Sea urchin-shaped micro-nano robot for optomagnetic coupling single cell puncture

CN120553766BActive Publication Date: 2026-08-18HARBIN INST OF TECH
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Patent Information

Application Number
CN202510652646.6
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2025-05-21
Publication Date
2026-08-18
Estimated Expiration
2045-05-21

AI Technical Summary

Technical Problem

同时,微纳机器人在实际应用过程中常会面临复杂多变的环境,且细胞膜屏障界面张力大、突破难,现有微纳机器人难以满足在复杂多变环境中对单细胞的穿刺,极大限制了微纳机器人在生物医疗领域的应用范围

Benefits of technology

[0028]提出一种用于光磁耦合单细胞穿刺的海胆形微纳机器人及其制备方法,制备出的海胆形微纳机器人主要由氧化铁及金两种材料构成,具有顺磁性,能够响应外部磁场的刺激并表现出运动行为,同时具有光热特性,能将近红外光的光能转化为热能,使表面金刺温度升高;

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Abstract

This invention relates to single-cell puncture technology, and more specifically, to a sea urchin-shaped micro / nanorobot for photomagnetic coupling single-cell puncture. The driving and control method involves using an iron oxide material that is paramagnetic, capable of responding to external magnetic field stimulation to precisely control the direction of motion of the sea urchin-shaped micro / nanorobot; and a gold material that is photothermal, capable of responding to external near-infrared light field stimulation to convert the light energy of the near-infrared light into heat energy, raising the temperature of the gold spikes on the surface, thus achieving puncture of the target cell. The single-cell puncture method involves forming an induced magnetic dipole moment inside the sea urchin-shaped micro / nanorobot; the sea urchin-shaped micro / nanorobot exhibiting motion behavior in a uniform rotating magnetic field; controlling the magnitude and direction of the applied magnetic field to control the speed and direction of motion of the sea urchin-shaped micro / nanorobot; adding a near-infrared light field to raise the temperature of the gold spikes; and the sea urchin-shaped micro / nanorobot using the gold spikes to puncture the cell.
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Description

Technical Field

[0001] This invention relates to single-cell puncture technology, and more particularly to a method for preparing and driving a sea urchin-shaped micro / nano robot and its optical-magnetic coupling single-cell puncture method, and more specifically to a sea urchin-shaped micro / nano robot for optical-magnetic coupling single-cell puncture. Background Technology

[0002] Single-cell biopsy is a technique that operates at the single-cell level. It primarily involves using specialized puncture tools, such as extremely fine glass needles or micropipettes, with the aid of visualization equipment like microscopes, to precisely puncture a single cell to extract, inject, or perform other related operations from within the cell. Most existing methods are based on glass needles or micropipettes, heavily reliant on the operator's experience and skill, and suffer from low precision and a high failure rate. Micro- and nanorobots, on the other hand, are small, high thrust-to-weight ratio, and highly controllable micro- and nano-actuators that can convert other forms of energy into mechanical energy for their own motion, enabling precise movement and complex functions within micro-environments. Due to their excellent mobility and flexible controllability, micro- and nanorobots can serve as micro- and nano-scale puncture needles, acting on the cell membrane of a single cell to achieve effective single-cell puncture, demonstrating enormous application potential in cell biopsy. However, most existing experiments involving micro- and nano-robots are conducted in laboratory still-water environments, where the environmental structure is relatively simple and the physicochemical characteristics are relatively stable. Secondly, most existing micro- and nano-robots use chemical fuels as energy input for propulsion, which are toxic, have short lifespans, weak driving capabilities, limited control methods, and limited scalability. In contrast, external physical field actuation offers advantages such as eliminating the need for toxic fuels, strong driving capabilities, and remote controllability, making it more valuable for applications. Furthermore, external physical field actuation allows for multi-field coupling, significantly improving driving control capabilities. Simultaneously, micro- and nano-robots often face complex and variable environments in practical applications, and the high interfacial tension and difficulty in overcoming cell membrane barriers mean that existing micro- and nano-robots struggle to perform single-cell punctures in complex and variable environments, greatly limiting their application scope in the biomedical field. Therefore, there is an urgent need to propose a single-cell puncture method based on coupled external physical fields using micro-nano robots. This method can overcome the shortcomings of existing chemically driven micro-nano robots, avoid contamination by toxic and harmful substances, drive precise movement of micro-nano robots in complex application environments, and significantly enhance the driving force during the movement of micro-nano robots. This will help micro-nano robots overcome various interface barriers in practical applications, achieve effective puncture of single cells in complex and variable practical application environments, significantly improve the application effect of micro-nano robots in single-cell puncture, and promote the development of biomedical technology. Summary of the Invention

[0003] The purpose of this invention is to provide a sea urchin-shaped micro / nano robot that can simultaneously respond to external light and magnetic field stimuli, as well as its preparation method and driving control method. It also provides a single-cell puncture method based on a photomagnetic coupling field using a sea urchin-shaped micro / nano robot, which enables effective puncture of single cells and broadens the application scope of micro / nano robots in biomedical fields such as cell puncture.

[0004] A method for fabricating a sea urchin-shaped micro / nano robot via optomagnetic coupling for single-cell puncture includes the following steps:

[0005] Step 1: Prepare elliptical iron oxide particles using chemical synthesis methods;

[0006] Step 2: Coat the surface of the iron oxide particles with a layer of silicon dioxide to obtain iron oxide / silicon dioxide particles;

[0007] Step 3: Pre-treat the surface of the iron oxide / silica particles obtained above to improve their surface activity and adhesion, and obtain aminated iron oxide / silica particles.

[0008] Step 4: Prepare a gold nanoparticle solution by chemical reduction, specifically by reducing gold chloro acid with sodium citrate;

[0009] Step 5: Immerse the aminated iron oxide / silica particles in a gold nanoparticle solution to allow the gold nanoparticle seeds to fully adhere to the surface of the aminated iron oxide / silica particles, thus obtaining iron oxide / silica / gold particles.

[0010] Step 6: Under suitable reaction conditions, gold ions are catalyzed to grow gold spikes on the surface of iron oxide / silica / gold particles using a seed-mediated growth method, thus obtaining a sea urchin-shaped micro / nano robot for photomagnetic coupling single-cell puncture.

[0011] A photomagnetically coupled sea urchin-shaped micro / nano robot is described. The sea urchin-shaped micro / nano robot is composed of two materials: iron oxide and gold. The interior is an iron oxide core, and the surface is a gold layer with gold nanoparticles.

[0012] A drive and control device for a sea urchin-shaped micro-nano robot consists of three parts: a magnetic field generator, a near-infrared light generator, and a microscope.

[0013] The magnetic field generating device uses a three-dimensional Helmholtz coil. A sinusoidal electrical signal is generated by a signal generator, amplified by an amplifier, and then input into the Helmholtz coil as a signal source. A support and a glass slide are placed in the middle of the Helmholtz coil to provide a platform for the sea urchin-shaped micro-nano robot, placing it at the center of the Helmholtz coil for observation using a microscope.

[0014] A drive control device for a sea urchin-shaped micro / nano robot can change the strength and direction of the magnetic field generated by three pairs of coils by adjusting the amplitude and phase of the sinusoidal electrical signal; by adjusting the magnetic field strength and direction in three dimensions respectively and combining them, a uniform rotating magnetic field in any direction in space can be generated; the near-infrared light generator is a near-infrared laser that can emit near-infrared light of 808nm.

[0015] A drive control method for an optically and magnetically coupled sea urchin-shaped micro / nano robot, wherein the iron oxide material constituting the sea urchin-shaped micro / nano robot is paramagnetic and can respond to the stimulation of an external magnetic field, thereby achieving precise control of the motion direction of the sea urchin-shaped micro / nano robot.

[0016] The gold material that makes up the sea urchin-shaped micro-nano robot has photothermal properties. It can respond to the stimulation of the external near-infrared light field, convert the light energy of the near-infrared light into heat energy, and raise the temperature of the gold spikes on the surface to achieve puncture of the target cells.

[0017] A drive control method for a magnetically coupled sea urchin-shaped micro / nano robot is provided. When the magnetic field generated by the adjustment coil is a planar rotating magnetic field perpendicular to the long axis of the sea urchin-shaped micro / nano robot, the sea urchin-shaped micro / nano robot rolls around its own long axis under the action of the planar rotating magnetic field in response to the magnetic field. By changing the direction of the uniform rotating magnetic field generated by the Helmholtz coil, the motion direction of the sea urchin-shaped micro / nano robot can be precisely controlled.

