A magneto-thermally co-regulated capsule robot

Abstract

The present invention belongs to the technical field of magnetically controlled soft robots. More specifically, it relates to a capsule robot with magnetic-thermal collaborative regulation. The robot body includes a capsule shell, and hollow air chambers are respectively arranged at both ends of the capsule shell. A loading cavity is arranged between the hollow air chambers; a material transmission window, a magnetic valve, and a fixed magnetic attraction component are arranged on the side wall of the loading cavity. The magnetic valve and the fixed magnetic attraction component are cooperatively arranged through magnetic attraction force to close the material transmission window; a thermal response module is arranged inside the loading cavity. The internal system structure and regulation method of the magnetic-thermal collaborative regulation capsule robot of the present invention are relatively simple. Through the bidirectional collaborative control of magnetic attraction force and magnetic induction heating, the controllable drug delivery and biopsy functions of the capsule robot are cleverly realized. There is no complex mechanical structure inside, and the wireless induction heating and magnetic drive methods have high safety.

Description

Technical Field

[0001] The present invention belongs to the technical field of magnetically controlled soft robots, and more specifically, relates to a capsule robot with magnetic-thermal collaborative regulation. Background Art

[0002] Oral administration is the most commonly used drug administration method, but its efficacy is easily affected by the gastrointestinal environment, that is, there is a first-pass effect, which greatly reduces the drug administration efficiency and application scenarios. How live bacteria drugs such as probiotics can tolerate gastric acid, digestive enzymes, and bile and maintain their activity to reach the target organ has become the key to the efficacy of live bacteria drugs. In addition, the release of some drugs in non-target areas poses a potential risk of harm to the human body.

[0003] In order to reduce the systemic side effects of drugs on humans and improve the local treatment effect of drugs, innovative drug release devices and on-demand drug delivery control methods have received extensive attention and research from scholars. For example, Chinese patent document CN112604146A discloses an implantable drug delivery device triggered by a pulsed magnetic field. The drug delivery device includes a drug storage outer shell, a magnetic piston assembly, and a magnetic fixed base assembly. This invention uses a magnetic field as an external excitation source, which has the advantages of being safe and harmless and having high responsiveness. However, the component materials have a relatively large density, and the processing requirements for the mechanical structure are relatively high. There are disadvantages such as a large capsule density and limited movement speed. In addition, the drug release of this drug delivery device only relies on the osmotic action of the drug itself to reach the designated target area, and the time required for drug release is relatively long.

[0004] The patent document with publication number CN115569298A discloses a magnetically controlled micro soft drug-loaded capsule robot and its preparation and driving method. The invention includes an upper soft capsule outer shell, an upper extrusion magnetic block component, an upper drug release magnetic block component, a top cross drug release port, and a lower soft capsule outer shell, a lower extrusion magnetic block component, a lower drug release magnetic block component, and a bottom cross drug release port. Each extrusion magnetic block and drug release magnetic block have different magnetization directions. Through an external three-dimensional Helmholtz coil magnetic field generating device, the rolling movement and extrusion drug release actions of the capsule robot in any direction can be realized. The assembly of each extrusion magnetic block component adopted in this invention is relatively complex, and it is difficult to precisely control the magnetic field when magnetic block components with different magnetization directions cooperate to release drugs. Therefore, it is challenging to achieve precisely controllable drug release.

[0005] In view of the advantages of magnetically controlled soft robots driven by an external magnetic field, such as wireless control and high adaptability. Therefore, integrating the advantages of wireless control and strong penetrability of magnetically controlled soft robots into a drug delivery capsule with drug delivery and biopsy functions is expected to achieve a capsule robot with a simpler structure, higher controllability, and higher control efficiency, which has very important clinical medical value. Summary of the Invention

[0006] In view of the deficiencies of the prior art, the purpose of the present invention is to provide a magnetic-thermal synergistic regulation capsule robot with controllable drug delivery and biopsy functions, so as to solve the technical problems of low drug delivery efficiency, complex capsule structure, complex control method and insufficient safety degree of the existing capsule robot.

[0007] To achieve the above object, the present invention provides a magnetic-thermal synergistic regulation capsule robot, which includes a robot body and a magnetic drive module, wherein:

[0008] The robot body includes a capsule shell, and hollow air chambers are respectively arranged at both ends of the capsule shell. A loading cavity is arranged between the hollow air chambers, and the loading cavity is isolated from the hollow air chambers;

[0009] A material transmission window, a magnetic valve and a fixed magnetic attraction component are arranged on the side wall of the loading cavity. The magnetic valve is a magnetized magnetic valve. The magnetized magnetic valve and the fixed magnetic attraction component are cooperatively arranged by magnetic attraction force to close the material transmission window, and one end of the magnetic valve is fixedly connected to the capsule shell, and the other end is a free end;

[0010] A thermal response module is arranged inside the loading cavity. The thermal response module includes a thermal control air chamber, magnetic nanoparticles and a low-boiling-point phase change liquid located inside the thermal control air chamber;

[0011] The magnetic drive module is used to apply a high-frequency magnetic field to the magnetic nanoparticles in the thermal response module;

[0012] During use, the magnetic drive module applies a high-frequency magnetic field to the magnetic nanoparticles in the thermal response module under the action of an external magnetic field excitation source, so that the temperature inside the thermal control air chamber rises, further causing the low-boiling-point phase change liquid to vaporize and turn into a gas state, and the volume of the thermal control air chamber increases. As the volume of the thermal control air chamber continuously increases, the pressure difference between the pressure inside the loading cavity and the external pressure gradually becomes larger, until the free end of the magnetized magnetic valve breaks away from the attraction of the fixed magnetic attraction component, and the magnetic valve is opened, thereby enabling material transmission or exchange between the loading cavity and the external environment.

[0013] Preferably, the material transmission window is one or more openings protruding outward from the inner wall of the loading cavity. The fixed magnetic attraction component is arranged on the periphery of the opening, and the magnetized magnetic valve is cooperatively arranged on the surface of the fixed magnetic attraction component away from the loading cavity by magnetic attraction force.

[0014] Further preferably, a groove is formed on the outer wall of the load cavity, the material transmission window is located at the bottom of the groove and protrudes upward, a middle through hole is provided on the fixed magnetic attraction assembly, and the fixed magnetic attraction assembly is sleeved on the material transmission window through the middle through hole in the groove; the magnetized magnetic valve covers and is arranged on the plane or curved surface where the material transmission window and the fixed magnetic attraction assembly are located in the groove by magnetic attraction force, so that the material transmission window is in a closed state.

[0015] Preferably, the fixed magnetic assembly is made of a magnetic material, the magnetic valve is made of a magnetic soft material, and the thermal control air chamber is made of an expandable soft material.

[0016] Preferably, the magnetization direction of the magnetized magnetic valve is single-radial magnetization.

[0017] Preferably, the magnetic nanoparticles are Fe3O4; the low-boiling-point phase change liquid is anhydrous ethanol or 3M7000.

[0018] Preferably, the external magnetic field excitation source is a high-frequency induction heating coil.

[0019] Further preferably, the magnetic field intensity of the high-frequency magnetic field applied by the high-frequency induction heating coil to the magnetic nanoparticles in the thermal response module is less than or equal to 100 mT; its frequency is greater than or equal to 1000 Hz.

[0020] Further preferably, the external magnetic field excitation source further includes a permanent magnet; the permanent magnet is used to apply an external magnetic field to the magnetized magnetic valve, so that the magnetized magnetic valve moves to the target position under the action of the magnetic moment; and / or so that the magnetized magnetic valve switches from the open state to the closed state under the action of the magnetic moment.

[0021] Preferably, the load cavity includes a plurality of sub-load cavities, and the material transmission window, the magnetic valve and the fixed magnetic attraction assembly are arranged on the side wall of each sub-load cavity; the thermal response module is arranged inside each sub-load cavity.

[0022] Generally speaking, compared with the prior art, the above technical solutions conceived by the present invention have the following

[0023] Beneficial effects:

[0024] (1) A magneto-thermal collaborative regulation capsule robot provided by the present invention includes a robot body and a magnetic drive module, wherein: the robot body includes a capsule housing, hollow air chambers are respectively arranged at both ends of the capsule housing, and a loading cavity is arranged between the hollow air chambers; a material transmission window, a magnetic valve and a fixed magnetic attraction assembly are arranged on the side wall of the loading cavity, and the magnetic valve and the fixed magnetic attraction assembly are cooperatively arranged through magnetic attraction force to close the material transmission window; a thermal response module is arranged inside the loading cavity, and the thermal response module includes a thermal control air chamber, magnetic nanoparticles and a low-boiling-point phase change liquid located inside the thermal control air chamber; during use, the magnetic drive module applies a high-frequency magnetic field to the magnetic nanoparticles in the thermal response module under the action of an external magnetic field excitation source, so that the temperature inside the thermal control air chamber rises, further causing the low-boiling-point phase change liquid to vaporize and transform into a gas state, and the volume of the thermal control air chamber increases. As the volume of the thermal control air chamber continuously increases, the pressure difference between the pressure inside the loading cavity and the pressure outside it gradually becomes larger until the magnetized magnetic valve partially breaks away from the attraction of the fixed magnetic attraction assembly, opening the magnetic valve, and then enabling material transmission or exchange between the loading cavity and the external environment. The magneto-thermal collaborative regulation capsule robot of the present invention has a relatively simple internal system structure and regulation method of the capsule. Through the two-way collaborative control of magnetic attraction force and magnetic induction heating, the controllable drug delivery and biopsy functions of the capsule robot are cleverly realized. There is no complex mechanical structure inside, and the wireless induction heating and magnetic drive methods have high safety. In addition, the phase change gas generated by the high-frequency heating of the low-boiling-point phase change liquid in the thermal control air chamber remains in the thermal control air chamber after cooling and is not carried into the human body, which has better practicability and safety compared with other manipulation methods. Combining the advantages of strong magnetic manipulation penetration ability and unrestricted action area, the magneto-thermal collaborative regulation capsule robot provided by the present invention provides a new technical path for the multi-functionalization of capsule robots.

[0025] (2) The present invention is easy to achieve precise targeted drug delivery of the capsule robot. In the preferred embodiment of the present invention, an external excitation magnetic field is generated by an induction heating coil. On the one hand, wireless induction heating can be performed on the thermal control air chamber through a high-frequency heating current, and Fe3O4 is heated to cause the low-boiling-point liquid to undergo liquid-gas phase change, thereby remotely opening the magnetic valve; on the other hand, the current frequency in the induction heating coil can be reduced to a low frequency, and then an alternating magnetic field is applied to control the up and down beating frequency of the magnetic valve, thereby accelerating or slowing down the exchange rate between the drug and the outside world; and a rotating magnetic field can also be applied to make the drug delivery capsule move directionally and targetedly under the action of a magnetic torque. Therefore, through the adjustment of the current frequency in the excitation coil, the capsule robot proposed by the present invention can not only achieve targeted drug release, but also accelerate or slow down the drug release, thereby realizing precise drug release and having high controllability.

