A robot for vascular embolization

Abstract

This invention belongs to the field of vascular embolization treatment device technology, and discloses a robot for vascular embolization, comprising magnetic particles and an elastic polymer substrate, wherein the magnetic particles are dispersed in the elastic polymer substrate; the robot's initial shape is a helical hollow structure, and the elastic polymer substrate is fibrous and distributed in a spiral shape; the robot can deform under the action of an external magnetic field. This invention improves the structure and composition of the robot, utilizing magnetic particles in conjunction with the elastic polymer substrate to form a spiral-shaped fiber, resulting in a magnetic robot with high maneuverability and shape reconfigurability. In particular, it can perform robotic embolization in the sub-millimeter region remotely, without restraint, and in a magnetically controllable manner. Compared with existing robots, the robot of this invention is compatible with current clinical catheters, has high flexibility in intravascular movement, good maneuverability, and can fulfill the needs of multifunctional embolization.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of vascular embolization treatment devices, and more particularly relates to a robot for vascular embolization. BACKGROUND

[0002] Cerebral aneurysm and brain tumor are the diseases with the highest mortality and disability rate in the world. Vascular embolization is a minimally invasive surgical method widely used in clinical practice. By releasing embolic agents (such as coils and particles) at the lesion site to reduce blood flow to the lesion, cerebral aneurysm rupture or brain tumor blood supply can be prevented, so as to achieve the purpose of treatment or palliative treatment. In the current embolization surgery, the surgeon first inserts a guide wire with a pre-bent tip into the femoral artery of the patient and manually pushes it through the blood vessels to the target lesion. Subsequently, a catheter is inserted through the guide wire and embolic agents are injected into the target lesion. However, the pre-bent guide wire cannot pass through the complex and rugged cerebral vascular network and smoothly approach the target lesion. Therefore, it is impossible to deliver embolic agents (coils and particles) to the designated location.

[0003] To address this challenge, guide wires / catheters with flexible control of the tip have attracted great interest in the past decade. These guide wires / catheters often have magnetic particles on the tip, and the movement of the tip is controlled by an external magnetic field to achieve functions such as selecting bifurcated blood vessels. Although the guidance of such guide wires / catheters has been enhanced, the delivery end of these guide wires / catheters still needs to be pulled and advanced using a "wired" method (the delivery end is often connected to a motor). For narrow blood vessels, the operability is greatly reduced. Especially when the guide wire / catheter is highly twisted and twisted, the wired driving method still has problems such as low flexibility and insufficient pushing force. Existing catheters still face great challenges in delivering embolic agents to blood vessels in the sub-millimeter region (i.e., with a diameter less than 1 millimeter).

[0004] Taking the existing platinum metal micro-spring-shaped embolic agent as an example, the platinum metal micro-spring-shaped embolic agent can only be released to the target location by injection and the like, and cannot move actively after being released, nor can it actively control the position of the embolic agent.

[0005] Recently, there are some small-sized wireless robots that can use blood flow to embolize in the sub-millimeter region. However, they passively drift in the blood flow, which can lead to non-targeted embolization in the blood vessels and cause safety problems. SUMMARY

[0006] In order to solve the problems of the current vascular embolization assembly (including the existing vascular robot) in the brain blood vessels, such as limited embolization site, low flexibility and poor control ability, the purpose of the present application is to provide a robot for vascular embolization, wherein the structure and composition of the robot are improved, and the whole structure with an initial shape of a spiral type hollow structure is formed by using magnetic particles and an elastic polymer base material, and the corresponding magnetic robot has the characteristics of high maneuverability and shape reconfigurability, and can perform robot embolization in a remote, unbound and magnetically controllable manner in the sub-millimeter region. The robot in the present application can be compatible with the current clinical catheter, has high flexibility in intravascular movement, good control stability, and can complete the demand of multifunctional embolization. By controlling the magnetic field, the robot shows reversible elongation / condensation shape deformation and spiral propulsion under flow conditions, allowing controllable navigation in a complex vascular system, such as robot embolization in the sub-millimeter region.

[0007] In order to achieve the above-mentioned purpose, according to one aspect of the present application, a robot for vascular embolization is provided, characterized in that it comprises magnetic particles and an elastic polymer base material, wherein the magnetic particles are dispersed in the elastic polymer base material; the initial shape of the robot is a spiral type hollow structure, the elastic polymer base material is in a fiber shape and is distributed in a thread shape; and the robot can be deformed under the action of an external magnetic field.

[0008] As a further preferred embodiment of the present application, the initial shape of the robot before deformation is a spiral type hollow structure, and the fiber-shaped elastic polymer base material is distributed in a thread shape.

