Micro-robot cluster capable of being used for lung high-load drug delivery and control method

Abstract

The invention discloses a micro-robot cluster capable of being used for lung high-load drug delivery and a control method, and the micro-robot cluster comprises a plurality of hydrogel microspheres which are used for carrying a large amount of drugs and forming a micro-robot cluster with a three-dimensional structure in a gas environment under the action of an external magnetic field; an external magnetic field is designed, and the designed external magnetic field is used for driving the micro-robot cluster and applying upward gradient force to the micro-robot cluster, so that the micro-robot cluster overcomes the received downward gravity and capillary force, and vertical lifting is achieved; and enabling the micro-robot cluster to be subjected to gradient force along the moving direction of the permanent magnet, and enabling the micro-robot cluster to crawl on the surface of the inner wall of the bronchial tube model so as to reach the tail end of the bronchial tube. The micro-robot cluster has high drug and cell loading capacity, and lung drug delivery and cell delivery can be accurately achieved.

Description

Technical Field

[0001] The present invention relates to the field of micro-nano robot technology, and in particular to a micro-robot cluster and a control method that can be used for high-load drug delivery in the lungs. Background Art

[0002] In nature, organisms can change the shape of their clusters and perform complex tasks in a collaborative manner. Inspired by biological clusters, researchers have conducted in-depth studies on swarm intelligence to elucidate the behavior of biological clusters and explore non-equilibrium phenomena, and further applied them in materials science, chemical technology, robotics, and biomedicine. By applying external physical fields and designing appropriate driving strategies, highly controllable wireless microrobot clusters have been developed in liquid environments, such as vortex clusters composed of paramagnetic particles, spiral clusters based on dielectric colloids, star clusters composed of silica microbeads, and colloid clusters that can be arranged in specific patterns. By adjusting the external field parameters, microrobot clusters can be navigated and reshaped to adapt to complex liquid environments. For example, a group of tree-like double-sided microrobots can be controlled to move toward a light source. Robotic clusters composed of smooth spiral nanorobots or spherical nanoparticles can move in vitreous with a biopolymer network. At the same time, multiple small clusters split from a ribbon cluster can be navigated synchronously to different targets. In addition, external field-driven microrobot clusters have also shown great application potential in different fields, such as micromanipulation, targeted delivery, and embolization therapy.

[0003] Complex clustering behaviors in liquids can originate from interactions between individuals. Some researchers have assembled monomers into reconfigurable clusters by regulating inter-microtubule protein interactions, electrostatic interactions between metal-dielectric double-sided colloidal particles, asymmetric polarizable monomers and living cells, and magnetic interactions between spherical colloidal particles. At the same time, the interaction between monomers and the surrounding liquid also affects clustering behavior. In a colloidal system composed of different types of monomers, light-induced local liquid flow selectively separates monomers into different clusters according to their types. In addition, fluid dynamic interactions caused by liquid-gas interface fluctuations and rotations caused by magnetic monomer oscillations can assemble dispersed monomers into dynamic clusters and perform navigation movements. However, in a gas environment, the effect of fluid dynamic interactions on monomers can be ignored, and the generation mechanism of microrobot clusters in a gas environment is different from that of clusters in existing fluid environments. To date, microrobot clusters containing a large number of monomers driven by external fields have not been developed in a gas environment. Therefore, existing microrobot clusters cannot be used in a gas-filled lung environment to achieve precise targeted drug delivery.

[0004] Therefore, the prior art needs to be improved. Summary of the invention

[0005] The technical problem to be solved by the present invention is that, in view of the defects of the prior art, the present invention provides a micro-robot cluster and a control method that can be used for high-load drug delivery in the lungs, so as to solve the problem that the existing micro-robot clusters cannot perform precise targeted drug delivery in the lung gas environment.

[0006] The technical solution adopted by the present invention to solve the technical problem is as follows:

[0007] In a first aspect, the present invention provides a microrobot cluster that can be used for high-load drug delivery in the lungs, comprising:

[0008] A plurality of hydrogel microspheres, wherein the plurality of hydrogel microspheres are used to carry a large amount of drugs and form a micro-robot cluster with a three-dimensional structure in a gas environment under the action of an external magnetic field;

[0009] The external magnetic field is designed to drive the micro-robot cluster, apply an upward gradient force to the micro-robot cluster, so that the micro-robot cluster can overcome the downward gravity and capillary force to achieve vertical lifting; and make the micro-robot cluster be subjected to the gradient force along the moving direction of the permanent magnet, so that the micro-robot cluster can crawl on the surface of the inner wall of the bronchial model to reach the end of the bronchus.

[0010] In one implementation, among the plurality of hydrogel microspheres, a portion of the hydrogel microspheres are water-soluble drug-loaded microspheres, and another portion of the hydrogel microspheres are cell-loaded microspheres.

[0011] In one implementation, the water-soluble drug-loaded microspheres are prepared from ferromagnetic particles of neodymium iron boron and biocompatible sodium alginate hydrogel.

[0012] In one implementation, the cell-loaded microspheres are prepared from cells, silica-coated ferromagnetic particles of neodymium iron boron, and biocompatible sodium alginate hydrogel.

[0013] In one implementation, the plurality of hydrogel microspheres change the interaction force between particles under the action of the external magnetic field to obtain microrobot clusters of different forms, thereby achieving shape reconstruction and navigation movement of the microrobot clusters.

[0014] In a second aspect, the present invention provides a control method for a microrobot cluster that can be used for high-load drug delivery in the lungs, comprising:

[0015] placing a plurality of hydrogel microspheres at the entrance of the trachea model, and placing the trachea model under a permanent magnet;

[0016] By applying an oscillating magnetic field, the hydrogel microspheres are driven to move and interact with surrounding microspheres to form a micro-robot cluster with a three-dimensional structure;

[0017] The microrobot cluster is driven to move to the end of the bronchus to achieve drug delivery to the deep lung tissue; or the microrobot cluster is driven to a targeted location to release the carried cells.

[0018] In one implementation, the step of applying an oscillating magnetic field to drive the hydrogel microspheres to move and interact with surrounding microspheres to form a microrobot cluster with a three-dimensional structure includes:

[0019] placing a permanent magnet at the end of the robotic arm above the hydrogel microsphere;

[0020] The driving motor controls the swing of the permanent magnet to provide a dynamic magnetic field gradient. Under the action of the gradient force and the magnetic torque, some of the hydrogel microspheres are separated from the ground and aggregate with the surrounding microspheres to form small three-dimensional aggregates.

[0021] The magnetic field is continuously applied to control the small three-dimensional aggregates to swing with the permanent magnet and attract the surrounding microspheres to form the micro-robot cluster with a three-dimensional structure.

[0022] In one implementation, driving the microrobot cluster to move to the end of the bronchus to achieve drug delivery to deep lung tissues includes:

[0023] Slowly moving the end of the robotic arm along the trachea direction, controlling the permanent magnet at the end to move along the trachea, and driving the micro-robot cluster to move forward in the trachea;

[0024] Continue to move the permanent magnet along the path from the trachea to the secondary bronchus, control the micro-robot cluster to pass through the main bronchus, and move to the secondary bronchus;

[0025] Applying an upward gradient force to the micro-robot cluster to guide the micro-robot cluster to crawl along the upper surface of the trachea to the third-order bronchus;

[0026] The microrobot cluster is guided to move to the end of the bronchus to achieve drug delivery to the deep lung tissue.

[0027] In one implementation, applying an upward gradient force to the micro-robot cluster to guide the micro-robot cluster to crawl on the upper surface of the trachea to the third-order bronchus includes:

[0028] When the micro-robot cluster moves to the secondary bronchus, the height of the permanent magnet is lowered to enhance the gradient force applied to the micro-robot cluster, so that the micro-robot cluster is vertically lifted to the upper surface of the trachea, and the permanent magnet is moved in the direction from the secondary bronchus to the tertiary bronchus to guide the micro-robot cluster to crawl on the upper surface of the trachea to the tertiary bronchus.

[0029] In one implementation, driving the microrobot cluster to a target location and releasing the carried cells comprises:

[0030] Increasing the pitch angle of the magnetic field, rearranging the micro-robot cluster, and controlling the micro-robot cluster to present an inclined state to achieve forward motion;

[0031] The magnetic field direction angle is adjusted in real time as needed to change the movement direction of the micro-robot cluster, and the micro-robot cluster is controlled to move to the target position.

[0032] The present invention adopts the above technical solution to achieve the following effects:

[0033] The present invention proposes a microrobot cluster that can be used for high-load drug delivery in the lungs. The microrobot cluster contains hydrogel microspheres composed of magnetic particles and sodium alginate hydrogel networks. By adjusting the external magnetic field parameters, the microrobot cluster can be driven to perform highly reconstructed and navigated movements. In addition, by applying a magnetic field gradient, the microrobot cluster can be vertically lifted and surface crawled in a gas environment, enabling it to move in a complex and unstructured lung environment and reach the end of the bronchus. The microrobot cluster of the present invention has a high drug and cell loading capacity and can accurately achieve lung drug delivery and cell delivery. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying creative work.

