阅读说明：本技术 基于空间非均匀聚焦涡旋声场的相变纳米液滴调控方法 (The phase transformation nano-liquid droplet for focusing vortex sound field based on spatial non-uniform regulates and controls method ) 是由 万明习 郭世放 郭叙言 王昕� 杜轩 于 2019-07-22 设计创作，主要内容包括：本发明提供一种基于空间非均匀聚焦涡旋声场的相变纳米液滴调控方法,通过调节球形聚焦超声换能器阵元间的相对功率和相位,产生声压非对称分布、环状波腹上存在声压极大值的非均匀聚焦涡旋声场,利用这一非均匀聚焦涡旋声场,将分散的相变纳米液滴聚集为微米尺寸的团状液滴聚集体,从而显著降低相变纳米液滴的相变阈值,利用单个微秒级短脉冲作用于聚集的相变纳米液滴,进而诱导液滴相变,聚集体中液滴的纳米尺寸分布确保了相变微泡的振动活性。本发明使得活体条件下相变纳米液滴的声调控具有更高的灵活度和安全性。(The present invention provides a kind of phase transformation nano-liquid droplet regulation method that vortex sound field is focused based on spatial non-uniform, by adjusting relative power and phase between spherical focusing ultrasonic transducer array element, generate acoustic pressure asymmetric distribution, there are the non-homogeneous focusing vortex sound fields of acoustic pressure maximum in cyclic annular antinode, utilize this non-homogeneous focusing vortex sound field, the phase transformation nano-liquid droplet of dispersion is collected as to the bulk drop aggregation of micron-scale, to significantly reduce the phase transformation threshold value of phase transformation nano-liquid droplet, the phase transformation nano-liquid droplet of aggregation is acted on using single Microsecond grade short pulse, and then induce drop phase transformation, the nano-scale distribution of drop ensures the vibration activity of phase-converted microbubbles in aggregation.The invention enables the tone controls of phase transformation nano-liquid droplet under condition of living body to have higher flexibility ratio and safety.)

1. a kind of phase transformation nano-liquid droplet regulation device for focusing vortex sound field based on spatial non-uniform, it is characterised in that: the regulation Device includes the ultrasonic cavitation energy converter (3) and spherical focusing ultrasonic transducer that focal regions can be overlapped, spherical focusing ultrasound The phase difference of the driving signal of the adjacent division array element of energy converter is consistent, and divides array element power not with other there are n Division array element same, for making to focus generation acoustic pressure maximum point in vortex sound field focal regions inner annular antinode, n >=1.

2. a kind of phase transformation nano-liquid droplet regulation device that vortex sound field is focused based on spatial non-uniform according to claim 1, It is characterized by: the division array element of the spherical focusing ultrasonic transducer is divided into A class division array element and B class division array element, A class point The quantity for splitting array element is greater than B class and divides array element, and the power W that two class of A, B divides array element meets: W_B=aW_A, wherein 0 < a < 1.

3. a kind of phase transformation nano-liquid droplet regulation device that vortex sound field is focused based on spatial non-uniform according to claim 1, It is characterized by: the phase difference of the driving signal of the spherical focusing ultrasonic transducer division array element is 2 π/N nonzero integer Times, N is array number.

4. a kind of phase transformation nano-liquid droplet regulation device that vortex sound field is focused based on spatial non-uniform according to claim 1, It is characterized by: the ultrasonic cavitation energy converter (3) emits single Microsecond grade short pulse ultrasound by certain frequency.

5. a kind of phase transformation nano-liquid droplet regulation device that vortex sound field is focused based on spatial non-uniform according to claim 1, It is characterized by: the regulation device further includes imitating body, the water tank (6) for placing imitative body and for observing and recording imitative body The high speed micro imaging system (2) of interior phase transformation nano-liquid droplet and phase-converted microbubbles.

