子进行偶联反应，得到荧光分子修饰的海藻酸钠；S1.1, coupling reaction of sodium alginate and fluorescent molecule to obtain sodium alginate modified with fluorescent molecule;
S1.2、将壳聚糖与带负电荷的荧光分子进行复合，得到荧光分子修饰的壳聚糖；S1.2, compounding chitosan with negatively charged fluorescent molecules to obtain chitosan modified with fluorescent molecules;
S2、将荧光分子修饰的海藻酸钠或荧光分子修饰的壳聚糖、光交联剂与光引发剂在溶剂中混合，配置为功能化光刻前驱液；S2, mixing fluorescent molecule-modified sodium alginate or fluorescent molecule-modified chitosan, a photocrosslinker and a photoinitiator in a solvent to prepare a functionalized photolithography precursor solution;
S3、将功能化光刻前驱液涂覆在基板表面，进行光刻，形成具有微纳机器人结构的功能层；S3, coating a functionalized photolithography precursor liquid on the surface of the substrate, performing photolithography, and forming a functional layer having a micro-nano robot structure;
S4、在功能层上涂覆磁性材料溶液烘烤形成磁性层，即制得微纳机器人。S4. Coating a magnetic material solution on the functional layer and baking it to form a magnetic layer, thereby obtaining a micro-nano robot.
优选地，步骤S1.1中，所述荧光分子修饰的海藻酸钠是由包括如下步骤的制备方法制得：在1-乙基-(3-二甲基氨基丙基)碳二亚胺盐酸盐和N-羟基琥珀酰亚胺(EDC和NHS)的存在下，海藻酸钠与带有氨基的四苯乙烯发生偶联反应，得到四苯乙烯荧光分子修饰的海藻酸钠。Preferably, in step S1.1, the sodium alginate modified with the fluorescent molecule is prepared by a preparation method comprising the following steps: in the presence of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide (EDC and NHS), sodium alginate is subjected to a coupling reaction with tetraphenylethylene having an amino group to obtain sodium alginate modified with the tetraphenylethylene fluorescent molecule.
更优选地，所述海藻酸钠与带有氨基的四苯乙烯的质量比为(30-100)：1。More preferably, the mass ratio of the sodium alginate to the tetraphenylethylene having an amino group is (30-100):1.
更优选地，所述带有氨基的四苯乙烯、EDC与NHS的质量比为(6-12)：1：(12-18)。More preferably, the mass ratio of the tetraphenylethylene with amino group, EDC and NHS is (6-12):1:(12-18).
更优选地，所述偶联反应的反应温度为15℃-40℃；反应时间为1-3h。More preferably, the reaction temperature of the coupling reaction is 15°C-40°C; and the reaction time is 1-3h.
优选地，步骤S1.2中，所述荧光分子修饰的壳聚糖是由包括如下步骤的制备方法制得：将壳聚糖与带有羧基的四苯乙烯在乙酸溶液中混合，得到羧化四苯乙烯荧光分子修饰的壳聚糖。Preferably, in step S1.2, the chitosan modified with fluorescent molecules is prepared by a preparation method comprising the following steps: mixing chitosan with tetraphenylethylene having carboxyl groups in an acetic acid solution to obtain chitosan modified with carboxylated tetraphenylethylene fluorescent molecules.
优选地，所述荧光分子修饰的海藻酸钠或荧光分子修饰的壳聚糖与光交联剂的质量比为1：(1-2)。Preferably, the mass ratio of the fluorescent molecule-modified sodium alginate or fluorescent molecule-modified chitosan to the photocrosslinking agent is 1:(1-2).
优选地，所述光交联剂与光引发剂的质量比为(10-100)：1。Preferably, the mass ratio of the photocrosslinker to the photoinitiator is (10-100):1.
优选地，所述光交联剂为聚乙二醇二丙烯酸酯或聚乙二醇二甲基丙烯酸酯。Preferably, the photocrosslinking agent is polyethylene glycol diacrylate or polyethylene glycol dimethacrylate.
优选地，所述光引发剂为2-羟基-2-甲基-1-[4-(2-羟基乙氧基)苯基]-1-丙酮(光引发剂2959)。Preferably, the photoinitiator is 2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone (photoinitiator 2959).
优选地，所述溶剂为水或乙酸溶液(2wt％)。Preferably, the solvent is water or acetic acid solution (2 wt %).
优选地，所述修饰荧光分子的海藻酸钠或荧光分子修饰的壳聚糖与溶剂的质量比为1：(10-30)。Preferably, the mass ratio of the sodium alginate modified with fluorescent molecules or chitosan modified with fluorescent molecules to the solvent is 1:(10-30).
优选地，步骤S3中，所述基板为但不限于硅片/玻璃等光滑平整的基板。Preferably, in step S3, the substrate is but not limited to a smooth and flat substrate such as a silicon wafer or glass.
优选地，步骤S3中，在涂覆功能化光刻前驱液前还包括对所述基板进行表面处理使其形成亲水表面的步骤。Preferably, in step S3, before coating the functionalized photolithography precursor solution, the step of surface treating the substrate to form a hydrophilic surface is also included.