[0009] As a further preferred embodiment of the present application, the robot has also been subjected to a magnetization treatment, so that the magnetic particles have a magnetization direction along the thread shape.

[0010] As a further preferred embodiment of the present application, the initial shape of the robot is obtained by forming a straight fiber in a thread shape; before the forming, the straight fiber has also been subjected to a magnetization treatment, and the direction of the applied magnetic field for magnetization is parallel to the fiber axial direction.

[0011] When the external magnetic field is opposite to the net magnetization direction of the robot, the fiber-shaped elastic polymer base material will be condensed;

[0012] When the external magnetic field is the same as the net magnetization direction of the robot, the fiber-shaped elastic polymer base material will be stretched, and the spiral diameter will be reduced;

[0013] When the external magnetic field is a helical magnetic field, and the rotation axis of the helical magnetic field is parallel to the net magnetization direction of the robot, the robot can perform helical precession; preferably, the frequency of the helical magnetic field is 0.1-100 Hz, and the magnetic field strength is 1-200 mT, and correspondingly, the movement speed of the robot is 0.01-10 mm / s.

[0014] As a further preferred embodiment of the present application, the initial shape of the robot satisfies: the helical diameter is 0.1-2 mm, the diameter of the fiber-shaped elastic polymer base material is 10-100 μm, and the total length of the fiber-shaped elastic polymer base material is 0.5-5 mm.

[0015] As a further preferred embodiment of the present application, the elastic polymer base material is one or more of silicone rubber, acrylate rubber, thermoplastic polyurethane, and styrene-ethylene / butylene-styrene block copolymer (SEBS).

[0016] The material of the magnetic particles is one or more of neodymium-iron-boron (NdFeB), samarium-cobalt (SmCo), barium-iron oxide (BaFeO), and iron-platinum alloy (FePt).

[0017] As a further preferred embodiment of the present application, the Young's modulus of the robot is lower than 10 MPa, and the residual magnetization is higher than 80 kA / m.

[0018] Preferably, the outer surface of the elastic polymer base material is further covered with a hydrogel coating layer, and the thickness of the hydrogel coating layer is 5-30 μm.

[0019] According to another aspect of the present application, the present application provides a vascular embolization operation instrument for the above-mentioned robot for vascular embolization, characterized in that the instrument comprises an external magnetic field generating device and the above-mentioned robot for vascular embolization; the external magnetic field generating device comprises a permanent magnet or an electromagnet.

[0020] The external magnetic field generating device is used to provide an external magnetic field, so as to control the deformation of the robot.

[0021] As a further preferred embodiment of the present application, the external magnetic field generating device can provide a rotating magnetic field, and the frequency of the magnetic field is 0.1-100 Hz, and the magnetic field strength is 1-200 mT.

[0022] According to still another aspect of the present application, the present application provides a preparation method of the above-mentioned robot for vascular embolization, characterized in that the preparation method is as follows: first, a composite straight fiber of magnetic particles and an elastic polymer base material is prepared, and the magnetic particles are uniformly dispersed in the elastic polymer base material; then, the straight fiber is magnetized along the fiber axis; and finally, the straight fiber is formed into a screw thread shape, so as to obtain the robot for vascular embolization; wherein the composite straight fiber is formed by hot stretching, extrusion type 3D printing, or injection molding.

[0023] Preferably, the preparation method comprises the following steps:

[0024] (1) compounding the magnetic particles with the elastic polymer substrate to obtain a composite;

[0025] (2) wrapping the composite with a thermoplastic resin as a sacrificial layer material, and then forming a straight fiber by heat stretching, extrusion 3D printing or injection molding;

[0026] (3) magnetizing the straight fiber obtained in step (2) along the fiber axis;

[0027] (4) winding the magnetized straight fiber on a heat conduction rod in the shape of a screw thread, and then heating and forming;

[0028] (5) removing the sacrificial layer material to obtain a robot for vascular embolization.

[0029] Compared with the prior art, the above technical scheme of the present application utilizes magnetic particles and an elastic polymer substrate to form a magnetic robot for vascular embolization, which can enter the blood vessel through a catheter or a syringe and realize wireless controllable movement and multi-modal deformation in the blood vessel under the control of an external magnetic field to adapt to complex curved blood vessels; the robot can deform and gather to block the blood supply at a specific position.

[0030] The magnetic robot in the present application has high maneuverability and reliable operability, can complete different functional embolization requirements, has a wide range of indications, including cerebral aneurysm and brain tumor, and specific treatment schemes include aneurysm coil embolization, tumor coil embolization and tumor microparticle embolization protection. It can be especially used for performing robot embolization to treat cerebral aneurysm and brain tumor.

