CN116327296A

CN116327296A - Robot for vascular embolism

Info

Publication number: CN116327296A
Application number: CN202310192145.5A
Authority: CN
Inventors: 臧剑锋; 刘旭睿
Original assignee: Huazhong University of Science and Technology
Current assignee: Huazhong University of Science and Technology
Priority date: 2023-03-02
Filing date: 2023-03-02
Publication date: 2023-06-27

Abstract

The invention belongs to the technical field of vascular embolism therapeutic equipment, and discloses a robot for vascular embolism, which 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, and the elastic polymer base material is fibrous and distributed according to the shape of threads; the robot can deform under the action of an externally applied magnetic field. The invention improves the structure and the composition of the robot, utilizes the magnetic particles to form the fiber with the initial shape of a thread shape by matching with the elastic polymer base material, and the correspondingly obtained magnetic robot has the characteristics of high maneuverability, shape reconfigurability and the like, and can particularly execute the embolism of the robot in a submillimeter area in a remote, unbound and magnetically controllable mode. Compared with the existing robots, the robot provided by the invention can be compatible with the existing clinical catheters, has high flexibility in intravascular movement and good control stability, and can meet the requirement of multifunctional embolism.

Description

Robot for vascular embolism

Technical Field

The invention belongs to the technical field of vascular embolism treatment instruments, and particularly relates to a robot for vascular embolism.

Background

Cerebral aneurysms and brain tumors are the diseases with the highest global mortality and disability rate at present. Vascular embolization is a minimally invasive surgical procedure that has been widely used clinically. By releasing embolic agents (e.g., coils and particles) at the lesion to reduce blood flow to the lesion, cerebral aneurysms can be prevented from rupture or blood supply to the brain tumor can be cut off, thereby achieving therapeutic or palliative purposes. In current embolization procedures, a surgeon first inserts a guidewire with a pre-curved tip into the femoral artery of the patient and manually pushes it through the blood vessel toward the target lesion. The catheter is then passed through a guidewire and embolic agent is injected into the target lesion. However, pre-curved leads cannot pass through the complex bumpy cerebrovascular network and successfully approach the target lesion. The embolic agent (coil and particles) cannot be delivered to a given location.

To address this challenge, guidewires/catheters with flexible control of the tip have attracted tremendous interest in the last decade. These flexible distal ends often have magnetic particles disposed on the distal end to regulate movement of the distal end by an externally applied magnetic field to perform functions such as selecting a bifurcated vessel. Although the introductory nature of such guidewires/catheters is enhanced, the delivery end of these guidewires/catheters still need to be pulled, advanced in a "wired" fashion (the delivery end often being connected to a motor), and the operability is greatly reduced for stenosed vessels. Especially when the wires/catheters are highly twisted and twisted, the wired drive still suffers from low maneuverability and insufficient propulsion, and existing catheters still present significant challenges in delivering embolic agents to vessels in the sub-millimeter region (i.e., less than 1 millimeter in diameter).

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 a target position by injection and the like, and the position of the embolic agent cannot be actively moved or actively regulated after the release.

Recently, there are some small-sized wireless robots that can use blood flow to embolize in the sub-millimeter region. However, passive drifting in the blood stream may lead to non-targeted embolization within the blood vessel and raise safety concerns.

Disclosure of Invention

In order to solve the problems of limited embolism position, low flexibility, poor control capability and the like of the existing vascular embolism assembly (including the existing vascular robot) in cerebral vessels, the invention aims to provide a robot for vascular embolism, wherein the structure and the composition of the robot are improved, and magnetic particles are matched with elastic polymer base materials to form an integral structure with an initial shape of a spiral hollow structure, so that the correspondingly obtained magnetic robot has the characteristics of high operability, shape reconfigurability and the like, and particularly, the robot embolism can be executed in a submillimeter area in a remote, unbound and magnetically controllable mode. Compared with the existing robots, the robot provided by the invention can be compatible with the existing clinical catheters, has high flexibility in intravascular movement and good control stability, and can meet the requirement of multifunctional embolism. By controlling the magnetic field, the robot exhibits reversible elongating/aggregating shape deformation and spiral propulsion under flow conditions, allowing for controlled navigation in complex vascular systems, such as robotic embolization in the sub-millimeter region.

To achieve the above object, according to one aspect of the present invention, there is provided a robot for vascular embolization, characterized by comprising magnetic particles and an elastic polymer substrate, wherein the magnetic particles are dispersed in the elastic polymer substrate; the initial shape of the robot is a spiral hollow structure, and the elastic polymer base material is fibrous and distributed according to the shape of threads; the robot can deform under the action of an external magnetic field.

As a further preferred aspect of the present invention, the initial shape of the robot before deformation is a spiral hollow structure, and the fibrous elastic polymer base material is distributed in the shape of a screw.

As a further preferred aspect of the present invention, the robot is further subjected to magnetization treatment so that the magnetic particles have magnetization directions distributed along the shape of the screw.

As a further preferred aspect of the present invention, the initial shape of the robot is obtained by shaping straight fibers in the shape of threads; before forming, the straight fiber is subjected to magnetization treatment, and the direction of a magnetic field applied by magnetization is parallel to the axial direction of the fiber;

when the external magnetic field is opposite to the net magnetization direction of the robot, the fibrous elastic polymer base material gathers;

when the external magnetic field is the same as the net magnetization direction of the robot, the fibrous elastic polymer substrate is stretched, and the spiral diameter is reduced;

when the external magnetic field is a spiral magnetic field and the rotating shaft of the spiral magnetic field is parallel to the net magnetization direction of the robot, the robot can perform spiral precession; preferably, the frequency of the spiral magnetic field is 0.1-100 Hz, the magnetic field strength is 1-200 mT, and the movement speed of the robot is 0.01-10 mm/s correspondingly.

As a further preferred aspect of the present invention, the initial shape of the robot satisfies: the spiral diameter is 0.1-2 mm, the diameter of the fibrous elastic polymer base material is 10-100 mu m, and the total length of the fibrous elastic polymer base material is 0.5-5 mm.

As a further preferred aspect of the present invention, the elastic polymer substrate is one or more of silicone-based rubber, acrylate rubber, thermoplastic polyurethane, styrene-ethylene/butylene-styrene block copolymer (SEBS);

the magnetic particles are made of one or more of neodymium iron boron (NdFeB), samarium cobalt (SmCo), barium-iron oxide (BaFeO) and iron platinum alloy (FePt).

As a further preferred aspect of the present invention, the young's modulus of the robot is lower than 10MPa and the residual magnetization is higher than 80kA/m;

preferably, the outer surface of the elastic polymer substrate is further covered with a hydrogel coating layer, and the thickness of the hydrogel coating layer is 5-30 μm.

According to another aspect of the present invention, there is provided a vascular embolization operation device of the above-described robot for vascular embolization, characterized by comprising an external magnetic field generating device and the above-described robot for vascular embolization; the external magnetic field generating device comprises a permanent magnet or an electromagnet;

the external magnetic field generating device is used for providing an external magnetic field so as to control the deformation of the robot.

As a further preferred aspect of the present invention, the external magnetic field generating device is capable of providing a rotating magnetic field having a magnetic field frequency of 0.1 to 100Hz and a magnetic field strength of 1 to 200mT.

According to still another aspect of the present invention, there is provided the above-mentioned preparation method of a robot for vascular embolism, characterized in that the preparation method comprises preparing composite straight fibers of magnetic particles and an elastic polymer base material, wherein the magnetic particles are uniformly dispersed in the elastic polymer base material; then, magnetizing the straight fiber along the fiber axial direction; then, forming the straight fiber into a thread shape, thereby obtaining a robot for vascular embolism; wherein the composite straight fiber is formed by hot stretching, extrusion type 3D printing or injection molding;

preferably, the preparation method comprises the following steps:

(1) Compounding magnetic particles with an elastic polymer base material to obtain a compound;

(2) Wrapping thermoplastic resin outside the composite by taking the thermoplastic resin as a sacrificial layer material, and forming straight fibers by hot stretching, extrusion type 3D printing or injection molding;

(3) Magnetizing the straight fiber obtained in the step (2) along the axial direction of the fiber;

(4) Winding the magnetized straight fiber on a heat conducting rod according to the shape of a thread, and then heating and forming;

(5) And removing the sacrificial layer material to obtain the robot for vascular embolism.