优选地，步骤S3中还包括如下步骤：在基板表面涂覆葡聚糖溶液，形成牺牲层，再将功能化光刻前驱液涂覆在牺牲层表面，进行光刻，形成具有微纳机器人结构的功能层。Preferably, step S3 also includes the following steps: coating a dextran solution on the surface of the substrate to form a sacrificial layer, coating a functionalized photolithography precursor solution on the surface of the sacrificial layer, and performing photolithography to form a functional layer having a micro-nano robot structure.
更优选地，在光刻后还包括采用超声辅助葡聚糖溶解。More preferably, after photolithography, ultrasound-assisted dextran dissolution is further included.
在本发明中，在基板上旋涂葡聚糖溶液，是因为葡聚糖膜层可溶于水，在制备完成后，置于水中溶解葡聚糖膜层，所制备的结构可以无损地从基板上剥离。In the present invention, the dextran solution is spin-coated on the substrate because the dextran film layer is soluble in water. After the preparation is completed, the dextran film layer is placed in water to dissolve, and the prepared structure can be peeled off from the substrate without damage.
优选地，步骤S3中，所述涂覆的方式为旋涂，具体工艺参数为：旋涂速度为100-3500rpm；旋涂时间10-60s。Preferably, in step S3, the coating method is spin coating, and the specific process parameters are: spin coating speed is 100-3500 rpm; spin coating time is 10-60 s.
优选地，步骤S3中，所述光刻的步骤具体为：在所述磁性层表面涂覆光刻胶，对所述光刻胶进行曝光、显影，完成光刻。Preferably, in step S3, the photolithography step specifically includes: coating photoresist on the surface of the magnetic layer, exposing and developing the photoresist, and completing the photolithography.
更优选地，所述曝光为紫外曝光。进一步优选地，所述紫外曝光的曝光时间为10-30s；光照强度30-60mW/cm2。More preferably, the exposure is ultraviolet exposure. Further preferably, the exposure time of the ultraviolet exposure is 10-30 s and the light intensity is 30-60 mW/cm2 .
优选地，步骤S4中，所述烘烤为在80-100℃下进行烘干。Preferably, in step S4, the baking is drying at 80-100°C.
本发明的第三方面是提供一种应用，所述应用为控制第一方面微纳机器人在磁场中运动。The third aspect of the present invention is to provide an application, which is to control the movement of the micro-nano robot of the first aspect in a magnetic field.
优选地，所述磁场为三维均匀旋转磁场。Preferably, the magnetic field is a three-dimensional uniform rotating magnetic field.
更优选地，所述三维均匀旋转磁场的场强为2-12mT。More preferably, the field strength of the three-dimensional uniform rotating magnetic field is 2-12 mT.
本发明的第四方面是提供所述微纳机器人在制备生物医疗产品、非疾病诊断和治疗目的的实时监测或非疾病诊断和治疗目的的智能化驱动中的应用。The fourth aspect of the present invention is to provide the application of the micro-nano robot in the preparation of biomedical products, real-time monitoring for non-disease diagnosis and treatment purposes, or intelligent driving for non-disease diagnosis and treatment purposes.
本发明的有益效果是：The beneficial effects of the present invention are:
本发明提供了一种微纳机器人，将功能性物质锁定在光交联剂聚合所形成的网络结构中，赋予微纳机器人特定的结构形状及功能，使得该磁控微纳机器人在磁场中可以实现快速定向运动，能够实现在微小空间尺度上对其进行智能化驱动，且功能性物质具有荧光特性，能更好地进行示踪定位。The present invention provides a micro-nano robot, which locks functional substances in a network structure formed by polymerization of a photocrosslinking agent, giving the micro-nano robot a specific structural shape and function, so that the magnetically controlled micro-nano robot can achieve rapid directional movement in a magnetic field, can be intelligently driven on a micro spatial scale, and the functional substances have fluorescent properties, which can better perform tracing and positioning.
具体来说，本发明与现有技术相比，具有以下的优点：Specifically, compared with the prior art, the present invention has the following advantages:
1)本发明采用先对初始材料功能化，后进行光刻制备微纳机器人的方法，相对于先光刻制备后功能化的方法，其功能化更均匀、更稳定；另外利用后负载磁性层的方式赋予微纳机器人磁性，更好地实现在旋转磁场条件下对其运动进行精确控制。1) The present invention adopts a method of first functionalizing the initial material and then performing photolithography to prepare the micro-nano robot. Compared with the method of first performing photolithography and then performing functionalization, the functionalization is more uniform and more stable. In addition, the micro-nano robot is endowed with magnetism by a post-loading magnetic layer, so as to better realize precise control of its movement under the condition of a rotating magnetic field.
2)本发明中的非手性二维平面荧光微纳机器人，制备方法简单快速，可进行规模化制备；微纳机器人的主体材料为海藻酸钠或壳聚糖，光交联剂和引发剂均为生物友好型材料，所制备得到的微纳机器人具有良好的生物相容性。本发明利用负载磁性层的方法赋予微纳机器人磁化特性，使其可在磁场驱动下进行运动，与磁控溅射负载磁性颗粒相比，方法简单高效，对设备的要求低，且经过烘烤后磁性颗粒与机器人的结合牢固不易脱落。2) The non-chiral two-dimensional planar fluorescent micro-nano robot in the present invention has a simple and rapid preparation method and can be prepared on a large scale; the main material of the micro-nano robot is sodium alginate or chitosan, and the photocrosslinker and initiator are both bio-friendly materials, and the prepared micro-nano robot has good biocompatibility. The present invention uses the method of loading a magnetic layer to give the micro-nano robot a magnetic property so that it can move under the drive of a magnetic field. Compared with magnetron sputtering loading magnetic particles, the method is simple and efficient, has low requirements on equipment, and after baking, the magnetic particles are firmly combined with the robot and are not easy to fall off.
