Ethyl cellulose micro-nanorobot, and preparation method and application thereof
By using ethyl cellulose multilayer stacking and infrared processing technology, a three-dimensional micro-nano robot with good biocompatibility was prepared, solving the preparation problem in the existing technology and realizing its application in the biomedical field.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- SOUTHERN UNIVERSITY OF SCIENCE AND TECHNOLOGY
- Filing Date
- 2024-04-28
- Publication Date
- 2026-04-21
AI Technical Summary
Existing technologies are insufficient for efficiently fabricating micro- and nano-robots with good biocompatibility and three-dimensional structures, which limits their application, especially in the biomedical field.
Using ethyl cellulose as the main material, a two-dimensional planar structure was transformed into a three-dimensional structure through a multi-layer stacking method combined with infrared isothermal treatment, thus fabricating a micro-nano robot with magnetic and functional layers.
This technology enables high-throughput, low-cost manufacturing of multifunctional micro-nano robots, improves the biocompatibility of materials, and allows for rapid and controllable movement in magnetic fields, thus promoting their application in the biomedical field.
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Figure CN118219232B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of micro-nano robotics, specifically to an ethyl cellulose micro-nano robot, its preparation method, and its application. Background Technology
[0002] With the development of technology, micro- and nano-level precision devices have gradually attracted attention due to their small size, high precision, and ability to enter confined spaces to assist in performing complex operations. Micro- and nano-robots are a special type of manipulable, intelligent, and automatically controlled micro- and nano-devices, with enormous application prospects in fields such as healthcare, real-time monitoring, intelligent manufacturing, and sensing.
[0003] In the microscopic world, such as with bacteria, the Reynolds number of their environment is as low as 10. -4 To achieve the movement of bacteria-sized microrobots under low Reynolds number conditions, their design must adhere to the scallop theorem, breaking the temporal symmetry of deformation. Inspired by the movement of natural microorganisms such as E. coli and sperm, scientists have created microrobots with biomimetic helical structures and achieved motion manipulation in low Reynolds number environments. However, fabricating three-dimensional helical microrobots requires sophisticated equipment and has low fabrication efficiency. Currently, three-dimensional microrobots are mainly fabricated using technologies such as laser direct writing and 3D printing. Furthermore, the fabrication of microrobots using 3D equipment requires high-quality materials, limiting their application to specific materials such as photoresists. These materials typically exhibit high biotoxicity and poor biocompatibility, restricting their use in the biomedical field. Summary of the Invention
[0004] To overcome the problems existing in the prior art, one objective of this invention is to provide an ethyl cellulose micro / nano robot. A second objective is to provide a method for preparing this ethyl cellulose micro / nano robot. A third objective is to provide applications for this ethyl cellulose micro / nano robot. This invention utilizes ethyl cellulose and other materials to prepare micro / nano robots, employs a multi-layer stacking method to multifunctionalize the micro / nano robot, and finally uses isothermal post-processing techniques to convert the two-dimensional planar structure into a three-dimensional micro / nano robot, achieving high-throughput, low-cost manufacturing and promoting the potential applications of micro / nano robots in the biomedical field.
[0005] To achieve the above objectives, the technical solution adopted by the present invention is as follows:
[0006] The first aspect of the present invention provides an ethyl cellulose micro / nano robot having a three-dimensional structure; the ethyl cellulose micro / nano robot includes a magnetic layer and a functional layer stacked together; the functional layer includes a functional substance and ethyl cellulose; the functional substance is selected from at least one of a drug, a fluorescent dye, a quantum dot, and a catalyst; the magnetic layer includes a magnetic material and ethyl cellulose.
[0007] Preferably, the drug is a small molecule drug.
[0008] More preferably, the drug is selected from doxorubicin or artemisinin, etc.
[0009] Preferably, the fluorescent dye is selected from at least one of fluorescein, methylene blue, and indocyanine green.
[0010] Preferably, the magnetic material is selected from at least one of iron, cobalt, nickel and their alloys or magnetic compounds.