[0035] Figure 1 (a) is a schematic diagram of the preparation of hydrogel microspheres; Figure 1 (b) is the prepared hydrogel microspheres; Figure 1 (c) is the diameter distribution diagram of hydrogel microspheres.

[0036] Figure 2 (a) is a schematic diagram of the magnetic field; Figure 2 (b) is a schematic diagram of hydrogel microspheres assembled into a microrobot cluster.

[0037] Figure 3 This is a diagram of the micro-robot cluster generation process.

[0038] Figure 4 It is a schematic diagram of the vertical lifting of a micro-robot cluster in a gas environment.

[0039] Figure 5 Schematic diagram of the delivery path of a microrobot cluster in the bronchial network of the lung.

[0040] Figure 6 (a) Schematic diagram of pH-triggered swelling and degradation of hydrogel microspheres; Figure 6 (b) is a schematic diagram of hydrogel microspheres carrying cells.

[0041] Figure 7 Flow chart of a control method for a microrobot swarm that can be used for high-load drug delivery in the lungs.

[0042] The purpose, features and advantages of the present invention will be further described with reference to the accompanying drawings in conjunction with the embodiments. DETAILED DESCRIPTION

[0043] In order to make the purpose, technical solution and advantages of the present invention clearer and more specific, the present invention is further described in detail below with reference to the accompanying drawings and examples. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0044] Exemplary Devices

[0045] Complex clustering behaviors in liquids can originate from interactions between individuals. Some researchers have assembled monomers into reconfigurable clusters by regulating inter-microtubule protein interactions, electrostatic interactions between metal-dielectric double-sided colloidal particles, asymmetric polarizable monomers and living cells, and magnetic interactions between spherical colloidal particles. At the same time, the interaction between monomers and the surrounding liquid also affects clustering behavior. In a colloidal system composed of different types of monomers, light-induced local liquid flow selectively separates monomers into different clusters according to their types. In addition, the fluid dynamics interactions caused by the fluctuations of the liquid-gas interface and the rotation caused by the oscillation of magnetic monomers can assemble dispersed monomers into dynamic clusters and perform navigation movements.

[0046] However, in a gas environment, the effect of fluid dynamics interactions on monomers can be ignored, and the generation mechanism of microrobot clusters in a gas environment is different from that of clusters in existing fluid environments. So far, microrobot clusters containing a large number of monomers driven by external fields have not been developed in a gas environment. Therefore, existing microrobot clusters cannot be used in the gas-filled lung environment to achieve precise targeted drug delivery.

[0047] In response to the above technical problems, an embodiment of the present invention provides a microrobot cluster that can be used for high-load drug delivery in the lungs. The microrobot cluster includes hydrogel microspheres composed of magnetic particles and sodium alginate hydrogel networks. By adjusting the external magnetic field parameters, the microrobot cluster can be driven to perform highly reconstructed and navigated movements. Moreover, by applying a magnetic field gradient, the microrobot cluster can be vertically lifted and surface crawled in a gas environment, enabling it to move in a complex and unstructured lung environment and reach the end of the bronchus. The microrobot cluster in the embodiment of the present invention has a high drug and cell loading capacity, and can accurately achieve lung drug delivery and cell delivery.

[0048] like Figure 1 As shown, an embodiment of the present invention provides a microrobot cluster that can be used for high-load drug delivery in the lungs, including: a plurality of hydrogel microspheres, wherein the plurality of hydrogel microspheres are used to carry a large amount of drugs and form a microrobot cluster with a three-dimensional structure in a gas environment under the action of an external magnetic field; an external magnetic field design, wherein the designed external magnetic field is used to drive the microrobot cluster, apply an upward gradient force to the microrobot cluster, so that the microrobot cluster overcomes the downward gravity and capillary force it is subjected to and achieves vertical lifting; and the microrobot cluster is subjected to a gradient force along the moving direction of the permanent magnet, so that the microrobot cluster achieves a surface crawling motion of the microrobot cluster on the inner wall of the bronchial model to reach the end of the bronchus.

[0049] In this embodiment, if Figure 1 As shown in (a), the microrobot cluster is composed of hydrogel microspheres, each of which contains magnetic particles and a sodium alginate hydrogel network. In the absence of an external oscillating magnetic field, the state of all the hydrogel microspheres is as follows: Figure 1 As shown in (b), these hydrogel microspheres do not form the state of the microrobot cluster; Figure 1 As shown in (c), the diameter of each hydrogel microsphere is about 650 μm.

