Magnetically-driven drug-loaded micro-robot with gas-assisted injection function and method

Abstract

The invention relates to a gas-assisted injection magnetic-driven drug-loading micro-robot and a method, the gas-assisted injection magnetic-driven drug-loading micro-robot comprises a spiral ferromagnetic driving structure, the spiral ferromagnetic driving structure is connected with a head through a connecting part, a cavity is formed in the head, an isolating layer is arranged in the cavity, and the isolating layer divides the cavity into a reaction liquid storage cabin and a drug-loading cabin; a plurality of first magnetic control ball valves, a plurality of second magnetic control ball valves and a plurality of third magnetic control ball valves are arranged on the outer wall of the reaction liquid storage cabin, the outer wall of the isolation layer and the outer wall of the medicine carrying cabin respectively, and a reaction layer is arranged on the inner wall of the medicine carrying cabin. According to the device, gas-assisted medicine injection can be achieved, and the medicine release efficiency is greatly improved.

Description

Technical Field

[0001] The invention belongs to the field of micro-nano robots, and in particular relates to a gas-assisted injection magnetically driven drug-carrying micro-robot and a method. Background Art

[0002] A microrobot is an artificial power device with a scale less than millimeters. It can absorb external energy and convert it into its own mechanical work, thereby completing special functional tasks in a small space. From the perspective of driving energy, microrobots can be divided into four types: external field drive, chemical drive, biological drive and hybrid drive. Among them, external field driven microrobots (such as light drive, electric field drive, ultrasonic drive, magnetic field drive) have shown great application potential in the fields of organ chips, bioengineering, trace detection, precision medicine, etc. due to their stable and controllable energy sources. Magnetic field drive is a typical external field drive method. The magnetic field has vector characteristics, and its size and direction can be precisely controlled. In addition, the magnetic field has the advantages of non-contact, non-toxic, and strong penetration, which has significant comparative advantages over other external field drive methods. At present, researchers have also developed various forms of magnetically driven microrobots, such as spiral, flapping wing, segmented, worm-shaped, etc., and have achieved good application demonstration effects.

[0003] Using magnetically driven microrobots to load drugs, and to control their transport and targeted release in narrow channels (such as blood vessels, organ chip channels, microfluidic channels, etc.) is one of the most common microrobot application scenarios. At present, although there are many solutions to achieve drug delivery by magnetically driven microrobots, they all face a common challenge and need to be continuously improved. That is, most of the drugs loaded by magnetically driven microrobots rely on the natural diffusion release of drug molecules, or are assisted by the reciprocating vibration of the robot in an external magnetic field. The release process is relatively slow and the efficiency is extremely low (usually tens of minutes to hours), which seriously weakens its application potential in emergency situations. In order to achieve the purpose of rapid release, there are also studies that adsorb drug molecules to the surface of magnetically driven microrobots through van der Waals forces, so that they are released directly from the surface. Although this may speed up the drug release process, it also brings contamination risks to the transport process. In order to avoid transport contamination, the robot surface needs to be re-sealed, which makes the drug loading process more complicated. Summary of the invention

[0004] The object of the present invention is to provide a gas-assisted injection magnetically driven drug-carrying microrobot and method, which can significantly improve the drug release efficiency by gas-assisted drug injection.

[0005] In order to solve the above problems, the technical solution of the present invention is: A gas-assisted injection magnetically driven drug-carrying microrobot comprises a spiral ferromagnetic drive structure, which is connected to a head via a connecting portion, a cavity is provided in the head, an isolation layer is provided in the cavity, the isolation layer separates the cavity into a reaction liquid storage cabin and a drug-carrying cabin, a plurality of first magnetically controlled ball valves, a second magnetically controlled ball valve and a plurality of third magnetically controlled ball valves are respectively provided on the outer wall of the reaction liquid storage cabin, the isolation layer and the outer wall of the drug-carrying cabin, and a reaction layer is provided on the inner wall of the drug-carrying cabin.

[0006] The first magnetically controlled ball valve, the second magnetically controlled ball valve and the third magnetically controlled ball valve are all made of ferromagnetic materials, and the magnetic moment pinning directions of the first magnetically controlled ball valve, the second magnetically controlled ball valve and the third magnetically controlled ball valve are the same as the directions of the through holes on the first magnetically controlled ball valve, the second magnetically controlled ball valve and the third magnetically controlled ball valve.

[0007] The reaction layer is a metal PT layer plated on the isolation layer.

[0008] The thickness of the metal PT layer is not less than 0.5 nanometers.

[0009] The through holes in the first magnetically controlled ball valve, the second magnetically controlled ball valve and the third magnetically controlled ball valve are elliptical in shape.

[0010] A plurality of assembly holes are arranged on the drug loading cabin, and each third magnetically controlled ball valve is assembled in each assembly hole. The axial directions of two adjacent assembly holes form an angle, which is greater than 20 degrees and less than 70 degrees.

[0011] A method for a magnetically driven drug-carrying microrobot with gas-assisted injection, comprising the following steps Step 1: Load the reaction liquid; apply a steady-state magnetic field perpendicular to the axis direction of the head, and the through-hole directions of the first magnetic-controlled ball valve, the second magnetic-controlled ball valve and the third magnetic-controlled ball valve will turn to the direction of the steady-state magnetic field. At this time, the first magnetic-controlled ball valve will be in an open state, and the micro-robot will be placed in a reaction liquid environment. The reaction liquid will be loaded into the reaction liquid storage cabin through the first magnetic-controlled ball valve; Step 2: loading the drug; rotating the direction of the external steady-state magnetic field toward the head to an angle of 20 to 70 degrees with the axis of the head, closing a third magnetically controlled ball valve located on the axis of the head, opening another third magnetically controlled ball valve, and closing the first magnetically controlled ball valve and the second magnetically controlled ball valve, stacking the microfluidic chip pipeline with solid ibuprofen medicine, placing the microrobot in the solid ibuprofen medicine, and applying a right-handed spiral magnetic field, the robot will spirally rotate in the solid medicine, and the auxiliary ibuprofen drug molecules will be loaded into the drug loading cabin through the opened third magnetically controlled ball valve; Step 3: Close all magnetically controlled ball valves; rotate the direction of the external steady-state magnetic field toward the spiral ferromagnetic drive structure to an angle of 20 to 70 degrees with the axis of the head. At this time, close the first magnetically controlled ball valve, the second magnetically controlled ball valve and the third magnetically controlled ball valve, apply a rotating magnetic field with a frequency greater than 5 Hz, and drive the robot to move to the target site for drug release; Step 4: Gas-assisted drug injection; after the microrobot reaches the target site, the direction of the external steady-state magnetic field is rotated to be parallel to the axis of the head. At this time, the second magnetically controlled ball valve and the third magnetically controlled ball valve will be opened. In this state, the reaction liquid molecules will flow to the drug loading compartment through the second magnetically controlled ball valve, and react with the reaction layer at the bottom of the loading compartment to generate gas. The gas expands and pushes the drug molecules to the third magnetically controlled ball valve, thereby realizing gas-assisted drug injection.

[0012] The beneficial effects of the present invention are: 1. The present invention sets different flow directions for the magnetically controlled ball valve, so that although the magnetically controlled ball valve has the same movement behavior under the external magnetic field, it can produce different opening and closing effects, which is very beneficial for loading the reaction solution and drug molecules in steps.

[0013] 2. By reacting the reaction liquid with the precious metal Pt to produce gas, gas-assisted drug injection can be achieved, thereby greatly improving the drug release efficiency of the microrobot.

[0014] 3. All steps are triggered by magnetic fields, enabling remote control of the microrobot. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The present invention will be further described below in conjunction with the accompanying drawings: Figure 1 It is a structural schematic diagram of the present invention, Figure 2 This is a schematic diagram of the structure of a ferromagnetic magnetically controlled ball valve according to the present invention. Figure 3 This is a schematic diagram of the cross-sectional structure of the medicine loading cabin of the present invention. Figure 4 This is a schematic diagram of the isolation layer structure of the present invention. Figure 5 It is a schematic diagram of the main process of the method of the present invention.

[0016] In the figure: spiral ferromagnetic drive structure 100, connecting part 200, isolation layer 300, head 400, storage compartment 401, drug loading compartment 402, reaction layer 500, first magnetically controlled ball valve 601, second magnetically controlled ball valve 602, third magnetically controlled ball valve 603, magnetic moment pinning direction 701, head axis 702, steady-state magnetic field direction 703, reaction liquid molecules 901, drug molecules 902, oxygen bubbles 903. DETAILED DESCRIPTION

[0017] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0018] like Figures 1 to 4 As shown, a gas-assisted injection magnetically driven drug-carrying microrobot includes a spiral ferromagnetic drive structure 100, which is connected to a bullet-shaped head 400 via a connecting portion 200, a cavity is provided in the head 400, an isolation layer 300 is provided in the cavity, and the isolation layer 300 separates the cavity into a storage cabin 401 and a drug-carrying cabin 402, two first magnetically controlled ball valves 601, a second magnetically controlled ball valve 602 and two third magnetically controlled ball valves 603 are respectively provided on the outer wall of the storage cabin 401, the isolation layer 300 and the outer wall of the drug-carrying cabin 402, and a reaction layer 500 is provided on the inner wall of the drug-carrying cabin 402.

[0019] The overall length of the micro robot is greater than 1 micron and less than 1 millimeter; the spiral ferromagnetic drive structure 100 is made of hard magnetic material, and the spiral ferromagnetic drive structure 100 includes at least one complete spiral, the spiral direction is a right-hand spiral, and the ratio of the pitch to the spiral radius is less than 5:1.

[0020] The first magnetically controlled ball valve 601, the second magnetically controlled ball valve 602 and the third magnetically controlled ball valve 603 have the same structure. The first magnetically controlled ball valve 601, the second magnetically controlled ball valve 602 and the third magnetically controlled ball valve 603 are all made of magnetic materials, such as cobalt-iron-boron or cobalt-iron-iron. The magnetic moment pinning direction 701 of the first magnetically controlled ball valve 601, the second magnetically controlled ball valve 602 and the third magnetically controlled ball valve 603 is the same as the direction of the through hole 610 on the first magnetically controlled ball valve 601, the second magnetically controlled ball valve 602 and the third magnetically controlled ball valve 603.

[0021] The reaction layer 500 is a metal PT layer plated on the isolation layer 300. The thickness of the metal PT layer is not less than 0.5 nanometers.

[0022] The through holes 610 in the first magnetically controlled ball valve 601, the second magnetically controlled ball valve 602 and the third magnetically controlled ball valve 603 are elliptical in shape. This structure can break the rotational symmetry of the magnetically controlled ball valves.

[0023] The first magnetically controlled ball valve 601, the second magnetically controlled ball valve 602 and the third magnetically controlled ball valve 603 are respectively assembled in the first assembly hole, the second assembly hole and the third assembly hole, the axis of the first assembly hole is perpendicular to the head axis 702, the axis of the second assembly hole is parallel to the head axis 702, one of the two third assembly holes is coaxial with the head axis 702, and the axis direction of the other third assembly hole forms an angle with the head axis 702, and the angle is 45°.

[0024] like Figure 5 As shown, a method for gas-assisted injection of a magnetically driven drug-carrying microrobot comprises the following steps: Step 1: Loading the reaction liquid; the micro robot is transferred to the microfluidic pipe 800 filled with hydrogen peroxide, and a steady-state magnetic field is applied perpendicular to the direction of the head axis 702. The through holes 610 of the first magnetically controlled ball valve 601, the second magnetically controlled ball valve 602 and the third magnetically controlled ball valve 603 will be turned to the direction of the steady-state magnetic field 703. At this time, the first magnetically controlled ball valve 601 will be in an open state, and the hydrogen peroxide reaction liquid molecules 901 will be loaded into the storage compartment 401 through the first magnetically controlled ball valve 601; Step 2: loading the drug; rotating the external steady-state magnetic field direction 703 toward the head 400 to form an angle of 45° with the head axis 702, closing a third magnetically controlled ball valve 603 located on the head axis 702, opening another third magnetically controlled ball valve 603, and closing the first magnetically controlled ball valve 601 and the second magnetically controlled ball valve 602, then stacking solid ibuprofen medicine in the microfluidic chip pipeline 800, placing the microrobot in the solid ibuprofen medicine, and applying a right-handed spiral magnetic field with a frequency greater than 5 Hz (due to the hysteresis of the magnetically controlled ball valve in response to the high-frequency spiral magnetic field, the high-frequency spiral magnetic field does not affect the opening and closing of the magnetically controlled ball valve), the robot will spirally rotate in the solid medicine, and the auxiliary ibuprofen drug molecules 902 will be loaded into the drug loading cabin 402 by the opened third magnetically controlled ball valve 603; Step three: Close all magnetically controlled ball valves; rotate the external steady-state magnetic field direction 703 toward the spiral ferromagnetic drive structure 100 to form an angle of 45° with the head axis 702. At this time, close the first magnetically controlled ball valve 601, the second magnetically controlled ball valve 602 and the third magnetically controlled ball valve 603, transfer the robot into the microfluidic chip pipeline 800 where the drug needs to be delivered, apply a right-handed rotating magnetic field with a frequency greater than 5 Hz, and select the direction of rotation of the magnetic field according to the planned path to drive the robot to the target site for drug release.

[0025] Step 4: Gas-assisted drug injection: After the microrobot reaches the target site, the external steady-state magnetic field direction 703 is rotated to be parallel to the head axis 702. At this time, the second magnetically controlled ball valve 602 and the third magnetically controlled ball valve 603 will be opened. In this state, hydrogen peroxide molecules will flow to the drug loading cabin 402 through the second magnetically controlled ball valve 602, and react with the metal PT layer in the drug loading cabin 402 to generate oxygen bubbles 903. This redox reaction occurs very quickly, and a large amount of oxygen expands, which will push the solid ibuprofen molecules out of the third magnetically controlled ball valve 603, realizing oxygen-assisted drug injection in the robot.

[0026] The contents described in the embodiments of this specification are merely an enumeration of the implementation forms of the inventive concept. The protection scope of the present invention should not be regarded as limited to the specific forms described in the embodiments. The protection scope of the present invention also extends to equivalent technical means that can be conceived by those skilled in the art based on the inventive concept.

Claims

1. A gas-assisted injection magnetically driven drug-carrying microrobot, characterized in that: The invention comprises a spiral ferromagnetic drive structure (100), wherein the spiral ferromagnetic drive structure (100) is connected to a head (400) via a connecting portion (200), wherein a cavity is provided in the head (400), wherein an isolation layer (300) is provided in the cavity, wherein the isolation layer (300) separates the cavity into a storage cabin (401) and a drug loading cabin (402), wherein a plurality of first magnetically controlled ball valves (601), a second magnetically controlled ball valve (602) and a plurality of third magnetically controlled ball valves (603) are respectively provided on the outer wall of the storage cabin (401), the isolation layer (300) and the outer wall of the drug loading cabin (402), and a reaction layer (500) is provided on the inner wall of the drug loading cabin (402).

2. The gas-assisted injection magnetically driven drug-carrying microrobot according to claim 1, characterized in that: The first magnetically controlled ball valve (601), the second magnetically controlled ball valve (602) and the third magnetically controlled ball valve (603) are all made of ferromagnetic materials, and the magnetic moment pinning directions (701) of the first magnetically controlled ball valve (601), the second magnetically controlled ball valve (602) and the third magnetically controlled ball valve (603) are the same as the directions of the through holes (610) on the first magnetically controlled ball valve (601), the second magnetically controlled ball valve (602) and the third magnetically controlled ball valve (603).

3. The gas-assisted injection magnetically driven drug-carrying microrobot according to claim 1, characterized in that: The reaction layer (500) is a metal PT layer plated on the isolation layer (300).

4. The gas-assisted injection magnetically driven drug-carrying microrobot according to claim 3, characterized in that: The thickness of the metal PT layer is not less than 0.5 nanometers.

5. A gas-assisted injection magnetically driven drug-carrying microrobot according to any one of claims 1 to 4, characterized in that: The through holes (610) in the first magnetically controlled ball valve (601), the second magnetically controlled ball valve (602) and the third magnetically controlled ball valve (603) are elliptical in shape.

6. A gas-assisted injection magnetically driven drug-carrying microrobot according to any one of claims 1 to 4, characterized in that: The first magnetically controlled ball valve (601), the second magnetically controlled ball valve (602) and the third magnetically controlled ball valve (603) are respectively assembled in the first assembly hole, the second assembly hole and the third assembly hole, the axis of the first assembly hole is perpendicular to the axis of the head (400), the axis of the second assembly hole is parallel to the axis of the head (400), one of the plurality of third assembly holes is coaxial with the axis of the head (400), and the axis directions of the other third assembly holes form an angle with the axis of the head (400), and the angle of the angle is greater than 20 degrees and less than 70 degrees.

7. A method for using the gas-assisted injection magnetically driven drug-carrying microrobot according to claim 6, characterized in that: The steps include: Step 1: loading the reaction liquid; applying a steady-state magnetic field perpendicular to the axis direction of the head (400), the through holes (610) of the first magnetically controlled ball valve (601), the second magnetically controlled ball valve (602) and the third magnetically controlled ball valve (603) will turn in the direction of the steady-state magnetic field (703), at which time the first magnetically controlled ball valve (601) will be in an open state, placing the micro robot in a reaction liquid (901) environment, and the reaction liquid (901) will be loaded into the storage compartment (401) through the first magnetically controlled ball valve (601); Step 2: loading the medicine; rotating the direction of the external steady-state magnetic field (703) toward the head (400) to an angle of 20 to 70 degrees with the axis of the head (400), closing a third magnetically controlled ball valve (603) located on the axis of the head (400), opening the other third magnetically controlled ball valves (603), and closing the first magnetically controlled ball valve (601) and the second magnetically controlled ball valve (602), placing the micro robot in the medicine, and applying a right-handed spiral magnetic field, the robot will spirally rotate in the medicine, and the auxiliary medicine molecules (902) will be loaded into the medicine loading chamber (402) through the opened third magnetically controlled ball valve (603); Step 3: Close all magnetically controlled ball valves; rotate the external steady-state magnetic field direction (703) toward the spiral ferromagnetic drive structure (100) to an angle of 20 to 70 degrees with the axis of the head (400). At this time, close the first magnetically controlled ball valve (601), the second magnetically controlled ball valve (602) and the third magnetically controlled ball valve (603), apply a rotating magnetic field with a frequency greater than 5 Hz, and drive the robot to move to the target site for drug release; Step 4: Gas-assisted injection of medicine; After the microrobot reaches the target site, the direction of the external steady-state magnetic field (703) is rotated to be parallel to the axis of the head (400). At this time, the second magnetically controlled ball valve (602) and the third magnetically controlled ball valve (603) will be opened. In this state, the reaction liquid molecules (901) will flow into the drug loading chamber (402) through the second magnetically controlled ball valve (602) and react with the reaction layer (500) in the drug loading chamber (402) to generate gas. The gas expands into bubbles and pushes the drug molecules (902) to flow toward the third magnetically controlled ball valve (603), thereby achieving gas-assisted drug injection.

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