CN114601509A - Design of a magnetically driven micro-nano robot and its preparation method and driving method - Google Patents
Design of a magnetically driven micro-nano robot and its preparation method and driving method Download PDFInfo
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- A61B17/00—Surgical instruments, devices or methods
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- A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
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- A61B90/00—Instruments, implements or accessories specially adapted for surgery or diagnosis and not covered by any of the groups A61B1/00 - A61B50/00, e.g. for luxation treatment or for protecting wound edges
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Abstract
本发明公开了一种磁驱动微纳米机器人的结构设计及其制备方法和驱动方式。磁驱动微纳米机器人的主体结构为梭形双叶带式螺旋，通过路径优化后的双光子聚合激光直写技术实现了机器人的真三维制作，并在机器人的表面溅射了用于磁驱动的镍层和用于提高机器人的生物相容性的钛层，使用锥形旋转均匀磁场对机器人进行驱动，并通过将三轴亥姆霍兹线圈磁场发生装置与微动台、CCD相机和超声三维诊断仪等仪器进行结合，实现了机器人的体外高精度驱动和体内可视化驱动。本发明提供的一种磁驱动微纳米机器人，由于其体积小且具有生物相容性，在生物医学、微流控、纳米工程等领域具有重要的应用价值。
The invention discloses a structure design of a magnetically driven micro-nano robot, a preparation method and a driving method thereof. The main structure of the magnetic-driven micro-nano robot is a shuttle-shaped double-leaf ribbon spiral. The true three-dimensional fabrication of the robot is realized by the path-optimized two-photon polymerization laser direct writing technology, and the surface of the robot is sputtered for magnetic drive. The nickel layer and the titanium layer for improving the biocompatibility of the robot are driven by a conical rotating uniform magnetic field, and the robot is driven by a three-axis Helmholtz coil magnetic field generator with a micro-movement stage, a CCD camera and an ultrasonic three-dimensional The combination of diagnostic instruments and other instruments realizes the in vitro high-precision driving and in vivo visualization driving of the robot. The magnetic-driven micro-nano robot provided by the invention has important application value in the fields of biomedicine, microfluidics, nano-engineering and the like due to its small size and biocompatibility.
Description
Technical Field
The invention belongs to the field of micro robots, and particularly relates to a structural design of a micro-nano magnetically-driven transportation and drilling robot, a preparation method of the micro-nano magnetically-driven transportation and drilling robot and a driving mode of the micro-nano magnetically-driven transportation and drilling robot.
Background
Over the past decade, due to advances in micro-nano fabrication and handling systems, various micro-nano robots have emerged that convert external energy into their own kinetic energy by consuming fuel in the surrounding medium, or by using external energy sources, such as light, ultrasound, electric fields, magnetic fields, or combinations thereof.
Among the various ways of driving the micro-nano robot, magnetic field driving is gradually the best choice for driving the micro-nano robot due to the advantages of non-invasiveness, contribution to reducing the size of the robot, no adverse interaction with biological tissues under various conditions, remote control, realization of various motion mechanisms, joint development of other technologies and the like, and meanwhile, the advantages also enable the magnetic driving micro-nano robot to have wide application prospects in the fields of drug delivery, cell classification, sensing, environment restoration, small object operation and the like in a living body.
The micro-nano robot mainly works in a low Reynolds number liquid environment due to the size of the micro-nano robot, so that the micro-nano robot has the characteristic of time reversibility, and the micro-nano robot needs to break the symmetry of deformation in time in order to realize movement in the low Reynolds number liquid environment.
The existing method for driving the magnetic micro-nano robot comprises the following steps: the micro-nano robot is driven by the rotating uniform magnetic field in a spiral propulsion mode, so that the micro-nano robot can be driven controllably with higher driving efficiency and control accuracy.
In the aspect of preparation technology, the two-photon polymerization laser direct writing technology has gradually become a mainstream method for manufacturing a magnetic drive micro-nano spiral robot due to the advantages of capability of processing any true three-dimensional structure, simple process, high resolution and the like.
As a result of bionic bacterial flagella, the appearance of the magnetically-driven micro-nano spiral robot marks the rapid development of the modern micro-nano robot technology and the micro-nano driving technology, however, compared with the spiral microorganism in nature, the artificially-made magnetically-driven micro-nano spiral robot has lower stability in the motion process and is easily influenced by the external complex environment, and in addition, in the process of actually driving the micro-nano spiral robot at a gas-liquid interface, a liquid interior or a solid-liquid interface by using the existing magnetically-driven system, undesirable conditions such as low motion efficiency, uncontrollable swing, serious transverse drift and the like still occur.
Disclosure of Invention
The invention provides a magnetic driving micro-nano spiral robot for minimally invasive surgery, which is characterized in that a micro-nano spiral robot which can be magnetized and has biocompatibility is manufactured through a two-photon polymerization laser direct writing technology and an ion sputtering technology, and the in-vitro high-precision driving and in-vivo visual driving of the micro-nano spiral robot are realized by combining a three-axis Helmholtz coil magnetic field generating device with instruments such as a micropositioner, a CCD camera, an ultrasonic three-dimensional diagnostic apparatus and the like.
The technical scheme of the invention is as follows.
The designed magnetic driving micro-nano spiral robot has a spindle-shaped double-leaf belt type spiral main body structure and the height of the robot
Pitch of thread
Lead, lead
Minimum diameter of
Maximum diameter, diameter
And the number of spiral turns n =1.5, and a nickel layer and a titanium layer with the thicknesses of 100nm and 20nm are sputtered on the surface of the robot respectively.
The method comprises the steps of processing a magnetically-driven micro-nano spiral robot by using methacrylic acid hydrogel GelMA through a two-photon polymerization laser direct writing technology, wherein an optimized true three-dimensional processing path is that the internal structure of the micro-nano spiral robot is scanned and processed to obtain the main structure of the robot, and then the surface profile of the robot is scanned and processed.
The micro-nano spiral robot is driven by a conical rotating uniform magnetic field B generated by a three-axis Helmholtz coil magnetic field generating device, and the precession angle of the conical rotating uniform magnetic field
Misalignment angle with micro-nano spiral robot
Of the same magnitude, wherein the conical rotating uniform magnetic field B is formed by a constant-magnitude magnetic field perpendicular to and rotating about the axis L
And a constant magnitude magnetic field parallel to the axis L
Combined to form the misalignment angle of the micro-nano spiral robot
It is the angle between the easy axis and the spiral axis.
Taking a micro-fluidic chip as an example, when a magnetically-driven micro-nano spiral robot is driven outside an organism, the driving device comprises a three-axis Helmholtz coil magnetic field generating device arranged on a desktop, a micro-stage support, an objective lens support and a light source support, wherein the micro-stage is connected to the micro-stage support through screws, an objective table is connected to the micro-stage support through screws, the micro-fluidic chip with the magnetically-driven micro-nano spiral robot is placed on the objective table, the objective lens support and a CCD camera support are connected to the objective lens support through screw pressing mechanisms, an objective lens is connected to the objective lens support through a screw pressing mechanism, a CCD camera is connected to the CCD camera support through screws and a CCD camera fixing piece, the light source support is connected to the light source support through a screw pressing mechanism, and a light source is connected to the light source support through screws, wherein the micro-stage is used for moving the micro-fluidic chip with the micro-nano spiral robot to the center of the three-axis Helmholtz coil magnetic field generating device The CCD camera and the objective lens are used for monitoring the position and the motion state of the micro-nano spiral robot in real time, and the light source is used for providing illumination to a certain degree for the monitoring process.
Taking a human body as an example, when the magnetically-driven micro-nano spiral robot is driven in a biological body, the driving device comprises a control host, an ultrasonic three-dimensional diagnostic apparatus and a large-scale three-axis Helmholtz coil magnetic field generating device, wherein the large-scale three-axis Helmholtz coil magnetic field generating device is used for generating a required control magnetic field at a specified position in the human body, the ultrasonic three-dimensional diagnostic apparatus is used for monitoring the position and the motion state of the magnetically-driven micro-nano spiral robot in the human body in real time, and the control host is used for processing image information fed back by the ultrasonic three-dimensional diagnostic apparatus and sending a corresponding driving signal to the large-scale three-axis Helmholtz coil magnetic field generating device according to the information.
The invention also provides a preparation method of the magnetic drive micro-nano spiral robot, which more specifically comprises the following steps:
the method comprises the following steps: spin-coating a photoresist on a glass substrate;
step two: putting the glass substrate coated with the photoresist in the first step into an oven for prebaking for 10 min;
step three: putting the glass substrate coated with the photoresist and subjected to the pre-baking in the step two into two-photon polymerization processing equipment, and processing the micro-nano spiral robot by using laser with the wavelength of 800nm according to a pre-programmed processing code;
step four: putting the glass substrate processed with the micro-nano spiral robot in the third step into an oven and then baking for 10 min;
step five: soaking the glass substrate which is processed with the micro-nano spiral robot and is baked in the fourth step in a developing solution for 10 min;
step six: taking out the glass substrate which is soaked in the developing solution in the step five and is processed with the micro-nano spiral robot from the developing solution, washing the glass substrate with absolute ethyl alcohol, and drying the glass substrate;
step seven: putting the glass substrate processed with the micro-nano spiral robot dried in the sixth step into an ion sputtering instrument, bombarding different targets by ions emitted by an ion source, and sputtering a nickel layer with the thickness of 100nm and a titanium layer with the thickness of 20nm on the surface of the micro-nano spiral robot in sequence;
step eight: carrying out radial magnetization on the micro-nano spiral robot sputtered with the nickel layer and the titanium layer in the seventh step by using a permanent magnet;
step nine: dropping a drop of distilled water on the glass substrate with the magnetized micro-nano spiral robot in the step eight, immersing the micro-nano spiral robot in the distilled water, and separating the micro-nano spiral robot from the glass substrate by using a microprobe;
step ten: moving the micro-nano spiral robot immersed in the distilled water separated from the glass substrate in the step nine into a glass test tube filled with a drug solution by using a liquid transfer device, and loading drug particles in the solution to the surface of the micro-nano spiral robot through electrostatic adsorption;
step eleven: and (5) moving the micro-nano spiral robot with the medicine particles loaded on the surface in the step (ten) into a micro-channel with an external magnetic field by using an injector.
The invention has the advantages.
(1) The magnetic driving micro-nano spiral robot designed by the invention is a micron-sized robot, has good biocompatibility and has the maximum diameter of
And the diameter of the capillary vessel of the organism is
Therefore, the micro-nano spiral robot can be matched with an injector to realize the minimally invasive surgery treatment of the organism through the blood circulation system of the organism.
(2) The magnetic driving micro-nano spiral robot designed by the invention belongs to a spiral belt type robot, and compared with the traditional spiral line type robot, the surface area of the robot is obviously increased, so that the load capacity of the robot is improved, and the transportation efficiency of the robot is improved.
(3) The magnetically-driven micro-nano spiral robot designed by the invention adopts a symmetrical double-blade design, and compared with the traditional single-blade design, the symmetry of the robot in the aspect of structure is improved, so that the stability of the robot in the motion process is improved.
(4) The magnetic driving micro-nano spiral robot designed by the invention has the fusiform geometric characteristics, compared with the cylindrical geometric characteristics, the fusiform geometric characteristics are favorable for reducing the head-on resistance of the robot in the moving process and the coupling effect between the robot and a solid wall surface, so that the moving performance of the robot is improved, including the forward propulsion speed of the robot, the transverse drift speed of the robot and the moving capability of the robot along the forward direction and the reverse direction are reduced, and the fusiform geometric characteristics are also favorable for improving the barrier penetrating capability of the robot, so that the moving reliability of the robot in a complex environment and the success rate of targeted medicine delivery are improved, and in addition, compared with the conical geometric characteristics, the fusiform geometric characteristics are more favorable for keeping the self balance of the robot in the moving process.
(5) The invention realizes the true three-dimensional manufacture of the magnetic driving micro-nano spiral robot by the two-photon polymerization laser direct writing technology, and in addition, the internal structure of the robot is firstly scanned and processed and then the surface contour of the robot is scanned and processed by further optimizing the processing path, thereby improving the surface quality and the structural strength of the robot.
(6) In the invention, a titanium layer with the thickness of 20nm is sputtered on the surface of the designed magnetically-driven micro-nano spiral robot, so that the biocompatibility of the robot is further improved.
(7) Compared with the traditional plane rotation uniform magnetic field, the conical rotation uniform magnetic field can eliminate the uncontrollable swing of the robot in the low-frequency driving process under the condition of ensuring that the precession angle of the rotation magnetic field is the same as the misalignment angle of the robot, so that the robot can move more reliably and stably at a low speed.
(8) According to the invention, the large triaxial Helmholtz coil magnetic field generating device is combined with the ultrasonic three-dimensional diagnostic apparatus through the control host, so that the in-vivo visual driving of the magnetically-driven micro-nano spiral robot harmless to organisms can be realized.
Drawings
Fig. 1 is a schematic structural diagram of a magnetically-driven micro-nano spiral robot.
Fig. 2 is a schematic diagram of an improved processing path for processing a magnetically-driven micro-nano spiral robot by a two-photon polymerization laser direct writing technology.
FIG. 3 is a view of rotating a uniform magnetic field through a plane perpendicular to the axis L
And a constant magnetic field parallel to the axis L
Schematic diagram of the resultant conical rotating uniform magnetic field B.
Fig. 4 is a schematic diagram of a magnetically-driven micro-nano spiral robot driven by a conical rotating uniform magnetic field.
Fig. 5 is a schematic diagram of a driving device when the magnetic driving micro-nano spiral robot is driven outside a living body.
Fig. 6 is an assembly schematic diagram of a three-axis helmholtz coil magnetic field generating device for driving a magnetically-driven micro-nano spiral robot outside a living body.
Fig. 7 is a schematic view of a driving apparatus for driving a magnetically driven micro-nano spiral robot in a living body.
Fig. 8 is a flow chart of preparing a magnetic driving micro-nano spiral robot.
Fig. 9 is a schematic diagram for comparing the structures of the spiral and spiral belt type magnetic driving micro-nano spiral robots with the cylindrical geometric feature, the conical geometric feature and the shuttle geometric feature respectively.
Fig. 10 is a schematic diagram of coupling contact between a helical ribbon type magnetic driving micro-nano helical robot and a solid surface, wherein the helical ribbon type magnetic driving micro-nano helical robot has a cylindrical geometric feature, a conical geometric feature and a fusiform geometric feature respectively.
Detailed Description
As shown in figure 1, a main structure 1 of the magnetic drive micro-nano spiral robot is a fusiform double-leaf belt type spiral, and the height of the robot
Pitch of thread
Lead of
Minimum diameter of
Maximum diameter, diameter
And the number of spiral turns n =1.5, and a nickel layer 2 and a titanium layer 3 having thicknesses of 100nm and 20nm, respectively, are sputtered on the surface of the robot.
The magnetic driving micro-nano spiral robot is processed by methacrylic acid hydrogel GelMA through a two-photon polymerization laser direct writing technology, wherein an optimized true three-dimensional processing path is shown in figure 2, the internal structure of the micro-nano spiral robot is firstly scanned to obtain the main body structure of the robot, and then the surface contour of the robot is scanned.
As shown in fig. 3 and 4, a three-axis helm is usedThe micro-nano spiral robot is driven by a conical rotating uniform magnetic field B generated by the Hotz coil magnetic field generating device, and the precession angle of the conical rotating uniform magnetic field
Misalignment angle with micro-nano spiral robot
Of the same magnitude, wherein the conical rotating uniform magnetic field B is formed by a constant-magnitude magnetic field perpendicular to and rotating about the axis L
And a constant magnitude magnetic field parallel to the axis L
Combined to form a misalignment angle of the micro-nano spiral robot
It is the angle between the easy axis and the spiral axis.
As shown in fig. 5 and 6, taking a micro-fluidic chip as an example, when a magnetically driven micro-nano spiral robot is driven outside a living body, the driving device includes a three-axis helmholtz coil magnetic field generating device 4 installed on a desktop 5, a micro-stage support 6, an objective support 9 and a light source support 18, the micro-stage 7 is connected to the micro-stage support 6 by screws, the objective stage 8 is connected to the micro-stage 7 by screws, a micro-fluidic chip 15 with the magnetically driven micro-nano spiral robot is placed on the objective stage 8, the objective support 10 and the CCD camera support 11 are connected to the objective support 9 by screw pressing mechanisms, the objective 14 is connected to the objective support 10 by screw pressing mechanisms, the CCD camera 12 is connected to the CCD camera support 11 by screws and a CCD camera fixing part 13, the light source support 16 is connected to the light source support 18 by screw pressing mechanisms, the light source 17 is connected to the light source support 16 through a screw, wherein the micro-motion stage 7 is used for moving a micro-fluidic chip with the micro-nano spiral robot to the center of the three-axis Helmholtz coil magnetic field generating device, the CCD camera 12 and the objective lens 14 are used for monitoring the motion state of the micro-nano spiral robot in real time, and the light source 17 is used for providing illumination to a certain degree for the monitoring process.
The magnetic driving micro-nano spiral robot is small in size and good in biocompatibility, so that the magnetic driving micro-nano spiral robot can be injected to a pathological change position in a living body through an injector, and then the robot is used for realizing minimally invasive surgery treatment on the living body.
As shown in fig. 7, taking a human body as an example, when a magnetically-driven micro-nano spiral robot is used in a biological body to perform minimally invasive surgery, the driving device includes a control host 19, an ultrasonic three-dimensional diagnostic apparatus 20 and a large three-axis helmholtz coil magnetic field generating device 21, where the large three-axis helmholtz coil magnetic field generating device 21 is used to generate a required control magnetic field at a specified position in the human body, the ultrasonic three-dimensional diagnostic apparatus 20 is used to monitor the position and motion state of the magnetically-driven micro-nano spiral robot in the human body in real time, and the control host 19 is used to process image information fed back by the ultrasonic three-dimensional diagnostic apparatus 20 and send a corresponding driving signal to the large three-axis helmholtz coil magnetic field generating device 21 according to the information.
As shown in fig. 8, the invention further provides a preparation method of the magnetic driving micro-nano spiral robot, which more specifically comprises the following steps:
the method comprises the following steps: spin-coating a photoresist 23 on a glass substrate 25;
step two: placing the glass substrate 25 coated with the photoresist 23 in the first step into an oven for prebaking for 10 min;
step three: putting the glass substrate 25 coated with the photoresist 23 and subjected to the pre-baking in the step two into two-photon polymerization processing equipment, and processing the micro-nano spiral robot 22 by using laser 24 with the wavelength of 800nm according to a processing code compiled in advance;
step four: putting the glass substrate 25 processed with the micro-nano spiral robot 22 in the third step into an oven and then baking for 10 min;
step five: soaking the glass substrate 25 which is processed with the micro-nano spiral robot 22 and is baked in the fourth step in a developing solution for 10 min;
step six: taking out the glass substrate 25 processed with the micro-nano spiral robot 22 soaked in the developing solution in the step five from the developing solution, washing the glass substrate with absolute ethyl alcohol, and drying the glass substrate;
step seven: putting the glass substrate 25 which is dried in the step six and is processed with the micro-nano spiral robot 22 into an ion sputtering instrument, bombarding different targets 27 by ions emitted by an ion source 26, and sputtering a nickel layer with the thickness of 100nm and a titanium layer with the thickness of 20nm on the surface of the micro-nano spiral robot 22 in sequence;
step eight: carrying out radial magnetization on the micro-nano spiral robot 22 sputtered with the nickel layer and the titanium layer in the seventh step by using a permanent magnet 28;
step nine: dropping a drop of distilled water 30 on the glass substrate 25 with the magnetized micro-nano spiral robot 22 in the step eight, immersing the micro-nano spiral robot 22 in the distilled water 30, and separating the micro-nano spiral robot 22 from the glass substrate 25 by using a microprobe 29;
step ten: moving the micro-nano spiral robot 22 immersed in the distilled water 30 separated from the glass substrate 25 in the ninth step into a glass test tube 32 filled with the drug solution by using a pipette 31, and loading drug particles in the solution onto the surface of the micro-nano spiral robot 22 through electrostatic adsorption;
step eleven: the micro-nano spiral robot 22 with the drug particles loaded on the surface in the step ten is moved into the micro channel 34 with the external magnetic field applied thereto by the syringe 33.
As shown in fig. 9 and 10, fig. 9 shows 6 different structural designs of the magnetic driving micro-nano spiral robot, which are respectively cylindrical single-leaf spiral, conical single-leaf spiral, fusiform single-leaf spiral, cylindrical double-leaf belt spiral, conical double-leaf belt spiral and fusiform double-leaf belt spiral from a to F, figure 10 shows the case of D, E driven at the solid-liquid interface and F-shaped magnetic driven micro-nano spiral robot, in the actual design process, the shuttle-shaped double-leaf belt type spiral design F is adopted, so that the load capacity and the barrier penetrating capacity of the robot are improved, the structural strength of the robot is enhanced, the symmetry of the robot in the structural aspect is improved, thereby reducing the head-on resistance of the robot in the moving process and the coupling effect between the robot and the solid wall surface, therefore, the reliability and stability of the robot in motion in a complex environment and the success rate and efficiency of targeted drug delivery are improved.
Before actually driving the micro-nano spiral robot, a constant magnetic field is applied to the robot to measure the misalignment angle of the robot
Then according to the misalignment angle of the robot
Precession angle to conical rotating uniform magnetic field
And adjusting to make the two equal in size, and adjusting the movement speed and the movement direction of the robot by adjusting the rotation frequency of the conical uniform rotating magnetic field and the direction of the rotating shaft in the process of actually driving the robot.
The magnetic field generating device capable of generating the conical rotating uniform magnetic field is combined with instruments such as a micropositioner and an ultrasonic diagnostic apparatus, and the application potential of the micro-nano spiral robot in the fields of biomedicine, microfluidics, nano engineering and the like can be further excited.
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