3)本发明的微纳机器人具有形状简单的特点，区别于其他微纳机器人，在三维均匀旋转磁场的控制下可实现运动。因此在精准生物医疗、可视化研究、实时监控检测、微纳加工制造、污染防护治理或环境修复等领域具有潜在的应用价值。3) The micro-nano robot of the present invention has the characteristics of simple shape, which is different from other micro-nano robots and can realize movement under the control of a three-dimensional uniform rotating magnetic field. Therefore, it has potential application value in the fields of precision biomedicine, visualization research, real-time monitoring and detection, micro-nano processing and manufacturing, pollution prevention and control, or environmental restoration.
附图说明BRIEF DESCRIPTION OF THE DRAWINGS
图1为实施例1微纳机器人正反面的显微镜及荧光显微镜图片；其中图1a为微纳机器人正面的显微镜图片；图1b为微纳机器人正面的荧光显微镜图片；图1c为微纳机器人反面的显微镜图片；图1d为微纳机器人反面的荧光显微镜图片；FIG1 is a microscope and fluorescence microscope picture of the front and back sides of the micro-nano robot of Example 1; FIG1a is a microscope picture of the front side of the micro-nano robot; FIG1b is a fluorescence microscope picture of the front side of the micro-nano robot; FIG1c is a microscope picture of the back side of the micro-nano robot; and FIG1d is a fluorescence microscope picture of the back side of the micro-nano robot;
图2为实施例2微纳机器人正反面的显微镜及荧光显微镜图片；FIG2 is a microscope and fluorescence microscope picture of the front and back sides of the micro-nano robot in Example 2;
图3为对比例1无磁性微纳机器人的结构显微镜图；FIG3 is a microscopic view of the structure of the non-magnetic micro-nano robot of Comparative Example 1;
图4为对比例1和2无磁性微纳机器人的荧光显微镜图；其中图4a为对比例1的无磁性微纳机器人的荧光显微镜图；图4b为对比例2的无磁性微纳机器人的荧光显微镜图。Figure 4 is a fluorescence microscope image of the non-magnetic micro-nano robot of Comparative Examples 1 and 2; Figure 4a is a fluorescence microscope image of the non-magnetic micro-nano robot of Comparative Example 1; Figure 4b is a fluorescence microscope image of the non-magnetic micro-nano robot of Comparative Example 2.
图5为对比例3微纳机器人正反面的显微镜及荧光显微镜图片；其中图5a为微纳机器人正面的显微镜图片；图5b为微纳机器人正面的荧光显微镜图片；图5c为微纳机器人反面的显微镜图片；图5d为微纳机器人反面的荧光显微镜图片；FIG5 is a microscope and fluorescence microscope picture of the front and back sides of the micro-nano robot of Comparative Example 3; FIG5a is a microscope picture of the front side of the micro-nano robot; FIG5b is a fluorescence microscope picture of the front side of the micro-nano robot; FIG5c is a microscope picture of the back side of the micro-nano robot; and FIG5d is a fluorescence microscope picture of the back side of the micro-nano robot;
图6为实施例1微纳机器人与细胞共培养后的细胞存活率图；FIG6 is a graph showing cell survival rates after co-culturing of the micro-nano robot and cells in Example 1;
图7为实施例2微纳机器人与细胞共培养后的细胞存活率图；FIG7 is a graph showing cell survival rates after co-culturing of the micro-nano robot and cells in Example 2;
图8为实施例1微纳机器人在不同时间点的位置及对应的运动姿态；FIG8 shows the position of the micro-nano robot at different time points and the corresponding motion postures of Example 1;
图9为实施例2微纳机器人在不同时间点的位置及对应的运动姿态。FIG9 shows the position of the micro-nano robot in Example 2 at different time points and the corresponding motion postures.
具体实施方式Detailed ways
以下通过具体的实施例对本发明的内容作进一步详细的说明。以下实施例中所用的原料，如无特殊说明，均可从常规商业途径得到或通过简单合成制备分离；所采用的工艺，如无特殊说明，均采用本领域的常规工艺。The present invention is further described in detail below through specific examples. The raw materials used in the following examples, unless otherwise specified, can be obtained from conventional commercial sources or separated by simple synthesis preparation; the processes used, unless otherwise specified, are conventional processes in the art.
实施例1Example 1
本实施例提供一种微纳机器人，其制备方法包括如下步骤：This embodiment provides a micro-nano robot, and the preparation method thereof comprises the following steps:
1)海藻酸钠荧光功能化1) Fluorescence functionalization of sodium alginate
按照质量比为50：1称取海藻酸钠与1-(4-氨基)-1,2,2-三苯乙烯，加入EDC/NHS(EDC、NHS与1-(4-氨基)-1,2,2-三苯乙烯质量比为1：15：9)，在室温条件下反应2h，制得四苯乙烯荧光分子修饰的海藻酸钠，纯化处理并冻干后保存备用。Sodium alginate and 1-(4-amino)-1,2,2-triphenylethylene were weighed in a mass ratio of 50:1, EDC/NHS (the mass ratio of EDC, NHS and 1-(4-amino)-1,2,2-triphenylethylene was 1:15:9) was added, and the mixture was reacted at room temperature for 2 h to obtain sodium alginate modified with tetraphenylethylene fluorescent molecules, which was purified, freeze-dried and stored for later use.