[0018] A method for driving and controlling a photomagnetically coupled sea urchin-shaped micro / nano robot involves applying a planar rotating magnetic field perpendicular to the robot's long axis as the robot rolls near a target cell, while simultaneously irradiating it with near-infrared light. The robot generates a photothermal effect due to surface plasmon resonance (i.e., the interaction of free electrons and photons on the metal surface region), converting the near-infrared light energy into heat energy and raising the temperature of the surface spikes. By coupling the planar rotating magnetic field and the near-infrared light field, the sea urchin-shaped micro / nano robot continues to roll around its long axis, approaching the target cell, and piercing the target cell using its numerous, small-tipped, and high-temperature spikes.

[0019] A method for single-cell puncture using a sea urchin-shaped micro / nano robot with optical-magnetic coupling includes the following steps:

[0020] Step 1: Pass a DC signal into the three-dimensional Helmholtz coil and amplify it by 2-4 times; Since the sea urchin-shaped micro-nano robot is made of paramagnetic iron oxide material, it is magnetized under the action of a magnetic field and an induced magnetic dipole moment is formed inside it;

[0021] Step 2: The sea urchin-shaped micro / nano robot is subjected to magnetic torque in a uniform rotating magnetic field and rotates around an axis perpendicular to the magnetic torque. During the rotation, the sea urchin-shaped micro / nano robot forms an interaction force with the substrate, thus exhibiting motion behavior.

[0022] Step 3: By controlling the relative magnitudes of the electrical signals input to the three sets of Helmholtz coils, and thus controlling the direction of the applied magnetic field, the movement direction and speed of the sea urchin-shaped micro-nano robot can be controlled.

[0023] Step 4: After the sea urchin-shaped micro-nano robot moves to the vicinity of the target cell under the action of a uniform rotating magnetic field, the uniform rotating magnetic field is continued to be applied, and a near-infrared light field is added at the same time. Under the irradiation of near-infrared light with an output power of 5-10W and a wavelength of 808nm, the gold nanoparticles in the gold spikes generate a photothermal effect due to the surface plasmon effect, which in turn raises the temperature of the gold spikes and improves the cell puncture ability of the sea urchin-shaped micro-nano robot.

[0024] Step 5: Under the coupling effect of a uniform rotating magnetic field and a near-infrared light field, the sea urchin-shaped micro-nano robot uses its numerous, small, and high-temperature gold spikes on its surface to finally achieve effective puncture of cells.

[0025] The motion behavior in step two refers to the urchin-shaped micro-nano robot rolling forward on the substrate around an axis perpendicular to the magnetic torque due to the effect of a uniform rotating magnetic field.

[0026] In step four, the surface plasmon effect generates a photothermal effect, that is, the free electrons on the surface of the gold nanostructure interact with the photons in the near-infrared light to form a local resonant electromagnetic field, which causes the surrounding molecules or atoms to absorb the light energy and convert it into heat energy.

[0027] The beneficial effects of this invention are as follows:

[0028] A sea urchin-shaped micro / nano robot for optomagnetic coupling single-cell puncture and its fabrication method are proposed. The fabricated sea urchin-shaped micro / nano robot is mainly composed of iron oxide and gold. It is paramagnetic, can respond to external magnetic field stimulation and exhibits motion behavior. At the same time, it has photothermal properties and can convert near-infrared light energy into heat energy, which increases the temperature of the gold spikes on the surface.

[0029] The fabricated sea urchin-shaped micro-nano robots have small and numerous gold spike tips on their surface, which can generate greater pressure when in contact with target cells, making it easier to break through the cell membrane of the target cells and significantly improving the cell piercing ability of the sea urchin-shaped micro-nano robots.

[0030] The fabricated sea urchin-shaped micro-nano robot can rotate along any axis. By controlling the strength and direction of the uniform rotating magnetic field generated by the Helmholtz coil, the speed and direction of the micro-nano robot can be precisely controlled.

[0031] The prepared sea urchin-shaped micro-nano robots can generate a photothermal effect in response to external near-infrared light field stimulation, which raises the temperature of the gold spikes on the surface. The high-temperature gold spikes can reduce the stability of the phospholipid bilayer, causing lipids and proteins in the cell membrane to denature, degrade or aggregate, resulting in damage to the integrity of the cell membrane structure and significantly improving the cell puncture capability of the sea urchin-shaped micro-nano robots.

[0032] The fabricated sea urchin-shaped micro-nano robots can move under the action of an optical-magnetic coupling field and achieve effective puncture of target cells based on their numerous, small-tip-size, and high-temperature gold spikes.

[0033] Using sea urchin-shaped micro-nano robots to puncture single cells can overcome the shortcomings of current single-cell puncture technology, improve puncture efficiency, provide a new approach to single-cell puncture technology, and promote the development of biomedical technology. Attached Figure Description

[0034] The present invention will now be described in further detail with reference to the accompanying drawings and specific implementation methods.

[0035] Figure 1 This is a flowchart illustrating the fabrication process of sea urchin-shaped micro / nano robots.

[0036] Figure 2 Scanning electron microscope image and energy dispersive spectroscopy (EDS) spectrum of a sea urchin-shaped micro / nano robot;

[0037] Figure 3 Diagram of a drive and control device for a sea urchin-shaped micro / nano robot;

[0038] Figure 4 A diagram illustrating the motion and cell puncture mechanism of sea urchin-shaped micro / nano robots under a photomagnetic coupling field;

[0039] Figure 5 This is an experimental diagram of motion control for a sea urchin-shaped micro / nano robot under an optical-magnetic coupling field.

[0040] Figure 6 This image shows a single-cell puncture experiment using a sea urchin-shaped micro / nano robot under a photomagnetic coupling field.

[0041] 1. Near-infrared light generator; 2. Object support; 3. Three-dimensional Helmholtz coil; 4. Microscope; 5. Glass slide. Detailed Implementation

[0042] This invention proposes a sea urchin-shaped micro / nano robot for optomagnetic coupling single-cell puncture, along with its fabrication and drive control methods. It also provides a single-cell puncture method for the sea urchin-shaped micro / nano robot based on an optomagnetic coupling field.

[0043] A flowchart of a method for fabricating a sea urchin-shaped micro / nano robot via optomagnetic coupling single-cell puncture is shown below. Figure 1As shown, its preparation process mainly includes six steps. Step one: ferric chloride reacts with sodium hydroxide to obtain ferric hydroxide colloid. The ferric hydroxide colloid obtained from the reaction is then heated, during which it will transform into ferric oxide and gradually grow, eventually growing into elliptical ferric oxide particles. The specific process is as follows: Sodium hydroxide solution (90 mL, 5 mol / L) is slowly added dropwise to ferric chloride solution (100 mL, 2 mol / L). The mixture is stirred with a mechanical stirrer for 5-10 minutes (preferably 10 minutes). Sodium sulfate solution (10 mL, 0.25 mol / L) is added, and the mixture is stirred with a mechanical stirrer for another 5-10 minutes (preferably 10 minutes). The resulting solution is transferred to a 250 mL Pyrex glass bottle and heated in a muffle furnace at 95-100°C (preferably 100°C) for 8-10 days (preferably 10 days). The resulting solution is centrifuged with anhydrous ethanol and washed 2-3 times (preferably 3 times) until the upper layer is clear. The resulting product is further centrifuged with deionized water and washed 2-3 times (preferably 3 times). The centrifuged product is then placed in a drying oven and dried at 70-80°C (preferably 80°C) for 10-12 hours (preferably 12 hours) to obtain elliptical iron oxide particles.

[0044] Step 2: Based on the elliptical iron oxide particles obtained above, iron oxide / silica particles with a surface coating of silica are prepared. The synthesis method is as follows: 0.1 g of the elliptical iron oxide particles prepared above are uniformly dispersed in a mixed solution of anhydrous ethanol (80 mL), deionized water (20 mL), and ammonia solution (1.0 mL, 25-28 wt%). Then, tetraethyl orthosilicate (70 mL) is added to the above solution, and the mixture is stirred at room temperature for 5-6 hours (preferably 6 hours). The mixture is then centrifuged, washed several times with anhydrous ethanol and deionized water until the supernatant is clear, and the centrifuged product is dried overnight at 70-80°C (preferably 80°C) to obtain iron oxide / silica particles coated with a silica layer.

[0045] Step 3: Perform surface pretreatment on the iron oxide / silica particles obtained above to obtain aminated iron oxide / silica particles. The surface pretreatment method is as follows: Take 30 mg of the iron oxide / silica particles coated with a layer of silica prepared above, add anhydrous ethanol (5 mL) and ultrasonically disperse. After dispersion, stir magnetically (preferably 400 rpm), add 3-aminopropyltriethoxysilane (50 μL), stir for 3-5 minutes (preferably 5 minutes), then add ammonia water (60 μL, 25-28 wt%), continue stirring for 10-12 hours (preferably 12 hours), after stirring, centrifuge multiple times (preferably 6000 rpm, 3 min), wash 3 times each with anhydrous ethanol and deionized water until the upper layer solution is clear, and then dry the centrifuged product in a drying oven (preferably 80℃, 4 h) to obtain surface aminated iron oxide / silica particles.

[0046] Step 4: Prepare the gold nanoparticle solution. The preparation method is as follows: Heat 100 mL of gold chloro acid (1 mM / L) in a flask to boiling, then add 15 mL of sodium citrate solution (38 mM / L), stir for 10-15 min (preferably 15 min), allow the solution to cool naturally to room temperature, and filter it through a filter with a pore size of 220 nm to obtain the gold nanoparticle solution.

[0047] Step 5: Allow the gold nanoparticle seeds to fully adhere to the surface of the aminated iron oxide / silica particles to obtain iron oxide / silica / gold particles. The specific process is as follows: Take 10 mg of aminated iron oxide / silica particles, add 50 mL of gold nanoparticle solution, and stir at room temperature for 20-24 h (preferably 24 h) to allow the gold nanoparticles to fully adhere to the surface of the aminated iron oxide / silica particles. After multiple centrifugations (preferably 6000 rpm, 3 min), obtain iron oxide / silica / gold particles, and dry them (preferably 80 °C, 12 h).

[0048] Step 6: By catalyzing the growth of gold ions onto the surface of iron oxide / silica / gold particles using gold nanoparticle seeds, a sea urchin-shaped micro / nanorobot for photomagnetic coupling single-cell puncture can be obtained. The specific procedure is as follows: Take 0.3 mg of iron oxide / silica / gold particles, add gold chloric acid solution (60 mL, 0.25 mM / L), stir thoroughly to dissolve, then simultaneously add dilute hydrochloric acid (600 μL, 1 mol / L), silver nitrate solution (600 μL, 3 mM / L), and sodium ascorbate solution (300 μL, 0.1 mol / L), stir for 1-3 min (preferably 3 min), centrifuge the solution multiple times (preferably 6000 rpm, 3 min), and wash off the lower solid layer with anhydrous ethanol and water to obtain the sea urchin-shaped micro / nanorobot for photomagnetic coupling single-cell puncture.

[0049] The sea urchin-shaped micro / nano robots prepared were characterized using scanning electron microscopy and energy dispersive spectroscopy. The characterization results are as follows: Figure 2 As shown in the figure, the analysis and characterization results show that the sea urchin-shaped micro-nano robot is mainly composed of two materials: iron oxide and gold. The interior is an iron oxide core, and the surface is a gold layer with gold nanoparticles.

[0050] A drive control device for urchin-shaped micro / nano robots used in opto-magnetic coupled single-cell puncture, such as Figure 3 As shown, the system mainly consists of three parts: a magnetic field generator, a near-infrared light generator, and a microscope. The magnetic field generator uses a three-dimensional Helmholtz coil. A sinusoidal electrical signal (4Vpp, 15Hz) is generated by a signal generator, amplified 2-4 times (preferably 4 times) by a power amplifier, and then input into the Helmholtz coil as the signal source. By controlling the relative amplitude and phase of the electrical signal input to the Helmholtz coil, a uniform rotating magnetic field in any direction can be generated in space. The near-infrared light generator produces 808nm near-infrared light as a light source to provide the optical field conditions for the photothermal effect of the micro-nano robot. A support and a glass slide are placed in the middle of the Helmholtz coil to provide a platform for the sea urchin-shaped micro-nano robot, which is then observed using a microscope.

[0051] The motion and cell puncture mechanism of sea urchin-shaped micro / nano robots under a photomagnetic coupled field are shown in the figure. Figure 4 As shown. First, a DC signal (4Vpp, 15Hz) is passed into the three-dimensional Helmholtz coil and amplified 2-4 times (preferably 4 times). Since the sea urchin-shaped micro / nano robot is made of paramagnetic iron oxide material, it is magnetized under the influence of the magnetic field, and an induced magnetic dipole moment is formed inside it. The sea urchin-shaped micro / nano robot is subjected to magnetic torque in a uniform rotating magnetic field and rotates around an axis perpendicular to the magnetic torque. During the rotation, the sea urchin-shaped micro / nano robot forms an interaction force with the substrate, thus exhibiting motion behavior. That is, the sea urchin-shaped micro / nano robot rolls forward on the substrate around an axis perpendicular to the magnetic torque due to the action of the uniform rotating magnetic field. By controlling the relative magnitude of the electrical signal amplitude input to the three sets of Helmholtz coils, and thus controlling the direction of the applied magnetic field, the motion direction and speed of the sea urchin-shaped micro / nano robot can be controlled.

[0052] Secondly, after the sea urchin-shaped micro / nanorobot moves to the vicinity of the target cell under the action of a uniform rotating magnetic field, the uniform rotating magnetic field is continued to be applied, and a near-infrared light field is added simultaneously. Under the irradiation of near-infrared light with an output power of 5-10W (preferably 10W) ​​and a wavelength of 808nm, the gold nanoparticles in the gold spikes generate a photothermal effect due to the surface plasmon effect. That is, the free electrons on the surface of the gold nanostructure interact with the photons in the near-infrared light to form a local resonant electromagnetic field, causing the surrounding molecules or atoms to absorb the light energy and convert it into heat energy, thereby increasing the temperature of the gold spikes and improving the cell puncture capability of the sea urchin-shaped micro / nanorobot. Under the coupling effect of the uniform rotating magnetic field and the near-infrared light field, the sea urchin-shaped micro / nanorobot ultimately achieves effective cell puncture by utilizing its numerous, small, and high-temperature gold spikes on its surface.

[0053] By conducting motion control experiments on a sea urchin-shaped micro / nano robot under an opto-magnetic coupled field, the robot's motion capability and controllability under this field were verified. The experimental results are shown in the figure below. Figure 5 As shown in the figure, under the influence of a photomagnetic coupling field, the sea urchin-shaped micro-nanorobot sequentially moves downward, rightward, upward, and leftward, eventually returning to its initial position. Furthermore, a single-cell puncture experiment was conducted using the sea urchin-shaped micro-nanorobot under a photomagnetic coupling field, verifying its ability to puncture single cells. After staining the cells, the sea urchin-shaped micro-nanorobot moved near the target cell under the influence of a magnetic field and punctured the target cell under the coupled field of near-infrared light and magnetic fields. The cell puncture experiment results and cell staining images are shown in the figure. Figure 6 As shown, the cells exhibit green fluorescence before puncture and red fluorescence after puncture.

Claims

1. A driving control method for a sea urchin-shaped micro-nano robot for optomagnetic coupling single-cell puncture, characterized in that, The fabrication method of sea urchin-shaped micro / nano robots includes the following steps: Step 1: Slowly add 90 mL of 5 mol / L sodium hydroxide solution dropwise to 100 mL of 2 mol / L ferric chloride solution, and stir with a mechanical stirrer for 5-10 minutes. Add 10 mL of 0.25 mol / L sodium sulfate solution, and continue stirring with a mechanical stirrer for 5-10 minutes. Transfer the resulting solution to a 250 mL Pierrex glass bottle and heat it in a muffle furnace at 95-100 ℃ for 8-10 days. Centrifuge the resulting solution with anhydrous ethanol and wash it 2-3 times until the upper layer is clear. Further centrifuge the resulting product with deionized water and wash it 2-3 times. Place the centrifuged product in a drying oven at 70-80 ℃ for 10-12 hours to obtain elliptical iron oxide particles. Step 2: The 0.1 g elliptical iron oxide particles prepared in Step 1 are uniformly dispersed in a mixed solution of 80 mL anhydrous ethanol, 20 mL deionized water, and 1.0 mL of 25-28 wt% ammonia solution. Then, 70 mL of tetraethyl orthosilicate is added to the mixed solution, and the mixture is stirred at room temperature for 5-6 hours. After centrifugation, the mixture is washed several times with anhydrous ethanol and deionized water until the upper layer is clear. The product obtained by centrifugation is dried overnight at 70-80 °C to obtain iron oxide / silica particles coated with a layer of silica. Step 3: Take 30 mg of iron oxide / silica particles coated with a layer of silica prepared in Step 2, add 5 mL of anhydrous ethanol and disperse by ultrasonication. After dispersion, stir magnetically, add 50 μL of 3-aminopropyltriethoxysilane, stir for 3-5 minutes, add 60 μL of 25-28 wt% ammonia water, and continue stirring for 10-12 hours. After stirring, centrifuge multiple times, wash 3 times each with anhydrous ethanol and deionized water until the upper layer solution is clear, and dry the centrifuged product in a drying oven to obtain surface-aminated iron oxide / silica particles. Step 4: Heat 100 mL of 1 mM gold chloro acid in a flask to boiling, then add 15 mL of 38 mM sodium citrate solution. Stir for 10-15 min, then allow the solution to cool naturally to room temperature and filter it through a 220 nm pore size filter to obtain the gold nanoparticle solution. Step 5: Take 10 mg of aminated iron oxide / silica particles, add 50 mL of gold nanoparticle solution, stir at room temperature for 20-24 h to allow the gold nanoparticles to fully adhere to the surface of the aminated iron oxide / silica particles, and obtain iron oxide / silica / gold particles by multiple centrifugations, and then dry them. Step 6: Take 0.3 mg of iron oxide / silica / gold particles, add 60 mL of 0.25 mM gold chloride solution, stir thoroughly to dissolve, then simultaneously add 600 μL of 1 mol / L dilute hydrochloric acid, 600 μL of 3 mM silver nitrate solution and 300 μL of 0.1 mol / L sodium ascorbate solution, stir for 1-3 min, centrifuge the solution multiple times, and wash off the lower solid layer with anhydrous ethanol and water to obtain the sea urchin-shaped micro-nano robot for optomagnetic coupling single cell puncture. The drive control device used in this control method consists of three parts: a magnetic field generator, a near-infrared light generator, and a microscope. The magnetic field generating device uses a three-dimensional Helmholtz coil. A sinusoidal electrical signal is generated by a signal generator, amplified by an amplifier, and then input into the three-dimensional Helmholtz coil as a signal source. A support and a glass slide are placed in the middle of the three-dimensional Helmholtz coil to provide a platform for the sea urchin-shaped micro-nano robot, placing it at the center of the three-dimensional Helmholtz coil; observation is then performed using a microscope. The strength and direction of the magnetic field generated by the three pairs of coils can be changed by adjusting the amplitude and phase of the sinusoidal electrical signal; by adjusting the strength and direction of the magnetic field in the three dimensions respectively and combining them, a uniform rotating magnetic field in any direction in space can be generated; the near-infrared light generating device is a near-infrared laser that can emit 808 nm near-infrared light. The iron oxide material that makes up the sea urchin-shaped micro-nano robot is paramagnetic and can respond to the stimulation of external magnetic fields, thus enabling precise control of the movement direction of the sea urchin-shaped micro-nano robot. The gold material that makes up the sea urchin-shaped micro-nano robot has photothermal properties. It can respond to the stimulation of the external near-infrared light field, convert the light energy of the near-infrared light into heat energy, and raise the temperature of the gold spikes on the surface to achieve puncture of the target cells. When the magnetic field generated by the adjustment coil is a planar rotating magnetic field perpendicular to the long axis of the sea urchin-shaped micro-nano robot, the sea urchin-shaped micro-nano robot rolls around its own long axis under the action of the planar rotating magnetic field. By changing the direction of the uniform rotating magnetic field generated by the Helmholtz coil, the motion direction of the sea urchin-shaped micro-nano robot can be precisely controlled. When the sea urchin-shaped microrobot rolls near the target cell, a planar rotating magnetic field perpendicular to its long axis is applied, while near-infrared light is added. At this time, the sea urchin-shaped microrobot generates a photothermal effect due to the surface plasmon effect, i.e., the interaction between free electrons and photons in the metal surface region, which forms electromagnetic oscillations. The light energy of the near-infrared light is converted into heat energy, and the temperature of the gold spikes on the surface increases. By coupling the planar rotating magnetic field and the near-infrared light field, the sea urchin-shaped microrobot continues to roll around its long axis to get closer to the target cell, and punctures the target cell with its numerous gold spikes with small tips and high temperature.

2. The driving control method for a sea urchin-shaped micro / nano robot for opto-magnetic coupling single-cell puncture according to claim 1, characterized in that, The output power of the near-infrared light field is 5-10W.

Citation Information

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