[0026] (3) The control method of the capsule robot provided by the present invention adopts a magnetic-thermal collaborative regulation control method. Both magnetic manipulation and thermal response driving have the characteristics of remote wireless driving. Due to the advantages of strong magnetic field penetration ability and unrestricted action area, the capsule robot can achieve precise quantitative and timed drug delivery and active biopsy functions, greatly improving the drug delivery efficiency and dosing stability. In addition, the capsule robot of the present invention opens the magnetic valve by wireless heating and has no strict requirement for the direction of the magnetic field. Therefore, the robot and its control method have good universality.

[0027] (4) It can achieve multi-functional reuse. After the thermal control air chamber of the capsule robot in the present invention is used by wireless induction heating, when the high-frequency heating magnetic field is removed and the temperature of the thermal control air chamber decreases, the thermal control air chamber can return to its initial size again. When the drug in the drug delivery cavity is released or the fixed-point biopsy function is completed, the capsule robot can be re-sterilized and the magnetic attraction plate can be sealed and then recycled for the second time, which better practices the concept of resource conservation.

[0028] (5) Hollow air chambers are respectively arranged at both ends of the capsule shell of the capsule robot of the present invention. The hollow air chambers can reduce the density of the entire capsule robot, thereby ensuring that the capsule robot has a strong ability to carry drugs; and can also realize the floating and sinking of the capsule robot in the liquid, making the movement of the capsule robot more flexible. Description of the Drawings

[0029] Figure 1 is a three-dimensional structure schematic diagram of the robot body of the capsule robot provided in the embodiment of the present invention: Figure 1 Content (a) is the robot body; Figure 1 Content (b) is the magnetic valve of the robot body; Figure 1 Content (c) is the magnetic attraction plate of the robot body; Figure 1 Content (d) is the thermal control air chamber of the robot body; Figure 1 Content (e) is the capsule shell of the robot body;

[0030] Figure 2 is a schematic diagram of the working principle of the capsule robot provided by the present invention when no drug is administered and the drug is released: Figure 2 Content (a) is a schematic diagram of the structure of the capsule robot at position A in the small intestine; Figure 2 Content (b) is a schematic diagram of the structure of the capsule robot at position B in the small intestine; Figure 2 Content (c) is a schematic diagram of the structure of the capsule robot at position C in the small intestine; Figure 2 Content (d) is an experimental result diagram when the capsule robot releases drugs;

[0031] Figure 3Schematic diagram of the working principle of the capsule robot for active biopsy in the present invention: Figure 3 Content (a): Schematic diagram of the structure of the capsule robot when it is not working; Figure 3 Content (b): Schematic diagram of the structure of the capsule robot after the thermal control air chamber expands; Figure 3 Content (c): Schematic diagram of the structure when tissue fluid enters the loading cavity; Figure 3 Content (d): Schematic diagram of the structure after the tissue fluid extraction is completed. Specific implementation manners

[0032] In order to make the objectives, technical solutions and advantages of the present invention clearer, the present 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 only used to explain the present invention and are not used to limit the present invention.

[0033] A magneto-thermal synergistic regulation capsule robot provided by the present invention includes a robot body and a magnetic drive module, wherein: the robot body includes a capsule housing, hollow air chambers are respectively arranged at both ends of the capsule housing, a loading cavity is arranged between the hollow air chambers, and the loading cavity is isolated from the hollow air chambers.

[0034] A material transmission window, a magnetic force valve and a fixed magnetic attraction component are arranged on the side wall of the loading cavity. The magnetic force valve is a magnetized magnetic force valve. The magnetized magnetic force valve and the fixed magnetic attraction component are cooperatively arranged by magnetic attraction force to close the material transmission window. One end of the magnetic force valve is fixedly connected to the capsule housing, and the other end is a free end; the material transmission window is used for material transmission or exchange between the loading cavity and the external environment when the magnetic force valve is opened.

[0035] A thermal response module is arranged inside the loading cavity, and the thermal response module is used to open the magnetic force valve. The thermal response module includes a thermal control air chamber, magnetic nanoparticles and a low-boiling-point phase change liquid located inside the thermal control air chamber;

[0036] The magnetic drive module is used to apply a high-frequency magnetic field to the magnetic nanoparticles in the thermal response module;

[0037] During use, under the action of an external magnetic field excitation source, the magnetic drive module applies a high-frequency magnetic field to the magnetic nanoparticles in the thermal response module, causing the temperature inside the thermal control chamber to rise. This further causes the low-boiling-point phase-change liquid to vaporize and turn into a gas, increasing the volume of the thermal control chamber. As the volume of the thermal control chamber continuously increases, the pressure difference between the pressure inside the load cavity and the pressure outside it becomes larger, causing the magnetized magnetic valve to partially break away (i.e., the free end of the magnetic valve breaks away) from the attraction of the fixed magnetic attraction component, thereby opening the magnetic valve and enabling material transfer or exchange between the load cavity and the external environment. On the other hand, when no high-frequency magnetic field is applied to the magnetic nanoparticles in the thermal response module, the magnetic valve fits well with the fixed magnetic attraction component through magnetic attraction, keeping the material transfer window in a closed state to isolate the load cavity from the external environment.

[0038] In the capsule robot of the present invention, the robot body includes a capsule shell. Hollow chambers are respectively provided at both ends of the capsule shell, and a load cavity is provided between the hollow chambers at both ends. The load cavity and the hollow chambers on both sides are in an isolated state. The load cavity is located inside the capsule shell. When the magnetic valve is in a closed state, the load cavity is a sealed space, which can be used for storing a drug solution or storing a biopsy tissue. The material transfer window provided in the capsule robot of the present invention serves as a window for drug or tissue fluid exchange or transfer between the internal load cavity and the external environment. When the magnetic valve is opened, the drug in the load cavity can reach the lesion area through the material transfer channel, or the tissue fluid in the target area can enter the load cavity, realizing the active biopsy function.

[0039] In some embodiments, the material transfer window is one or more openings protruding outward from the inner wall of the load cavity. The material transfer window and the load cavity are of an integral structure. The fixed magnetic attraction component is provided around the opening, and the magnetized magnetic valve is arranged on the surface of the fixed magnetic attraction component away from the load cavity through magnetic attraction.

[0040] The magnetic valve and the fixed magnetic attraction component can be arranged in various ways as long as they can close the material transfer window provided on the side wall of the load cavity through magnetic attraction. In a preferred embodiment, a groove is formed on the outer wall of the load cavity. The material transfer window is located at the bottom of the groove and protrudes upward. The fixed magnetic attraction component is provided with a middle through hole, and the height of the middle through hole is the same as the height of the upward protrusion of the material transfer window. The fixed magnetic attraction component is sleeved on the material transfer window through the middle through hole in the groove. The magnetized magnetic valve covers and is arranged on the plane or curved surface where the material transfer window and the fixed magnetic attraction component are located through magnetic attraction in the groove, so as to keep the material transfer window in a closed state.

[0041] One end of the magnetic valve can be fixedly connected to the capsule housing in a variety of connection ways. In some embodiments, one end of the magnetic valve is fixedly connected to the capsule housing through an adhesive, such as medical silicone glue KJ998 and AA3211UV glue with good biocompatibility.

[0042] The substance transmission window of the present invention can be of various shapes, including but not limited to circular, square, etc. In some embodiments, the fixed magnetic attraction component is a magnetic attraction plate provided with a through hole in the middle, and the cross-section of the through hole can also be of various shapes. In order to facilitate sleeving the middle through hole of the fixed magnetic attraction component on the protruding substance transmission window, in some embodiments, the shape of the middle through hole is the same as that of the substance transmission window, and the inner diameter of the through hole is the same as the outer diameter of the upward protruding part of the substance transmission window.

[0043] The fixed magnetic attraction component, the magnetic valve and the thermal response module constitute the switch of the magnetic-thermal synergistic regulation capsule robot of the present invention, and they are all made of magnetic materials or contain magnetic materials. In some embodiments, the fixed magnetic component is made of a magnetic material, and the magnetic valve is made of a magnetic soft material. The magnetic valve is made of a permanent magnetic material (such as magnetic particles such as NdFeB, C r O2, etc.) and a soft material (such as silicone, TPE material, hydrogel and other materials with an elastic modulus below GPa) at the micron scale and below, and is a magnetic soft composite material; the fixed magnetic attraction component is made of a permanent magnetic material and a non-magnetic material (such as silicone, TPE material, hydrogel, etc.) at the micron scale and below. Since it does not need to deform, the selection ranges of its permanent magnetic material and non-magnetic material are wider. The permanent magnetic material can be not only NdFeB magnetic particles, but also ferromagnetic particles, etc., and the non-magnetic material can be a soft or hard material. In some embodiments, the pre-prepared mixed solution of the fixed magnetic attraction component is evenly added to a mold, and it is placed in an incubator at 70 °C for curing. After it is completely cured, demolding is carried out to obtain the prepared fixed magnetic attraction component; the preparation of the magnetic switch valve is the same. The magnetic nanoparticles contained in the thermal response module are magnetic nanoparticles that can generate heat under the action of a high-frequency magnetic field to increase the internal temperature of the thermal control air chamber, including but not limited to Fe3O4, etc. The thermal control air chamber can be made by 3D printing technology and spin coating, and then a mixed solution of a low-boiling-point phase-change liquid and magnetic nanoparticles is injected into the thermal control air chamber by a syringe, and finally the thermal control air chamber is sealed to produce a complete thermal control air chamber.

[0044] In some embodiments, in order to accurately achieve the functions of targeted drug delivery and targeted biopsy to a specified target area, the magnetization direction of the magnetized magnetic valve is a single radial magnetization, so as to facilitate the control of the directional movement of the capsule robot.

[0045] In some embodiments, a pulse magnetization device is used to magnetize the magnetic valve; the pulse magnetization device includes a pulse power supply, a magnetizing coil, a discharge capacitor, a discharge switch, and a magnetization mold; when the pulse magnetization device works, the magnetization mold with the magnetic valve placed inside is arranged inside the magnetizing coil; when a sinusoidal half-wave pulse current is passed through the magnetizing coil, a strong pulse magnetic field is generated in the internal space of the coil, so as to perform single-radial magnetization on the magnetic valve placed inside the magnetization mold.

[0046] In some embodiments, the magnetizing coil is wound by flat copper wire, and a reinforcing material is arranged on its periphery, and the central area of its coil skeleton is set to be hollow, so that when the pulse current flows through the magnetizing coil, a relatively uniform axial pulse magnetic field is generated in the central area to magnetize the magnetic valve.

[0047] In some embodiments, the die method is used to perform single-radial magnetization on the magnetic valve. Specifically, first, the processed magnetic valve is placed in a prefabricated magnetization mold groove, and finally, the magnetization mold carrying the magnetic valve is integrally placed in the magnetizing coil for overall axial magnetization.