2)配置功能化前驱液2) Prepare functionalized precursor solution
将1.0g四苯乙烯荧光分子修饰的海藻酸钠溶于19g超纯水中，溶解完全后加入1.2mL PEGDA(分子量为700，质量为1.344g)并混合均匀；加入0.2mL(0.2g/mL)的光引发剂2959(2-羟基-2-甲基-1-[4-(2-羟基乙氧基)苯基]-1-丙酮)的甲醇溶液，混合均匀后得到功能化光刻前驱液。1.0 g of sodium alginate modified with tetraphenylethylene fluorescent molecules was dissolved in 19 g of ultrapure water. After complete dissolution, 1.2 mL of PEGDA (molecular weight 700, mass 1.344 g) was added and mixed evenly. 0.2 mL (0.2 g/mL) of a methanol solution of a photoinitiator 2959 (2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone) was added and mixed evenly to obtain a functionalized photolithography precursor solution.
3)光刻3) Photolithography
将洁净的硅片进行Plasma处理，得到亲水表面，然后旋涂5wt％的葡聚糖溶液，旋涂角速度为1000rpm，时长30s，旋涂后置于95℃的热板上烘烤4min直至烘干。在葡聚糖层上涂覆步骤2)配制的功能化光刻前驱液，旋涂角速度200rpm，时长20s，风干后进行紫外曝光22s(44±0.4mW/cm2)、显影，完成光刻，在水溶液中剥离得到仅由功能化前驱液形成的近似弧形的无磁性的微纳机器人结构。The clean silicon wafer was plasma treated to obtain a hydrophilic surface, and then 5wt% dextran solution was spin-coated at an angular speed of 1000rpm for 30s. After spin-coating, it was placed on a hot plate at 95°C and baked for 4min until it was dried. The functionalized photolithography precursor solution prepared in step 2) was coated on the dextran layer at an angular speed of 200rpm for 20s. After air drying, it was exposed to ultraviolet light for 22s (44±0.4mW/cm2 ) and developed to complete the photolithography. The solution was peeled off in an aqueous solution to obtain a non-magnetic micro-nano robot structure that was approximately arc-shaped and formed only by the functionalized precursor solution.
4)负载磁性层4) Loading magnetic layer
将步骤3)所得到微纳机器人结构的分散液均匀单层分散于干净的硅片上，烘干后旋涂浓度为400mg/mL的Fe3O4的γ-丁内酯(GBL)溶液，旋涂速度200rpm，时长10s，后置于热板上95℃烘干，冲洗后得到具有双层结构负载磁性Fe3O4纳米颗粒的磁性微纳机器人，其正反面的显微镜及荧光显微镜图片如图1中的a-b所示，其中图1a为微纳机器人正面的显微镜图片；图1b为微纳机器人正面的荧光显微镜图片；图1c为微纳机器人反面的显微镜图片；图1d为微纳机器人反面的荧光显微镜图片；图1b中微纳机器人因具有荧光分子修饰的海藻酸钠而呈现荧光。The dispersion of the micro-nano robot structure obtained in step 3) is uniformly dispersed in a single layer on a clean silicon wafer, and after drying, a γ-butyrolactone (GBL) solution ofFe3O4 with a concentration of 400 mg/mL is spin-coated at a speed of 200 rpm for 10 s, and then placed on a hot plate for drying at 95°C. After rinsing, a magnetic micro-nano robot with a double-layer structure loaded with magneticFe3O4nanoparticles is obtained, and the microscope and fluorescence microscope images of the front and back sides are shown in ab of Figure 1, wherein Figure 1a is a microscope image of the front side of the micro-nano robot; Figure 1b is a fluorescence microscope image of the front side of the micro-nano robot; Figure 1c is a microscope image of the back side of the micro-nano robot; Figure 1d is a fluorescence microscope image of the back side of the micro-nano robot; the micro-nano robot in Figure 1b exhibits fluorescence due to the sodium alginate modified with fluorescent molecules.
实施例2Example 2
本实施例提供一种微纳机器人，其制备方法包括如下步骤：This embodiment provides a micro-nano robot, and the preparation method thereof comprises the following steps:
1)壳聚糖荧光功能化1) Fluorescence functionalization of chitosan
1.0g壳聚糖溶于19g乙酸溶液(2wt％)，溶解完全后加入0.5mL的带有羧基的四苯乙烯(TPECOOH)的四氢呋喃溶液(20mg/mL)并混合均匀，壳聚糖分子中的质子化氨基与TPECOOH中的羧基之间由于静电相互作用而复合在一起，得到四苯乙烯荧光分子修饰的壳聚糖的乙酸溶液。1.0 g of chitosan was dissolved in 19 g of acetic acid solution (2 wt%). After complete dissolution, 0.5 mL of tetrahydrofuran solution (20 mg/mL) of tetraphenylethylene (TPECOOH) with carboxyl groups was added and mixed evenly. The protonated amino groups in the chitosan molecules and the carboxyl groups in TPECOOH were complexed due to electrostatic interaction to obtain an acetic acid solution of chitosan modified with tetraphenylethylene fluorescent molecules.
2)配置功能化前驱液2) Prepare functionalized precursor solution
向步骤1)含四苯乙烯荧光分子修饰的壳聚糖的乙酸溶液中加入1.5mL PEGDA(分子量为700，质量为1.68g)和加入0.1mL(0.2g/mL)的光引发剂2959(2-羟基-2-甲基-1-[4-(2-羟基乙氧基)苯基]-1-丙酮)的甲醇溶液，混合均匀后得到光刻前驱液。To the acetic acid solution of chitosan modified with tetraphenylethylene fluorescent molecules in step 1), 1.5 mL of PEGDA (molecular weight 700, mass 1.68 g) and 0.1 mL (0.2 g/mL) of a methanol solution of a photoinitiator 2959 (2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone) were added, and the mixture was evenly mixed to obtain a photolithography precursor solution.
3)光刻3) Photolithography
将洁净的硅片进行Plasma处理，得到亲水表面，然后旋涂5wt％的葡聚糖溶液，旋涂角速度为1000rpm，时长30s，旋涂后置于95℃的热板上烘烤4min直至烘干。在葡聚糖层上涂覆步骤2)配制的功能化光刻前驱液，旋涂角速度2000rpm，时长30s，风干后进行紫外曝光17s(44±0.4mW/cm2)、显影，完成光刻，在乙酸溶液(2wt％)中剥离得到仅由功能化前驱液形成的近似弧形的无磁性的微纳机器人结构。The clean silicon wafer was plasma treated to obtain a hydrophilic surface, and then 5wt% dextran solution was spin-coated at an angular speed of 1000rpm for 30s. After spin-coating, it was placed on a hot plate at 95°C and baked for 4min until it was dried. The functionalized photolithography precursor solution prepared in step 2) was coated on the dextran layer at an angular speed of 2000rpm for 30s. After air drying, it was exposed to ultraviolet light for 17s (44±0.4mW/cm2 ) and developed to complete photolithography. The surface was peeled off in an acetic acid solution (2wt%) to obtain a nearly arc-shaped non-magnetic micro-nano robot structure formed only by the functionalized precursor solution.
4)负载磁性层4) Loading magnetic layer
将步骤3)所得到微纳机器人结构的分散液单层均匀分散于干净的硅片上，烘干后旋涂浓度为400mg/mL的Ni纳米颗粒的γ-丁内酯(GBL)溶液，旋涂速度200rpm，时长10s，后置于热板上95℃烘干，冲洗后得到具有双层结构负载磁性Ni纳米颗粒的磁性微纳机器人，其正反面的显微镜及荧光显微镜图片如图2中的a-b所示，其中图2a为微纳机器人正面的显微镜图片；图2b为微纳机器人正面的荧光显微镜图片；图2c为微纳机器人反面的显微镜图片；图2d为微纳机器人反面的荧光显微镜图片；图2b中微纳机器人因具有荧光分子修饰的壳聚糖而呈现荧光。反面的荧光显微镜图片；图2b中微纳机器人因具有荧光分子修饰的壳聚糖而呈现荧光。The dispersion liquid monolayer of the micro-nano robot structure obtained in step 3) is uniformly dispersed on a clean silicon wafer, and after drying, a γ-butyrolactone (GBL) solution of Ni nanoparticles with a concentration of 400 mg/mL is spin-coated at a speed of 200 rpm for 10 seconds, and then placed on a hot plate for drying at 95°C. After rinsing, a magnetic micro-nano robot with a double-layer structure loaded with magnetic Ni nanoparticles is obtained, and the microscope and fluorescence microscope images of the front and back sides are shown in a-b in Figure 2, wherein Figure 2a is a microscope image of the front side of the micro-nano robot; Figure 2b is a fluorescence microscope image of the front side of the micro-nano robot; Figure 2c is a microscope image of the back side of the micro-nano robot; Figure 2d is a fluorescence microscope image of the back side of the micro-nano robot; the micro-nano robot in Figure 2b exhibits fluorescence due to chitosan modified with fluorescent molecules. Fluorescence microscope image of the back side; the micro-nano robot in Figure 2b exhibits fluorescence due to chitosan modified with fluorescent molecules.
对比例1Comparative Example 1
仅由荧光分子功能化海藻酸钠前驱液形成的近似弧形的无磁性微纳机器人，其制备方法包括以下步骤：The preparation method of the arc-shaped non-magnetic micro-nano robot formed only by a fluorescent molecule functionalized sodium alginate precursor solution comprises the following steps:
将洁净的硅片进行Plasma处理，得到亲水表面，然后旋涂5wt％的葡聚糖溶液，旋涂角速度为500rpm，时长60s。旋涂后置于95℃的热板上烘烤4min直至烘干。涂覆实施例1步骤2)的功能化荧光前驱液，旋涂角速度1000rpm，时长60s。风干后将样本置于载物台上，上方搭载掩膜版，置于紫外线下曝光后于水溶液中显影并剥离，得到透明的无磁性的微纳机器人。如图3所示，该微纳机器人表面没有黑色Fe3O4磁性层，仅为功能化前驱液形成的透明结构，图4中a为其荧光显微镜图。The clean silicon wafer was plasma treated to obtain a hydrophilic surface, and then 5wt% dextran solution was spin-coated at an angular speed of 500rpm for 60s. After spin coating, it was placed on a hot plate at 95°C and baked for 4min until dried. The functionalized fluorescent precursor solution of step 2) of Example 1 was applied at an angular speed of 1000rpm for 60s. After air drying, the sample was placed on a stage, a mask was placed on top, and after exposure to ultraviolet light, it was developed in an aqueous solution and peeled off to obtain a transparent, non-magnetic micro-nano robot. As shown in Figure 3, there is noblackFe3O4 magnetic layer on the surface of the micro-nano robot, but only a transparent structure formed by the functionalized precursor solution. Figure 4a is its fluorescence microscope image.
对比例2Comparative Example 2
仅由海藻酸钠前驱液形成的近似弧形的无磁性微纳机器人，其制备方法包括以下步骤：The preparation method of the arc-shaped non-magnetic micro-nano robot formed only by sodium alginate precursor liquid comprises the following steps:
1)配置前驱液；1) Prepare precursor solution;
1.0g海藻酸钠溶于19g超纯水中，溶解完全后加入1.2mL PEGDA(分子量为700，质量为1.344g)并混合均匀。加入0.2mL(0.2g/mL)的光引发剂2959(2-羟基-2-甲基-1-[4-(2-羟基乙氧基)苯基]-1-丙酮)的甲醇溶液，混合均匀后得到海藻酸钠光刻前驱液。1.0 g of sodium alginate was dissolved in 19 g of ultrapure water, and after complete dissolution, 1.2 mL of PEGDA (molecular weight 700, mass 1.344 g) was added and mixed evenly. 0.2 mL (0.2 g/mL) of a methanol solution of a photoinitiator 2959 (2-hydroxy-2-methyl-1-[4-(2-hydroxyethoxy)phenyl]-1-propanone) was added and mixed evenly to obtain a sodium alginate photolithography precursor solution.
2)光刻；2) Photolithography;
将洁净的硅片进行Plasma处理，得到亲水表面，然后旋涂5wt％的葡聚糖溶液，旋涂角速度为1000rpm，时长30s。旋涂后置于95℃的热板上烘烤4min直至烘干。于葡聚糖层上涂覆步骤1)配制的光刻前驱液，旋涂角速度1000rpm，时长30s。风干后进行光刻，于水溶液中剥离得到仅由海藻酸钠前驱液形成的近似弧形的无磁性的微纳机器人结构。如图4b所示是其在与对比例1同样条件下的荧光显微镜图。The clean silicon wafer was plasma treated to obtain a hydrophilic surface, and then 5wt% dextran solution was spin-coated at an angular speed of 1000rpm for 30s. After spin coating, it was placed on a hot plate at 95°C and baked for 4min until dried. The photolithography precursor solution prepared in step 1) was coated on the dextran layer at an angular speed of 1000rpm for 30s. After air drying, photolithography was performed, and the non-magnetic micro-nano robot structure approximately in the shape of an arc formed only by the sodium alginate precursor solution was peeled off in an aqueous solution. As shown in Figure 4b, it is a fluorescence microscope image under the same conditions as Comparative Example 1.
对比例3Comparative Example 3
仅由荧光分子功能化壳聚糖前驱液形成的近似弧形的无磁性微纳机器人，其制备方法包括以下步骤：The preparation method of the arc-shaped non-magnetic micro-nano robot formed only by a fluorescent molecule functionalized chitosan precursor solution comprises the following steps:
将洁净的硅片进行Plasma处理，得到亲水表面，然后旋涂5wt％的葡聚糖溶液，旋涂角速度为500rpm，时长60s。旋涂后置于95℃的热板上烘烤4min直至烘干。涂覆实施例2步骤2)的功能化荧光前驱液，旋涂角速度1000rpm，时长60s。风干后将样本置于载物台上，上方搭载掩膜版，置于紫外线下曝光后于水溶液中显影并剥离，得到透明的无磁性的微纳机器人，如图5a和5b所示。该微纳机器人表面没有磁性层，仅为功能化前驱液形成的透明结构，其正反面因具有荧光分子修饰的壳聚糖而呈现荧光，如图5b和5d所示。The clean silicon wafer was plasma treated to obtain a hydrophilic surface, and then 5wt% dextran solution was spin-coated at an angular speed of 500rpm for 60s. After spin coating, it was placed on a hot plate at 95°C and baked for 4min until dried. The functionalized fluorescent precursor solution of step 2) of Example 2 was applied at an angular speed of 1000rpm for 60s. After air drying, the sample was placed on a stage, a mask was placed on top, and after exposure to ultraviolet light, it was developed in an aqueous solution and peeled off to obtain a transparent, non-magnetic micro-nano robot, as shown in Figures 5a and 5b. There is no magnetic layer on the surface of the micro-nano robot, but only a transparent structure formed by the functionalized precursor solution. The front and back sides of the micro-nano robot are fluorescent due to chitosan modified with fluorescent molecules, as shown in Figures 5b and 5d.