Compared with the prior art, the magnetic robot for vascular embolism is formed by utilizing the magnetic particles and the elastic polymer base material, can enter a blood vessel through a catheter or a syringe, and can realize wireless controllable movement and multi-mode deformation in the blood vessel under the control of an external magnetic field to adapt to the blood vessel with complex bending; the robot may deform and aggregate to block the blood flow supply at a particular location.

The magnetic robot has the characteristics of high operability and reliable operability, can meet the embolism requirements of different functions, has wide application, comprises cerebral aneurysms and cerebral tumors, and has specific treatment schemes of aneurysm coil embolism, tumor coil embolism and tumor particle embolism protection. In particular for performing robotic embolic treatment of cerebral aneurysms and brain tumors.

Moreover, the preparation method of the robot is simple and feasible, and the preparation can be finished only by magnetizing, molding and demolding the straight microfiber. The straight microfiber is prepared by compounding an elastomer material base material and magnetic particles, can be formed by using processes such as hot stretching, extrusion type 3D printing, photo-curing type 3D printing, injection molding and the like, has the diameter of 10-500 mu m including a sacrificial layer, and can flexibly adjust the corresponding fiber diameter (specifically, the fiber diameter after the sacrificial layer is removed) according to the target blood vessel size.

Specifically, the robot of the invention has the following beneficial effects:

1. the initial shape of the magnetic robot may be a spiral geometry with customizable dimensions, for example, the spiral diameter of the robot may be set between 0.1 and 2mm, the fiber diameter of the robot may be set between 10 and 500 μm, and the length of the robot may be set between 0.5 and 5mm, compatible with existing commercial catheters (e.g., headway microcatheters, terumo) to maximize its clinical efficacy.

The robot may further operate in the vessel under flow conditions by controlling the driving magnetic field. The various morphological modes of the robot include, for example, an initial state, a stretched state (in which the fibrous elastic polymer base material is, for example, in a stretched fibrous state), and a gathered state (in which the fibrous elastic polymer base material is, for example, in a gathered fibrous state); the shape modes of the robot can be mutually switched, and the robot can be deformed from an initial state to a stretched state, from the stretched state to the initial state, from the initial state to the aggregation state, and from the aggregation state to the initial state under the drive of a magnetic field. Typical functions include precession, elongation, aggregation and retrieval, applicable to a variety of embolic applications, such as: aneurysm coil embolization, tumor coil embolization, and tumor particulate embolization protection. Taking the robot in the aggregation state as an example, the robot in the aggregation state can be used as an embolic agent for preventing or changing the blood flow direction or as a protecting device of a healthy blood vessel. Taking elongation as an example (corresponding to the stretched state), the spiral diameter of the robot may for example achieve a variation between 0.1mm and 1mm.

2. The robot of the present invention may be compatible with the commercial catheterization paradigm, and standard catheterization may be performed by first passing a commercial catheter through the vessel until endovascular advancement ceases at the vessel segment. Thereafter, a robot having a spiral diameter slightly larger than the diameter of the vessel segment may be delivered from the catheter into the blood. The robot can be released and recovered through the microcatheter used clinically at present, the size of the microcatheter commonly used at present is 300-900 mu m, the robot can be effectively compatible with the robot in the invention, the operation safety is high, and the delivery speed is high. The robot can spiral under the magnetic field and can freely move in the blood vessel in a stable and controllable mode; the movement speed of the robot changes along with the change of the magnetic field frequency, the magnetic field frequency is increased, and the speed of the robot is increased; the increase of the magnetic field intensity and the movement speed of the robot are also increased, so that the movement of the robot can be flexibly controlled by regulating and controlling the external magnetic field. In addition, before the spiral precession, the robot can be deformed into a stretching state, so that the spiral diameter is greatly reduced, and the spiral is carried out by applying a magnetic field to spiral in, so that the device can adapt to blood vessels with different sizes, such as blood vessels with 0.1-2 mm.

3. With the robot in all states, by contact with the blood vessel, it is possible to anchor to the vessel wall in the absence of a magnetic field, thereby preventing it from being washed away in the blood stream, and anchoring can still be achieved at blood flow speeds higher than 10 cm/s. That is, the robot of the present invention can be used to resist a blood flow velocity of not less than 10cm/s without a magnetic field residing in a blood vessel (of course, a blood flow velocity of less than 10cm/s can have an anchor effect). In the initial state, the robot can anchor the stent-like in an environment with the flow velocity of more than 10cm/s by utilizing friction force between the robot and the pipe wall under the condition of no magnetic field. Of course, in the case of the aggregation state, the diameter tends to be large in the aggregation state, so that the friction force between the pipe wall and the pipe wall is increased, and the anchoring is facilitated.

4. In addition, the robot can be used as a carrier to simultaneously load a plurality of functional materials by utilizing the aggregation state of the robot, and can realize a plurality of functions such as medicine loading, cell loading and the like. Of course, the robot may be kept stable in the state of aggregation in the environment where the flow velocity is more than 10cm/s in the absence of a magnetic field, or may be moved in the state of aggregation.

5. Because the magnetic particles used in the present application can be clearly distinguished from human tissue under ultrasound and X-rays, the robots of the present application are compatible with current clinical medical imaging, such as ultrasound imaging systems, digital Subtraction Angiography (DSA).

Meanwhile, the robot can be controlled through an externally applied magnetic field, so that the wireless vascular robot has great application prospect and value in the field of minimally invasive surgery. The external magnetic field generating device can be independently arranged, and the remote wireless multidimensional control such as translation, rotation, steering and the like can be performed based on the prior art.

In conclusion, the robot disclosed by the invention can move in a blood vessel more safely and controllably, can enter into a region which is difficult to reach by a catheter, and provides a solution for cerebral aneurysm and tumor treatment in a more minimally invasive manner.

Drawings

Fig. 1 is a schematic diagram of functions and potential application scenarios of a magnetic robot of the present invention (embolic agent capable of being used for coil embolization of aneurysms and tumors, and also capable of being used for matching embolic particles and performing embolic protection, wherein B in the figure is an externally applied magnetic field schematic diagram, and includes (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 the like, and in the example corresponding to fig. 1, the net magnetization direction of the robot is the same as the axial direction of a blood vessel, that is, the net magnetization direction of the robot is along the axial direction of the blood vessel.

Fig. 2 is a schematic view of the manufacturing process of the robot of the present invention and an optical image of magnetic soft microfibers of different fiber diameters and spiral diameters.

Fig. 3 is a schematic view of a deformation mechanism of the robot of the present invention.

Fig. 4 is a schematic view of a magnetic field generating device and its spatial degree of freedom.

Fig. 5 is a schematic view of a control strategy of the robot according to the present invention.

FIG. 6 is a schematic view and a physical diagram of different operation modes of the robot gathering state according to the present invention; the diagram (a) in fig. 6 corresponds to the schematic diagram, and the diagram (b) in fig. 6 corresponds to the physical diagram, and they respectively correspond to standing, overall movement and decoupling of the aggregation state from top to bottom (decoupling refers to the restoration of the robot from the aggregation state to the initial state).

Fig. 7 is a real model diagram of an aneurysm.

Fig. 8 is a physical diagram of a multi-bifurcated tumor vessel model (assuming branch 2 is a tumor vessel and branches 1 and 3 are healthy vessels). The figure corresponds to the entry of 2 robots into the blood vessel and the embolism of the branch 2 blood vessel, wherein the left figure corresponds to the real-time position of the robot 1 when the robot 1 moves to the target position in the branch 2 and is focused and anchored, and the robot 2 starts moving at the 0s, 7.7s, 17.3s and 24.4 s; the right figure corresponds to a diagram of the overall embolic effect from which the embolic effect of branch 2 can be verified, with both

robots

1, 2 having been moved to the target location in branch 2 and anchored (embolizing the branch 2 vessel) and then released contrast agent.

FIG. 9 is a physical diagram of a multi-branched tumor vessel model (assuming branch 2 and branch 3 are tumor vessels and branch 1 is a healthy vessel; the scale bars in the figure represent 2 mm). Wherein the upper left graph corresponds to real-time positions of the robot at 0s, 8.9s, 20.2s, 35.2s, 53.5s after starting to move (the robot has moved to the target position in branch 1 at 53.5s, and is focused and anchored); the upper right plot corresponds to a comparison plot of the effect of each branch at 0s and 30s after release of embolic particles having 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 graph corresponds to real-time positions of the robots at 0s, 6.3s, 14.1s, 36.4s and 56.6s after the robots begin to recover; the lower right plot corresponds to the overall embolic effects plot from which the embolic effects of branch 2 and branch 3 can be verified after release of contrast agent.

Fig. 10 is a schematic diagram of an in vivo experimental platform. As shown, the robot is released into femoral artery blood vessel of living rabbit through catheter under the guidance of X-ray, and then is manipulated under the guidance of magnetic field.

FIG. 11 is a photograph of a fluorescence image of a magnetic robot of the present invention magnetically guided to a target location and focused. The figure corresponds to that the robot enters a blood vessel under the guidance of an external magnetic field and reaches a designated position to perform aggregation embolism; contrast agent is then released to contrast the blood flow situation before and after the embolism.

FIG. 12 is a staining chart of vascular tissue sections. Corresponding to 3 slice positions in the figure, wherein position 2 uses robot gathering anchors; from the figure, it is seen that the thrombus is formed at the position 1, and the effectiveness of the thrombus is verified (the green line mark portion in the right drawing corresponds to the robot region in the figure).

Detailed Description

The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention. In addition, the technical features of the embodiments of the present invention described below may be combined with each other as long as they do not collide with each other.

Example 1

The robot for vascular embolism comprises magnetic particles and an elastic polymer base material, wherein the magnetic particles are dispersed in the elastic polymer base material, the elastic polymer base material is fibrous and distributed in a thread shape when not deformed, and the initial shape of the robot is a spiral hollow structure; the robot can deform under the action of an external magnetic field.

Taking a spiral hollow structure with an initial shape of the robot before deformation as a fixed value of a spiral diameter and a fixed value of a spiral pitch as an example, the robot can deform in a blood vessel according to an external magnetic field, and can flexibly switch different states such as movement, residence and the like in the blood vessel (of course, other spiral shapes have similar effects, for example, a spiral shape with a continuously changing spiral diameter and/or spiral pitch and the like). The specific dimensions of the spiral diameter, the fiber diameter, the robot length (i.e., the total length of the fibrous elastic polymer substrate) and the like can be flexibly adjusted according to the size of the target blood vessel.

The following describes in detail an initial shape of the robot before deformation as a spiral hollow structure:

as shown in fig. 1, the resulting robot of the present invention can be anchored to a blood vessel by friction after release (the robot will generate friction after release to the vessel, local contact with the vessel wall), navigate through the blood flow by spiral propulsion, by elongating through a stenosed region, and by occluding the blood flow. The microfiber robot in the aggregation state can be used as an embolic agent for aneurysms and tumor coil embolization and can also be used as a protective device for tumor selective microparticle embolization.

Its preparation is shown in fig. 2, and may comprise the steps of: the magnetic fiber is thermally stretched, magnetized by a strong pulse magnetic field (-2.5T), and molded/demolded into a spiral shape. The magnetic composite material of the present invention is prepared by dispersing non-magnetized magnetic particles (e.g., neodymium iron boron, ndFeB) in a soft elastomer matrix (e.g., poly (styrene-b- (ethylene-co-butylene) -b-styrene), SEBS) by a chemical solution. Due to the limited stretchability of soft magnetic elastomer composites, thermoplastic Polycarbonate (PC) may be incorporated as a co-stretched sacrificial layer. Taking as an example ferromagnetic neodymium iron (i.e. ferromagnetic rare earth neodymium iron boron (NdFeB) particles with an average diameter of 5 μm), soft base styrene-ethylene-butylene-styrene (SEBS) material, polycarbonate (PC) particles:

(S1) the ferromagnetic NdFeB particles are mixed in a pre-dissolved SEBS/hexane solution (in this example, the volume ratio of SEBS to hexane is 15:85, of course, other ratios commonly used in the prior art can be used) so that the volume fraction of NdFeB is 20%. After mechanical stirring for 30 minutes and ultrasonic dispersion for 1 hour, the NdFeB/SEBS/hexane suspension was poured into a mold and completely dried in a fume hood, the obtained NdFeB/SEBS film was peeled off from the mold, and cut into small pieces of magnetic SEBS (M-SEBS), and the SEBS small pieces were rolled into a hollow cylinder to obtain an SEBS cylinder.

(S2) to support PC clad manufacturing, the completely dried PC pellets were charged into a mold between hot presses and hot pressed into a rectangular parallelepiped at 230 ℃. The PC cuboid is turned into a PC tube, the outer diameter of the PC tube can be in the order of centimeters, and the inner diameter of the PC tube is slightly larger than that of the SEBS cylinder. The SEBS cylinder was then inserted into a PC tube to make a monolithic preform.

(S3) after the above-mentioned cm-sized cylindrical structure is thermally consolidated in an assembled manner, the preform composed of the magnetic soft core (i.e., M-SEBS core) and the sacrificial clad (i.e., PC clad) is then thermally drawn into magnetic ultrafine fibers of different diameters in a custom-made thermal drawing tower at 230 ℃. When the draw ratio is between 100 and 200, the diameter of the magnetic fiber can be adjusted between 20 and 90 μm.

(S4) the magnetic ultrafine fibers are magnetized first by a 2.5T impact magnetic field (the magnetic field direction is parallel to the fibers) generated by a digital pulse magnetizer. The fibers with PC cladding were then wrapped with tweezers onto a high thermal conductivity rod using the same spiral parameters. Adhesive tape is used to ensure intimate contact of the fibers with the rod. The rod with the ultrafine fibers was then placed on a hot plate at 90℃for 30 minutes.

(S5) after the magnetic ultrafine fibers are molded into a spiral structure, separating from the rod. The sacrificial PC cladding was removed by chemoselective removal with N, N-dimethylacetamide until the cladding was completely dissolved. Finally, the robot is cut to the desired length (the resulting product is similar in shape to a coil spring). At this time, the screw shape (corresponding to parameters such as screw diameter and screw pitch) of the robot corresponds to the initial state (neither stretching nor aggregation). For example, as shown in fig. 2, based on the method, a series of robots with different sizes can be manufactured, and the fiber diameter and the screw diameter can be adjusted according to actual needs.

Example 2

Taking a prepared spiral robot with a fiber diameter of 60 μm and a spiral diameter of 1mm as an example, based on the specific control strategy of the robot in a blood vessel, the following can be adopted:

deformation mechanism of robot: as shown in fig. 3, the robot is magnetized along the direction of the spiral structure (the magnetizing step is as exemplified by step S4 of embodiment 1), with a net magnetization direction along its center axis. Then the robot is placed in the blood vessel, so that the net magnetization direction of the robot is the same as the blood vessel axial direction and the blood flow direction. By applying the same driving magnetic field (magnetic field strength, e.g. 40 mT) as the net magnetization direction (along the vessel axis), the magnetic microfiber robot is elongated and the spiral diameter is reduced from an initial diameter of 1mm to 0.1mm. When the magnetic field is removed, the robot changes from the stretched state to the initial state. In contrast, 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 20mT, for example), the micro-fiber robot gathers, and at this time, the micro-robot can still maintain the gathering state after the magnetic field is removed due to the self-winding of the fiber.

Because the robot in the invention needs to utilize magnetic field to regulate and control the state, a cubic magnet can be used as a magnetic field source, as shown in fig. 4, a cubic magnet with a side length of 5cm and a residual magnetic flux density of 1.38T can be used (of course, according to different actual requirements of residual magnetic flux density, the current technology can be referred to, and different ferromagnetic materials can be used for constructing the magnetic field source with a preset shape). The magnetic field distribution of the cubic magnet in space can be changed by performing horizontal movement, vertical movement, rotation and other operations on the magnetic field source, so that the magnetic field configuration required by a static magnetic field, a rotating magnetic field and the like can be obtained. The mode of controlling the magnet comprises manual control, displacement platform control, mechanical arm control and the like. As shown in fig. 5, the robot can be elongated, gathered and spirally propelled by controlling the distance of the cubic magnet to the robot to be 50-100 mm and the rotation frequency to be 0.5-10 Hz. The robot may spiral at a speed of 0.1-10 mm/s relative to the vessel wall in the simulated blood.