[0048] In some embodiments, the magnetic nanoparticles inside the thermal control air chamber are Fe3O4; the low-boiling-point phase-change liquid is anhydrous ethanol or 3M7000; the thermal control air chamber is made of an expandable soft material, such as a silicone-based soft material, including but not limited to liquid platinum silicone Ecoflex 0030, etc. In some embodiments, the soft material Ecoflex 0030 is added to the processed mold by the die method to complete the production.

[0049] The magnetic nanoparticles in the thermal control air chamber generate heat under the action of a high-frequency magnetic field, so that the temperature inside the thermal control air chamber rises. The increase in the temperature of the thermal control air chamber can cause the low-boiling-point phase-change liquid inside the thermal control air chamber to undergo a phase change from liquid phase to gas phase, generating gas and causing the volume of the thermal control air chamber to expand, thereby squeezing the air in the object-carrying cavity, so as to separate one end of the magnetic valve that is not solid with the capsule shell from the attraction of the fixed magnetic adsorption component, and open the magnetic valve, and further enable material transfer or exchange between the object-carrying cavity and the external environment.

[0050] In some embodiments, the capsule shell is manufactured by using a light-curing 3D printing technology. The capsule shell is made of medical rubber, medical plastic and other materials with good biosecurity and not affected by gastrointestinal environments such as gastric acid. Specifically, for example, MED610, transparent non-fluorescent resin materials, etc. can be used.

[0051] In some embodiments, the external magnetic field excitation source is a high-frequency induction heating coil. The high-frequency magnetic field applied by the high-frequency induction heating coil to the magnetic nanoparticles in the thermal response module has a magnetic field strength less than or equal to 100 mT; and its frequency is greater than or equal to 1000 Hz.

[0052] For the magneto-thermal co-regulation capsule robot of the present invention, initially, the magnetic attraction force of the magnetic valve and the fixed magnetic attraction component is used to close the substance transmission window. Then, after reaching the target position, the high-frequency magnetic field applied by an external magnetic field excitation source such as a high-frequency induction heating coil is used to expand the thermal control air chamber to open the substance transmission window for drug delivery or biopsy sampling. Further, after the drug delivery or biopsy is completed, an external magnetic field excitation source such as a permanent magnet can be used to apply a magnetic field force perpendicular to the magnetic valve and inward to the magnetic valve, so that the magnetic valve switches from the open state to the closed state. Further, according to needs, the thermal control air chamber can be expanded by a high-frequency magnetic field to switch the magnetic valve to the open state, thus realizing the free switching between the open and closed states. In addition, the magnetic valve of the present invention is a magnetized magnetic valve. When the magnetization direction of the magnetic valve is a single radial magnetization, during use, when an external magnetic field excitation source such as a permanent magnet is used to apply a rotating magnetic field to the magnetic valve, the magnetic valve can drive the entire capsule robot to move to the target position under the drive of the rotating magnetic field, for targeted drug delivery and active tissue fluid biopsy functions. Further, during the drug delivery or biopsy sampling process, the current frequency in the high-frequency induction heating coil can also be reduced to a low frequency, and an alternating magnetic field can be applied to control the up and down beating frequency of the magnetic valve, thereby accelerating or slowing down the exchange rate between the drug and the outside (or the exchange rate between the tissue fluid and the loading cavity).

[0053] In some embodiments, the loading cavity includes a plurality of sub-loading cavities symmetrically arranged up and down. The side walls of the symmetrically arranged sub-loading cavities are symmetrically provided with the substance transmission window, the magnetic valve, and the fixed magnetic attraction component; a thermal response module is arranged inside each sub-loading cavity to realize bilateral transmission or exchange of substances, thereby making it possible to mix multiple drugs.

[0054] In some embodiments, the fabrication of the magneto-thermal co-regulation capsule robot of the present invention includes the following steps:

[0055] (1) The capsule shell and the thermal control air chamber are respectively printed and prepared by using a stereolithography 3D printing technology; the capsule shell can be divided into an upper shell and a lower shell, and they are printed and prepared separately.

[0056] (2) A mixed solution of a low-boiling-point phase-change liquid and magnetic nanoparticles is injected into the thermal control air chamber made by 3D printing technology by using a syringe, and finally the injection needle opening is sealed.

[0057] (3) Place the processed thermal control gas chamber into the loading cavity of the lower housing, and arrange the fixed magnetic attraction assembly around the material transmission window so that the fixed magnetic attraction assembly and the surface of the material transmission window are on the same plane or curved surface;

[0058] (4) Use a pulsed magnetization device to magnetize the magnetic valve axially as a whole to obtain a magnetic valve magnetized in a single radial direction; then cover the magnetized magnetic valve on the plane or curved surface where the fixed magnetic attraction assembly and the material transmission window are located, and seal and bond the upper housing and the lower housing to obtain the capsule robot.

[0059] The method for controllable drug delivery using the capsule robot of the present invention specifically includes the following steps: when the capsule robot containing drugs reaches the lesion site through the control of an external rotating magnetic field, since the thermal control gas chamber is in the unopened state, the fixed magnetic attraction assembly and the magnetic valve keep the material transmission window sealed well through magnetic attraction force, and the drug is in the unreleased state; at this time, use an external magnetic field excitation source to apply an alternating high-frequency magnetic field outside the human body, so that the low-boiling-point phase-change liquid in the thermal control gas chamber expands due to heat, and the continuous expansion of the thermal control gas chamber causes the free end of the magnetic valve to open, resulting in the release of the drug in the loading cavity to the lesion area. And the magnetic valve can also be repeatedly closed and opened by repeatedly changing the magnetic field direction of the external magnetic field excitation source in the magnetic drive module, so as to accelerate the full release of the drug.