实验分析experiment analysis
1、生物毒性测试1. Biological toxicity test
本测试例中，对实施例1和实施例2中所制备的微纳机器人进行生物毒性测试，具体步骤为：In this test example, the micro-nano robots prepared in Example 1 and Example 2 were subjected to a biological toxicity test, and the specific steps were as follows:
以4×105/mL的密度接种MCF 10A细胞于培养皿中，细胞贴壁后加入不同浓度的磁控微纳机器人粉碎后的分散液，并置于37℃和5％ CO2条件下培养，继续培养24h后，利用细胞计数试剂盒(CCK8)测定细胞的存活率。MCF10A cells were inoculated at a density of 4×105 /mL in a culture dish. After the cells adhered to the wall, different concentrations of the dispersion after the magnetically controlled micro-nano robot was added and cultured at 37°C and 5% CO2. After culturing for 24 hours, the cell survival rate was determined using a cell counting kit (CCK8).
图6为实施例1所制备的微纳机器人的细胞存活率结果，由图可知随着微纳机器人粉碎材料的浓度逐渐增大，其细胞存活率逐渐降低，但当其浓度增大至10mg/mL时，其存活率仍在80％以上，表明当浓度在0-10mg/mL范围内，磁控微纳机器人表现出无明显的细胞毒性，生物相容性良好。Figure 6 shows the cell survival rate results of the micro-nano robot prepared in Example 1. It can be seen from the figure that as the concentration of the micro-nano robot crushed material gradually increases, its cell survival rate gradually decreases, but when its concentration increases to 10 mg/mL, its survival rate is still above 80%, indicating that when the concentration is in the range of 0-10 mg/mL, the magnetically controlled micro-nano robot shows no obvious cytotoxicity and good biocompatibility.
图7为实施例2所制备的微纳机器人的细胞存活率结果，由图可知随着微纳机器人粉碎材料的浓度逐渐增大，其细胞存活率逐渐降低，但当其浓度增大至20mg/mL时，其存活率仍在80％以上，表明当浓度在0-20mg/mL范围内，磁控微纳机器人表现无明显的细胞毒性，生物相容性良好。Figure 7 shows the cell survival rate results of the micro-nano robot prepared in Example 2. It can be seen from the figure that as the concentration of the micro-nano robot crushed material gradually increases, its cell survival rate gradually decreases, but when its concentration increases to 20 mg/mL, its survival rate is still above 80%, indicating that when the concentration is in the range of 0-20 mg/mL, the magnetically controlled micro-nano robot exhibits no obvious cytotoxicity and has good biocompatibility.
2、运动性能测试2. Sports performance test
本测试例中，对实施例1和实施例2中得到的微纳机器人进行运动性能测试：In this test example, the motion performance test was performed on the micro-nano robots obtained in Example 1 and Example 2:
分别将实施例1和实施例2的微纳机器人置于去离子水中，施加大小为8mT的三维均匀旋转磁场，磁场发生器为三维亥姆霍兹线圈系统，调节其运动频率为2Hz，控制其运动，观察其运动稳定性。The micro-nano robots of Example 1 and Example 2 were placed in deionized water respectively, and a three-dimensional uniform rotating magnetic field of 8 mT was applied. The magnetic field generator was a three-dimensional Helmholtz coil system. The movement frequency was adjusted to 2 Hz, and the movement was controlled to observe the movement stability.
实施例1的微纳机器人在运动过程中不同时间点的位置及对应的运动姿态如图8所示，结果表明，其运动的平均速度为82.02μm/s，其运动轨迹基本呈直线如图8中所示，表明其运动性能稳定。因此可通过磁场对其进行定向运动的操控。The positions of the micro-nano robot of Example 1 at different time points during the movement and the corresponding movement postures are shown in FIG8 . The results show that the average speed of the micro-nano robot is 82.02 μm/s, and the movement trajectory is basically a straight line as shown in FIG8 , indicating that the movement performance is stable. Therefore, the directional movement of the micro-nano robot can be controlled by the magnetic field.
实施例2的微纳机器人在运动过程中不同时间点的位置及对应的运动姿态如图9所示，结果表明，其运动的平均速度为350.36μm/s，其运动轨迹基本呈直线如图9中所示，表明其运动性能稳定。因此可通过磁场对其进行定向运动的操控。The positions of the micro-nano robot of Example 2 at different time points during the movement and the corresponding movement postures are shown in FIG9 . The results show that the average speed of the micro-nano robot is 350.36 μm/s, and the movement trajectory is basically a straight line as shown in FIG9 , indicating that the movement performance is stable. Therefore, the directional movement of the micro-nano robot can be controlled by the magnetic field.
测试结果显示，按照本发明的方法制得的磁控微纳机器人在磁场中可以实现快速定向运动，能够实现在微小空间尺度上对其进行智能化驱动，且其具有荧光特性，因此在精准生物医疗、可视化研究、实时监控检测、微纳加工制造、污染防护治理或环境修复等领域具有潜在的应用价值。The test results show that the magnetically controlled micro-nano robot prepared according to the method of the present invention can achieve rapid directional movement in a magnetic field, can be intelligently driven on a microscopic spatial scale, and has fluorescent properties. Therefore, it has potential application value in the fields of precision biomedicine, visualization research, real-time monitoring and detection, micro-nano processing and manufacturing, pollution prevention and control, or environmental restoration.
上述实施例为本发明较佳的实施方式，但本发明的实施方式并不受上述实施例的限制，其他的任何未背离本发明的精神实质与原理下所作的改变、修饰、替代、组合、简化，均应为等效的置换方式，都包含在本发明的保护范围之内。The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410519752.2ACN118305769A (en) | 2024-04-28 | 2024-04-28 | Micro-nano robot and preparation method and application thereof |
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410519752.2ACN118305769A (en) | 2024-04-28 | 2024-04-28 | Micro-nano robot and preparation method and application thereof |
| Publication Number | Publication Date |
|---|---|
| CN118305769Atrue CN118305769A (en) | 2024-07-09 |
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410519752.2APendingCN118305769A (en) | 2024-04-28 | 2024-04-28 | Micro-nano robot and preparation method and application thereof |
| Country | Link |
|---|---|
| CN (1) | CN118305769A (en) |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103396786A (en)* | 2013-08-06 | 2013-11-20 | 武汉大学 | Reversibly assembled and decomposable fluorescent magnetic nano material and nano biological probe and preparation methods thereof |
| US20150080802A1 (en)* | 2012-03-16 | 2015-03-19 | National University Of Singapore | Novel Method To Fabricate Polymeric Microneedles |
| CN104449674A (en)* | 2014-11-24 | 2015-03-25 | 合肥学院 | Chitosan rod-like microcrystalline fluorescent probe, preparation method and trace metal ion detecting method |
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150080802A1 (en)* | 2012-03-16 | 2015-03-19 | National University Of Singapore | Novel Method To Fabricate Polymeric Microneedles |
| CN103396786A (en)* | 2013-08-06 | 2013-11-20 | 武汉大学 | Reversibly assembled and decomposable fluorescent magnetic nano material and nano biological probe and preparation methods thereof |
| CN104449674A (en)* | 2014-11-24 | 2015-03-25 | 合肥学院 | Chitosan rod-like microcrystalline fluorescent probe, preparation method and trace metal ion detecting method |
| Title |
|---|
| WANG, HY: "Fabrication of Bilayer Magnetically Actuated L-Shaped Microrobot Based on Chitosan via Photolithography", POLYMERS, vol. 14, no. 24, 1 January 2023 (2023-01-01), pages 1 - 15* |
| Publication | Publication Date | Title |
|---|---|---|
| Liu et al. | Recent developments in polydopamine: an emerging soft matter for surface modification and biomedical applications | |
| Rodríguez-Hernández et al. | Preparation of shell cross-linked nano-objects from hybrid-peptide block copolymers | |
| Li et al. | Block copolymer modified surfaces for conjugation of biomacromolecules with control of quantity and activity | |
| Xu et al. | Toward designer magnetite/polystyrene colloidal composite microspheres with controllable nanostructures and desirable surface functionalities | |
| Yan et al. | Poly (acrylic acid)-Lined Nanotubes of Poly (butyl methacrylate)-b lock-poly (2-cinnamoyloxyethyl methacrylate) | |
| Liu et al. | Preparation of magnetic microspheres from water-in-oil emulsion stabilized by block copolymer dispersant | |
| Liu et al. | Fabrication and functionalization of dendritic poly (amidoamine)-immobilized magnetic polymer composite microspheres | |
| CN1302831A (en) | Magnetic high-molecular microsphere and its preparing process | |
| CN102436885A (en) | Method for dispersing iron-based magnetic nanocrystals | |
| Liu et al. | Effective gene delivery based on facilely synthesized “core–shell” Ag@ PDA@ PEI nanoparticles | |
| CN113866073B (en) | Enzyme-sensitive nanomaterials for efficient capture of cancer cells and preparation methods and applications thereof | |
| CN118305769A (en) | Micro-nano robot and preparation method and application thereof | |
| CN107970224B (en) | Preparation method and application of lipid-modified magnetic graphene oxide composite material | |
| CN110734524A (en) | Preparation method of cationic polymer-modified magnetic shell-core microspheres | |
| Nguyen et al. | Rational design of stimuli‐responsive magnetic polymer hybrid (nano) materials | |
| CN115651451B (en) | Magnetic control micro-nano robot with biocompatibility and manufacturing method and application thereof | |
| CN102875823B (en) | Preparation method of magnetic microgel granules | |
| CN108904895A (en) | A kind of preparation method of anti-bacterial attachment nano coating | |
| TWI445550B (en) | Magnetic composite nanoparticles having multiple reactive functional groups of the method for its preparation | |
| Xiong et al. | Magnetically-actuated hydrogel-based achiral planar microswimmers for SERS detection: In situ coprecipitation for continuous loading of iron oxide nanoparticles | |
| CN105273209A (en) | Preparation for modified chitosan poly(2-acrylamide-2-methylpropanesulfonic acid) composite microballoon | |
| Huang et al. | Rapid formation of antifouling coatings via cation–π interactions | |
| CN104630127A (en) | Cell culture substrate capable of inducing enhancement of cell adhesion and preparation method thereof | |
| WO2020048126A1 (en) | Chiral separation method emulating magnetic mineral processing, dedicated magnetically enriched nanoinhibitor | |
| CN108014092A (en) | A kind of preparation method and application of magnetic oxygenated graphene-nucleoprotamine/sodium carboxymethylcellulose compound |
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |