A kind of micro robot cluster targeted drug delivery system and method of magnetoacoustic composite drive

Abstract

This invention discloses a magnetoacoustic composite-driven microrobot cluster targeted drug delivery system and method, belonging to the field of micro-nano robotics technology. It includes multiple helical microrobot units, each consisting of a magnetically responsive elastomer body, a drug loading cavity, and an acoustically responsive interface layer; a rotating magnetic field generator for generating a rotating magnetic field and magnetic field gradient; an ultrasonic standing wave field generator for generating an ultrasonic standing wave field; and a control unit. This invention utilizes the aforementioned magnetoacoustic composite-driven microrobot cluster targeted drug delivery system and method to achieve efficient cluster displacement, targeted residence, and controllable drug release in low Reynolds number biofluid environments.

Description

Technical Field

[0001] This invention relates to the field of micro-nano robotics, and in particular to a magnetoacoustic composite driven microrobot cluster targeted drug delivery system and method. Background Technology

[0002] Targeted drug delivery is one of the core technologies of precision medicine. Microrobots, with their micrometer- to millimeter-scale feature size and flexible movement capabilities, hold the promise of overcoming the bottlenecks of traditional drug delivery methods in terms of spatial accessibility, local drug concentration, and systemic toxicity. In recent years, significant progress has been made in driving microrobots to complete drug delivery or local intervention tasks using external driving sources (such as magnetic fields, light fields, and sound fields).

[0003] Among various propulsion methods, magnetic propulsion stands out as the most promising approach for clinical translation due to its advantages such as good biocompatibility, deep penetration, and remote, non-invasive control. Magnetic propulsion utilizes alternating magnetic fields to control the movement of magnetic materials, enabling helical propulsion or wave-like deformation propulsion. Existing studies have reported on the precise navigation of magnetically controlled microrobots in physiological flow environments and the ability to trigger drug release via high-frequency magnetic fields.

[0004] In terms of acoustic actuation, sound fields drive microrobots through ultrasonic radiation, acoustic flow, or acoustic cavitation effects, with standing wave field manipulation enabling micrometer-level positioning. Research shows that sound waves can serve as a control medium for microrobots, enabling self-organization and collective intelligent behavior in robot swarms.

[0005] In terms of swarm collaboration, existing research has proposed navigation and control strategies for magnetically controlled microrobot swarms, enabling adaptive and precise operation in fluid environments.

[0006] Existing technologies have the following main shortcomings when applied to clinical applications of in vivo targeted drug delivery: First, the driving efficiency and displacement sufficiency are insufficient. In low Reynolds number biological fluid environments (such as blood and lymph), inertial forces almost disappear, and viscous forces dominate the dynamic behavior. In traditional single magnetic field-driven helical or wave propulsion modes, the overall displacement velocity of microrobot swarms is limited, and the propulsion efficiency is usually less than 5%. Existing research lacks a systematic multiphysics (magnetism-elasticity-fluidity-acoustics) coupling model to quantitatively analyze and optimize the displacement efficiency of swarms in viscoelastic fluids.

[0007] Second, swarm control and targeted stationarization are challenging. Under a globally uniform magnetic field signal, all robots within the workspace receive the same control input, making it difficult to achieve differentiated and precise control of large-scale swarms. Furthermore, once the swarm reaches the target, how to manage blood flow shear forces (approximately 1~10 dyn / cm) remains a significant hurdle. 2To achieve stable residence, prevent being washed away, and form sufficient coverage of the lesion area in an environment of 0.1~1 Pa, existing technologies lack quantitative theoretical analysis and control strategies. Summary of the Invention

[0008] The purpose of this invention is to provide a magnetoacoustic composite driven microrobot cluster targeted drug delivery system and method to solve the problems of insufficient efficiency of single drive, difficulty in cluster control, insufficient displacement in low Reynolds number fluids, and lack of effective constraints on targeted residence in the prior art.

[0009] To achieve the above objectives, the present invention provides a magnetoacoustic composite driven microrobot swarm targeted drug delivery system, comprising: Multiple microrobot units, each microrobot comprising a magnetically responsive body, a drug-carrying cavity, and an acoustically responsive interface; A rotating magnetic field generator is used to generate a controllable rotating magnetic field and magnetic field gradient. An ultrasonic standing wave field generator is used to generate an ultrasonic sound field capable of exerting acoustic radiation force on a cluster of microrobots. The control unit is used to execute hierarchical control strategies.

[0010] Preferably, the magnetically responsive elastomer body of the microrobot is composed of magnetic particles and PDMS elastomer, with the volume fraction of magnetic particles being 10% to 20% and the elastic modulus being 50 kPa to 200 kPa; the microrobot has a helical shape with a helical radius of 20 μm to 100 μm, a pitch of 50 μm to 200 μm, and a total length of 100 μm to 500 μm.

[0011] Preferably, the rotating magnetic field generator includes three sets of orthogonal Helmholtz coils and three sets of orthogonal Maxwell coils, generating a magnetic field amplitude of 5mT to 15mT, a rotation frequency of 5Hz to 15Hz, and a magnetic field gradient of 1T / m to 5T / m.

[0012] Preferably, the ultrasonic standing wave field generating device includes two opposing ultrasonic transducer arrays with an operating frequency of 1MHz to 5MHz and a sound pressure amplitude of 100kPa to 300kPa.

[0013] A method for targeted drug delivery using a cluster of microrobots driven by a magnetoacoustic composite mechanism, comprising the following steps: S1. Introducing a cluster of microrobots into a fluid environment; S2. Apply a rotating magnetic field through a rotating magnetic field generator to drive the cluster to move toward the target area; S3. Monitor the cluster position in real time. When the distance between the cluster centroid and the target area is less than a preset threshold, it is determined that the target area has been reached. S4. Turn off or reduce the rotating magnetic field, and turn on the ultrasonic standing wave field through the ultrasonic standing wave field generator to constrain the cluster to the sound pressure node. S5. Apply a high-frequency alternating magnetic field to trigger drug release.

[0014] Preferably, the frequency of the rotating magnetic field in S2 is no greater than 0.8 times the maximum synchronization frequency, which is defined as follows: ; in, The maximum synchronization frequency, For the effective magnetic moment of a single microrobot, The amplitude of the rotating magnetic field. denoted as the rotational drag coefficient of the microrobot.

[0015] Preferably, in S2, the average displacement velocity of the microrobot satisfies: ; in, The average displacement velocity of the microrobot. The angular frequency of the magnetic field rotation. The step displacement is for a single rotation cycle. The rotation-translational coupling coefficient is... The pitch of the helix for a microrobot.

[0016] Preferably, the constraint capability of the ultrasonic stationary field in S4 is characterized by a constraint index, and the constraint index is not less than 10. The constraint index is defined as follows: ; in, To constrain the index, This represents the maximum potential energy of the acoustic radiation force. Boltzmann's constant, Body temperature.

[0017] Preferably, the high-frequency alternating magnetic field in S5 is generated by a rotating magnetic field generator with a frequency of 50kHz and an amplitude of 20mT, using a pulse mode; the robot temperature is raised to 42℃~45℃ through induction heating, triggering drug release.

[0018] Therefore, the present invention employs the above-mentioned magnetoacoustic composite driven microrobot cluster targeted drug delivery system and method, which has the following beneficial effects: (1) This invention achieves an average displacement velocity of 0.6~1.2 mm / s for the cluster through a magnetic-acoustic composite drive, which is about 2~3 times higher than the 0.2~0.5 mm / s driven by a single magnetic field. At a typical target distance of 50 mm, the delivery time is shortened to 1~2 minutes, meeting the time window requirements for rapid clinical intervention.

[0019] (2) The multi-physics field coupled dynamics model proposed in this invention accurately describes the force state of the microrobot in a low Reynolds number environment. By optimizing the dimensionless parameters, the propulsion efficiency reaches 15%~25%, which is significantly improved compared with the 5%~10% of the traditional design.

[0020] (3) This invention achieves directional aggregation (aggregation radius < 500 μm) and stable positioning (dwelling time > 300 seconds, displacement drift < 50 μm) of the cluster during the navigation phase and during the dwell phase through the coupling control mechanism of magnetic dipole interaction and acoustic field constraint.

[0021] (4) This invention provides the quantitative optimal range of key system parameters, which provides direct guidance for engineering implementation. All driving parameters meet the FDA biosafety limit requirements. The PDMS, NdFeB and other materials used have good biocompatibility, which lays the theoretical and experimental foundation for the clinical translation of the system.

[0022] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0023] Figure 1 This is an architecture diagram of a magnetoacoustic composite driven microrobot cluster targeted drug delivery system according to the present invention; Figure 2 This is a flowchart of a magnetoacoustic composite driven microrobot cluster targeted drug delivery method according to the present invention. Detailed Implementation

[0024] The following detailed description of embodiments of the invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely illustrates selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the invention without inventive effort are within the scope of protection of the invention.

[0025] Example like Figure 1 As shown, this invention provides a magnetoacoustic composite-driven microrobot swarm targeted drug delivery system, comprising: Multiple microrobot units, each microrobot comprising a magnetically responsive body, a drug-carrying cavity, and an acoustically responsive interface.

[0026] When a microrobot moves in a biological fluid (such as blood or cerebrospinal fluid), the characteristic Reynolds number is defined as... Blood density was measured. Characteristic velocity , characteristic length Dynamic viscosity Calculated Under low Reynolds number conditions, inertial forces are negligible, viscous forces dominate the dynamic behavior, and fluid motion is described by the Stokes equations. Therefore, the microrobot in this embodiment adopts a helical configuration, utilizing a rotating magnetic field to generate propulsion and overcome viscous drag.

[0027] The magnetically responsive elastomer body of the microrobot is composed of magnetic particles and PDMS elastomer. The magnetic particles are NdFeB with an average particle size of 5 μm and a saturation magnetization of [missing information]. The volume fraction of magnetic particles is 10%~20% (preferably 15% in this embodiment), and the elastic modulus is 50kPa~200kPa (measured value 100kPa in this embodiment). For hard magnetic materials, the magnetic moment is approximately constant after pre-magnetization. ,in The volume of the magnetic material. In this embodiment, the volume of the magnetic material... (percentage of total volume) Effective magnetic moment 。

[0028] The microrobot has a helical shape with a helical radius of 20μm–100μm (50μm in this embodiment), a pitch of 50μm–200μm (100μm in this embodiment), and a total length of 100μm–500μm (300μm in this embodiment). The equivalent radius of the main body is approximately 25μm. The drug-loading cavity, located on the robot's central axis, is cylindrical with a diameter of 15μm and a length of 200μm, and is used to load therapeutic drugs. The acoustic response interface layer is a P(VDF-TrFE) coating with a thickness of approximately 2μm, used to sense ultrasonic fields and generate acoustic radiation force responses.

[0029] Fabrication method of the microrobot: Magnetic particles and PDMS prepolymer were mixed in a selected ratio and degassed under vacuum for 30 minutes; a helical structure was directly written using femtosecond laser two-photon polymerization technology (laser wavelength 780nm, power 15mW, scanning speed 50μm / s), and thermosetting at 65℃ for 2 hours; pre-magnetization was performed along the long axis in a 1T strong magnetic field to obtain an effective magnetic moment of approximately 2.0×10⁻⁶. - 9 A·m 2 The acoustic response coating was applied by dip-coating and annealed at 80°C for 30 minutes. Finally, the drug (such as doxorubicin) was loaded into the drug loading chamber by microinjection, with a drug loading of approximately 50 pg / robot.

[0030] A rotating magnetic field generator is used to generate a controllable rotating magnetic field and magnetic field gradient. The generator includes three sets of orthogonal Helmholtz coils and three sets of orthogonal Maxwell coils, enabling independent control of the magnetic field vector and gradient. The Helmholtz coils have a diameter of 300 mm and 200 turns, used to generate a uniform rotating magnetic field; the Maxwell coils generate the magnetic field gradient. It is driven by a six-channel programmable power supply (maximum output ±10A, resolution 1mA). The generated magnetic field amplitude is 5mT to 15mT (10mT in this embodiment), the rotation frequency is 5Hz to 15Hz (10Hz in this embodiment), and the magnetic field gradient is 1T / m to 5T / m (2T / m in this embodiment).

[0031] The rotating magnetic field can be represented as in ω is the rotational angular frequency. The magnetic moment of the microrobot. Subjected to magnetic torque in an external magnetic field This torque drives the helical rotor to rotate. The propulsive force generated by the rotor's rotation balances the fluid resistance, giving the robot forward speed. Under low Reynolds number conditions, there is a coupling relationship between translational velocity and angular velocity; the propulsive speed can be approximated as... in For the translation-rotation coupling tensor, Let be the rotational resistance tensor.

[0032] An ultrasonic standing wave field generator is used to generate an ultrasonic sound field capable of applying acoustic radiation force to a cluster of microrobots. It includes two opposing ultrasonic transducer arrays (e.g., two transducer arrays placed opposite each other along the z-axis; it may further include two transducer arrays placed opposite each other along the y-axis), operating at a frequency of 1MHz to 5MHz and a sound pressure amplitude of 100kPa to 300kPa. By adjusting the phase and amplitude of each transducer, a stable distribution of sound pressure nodes and anti-nodes can be established in the target area, achieving three-dimensional constraint on the microrobot cluster.

[0033] In this embodiment, two opposing piezoelectric ultrasonic transducer arrays (center frequency 2.25MHz, diameter 25mm) are placed on opposite sides of the workspace and driven by a dual-channel signal generator (bandwidth 10MHz) and a power amplifier (gain 50dB). By adjusting the phase difference (0~2π) between the two arrays, the position of the sound pressure node can be moved axially.

[0034] In the ultrasonic standing wave field, the sound pressure distribution is as follows: in , The speed of sound in blood. For radius... Much smaller than wavelength For spherical particles, the acoustic radiation force can be described by Gorkov's potential energy theory: ,in , , is the scattering coefficient.

[0035] For a one-dimensional standing wave field, the potential energy simplifies to: in Define the acoustic contrast factor. when At that time, the particles move towards the sound pressure node. ( (Location) movement. In this embodiment, the acoustic contrast factor of the PDMS robot relative to blood. Therefore, the cluster is constrained to the sound pressure nodes.

[0036] The control unit executes a hierarchical control strategy; it is connected to the rotating magnetic field generator, the ultrasonic standing wave field generator, and the imaging feedback system. The imaging feedback system includes an inverted fluorescence microscope (10× objective) and a high-speed CMOS camera (200fps) for real-time tracking of the cluster's position.

[0037] like Figure 2 As shown, a method for targeted drug delivery using a cluster of microrobots driven by a magnetoacoustic composite actuation includes the following steps: S1. Introduce a cluster of microrobots into a fluid environment.

[0038] The prepared cluster of microrobots (numbering 10) 2 ~10 4 (500 samples in this embodiment) are suspended in simulated blood (viscosity) ,density In this procedure, a microfluidic channel (500 μm wide, 200 μm deep) is introduced via syringe. One end of the channel serves as the release point, and the other end as the target area, 50 mm apart. This operation is performed in an in vitro fluid model.

[0039] In this fluid environment, the Reynolds number Take a typical speed. , characteristic length Calculated This verifies the low Reynolds number condition. At this point, the fluid motion is governed by the Stokes equations. , Description. The hydrodynamic drag acting on a microrobot can be written as: ,in Let be the drag tensor. For a slender helix, the drag tensor is anisotropic: axial drag coefficient. Lateral drag coefficient Substitute ,have to The lateral resistance is approximately 1.9 times that of the axial resistance.

[0040] S2. Apply a rotating magnetic field through a rotating magnetic field generator to drive the cluster to move toward the target area; the control unit starts the rotating magnetic field generator, sets the magnetic field amplitude to 10mT, the rotation frequency to 10Hz, the magnetic field gradient to 2T / m, and applies a bias magnetic field of 5mT to control the direction of movement.

[0041] The frequency of the rotating magnetic field shall not exceed 0.8 times the maximum synchronization frequency, which is defined as follows: ; in, The maximum synchronization frequency, For the effective magnetic moment of a single microrobot, in this embodiment , The amplitude of the rotating magnetic field is shown in this embodiment. , denoted as the rotational drag coefficient of the microrobot.

[0042] The formula for calculating the rotational drag coefficient for slender spirals is as follows: ; Calculated Actual The requirements are met.

[0043] Driven by a rotating magnetic field, the microrobots generate axial propulsion through the interaction between their helical surfaces and the fluid. The average displacement velocity of the cluster satisfies: ; in, The average displacement velocity of the microrobot. The frequency of the magnetic field rotation is taken as ω. , The step displacement is for a single rotation cycle. The rotation-translational coupling coefficient is dimensionless; in this embodiment, it is taken as 0.65. The helical pitch of the microrobot is 100 μm in this embodiment. The calculated step displacement is 65 μm, and the average velocity... For a target distance of 50mm, the theoretical displacement time is approximately 77 seconds.

[0044] S3. Monitor the cluster position in real time. When the distance between the cluster centroid and the target area is less than a preset threshold, determine that the cluster has reached the target area.

[0045] Magnetic field gradient generated by Maxwell coils Apply a magnetic force to each robot: ; The force points in the direction of increasing magnetic field strength. The magnitude of the magnetic force is approximately... In low Reynolds number environments, a steady-state velocity is achieved when magnetic force and viscous drag are in equilibrium. Simultaneously, the magnetic gradient force causes the cluster to converge towards the center of the workspace, with a convergence radius of [missing information]. Substitute , ,have to This ensures that the cluster remains tightly clustered during navigation.

[0046] S4. Turn off or reduce the rotating magnetic field, and activate the ultrasonic standing wave field generator to confine the cluster to the sound pressure node. After reaching the target area, the control unit turns off the rotating magnetic field (or reduces its amplitude to below 2 mT), and then activates the ultrasonic standing wave field generator. Set the operating frequency to 2.25 MHz and the sound pressure amplitude to 200 kPa, and adjust the phase difference between the two sets of opposing ultrasonic transducer arrays to align the sound pressure node with the target area. The microrobot is confined to the vicinity of the sound pressure node under the action of acoustic radiation force.

[0047] The confinement capability of ultrasonic waves in a stationary field is characterized by a confinement index, which must be no less than 10. The confinement index is defined as the ratio of the maximum acoustic radiation potential energy to the thermal motion capability. ; in, To constrain the index, This represents the maximum potential energy of the acoustic radiation force. Boltzmann's constant, Body temperature.

[0048] According to Gor'kov's potential energy theory, for the robot in this embodiment (equivalent radius) 25 m acoustic contrast factor , ; Substitution , ,have to . ,body temperature ,but It is much larger than the threshold. (Constraint radius) .

[0049] The typical range of shear stress on the blood vessel wall is 1~10 dyn / cm 2 (i.e., 0.1~1 Pa). The fluid drag force acting on a single robot is: ; Pick Projected area drag coefficient ,have to The normal component of acoustic radiation force Static friction coefficient Maximum static friction Still greater than Therefore, the cluster can remain stably hosted.

[0050] S5. Apply a high-frequency alternating magnetic field to trigger drug release.

[0051] In the stationary state, the control unit again generates a high-frequency alternating magnetic field via a rotating magnetic field generator (no additional hardware required). The high-frequency alternating magnetic field has a frequency of 50 kHz and an amplitude of 20 mT, operating in pulse mode (50% duty cycle). Magnetic particles inside the robot experience hysteresis loss in the alternating magnetic field, inductively heating the robot to 42℃~45℃. This temperature rise triggers a volume phase change in the thermally responsive polymer (such as PNIPAM) sealing the drug delivery chamber, opening the chamber and releasing the drug into the target area. The drug release rate can be precisely controlled by adjusting the pulse duty cycle or the duration of action. After release, all driving fields are shut off, and the robot can gradually degrade or be expelled with the bloodstream.

[0052] Propulsion efficiency of microrobots Defined as the ratio of useful propulsion power to input drive power: ; Propulsion efficiency and dimensionless parameter magnetic number and fluid number Related, among which magnetic number , fluid number In this embodiment, ,have to ;Pick Theoretical advancement efficiency That is, approximately 18% of the magnetic energy is converted into effective propulsion work. The experimentally measured efficiency matches the theoretical value.

[0053] Parameter optimization: Based on the multiphysics coupling model and numerical simulation, this invention provides the following optimal parameter ranges: magnetic field amplitude Rotation frequency The optimal frequency is (Approximately 10.9Hz in this embodiment); ultrasonic frequency sound pressure amplitude Recommended Pa level: 200 kPa; Cluster size The specific dosage depends on the target dose and the working space.

[0054] All driving parameters comply with biosafety limits (magnetic field ≤15mT, ultrasonic intensity). (SAR≤2W / kg, temperature rise≤5℃), possessing clinical translation potential.

[0055] Therefore, the present invention employs a magnetoacoustic composite driven microrobot swarm targeted drug delivery system and method, which significantly improves the swarm's displacement velocity, propulsion efficiency, and targeted dwell stability in a low Reynolds number biofluid environment, thereby achieving precise and controllable targeted drug delivery.

[0056] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. A micro-robot cluster targeting drug delivery system driven by magnetoacoustic composite, characterized in that, include: Multiple microrobot units, each microrobot comprising a magnetically responsive body, a drug-carrying cavity, and an acoustically responsive interface; A rotating magnetic field generator is used to generate a controllable rotating magnetic field and magnetic field gradient. An ultrasonic standing wave field generator is used to generate an ultrasonic sound field capable of exerting acoustic radiation force on a cluster of microrobots. The control unit is used to execute hierarchical control strategies. 2.The micro robot cluster targeting drug delivery system of claim 1, wherein: The magnetically responsive elastomer body of the microrobot is composed of magnetic particles and PDMS elastomer. The volume fraction of the magnetic particles is 10% to 20%, and the elastic modulus is 50 kPa to 200 kPa. The microrobot has a helical shape with a helical radius of 20 μm to 100 μm, a pitch of 50 μm to 200 μm, and a total length of 100 μm to 500 μm. 3.The micro robot cluster targeting drug delivery system of claim 1, wherein: The rotating magnetic field generator includes three sets of orthogonal Helmholtz coils and three sets of orthogonal Maxwell coils, generating a magnetic field amplitude of 5mT to 15mT, a rotation frequency of 5Hz to 15Hz, and a magnetic field gradient of 1T / m to 5T / m. 4.The micro robot cluster targeting drug delivery system of claim 1, wherein: The ultrasonic standing wave field generator consists of two opposing ultrasonic transducer arrays with a working frequency of 1MHz to 5MHz and a sound pressure amplitude of 100kPa to 300kPa.

5. The method of targeted drug delivery of the micro-robot cluster driven by the magnetic-acoustic composite field, applied to the system of targeted drug delivery of the micro-robot cluster driven by the magnetic-acoustic composite field according to any one of claims 1-4, characterized in that, Includes the following steps: S1. Introducing a cluster of microrobots into a fluid environment; S2. Apply a rotating magnetic field through a rotating magnetic field generator to drive the cluster to move toward the target area; S3. Monitor the cluster position in real time. When the distance between the cluster centroid and the target area is less than a preset threshold, it is determined that the target area has been reached. S4. Turn off or reduce the rotating magnetic field, and turn on the ultrasonic standing wave field through the ultrasonic standing wave field generator to constrain the cluster to the sound pressure node. S5. Apply a high-frequency alternating magnetic field to trigger drug release.

6. The method of claim 5, wherein the magnetic acoustic composite field is generated by a magnetic field generator and an acoustic field generator. The frequency of the rotating magnetic field in S2 is no greater than 0.8 times the maximum synchronization frequency, which is defined as follows: ； wherein, is the maximum synchronization frequency, is the effective magnetic moment of a single microrobot, is the rotating magnetic field amplitude, is the rotating resistance coefficient of the microrobot.

7. The method of claim 5, wherein the micro-robot cluster is a magnetic acoustic composite driven micro-robot cluster. In S2, the average displacement velocity of the microrobot satisfies: ； wherein, is the average displacement velocity of the microrobot, is the magnetic field rotation angular frequency, is the step displacement for a single rotation period, is the rotation-translational coupling coefficient, is the helical pitch of the microrobot.

8. The method of claim 5, wherein the micro-robot cluster is a magnetic acoustic composite driven micro-robot cluster. The confinement capability of ultrasonic waves in S4 is characterized by a confinement index, which is not less than 10. The definition of the confinement index is as follows: ； wherein, is the constraint index, is the acoustic radiation force potential maximum, is the Boltzmann constant, is the body temperature.

9. The method of claim 5, wherein the micro-robot cluster is a magnetic-acoustic composite driven micro-robot cluster. The high-frequency alternating magnetic field in S5 is generated by a rotating magnetic field generator with a frequency of 50kHz and an amplitude of 20mT, using a pulse mode; the robot's temperature is raised to 42℃~45℃ through induction heating, triggering drug release.

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