CN116269518A - Magnetic control capsule robot with controllable drug delivery and biopsy functions and manufacturing method thereof - Google Patents

Abstract

The invention belongs to the technical field of magnetically controlled soft robots, and in particular relates to a magnetically controlled capsule robot with controllable drug delivery and biopsy functions and a manufacturing method thereof. The invention provides a magnetic control capsule robot, which comprises a robot body and a magnetic field driving control module, wherein the robot body comprises a capsule shell, hollow air chambers are respectively arranged at two ends of the capsule shell, and a carrying cavity is arranged between the hollow air chambers respectively arranged at two ends; the side wall of the object carrying cavity is provided with a substance transmission channel, a magnetic attraction lock arranged around the substance transmission channel and a magnetic switch valve matched with the magnetic attraction lock. The internal system structure and the regulation and control method of the magnetically controlled capsule robot are simple. The controllable drug delivery and biopsy functions of the magnetic control capsule robot are skillfully realized through the bidirectional magnetic control of the magnetic attraction force and the magnetic moment. The magnetically controlled capsule robot provided by the invention provides a brand new technical path for the multifunction of the capsule robot by combining the advantages of strong magnetic control penetrating capability and unlimited action area.

Description

Magnetic control capsule robot with controllable drug delivery and biopsy functions and manufacturing method thereof

Technical Field

The invention belongs to the technical field of magnetically controlled soft robots, and in particular relates to a magnetically controlled capsule robot with controllable drug delivery and biopsy functions and a manufacturing method thereof.

Background

The oral administration is the most commonly adopted administration mode of the drug therapy, but the drug effect is easily influenced by gastrointestinal environment, namely, the first pass effect exists, so that the drug administration efficiency and the application scene are greatly reduced. How live bacteria such as probiotics can resist gastric acid, digestive enzyme and bile and keep activity to reach target organs becomes key to the efficacy of the live bacteria. In addition, part of the drug release in non-target areas is a potential hazard to the human body.

In order to reduce systemic side effects of drugs on humans and to improve the local therapeutic effects of drugs, innovative drug delivery devices and on-demand drug delivery control methods have received extensive attention and research by students. Such as Chinese patent number: CN112604146a discloses an implantable drug delivery device based on pulsed magnetic field triggering, the drug delivery device comprises a drug storage shell, a magnetic piston component and a magnetic fixed base component, the invention uses magnetic field as an external excitation source, and has the advantages of safety, innocuity, high responsiveness and the like, however, the component material density is higher, the processing requirement on the mechanical structure is higher, and the defects of high capsule density and limited movement rate exist. Furthermore, the drug delivery of the drug delivery device relies solely on the osmotic action of the drug itself to reach a designated target area, which requires a longer time for drug delivery.

Patent specification with publication number CN114306901a discloses a drug-carrying capsule and an implantable drug delivery device comprising the same, wherein the drug and a biocompatible photosensitive material are mixed, and a solid-liquid two-phase integrated photo-curing three-dimensional printing technology is used to mold the drug-encapsulating capsule in one step. The medicine capsules are extruded and exploded one by driving the magnet in the medicine feeding equipment, so that the fixed-point release of medicines is realized, the multi-medicine-room structure is set, and the on-demand combined release of multiple kinds of medicines can be realized. However, the conical tip in its drug-loaded capsule presents a safety risk to tissues and organs within the patient's body, and the directional movement of the magnet tends to cause an overall deflection of the entire drug-loaded capsule, so achieving accurate drug release presents a challenge.

In view of the advantages of infinite freedom, strong deformability, high adaptability and the like of the magnetically controlled soft robot driven by the externally applied magnetic field. Therefore, the advantages of wireless control and strong penetrability of the magnetic control soft robot are integrated into the drug delivery capsule with drug delivery and biopsy functions, and the magnetic control capsule robot with simpler structure, higher controllability and higher control efficiency is hopeful to be realized, so that the magnetic control soft robot has very important clinical medical value.

Disclosure of Invention

Aiming at the defects of the prior art, the invention aims to provide a magnetic control capsule robot with controllable drug delivery and biopsy functions and a manufacturing method thereof, so as to solve the problems of low drug delivery efficiency, complex capsule structure and control, insufficient safety degree and the like of the magnetic control capsule robot in the prior art.

In order to achieve the above purpose, the invention provides a magnetically controlled capsule robot, comprising a robot body and a magnetic field driving control module; wherein:

the robot body comprises a capsule shell, wherein hollow air chambers are respectively arranged at two ends of the capsule shell, a carrying cavity is arranged between the hollow air chambers, and the carrying cavity is isolated from the hollow air chambers;

a material transmission channel, a magnetic attraction lock arranged around the material transmission channel and a magnetic switch valve matched with the magnetic attraction lock are arranged on the side wall of the material carrying cavity; the magnetic switch valve is a magnetized magnetic switch valve; the material transmission channel is used for enabling the material carrying cavity to carry out material transmission or exchange with the external environment under the state that the magnetic switch valve is opened; the magnetic attraction lock and the magnetized magnetic switch valve are matched through magnetic attraction force, so that the magnetic switch valve is in a closed state, and the object carrying cavity and the external environment are kept in an isolated state when the magnetic control capsule robot does not work;

the magnetic field driving control module is used for applying magnetic field acting force to the magnetized magnetic switch valve under the action of an external magnetic field excitation source so as to realize the opening or closing of the magnetic switch valve.

Preferably, the substance transmission channel is one or more openings arranged on the side wall of the capsule shell in a protruding way towards the inside or the outside of the capsule, a magnetic attraction lock recess is formed between the periphery of the opening and the side wall of the capsule shell, and the magnetic attraction lock recess is used for fixedly arranging the magnetic attraction lock; when the magnetic switch valve is in a closed state, the magnetic switch valve covers the surfaces of the magnetic attraction lock and the material transmission channel and is used for closing the material transmission channel so as to isolate the material carrying cavity from the external environment; the magnetic switch valve can deform under the control of the magnetic field driving control module to enable the substance transmission channel to reach an open state, so that the substance transmission or exchange is carried out between the substance carrying cavity and the external environment.

Preferably, the magnetization direction of the magnetized magnetic switch valve is unidirectional magnetization or symmetrical magnetization with opposite directions at two ends; when the magnetic switch valve is used, magnetic field acting force is applied to the magnetized magnetic switch valve under the action of an external magnetic field excitation source, so that the magnetized magnetic switch valve deforms under the action of magnetic moment, and the opening of the magnetic switch valve is realized.

Preferably, the external magnetic field excitation source is a permanent magnet or a helmholtz coil.

Preferably, the carrying cavity comprises two or more independent mutually isolated sub-carrying cavities, and the side wall of each sub-carrying cavity is provided with the substance transmission channel, a magnetic attraction lock arranged around the substance transmission channel and a magnetic switch valve matched with the magnetic attraction lock so as to realize multi-channel transmission or exchange of substances.

According to another aspect of the present invention, there is provided a method for manufacturing the magnetically controlled capsule robot, comprising the steps of:

(1) Dividing the capsule shell into a base and a top cover, and respectively preparing the base and the top cover of the capsule shell by adopting a photo-curing 3D printing technology;

(2) The magnetic attraction lock is fixedly arranged at the periphery of a substance transmission channel arranged on the side wall of the object carrying cavity of the capsule shell; and the magnetized magnetic switch valve is matched with the magnetic attraction lock, and then the base and the top cover of the magnetic control capsule robot are packaged to obtain the magnetic control capsule robot.

In general, the above technical solutions conceived by the present invention have the following compared with the prior art

The beneficial effects are that:

(1) The invention provides a magnetic control capsule robot with drug delivery and biopsy functions, which comprises a robot body and a magnetic field driving control module; wherein: the robot body comprises a capsule shell, wherein hollow air chambers are respectively arranged at two ends of the capsule shell, and a carrying cavity is arranged between the hollow air chambers respectively arranged at two ends; the side wall of the carrying cavity is provided with a substance transmission channel, a magnetic attraction lock arranged around the substance transmission channel and a magnetic switch valve matched with the magnetic attraction lock through magnetic attraction. The system structure and the regulating method in the capsule are simple. The system skillfully realizes the controllable drug delivery and biopsy functions of the magnetic control capsule robot through the bidirectional magnetic control of the magnetic attraction force and the magnetic moment, has no complicated mechanical structure, and has higher safety by adopting a magnetic control mode. The magnetic control capsule robot is used for drug delivery and biopsy sampling, and has the advantages of no pain, no wound, no anesthesia, no cross infection risk and the like.

(2) The invention is easy to realize quantitative fixed-point accurate drug delivery of the magnetic control capsule robot. In the preferred embodiment of the invention, the applied excitation magnetic field is generated by the Helmholtz coil, and on one hand, the opening angle of the magnetic switch valve can be controlled by adjusting the amplitude of the current in the Helmholtz coil, so that the size of the application window can be controlled; on the other hand, the up-down beating frequency of the magnetic switch valve can be controlled by regulating and controlling the frequency of the current in the Helmholtz coil, so that the exchange rate of the medicine and the outside is accelerated or slowed down. Therefore, the magnetic control capsule robot provided by the invention can not only accelerate the release of the medicine, but also slow down the release of the medicine through the adjustment of the current amplitude and the frequency in the exciting coil, thereby realizing the accurate release of the medicine and having higher controllability.

(3) The capsule robot control method provided by the invention adopts a magnetic control method and has the characteristic of remote wireless driving. Due to the advantages of strong magnetic field penetrating capability and unrestricted action area, the magnetic control capsule robot can realize accurate quantitative and timed drug application and active biopsy functions, and greatly improves drug application efficiency and drug application stability of the drug. Furthermore, the double sided dosing channel design provides the possibility of window opening for arbitrary magnetic field direction and on-demand mixed dosing of multiple drugs.

(4) Can realize the multi-functional reuse. In the invention, the closing and opening processes of the drug delivery channel of the magnetic control capsule robot are mutually independent, and when the drug in the drug delivery cavity is released or the fixed-point biopsy function is completed, the magnetic control capsule robot can be recycled after being disinfected again, so that the concept of saving resources is better practiced.

(5) The two ends of the capsule shell of the magnetic control capsule robot are respectively provided with the hollow air chambers, the density of the whole magnetic control capsule robot can be reduced by the hollow air chambers, the whole density of the magnetic control capsule robot can be regulated and controlled by regulating the size of the hollow air chambers, the floating and sinking of the capsule robot can be realized by regulating the solution dosage in the object carrying cavity, and the capsule robot is ensured to have stronger capability of carrying medicines.

(6) The magnetic attraction lock and the magnetic switch valve in the magnetic control capsule robot form a switch of the magnetic control capsule robot, and the magnetic attraction lock and the magnetic switch valve are both made of magnetic soft materials. The magnetic attraction between the magnetic attraction lock and the magnetic switch valve is used for closing the drug release valve or tissue fluid suction valve of the magnetic control capsule, and the opening and closing of the magnetic switch valve and the opening sizes corresponding to different deformation degrees are realized by combining the regulation and control of an external magnetic field, so that the controllable drug release and active biopsy functions of the magnetic control capsule robot are realized.

Drawings

Fig. 1 is a schematic three-dimensional structure of a robot body of a magnetically controlled capsule robot according to an embodiment of the present invention: fig. 1 content (a) is a housing of a robot body; fig. 1 content (b) is a top cover of the robot body, and fig. 1 content (c) is a base of the robot body;

fig. 2 is a schematic diagram of the working principle of the magnetically controlled capsule robot provided by the invention when the magnetically controlled capsule robot is not used for drug administration and drug release: FIG. 2 (a) is a schematic three-dimensional structure of the magnetic control capsule when not administered; FIG. 2 (b) is a schematic three-dimensional structure of the magnetic control capsule for releasing drug; FIG. 2 (c) is a graph showing experimental results when the magnetically controlled capsule is not administered; FIG. 2 (d) is a graph showing the experimental results of the release of the drug from the magnetically controlled capsule;

fig. 3 is a schematic diagram of a magnetization and magnetizing circuit structure of a magnetic switch valve of the magnetically controlled capsule robot provided by the embodiment of the invention;

fig. 4 is a schematic diagram of a bidirectional magnetic switch valve according to an embodiment of the present invention: FIG. 4 (a) is a three-dimensional block diagram of a bi-directional magnetic switch valve; fig. 4 (b) is a schematic diagram of operation in the forward magnetic field; FIG. 4 (c) is a schematic diagram of operation in the reverse magnetic field;

fig. 5 is a schematic diagram of a drug delivery process of the magnetically controlled capsule robot provided by the embodiment of the invention under different external excitation: FIG. 5 (a) shows the absence of an externally applied magnetic field; FIG. 5 (b) shows an externally applied magnetic field; FIG. 5 (c) shows the switching off of the applied magnetic field; fig. 5 (d) shows the applied magnetic field being turned on again.

Detailed Description

The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.

The invention provides a magnetic control capsule robot, which comprises a robot body and a magnetic field driving control module; wherein: the robot body comprises a capsule shell, wherein hollow air chambers are respectively arranged at two ends of the capsule shell, a carrying cavity is arranged between the hollow air chambers respectively arranged at two ends, and the carrying cavity is isolated from the hollow air chambers; a material transmission channel, a magnetic attraction lock arranged around the material transmission channel and a magnetic switch valve matched with the magnetic attraction lock are arranged on the side wall of the material carrying cavity; the magnetic switch valve is a magnetized magnetic switch valve; the material transmission channel is used for transmitting or exchanging materials between the material carrying cavity and the external environment in the state that the magnetic switch valve is opened; the magnetic attraction lock and the magnetized magnetic switch valve are matched through magnetic attraction force, so that the magnetic switch valve is in a closed state, and the object carrying cavity and the external environment are in an isolated state when the magnetic control capsule robot does not work.

The magnetic field driving control module is used for applying magnetic field acting force to the magnetized magnetic switch valve under the action of an external magnetic field excitation source so as to realize the opening or closing of the magnetic switch valve; when the magnetic switch valve is opened, the material transmission channel can be used for transmitting or exchanging materials between the material carrying cavity and the external environment.

In some embodiments, the capsule shell is manufactured by using a photo-curing 3D printing technology, and various printing modes can be adopted, for example, the capsule shell can be divided into a base and a top cover, and the base and the top cover are respectively printed and then assembled. The capsule shell is made of medical rubber, medical plastic and other materials which have good biological safety and are not influenced by stomach and intestine environments such as gastric acid, and can be made of MED610, transparent fluorescent-free resin materials and the like.

The invention discloses a magnetic control capsule robot, which comprises a capsule shell, wherein hollow air chambers are respectively arranged at two ends of the capsule shell, a carrying cavity is arranged between the hollow air chambers arranged at two ends, and the carrying cavity and the hollow air chambers at two sides of the carrying cavity are in an isolated state. The carrying cavity is positioned in the capsule shell, and when the magnetic switch valve is in a closed state, the carrying cavity is a closed space which is used for storing the drug solution or storing the biopsy tissue. The material transmission channel arranged in the magnetic control capsule robot is used as a medicine or tissue fluid exchange window between the internal object carrying cavity and the external environment, so that when the magnetic switch valve is opened, medicine in the object carrying cavity can reach a focus area through the material transmission channel, or tissue fluid in a target area enters the object carrying cavity, and an active biopsy function is realized.

In some embodiments, the substance transmission channel is one or more openings on the side wall of the capsule shell, which are arranged to protrude towards the inside or the outside of the capsule, and the periphery of the opening and the side wall of the capsule shell form a magnetic attraction lock recess, and the magnetic attraction lock recess is used for fixedly arranging the magnetic attraction lock; when the magnetic switch valve is in a closed state, the magnetic switch valve covers the surfaces of the magnetic attraction lock and the material transmission channel and is used for closing the material transmission channel so as to isolate the material carrying cavity from the external environment; the magnetic switch valve can deform under the control of the magnetic field driving control module to enable the substance transmission channel to reach an open state, so that the substance transmission or exchange is carried out between the substance carrying cavity and the external environment.

In some embodiments, the magnetization direction of the magnetized magnetic switch valve is unidirectional magnetization or symmetrical magnetization with opposite directions of two ends, so as to control the opening and closing of the magnetic switch valve. When the magnetic switch valve is used, magnetic field acting force is applied to the magnetized magnetic switch valve under the action of an external magnetic field excitation source, so that the magnetized magnetic switch valve deforms under the action of magnetic moment, and the opening of the magnetic switch valve is realized.

In some embodiments, when the magnetization direction is unidirectional along one direction, the deformation becomes a side opening with one end tilted; when the magnetization direction is symmetrical magnetization with opposite directions of both ends, the deformation becomes curled from both ends to the middle.

In some embodiments, the magnetic switch valve is magnetized by a pulse magnetizing module, and the pulse magnetizing module may include a pulse power supply, a magnetizing coil, a discharge capacitor, a discharge switch, a freewheel loop and a magnetizing die; the pulse power supply is used for providing oscillation damping or sine half-wave pulse current for the magnetizing coil; the magnetizing coil is used for magnetizing the magnetic switch valve; the discharge capacitor is used for storing electric energy; the discharge switch is used for triggering a conduction discharge loop, so that pulse current provided by the discharge capacitor can flow into the magnetizing coil; the free-wheeling loop comprises a free-wheeling diode and a free-wheeling resistor and is used for adjusting current waveforms; the magnetizing mould is used for fixedly arranging the magnetic switch valve; when the pulse magnetizing module works, a magnetizing die provided with the magnetic switch valve is arranged inside the magnetizing coil; when oscillation damping or sine half-wave pulse current is introduced into the magnetizing coil, a strong pulse magnetic field is generated in the inner space of the coil, so that the magnetic switch valve arranged in the magnetizing die is subjected to non-oscillation magnetizing or oscillation demagnetizing. When the freewheel resistor is small (can be as low as 0), the discharge current is in a non-oscillating waveform, and a non-oscillating magnetic field can be generated after the discharge current flows into the coil for magnetizing the magnetic switch valve.

The magnetic attraction lock and the magnetic switch valve form a switch of the magnetic capsule robot, which are all made of magnetic materials, wherein the magnetic switch valve is made of permanent magnetic materials (such as NdFeB and C) _r O ₂ The magnetic particles) and soft materials (such as silica gel, TPE material, hydrogel and other materials with the elastic modulus of GPa below) are prepared, and the magnetic soft composite material is prepared; the magnetic attraction lock is made of permanent magnetic materials and non-magnetic materials (such as silica gel, TPE materials, hydrogel and the like) with the dimensions of micron-sized or below, and the permanent magnetic materials and the non-magnetic materials have wider selection range because the magnetic attraction lock does not need to be deformed, wherein the permanent magnetic materials can be NdFeB magnetic particles, ferromagnetic particles and the like, and the non-magnetic materials can be soft or hard materials. In some embodiments, uniformly adding the prefabricated mixed solution of the magnetic attraction lock into a magnetic attraction lock mold, placing the magnetic attraction lock mold in an incubator at 70 ℃ for curing, and demolding after the magnetic attraction lock is completely cured to obtain the manufactured magnetic attraction lock; the preparation of the magnetic switch valve is the same.

The magnetic attraction lock is arranged in the magnetic attraction lock recess at the periphery of the material transmission channel in the magnetic control capsule robot, the surface of the magnetic attraction lock is flush with the surface of the material transmission channel, the magnetic switch valve is arranged on the surfaces of the magnetic attraction lock and the material transmission channel in a covering mode, and the magnetic attraction lock and the material transmission channel are bonded together in a sealing mode through magnetic attraction, so that the material transmission channel is sealed, and the material carrying cavity is isolated from the external environment. The magnetic attraction modes between the magnetic attraction lock and the magnetic switch valve can be two, wherein the magnetic attraction lock can be magnetized or not, for example, when the magnetic attraction lock is made of a permanent magnetic material, the magnetic attraction lock can not be magnetized, and the magnetic attraction similar to magnet attraction can be formed between the magnetic attraction lock and the magnetic switch valve; in a preferred embodiment, in order to further enhance the attractive force of the magnetic attraction lock and the magnetic switch valve, the magnetic attraction lock containing magnetic materials can be magnetized, so that the attractive effect similar to a permanent magnet is generated between the magnetic attraction lock and the magnetized magnetic switch valve.

In some embodiments, the magnetizing coil is wound by a flat copper wire, the periphery of the magnetizing coil is provided with a reinforcing material, and the central area of the coil skeleton of the magnetizing coil is hollow, so that a relatively uniform axial pulse magnetic field is generated in the central area when pulse current flows through the magnetizing coil to magnetize the magnetic switch valve.

In some embodiments, the two ends of the magnetic switch valve are symmetrically and reversely magnetized by adopting a die method, which is specifically as follows: the method comprises the steps of firstly symmetrically folding the processed magnetic switch valve, then placing the folded magnetic switch valve into a prefabricated magnetizing mould groove, and finally integrally placing a magnetizing mould carrying the magnetic switch valve into the magnetizing coil for integral axial magnetizing.

In some embodiments, the external magnetic field excitation source is a permanent magnet or a helmholtz coil.

In some embodiments, the external magnetic field excitation source applies a magnetic field acting force of 50 hz or less and 100mT or less to the magnetized magnetic switch valve, so that the magnetized magnetic switch valve deforms under the action of magnetic moment, and the opening of the magnetic switch valve is realized.

In some embodiments, the carrying cavity includes two or more independent sub-carrying cavities, and each side wall of the sub-carrying cavity is provided with the substance transmission channel, a magnetic attraction lock arranged around the substance transmission channel, and a magnetic switch valve matched with the magnetic attraction lock, so as to realize multi-channel transmission or exchange of substances.

In a preferred embodiment, the carrying cavity comprises sub-carrying cavities which are arranged up and down symmetrically, wherein the sub-carrying cavities are symmetrically provided with the substance transmission channel, a magnetic attraction lock which surrounds the substance transmission channel and a magnetic switch valve which is matched with the magnetic attraction lock, so that double-side transmission or exchange of substances is realized, and multiple medicines are possible to be mixed.

The invention also provides a manufacturing method of the magnetic control capsule robot, which comprises the following steps:

(1) The robot body of the magnetic control capsule robot is divided into a base and a top cover, and the base and the top cover of the capsule shell are respectively prepared by adopting a photocuring 3D printing technology;

(2) The magnetic attraction lock is fixedly arranged at the periphery of a substance transmission channel arranged on the side wall of the object carrying cavity of the capsule shell; and the magnetized magnetic switch valve is matched with the magnetic attraction lock, and then the base and the top cover of the magnetic control capsule robot are packaged to obtain the magnetic control capsule robot.

In some embodiments, the magnetic lock is embedded into a magnetic lock recess formed by the periphery of the substance transmission channel and the side wall of the capsule shell for fixing. Specifically, the material transmission channel arranged on the capsule shell of the magnetically controlled capsule robot can be one or more openings protruding towards the inside of the capsule and arranged on the side wall of the object carrying cavity of the capsule shell, or one or more openings protruding towards the outside of the capsule and arranged on the side wall of the object carrying cavity. When the opening is arranged to protrude inwards, the periphery of the opening and the inner wall of the capsule shell form a magnetic attraction lock recess, and at the moment, the magnetic attraction lock is embedded into the magnetic attraction lock recess formed by the periphery of the substance transmission channel and the inner wall of the capsule shell for fixing and arranging; when the opening is arranged to protrude outwards, the periphery of the opening and the outer wall of the capsule shell form a magnetic attraction lock recess, and at the moment, the magnetic attraction lock is embedded into the magnetic attraction lock recess formed by the periphery of the substance transmission channel and the outer wall of the capsule shell for fixing.

In some embodiments, step (2) firstly charges a discharge capacitor in the pulse magnetizing module, then triggers a discharge switch to discharge the magnetizing coil, generates a uniform axial magnetic field in a central region of the coil, and axially and integrally magnetizes the folded magnetic switch valve arranged in the magnetizing die to obtain the magnetic switch valve with two ends of which are symmetrically magnetized in opposite directions.

In some embodiments, in order to improve the controllability of the magnetic switch valve, the magnetized magnetic switch valve can be ensured to have higher remanence characteristics by improving the magnetizing voltage of the pulse power supply, so that the switching-on and switching-off capability of the magnetic switch valve is improved.

The method for controllably dosing by using the magnetic control capsule robot comprises the following steps: when the magnetic control capsule robot filled with the medicine reaches the focus, the medicine is in an unreleased state due to the magnetic attraction effect of the magnetic attraction lock on the magnetic switch valve; at the moment, an external magnetic field excitation source is used for applying a magnetic field outside a human body, so that two ends of the magnetic switch valve are subjected to magnetic moment action, the magnetic switch valve is opened, a medicine solution is released to a focus for administration, the magnetic field is reversed when the medicine is released or reaches the release amount, administration is stopped, and the magnetic switch valve can be repeatedly closed and opened by repeatedly changing the magnetic field direction of the external magnetic field excitation source in the magnetic field driving control module, so that the full release of the medicine is accelerated.

The method for taking the biopsy sample by using the magnetic control capsule robot comprises the following steps: when the magnetically controlled capsule robot reaches the biopsy target area, an external magnetic field excitation source is used for applying a magnetic field outside the human body, so that the two ends of the magnetic switch valve are subjected to magnetic moment to inwards bend and deform, and the substance transmission channel is opened, so that tissue fluid in a designated area enters the object carrying cavity. When enough tissue fluid is extracted from the object carrying cavity, the magnetic field of the magnetic field driving control module is reversed, so that the magnetic switch valve is closed, and the active biopsy function of the designated area is completed.

When the magnetic control capsule robot is used for controllable drug delivery, the substance transmission channel is a drug delivery channel, the drug carrying cavity is a drug carrying cavity, wherein the magnetic switch valve is used for releasing the drug in the magnetic control capsule robot, and the magnetic switch valve is arranged between the drug delivery channel and the drug carrying cavity. When the magnetic switch valve is in a closed state, namely the magnetic switch valve is subjected to the action of the gradient magnetic field force of the magnetic attraction lock, the medicine inside the magnetic control capsule is ensured not to exchange with the outside; when the external magnetic field of the magnetic field driving control module acts, the magnetic moment born by the magnetic switch valve is larger than the magnetic attraction force generated by the magnetic attraction lock, and the magnetic switch valve is changed from the closed state to the open state at the moment, so that the medicine in the medicine carrying cavity can reach the focus area in the human body through the medicine feeding channel. Furthermore, in order to accelerate the release of the medicine in the human tissue, the magnetic switch valve can be closed and opened by repeatedly changing the magnetic field direction of the magnetic field driving control module, and the beating action of the valve is utilized to accelerate the exchange of the medicine solution and the tissue fluid in the human body, so that the medicine feeding efficiency is improved to a great extent.

On the other hand, if the magnetically controlled capsule robot is used for active biopsy, the magnetic switch valve is used for opening a substance transmission channel when the magnetically controlled capsule reaches a focus area, so that tissue fluid in a designated area is extracted. When the magnetic field driving control module does not work, the magnetic switch valve is under the action of the magnetic attraction lock, so that the inside of the object carrying cavity is kept in an isolated state with the external environment; when the magnetic field driving control module applies an external magnetic field, the magnetic switch valve is bent and deformed inwards under the action of magnetic moment, and the substance transmission channel is opened, so that tissue fluid in a designated area enters the carrying cavity. When enough tissue fluid is extracted from the object carrying cavity, the externally applied magnetic field of the magnetic field driving control module is reversed, so that the magnetic switch valve is closed, and the active biopsy function of the designated area is completed.

The method for realizing fixed-point drug delivery and biopsy by the magnetic control capsule robot can adopt the methods of imaging equipment assistance, magnetic positioning or gastrointestinal peristalsis timing monitoring and the like which are conventionally used in the prior art to realize fixed points.

The internal system structure and the regulation method of the magnetic control capsule are simple, the functions of fixed-point drug delivery and biopsy according to the needs of the magnetic control capsule are skillfully realized through the bidirectional magnetic control of the magnetic attraction force and the magnetic moment, and the drug delivery progress can be accelerated and slowed down through controlling the amplitude and the frequency of the current of the externally applied excitation field. Furthermore, the double sided dosing channel design provides the possibility of window opening for arbitrary magnetic field direction and on-demand mixed dosing of multiple drugs. The magnetically controlled capsule robot provided by the invention provides a brand new technical path for the multifunction of the capsule robot by combining the advantages of strong magnetic control penetrating capability and unlimited action area.

In some embodiments, as shown in fig. 1, a magnetic control capsule robot for controllable drug delivery includes a robot body, where the robot body includes a capsule shell, and when the robot body is manufactured, a three-dimensional model of the capsule shell is firstly constructed by using Solidworks software, then the three-dimensional model is exported in STL files, and the exported files are put into slicing software for processing and then put into a 3D printer for printing and manufacturing. Considering the safety of the capsule robot, the capsule shell is printed and manufactured by adopting a material MED610 with better biocompatibility. In order to facilitate the assembly of the capsule robot, the capsule shell is divided into an upper part and a lower part, and the top cover 1 and the base 2 are formed as shown in the content (a) of fig. 1; after the magnetic switch valve and the magnetic attraction lock are assembled to the base 2, the upper part and the lower part of the capsule shell are subjected to sealing treatment; wherein the top cover 1 is of a semi-ellipsoidal structure and consists of two hemispherical hollow air chambers 1a and a semi-cylindrical dosing cavity 1b, as shown in the content (b) of fig. 1; the base 2 is shown in the content (c) of fig. 1, and consists of two hemispherical hollow air chambers 2a, a magnetic attraction locking groove 2b and a drug delivery channel 2 c; the number of the drug delivery channels 2c is 2, and the drug delivery channels are openings which are arranged on the inner wall of the capsule shell and protrude towards the inside of the capsule, and the periphery of the openings and the inner wall of the capsule shell form a recess, namely a magnetic attraction locking groove 2b.

As shown in fig. 2 (a), the magnetic lock 2d is embedded in the magnetic lock groove 2b to realize fixed arrangement, and the magnetized magnetic switch valve 2e covers the surfaces of the magnetic lock 2d and the substance transmission channel, namely the administration channel 2c, and is used for sealing the administration channel 2c so as to isolate the administration cavity (namely the carrying cavity) from the external environment; the magnetic switch valve 2e can be curled inwards from two ends to reach an open state under the control of the magnetic field driving control module, as shown in fig. 2 (b), and is used for opening the substance transmission channel, namely the drug administration channel 2c, so that the drug in the drug administration cavity is released to the external environment for drug transmission. The top cover 1 and the base 2 together form a capsule shell with the appearance of a capsule, and the capsule shell is processed by transparent resin material MED 610. The hollow air chamber in the capsule structure is used for reducing the density of the whole magnetic control capsule robot, and simultaneously, the capsule robot floats upwards and sinks through the adjustment of the solution dosage in the carrier cavity, so that the capsule robot is ensured to have stronger capability of carrying medicines.

In some embodiments, the pulse magnetizing module shown in fig. 3, namely, the magnetizing circuit structure is used to realize symmetrical magnetization of the magnetic switch valve, and specifically includes a discharge capacitor 3, a discharge switch 5, a magnetizing coil 7-3, a line impedance 6 (including a line resistor 6-1 and an inductor 6-2), a freewheel loop 4 (including a diode 4-1 and a freewheel resistor 4-2), and a magnetizing die 7-2. As shown in fig. 3, before discharging, the magnetic switch valve 2e is symmetrically folded to obtain the magnetic switch valve 2e in a folded state, then the magnetic switch valve 2e is placed inside the magnetizing die 7-2, and then the magnetizing die 7-2 and the magnetic switch valve 2e are integrally placed in the magnetizing coil 7-3 for magnetizing. Further, the capacitor 3 is charged, and then the discharge switch 5 is closed to discharge the magnetizing coil 7-3. Based on this, the central region of the magnetizing coil 7-3 generates a uniform pulsed magnetic field 7-1, which causes the particles in the magnetic switching valve to form radial magnetization distribution characteristics as shown at 9 (magnetization directions are shown at 9-1 and 9-2, respectively).

The schematic diagrams of the structure of the experimentally manufactured magnetically controlled capsule robot without releasing the medicine and after releasing the medicine are shown in fig. 2 content (c) and content (d). Firstly, the robot body of the magnetic control capsule robot reaches a focus through the peristaltic action of intestines and stomach of a human body, and the medicine is in an unreleased state due to the electromagnetic attraction action of the magnetic attraction lock 2d on the magnetic switch valve 2e, and a three-dimensional structure schematic diagram and an experimental result are respectively shown in a content (a) and a content (c) of fig. 3; at this time, the magnetic field 8 is applied outside the human body through the Helmholtz coil, so that the two ends of the magnetic switch valve 2e are subjected to the action of magnetic moment, the magnetic switch valve is opened, so that the drug solution is released to the focus for administration, the three-dimensional structure schematic diagram and the experimental result are shown in the content (b) and the content (d) of fig. 3, when the drug release is finished or the drug reaches the release amount, the magnetic field is reversed, the administration is stopped, and the magnetic switch valve can be repeatedly closed and opened by repeatedly changing the magnetic field direction of the control module, so that the full release of the drug is accelerated.

In some examples, the applied magnetic field 8 employed in the magnetic field drive control module to open and close the magnetic switch valve is generated by a helmholtz coil. Preferably, when the magnetic control capsule robot reaches a designated place and medicine is required to be released, sinusoidal pulse current is introduced into the Helmholtz coil, so that an oscillating magnetic field with alternating directions is generated to repeatedly open and close the magnetic switch valve; at the same time, the repeated oscillation of the magnetic switch valve can cause the accelerated flow of surrounding liquid, thereby further accelerating the release efficiency of the medicine.

In some embodiments, the magnetically controlled capsule robot is further designed into a double-sided dosing channel, namely, besides the dosing channel, the magnetic attraction lock and the magnetic switch valve are arranged on the base of the capsule shell, a set of magnetic attraction lock and magnetic switch valve are correspondingly arranged on the top cover at the upper part. As shown in fig. 4, content (a) is a schematic diagram of a two-channel robot body structure, content (b) is an upward magnetic field direction working schematic diagram and content (c) is a downward magnetic field direction working schematic diagram, wherein: 14a is an upper administration channel and 14b is a lower administration channel. The design can further improve the flexibility and the controllability of the magnetic control capsule robot. Specifically, when the upper magnetic switch valve 15a and the lower magnetic switch valve 15b are excited by an upward external magnetic field 15c, the upper magnetic switch valve 15a is in a closed state due to the constraint action of the capsule shell, and the lower magnetic switch valve 15b is under the action of magnetic moment so that the lower drug administration channel is opened to release the drug; conversely, when the upper magnetic switch valve 16a and the lower magnetic switch valve 16b are excited by an externally applied magnetic field 16c in a downward direction, the upper magnetic switch valve 16a acts on the magnetic moment to open the upper administration channel for releasing the drug, and the lower magnetic switch valve 16b is in a closed state under the constraint of the capsule housing. Based on the above analysis, the design of such a double-sided dosing channel ensures that the dosing channel on one side of the magnetically controlled capsule robot is always in an open state no matter under the action of a forward or reverse magnetic field, the structural design can further improve the dosing efficiency of the dosing capsule, and when a baffle is arranged between the top cover 1 and the base 2 of the capsule shell, the dosing cavity on the upper part and the dosing cavity on the lower part are isolated, different medicines can be placed in the upper dosing cavity and the lower dosing cavity, so that mixed dosing of different medicines is possible.

In other examples, in order to verify the practicability of the magnetically controlled capsule robot, a simulated drug administration experiment diagram of the magnetically controlled capsule robot is shown in fig. 5, and fig. 5 (a) shows that the magnetically controlled capsule robot carrying the drug is put into clear water, and it can be seen that the drug 17a in the magnetically controlled capsule 17b is not released into clear water when no external magnetic field is applied; when an externally applied magnetic field 18 is applied, the drug 17a is released through the drug delivery channel as shown in fig. 5 (b); further, when the externally applied magnetic field 18 is turned off, as can be seen from fig. 5 (c), the administration channel of the magnetically controlled capsule 17b is in a closed state, and no obvious permeation phenomenon of the drug 17a occurs; when the externally applied magnetic field 18 is further turned on, the medicine 17a in the magnetic control capsule 17b is released again into the external clean water environment, as shown in fig. 5 (d). The drug administration simulation experiment shows that the magnetic control capsule robot provided by the invention is expected to realize accurate quantitative and timed drug administration and has higher controllability.

In other embodiments, the magnetically controlled capsule robot described above is used for active biopsy. When the magnetically controlled capsule robot reaches the biopsy target area, an external magnetic field excitation source is used for applying a magnetic field outside the human body, so that the two ends of the magnetic switch valve are subjected to magnetic moment to inwards bend and deform, and the substance transmission channel is opened, so that tissue fluid in a designated area enters the object carrying cavity. When enough tissue fluid is extracted from the object carrying cavity, the magnetic field of the magnetic field driving control module is reversed, so that the magnetic switch valve is closed, and the active biopsy function of the designated area is completed.

The results fully prove that the magnetic control capsule realizes the functions of fixed-point drug delivery and biopsy according to the needs through the bidirectional magnetic control of magnetic attraction and magnetic moment, the drug delivery device has a simple and light structure, and the magnetic control capsule can be opened and closed repeatedly remotely through an alternating magnetic field, so that the magnetic control capsule has the advantages of wireless driving and strong controllability, and has certain medical potential value.

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

Claims (10)

1. The magnetic control capsule robot is characterized by comprising a robot body and a magnetic field driving control module; wherein:

the robot body comprises a capsule shell, wherein hollow air chambers are respectively arranged at two ends of the capsule shell, a carrying cavity is arranged between the hollow air chambers, and the carrying cavity is isolated from the hollow air chambers;

a material transmission channel, a magnetic attraction lock arranged around the material transmission channel and a magnetic switch valve matched with the magnetic attraction lock are arranged on the side wall of the material carrying cavity; the magnetic switch valve is a magnetized magnetic switch valve; the material transmission channel is used for enabling the material carrying cavity to carry out material transmission or exchange with the external environment under the state that the magnetic switch valve is opened; the magnetic attraction lock and the magnetized magnetic switch valve are matched through magnetic attraction force, so that the magnetic switch valve is in a closed state, and the object carrying cavity and the external environment are kept in an isolated state when the magnetic control capsule robot does not work;

the magnetic field driving control module is used for applying magnetic field acting force to the magnetized magnetic switch valve under the action of an external magnetic field excitation source so as to realize the opening or closing of the magnetic switch valve.

2. The magnetically controlled capsule robot of claim 1, wherein the material transfer channel is one or more openings on the side wall of the capsule housing protruding toward the inside or the outside of the capsule, and a magnetic latching recess is formed between the periphery of the opening and the side wall of the capsule housing, and the magnetic latching recess is used for fixedly arranging the magnetic latching;

when the magnetic switch valve is in a closed state, the magnetic switch valve covers the surfaces of the magnetic attraction lock and the material transmission channel and is used for closing the material transmission channel so as to isolate the material carrying cavity from the external environment; the magnetic switch valve can deform under the control of the magnetic field driving control module to enable the substance transmission channel to reach an open state, so that the substance transmission or exchange is carried out between the substance carrying cavity and the external environment.

3. The magnetically controlled capsule robot of claim 2, wherein the magnetization direction of the magnetized magnetic switch valve is unidirectional magnetization or symmetrical magnetization with opposite directions at two ends;

when the magnetic switch valve is used, magnetic field acting force is applied to the magnetized magnetic switch valve under the action of an external magnetic field excitation source, so that the magnetized magnetic switch valve deforms under the action of magnetic moment, and the opening of the magnetic switch valve is realized.

4. The magnetically controlled capsule robot of claim 3, wherein the magnetic switch valve is magnetized by a pulse magnetizing module, the pulse magnetizing module comprising a pulse power supply, a magnetizing coil, a discharge capacitor, a discharge switch, a freewheel loop and a magnetizing die; wherein,,

the pulse power supply is used for providing oscillation damping or sine half-wave pulse current for the magnetizing coil; the magnetizing coil is used for magnetizing the magnetic switch valve; the discharge capacitor is used for storing electric energy; the discharge switch is used for triggering a conduction discharge loop, so that pulse current provided by the discharge capacitor can flow into the magnetizing coil; the free-wheeling loop comprises a free-wheeling diode and a free-wheeling resistor and is used for adjusting current waveforms; the magnetization die is used for fixedly placing the magnetic switch valve;

when the pulse magnetizing module works, a magnetizing die with the magnetic switch valve arranged inside is arranged inside the magnetizing coil; when oscillation damping or sine half-wave pulse current is introduced into the magnetizing coil, a strong pulse magnetic field is generated in the inner space of the coil, so that the magnetic switch valve arranged in the magnetizing die is subjected to non-oscillation magnetizing or oscillation demagnetizing.

5. The magnetically controlled capsule robot of claim 4, wherein when the magnetic switch valve is magnetized by a mold method, the method comprises the following steps: the processed magnetic switch valve is placed in a prefabricated magnetizing die, and the magnetizing die with the magnetic switch valve is integrally placed in the magnetizing coil to be magnetized axially integrally, so that the magnetic switch valve with unidirectional magnetization direction is obtained;

when the magnetic switch valve is magnetized by adopting a die method, the two ends of the magnetic switch valve are symmetrically and reversely magnetized, and the method specifically comprises the following steps: the method comprises the steps of firstly symmetrically folding the processed magnetic switch valve, then placing the folded magnetic switch valve into a prefabricated magnetizing die, and finally integrally placing the magnetizing die carrying the magnetic switch valve into a magnetizing coil to axially magnetize the whole body to obtain the magnetic switch valve with the magnetization directions of two opposite ends and symmetrically magnetized.

6. The magnetically controlled capsule robot of claim 1, wherein the external magnetic field excitation source is a permanent magnet or a helmholtz coil.

7. The magnetically controlled capsule robot of claim 1, wherein the carrying cavities comprise two or more sub-carrying cavities which are independent and isolated from each other, and the side wall of each sub-carrying cavity is provided with the substance transmission channel, a magnetic attraction lock arranged around the substance transmission channel and a magnetic switch valve matched with the magnetic attraction lock so as to realize multi-channel transmission or exchange of substances.

8. The method of manufacturing a magnetically controlled capsule robot according to any one of claims 1 to 7, comprising the steps of:

(1) Dividing the capsule shell into a base and a top cover, and respectively preparing the base and the top cover of the capsule shell by adopting a photo-curing 3D printing technology;

(2) The magnetic attraction lock is fixedly arranged at the periphery of a substance transmission channel arranged on the side wall of the object carrying cavity of the capsule shell; and the magnetized magnetic switch valve is matched with the magnetic attraction lock, and then the base and the top cover of the magnetic control capsule robot are packaged to obtain the magnetic control capsule robot.

9. The method of claim 8, wherein the capsule shell is made of a medical polymer material, preferably medical rubber or medical plastic.

10. The method of claim 8, wherein the magnetic lock is made of a magnetic material and the magnetic switch valve is made of a magnetic soft material.

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