[0031] Moreover, the preparation method of the robot is simple and feasible, and only needs to go through magnetization, forming and demolding of straight microfibers to complete the preparation. The straight microfibers are prepared by compounding an elastomer material substrate and magnetic particles, and can be formed by heat stretching, extrusion 3D printing, light curing 3D printing, injection molding and the like. The diameter of the straight microfiber including a sacrificial layer is between 10-500 μm, and the corresponding fiber diameter (specifically the fiber diameter after removing the sacrificial layer) can be flexibly adjusted according to the size of the target blood vessel.

[0032] Specifically, the robot in the present application has the following beneficial effects:

[0033] 1. The initial shape of the magnetic robot can be a helical geometry with customizable dimensions. For example, the helical diameter of the robot can be set between 0.1 and 2 mm, the fiber diameter of the robot can be set between 10 and 500 μm, and the length of the robot can be set between 0.5 and 5 mm. It is compatible with existing commercial catheters (such as Headway microcatheters, Terumo) to maximize their clinical efficacy.

[0034] The robot can be manipulated within blood vessels under flowing conditions by controlling a driving magnetic field. The robot has multiple morphological modes, including an initial state, a stretched state (in which the fibrous elastic polymer substrate is, for example, in a stretched fibrous state), and a clustered state (in which the fibrous elastic polymer substrate is, for example, in a clustered fibrous state); furthermore, the robot's morphological modes can be interchanged. Driven by the magnetic field, the robot can deform from the initial state to the stretched state, from the stretched state back to the initial state, from the initial state to the clustered state, and from the clustered state back to the initial state. Typical functions include helical precession, elongation, aggregation, and retrieval, applicable to various embolization applications, such as aneurysm coil embolization, tumor coil embolization, and tumor microparticle embolization protection. Taking the clustered state as an example, the robot can act as an embolic agent to block or alter blood flow, or as a protective device for healthy blood vessels. Taking the elongated state (corresponding to the stretched state), the robot's helical diameter can vary from 0.1 mm to 1 mm.

[0035] 2. The robot in this invention is compatible with commercial catheter-based interventional procedures. Standard catheter insertion can begin by inserting a commercial catheter through a blood vessel until it stops within the vessel segment. Subsequently, a robot with a helical diameter slightly larger than the vessel segment diameter can be delivered into the bloodstream through the catheter. The robot can be released and retrieved via currently used clinical microcatheters, which are typically 300–900 μm in size, effectively compatible with the robot of this invention. This ensures high operational safety and fast delivery. The robot can spiral precession under a magnetic field, moving freely and stably within the blood vessel. The robot's speed changes with the magnetic field frequency; an increase in frequency and intensity also increases speed. Therefore, the robot's movement can be flexibly controlled by adjusting the applied magnetic field. Furthermore, before spiral precession, the robot can be deformed into a stretched state, significantly reducing the helical diameter. Applying a magnetic field before spiraling allows it to adapt to blood vessels of different sizes, such as 0.1–2 mm.

[0036] 3. For the robot in all states, by contacting the blood vessel, it can anchor itself to the vessel wall in the absence of a magnetic field, thus preventing it from being washed away in the blood flow. Anchoring can still be achieved at blood flow velocities higher than 10 cm / s. In other words, the robot of this invention can remain in the blood vessel without a magnetic field and can withstand blood flow velocities of at least 10 cm / s (of course, it can also achieve an anchoring effect at blood flow velocities less than 10 cm / s). In its initial state, the robot of this invention can achieve stent-like anchoring in an environment with a flow velocity greater than 10 cm / s by utilizing the friction between itself and the vessel wall, even without a magnetic field. Of course, in a clustered state, since the diameter tends to be larger, the friction between it and the vessel wall will increase, making anchoring even more effective.

[0037] 4. Furthermore, by utilizing the robot's aggregated state, the robot in this invention can serve as a carrier to simultaneously carry multiple functional materials, enabling it to perform various functions such as drug delivery and cell delivery. Of course, in its aggregated state, the robot can maintain structural stability in the absence of a magnetic field and in environments with flow velocities greater than 10 cm / s, and can also move in this aggregated state.

[0038] 5. Since the magnetic particles used in this application can be clearly distinguished from human tissue under ultrasound and X-ray, the robot of this application can be compatible with current clinical medical imaging, such as ultrasound imaging systems and digital subtraction angiography (DSA).

[0039] Meanwhile, since the robot in this application can be controlled by an external magnetic field, this wireless vascular robot has enormous application prospects and value in the field of minimally invasive surgery. An external magnetic field generator can be set up independently, enabling remote wireless multi-dimensional control based on existing technology, such as translation, rotation, and steering.