[0060] The method for biopsy sampling using the capsule robot of the present invention includes the following steps: control the capsule robot to reach the biopsy target area through a rotating magnetic field, use an external magnetic field excitation source to apply an alternating high-frequency magnetic field outside the human body to expand the thermal control gas chamber, and the free end of the magnetic valve bends upward due to the pressure inside the loading cavity, and the material transmission window opens, so that the tissue fluid in the specified area enters the loading cavity. When enough tissue fluid is extracted in the loading cavity, apply a magnetic field acting force perpendicular to the inside (pointing to the inside of the capsule) to the magnetic valve using a permanent magnet, so as to close the magnetic valve, that is, the active biopsy function of the specified area is completed.

[0061] When the capsule robot of the present invention is used for controlled drug delivery, the substance transmission window is the drug delivery window, and the loading cavity is the drug-loading cavity. The magnetic valve provided therein can also drive the directional movement of the capsule robot and accelerate the release of the internal drug under the action of the magnetic field driving module, and it is arranged outside the fixed magnetic attraction component. The thermal control air chamber is used to control the opening and closing of the magnetic valve. When the thermal control air chamber does not expand due to heat, the air pressure on both sides of the magnetic valve is in a balanced state, so as to ensure that the drug inside the capsule does not exchange with the outside; when an external magnetic field such as a high-frequency induction heating coil of the magnetic drive module acts, the magnetic nanoparticles in the thermal control air chamber cause the low-boiling liquid in the thermal control air chamber to undergo gas-liquid phase change due to wireless heating. At this time, the magnetic valve changes from the closed state to the open state, so the drug in the drug-loading cavity can reach the lesion area in the human body through the drug delivery window. Further, in order to accelerate the release of the drug in the human tissue, the magnetic field direction of the magnetic field driving control module can be repeatedly changed to repeatedly close and open the magnetic valve. For example, the frequency of the high-frequency induction heating coil can be reduced to a low frequency (the frequency is 20-30 Hz), and then an alternating magnetic field with alternating positive and negative magnetic field directions is applied to make the magnetic valve alternately open and close, and the flapping action of the magnetic valve is used to accelerate the exchange of the drug solution and the internal tissue fluid of the human body, thereby greatly improving the drug delivery efficiency.

[0062] On the other hand, if the capsule robot is used for active biopsy, the role of the thermal control air chamber is to open the magnetic valve when the capsule robot reaches the lesion area, so as to extract the tissue fluid in the specified area; and the magnetic valve can wirelessly control the capsule robot to move directionally and accelerate the extraction of the tissue fluid in the specified target area through an external magnetic field. When the thermal response module does not work, the air pressure inside and outside the magnetic valve remains balanced, thus ensuring that the inside of the loading cavity is isolated from the external environment; when the magnetic drive module applies a high-frequency magnetic field, the magnetic nanoparticles in the thermal control air chamber cause the low-boiling liquid in the thermal control air chamber to undergo gas-liquid phase change due to wireless heating. At this time, the magnetic valve changes from the closed state to the open state, and the substance transmission window opens, so that the tissue fluid in the specified area enters the loading cavity. When enough tissue fluid is extracted in the loading cavity, the external magnetic field of the external magnetic field excitation source of the magnetic drive module is reversed to close the magnetic valve, that is, the active biopsy function of the specified area is completed. Further, the capsule robot that has extracted the tissue fluid can be directionally moved out of the body through a rotating magnetic field.

[0063] The method for the capsule robot of the present invention to achieve fixed-point drug delivery and biopsy can not only use methods such as imaging equipment assistance, magnetic positioning, or gastrointestinal peristalsis timing monitoring commonly used in the prior art to achieve fixation, but also drive the capsule shell to move directionally by applying an external magnetic field to the magnetized magnetic valve and reach the target position.

[0064] The internal system structure and control method of the magnetic-thermal synergistic regulation capsule robot of the present invention are both simple. Through the coordinated control of the thermal response module and the magnetic drive module, the on-demand fixed-point drug delivery and biopsy functions of the capsule robot are cleverly realized, and the drug delivery progress can be accelerated and slowed down by controlling the amplitude and frequency of the externally applied excitation field current. In addition, the design of multiple drug delivery channels provides the possibility of window opening in any magnetic field direction and on-demand mixed drug delivery of multiple drugs. Combining the advantages of strong magnetic manipulation penetration ability and unrestricted action area, the capsule robot provided by the present invention provides a new technical path for the multifunctionalization of capsule robots.

[0065] In some embodiments, such as Figure 1 shown, a magnetic-thermal synergistic regulation capsule robot for controllable drug delivery or biopsy includes a robot body, and the robot body includes a capsule shell. When manufacturing the capsule shell, first use Solidworks software to construct a three-dimensional model of the capsule shell, then export the three-dimensional model as an STL file, and then put the exported file into a slicing software for processing and then into a 3D printer for printing and manufacturing. Considering the safety of the capsule robot, the capsule shell is printed and manufactured using a material MED610 with good biocompatibility. The capsule shell is composed of two hemispherical hollow air chambers 5a, a hollow cylindrical loading cavity 5b (i.e., drug loading cavity), and a mass exchange window 5c, as Figure 1 shown in content (e); wherein the two hemispherical hollow air chambers 5a are used to adjust the density of the capsule robot, and the floating and sinking of the capsule robot are realized by adjusting the solution dose in the loading cavity, ensuring that the capsule robot has a strong ability to carry drugs.

[0066] A groove 5d is provided on the outer wall of the loading cavity, and the mass transfer window 5c is located at the bottom of the groove 5d and protrudes upward, as Figure 1 shown in content (e); the fixed magnetic attraction component, that is, the magnetic attraction plate 3a, is provided with a middle through hole 3b in the middle (as Figure 1 shown in content (c)), and the middle through hole 3b of the magnetic attraction plate 3a is sleeved on the mass transfer window 5c in the groove and their surfaces are flush; the magnetized magnetic valve 2a covers and is arranged on the plane where the mass transfer window 5c and the magnetic attraction plate 3a are located through magnetic attraction in the groove, so that the mass transfer window 5c is in a closed state, as Figure 1 shown in content (a).

[0067] The magnetic attraction plate 3a is made of a magnetic soft material. Specifically, a pre-prepared mixture of NdFeB magnetic particles and silica gel is evenly added to a mold, and it is placed in an incubator at 70 °C for curing. After it is completely cured, demolding is carried out to obtain the manufactured magnetic attraction plate. After being manufactured, it is sleeved around the mass transfer window 5c and assembled and sealed; the magnetic valve 2a is a magnetized magnetic valve, and its magnetization direction after magnetization is asFigure 1 The single radial magnetization 2b in content (b) is shown. The magnetic force valve 2a is made of a magnetic soft material, is covered and arranged on the plane where the magnetic attraction plate 3a and the material transmission window 5c are located, and is hermetically attached to the magnetic attraction plate 3a by magnetic attraction force to close the material transmission window 5c. One end of the magnetic force valve 2a is fixedly connected to the capsule shell by an adhesive AA3211 UV glue, and the other end is not fixed and is a free end.

[0068] The magnetic force valve 2a is a magnetically controlled soft material. The specific manufacturing method is as follows: a pre-prepared mixture of NdFeB magnetic particles and silica gel is evenly added to a mold, and it is placed in an incubator at 70 °C for curing. After it is completely cured, demolding is carried out to obtain the manufactured magnetic force valve 2a. After being magnetized by a magnetizing device, under the drive of an external magnetic field permanent magnet, it can be subjected to a magnetic torque so that the capsule robot can achieve remote wireless control.

[0069] As Figure 1 As shown in content (a) and content (d), the magneto-thermal cooperative regulation capsule robot includes a thermal control gas chamber 4 and a low-boiling-point phase-change liquid absolute ethanol 4a and magnetic nanoparticles Fe3O4 4b located inside the thermal control gas chamber 4. The thermal control gas chamber 4 is a gas chamber printed from a soft material Ecoflex0030 4c. An injection channel 4d is also arranged on the thermal control gas chamber 4. The injection channel 4d can be used to inject the low-boiling-point phase-change liquid absolute ethanol 4a and the magnetic nanoparticles Fe3O4 4b into the thermal control gas chamber 4 as needed. The low-boiling-point phase-change liquid 4a is mainly used as a thermal response phase-change switch. When the temperature of the gas chamber rises due to the high-frequency magnetic field applied by the magnetic field driving module for the iron oxide particles in the thermal control gas chamber 4, the low-boiling-point phase-change liquid changes from a liquid state to a gaseous state, causing the volume of the thermal control gas chamber to increase.

[0070] In some examples, the process schematic diagrams of the magneto-thermal cooperative regulation capsule robot before releasing the drug and after releasing the drug after directional movement are as Figure 2As shown in content (a), content (b), content (c) and content (d). First, under the control of an external rotating magnetic field (provided by permanent magnet 6), the robotic body of the capsule robot causes the magnetic valve 2a to move directionally following the rotation of the external magnetic field due to the magnetic torque. As the permanent magnet 6 moves, the capsule body 1 continuously moves from point A in the small intestine 8 to point B, then passes through point C, and finally reaches the target point D. After that, the applied external rotating magnetic field is removed. At this time, the high-frequency heating magnetic field 9 (magnetic field intensity is 20 mT, frequency is 100 kHz) in the magnetic drive module is turned on. After a period of time, the magnetic nanoparticles 4b in the thermal control chamber 4 cause the low-boiling-point phase-change liquid 3M7000 to undergo liquid-gas phase change due to electromagnetic induction heating, and the volume of the thermal control chamber changes sharply, resulting in the air pressure in the drug-loading cavity of the capsule body being much greater than the external environment of the capsule. Therefore, the internal and external air pressure difference causes the free end of the magnetic valve 2a to bend and deform, and the mass exchange window 5c is in an open state. At this time, the drug 7 in the drug-loading cavity 5b is administered through the mass exchange window 5c. At this time, the frequency of the induction heating coil is reduced to about 20 Hz, and the magnetic valve is repeatedly closed and opened by repeatedly changing the magnetic field direction of the induction heating coil, which enables the solution near the capsule body to move continuously, thus accelerating the full release of the drug.

[0071] In some other embodiments, the above capsule robot is used for active biopsy, and the process schematic diagram is as Figure 3 shown. As Figure 3 shown in content (a), after the capsule robot reaches the biopsy target area through the rotating magnetic field (provided by permanent magnet 6), the high-frequency heating magnetic field 9 (magnetic field intensity is 20 mT, frequency is 100 kHz) in the magnetic drive module is turned on. After a period of time, the magnetic nanoparticles 4b in the thermal control chamber 4 cause the low-boiling-point phase-change liquid (Novec 7000, boiling point 49 °C) to undergo liquid-gas phase change due to electromagnetic induction heating, and the volume of the thermal control chamber 4 changes sharply, resulting in the air pressure in the drug-loading cavity of the capsule body being much greater than the external environment of the capsule. The free end of the magnetic valve 2a bends and deforms to open the mass exchange window 5c, as Figure 3 shown in content (b); at this time, the frequency of the applied excitation magnetic field 9 is reduced to about 20 Hz, and the magnetic valve is repeatedly closed and opened by repeatedly changing the magnetic field direction of the induction heating coil, which enables the tissue fluid near the capsule body to move continuously, so that the tissue fluid 10 in the specified area enters the loading cavity, as Figure 3 shown in content (c). After a period of time, when the temperature in the thermal control chamber drops, the volume of the thermal control chamber will shrink back to the initial size again. When enough tissue fluid is extracted in the loading cavity 5b, a magnetic field force perpendicular to the magnetic valve and inward can be applied to the magnetic valve through an external magnetic field excitation source such as a permanent magnet, so as to close the magnetic valve, as Figure 3 shown in content (d), that is, the active biopsy function is completed.

[0072] Through the collaborative control of thermal response and magnetic drive, the present invention realizes the functions of on-demand and fixed-point drug delivery and biopsy of the magnetic-thermal collaborative regulation capsule robot. The drug delivery device has a simple and lightweight structure, and the capsule can be remotely turned on and off repeatedly through an alternating magnetic field, with the advantages of wireless drive and strong controllability, and has certain potential medical value.

[0073] Those skilled in the art can easily understand that the above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, and improvements made within the spirit and principle of the present invention should be included within the protection scope of the present invention.

Claims

1. A magnetic-thermal collaborative regulation capsule robot, characterized in that, It includes a robot body and a magnetic drive module, where: The robot body includes a capsule housing. Hollow air chambers are respectively arranged at both ends of the capsule housing. A loading cavity is arranged between the hollow air chambers, and the loading cavity is isolated from the hollow air chambers; A material transmission window, a magnetic valve, and a fixed magnetic attraction assembly are arranged on the side wall of the loading cavity. The magnetic valve is a magnetized magnetic valve. The magnetized magnetic valve and the fixed magnetic attraction assembly are arranged in cooperation through magnetic attraction force to close the material transmission window. One end of the magnetic valve is fixedly connected to the capsule housing, and the other end is a free end; A thermal response module is arranged inside the loading cavity. The thermal response module includes a thermal control air chamber, magnetic nanoparticles, and a low-boiling-point phase-change liquid located inside the thermal control air chamber; The magnetic drive module is used to apply a high-frequency magnetic field to the magnetic nanoparticles in the thermal response module; During use, the magnetic drive module applies a high-frequency magnetic field to the magnetic nanoparticles in the thermal response module under the action of an external magnetic field excitation source, so that the temperature inside the thermal control air chamber rises, further causing the low-boiling-point phase-change liquid to vaporize and turn into a gas state, and making the volume of the thermal control air chamber increase. As the volume of the thermal control air chamber continues to increase, the pressure difference between the inside and outside of the loading cavity gradually becomes larger until the free end of the magnetized magnetic valve breaks away from the attraction of the fixed magnetic attraction assembly, opening the magnetic valve, and then enabling material transmission or exchange between the loading cavity and the external environment.

2. The capsule robot according to claim 1, characterized in that, The material transmission window is one or more openings protruding outward from the inner wall of the loading cavity. The fixed magnetic attraction assembly is arranged around the opening, and the magnetized magnetic valve is arranged on the surface of the side of the fixed magnetic attraction assembly away from the loading cavity through magnetic attraction force.

3. The capsule robot according to claim 2, characterized in that, A groove is formed on the outer wall of the loading cavity. The material transmission window is located at the bottom of the groove and protrudes upward. An intermediate through hole is arranged on the fixed magnetic attraction assembly, and the fixed magnetic attraction assembly is sleeved on the material transmission window through the intermediate through hole in the groove; the magnetized magnetic valve covers the plane or curved surface where the material transmission window and the fixed magnetic attraction assembly are located through magnetic attraction force in the groove, so that the material transmission window is in a closed state.

4. The capsule robot according to claim 1, characterized in that, The fixed magnetic assembly is made of a magnetic material, the magnetic valve is made of a magnetic soft material, and the thermal control air chamber is made of an expandable soft material.

5. The capsule robot according to claim 1, characterized in that, The magnetization direction of the magnetized magnetic valve is a single radial magnetization.

6. The capsule robot according to claim 1, characterized in that, The magnetic nanoparticles are Fe3O4; the low-boiling-point phase-change liquid is anhydrous ethanol or 3M7000.

7. The capsule robot according to claim 1, characterized in that, The external magnetic field excitation source is a high-frequency induction heating coil.

8. The capsule robot according to claim 7, characterized in that, The magnetic field intensity of the high-frequency magnetic field applied by the high-frequency induction heating coil to the magnetic nanoparticles in the thermal response module is less than or equal to 100 mT; its frequency is greater than or equal to 1000 Hz.

9. The capsule robot according to claim 1, characterized in that, The external magnetic field excitation source further includes a permanent magnet; the permanent magnet is used to apply an external magnetic field to the magnetized magnetic valve, so that the magnetized magnetic valve moves to a target position under the action of a magnetic torque; and / or to switch the magnetized magnetic valve from an open state to a closed state under the action of a magnetic torque.

10. The capsule robot according to claim 1, characterized in that, The object-carrying cavity includes a plurality of sub-object-carrying cavities, and the material transmission window, the magnetic valve, and the fixed magnetic attraction assembly are arranged on the side wall of each sub-object-carrying cavity; the thermal response module is arranged inside each sub-object-carrying cavity.

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