[0011] More preferably, the magnetic material is selected from at least one of Fe3O4, cobalt ferrite, nickel ferrite, iron-chromium-cobalt alloy, and aluminum-nickel-cobalt alloy.
[0012] Preferably, the particle size of the magnetic material is 10-500 nm.
[0013] Preferably, the ethyl cellulose micro / nano robot further includes a protective layer disposed on the functional layer; the protective layer comprises ethyl cellulose.
[0014] To protect the unstable functional substances in the functional layer, pure ethyl cellulose can be used as the outermost protective layer, wrapping the functional layer between the magnetic layer and the protective layer to prevent environmental conditions from damaging the functional substances.
[0015] Preferably, the three-dimensional structure is an arc-shaped structure; the circumferential angle of the arc-shaped structure is 91°-179°.
[0016] Preferably, in the magnetic layer, the mass ratio of the magnetic material to ethyl cellulose is (1-20):10.
[0017] Preferably, in the functional layer, the mass ratio of the functional substance to ethyl cellulose is (1-100):1000.
[0018] Preferably, the functional layer is a single-layer functional layer or a multi-layer functional layer; the multi-layer functional layers are loaded with different functional substances respectively.
[0019] Preferably, the three-dimensional structure of the ethyl cellulose micro-nano robot is formed by shrinking and curling ethyl cellulose after infrared radiation.
[0020] The second aspect of this invention provides a method for fabricating the micro / nano robot described in the first aspect, comprising the following steps:
[0021] S1. A magnetic precursor solution is prepared by mixing magnetic materials and ethyl cellulose in a solvent; a functional precursor solution is prepared by mixing functional substances and ethyl cellulose in a solvent.
[0022] S2. Coat the magnetic precursor liquid onto the substrate and heat to form a magnetic layer; coat the magnetic layer with a functional precursor liquid and heat to form a functional layer, thus obtaining a film with a multilayer structure.
[0023] S3. The membrane with the multilayer structure is subjected to infrared radiation to obtain the ethyl cellulose micro-nano robot.
[0024] Preferably, in step S1, the solvent of the magnetic precursor liquid is an alcohol solvent. More preferably, the solvent is ethanol.
[0025] Preferably, in step S1, the solvent of the functional precursor solution is an alcohol solvent. More preferably, the solvent is ethanol.
[0026] Preferably, in step S1, the viscosity of ethyl cellulose in the magnetic precursor liquid or functional precursor liquid is 270-330 mPa·s at 25°C.
[0027] Preferably, in step S1, the concentration of ethyl cellulose in the magnetic precursor liquid or functional precursor liquid is 1-30 wt%, for example, 1 wt%, 2 wt%, 5 wt%, 10 wt%, 15 wt%, 20 wt%, 25 wt%, or 30 wt%.
[0028] Preferably, in step S2, the heating temperature for forming the magnetic layer is 60-70°C.
[0029] Preferably, in step S2, the heating temperature for forming the functional layer is 60-70°C.
[0030] Preferably, in step S2, the heating time for forming the magnetic layer is 5-10 minutes.
[0031] Preferably, in step S2, the heating time for forming the functional layer is 5-10 minutes.
[0032] Preferably, in step S2, the substrate is a silicon wafer or other substrate with a flat surface.
[0033] Preferably, step S2 further includes a step of surface treatment of the substrate to form a hydrophilic surface before coating the functionalized precursor liquid.
[0034] Preferably, step S2 further includes the following steps: coating a dextran solution onto the substrate surface to form a sacrificial layer, then coating a functionalized precursor liquid onto the surface of the sacrificial layer, and baking to form a functional layer.
[0035] More preferably, it also includes using ultrasound-assisted dextran dissolution to peel off a multilayer membrane structure.
[0036] More preferably, the glucose solution has a mass fraction concentration of 1-20 wt%, for example 1 wt%, 3 wt%, 5 wt%, 8 wt%, 10 wt%, or 20 wt%, preferably 10 wt%.
[0037] In this invention, a dextran solution is spin-coated onto the substrate because the dextran film is soluble in water. After preparation, the dextran film is dissolved in water, and the multilayer structure can be peeled off from the substrate without damage.
[0038] Preferably, in step S2, the magnetic precursor liquid or functional precursor liquid is coated by spin coating, and the specific process parameters are: spin coating speed of 100-3500 rpm; spin coating time of 20-60 s.
[0039] Preferably, in step S2, the step specifically involves coating a functional layer onto the surface of the magnetic layer and baking it to form a multilayer film structure.
[0040] Preferably, in step S3, the infrared laser wavelength used for infrared radiation is 750-850nm and the power is 1-3W.
[0041] Preferably, in step S3, the infrared radiation duration is 1-5 minutes.
[0042] Preferably, step S3 further includes a step of pre-cutting the multilayered membrane before infrared radiation.
[0043] More preferably, the pre-cut size is (500-4000) μm × (300-600) μm.
[0044] A third aspect of the present invention is to provide the application of the micro-nano robots described in the first aspect 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.
[0045] Preferably, the intelligent drive controls the movement of the first aspect micro-nano robot in the magnetic field. More preferably, the magnetic field is a three-dimensional uniform rotating magnetic field.
[0046] The beneficial effects of this invention are:
[0047] This invention provides an ethyl cellulose micro / nano robot. Using ethyl cellulose, a natural polymer and its derivative, as the main material for preparing the micro / nano robot not only improves the biocompatibility of the material, but also allows the micro / nano robot to be transformed from a two-dimensional planar structure into a three-dimensional structure through infrared radiation post-processing, giving the micro / nano robot a specific structural shape. This enables the magnetically controlled micro / nano robot to achieve rapid and controllable movement in a magnetic field, and allows for intelligent actuation at a microscale. In addition, the functional layer can carry various functional substances such as drugs and fluorescent dyes, promoting the potential application of micro / nano robots in the biomedical field.
[0048] Specifically, compared with the prior art, the present invention has the following advantages:
[0049] 1) The structure of the ethyl cellulose micro-nano robot of the present invention adopts a multi-layer stacking method, which can realize the customization of multi-functional micro-nano robots compared with single-function robots.
[0050] 2) Compared with the direct fabrication of micro-nano robots with three-dimensional structures using technologies such as laser direct writing and 3D printing, this invention uses a post-processing method to transform two-dimensional planar non-chiral structures into three-dimensional micro-nano robots. This method is simple and has high fabrication efficiency.
[0051] 3) The micro-nano robot of the present invention has the characteristic of simple shape, which distinguishes it from other micro-nano robots. It can achieve movement under the control of a three-dimensional uniform rotating magnetic field, and therefore has potential application value in the fields of precision biomedical equipment, visualization research, real-time monitoring and detection, micro-nano processing and manufacturing, pollution prevention and control or environmental remediation. Attached Figure Description
[0052] Figure 1 This is a cross-sectional schematic diagram of the micro-nano robot in Example 1;
[0053] Figure 2 This is a cross-sectional schematic diagram of the micro-nano robot in Example 2;
[0054] Figure 3 This is a cross-sectional schematic diagram of the micro-nano robot in Example 3;
[0055] Figure 4 The images shown are (a) of each monolayer film in Comparative Example 1 and (b) under ultraviolet light.
[0056] Figure 5 The image shows (a) of the thin film in Comparative Example 2 and (b) under ultraviolet light.
[0057] Figure 6 The image shows the actual thin film in Comparative Example 3 (a) and its image under ultraviolet light (b).
[0058] Figure 7 The solubility of different cellulose molecules in ethanol;
[0059] Figure 8 This is a graph showing the cell viability after co-culturing micro-nano robots with cells in Example 1;
[0060] Figure 9 The images show the instantaneous rotational motion of the micro-nano robot in Example 1 at different time points; the scale bar is 50 μm.