[0040] In summary, the robot of this invention can not only move more safely and controllably within blood vessels, but also enter areas that are difficult for catheters to reach, providing a solution for the treatment of cerebral aneurysms and tumors in a more minimally invasive manner. Attached Figure Description

[0041] Figure 1 This is a schematic diagram illustrating the function and potential application scenarios of the magnetic robot of the present invention (it can be used as an embolizing agent for coil embolization of aneurysms and tumors, and can also be used in conjunction with embolizing particles for embolization protection; B in the figure is a schematic diagram of an external magnetic field, including ① a rotating magnetic field, ② a magnetic field in the same direction as the net magnetization direction of the robot, ③ a magnetic field in the opposite direction to the net magnetization direction of the robot, and other possible situations). Figure 1 In the corresponding example, the robot's net magnetization direction is the same as the blood vessel axis, that is, the robot's net magnetization direction is along the blood vessel axis.

[0042] Figure 2Manufacturing process of the robot and optical images of the magnetic soft microfibers with different fiber diameters and helix diameters.

[0043] Figure 3 Schematic diagram of the deformation mechanism of the robot.

[0044] Figure 4 Schematic diagram of the magnetic field generating device and its spatial degrees of freedom.

[0045] Figure 5 Schematic diagram of the control strategy of the robot.

[0046] Figure 6 Schematic diagram and physical image of different control modes of the robot in the aggregation state; wherein, Figure 6 (a) in the schematic diagram, Figure 6 (b) in the physical image, they correspond to the static state, the overall movement and the decoupling (decoupling refers to the robot returning to the initial state from the aggregation state) of the aggregation state from top to bottom, respectively.

[0047] Figure 7 Physical image of an aneurysm model.

[0048] Figure 8 Physical image of a multi-branch tumor blood vessel model (assuming branch 2 is a tumor blood vessel, and branch 1 and branch 3 are healthy blood vessels). The corresponding images are two robots entering the blood vessel and embolizing the branch 2 blood vessel, wherein the left image corresponds to robot 1 having moved to the target position in branch 2 and anchored, and the real-time positions of robot 2 at 0s, 7.7s, 17.3s, and 24.4s after starting to move; the right image corresponds to robots 1 and 2 having moved to the target position in branch 2 and anchored (embolizing the branch 2 blood vessel), and then releasing contrast agent, the overall embolization effect diagram, from which the embolization effect of branch 2 can be verified.

[0049] Figure 9 Physical image of a multi-branch tumor blood vessel model (assuming branch 2 and branch 3 are tumor blood vessels, and branch 1 is a healthy blood vessel; the scales in the figure are all 2mm). Among them, the upper left image corresponds to the real-time positions of the robot at 0s, 8.9s, 20.2s, 35.2s, and 53.5s after starting to move (the robot has moved to the target position in branch 1 and anchored at 53.5s); the upper right image corresponds to the effect comparison diagram of each branch at 0s and 30s after releasing embolic particles with a diameter of about 200 microns (since branch 1 has been protected by the robot, embolic particles will not flow into branch 1); the lower left image corresponds to the real-time positions of the robot at 0s, 6.3s, 14.1s, 36.4s, and 56.6s after starting to recover; the lower right image corresponds to the overall embolization effect diagram after releasing contrast agent, from which the embolization effect of branch 2 and branch 3 can be verified.

[0050] Figure 10 The schematic diagram of in vivo experimental platform. As shown in the figure, under the guidance of X-ray, the robot is released into the femoral artery of a live rabbit through a catheter, and then the robot is manipulated under the guidance of a magnetic field.

[0051] Figure 11 The fluorescent imaging photo of the magnetic robot of the present application being guided to the target position by magnetic force and gathering. The figure corresponds to the robot entering the blood vessel under the guidance of the external magnetic field, reaching the designated position for gathering embolization; then releasing the contrast agent to contrast the blood flow before and after embolization.

[0052] Figure 12 The blood vessel tissue section staining diagram. The figure corresponds to three section positions, of which position 2 uses the robot gathering anchor; it can be seen from the figure that position 1 forms a thrombus, verifying the effectiveness of embolization (the green line marked part in the right figure corresponds to the robot area). DETAILED DESCRIPTION

[0053] In order to make the purpose, technical scheme and advantages of the present application clearer, the present application will be further described in detail below in combination with the drawings and examples. It should be understood that the specific examples described herein are only used to explain the present application and are not used to limit the present application. In addition, the technical features involved in each embodiment of the present application described below can be combined with each other as long as they do not conflict with each other.

[0054] Example 1

[0055] The robot for vascular embolization in the present application comprises magnetic particles and an elastic polymer substrate, wherein the magnetic particles are dispersed in the elastic polymer substrate, the elastic polymer substrate is in a fiber shape and is distributed in the shape of a thread when not deformed, and correspondingly, the initial shape of the robot is a spiral hollow structure; the robot can be deformed under the action of an external magnetic field.

[0056] Taking the spiral hollow structure with a spiral diameter and a pitch as constant values as the initial shape of the robot before deformation as an example, the robot can be deformed in the blood vessel according to an external magnetic field, and can flexibly switch between different states such as motion, residence, etc. in the blood vessel (of course, other spiral shapes also have similar effects, for example, spiral shapes with varying spiral diameters and / or pitches, etc.). The specific sizes such as the spiral diameter, the fiber diameter and the length of the robot (i.e. the total length of the fiber-shaped elastic polymer substrate) can be flexibly adjusted according to the size of the target blood vessel.

[0057] Taking the spiral hollow structure as the initial shape of the robot before deformation as an example, a detailed description is made as follows:

[0058] For example, the robot is in a spiral hollow structure before deformation, and the spiral diameter and the pitch are constant values. When the robot is in the blood vessel, the external magnetic field is applied to the robot to make the robot deformed, and the robot is in a spiral hollow structure after deformation, and the spiral diameter and the pitch are variable values. Figure 1As shown, the robot obtained by the present application can be anchored on the blood vessel by friction force after being released (the robot will generate friction force after being released into the blood vessel and locally contacting with the blood vessel wall), navigated in the blood flow by screw propulsion, passed through the stenosis area by elongation, and stopped the blood flow by gathering. The micro fiber robot in the gathering state can be used as embolic agent for aneurysm and tumor coil embolization, and also as protective device for selective microparticle embolization of tumors.

[0059] It is prepared as follows Figure 2 As shown, it can include the following steps: thermal stretching of the magnetic fiber, strong pulse magnetic field (~ 2.5T) magnetization, and shaping / demolding into a spiral shape. The magnetic composite material in the present application is prepared by dispersing non-magnetized magnetic microparticles (such as neodymium iron boron NdFeB) in a soft elastomer matrix (such as poly(styrene-b-(ethylene-co-butylene)-b-styrene), SEBS) by chemical solution. Due to the limited stretchability of the soft magnetic elastomer composite, thermoplastic polycarbonate (PC) can be introduced as a co-stretching sacrificial layer. Taking the use of ferromagnetic neodymium iron (i.e., ferromagnetic rare earth neodymium iron boron (NdFeB) particles with an average diameter of 5 μm), a soft base styrene-ethylene-butylene-styrene (SEBS) material, and polycarbonate (PC) particles as an example:

[0060] (S1) Mix the ferromagnetic NdFeB particles in the pre-dissolved SEBS / hexane solution (in this example, the volume ratio of SEBS to hexane in the SEBS / hexane solution is 15:85, of course, other ratios commonly used in the prior art can also be used), so that the volume fraction of NdFeB is 20%. After mechanical stirring for 30 minutes and ultrasonic dispersion for 1 hour, pour the NdFeB / SEBS / hexane suspension into a mold and completely dry in a fume hood, then peel off the obtained NdFeB / SEBS film from the mold, cut it into small pieces of magnetic SEBS (M-SEBS), and then roll the SEBS small pieces into a hollow cylinder to obtain an SEBS cylinder.

[0061] (S2) In order to support the manufacture of PC cladding, completely dry PC particles are loaded into the mold between the hot press and hot pressed into a cuboid at 230°C. The PC cuboid is turned into a PC tube, which can have a centimeter-level outer diameter and a slightly larger inner diameter than the SEBS cylinder. Then the SEBS cylinder is inserted into the PC tube to make a whole preform.

[0062] (S3) After the above-mentioned centimeter-level cylindrical structure is heat consolidated in an assembled manner, the preform composed of a magnetic soft core (i.e., M-SEBS core) and a sacrificial cladding (i.e., PC cladding) is then heat stretched into magnetic ultrafine fibers with different diameters in a custom heat stretching tower at 230°C. When the stretching ratio is between 100 and 200, the diameter of the magnetic fiber can be adjusted between 20-90 μm.

[0063] (S4) The magnetic microfiber is first magnetized by a 2.5T impulse magnetic field (the magnetic field direction is parallel to the fiber) generated by a digital pulse magnetizer. Then the fiber with PC cladding is wrapped on a high thermal conductivity rod with the same spiral parameters using tweezers. Adhesive tape is used to ensure the tight contact between the fiber and the rod. Then the rod with microfiber is placed on a hot plate at 90°C for 30 minutes.

[0064] (S5) After the magnetic microfiber is molded into a spiral structure, it is separated from the rod. The sacrificial PC cladding is chemically selectively removed by N, N-dimethylacetamide until the cladding is completely dissolved. Finally, the robot is cut into the desired length (the resulting product is similar in shape to a spiral spring). At this time, the spiral morphology of the robot (corresponding to the spiral diameter, pitch, etc.) corresponds to the initial state (neither stretched nor aggregated). For example, as shown in Figure 2 , based on this method, a series of robots of different sizes can be processed, and the fiber diameter and spiral diameter can be adjusted according to actual needs.

[0065] Example 2

[0066] Taking the spiral robot with a fiber diameter of 60μm and a spiral diameter of 1mm as an example, based on the present application, the specific control strategy of the robot in the blood vessel can be as follows:

[0067] The deformation mechanism of the robot: as shown in Figure 3 , the robot is magnetized along the direction of the spiral structure (the magnetization step is exemplified in step S4 of example 1), and has a net magnetization direction along the central axis. Then the robot is placed in the blood vessel, so that the net magnetization direction of the robot is the same as the axial direction of the blood vessel, and the same as the direction of the blood flow. By applying a driving magnetic field with the same direction as the net magnetization direction (along the axial direction of the blood vessel) (the magnetic field strength is for example 40mT), the magnetic microfiber robot is elongated, and the spiral diameter is reduced from the initial diameter of 1mm to 0.1mm. When the magnetic field is removed, the robot changes from the stretched state to the initial state. Conversely, when the external magnetic field is opposite to the net magnetization direction (along the axial direction of the blood vessel) (the magnetic field strength is for example 20mT), the microfiber robot is aggregated, and at this time, due to the winding of the fiber itself, the micro robot can still maintain the aggregated state after the magnetic field is removed.

[0068] Since the robot in the present application needs to be regulated by a magnetic field, a cubic magnet can be used as a magnetic field source, as shown in Figure 4As shown, a cubic magnet with a side length of 5 cm and a residual magnetic flux density of 1.38 T can be used (of course, according to actual needs of different residual magnetic flux densities, different ferromagnetic materials can be used to construct a magnetic field source with a preset shape according to the prior art). By moving the magnetic field source horizontally, vertically, rotating, etc., the magnetic field distribution of the cubic magnet in space can be changed to obtain the required magnetic field configuration of the static magnetic field, the rotating magnetic field, etc. The ways of controlling the magnet include manual control, displacement platform control, mechanical arm control, etc. For example Figure 5 As shown, by controlling the distance between the cubic magnet and the robot to be 50-100 mm and the rotation frequency to be 0.5-10 Hz, the robot can be elongated, gathered, and helically propelled. The helical propulsion speed of the robot relative to the blood vessel wall in the simulated blood can be 0.1-10 mm / s.

[0069] For example, as shown in the robot in the gathered state, Figure 6 As shown, after the robot is deformed to the gathered state, the robot can be anchored in the blood flow environment relying on the friction force in the absence of a magnetic field (at this time, since it is in the gathered state, the friction force will be greater due to the existence of elastic potential energy. In addition, Figure 6 As shown, the blood flow rate is 100 mm / s; it can be predicted that when the blood flow rate is lower than 100 mm / s, the robot will be more stable and also have an anchoring effect), the magnetic field can be applied to move the whole in the gathered state, at this time, the angle between the magnetic field and the initial net magnetization direction of the robot (along the blood vessel axial direction) can be 30-80 degrees (to ensure that there is a certain magnetic field component perpendicular to the central axis direction of the blood vessel to avoid decoupling), and the distance can be 50-100 mm. When a magnetic field opposite to the initial net magnetization direction (along the blood vessel axial direction) is applied, the microfiber robot can deform back to the initial helical state.

[0070] Embodiment 3

[0071] To verify the effect of the application, the robot is applied to aneurysm coil embolization, and the specific method can be as follows:

[0072] As shown in the robot in the gathered state, Figure 7 As shown in the aneurysm coil embolization, the robot first moves to the aneurysm in a helical propulsion manner under the guidance of an external magnetic field, wherein the distance between the cubic magnet and the robot can be 50-100 mm, and the rotation frequency of the cubic magnet can be 0.5-5 Hz. When reaching the vicinity of the aneurysm, the cubic magnet applies a magnetic field opposite to the initial net magnetization direction (along the blood vessel axial direction), and the robot changes to the gathered state. At this time, the magnetic force is applied to pull the gathered body into the aneurysm.

[0073] To observe the embolization effect, subsequently, a contrast agent is injected to observe the flow direction. By comparing the aneurysm before embolization and the aneurysm after embolization, it is found that the flow rate in the aneurysm lumen after embolization is significantly reduced.

[0074] Example 4

[0075] To verify the effectiveness of this invention, the robot was applied to tumor coil embolization. The specific method is as follows:

[0076] Figure 8 The diagram shows a multi-branched tumor vessel model, where branch 2 represents the tumor vessel, while branches 1 and 3 represent healthy vessels. First, a robot is guided to branch 2, with a cubic magnet positioned 50–100 mm away from the robot, and the magnet's rotation frequency ranging from 0.5 to 5 Hz. However, it was found that a single clustered robot could not completely block branch 2. Therefore, a second robot was deployed in branch 2 to achieve double clustering (the position of the second robot changes over time, such as...). Figure 8 (As shown). Furthermore, by controlling the shape parameters of each robot (such as fiber diameter and initial spiral diameter), the magnitude of the manipulating magnetic field for each robot can be made different, thus allowing for individual robot control. This ensures that the two external magnetic fields do not interfere with each other. Moreover, this method of using multiple robots in combination maximizes the embolization effect while ensuring the maneuverability of each individual robot. (While using a single robot with sufficiently long fibers may result in similar embolization effects, excessively long fibers reduce the robot's maneuverability in confined blood vessel spaces, hindering effective embolization. Therefore, using multiple robots in combination yields better overall results.)

[0077] To observe the embolization effect, contrast agent was injected and the blood flow direction was observed. The contrast agent flow was normal in the protected branches 1 and 3, with no obvious obstruction. However, the contrast agent could not pass through branch 2, resulting in obstruction.

[0078] Example 5

[0079] To verify the effectiveness of this invention, the robot was applied to tumor embolization protection. The specific method is as follows:

[0080] Figure 9 The diagram shows a multi-branched tumor vessel model, assuming branches 2 and 3 are tumor vessels, while branch 1 is a healthy vessel. To prevent embolic particles from flowing into the healthy branch 1, a microfiber robot is first guided to branch 1 and aggregated. The distance between the cubic magnet and the robot can be 50–100 mm, and the rotation frequency of the cubic magnet can be 0.5–5 Hz. Then, embolic particles (average diameter 250 μm) are released into the fluid, selectively blocking branches 2 and 3 (during the embolization operation, the robot's position changes over time, such as...). Figure 9The particle embolization is completed, the gathered micro-fiber robot can be safely recovered and retrieved (wherein the distance between the cubic magnet and the robot can also be 50-100 mm, and the rotating frequency of the cubic magnet can also be 0.5-5 Hz, and only the direction of the external magnetic field needs to be turned). During the recovery operation, the magnetic field with the opposite rotating direction to the initial rotating magnetic field is applied, and the change of the position of the robot with time is as shown in Figure 9

[0081] To observe the embolization protection effect, finally, the contrast agent is injected to observe the blood flow direction. The contrast agent in branch 1 flows normally, and no obvious obstruction is found, and the contrast agent in branch 2 and branch 3 cannot pass, and obstruction occurs.

[0082] Example 6

[0083] To verify the effect of the application, the robot is applied to the animal body for vascular embolization, and the specific method can be as follows:

[0084] The in-vivo experiment platform as shown in Figure 10 is adopted, in a digital subtraction angiography (DSA) room, through real-time image observation, the femoral artery of a rabbit is punctured, a catheter is inserted into the femoral artery, and then the robot is released through the catheter.

[0085] Under the control of the external magnetic field, the distance between the cubic magnet and the robot is 50-100 mm, and the rotating frequency of the cubic magnet is 0.5-5 Hz. The robot is guided to move in the blood vessel, and under the guidance of the fluorescence imaging, as shown in Figure 11 Figure 11 It is shown that the magnetic robot is guided to the target position by the magnetic force and is gathered. Then, whether the vascular embolization is completed is verified by comparing the injection of the contrast agent. Before embolization, it can be seen that the entire femoral artery has iodine contrast agent. After embolization, no contrast agent is observed due to the blockage of the gathered micro-fiber bundle. The gathered micro-fiber bundle hinders the blood flow from the proximal end to the distal end of the artery, resulting in the formation of a blood clot in the artery after one week of embolization. Finally, the embolization performance and safety of the robot are verified by vascular tissue section staining, and the result is as shown in Figure 12 It can be seen that a stable blood clot is generated in the blood vessel, verifying the effectiveness of the robot in the in-vivo vascular embolization.

