Microrobot swarms and control methods for high-volume drug delivery to the lungs

Abstract

This invention discloses a microrobot cluster and its control method for high-volume drug delivery to the lungs, comprising: multiple hydrogel microspheres carrying a large amount of drug, forming a three-dimensional microrobot cluster in a gaseous environment under the influence of an external magnetic field; an external magnetic field designed to drive the microrobot cluster, applying an upward gradient force to the cluster to overcome downward gravity and capillary forces, achieving vertical lifting; and subjecting the cluster to a gradient force along the direction of movement of a permanent magnet, enabling the cluster to crawl along the inner wall of a bronchial model to reach the bronchial terminal. The microrobot cluster of this invention has a high drug and cell loading capacity, enabling precise drug and cell delivery to the lungs.

Description

Technical Field

[0001] This invention relates to the field of micro-nano robotics, and more particularly to a cluster of microrobots and a control method for delivering high-volume drugs to the lungs. Background Technology

[0002] In nature, organisms can alter the shape of their swarms and collaboratively perform complex tasks. Inspired by biological swarms, researchers have conducted in-depth studies on swarm intelligence to elucidate biological swarm behavior and explore non-equilibrium phenomena, further finding applications in materials science, chemical technology, robotics, and biomedicine. By applying external physical fields and designing appropriate driving strategies, highly controllable wireless microrobot swarms have been developed in liquid environments, such as vortex-like swarms composed of paramagnetic particles, helical swarms based on dielectric colloids, star-shaped swarms composed of silica microbeads, and colloidal swarms capable of arranging into specific patterns. By adjusting external field parameters, microrobot swarms can be navigated and reshaped to adapt to complex liquid environments. For example, a group of tree-like bifacial microrobots can be controlled to move towards a light source. Robot swarms composed of smooth helical nanorobots or spherical nanoparticles can move in a vitreous body with a biopolymer network. Simultaneously, multiple smaller swarms splitting from a ribbon-like swarm can be synchronously navigated to different targets. Furthermore, field-driven microrobot swarms have demonstrated great application potential in various fields, such as micromanipulation, targeted delivery, and embolization therapy.

[0003] Complex clustering behavior in liquids can originate from interactions between individuals. Researchers have demonstrated the ability to assemble monomers into reconfigurable clusters by modulating microtubule-protein interactions, electrostatic interactions between metal-dielectric double-sided colloidal particles, between asymmetric polarizable monomers, and between living cells, as well as magnetic interactions between spherical colloidal particles. Simultaneously, interactions between monomers and the surrounding liquid also influence clustering behavior. In colloidal systems composed of different types of monomers, light-induced localized liquid flow selectively separates monomers into different clusters based on their type. Furthermore, fluid dynamic interactions caused by liquid-gas interface fluctuations due to magnetic monomer oscillations and rotation can assemble dispersed monomers into dynamic clusters for navigational movement. However, in gaseous environments, the influence of fluid dynamic interactions on monomers is negligible, and the generation mechanism of microrobot clusters in gaseous environments differs from that in existing fluid environments. To date, microrobot clusters containing a large number of monomers driven by external fields have not been developed in gaseous environments. Therefore, existing microrobot clusters cannot be used in gas-filled lung environments for precise targeted drug delivery.

[0004] Therefore, existing technologies still need improvement. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to address the shortcomings of the prior art by providing a microrobot cluster and control method for high-volume drug delivery to the lungs, thereby solving the problem that existing microrobot clusters cannot perform precise targeted drug delivery in the lung gas environment.

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

[0007] In a first aspect, the present invention provides a cluster of microrobots that can be used for high-volume drug delivery to the lungs, comprising:

[0008] Multiple hydrogel microspheres are used to carry a large amount of drug and form a cluster of microrobots with a three-dimensional structure in a gaseous environment under the action of an external magnetic field.

[0009] An external magnetic field is designed to drive the microrobot cluster, applying an upward gradient force to the microrobot cluster so that it overcomes the downward gravity and capillary force and achieves vertical lifting; and applying a gradient force along the direction of movement of the permanent magnet to the microrobot cluster so that it can crawl on the surface of the inner wall of the bronchus model to reach the end of the bronchus.

[0010] In one implementation, a portion of the plurality of 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 neodymium iron boron particles and biocompatible sodium alginate hydrogel.

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

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

[0014] Secondly, the present invention provides a control method for a swarm of microrobots that can be used for high-volume drug delivery to the lungs, comprising:

[0015] Multiple hydrogel microspheres were placed at the inlet of the trachea model, and the trachea model was placed below the permanent magnet;

[0016] By applying an oscillating magnetic field, the hydrogel microspheres are driven to move and interact with the surrounding microspheres, forming a cluster of microrobots with a three-dimensional structure.

[0017] The microrobot cluster can be driven to move to the end of the bronchus to deliver drugs to deep lung tissues; or the microrobot cluster can be driven to a target location to release the cells it carries.

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

[0019] The permanent magnet located at the end of the robotic arm is placed above the hydrogel microspheres;

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

[0021] A magnetic field is continuously applied to control the small three-dimensional aggregate 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 cluster of microrobots to move to the end of the bronchus to deliver drugs to deep lung tissue includes:

[0023] The end of the robotic arm is slowly moved along the direction of the trachea, and the permanent magnet at the end is controlled to move along the trachea, driving the cluster of microrobots to move forward inside the trachea;

[0024] The permanent magnet continues to move along the path from the trachea to the secondary bronchus, controlling the cluster of microrobots to pass through the main bronchus and move to the secondary bronchus.

[0025] An upward gradient force is applied to the microrobot cluster to guide it to crawl along the upper surface of the trachea to the tertiary bronchus.

[0026] The microrobot cluster is guided to move to the end of the bronchus to deliver drugs to the deep tissues of the lungs.

[0027] In one implementation, applying an upward gradient force to the microrobot cluster to guide it to crawl along the upper surface of the trachea to the tertiary bronchi includes:

[0028] When the cluster of microrobots moves to the secondary bronchus, the height of the permanent magnet is reduced to enhance the gradient force applied to the cluster of microrobots, causing the cluster of microrobots to be vertically lifted to the upper surface of the trachea. The permanent magnet is then moved along the direction from the secondary bronchus to the tertiary bronchus, guiding the cluster of microrobots to crawl on the upper surface of the trachea to the tertiary bronchus.

[0029] In one implementation, driving the cluster of microrobots to a target location and releasing the carried cells includes:

[0030] By increasing the magnetic field pitch angle, rearranging the cluster of microrobots, and controlling the cluster of microrobots to tilt, forward movement can be achieved.

[0031] The magnetic field direction angle can be adjusted in real time as needed to change the movement direction of the microrobot cluster and control the microrobot cluster to move to the target position.

[0032] The present invention, by employing the above technical solution, has the following effects:

[0033] This invention proposes a microrobot swarm for high-volume drug delivery to the lungs. The swarm comprises hydrogel microspheres composed of magnetic particles and a sodium alginate hydrogel network. By adjusting external magnetic field parameters, the swarm can be driven to perform highly reconfigurable and navigable movements. Furthermore, by applying a magnetic field gradient, the swarm can perform vertical lifting and surface crawling in a gaseous environment, enabling it to move within the complex and unstructured lung environment and reach the terminal bronchial tract. This invention's microrobot swarm exhibits high drug and cell loading capacity, enabling precise drug and cell delivery to the lungs. Attached Figure Description

[0034] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the structures shown in these drawings without creative effort.

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

[0037] Figure 3 This is a diagram illustrating the process of generating a cluster of microrobots.

[0038] Figure 4 This is a schematic diagram of the vertical lifting of a cluster of microrobots in a gaseous environment.

[0039] Figure 5 This is a schematic diagram of the delivery path of a cluster of microrobots in the bronchial network of the lungs.

[0040] Figure 6 (a) is 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 This is a flowchart of a control method for a swarm of microrobots that can be used for high-volume drug delivery to the lungs.

[0042] The objectives, features, and advantages of this invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0043] To make the objectives, technical solutions, and advantages of this invention clearer and more explicit, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

[0044] Exemplary device

[0045] Complex clustering behaviors in liquids can originate from interactions between individuals. Researchers have demonstrated how to assemble monomers into reconfigurable clusters by modulating microtubule-protein interactions, electrostatic interactions between metal-dielectric double-sided colloidal particles, between asymmetric polarizable monomers, and between living cells, as well as magnetic interactions between spherical colloidal particles. Simultaneously, interactions between monomers and the surrounding liquid also influence clustering behavior. In colloidal systems composed of different types of monomers, light-induced localized liquid flow selectively separates monomers into different clusters based on their type. Furthermore, fluid dynamic interactions caused by liquid-gas interface fluctuations induced by magnetic monomer oscillations and rotation can assemble dispersed monomers into dynamic clusters and enable them to navigate.

[0046] However, in a gaseous environment, the effects of hydrodynamic interactions on individual cells are negligible, and the generation mechanism of microrobot swarms in a gaseous environment differs from that in existing fluid environments. To date, field-driven microrobot swarms comprising a large number of cells have not been developed in a gaseous environment. Therefore, existing microrobot swarms cannot be used in the gas-filled lung environment for precise targeted drug delivery.

[0047] To address the aforementioned technical problems, this invention provides a microrobot cluster for high-volume drug delivery to the lungs. This microrobot cluster comprises hydrogel microspheres composed of magnetic particles and a sodium alginate hydrogel network. By adjusting external magnetic field parameters, the microrobot cluster can be driven to perform highly reconfigurable and navigable movements. Furthermore, by applying a magnetic field gradient, the microrobot cluster can perform vertical lifting and surface crawling in a gaseous environment, enabling it to move within the complex and unstructured lung environment and reach the terminal bronchial tract. The microrobot cluster in this invention possesses high drug and cell loading capabilities, enabling precise drug and cell delivery to the lungs.

[0048] like Figure 1 As shown, this embodiment of the invention provides a microrobot cluster for high-volume drug delivery to the lungs, comprising: multiple hydrogel microspheres, wherein the multiple hydrogel microspheres are used to carry a large amount of drug and form a microrobot cluster with a three-dimensional structure in a gaseous environment under the action of an external magnetic field; an external magnetic field is designed to drive the microrobot cluster, apply an upward gradient force to the microrobot cluster, enabling the microrobot cluster to overcome the downward gravity and capillary force and achieve vertical lifting; and subject the microrobot cluster to a gradient force along the direction of movement of a permanent magnet, enabling the microrobot cluster to crawl on the surface of the inner wall of a bronchial model to reach the end of the bronchus.

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

[0050] The specific implementation method involves using an external oscillating magnetic field. Hydrogel microspheres oscillate in a gaseous environment with the magnetic field and interact with surrounding particles, forming a cluster of microrobots with a three-dimensional structure. As an example, the magnetic field distribution is as follows: Figure 2 As shown in (a), under the influence of this magnetic field, a cluster of microrobots with a three-dimensional structure is formed, as shown in Figure (a). Figure 2 As shown in (b). The specific process of generating a micro-robot swarm is as follows: Figure 3As shown, the hydrogel microspheres are initially horizontal in the gaseous environment. After being subjected to an external oscillating magnetic field, the hydrogel microspheres oscillate with the magnetic field in the gaseous environment and interact with the surrounding particles, presenting a stacked cluster of microrobots with a three-dimensional structure.

[0051] like Figure 4 As shown, by adjusting the external magnetic field parameters using permanent magnets, a cluster of microrobots can be driven to perform highly reconfigurable and navigable movements. By applying a magnetic field gradient, the cluster can perform vertical lifting and surface crawling in a gaseous environment, enabling it to move through the complex and unstructured lung environment and reach the terminal bronchi. Furthermore, the cluster possesses a high drug loading capacity and can swell and degrade in environments with specific pH values, releasing the loaded drugs. The cluster can also perform cell delivery, maintaining the viability of the carried cells and allowing them to proliferate further after release.

[0052] In this embodiment, among the plurality of hydrogel microspheres, a portion are drug-loaded microspheres, and the other portion are cell-loaded microspheres. The drug-loaded microspheres are prepared from ferromagnetic neodymium iron boron particles and biocompatible sodium alginate hydrogel. The cell-loaded microspheres are prepared from cells, silica-coated neodymium iron boron particles, and biocompatible sodium alginate hydrogel. Under the influence of the external magnetic field, the interaction forces between the multiple hydrogel microspheres are altered, resulting in microrobot clusters of different morphologies, enabling shape reconstruction and navigation of the microrobot clusters.

[0053] In practical applications, the external magnetic field is used to drive the hydrogel microspheres. Considering the formation of a three-dimensional robot swarm in a gaseous environment, an oscillating magnetic field in the yz plane is employed, as shown in the image. Figure 2 As shown in (a). By adjusting the magnetic field parameters, the interaction between particles can be altered, enabling the cluster to reshape and navigate. For example, increasing the field strength or magnetic field ratio can enhance the attractive force between particles and the magnetic torque on the cluster, thereby increasing the cluster height; increasing the pitch angle can tilt the cluster, causing it to move in the tilting direction under the influence of gravity while oscillating with the magnetic field; adjusting the orientation angle can change the tilting direction of the cluster, thereby adjusting the direction of cluster movement.

[0054] In addition, such as Figure 5 As shown, considering the three-dimensional structure of the bronchial network in the lungs, a dynamic magnetic field gradient was used to apply an upward gradient force to the microrobot cluster, enabling the cluster to overcome the downward gravity and capillary force and achieve vertical lifting of the cluster. Furthermore, by moving the permanent magnet, the cluster was subjected to a gradient force along the direction of movement of the permanent magnet, which enabled the cluster to crawl on the surface of the inner wall of the bronchial model to reach the end of the bronchus.

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

[0056] The contained ferromagnetic particles enable the hydrogel microspheres to respond to an external magnetic field. The large amount of water contained within the microspheres allows for the large-scale loading of drugs. For example... Figure 6 As shown in (a), hydrogel microspheres loaded with water-soluble drugs swell and degrade due to the deprotonation of carboxyl groups on alginate under specific pH conditions, achieving controlled drug release. Figure 6 As shown in (b), the porous hydrogel network in the cell-loaded hydrogel microspheres enables cell loading and avoids cell leakage during delivery.

[0057] It is 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 steps for the generation and movement of the microrobot swarm in a gaseous environment are as follows:

[0059] A. Place multiple hydrogel microspheres at the inlet of the trachea model, and place the trachea model below the permanent magnet.

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

[0061] C. A magnetic field is continuously applied, causing the small three-dimensional aggregates to continue to oscillate with the magnetic field. By attracting surrounding particles to grow and merge with each other, they eventually form a cluster of micro-robots with a three-dimensional structure.

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

[0063] E. Adjust the magnetic field direction angle in real time as needed to change the direction of cluster movement and make it move to the target position.

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

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

[0066] B1. The drive motor causes the permanent magnet to oscillate, providing a dynamic magnetic field gradient. Under the action of gradient force and magnetic torque, some magnetic hydrogel microspheres detach from the ground and aggregate with surrounding particles, forming small three-dimensional aggregates. These three-dimensional aggregates oscillate with the permanent magnet and attract surrounding particles, eventually assembling into a cluster of three-dimensional microrobots.

[0067] C1. Then, the end of the robotic arm is slowly moved along the direction of the trachea, causing the permanent magnet at the end to move along the trachea, thereby allowing the cluster of microrobots to advance inside the trachea.

[0068] D1. Continue moving the permanent magnet along the path from the trachea to the secondary bronchi, so that the cluster of microrobots passes through the main bronchus and moves to the secondary bronchi.

[0069] E1. When the cluster moves to the secondary bronchus, the height of the permanent magnet is reduced to enhance the gradient force applied to the cluster, causing it to be vertically lifted to the upper surface of the trachea. The permanent magnet is then moved further along the direction from the secondary bronchus to the tertiary bronchus, guiding the cluster to crawl along the upper surface of the trachea to the tertiary bronchus.

[0070] D1. Ultimately, guide the cluster of microrobots to move to the end of the bronchus to deliver drugs to the deep lung tissues.

[0071] As a further example, the specific steps for cell delivery using the aforementioned microrobot swarm are as follows:

[0072] A2. Silica-coated magnetic particles were prepared by the Stuber process. Cells, magnetic particles and sodium alginate were mixed in water to prepare hydrogel microspheres carrying cells, and the microspheres were placed under a magnetic field.

[0073] B2. Drive hydrogel microspheres to form a cluster of microrobots and change the pitch and azimuth angles of the magnetic field to deliver the cluster to the target position.

[0074] C2. At the target location, due to environmental influences, the cluster naturally swells and degrades, releasing the cells it carries.

[0075] The above-described technical solution in this embodiment has the following effects:

[0076] This embodiment proposes a microrobot cluster for high-load drug delivery to the lungs. The cluster comprises hydrogel microspheres composed of magnetic particles and a sodium alginate hydrogel network. By adjusting external magnetic field parameters, the cluster can be driven to perform highly reconfigurable and navigable movements. Furthermore, by applying a magnetic field gradient, the cluster can perform vertical lifting and surface crawling in a gaseous environment, enabling it to move within the complex and unstructured lung environment and reach the terminal bronchial tract. This embodiment's microrobot cluster exhibits high drug and cell loading capacity, enabling precise drug and cell delivery to the lungs.

[0077] Exemplary methods

[0078] like Figure 7 As shown, this embodiment of the invention provides a control method for a swarm of microrobots that can be used for high-volume drug delivery to the lungs, comprising the following steps:

[0079] Step S100: Place multiple hydrogel microspheres at the inlet of the trachea model and place the trachea model below the permanent magnet;

[0080] Step S200: By applying an oscillating magnetic field, the hydrogel microspheres are driven to move and interact with the surrounding microspheres to form a cluster of microrobots with a three-dimensional structure.

[0081] In step S300, the microrobot cluster is driven to move to the end of the bronchus to deliver drugs to the deep lung tissue; or the microrobot cluster is driven to the target location to release the cells it carries.

[0082] In this embodiment, the step of 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 includes: placing a permanent magnet located at the end of a robotic arm above the hydrogel microspheres; driving a motor to control the permanent magnet to swing, providing a dynamic magnetic field gradient, under the action of gradient force and magnetic torque, some of the hydrogel microspheres detach from the ground and aggregate with surrounding microspheres to form a small three-dimensional aggregate; continuously applying a magnetic field to control the small three-dimensional aggregate to swing with the permanent magnet and attract surrounding microspheres to form the micro-robot cluster with a three-dimensional structure.

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

[0084] The specific implementation method involves using an external oscillating magnetic field. Hydrogel microspheres oscillate in a gaseous environment with the magnetic field and interact with surrounding particles, forming a cluster of microrobots with a three-dimensional structure. As an example, the magnetic field distribution is as follows: Figure 2 As shown in (a), under the influence of this magnetic field, a cluster of microrobots with a three-dimensional structure is formed, as shown in Figure (a). Figure 2 As shown in (b). The specific process of generating a micro-robot swarm is as follows: Figure 3 As shown, the hydrogel microspheres are initially horizontal in the gaseous environment. After being subjected to an external oscillating magnetic field, the hydrogel microspheres oscillate with the magnetic field in the gaseous environment and interact with the surrounding particles, presenting a stacked cluster of microrobots with a three-dimensional structure.

[0085] like Figure 4 As shown, by adjusting the external magnetic field parameters using permanent magnets, a cluster of microrobots can be driven to perform highly reconfigurable and navigable movements. By applying a magnetic field gradient, the cluster can perform vertical lifting and surface crawling in a gaseous environment, enabling it to move through the complex and unstructured lung environment and reach the terminal bronchi. Furthermore, this cluster of microrobots possesses a high drug loading capacity and can swell and degrade in environments with specific pH values, releasing the loaded drug.

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

[0087] Specifically, applying an upward gradient force to the microrobot cluster to guide it to crawl along the upper surface of the trachea to the tertiary bronchus includes: when the microrobot cluster moves to the secondary bronchus, lowering the height of the permanent magnet to enhance the gradient force applied to the microrobot cluster, causing the microrobot cluster to be vertically lifted to the upper surface of the trachea, and moving the permanent magnet along the direction from the secondary bronchus to the tertiary bronchus to guide the microrobot cluster to crawl along the upper surface of the trachea to the tertiary bronchus.

[0088] As an example, hydrogel microspheres are driven by an external magnetic field. Considering the formation of a swarm of robots with a three-dimensional structure in a gaseous environment, an oscillating magnetic field in the yz plane is employed, as shown in the diagram. Figure 2 As shown in (a). By adjusting the magnetic field parameters, the interaction between particles can be altered, enabling the cluster to reshape and navigate. For example, increasing the field strength or magnetic field ratio can enhance the attractive force between particles and the magnetic torque on the cluster, thereby increasing the cluster height; increasing the pitch angle can tilt the cluster, causing it to move in the tilting direction under the influence of gravity while oscillating with the magnetic field; adjusting the orientation angle can change the tilting direction of the cluster, thereby adjusting the direction of cluster movement.

[0089] In addition, such as Figure 5 As shown, considering the three-dimensional structure of the bronchial network in the lungs, a dynamic magnetic field gradient was used to apply an upward gradient force to the microrobot cluster, enabling the cluster to overcome the downward gravity and capillary force and achieve vertical lifting of the cluster. Furthermore, by moving the permanent magnet, the cluster was subjected to a gradient force along the direction of movement of the permanent magnet, which enabled the cluster to crawl on the surface of the inner wall of the bronchial model to reach the end of the bronchus.

[0090] In this embodiment, the microrobot cluster can also deliver cells and maintain the activity of the carried cells, allowing them to proliferate further after release. Driving the microrobot cluster to the target location and releasing the carried cells includes: increasing the magnetic field pitch angle, rearranging the microrobot cluster, controlling the microrobot cluster to tilt to achieve forward movement; and adjusting the magnetic field direction angle in real time as needed to change the movement direction of the microrobot cluster and control the microrobot cluster to move to the target location.

[0091] In this embodiment, the hydrogel microspheres serve as monomers, enabling cargo loading and release. There are two types of hydrogel microspheres: for water-soluble drug loading, the hydrogel microspheres are prepared from ferromagnetic neodymium iron boron particles and biocompatible sodium alginate hydrogel; while for cell loading, the hydrogel microspheres are prepared from cells, silica-coated ferromagnetic neodymium iron boron particles, and biocompatible sodium alginate hydrogel.

[0092] The contained ferromagnetic particles enable the hydrogel microspheres to respond to an external magnetic field. The large amount of water contained within the microspheres allows for the large-scale loading of drugs. For example... Figure 6 As shown in (a), hydrogel microspheres loaded with water-soluble drugs swell and degrade due to the deprotonation of carboxyl groups on alginate under specific pH conditions, achieving controlled drug release. Figure 6 As shown in (b), the porous hydrogel network in the cell-loaded hydrogel microspheres enables cell loading and avoids cell leakage during delivery.

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

[0094] The above-described technical solution in this embodiment has the following effects:

[0095] This embodiment proposes a control method for a microrobot swarm capable of high-volume drug delivery to the lungs. By adjusting external magnetic field parameters, the microrobot swarm can be driven to perform highly reconfigurable and navigable movements. Furthermore, by applying a magnetic field gradient, the microrobot swarm can perform vertical lifting and surface crawling in a gaseous environment, enabling it to move within the complex and unstructured lung environment and reach the terminal bronchial tract. The microrobot swarm of this embodiment possesses high drug and cell loading capabilities, enabling precise drug and cell delivery to the lungs.

[0096] Those skilled in the art will understand that all or part of the processes in the methods of the above embodiments can be implemented by a computer program instructing related hardware. The computer program can be stored in a non-volatile storage medium, and when executed, it can include the processes of the embodiments of the methods described above. Any references to memory, storage, database, or other media used in the embodiments provided by this invention can include both non-volatile and volatile memory.

[0097] In summary, this invention provides a microrobot cluster and control method for high-volume drug delivery to the lungs. The method includes: multiple hydrogel microspheres, which carry a large amount of drug and form a three-dimensional microrobot cluster in a gaseous environment under the influence of an external magnetic field; an external magnetic field design to drive the microrobot cluster, applying an upward gradient force to the cluster to overcome downward gravity and capillary forces, achieving vertical lifting; and subjecting the cluster to a gradient force along the direction of movement of a permanent magnet, enabling it to crawl along the surface of a bronchial model to reach the bronchial terminal. The microrobot cluster of this invention has high drug and cell loading capacity, enabling precise drug and cell delivery to the lungs.

[0098] It should be understood that the application of the present invention is not limited to the examples above. Those skilled in the art can make improvements or modifications based on the above description, and all such improvements and modifications should fall within the protection scope of the appended claims.

Claims

1. A cluster of microrobots for high-volume drug delivery to the lungs, characterized in that, include: Multiple hydrogel microspheres are used to carry a large amount of drug and form a cluster of microrobots with a three-dimensional structure in a gaseous environment under the action of an external magnetic field. An external magnetic field is designed to drive the microrobot cluster, applying an upward gradient force to the microrobot cluster so that it overcomes the downward gravity and capillary force and achieves vertical lifting; and applying a gradient force along the direction of movement of the permanent magnet to the microrobot cluster so that it can crawl on the surface of the inner wall of the bronchus model to reach the end of the bronchus. Of the plurality of hydrogel microspheres, a portion of the hydrogel microspheres are loading microspheres for water-soluble drugs, and another portion of the hydrogel microspheres are loading microspheres for cells. The water-soluble drug-loaded microspheres are prepared from ferromagnetic neodymium iron boron particles and biocompatible sodium alginate hydrogel; The cell-loaded microspheres are prepared from cells, silica-coated neodymium iron boron ferromagnetic particles, and biocompatible sodium alginate hydrogel. Multiple hydrogel microspheres change the interaction force between particles under the action of the external magnetic field to obtain microrobot clusters of different shapes, thereby realizing the shape reconstruction and navigation motion of the microrobot clusters.

2. A control method for a swarm of microrobots for high-volume drug delivery to the lungs as described in claim 1, characterized in that, include: Multiple hydrogel microspheres were placed at the inlet of the trachea model, and the trachea model was placed below the permanent magnet; By applying an oscillating magnetic field, the hydrogel microspheres are driven to move and interact with the surrounding microspheres, forming a cluster of microrobots with a three-dimensional structure. The microrobot cluster can be driven to move to the end of the bronchus to deliver drugs to deep lung tissues; or the microrobot cluster can be driven to a target location to release the cells it carries.

3. The control method for a swarm of microrobots for high-volume drug delivery to the lungs according to claim 2, characterized in that, The process involves applying an oscillating magnetic field to drive the hydrogel microspheres to move and interact with surrounding microspheres, forming a cluster of microrobots with a three-dimensional structure, including: The permanent magnet located at the end of the robotic arm is placed above the hydrogel microspheres; The drive motor controls the oscillation of the permanent magnet to provide a dynamic magnetic field gradient. Under the action of gradient force and magnetic torque, some of the hydrogel microspheres detach from the ground and aggregate with the surrounding microspheres to form small three-dimensional aggregates. A magnetic field is continuously applied to control the small three-dimensional aggregate to swing with the permanent magnet and attract the surrounding microspheres to form the micro-robot cluster with a three-dimensional structure.

4. The control method for a swarm of microrobots for high-volume drug delivery to the lungs according to claim 2, characterized in that, The process of driving the microrobot cluster to move to the end of the bronchus to deliver drugs to deep lung tissue includes: The end of the robotic arm is slowly moved along the direction of the trachea, and the permanent magnet at the end is controlled to move along the trachea, driving the cluster of microrobots to move forward inside the trachea; The permanent magnet continues to move along the path from the trachea to the secondary bronchus, controlling the cluster of microrobots to pass through the main bronchus and move to the secondary bronchus. An upward gradient force is applied to the microrobot cluster to guide it to crawl along the upper surface of the trachea to the tertiary bronchus. The microrobot cluster is guided to move to the end of the bronchus to deliver drugs to the deep tissues of the lungs.

5. The control method for a swarm of microrobots for high-volume drug delivery to the lungs according to claim 4, characterized in that, Applying an upward gradient force to the microrobot cluster to guide it to crawl along the upper surface of the trachea to the tertiary bronchi includes: When the cluster of microrobots moves to the secondary bronchus, the height of the permanent magnet is reduced to enhance the gradient force applied to the cluster of microrobots, causing the cluster of microrobots to be vertically lifted to the upper surface of the trachea. The permanent magnet is then moved along the direction from the secondary bronchus to the tertiary bronchus, guiding the cluster of microrobots to crawl on the upper surface of the trachea to the tertiary bronchus.

6. The control method for a swarm of microrobots for high-volume drug delivery to the lungs according to claim 2, characterized in that, The process of driving the cluster of microrobots to a target location and releasing the carried cells includes: By increasing the magnetic field pitch angle, rearranging the cluster of microrobots, and controlling the cluster of microrobots to tilt, forward movement can be achieved. The magnetic field direction angle can be adjusted in real time as needed to change the movement direction of the microrobot cluster and control the microrobot cluster to move to the target position.

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