[0061] Figure 10 The image shows the instantaneous motion state of the micro-nano robot at different points in time in Example 1. Detailed Implementation
[0062] The present invention will be further described in detail below through specific embodiments. Unless otherwise specified, the raw materials used in the following embodiments can be obtained from conventional commercial channels or prepared and isolated through simple synthesis; unless otherwise specified, the processes employed are conventional processes in the art.
[0063] Example 1
[0064] This embodiment provides an ethyl cellulose micro / nano robot, and the schematic diagram of the synthesis steps and structure of the micro / nano robot is shown below. Figure 1 As shown, the micro-nano robot, comprising a superimposed protective layer, a functional layer, and a magnetic layer, is transformed from a two-dimensional planar structure into a three-dimensional structure through infrared radiation post-processing. The fabrication method includes the following steps:
[0065] 1) Precursor solution for preparing the magnetic layer, functional layer, and protective layer:
[0066] Magnetic precursor solution: 1.0 g of ethyl cellulose (270-330 mPa·S) and 1.0 g of Fe3O4 nanoparticles (200 nm) were mixed and dissolved in 9.0 g of ethanol. After stirring and mixing, the magnetic precursor solution was obtained.
[0067] Functional precursor solution: 1.0 g ethyl cellulose (270-330 mPa·S) and 10 mg doxorubicin were mixed and dissolved in 9.0 g ethanol. The mixture was stirred and stirred to obtain the functional precursor solution.
[0068] Protective precursor solution: 1.0 g ethyl cellulose (270-330 mPa·S) was dissolved in 9.0 g ethanol to obtain the protective precursor solution.
[0069] 2) Fabrication of multilayer stacked structures:
[0070] The clean silicon wafer was subjected to Plasma treatment to obtain a hydrophilic surface, and then a 10 wt% dextran solution was spin-coated at an angular speed of 500 rpm for 30 seconds. After spin-coating, it was placed on a hot plate at 95°C and baked for 4 minutes until dry to form a dextran layer.
[0071] A magnetic precursor solution was coated onto a dextran layer at a spin coating speed of 2000 rpm for 30 s, and then dried at 65°C to form a magnetic layer. A functional precursor solution was then spin-coated onto the magnetic layer at a spin coating speed of 2000 rpm for 30 s, and then baked on a hot plate at 65°C for 10 min until completely dry to form a functional layer. Finally, a protective precursor solution was spin-coated onto the functional layer at a spin coating speed of 2000 rpm for 60 s, and then baked again on a hot plate at 65°C for 10 min until completely dry to form a protective layer. The film with a multilayer structure was then peeled off in water.
[0072] 3) Preparation of ethyl cellulose micro / nano robots.
[0073] The above-mentioned multilayered thin film was cut into rectangles with a length of ~2000μm and a width of ~400μm using a cutter. The rectangles were then irradiated with an infrared laser with a wavelength of 808nm and a power of 2W for 2 minutes until they were bent and solidified into an arc shape, thus obtaining an arc-shaped magnetically controlled micro-nano robot.
[0074] Example 2
[0075] This embodiment provides an ethyl cellulose micro / nano robot, and the schematic diagram of the synthesis steps and structure of the micro / nano robot is shown below. Figure 2 As shown, the micro-nano robot, comprising a superimposed functional layer and a magnetic layer, is transformed from a two-dimensional planar structure into a three-dimensional structure through infrared radiation post-processing. The fabrication method includes the following steps:
[0076] 1) Precursor solution for preparing magnetic and functional layers:
[0077] Magnetic precursor solution: 1.0 g of ethyl cellulose (270-330 mPa·S) and 1.0 g of Fe3O4 nanoparticles (200 nm) were mixed and dissolved in 9.0 g of ethanol. After stirring and mixing, the magnetic precursor solution was obtained.
[0078] Functional precursor solution: 1.0 g ethyl cellulose (270-330 mPa·S) and 10 mg doxorubicin were mixed and dissolved in 9.0 g ethanol. The mixture was stirred and stirred to obtain the functional precursor solution.
[0079] 2) Fabrication of multilayer stacked structures:
[0080] The clean silicon wafer was subjected to Plasma treatment to obtain a hydrophilic surface, and then a 5 wt% dextran solution was spin-coated at an angular speed of 1000 rpm for 20 seconds. After spin-coating, it was placed on a hot plate at 95°C and baked for 4 minutes until dry to form a dextran layer.
[0081] A magnetic precursor solution was coated onto the dextran layer by spin coating at an angular speed of 3000 rpm for 30 s, followed by drying at 65°C for 10 min to form a magnetic layer. Then, a functional precursor solution was spin coated onto the magnetic layer at an angular speed of 500 rpm for 30 s, and baked on a hot plate at 65°C for 10 min to form a functional layer. The entire layer was then dried and peeled off in water to obtain a film with a bilayer structure.
[0082] 3) Preparation of ethyl cellulose micro / nano robots.
[0083] The above-mentioned multilayered thin film was cut into rectangles with a length of ~3000μm and a width of ~500μm using a cutter. The rectangles were then irradiated with an infrared laser with a wavelength of 808nm and a power of 2W for 2 minutes until they were bent and solidified into an arc shape, thus obtaining an arc-shaped magnetically controlled micro-nano robot.
[0084] Example 3
[0085] This embodiment provides an ethyl cellulose micro / nano robot, and the schematic diagram of the synthesis steps and structure of the micro / nano robot is shown below. Figure 3 As shown, the micro-nano robot, comprising a functional layer b, a functional layer a, and a magnetic layer stacked together, is transformed from a two-dimensional planar structure into a three-dimensional structure through infrared radiation post-processing. The fabrication method includes the following steps:
[0086] 1) Precursor solution for preparing magnetic and functional layers:
[0087] Magnetic precursor solution: 1.0 g of ethyl cellulose (270-330 mPa·S) and 1.0 g of Fe3O4 nanoparticles (200 nm) were mixed and dissolved in 9.0 g of ethanol. After stirring and mixing, the magnetic precursor solution was obtained.
[0088] Functional precursor solution a: 1.0 g ethyl cellulose (270-330 mPa·S) and 10 mg doxorubicin were mixed and dissolved in 9.0 g ethanol. After stirring and mixing, functional precursor solution a was obtained.
[0089] Functional precursor solution b: 1.0 g ethyl cellulose (270-330 mPa·S) and 10 mg methylene blue were dissolved in 9.0 g ethanol and stirred until homogeneous to obtain functional precursor solution b.
[0090] 2) Fabrication of multilayer stacked structures:
[0091] The clean silicon wafer was subjected to Plasma treatment to obtain a hydrophilic surface, and then a 5 wt% dextran solution was spin-coated at an angular speed of 1000 rpm for 30 seconds. After spin-coating, it was placed on a hot plate at 95°C and baked for 4 minutes until dry to form a dextran layer.
[0092] A magnetic precursor solution was coated onto a dextran layer at a spin coating speed of 2000 rpm for 30 s, and then dried at 65°C for 10 min to form a magnetic layer. A functional precursor solution was then spin-coated onto the magnetic layer at a spin coating speed of 1000 rpm for 30 s, and then baked on a hot plate at 65°C for 10 min to form functional layer a. Finally, functional precursor solution b was spin-coated onto the functional layer at a spin coating speed of 2000 rpm for 30 s, and then dried again to form functional layer b. The film with a multilayer structure was then peeled off in water.
[0093] 3) Preparation of ethyl cellulose micro / nano robots.
[0094] The above-mentioned multilayered thin film was cut into rectangles with a length of ~1000μm and a width of ~500μm using a cutter. The rectangles were then irradiated with an infrared laser with a wavelength of 808nm and a power of 2W for 2 minutes until they were bent and solidified into an arc shape, thus obtaining an arc-shaped magnetically controlled micro-nano robot.
[0095] Comparative Example 1
[0096] This comparative example provides four types of monolayer thin films, the preparation methods of which include the following steps:
[0097] 1) Precursor solutions for the magnetic layer, functional layer a, functional layer b, and protective layer:
[0098] The preparation methods for the magnetic precursor liquid, functional precursor liquid a, and functional precursor liquid b are as described in Example 3, and the preparation method for the protective precursor liquid is as described in Example 1.
[0099] 2) Preparation of monolayer thin films:
[0100] The clean silicon wafer was subjected to Plasma treatment to obtain a hydrophilic surface, and then a 5 wt% dextran solution was spin-coated at an angular speed of 1000 rpm for 30 seconds. After spin-coating, it was placed on a hot plate at 95°C and baked for 4 minutes until dry to form a dextran layer.
[0101] Four types of monolayer films were obtained by coating the dextran layer with magnetic precursor liquid, functional precursor liquid a, functional precursor liquid b, or protective precursor liquid, respectively, by spin coating at an angular speed of 2000 rpm for 30 s, baking at 65°C for 10 min, and peeling off in water.
[0102] Each monolayer film in Comparative Example 1 is as follows Figure 4 As shown in Figure a, the image under ultraviolet light is as follows. Figure 4 As shown in Figure b.
[0103] Comparative Example 2
[0104] This comparative example provides a non-magnetic bilayer thin film comprising two functional layers, and its preparation method includes the following steps:
[0105] 1) Prepare the precursor solution for the functional layer:
[0106] Functional precursor solution a: 1.0 g ethyl cellulose (270-330 mPa·S) and 10 mg doxorubicin were mixed and dissolved in 9.0 g ethanol. After stirring and mixing, functional precursor solution a was obtained.
[0107] Functional precursor solution b: 1.0 g ethyl cellulose (270-330 mPa·S) and 10 mg methylene blue were dissolved in 9.0 g ethanol and stirred until homogeneous to obtain functional precursor solution b.
[0108] 2) Fabrication of a double-layer stacked structure:
[0109] The clean silicon wafer was subjected to Plasma treatment to obtain a hydrophilic surface, and then a 10 wt% dextran solution was spin-coated at an angular speed of 1000 rpm for 20 seconds. After spin-coating, it was placed on a hot plate at 95°C and baked for 4 minutes until dry to form a dextran layer.
[0110] A functional precursor solution a was coated onto a dextran layer at a spin coating speed of 1000 rpm for 30 s, followed by baking at 65°C for 10 min to form a functional layer b. Then, functional precursor solution b was spin-coated onto functional layer a at a spin coating speed of 2000 rpm for 30 s, and baked on a hot plate at 65°C for 10 min to form functional layer b. The film containing the bilayer structure was then peeled off in water. The bilayer film prepared in Comparative Example 2 is shown below. Figure 5 As shown in Figure a, the image under ultraviolet light is as follows. Figure 5 As shown in Figure b.
[0111] Comparative Example 3
[0112] This comparative example provides a multilayer thin film, including a magnetic layer, a functional layer a, a functional layer b, and a protective layer, and its preparation method includes the following steps:
[0113] 1) Precursor solution for preparing magnetic and functional layers:
[0114] Magnetic precursor solution: 1.0 g of ethyl cellulose (270-330 mPa.S) and 1.0 g of Fe3O4 nanoparticles (200 nm) were mixed and dissolved in 9.0 g of ethanol. After stirring and mixing, the magnetic precursor solution was obtained.
[0115] Functional precursor solution a: 1.0 g ethyl cellulose (270-330 mPa·s) and 10 mg doxorubicin were mixed and dissolved in 9.0 g ethanol. After stirring and mixing, functional precursor solution a was obtained.
[0116] Functional precursor solution b: 1.0 g ethyl cellulose (270-330 mPa·s) and 10 mg methylene blue were combined and dissolved in 9.0 g ethanol. After stirring and mixing, functional precursor solution b was obtained.
[0117] Protective precursor solution: 1.0 g ethyl cellulose (270-330 mPa·s) was dissolved in 9.0 g ethanol to obtain the protective precursor solution.
[0118] 2) Fabrication of multilayer stacked structures:
[0119] The clean silicon wafer was subjected to Plasma treatment to obtain a hydrophilic surface, and then a 5 wt% dextran solution was spin-coated at an angular speed of 1000 rpm for 30 seconds. After spin-coating, it was placed on a hot plate at 95°C and baked for 4 minutes until dry to form a dextran layer.