[0086] Those skilled in the art can easily understand that the above description is only a preferred embodiment of the application, and is not used to limit the application, and any modification, equivalent replacement and improvement made within the spirit and principle of the application shall be included in the protection scope of the application.​​

Claims

1. A robot for vascular embolization, characterized by, The robot comprises magnetic particles and an elastic polymer base material, wherein the magnetic particles are dispersed in the elastic polymer base material; the initial shape of the robot is a spiral hollow structure, the elastic polymer base material is in a fiber shape and is distributed in a spiral shape; the robot can be deformed under the action of an external magnetic field; The initial shape of the robot satisfies that the spiral diameter is 0.1-2 mm, the diameter of the fiber-shaped elastic polymer base material is 10-100 μm, and the total length of the fiber-shaped elastic polymer base material is 0.5-5 mm. The initial shape of the robot is obtained by forming straight fibers in a spiral shape; before the forming, the straight fibers are subjected to a magnetization treatment, and the direction of the magnetic field applied in the magnetization treatment is parallel to the fiber axial direction. When the external magnetic field is opposite to the net magnetization direction of the robot, the fiber-shaped elastic polymer base material will be gathered, and at this time, if the magnetic field is removed, the robot can still maintain the gathered state. When the external magnetic field is the same as the net magnetization direction of the robot, the fiber-shaped elastic polymer base material will be stretched, and the spiral diameter will be reduced, and at this time, if the magnetic field is removed, the robot will change from the stretched state to the initial shape. When the external magnetic field is a spiral magnetic field and the rotation axis of the spiral magnetic field is parallel to the net magnetization direction of the robot, the robot can perform spiral precession.

2. The robot for vascular embolization according to claim 1, wherein, The robot is further subjected to a magnetization treatment, so that the magnetic particles have a magnetization direction distributed along the spiral shape.

3. The robot for vascular embolization according to claim 1, wherein When the external magnetic field is a spiral magnetic field and the rotation axis of the spiral magnetic field is parallel to the net magnetization direction of the robot, the frequency of the spiral magnetic field is 0.1-100 Hz, the magnetic field strength is 1-200 mT, and correspondingly, the movement speed of the robot is 0.01-10 mm / s.

4. The robot for use in vascular embolization according to claim 1, wherein, The elastic polymer base material is one or more of a silicon-based rubber, an acrylate rubber, a thermoplastic polyurethane, and a styrene-ethylene / butylene-styrene block copolymer (SEBS). The material of the magnetic particles is one or more of neodymium-iron-boron (NdFeB), samarium-cobalt (SmCo), barium-iron oxide (BaFeO), and iron-platinum alloy (FePt).

5. The robot for use in vascular embolization according to claim 1, wherein, The Young's modulus of the robot is lower than 10 MPa, and the residual magnetization strength is higher than 80 kA / m.

6. The robot for use in vascular embolization according to claim 5, wherein, The outer surface of the elastic polymer base material is further covered with a hydrogel coating, and the thickness of the hydrogel coating is 5-30 μm.

7. The apparatus for vascular embolization operation using the robot according to any one of claims 1 to 6, characterized by The robot for vascular embolization according to any one of claims 1-6 and an external magnetic field generating device; the external magnetic field generating device comprises a permanent magnet or an electromagnet; The external magnetic field generating device is used to provide an external magnetic field, so as to control the deformation of the robot.

8. An apparatus for embolotherapy according to claim 7, wherein The external magnetic field generating device can provide a rotating magnetic field, the frequency of the magnetic field is 0.1-100 Hz, and the magnetic field strength is 1-200 mT.

9. The method for manufacturing the robot for vascular embolization as described in any one of claims 1-6, characterized in that, The preparation method is to first prepare a composite straight fiber of magnetic particles and an elastic polymer base material, wherein the magnetic particles are uniformly dispersed in the elastic polymer base material; then, the straight fiber is magnetized along the fiber axis; and then, the straight fiber is formed into a threaded shape, thereby obtaining a robot for vascular embolization; wherein the composite straight fiber is formed by heat stretching, extrusion type 3D printing or injection molding.

10. The method of claim 9, wherein the step of preparing is characterized by, The preparation method comprises the following steps: (1) combining magnetic particles with an elastic polymer base material to obtain a composite; (2) wrapping a thermoplastic resin as a sacrificial layer material outside the composite, and then forming a straight fiber by heat stretching, extrusion type 3D printing or injection molding; (3) magnetizing the straight fiber obtained in step (2) along the fiber axis; (4) winding the magnetized straight fiber on a heat conduction rod in a threaded shape, and then heating and forming; (5) removing the sacrificial layer material, and the robot for vascular embolization can be obtained.

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