Taking the robot in the aggregation state as shown in fig. 6 for example, after the deformation is completed in the aggregation state, the robot can be anchored in a blood flow environment under the condition of no magnetic field by virtue of friction force (in this case, due to the aggregation state, the friction force is larger due to the existence of elastic potential energy), in addition, the blood flow rate shown in fig. 6 is 100mm/s, and it is expected that the robot is more stable and has an anchoring effect when the blood flow rate is lower than 100mm/s, the applied magnetic field can integrally move in the aggregation state, and at this time, the magnetic field and the initial net magnetization direction (along the axial direction of a blood vessel) of the robot can be kept at an angle of 30-80 degrees (a certain magnetic field component exists in the direction perpendicular to the central axis of the blood vessel, and decoupling is avoided) and the distance is 50-100 mm. The microfiber robot may deform back to the original helical state when a magnetic field is applied that is parallel and opposite to the original net magnetization direction (along the vessel axis).

Example 3

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

as shown in fig. 7, in the aneurysm coil plug, the robot first moves to the aneurysm in a spiral pushing manner under the guidance of an external magnetic field, wherein the distance from the cubic magnet to the robot may be 50-100 mm, and the rotation frequency of the cubic magnet may be 0.5-5 Hz. Upon reaching the vicinity of the aneurysm, the cubic magnet applies a magnetic field opposite to the initial net magnetization direction (along the vessel axis), and the robot transitions to a concentrated state. At this point the magnetic force is applied to pull the aggregate into the aneurysm.

To observe the embolic effect, a contrast agent is then injected and its flow direction is observed. Comparing the pre-embolic and post-embolic aneurysms, a significant reduction in the flow rate within the lumen of the aneurysm after embolization is found.

Example 4

In order to verify the effect of the invention, the robot is applied to tumor coil embolism, and the specific method can be as follows:

fig. 8 shows a multi-bifurcated tumor vessel model assuming branch 2 as the tumor vessel and branches 1 and 3 as healthy vessels. First a robot is guided to branch 2, wherein the distance of the cubic magnet from the robot is 50-100 mm and the rotation frequency of the cubic magnet is 0.5-5 Hz. But it was found that one clustered robot could not completely block branch 2. Thus, a second robot is deployed in branch 2 to achieve a double gathering (the second robot's position changes over time as shown in fig. 8). In addition, the shape parameters (such as fiber diameter and spiral diameter in the initial state) of each robot can be controlled, so that the control magnetic fields of different robots are different, the robots are controlled respectively, and the 2 external magnetic fields are not influenced. In addition, the mode of matching a plurality of robots is adopted, and simultaneously, the maximum embolism effect can be realized while the operability of a single robot is ensured (if a single robot with a long enough fiber length is adopted, although the embolism effect is different, the flexibility of the robot in the operation of a narrow vascular space is reduced when the fiber length of the single robot is overlong, the actual embolism operation is not facilitated, and therefore, the overall effect is better by adopting the mode of matching a plurality of robots).

To observe the embolic effect, finally, contrast agent is injected to observe the blood flow direction. Wherein the protected branch 1 and branch 3 contrast agent flow normally, no significant blockage is found, contrast agent in branch 2 cannot pass, and blockage occurs.

Example 5

In order to verify the effect of the invention, the robot is applied to tumor embolism protection, and the specific method can be as follows:

fig. 9 shows a multi-bifurcated tumor vessel model assuming branch 2 and branch 3 are tumor vessels and branch 1 is a healthy vessel. To prevent embolic particles from flowing into healthy branch 1, the microfiber robot is first directed to branch 1 and gathered. 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. Embolic particles (250 μm average diameter) are then released into the fluid, selectively occluding branch 2 and branch 3 (the position of the robot changes over time during the embolization operation, as shown in fig. 9). After the particle embolism is completed, the gathered micro fiber robot can be safely recovered and retrieved (wherein the distance between the cubic magnet and the robot can be 50-100 mm, the rotation frequency of the cubic magnet can be 0.5-5 Hz, and only the direction of an external magnetic field needs to be changed). In the recovery operation, a magnetic field having a rotation direction opposite to the initial rotation magnetic field is applied, and the position of the robot is changed with time as shown in fig. 9.

To observe the embolic protection effect, finally, contrast agent is injected to observe the blood flow direction. Wherein the protected branch 1 contrast agent flows normally, no significant blockage is found, and the contrast agents in branch 2 and branch 3 cannot pass, and blockage occurs.

Example 6

In order to verify the effect of the invention, the robot is applied to the vascular embolism in an animal body, and the specific method can be as follows:

using the in vivo experimental platform shown in fig. 10, catheters were inserted into the femoral artery by real-time image observation in a digital subtraction angiography room (DSA), followed by catheter release of the robot.

Under the control of an external magnetic field, the distance between the cubic magnet and the robot is 50-100 mm, and the rotation frequency of the cubic magnet is 0.5-5 Hz. Guiding the robot to move in the blood vessel, under the guidance of fluorescence imaging, as shown in fig. 11, fig. 11 shows that the magnetic robot is magnetically guided to the target position and gathered. It is then verified whether vascular embolization is complete by contrast injection of contrast agent. Prior to embolization, the entire femoral artery can be seen to have iodine contrast. After embolization, no contrast agent was observed due to clogging of the aggregated microfiber bundles. The accumulated microfiber bundles obstruct blood flow from the proximal to the distal end of the artery, resulting in thrombus formation in the artery one week after embolization. Finally, the embolization performance and safety of the robot are verified by staining the vascular tissue sections, and the result is shown in fig. 12, which shows that stable thrombus is generated in the blood vessel, and the effectiveness of the robot in embolizing in the living blood vessel is verified.

It will be readily appreciated by those skilled in the art that the foregoing description is merely a preferred embodiment of the invention and is not intended to limit the invention, but any modifications, equivalents, improvements or alternatives falling within the spirit and principles of the invention are intended to be included within the scope of the invention.

Claims

1. 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 initial shape of the robot is a spiral hollow structure, and the elastic polymer base material is fibrous and distributed according to the shape of threads; the robot can deform under the action of an external magnetic field.

2. A robot for vascular embolization according to claim 1, wherein the robot is further subjected to magnetization treatment such that the magnetic particles have magnetization directions distributed along the shape of the screw.

3. The robot for vascular embolization according to claim 1, wherein the initial shape of the robot is obtained by shaping straight fibers in the shape of threads; before forming, the straight fiber is subjected to magnetization treatment, and the direction of a magnetic field applied by magnetization is parallel to the axial direction of the fiber;

4. The robot for vascular embolization of claim 1, wherein the initial shape of the robot satisfies: the spiral diameter is 0.1-2 mm, the diameter of the fibrous elastic polymer base material is 10-100 mu m, and the total length of the fibrous elastic polymer base material is 0.5-5 mm.

5. The robot for vascular embolization of claim 1, wherein the elastic polymeric substrate is one or more of silicone-based rubber, acrylate rubber, thermoplastic polyurethane, styrene-ethylene/butylene-styrene block copolymer (SEBS);

6. The robot for vascular embolization according to claim 1, wherein the young's modulus of the robot is lower than 10MPa and the remanent magnetization is higher than 80kA/m;

7. Vascular embolization operation device based on a robot for vascular embolization according to any of claims 1-6, characterized by comprising an external magnetic field generating device and a robot for vascular embolization according to any of claims 1-6; the external magnetic field generating device comprises a permanent magnet or an electromagnet;

8. The vascular embolization device of claim 7, wherein the external magnetic field generating apparatus is capable of providing a rotating magnetic field having a magnetic field frequency of 0.1-100 Hz and a magnetic field strength of 1-200 mT.

9. The method for preparing a robot for vascular embolization according to any one of claims 1 to 6, wherein the method comprises preparing composite straight fibers of magnetic particles and an elastic polymer matrix, wherein the magnetic particles are uniformly dispersed in the elastic polymer matrix; then, magnetizing the straight fiber along the fiber axial direction; then, forming the straight fiber into a shape of a thread, thereby obtaining a robot for vascular embolism; wherein the composite straight fiber is formed by hot stretching, extrusion type 3D printing or injection molding;

preferably, the preparation method comprises the following steps: