CN117095787A - Application of quantitative relation between ultrasonic parameters and drug particle manipulation in ultrasonic system - Google Patents
Application of quantitative relation between ultrasonic parameters and drug particle manipulation in ultrasonic system Download PDFInfo
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Abstract
The application relates to the technical field of ultrasonic systems, and discloses an application of a quantitative relation between ultrasonic parameters and drug particle manipulation in an ultrasonic system, which comprises the following steps: establishing a standing wave field particle motion regulation model, adopting three-dimensional modeling, and taking a concave spherical focusing transducer as a model of a sound field generator; the transducer radiates the simulation of the sound field, adopt the hot-viscous acoustic module to calculate, the hot-viscous acoustic module is used for solving the sound field comprising heat loss and viscous loss; simulation of a dynamic process of drug particle aggregation; the control position is adjusted by adjusting the intensity of the sound field to compensate other acting forces; designing an ultrasonic drug delivery transducer to adapt to the actual requirements of the traditional Chinese medicine on pain; and (5) constructing a dosing experiment system. The application can simulate a free field environment, can simulate a particle aggregation dynamic process by utilizing the data of the concave spherical focusing transducer model, and can calculate monopole and dipole scattering coefficients according to particle properties when acoustic radiation force is added.
Description
Technical Field
The application relates to the technical field of ultrasonic systems, in particular to application of a quantitative relation between ultrasonic parameters and drug particle manipulation in an ultrasonic system.
Background
In recent years, a local drug delivery technology, i.e. external field force (ultrasound, optical field, magnetic field, etc.), is proposed to drive micro-nano particles (microbubbles carrying drugs, micro-nano drug droplets, solid particles) to aggregate and release drugs at fixed points.
The technology can improve the concentration of the medicine at the target part, reduce the toxic and side effects of the medicine on normal tissues of the whole body, and brings great attention to people. And how to utilize various external force fields to effectively control the micro-nano drug particles so that the micro-nano drug particles can move along a designated path in a blood flow field and gather in target focus tissues, thus becoming one of core technologies of the treatment means.
The ultrasonic drug delivery process is mainly divided into two processes, namely, the micro-nano drugs are firstly controlled to be gathered at the fixed point, and then the micro-nano particles gathered at the fixed point are smashed to release the drugs, so that the concentration of local drug delivery is improved, and a good treatment effect is achieved.
In the process, how to gather the medicine at the fixed point is an important problem, and the quantitative relation research of ultrasonic parameters and medicine particle manipulation is completed, so that a scientific experimental foundation can be laid for the design of an ultrasonic system.
For this reason, there is a need for the use of quantitative relationships of ultrasound parameters to drug particle manipulation in ultrasound systems.
Disclosure of Invention
(one) solving the technical problems
Aiming at the defects of the prior art, the application provides the application of the quantitative relation between ultrasonic parameters and drug particle manipulation in an ultrasonic system, and solves the problems in the background art.
(II) technical scheme
In order to achieve the above purpose, the present application provides the following technical solutions:
use of a quantitative relationship of ultrasound parameters to drug particle manipulation in an ultrasound system, comprising:
establishing a standing wave field particle motion regulation model, wherein the standing wave field particle motion regulation system adopts three-dimensional modeling, a concave spherical focusing transducer is used as a model of a sound field generator, the center O of an aperture plane of the transducer is used as an origin, two vertical axes are selected in the aperture plane through the origin O to be determined as an x axis and a y axis, and a connecting line of the center points of the upper transducer and the lower transducer is used as a z axis, so that a three-dimensional rectangular coordinate system is established;
the simulation of the transducer radiation sound field is calculated by adopting a hot-viscosity acoustic module, the hot-viscosity acoustic module is used for solving a sound field containing heat loss and viscous loss, a partial differential equation is used during solving, the solved partial differential equation contains parameters of dynamic viscosity, bulk viscosity and thermal expansion coefficient of a medium, and xOz tangent plane sound pressure of the three-dimensional steady-state sound field is calculated;
simulation of a dynamic process of drug particle aggregation;
the control position is adjusted by adjusting the intensity of the sound field to compensate other acting forces;
designing an ultrasonic drug delivery transducer to adapt to the actual requirements of the traditional Chinese medicine on pain; and
and constructing a drug administration experimental system.
As a preferable technical scheme, in a model taking a concave spherical focusing transducer as a sound field generator, a light area is a cylindrical water area with the height of 20mm and the radius of 10mm, a dark area is two concave spherical ultrasonic focusing transducers, the aperture radius of the concave spherical ultrasonic focusing transducers is 4.53mm, and the curvature radius or focal length of the concave spherical ultrasonic focusing transducers is 10mm.
In the preferred technical scheme, in a model taking a concave spherical focusing transducer as a sound field generator, the frequency of ultrasonic emitted by the transducer is set to be 1MHz, dark arrows are the radiation direction of the sound field of the transducer, and other wall surfaces except the surface of the transducer are attached with sound absorption materials to simulate a free field environment.
As the preferable technical scheme, the xOz tangential plane sound pressure of the three-dimensional steady-state sound field is obtained through calculation, the focusing transducer can realize sound wave focusing on the z axis by utilizing the interference effect of sound waves, and the two focused sound waves form a local standing wave sound field.
As an optimal technical scheme, after the physical field numerical calculation for driving the particles to move is completed, a particle tracking module in COMSOL software is adopted for the motion simulation of the particles under the action of a sound field and a sound flow field.
As a preferable technical scheme, the particle tracking module is used for calculating the motion trail of the particles under drag force, gravity, magnetic force or user-defined acting force, and can endow the particles with the properties of quality, size, density and compression coefficient.
As a preferable technical scheme, the data of the concave spherical focusing transducer model is utilized to simulate the particle aggregation dynamic process;
the interaction force between particles, the gravity and the buoyancy of the particles are ignored in the simulation, and the acoustic radiation force and the acoustic flow drag force are added in the model, so that the particles move under the action of the acoustic radiation force and the acoustic flow drag force only.
As a preferred technical solution, monopole and dipole scattering coefficients are calculated according to particle properties when adding acoustic radiation force;
and (3) uniformly distributing the pellets in the xOz tangential plane sound field at the initial moment, setting a boundary condition to be particle disappearance, and calculating a particle pellet motion change track in 6 seconds.
As a preferable technical scheme, the sound field intensity can be adjusted by changing the amplitude value of the array surface, so that the maximum sound pressure value of the sound field is respectively 0.074Mpa, 0.147Mpa and 0.295Mpa, the size ratio is 1:2:4, the sound radiation force ratio corresponding to the three sound fields with different intensities is calculated to be 1:4:16, and the sound flow drag force ratio is 1:4:16;
since there is a relationship between vibration velocity and sound pressure:p 1 and v 1 Is the first order of sound pressure and vibration velocity, v 2 Is the second order quantity of vibration speed, so the magnitude and p of sound radiation force 2 In direct proportion to p, the drag of the acoustic stream is also proportional to p when the particles are stationary (u=0) 2 In the process of increasing the sound field intensity, the relative magnitudes of the sound radiation force and the sound flow drag force are consistent, the directional distribution of the resultant force in space is not changed, and the binding state of particles in the sound field is unchanged.
As an optimal technical scheme, the ultrasonic drug delivery transducer adopts a multipoint signal feedback technology to ensure that the transducer works at a resonance point, and the development of an ultrasonic excitation system is completed by using a Kalman filtering algorithm and fuzzy dynamic parameter PID control based on a Gaussian curve.
As the optimal technical scheme, the design and the manufacture of the ultrasonic drug delivery transducer are completed, the ultrasonic drug delivery transducer is a concave spherical focusing transducer, the center frequency of the ultrasonic drug delivery transducer is 2MHz, the curvature radius or focal length is 20mm, and the aperture radius is 9.07mm.
As a preferable technical scheme, the experimental system basically comprises a signal generating system, an ultrasonic transducer and a mechanical clamping device, wherein the mechanical clamping device can use a mechanical clamping arm;
the mechanical clamping arm is a six-axis mechanical clamping arm;
the signal generating system mainly comprises a signal generator.
As a preferable technical scheme, a distilled water immersion device is added into a water tank before a test, a transducer is connected with a signal generating system, a continuous sine wave signal with the frequency of 2MHz is emitted by a signal generator, and after the continuous sine wave signal passes through a power amplifier, the real-time voltage is read by an oscilloscope;
the method for adding particles by adopting the mode of sucking the particle hovering solution by the rubber head dropper comprises the following specific operations: pouring the particles into a small beaker, adding water, stirring the particles in an experiment to enable the particles to be in a hovering state, sucking the aqueous solution containing the particles by using a dropper after the transducer is started, repeatedly and slowly adding the particles to the sound wave radiation area for a plurality of times, and performing experiment record after the constraint state of the particles is stable.
As the preferable technical scheme, the vernier caliper is used for adjusting the center distance between two transducers to be 30mm, a signal generator and a power amplifier are turned on, an oscilloscope displays that the peak-to-peak value of input voltage is 13.6V, and particles with the four sizes are added to a standing wave field under the conditions of constant transducer distance and output power;
when in experiment, a micro-focus digital camera is used for photographing and recording, a black backboard is stuck on the back of the clamping device to increase the identification degree of white particles, after an image is obtained, simple image processing is carried out on the image, and contrast and definition are improved after brightness is reduced;
setting the distance between the transducers to be 30mm, selecting particles with the radius of 150 mu m, adjusting the input voltage of the transducers, and carrying out a comparison experiment by using three different power gears of the transducers;
wherein, three different power gears are 6.37V, 13.61V and 20.12V respectively;
under the condition of 6.37V of input voltage, particles are released from the rubber head dropper and then directly flush through the standing wave field area, and the radiation sound field area floats from the other side.
(III) beneficial effects
The application provides application of a quantitative relation between ultrasonic parameters and drug particle manipulation in an ultrasonic system, and has the following beneficial effects:
1. in the application, the frequency of ultrasonic emitted by the transducer is set to be 1MHz in the model, the dark arrow is the radiation direction of the sound field of the transducer, and other wall surfaces except the surface of the transducer are attached with sound absorption materials, so that the free field environment can be simulated.
2. In the application, simulation of the radiation sound field of the transducer is calculated by adopting a hot-viscosity acoustic module, and the module is used for solving the sound field containing heat loss and viscous loss.
3. In the application, under the interference effect of sound waves, the focusing transducer can focus sound waves on the z-axis, and the two focused sound waves form a local standing wave sound field.
4. In the application, after the numerical calculation of the physical field for driving the particles to move is completed, a particle tracking module in COMSOL software is adopted for the motion simulation of the particles under the action of a sound field and a sound flow field, and the module is used for calculating the motion trail of the particles under drag force, gravity, magnetic force or user-defined acting force, and can endow the particles with the properties of quality, size, density, compression coefficient and the like.
5. According to the application, the data of the concave spherical focusing transducer model can be utilized to simulate the particle aggregation dynamic process.
6. In the application, monopole and dipole scattering coefficients can be calculated according to particle properties when adding acoustic radiation force.
7. In the application, researches show that as the intensity of a sound field continuously increases, when the sound flow field transits from laminar flow to turbulent flow, the flow field distribution changes and is more complex, and in practical application, the control position can be adjusted by adjusting the intensity of the sound field to compensate other acting forces.
8. In the application, the ultrasonic drug delivery transducer adopts a multipoint signal feedback technology to ensure that the transducer works at an optimal resonance point, and the development of an ultrasonic excitation system is completed by using a Kalman filtering algorithm and fuzzy dynamic parameter PID control based on a Gaussian curve.
9. In the application, the drug administration experiment can be performed by constructing a drug administration experiment system, such as a drug delivery experiment platform.
Specifically, the drug experiment can be performed by constructing a static particle capturing experiment platform and a dynamic particle moving experiment platform.
10. In the application, in order to verify the influence of the emission power of a transducer on the movement of particles, the distance between transducers is set to be 30mm, particles with the radius of 150 mu m are also selected, and three power gears of the transducer, namely 6.37V, 13.61V and 20.12V, are respectively adjusted to carry out comparison experiments, and when the input voltage is 6.37V, the particles directly flow through a standing wave field area after being released from a rubber head dropper, and drift out of a radiation sound field area from the other side.
Drawings
FIG. 1 is a three-dimensional rectangular coordinate system modeling diagram of a concave spherical focusing transducer;
FIG. 2 is a diagram of a concave spherical transducer model focused acoustic field;
FIG. 3 is a graph of particle aggregation dynamics;
FIG. 4 is a pictorial view of a concave spherical focusing transducer;
FIG. 5 is a physical diagram of a static particle capture experiment platform in the drug administration experiment system;
FIG. 6 is a physical diagram of a dynamic particle movement experimental platform in the drug administration experimental system;
FIG. 7 is a graph comparing the binding results of standing wave fields to particles of different sizes;
fig. 8 is a transient view of drug addition in the sound field.
Detailed Description
The following description of the embodiments of the present application will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present application, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the application without making any inventive effort, are intended to be within the scope of the application.
Examples
In recent years, a local drug delivery technology, i.e. external field force (ultrasound, optical field, magnetic field, etc.), is proposed to drive micro-nano particles (microbubbles carrying drugs, micro-nano drug droplets, solid particles) to aggregate and release drugs at fixed points.
The technology can improve the concentration of the medicine at the target part, reduce the toxic and side effects of the medicine on normal tissues of the whole body, and brings great attention to people. And how to utilize various external force fields to effectively control the micro-nano drug particles so that the micro-nano drug particles can move along a designated path in a blood flow field and gather in target focus tissues, thus becoming one of core technologies of the treatment means.
The ultrasonic drug delivery process is mainly divided into two processes, namely, the micro-nano drugs are firstly controlled to be gathered at the fixed point, and then the micro-nano particles gathered at the fixed point are smashed to release the drugs, so that the concentration of local drug delivery is improved, and a good treatment effect is achieved.
In the process, how to gather the medicine at the fixed point is an important problem, and the quantitative relation research of ultrasonic parameters and medicine particle manipulation is completed, so that a scientific experimental foundation can be laid for the design of an ultrasonic system.
The inventor aims at solving the technical problems, realizes and completes the application of the quantitative relation between ultrasonic parameters and drug particle manipulation in an ultrasonic system, and adopts the following technical scheme:
as shown in fig. 1-8, the embodiment of the application provides a technical scheme that:
1. and (3) completing establishment of a standing wave field particle motion regulation model:
1. three-dimensional modeling:
the standing wave field particle motion regulation and control system adopts three-dimensional modeling, a model schematic diagram is shown in figure 1, a concave spherical focusing transducer is used as a model of a sound field generator, a light area is a cylindrical water area with the height of 20mm and the radius of 10mm, a dark area is two concave spherical ultrasonic focusing transducers, the aperture radius is 4.53mm, and the curvature radius (focal length) is 10mm;
the frequency of ultrasonic emitted by the transducer is set to be 1MHz in the model, dark arrows indicate the radiation direction of the sound field of the transducer, and sound absorption materials are attached to other wall surfaces except the surface of the transducer to simulate the free field environment.
As shown in fig. 1, a three-dimensional rectangular coordinate system is established by taking the center O of the aperture plane of the transducer in fig. 1 as an origin, selecting two vertical axes in the aperture plane through the origin O to be an x-axis and a y-axis, and taking a connecting line of the center points of the upper transducer and the lower transducer as a z-axis.
2. Sound field simulation:
the simulation of the transducer radiation sound field is calculated by adopting a hot-viscous acoustic module, and the module is used for solving the sound field containing heat loss and viscous loss, and compared with a common pressure acoustic module, the solved partial differential equation contains the dynamic viscosity, the bulk viscosity, the thermal expansion coefficient and other material parameters of a medium, and the material parameters of a water area need to be modified and added according to the table 1 in the material properties.
Table 1 material parameters of waters
The xOz tangent plane sound pressure of the three-dimensional steady-state sound field is calculated as shown in fig. 2, and in fig. 2, it is seen that the focusing transducer can focus sound waves on the z axis by utilizing the interference effect of sound waves, and the two focused sound waves form a local standing wave sound field.
3. Drug particle aggregation dynamic process simulation:
after the physical field numerical calculation for driving the particles to move is completed, a particle tracking module in COMSOL software is adopted for the movement simulation of the particles under the action of a sound field and a sound flow field, and the module is used for calculating the movement track of the particles under drag force, gravity, magnetic force or user-defined acting force, and can endow the particles with the properties of quality, size, density, compression coefficient and the like.
And carrying out particle aggregation dynamic process simulation by using the data of the concave spherical focusing transducer model. The interaction force between particles, the gravity and the buoyancy of the particles are ignored in the simulation, and the acoustic radiation force and the acoustic flow drag force are added in the model, so that the particles move under the action of the two forces only.
Monopole and dipole scattering coefficients need to be calculated from particle properties when adding acoustic radiation forces.
And (3) uniformly distributing the pellets in the xOz tangential plane sound field at the initial moment, setting a boundary condition to be particle disappearance, and calculating a particle pellet motion change track in 6 seconds.
FIG. 3 is a graph of the dynamic process of particle aggregation, showing the local standing wave field region with coordinates (-1.5, 8.6 mm), (-1.5, 11.4 mm), (1.5, 8.6 mm) and (1.5, 11.4 mm) as vertices, with background being the time-averaged potential U in the region calculated by equation (2.26) rad 。
The particle pellets at the moment 0 are uniformly distributed in a plane and move under the action of a combined force, the movement trend of the particle clusters is rapid longitudinal aggregation, then the transverse aggregation is completed at a relatively slow speed, and finally the stable state is reached at the time of 6s and the particles are aggregated in U rad Is near the minimum value of (2).
4. Influence of sound field intensity on manipulation:
studies have shown that as the acoustic field intensity continues to increase, the flow field distribution changes and is more complex as the acoustic flow field transitions from laminar to turbulent, so the acoustic flow field studied by the present application is only within the range of laminar flow.
The amplitude value of the array surface is changed, the intensity of the sound field can be adjusted, the maximum sound pressure value of the sound field is respectively 0.074Mpa, 0.147Mpa and 0.295Mpa, the size ratio is 1:2:4, the sound radiation force ratio corresponding to the three sound fields with different intensities is calculated to be 1:4:16, and the sound flow drag force ratio is equal to 1:4:16.
Since there is a relationship between vibration velocity and sound pressure:p 1 and v 1 Is the first order of sound pressure and vibration velocity, v 2 Is the second order quantity of vibration speed, so the magnitude and p of sound radiation force 2 In direct proportion to p, the drag of the acoustic stream is also proportional to p when the particles are stationary (u=0) 2 In direct proportion to indicate the soundIn the process of increasing the field intensity, the relative magnitudes of the acoustic radiation force and the acoustic flow drag force are consistent, the directional distribution of the resultant force in the space is not changed, and the binding state of the particles in the acoustic field is unchanged.
The state mentioned here is unchanged because gravity and buoyancy of the particles are ignored, and in practical application, the control position needs to be adjusted by adjusting the intensity of the sound field to compensate other acting forces.
2. The ultrasonic drug delivery transducer is designed to adapt to the actual requirements of the traditional Chinese medicine on pain:
the ultrasonic drug delivery transducer adopts a multipoint signal feedback technology to ensure that the transducer works at an optimal resonance point, and uses a Kalman filtering algorithm and fuzzy dynamic parameter PID control based on a Gaussian curve to complete the development of an ultrasonic excitation system.
Designing and manufacturing an ultrasonic drug delivery transducer:
the design and the manufacture of the ultrasonic drug delivery transducer are completed, and the transducer is a concave spherical focusing transducer, the center frequency of the transducer is 2MHz, the curvature radius (focal length) is 20mm, and the aperture radius is 9.07mm.
As shown in fig. 4, fig. 4 is a real image of the transducer, and the performance parameters thereof are shown in table 2.
Table 2 performance parameters of concave spherical focusing transducers
3. Constructing a dosing experiment system:
the experimental system basically comprises a signal generating system, an ultrasonic transducer and a mechanical clamping device (namely, a six-axis mechanical clamping arm), wherein the mechanical clamping device (namely, the six-axis mechanical clamping arm) can use a mechanical clamping arm, the mechanical clamping arm can be a six-axis mechanical clamping arm, and the signal generating system mainly comprises a signal generator.
The two experimental platforms are set up as shown in fig. 5 and 6:
wherein, fig. 5 is a static particle capturing experiment platform, and fig. 6 is a dynamic particle moving experiment platform.
Drug delivery experiments were set up:
and adding a distilled water immersing device into the water tank before the test, connecting the transducer with the signal generating system, setting the signal generator to emit a continuous sine wave signal with the frequency of 2MHz, and reading real-time voltage by using an oscilloscope after passing through a power amplifier.
Because white polystyrene particles are selected as the ultrasonic capturing target, the density of the white polystyrene particles is slightly higher than that of water, a part of particles form agglomeration and float on the water surface after being added into the water, and the particles can sink into the bottom of a water tank after standing for a period of time, and cannot be sent into a standing wave field area.
Therefore, the method of sucking the particle hovering solution by the rubber head dropper is adopted to add particles, the particles are poured into a small beaker to be added with water, the particles are stirred in an experiment to be in a hovering state, after the transducer is started, the dropper is used to suck the aqueous solution containing the particles, the particles are repeatedly and slowly added to the sound wave radiation area, and after the constraint state of the particles is stable, the experiment record is carried out.
Experiments were performed with four polystyrene particles (instead of drugs) with radii of 150 μm, 75 μm, 37.5 μm and 7.5 μm, each set of experiments requiring cleaning of the water tank and addition with a dedicated glue head dropper, in order to prevent mixing of different sized particles together.
And adjusting the center distance between the two transducers to be 30mm by using a vernier caliper, opening a signal generator and a power amplifier, displaying 13.6V of peak-to-peak value of input voltage by an oscilloscope, and adding particles with the four sizes to a standing wave field under the conditions of constant transducer distance and output power.
In the experiment, a micro-focus digital camera is used for photographing and recording, a black backboard is stuck on the back of a clamping device (namely, a six-axis mechanical clamping arm) to increase the identification degree of white particles, after an image is obtained, simple image processing is carried out on the image, after the brightness is reduced, the contrast and the definition are improved, and the obtained experimental result is shown in fig. 7.
In order to verify the influence of the transmitting power of the transducer on the movement of particles, the distance between the transducers is set to be 30mm, particles with the radius of 150 mu m are selected, and the input voltage of the transducer is adjusted to be three power levels of low, medium and high for comparison experiments, namely 6.37V, 13.61V and 20.12V respectively.
Fig. 8 is a transient view of the particle adding process under the input voltage of 6.37V, the left side of each photo is the tip of the rubber head dropper, the particles in the circle are observation targets, and it can be seen that the particles directly rush through the standing wave field area after being released from the rubber head dropper, and drift out of the radiation sound field area from the other side.
This phenomenon shows that in a low power standing wave field, since the released particles have a certain initial velocity, the standing wave field generates insufficient acoustic radiation force to stop the particles, so that the addition and binding of the particles are not favored under the condition of lower power, and the part of research is advanced later.
The drug particles can also be traditional Chinese medicine particles, freeze-dried powder and the like.
It is noted that relational terms such as first and second, and the like are used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Moreover, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.
Although embodiments of the present application have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the principles and spirit of the application, the scope of which is defined in the appended claims and their equivalents.
Claims (10)
1. Use of a quantitative relationship of ultrasound parameters to drug particle manipulation in an ultrasound system, comprising:
establishing a standing wave field particle motion regulation model, wherein the standing wave field particle motion regulation system adopts three-dimensional modeling, a concave spherical focusing transducer is used as a model of a sound field generator, the center O of an aperture plane of the transducer is used as an origin, two vertical axes are selected in the aperture plane through the origin O to be determined as an x axis and a y axis, and a connecting line of the center points of the upper transducer and the lower transducer is used as a z axis, so that a three-dimensional rectangular coordinate system is established;
the simulation of the transducer radiation sound field is calculated by adopting a hot-viscosity acoustic module, the hot-viscosity acoustic module is used for solving a sound field containing heat loss and viscous loss, a partial differential equation is used during solving, the solved partial differential equation contains parameters of dynamic viscosity, bulk viscosity and thermal expansion coefficient of a medium, and xOz tangent plane sound pressure of the three-dimensional steady-state sound field is calculated;
simulation of a dynamic process of drug particle aggregation;
the control position is adjusted by adjusting the intensity of the sound field to compensate other acting forces;
designing an ultrasonic drug delivery transducer to adapt to the actual requirements of the traditional Chinese medicine on pain; and
and constructing a drug administration experimental system.
2. Use of the quantitative relationship of ultrasound parameters to drug particle manipulation in an ultrasound system according to claim 1, wherein: in the model using a concave spherical focusing transducer as a sound field generator, the light area is a cylindrical water area with the height of 20mm and the radius of 10mm, the dark area is two concave spherical ultrasonic focusing transducers, the aperture radius of the two concave spherical ultrasonic focusing transducers is 4.53mm, and the curvature radius or focal length of the two concave spherical ultrasonic focusing transducers is 10mm.
3. Use of the quantitative relationship of ultrasound parameters to drug particle manipulation in an ultrasound system according to claim 2, wherein: in a model using a concave spherical focusing transducer as a sound field generator, the frequency of ultrasonic emitted by the transducer is set to be 1MHz, dark arrows are the radiation direction of the sound field of the transducer, sound absorption materials are attached to other wall surfaces except the surface of the transducer, and a free field environment is simulated.
4. Use of the quantitative relationship of ultrasound parameters to drug particle manipulation in an ultrasound system according to claim 1, wherein: the xOz tangential plane sound pressure of the three-dimensional steady-state sound field is obtained through calculation, the focusing transducer can focus sound waves on the z axis by utilizing the interference effect of sound waves, and the two focused sound waves form a local standing wave sound field.
5. Use of the quantitative relationship of ultrasound parameters to drug particle manipulation in an ultrasound system according to claim 1, wherein: after the physical field numerical calculation for driving the particles to move is completed, a particle tracking module in COMSOL software is adopted for the motion simulation of the particles under the action of a sound field and a sound flow field.
6. Use of the quantitative relationship of ultrasound parameters to drug particle manipulation according to claim 5 in an ultrasound system, characterized in that: the particle tracking module is used for calculating the motion trail of the particles under drag force, gravity, magnetic force or user-defined acting force, and can endow the particles with the properties of quality, size, density and compression coefficient.
7. Use of a quantitative relationship of ultrasound parameters to drug particle manipulation according to claim 1 or 2 or 3 in an ultrasound system, characterized in that: performing particle aggregation dynamic process simulation by using data of a concave spherical focusing transducer model;
the interaction force between particles, the gravity and the buoyancy of the particles are ignored in the simulation, and the acoustic radiation force and the acoustic flow drag force are added in the model, so that the particles move under the action of the acoustic radiation force and the acoustic flow drag force only.
8. Use of the quantitative relationship of ultrasound parameters to drug particle manipulation in an ultrasound system according to claim 7, wherein: calculating monopole and dipole scattering coefficients according to particle properties when adding acoustic radiation force;
and (3) uniformly distributing the pellets in the xOz tangential plane sound field at the initial moment, setting a boundary condition to be particle disappearance, and calculating a particle pellet motion change track in 6 seconds.
9. Use of the quantitative relationship of ultrasound parameters to drug particle manipulation in an ultrasound system according to claim 1, wherein: the intensity of the sound field can be adjusted by changing the amplitude value of the array surface, so that the maximum sound pressure value of the sound field is respectively 0.074Mpa, 0.147Mpa and 0.295Mpa, the size ratio is 1:2:4, the sound radiation force ratio corresponding to the three sound fields with different intensities is calculated to be 1:4:16, and the sound flow drag force ratio is equal to 1:4:16;
since there is a relationship between vibration velocity and sound pressure: v= - (1/ρ) ≡ pdt, p 1 And v 1 Is the first order of sound pressure and vibration velocity, v 2 Is the second order quantity of vibration speed, so the magnitude and p of sound radiation force 2 In direct proportion to p, the drag of the acoustic stream is also proportional to p when the particles are stationary (u=0) 2 In a proportional relation, the relative magnitudes of the sound radiation force and the sound flow drag force are consistent in the process of increasing the sound field intensity, the directional distribution of resultant force in space is not changed, and the binding state of particles in the sound field is unchanged;
the ultrasonic drug delivery transducer adopts a multipoint signal feedback technology to ensure that the transducer works at a resonance point, and uses a Kalman filtering algorithm and fuzzy dynamic parameter PID control based on a Gaussian curve to complete the development of an ultrasonic excitation system;
completing the design and manufacture of an ultrasonic drug delivery transducer, wherein the ultrasonic drug delivery transducer is a concave spherical focusing transducer, the center frequency of the ultrasonic drug delivery transducer is 2MHz, the curvature radius or focal length is 20mm, and the aperture radius is 9.07mm;
the experimental system basically comprises a signal generating system, an ultrasonic transducer and a mechanical clamping device, wherein the mechanical clamping device can use a mechanical clamping arm;
the mechanical clamping arm is a six-axis mechanical clamping arm;
the signal generating system mainly comprises a signal generator;
adding a distilled water immersing device into the water tank before the test, connecting the transducer with the signal generating system, setting the continuous sine wave signal with the frequency of 2MHz emitted by the signal generator, and reading real-time voltage by using an oscilloscope after passing through a power amplifier;
the method for adding particles by adopting the mode of sucking the particle hovering solution by the rubber head dropper comprises the following specific operations: pouring the particles into a small beaker, adding water, stirring the particles in an experiment to enable the particles to be in a hovering state, sucking the aqueous solution containing the particles by using a dropper after the transducer is started, repeatedly and slowly adding the particles to the sound wave radiation area for a plurality of times, and performing experiment record after the constraint state of the particles is stable.
10. Use of the quantitative relationship of ultrasound parameters to drug particle manipulation in an ultrasound system according to claim 9, wherein: the center distance between the two transducers is adjusted to be 30mm by utilizing a vernier caliper, a signal generator and a power amplifier are turned on, an oscilloscope displays that the peak-to-peak value of an input voltage is 13.6V, and particles with the four sizes are added to a standing wave field under the conditions of constant transducer distance and output power;
when in experiment, a micro-focus digital camera is used for photographing and recording, a black backboard is stuck on the back of the clamping device to increase the identification degree of white particles, after an image is obtained, simple image processing is carried out on the image, and contrast and definition are improved after brightness is reduced;
setting the distance between the transducers to be 30mm, selecting particles with the radius of 150 mu m, adjusting the input voltage of the transducers, and carrying out a comparison experiment by using three different power gears of the transducers;
wherein, three different power gears are 6.37V, 13.61V and 20.12V respectively;
under the condition of 6.37V of input voltage, particles are released from the rubber head dropper and then directly flush through the standing wave field area, and the radiation sound field area floats from the other side.
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