[0050] The specific implementation method is that under the action of an external oscillating magnetic field, the hydrogel microspheres swing with the magnetic field in the gas environment and interact with the surrounding particles to form a micro-robot cluster with a three-dimensional structure. As an example, the magnetic field distribution is as follows: Figure 2 As shown in (a), under the action of this magnetic field, a micro robot cluster with a three-dimensional structure is formed. Figure 2 The specific micro-robot cluster generation process is as follows: Figure 3As shown, the initial state of the hydrogel microspheres in the gas environment is horizontal. After the action of the external oscillating magnetic field, the hydrogel microspheres swing with the magnetic field in the gas environment and interact with the surrounding particles, presenting a stacked micro-robot cluster with a three-dimensional structure.

[0051] like Figure 4 As shown, by adjusting the external magnetic field parameters by permanent magnets, the microrobot cluster can be driven to perform highly reconfigurable and navigational movements. By applying a magnetic field gradient, the microrobot cluster can perform vertical lifting and surface crawling in a gas environment, enabling it to move in a complex and unstructured lung environment and reach the end of the bronchus. In addition, the microrobot cluster has a high drug loading capacity and can swell and degrade in an environment with a specific pH value to release the loaded drugs. The microrobot cluster can also perform cell delivery and maintain the activity of the carried cells, allowing the cells to proliferate further after being released.

[0052] In this embodiment, among the multiple hydrogel microspheres, a part of the hydrogel microspheres are water-soluble drug-loaded microspheres, and another part of the hydrogel microspheres are cell-loaded microspheres. The water-soluble drug-loaded microspheres are prepared from ferromagnetic particles of neodymium iron boron and biocompatible sodium alginate hydrogel. The cell-loaded microspheres are prepared from cells, silica-coated ferromagnetic particles of neodymium iron boron and biocompatible sodium alginate hydrogel. Under the action of the external magnetic field, the multiple hydrogel microspheres change the interaction force between the particles to obtain microrobot clusters of different forms, thereby realizing the shape reconstruction and navigation movement of the microrobot clusters.

[0053] In practical application scenarios, the external magnetic field is used to drive the hydrogel microspheres. Considering the formation of a robot cluster with a three-dimensional structure in a gas environment, an oscillating magnetic field in the yz plane is used. Figure 2 As shown in (a). By adjusting the magnetic field parameters, the interaction between particles can be changed, allowing the cluster to reshape and navigate. For example, increasing the field strength or magnetic field ratio can enhance the attraction between particles and the magnetic torque on the cluster, thereby increasing the cluster height. Increasing the pitch angle can tilt the cluster, so that when the cluster swings with the magnetic field, it moves in the tilted direction under the influence of gravity. Adjusting the direction angle can change the tilt direction of the cluster, thereby adjusting the cluster movement direction.

[0054] In addition, if Figure 5 As shown, considering the three-dimensional structure of the lung bronchial network, a dynamic magnetic field gradient is used to apply an upward gradient force to the micro-robot cluster, so that the cluster can overcome the downward gravity and capillary force, thereby achieving vertical lifting of the cluster. Further, by moving the permanent magnet, the cluster is subjected to a gradient force along the movement direction of the permanent magnet, thereby achieving the surface crawling movement of the cluster on the inner wall of the bronchial model to reach the end of the bronchus.

[0055] The hydrogel microspheres, as monomers, provide the possibility for cargo loading and release. There are two types of hydrogel microspheres. For the loading type of water-soluble drugs, the hydrogel microspheres are prepared from ferromagnetic particles of neodymium iron boron and biocompatible sodium alginate hydrogel; and for the cell loading type, the hydrogel microspheres are prepared from cells, silica-coated ferromagnetic particles of neodymium iron boron and biocompatible sodium alginate hydrogel.

[0056] The included ferromagnetic particles enable the hydrogel microspheres to respond to external magnetic fields. A large amount of water is contained in the microspheres, making it possible to load a large amount of drugs. Figure 6 As shown in (a), hydrogel microspheres loaded with water-soluble drugs, under a specific pH environment, the deprotonation of the carboxyl groups on the alginate causes the microspheres to swell and degrade, achieving controlled release of the drug. Figure 6 As shown in (b), in the cell-loaded hydrogel microspheres, the porous hydrogel network makes cell loading possible and avoids cell leakage during the delivery process.

[0057] It can be understood that the biocompatible ferromagnetic particles and hydrogel network in the microrobot cluster of this embodiment ensure the activity of the carried cells.

[0058] As an example, the specific implementation steps of the generation and movement of the micro-robot cluster in the gas environment are as follows:

[0059] A. Multiple hydrogel microspheres were placed at the entrance of the trachea model, and the trachea model was placed under a permanent magnet.

[0060] B. By applying an oscillating magnetic field, the microspheres are driven to move and interact with surrounding microspheres to form small three-dimensional aggregates.

[0061] C. Continue to apply the magnetic field so that the small three-dimensional aggregates continue to swing with the magnetic field, grow by attracting surrounding particles, and merge with each other, eventually forming a micro-robot cluster with a three-dimensional structure.

[0062] D. Increase the pitch angle of the magnetic field to rearrange the microspheres, tilt the microrobot cluster, and achieve forward motion.

[0063] E. Adjust the magnetic field direction angle in real time as needed to change the movement direction of the cluster so that it moves to the target location.

[0064] As a further example, the specific implementation steps of the microrobot cluster in lung drug delivery are as follows:

[0065] A1. Place the prepared magnetic hydrogel microspheres at the tracheal entrance and place the permanent magnet at the end of the robotic arm above the microspheres.

[0066] B1. The driving motor makes the permanent magnet swing, providing a dynamic magnetic field gradient. Under the action of the gradient force and magnetic torque, some magnetic hydrogel microspheres break away from the ground and aggregate with surrounding particles to form small three-dimensional aggregates. These three-dimensional aggregates swing with the permanent magnet and attract surrounding particles, eventually assembling into a three-dimensional micro-robot cluster.

[0067] C1. Then, the end of the robotic arm is slowly moved along the trachea, so that the permanent magnet at the end moves along the trachea, thereby allowing the micro-robot cluster to move forward in the trachea.

[0068] D1. Continue to move the permanent magnet along the path from the trachea to the secondary bronchus, allowing the microrobot cluster to pass through the main bronchus and move to the secondary bronchus.

[0069] E1. When the cluster moves to the secondary bronchus, the height of the permanent magnet is lowered to enhance the gradient force applied to the cluster, so that the cluster is lifted vertically to the upper surface of the trachea. The permanent magnet is further moved along the direction from the secondary bronchus to the tertiary bronchus to guide the cluster to crawl on the upper surface of the trachea to the tertiary bronchus.

[0070] D1. Ultimately guide the microrobot cluster to move to the end of the bronchus to achieve drug delivery in the deep lung tissue.

[0071] As a further example, the specific steps of implementing cell delivery using the microrobot cluster are as follows:

[0072] A2. Prepare silica-coated magnetic particles by the Stober method, mix cells, magnetic particles and sodium alginate in water to prepare hydrogel microspheres carrying cells, and place the microspheres under a magnetic field.

[0073] B2. Drive the hydrogel microspheres to form a microrobot cluster, and change the magnetic field pitch angle and direction angle to deliver the cluster to the targeted location.

[0074] C2. At the targeted location, due to environmental influences, the clusters naturally swell and degrade, releasing the carried cells.

[0075] This embodiment adopts the above technical solution to achieve the following effects:

[0076] This embodiment proposes a microrobot cluster that can be used for high-load drug delivery in the lungs. The microrobot cluster contains hydrogel microspheres composed of magnetic particles and sodium alginate hydrogel networks. By adjusting the external magnetic field parameters, the microrobot cluster can be driven to perform highly reconstructed and navigated movements. In addition, by applying a magnetic field gradient, the microrobot cluster can be vertically lifted and surface crawled in a gas environment, enabling it to move in a complex and unstructured lung environment and reach the end of the bronchus. The microrobot cluster of this embodiment has a high drug and cell loading capacity and can accurately achieve lung drug delivery and cell delivery.

[0077] Exemplary Methods

[0078] like Figure 7 As shown, an embodiment of the present invention provides a control method for a micro-robot cluster that can be used for high-load drug delivery in the lungs, comprising the following steps:

[0079] Step S100, placing a plurality of hydrogel microspheres at the entrance of the trachea model, and placing the trachea model under a permanent magnet;

[0080] Step S200, applying an oscillating magnetic field to drive the hydrogel microspheres to move and interact with surrounding microspheres to form a micro-robot cluster with a three-dimensional structure;

[0081] Step S300, driving the microrobot cluster to move to the end of the bronchus to achieve drug delivery in the deep lung tissue; or driving the microrobot cluster to a targeted location to release the carried cells.

[0082] In this embodiment, the hydrogel microspheres are driven to move and interact with surrounding microspheres by applying an oscillating magnetic field to form a micro-robot cluster with a three-dimensional structure, including: placing a permanent magnet located at the end of a robotic arm above the hydrogel microspheres; a driving motor controls the permanent magnet to swing and provides a dynamic magnetic field gradient, and under the action of the gradient force and the magnetic torque, some of the hydrogel microspheres are separated from the ground and aggregate with surrounding microspheres to form small three-dimensional aggregates; the magnetic field is continuously applied to control the small three-dimensional aggregates to swing with the permanent magnet and attract the surrounding microspheres to form the micro-robot cluster with a three-dimensional structure.

[0083] As an example, Figure 1 As shown in (a), the microrobot cluster is composed of hydrogel microspheres, each of which contains magnetic particles and a sodium alginate hydrogel network. In the absence of an external oscillating magnetic field, the state of all the hydrogel microspheres is as follows: Figure 1 As shown in (b), these hydrogel microspheres do not form the state of the microrobot cluster; Figure 1As shown in (c), the diameter of each hydrogel microsphere is about 650 μm.

[0084] The specific implementation method is that under the action of an external oscillating magnetic field, the hydrogel microspheres swing with the magnetic field in the gas environment and interact with the surrounding particles to form a micro-robot cluster with a three-dimensional structure. As an example, the magnetic field distribution is as follows: Figure 2 As shown in (a), under the action of this magnetic field, a micro robot cluster with a three-dimensional structure is formed. Figure 2 The specific micro-robot cluster generation process is as follows: Figure 3 As shown, the initial state of the hydrogel microspheres in the gas environment is horizontal. After the action of the external oscillating magnetic field, the hydrogel microspheres swing with the magnetic field in the gas environment and interact with the surrounding particles, presenting a stacked micro-robot cluster with a three-dimensional structure.

[0085] like Figure 4 As shown, by adjusting the external magnetic field parameters through permanent magnets, the micro-robot cluster can be driven to perform highly reconfigurable and navigational movements. By applying a magnetic field gradient, the micro-robot cluster can perform vertical lifting and surface crawling in a gas environment, enabling it to move in a complex and unstructured lung environment and reach the end of the bronchus. In addition, the micro-robot cluster has a high drug loading capacity and can swell and degrade in an environment with a specific pH value to release the loaded drug.

[0086] In this embodiment, the method of driving the micro-robot cluster to move to the terminal end of the bronchus to achieve drug delivery in deep lung tissue includes: slowly moving the terminal end of the robotic arm along the direction of the trachea, controlling the permanent magnet located at the terminal end to move along the trachea, and driving the micro-robot cluster to advance in the trachea; continuing to move the permanent magnet along the path from the trachea to the secondary bronchus, controlling the micro-robot cluster to pass through the main bronchus and move to the secondary bronchus; applying an upward gradient force to the micro-robot cluster, guiding the micro-robot cluster to crawl on the upper surface of the trachea to the tertiary bronchus; guiding the micro-robot cluster to move to the terminal end of the bronchus to achieve drug delivery in deep lung tissue.

[0087] Specifically, the upward gradient force is applied to the micro-robot cluster to guide the micro-robot cluster to crawl on the upper surface of the trachea to the tertiary bronchi, including: when the micro-robot cluster moves to the secondary bronchi, the height of the permanent magnet is lowered to enhance the gradient force applied to the micro-robot cluster, so that the micro-robot cluster is vertically lifted to the upper surface of the trachea, and the permanent magnet is moved along the direction from the secondary bronchi to the tertiary bronchi to guide the micro-robot cluster to crawl on the upper surface of the trachea to the tertiary bronchi.

[0088] As an example, hydrogel microspheres are driven by an external magnetic field. Consider forming a robot cluster with a three-dimensional structure in a gas environment, using an oscillating magnetic field in the yz plane. Figure 2 As shown in (a). By adjusting the magnetic field parameters, the interaction between particles can be changed, allowing the cluster to reshape and navigate. For example, increasing the field strength or magnetic field ratio can enhance the attraction between particles and the magnetic torque on the cluster, thereby increasing the cluster height. Increasing the pitch angle can tilt the cluster, so that when the cluster swings with the magnetic field, it moves in the tilted direction under the influence of gravity. Adjusting the direction angle can change the tilt direction of the cluster, thereby adjusting the cluster movement direction.

[0089] In addition, if Figure 5 As shown, considering the three-dimensional structure of the lung bronchial network, a dynamic magnetic field gradient is used to apply an upward gradient force to the micro-robot cluster, so that the cluster can overcome the downward gravity and capillary force, thereby achieving vertical lifting of the cluster. Further, by moving the permanent magnet, the cluster is subjected to a gradient force along the movement direction of the permanent magnet, thereby achieving the surface crawling movement of the cluster on the inner wall of the bronchial model to reach the end of the bronchus.

[0090] In this embodiment, the micro-robot cluster can also deliver cells and maintain the activity of the carried cells, so that the cells can further proliferate after being released. The driving of the micro-robot cluster to the target position and releasing the carried cells includes: increasing the pitch angle of the magnetic field, rearranging the micro-robot cluster, controlling the micro-robot cluster to present an inclined state, and realizing forward movement; adjusting the magnetic field direction angle in real time as needed, changing the movement direction of the micro-robot cluster, and controlling the micro-robot cluster to move to the target position.

[0091] In this embodiment, the hydrogel microspheres are used as monomers to provide the possibility for cargo loading and release. There are two types of hydrogel microspheres. For the loading type of water-soluble drugs, the hydrogel microspheres are prepared from ferromagnetic particles of neodymium iron boron and biocompatible sodium alginate hydrogel; and for the cell loading type, the hydrogel microspheres are prepared from cells, silica-coated ferromagnetic particles of neodymium iron boron and biocompatible sodium alginate hydrogel.

[0092] The included ferromagnetic particles enable the hydrogel microspheres to respond to external magnetic fields. A large amount of water is contained in the microspheres, making it possible to load a large amount of drugs. Figure 6 As shown in (a), hydrogel microspheres loaded with water-soluble drugs, under a specific pH environment, the deprotonation of the carboxyl groups on the alginate causes the microspheres to swell and degrade, achieving controlled release of the drug. Figure 6 As shown in (b), in the cell-loaded hydrogel microspheres, the porous hydrogel network makes cell loading possible and avoids cell leakage during the delivery process.

[0093] It can be understood that the biocompatible ferromagnetic particles and hydrogel network in the microrobot cluster of this embodiment ensure the activity of the carried cells.

[0094] This embodiment adopts the above technical solution to achieve the following effects:

[0095] This embodiment proposes a control method for a micro-robot cluster that can be used for high-load drug delivery in the lungs. By adjusting the external magnetic field parameters, the micro-robot cluster can be driven to perform highly reconstructed and navigation movements. In addition, by applying a magnetic field gradient, the micro-robot cluster can be vertically lifted and surface crawled in a gas environment, enabling it to move in a complex and unstructured lung environment and reach the end of the bronchus. The micro-robot cluster of this embodiment has a high drug and cell loading capacity and can accurately achieve lung drug delivery and cell delivery.

[0096] Those skilled in the art can understand that all or part of the processes in the above-mentioned embodiments can be implemented by instructing related hardware through a computer program, and the computer program can be stored in a non-volatile storage medium. When the computer program is executed, it can include the processes of the embodiments of the above-mentioned methods. Among them, any reference to memory, storage, database or other media used in the embodiments provided by the present invention can include non-volatile and volatile memory.

[0097] In summary, the present invention provides a microrobot cluster and control method that can be used for high-load drug delivery in the lungs, the method comprising: a plurality of hydrogel microspheres, a plurality of the hydrogel microspheres are used to carry a large amount of drugs, and form a microrobot cluster with a three-dimensional structure in a gas environment under the action of an external magnetic field; an external magnetic field design, the designed external magnetic field is used to drive the microrobot cluster, apply an upward gradient force to the microrobot cluster, so that the microrobot cluster overcomes the downward gravity and capillary force it is subjected to, and achieves vertical lifting; and the microrobot cluster is subjected to a gradient force along the moving direction of the permanent magnet, so that the microrobot cluster crawls on the surface of the inner wall of the bronchial model to reach the end of the bronchus. The microrobot cluster of the present invention has a high drug and cell loading capacity, and can accurately achieve pulmonary drug delivery and cell delivery.

[0098] It should be understood that the application of the present invention is not limited to the above examples. For ordinary technicians in this field, improvements or changes can be made based on the above description. All these improvements and changes should fall within the scope of protection of the claims attached to the present invention.

Claims

1. A microrobot cluster that can be used for high-load drug delivery in the lungs, characterized in that: include: A plurality of hydrogel microspheres, wherein the plurality of hydrogel microspheres are used to carry a large amount of drugs and form a micro-robot cluster with a three-dimensional structure in a gas environment under the action of an external magnetic field; The external magnetic field is designed to drive the micro-robot cluster, apply an upward gradient force to the micro-robot cluster, so that the micro-robot cluster can overcome the downward gravity and capillary force to achieve vertical lifting; and make the micro-robot cluster be subjected to the gradient force along the moving direction of the permanent magnet, so that the micro-robot cluster can crawl on the surface of the inner wall of the bronchial model to reach the end of the bronchus.

2. The microrobot cluster for high-load drug delivery in the lungs according to claim 1, characterized in that: Among the plurality of hydrogel microspheres, a portion of the hydrogel microspheres are water-soluble drug-loaded microspheres, and another portion of the hydrogel microspheres are cell-loaded microspheres.

3. The microrobot cluster for high-load drug delivery in the lungs according to claim 2, characterized in that: The water-soluble drug-loaded microspheres are prepared from ferromagnetic particles of neodymium iron boron and biocompatible sodium alginate hydrogel.

4. The microrobot cluster for high-load drug delivery in the lungs according to claim 2, characterized in that: The cell-loaded microspheres are prepared from cells, silicon dioxide-coated ferromagnetic particles of neodymium iron boron and biocompatible sodium alginate hydrogel.

5. The microrobot cluster for high-load drug delivery in the lungs according to claim 1, characterized in that: The plurality of hydrogel microspheres change the interaction force between particles under the action of the external magnetic field to obtain micro-robot clusters of different forms, thereby achieving shape reconstruction and navigation movement of the micro-robot clusters.

6. A control method for a microrobot cluster that can be used for high-load drug delivery in the lungs, characterized in that: include: placing a plurality of hydrogel microspheres at the entrance of the trachea model, and placing the trachea model under a permanent magnet; By applying an oscillating magnetic field, the hydrogel microspheres are driven to move and interact with surrounding microspheres to form a micro-robot cluster with a three-dimensional structure; The microrobot cluster is driven to move to the end of the bronchus to achieve drug delivery to the deep lung tissue; or the microrobot cluster is driven to a targeted location to release the carried cells.

7. The control method of a microrobot cluster for high-load drug delivery in the lungs according to claim 6, characterized in that: The method drives the hydrogel microspheres to move and interact with surrounding microspheres by applying an oscillating magnetic field to form a micro-robot cluster with a three-dimensional structure, comprising: placing a permanent magnet at the end of the robotic arm above the hydrogel microsphere; The driving motor controls the swing of the permanent magnet to provide a dynamic magnetic field gradient. Under the action of the gradient force and the magnetic torque, some of the hydrogel microspheres are separated from the ground and aggregate with the surrounding microspheres to form small three-dimensional aggregates. The magnetic field is continuously applied to control the small three-dimensional aggregates to swing with the permanent magnet and attract the surrounding microspheres to form the micro-robot cluster with a three-dimensional structure.

8. The control method of a microrobot cluster for high-load drug delivery in the lungs according to claim 6, characterized in that: The method of driving the microrobot cluster to move to the end of the bronchus to achieve drug delivery to deep lung tissues includes: Slowly moving the end of the robotic arm along the trachea direction, controlling the permanent magnet at the end to move along the trachea, and driving the micro-robot cluster to move forward in the trachea; Continue to move the permanent magnet along the path from the trachea to the secondary bronchus, control the micro-robot cluster to pass through the main bronchus, and move to the secondary bronchus; Applying an upward gradient force to the micro-robot cluster to guide the micro-robot cluster to crawl along the upper surface of the trachea to the third-order bronchus; The microrobot cluster is guided to move to the end of the bronchus to achieve drug delivery to the deep lung tissue.

9. The control method of a microrobot cluster for high-load drug delivery in the lungs according to claim 8, characterized in that: The step of applying an upward gradient force to the micro-robot cluster to guide the micro-robot cluster to crawl on the upper surface of the trachea to the third-order bronchus comprises: When the micro-robot cluster moves to the secondary bronchus, the height of the permanent magnet is lowered to enhance the gradient force applied to the micro-robot cluster, so that the micro-robot cluster is vertically lifted to the upper surface of the trachea, and the permanent magnet is moved in the direction from the secondary bronchus to the tertiary bronchus to guide the micro-robot cluster to crawl on the upper surface of the trachea to the tertiary bronchus.

10. The control method of a microrobot cluster for high-load drug delivery in the lungs according to claim 6, characterized in that: The step of driving the microrobot cluster to a target location and releasing the carried cells comprises: Increasing the pitch angle of the magnetic field, rearranging the micro-robot cluster, and controlling the micro-robot cluster to present an inclined state to achieve forward motion; The magnetic field direction angle is adjusted in real time as needed to change the movement direction of the micro-robot cluster, and the micro-robot cluster is controlled to move to the target position.

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