[0120] A magnetic precursor solution was coated onto a dextran layer at a spin coating speed of 2000 rpm for 30 s, followed by drying to form a magnetic layer. Then, functional precursor solutions b and a were sequentially spin-coated onto the magnetic layer and dried (65°C, 10 min) at spin coating speeds of 3000 rpm and 1000 rpm, respectively, for 30 s each. Finally, a protective precursor solution was spin-coated onto functional layer a at a spin coating speed of 3000 rpm for 30 s, followed by baking at 65°C for 10 min. The film was then peeled off in water to obtain a multilayered film. The multilayered film prepared in Comparative Example 3 is shown below. Figure 6 As shown in Figure a, the image under ultraviolet light is as follows. Figure 6 As shown in Figure b.
[0121] Experimental Analysis
[0122] 1. Solubility test of different celluloses in ethanol
[0123] 1.0 g of hydroxypropyl cellulose, ethyl cellulose, carboxymethyl cellulose, and cellulose acetate were added to 9.0 g of ethanol, respectively, and stirred until well mixed to obtain four solutions. The solubility of different celluloses in ethanol is shown in the figure below. Figure 7 As shown, where Figure 7 a is an ethanol solution of hydroxypropyl cellulose. Figure 7 b is an ethanol solution of ethyl cellulose. Figure 7 c is an ethanol solution of carboxymethyl cellulose. Figure 7d represents an ethanol solution of cellulose acetate. The test results show that only ethyl cellulose dissolves well and is clear and transparent, making it suitable for spin-coating. Hydroxypropyl cellulose is not completely soluble and is soluble in water; therefore, the robot prepared from it is not suitable for use in an aqueous medium. Carboxymethyl cellulose and cellulose acetate are almost insoluble in ethanol and cannot be used to prepare robots according to this method.
[0124] 2. Biotoxicity test
[0125] In this test example, the micro-nano robot prepared in Example 1 was subjected to a biotoxicity test. The specific steps are as follows:
[0126] With 5×10 5 MCF 10A cells were seeded at a density of 1 / mL in culture dishes. After the cells adhered, different concentrations of magnetically controlled micro-nano robot-induced fragmentation were added to the dispersion, and the cells were cultured at 37°C and 5% CO2. After 24 hours of culture, the cell viability was determined using a cell counting kit (CCK8).
[0127] Figure 8 The cell survival rate of the micro-nano robot prepared in Example 1 was shown. When the concentration of the added micro-nano robot material increased from 0 mg / mL to 20 mg / mL, the cell survival rate decreased slightly, but was still higher than 81%, indicating that the micro-nano robot had no obvious cytotoxicity in the concentration range of 0-20 mg / mL.
[0128] 3. Sports performance test
[0129] In this test example, the motion performance of the micro-nano robot of Example 1 was tested:
[0130] The micro-nano robot from Example 1 was placed in deionized water, and a three-dimensional rotating magnetic field was applied. The magnetic field generator was a three-dimensional Helmholtz coil system. By controlling the magnetic field, its motion performance was tested, mainly in two aspects:
[0131] a) Rotation in place: Under the conditions of magnetic field strength of 10mT and frequency of 1Hz, the instantaneous state diagrams of the in-place rotation motion of the micro-nano robot in Example 1 at different time points are shown below. Figure 9 As shown.
[0132] b) Forward motion: The instantaneous state diagrams of the micro-nano robot's motion at different time points under the conditions of a magnetic field strength of 12mT and a frequency of 1Hz are shown below. Figure 10 As shown in the figure, the micro-nano robot can achieve forward movement, and its movement trajectory is basically a straight line. Its average speed is 176.3398 μm / s, indicating that its motion performance is stable and its directional movement can be controlled by a magnetic field.
[0133] This test demonstrates that the micro-nano robot in this invention has good motion performance in deionized water, and further proves that the prepared robot has magnetic control performance, enabling intelligent driving at a tiny spatial scale. Therefore, it has potential application value in fields such as precision biomedicine, real-time sensing and monitoring, micro-nano fabrication, pollution prevention and control, or environmental remediation.
[0134] The multilayer film of Comparative Example 3 was cut into a rectangular size with the same cutting knife as that of Example 1 and subjected to the same motion performance test. Since the multilayer film of Comparative Example 3 is a planar structure, it cannot be driven to move by a uniform rotating magnetic field.
[0135] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.
Claims
1. An ethyl cellulose micro / nano robot, characterized in that, The ethyl cellulose micro / nano robot has a three-dimensional structure; the ethyl cellulose micro / nano robot includes a magnetic layer and a functional layer stacked together; the functional layer includes a functional substance and ethyl cellulose; the functional substance is selected from at least one of drugs, fluorescent dyes, quantum dots, and catalysts; the magnetic layer includes a magnetic material and ethyl cellulose; The preparation method of the ethyl cellulose micro / nano robot includes the following steps: S1. A magnetic precursor solution is prepared by mixing magnetic materials and ethyl cellulose in a solvent; a functional precursor solution is prepared by mixing functional substances and ethyl cellulose in a solvent. S2. Coat the magnetic precursor liquid onto the substrate and heat to form a magnetic layer; coat the magnetic layer with a functional precursor liquid and heat to form a functional layer, thus obtaining a film with a multilayer structure. S3. The membrane with the multilayer structure is subjected to infrared radiation to obtain the ethyl cellulose micro-nano robot.
2. The ethyl cellulose micro / nano robot according to claim 1, characterized in that, The drug is a small molecule drug; And / or, the fluorescent dye is selected from at least one of fluorescein, methylene blue, and indocyanine green; And / or, the magnetic material is selected from at least one of iron, cobalt, nickel and their alloys or magnetic compounds.
3. The ethyl cellulose micro / nano robot according to claim 1, characterized in that, The ethyl cellulose micro / nano robot also includes a protective layer disposed on the functional layer; the protective layer comprises ethyl cellulose.
4. The ethyl cellulose micro / nano robot according to claim 1, characterized in that, The three-dimensional structure is an arc-shaped structure.
5. The ethyl cellulose micro / nano robot according to claim 1, characterized in that, In the magnetic layer, the mass ratio of the magnetic material to ethyl cellulose is (1-20):10; And / or, in the functional layer, the mass ratio of the functional substance to ethyl cellulose is (1-100):1000.
6. The method for preparing the ethyl cellulose micro / nano robot according to any one of claims 1-5, characterized in that, Includes the following steps: S1. A magnetic precursor solution is prepared by mixing magnetic materials and ethyl cellulose in a solvent; a functional precursor solution is prepared by mixing functional substances and ethyl cellulose in a solvent. S2. Coat the magnetic precursor liquid onto the substrate and heat to form a magnetic layer; coat the magnetic layer with a functional precursor liquid and heat to form a functional layer, thus obtaining a film with a multilayer structure. S3. The membrane with the multilayer structure is subjected to infrared radiation to obtain the ethyl cellulose micro-nano robot.
7. The method for preparing ethyl cellulose micro / nano robots according to claim 6, characterized in that, In step S2, the heating temperature for forming the magnetic layer is 60-70 ℃; And / or, the heating temperature for forming the functional layer is 60-70 °C.
8. The method for preparing ethyl cellulose micro / nano robots according to claim 6, characterized in that, Step S2 also includes the following steps: coating a dextran solution onto the substrate surface to form a sacrificial layer, then coating a magnetic precursor liquid onto the surface of the sacrificial layer and heating to form a magnetic layer.
9. The method for preparing ethyl cellulose micro / nano robots according to claim 6, characterized in that, The infrared laser used for infrared radiation in step S3 has a wavelength of 750-850 nm and a power of 1-3 W.
10. The application of the ethyl cellulose micro / nano robot according to any one of claims 1-5 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.
Citation Information
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