6. a kind of phase transformation nano-liquid droplet for focusing vortex sound field based on spatial non-uniform regulates and controls method, it is characterised in that: the regulation Method the following steps are included:

1) it is consistent by adjusting the phase difference for the driving signal of adjacent division array element for making spherical focusing ultrasonic transducer, and There are the more than one division array elements different from other division array element power, so that the spherical focusing ultrasonic transducer be made to produce A raw center is pressed in a low voice, peripheral annular high sound pressure is distributed and non-homogeneous poly- with acoustic pressure maximum point on loud pressure area Burnt vortex sound field；

2) assemble phase transformation nano-liquid droplet using the non-homogeneous focusing vortex sound field；

3) phase-converted microbubbles are formed using the phase transformation nano-liquid droplet of ultrasonic cavitation energy converter (3) induced aggregation.

7. a kind of phase transformation nano-liquid droplet for focusing vortex sound field based on spatial non-uniform regulates and controls method according to claim 6, It is characterized by: phase transformation nano-liquid droplet is gathered in acoustic pressure maximum in the non-homogeneous focusing vortex sound field in the step 2) Acoustic pressure large area where point.

8. a kind of phase transformation nano-liquid droplet for focusing vortex sound field based on spatial non-uniform regulates and controls method according to claim 6, It is characterized by: the regulation method is further comprising the steps of: being received using high speed micro imaging system (2) to intracorporal phase transformation is imitated Rice drop is positioned at this and imitates and intracorporal non-homogeneous focus accumulation process under vortex sound field reflecting and observed, record in focal regions.

9. a kind of phase transformation nano-liquid droplet for focusing vortex sound field based on spatial non-uniform regulates and controls method according to claim 8, It is characterized by: the regulation method is further comprising the steps of: being received using high speed micro imaging system (2) to the phase transformation after aggregation The phase transformation of rice drop and the evanishment for being formed by phase-converted microbubbles are observed, are recorded.

10. a kind of phase transformation nano-liquid droplet for focusing vortex sound field based on spatial non-uniform regulates and controls method according to claim 6, It is characterized by: the division array element of the spherical focusing ultrasonic transducer is divided into A class division array element and B class division array element, A class point The quantity for splitting array element is greater than B class and divides array element, and the power W that two class of A, B divides array element meets: W_B=aW_A, wherein 0 < a < 1；It is described The phase difference that spherical focusing ultrasonic transducer divides the driving signal of array element is 2 π/N non-zero integer multiples, and N is array number.

Technical field

The invention belongs to ultrasonic physics, ultrasound detection and control fields, and in particular to one kind is focused based on spatial non-uniform The phase transformation nano-liquid droplet of vortex sound field regulates and controls method.

Background technique

In recent years, space-time controllability of nano-carrier during drug delivery has caused materials chemistry and drug delivery to be led Corresponding technology and methods have also been developed in the great attention in domain, every subjects, wherein the targeted drug Transfer Technology of ultrasonic mediation Because its is noninvasive and the advantages such as good penetration become a big hot spot of the research direction.Currently, in ultrasound field, by perfluorinated The phase transformation nano-liquid droplet of carbon and coating (lipid, protein, surfactant etc.) composition is in terms of the space-time controlled release for realizing drug Present huge potentiality.Under the ultrasonication of some strength, phase transformation nano-liquid droplet can be undergone phase transition, and it is micro- to be changed into phase transformation Bubble, the phenomenon are also referred to as sound and cause drop gasification, and minimum acoustic pressure needed for corresponding drop phase transformation is its phase transformation threshold value.Study table Bright, phase-converted microbubbles can promote the extravasation of drug and enhance cell to lead to the miniflow and shear stress generated when ultrasound interaction Permeability, to promote situ absorption of the drug in cell.Phase transformation nano-liquid droplet is in ultrasound thermal ablation, ultrasound thrombolysis, blood at present The fields such as brain barrier open are widely used, however drop undergoes phase transition required minimum acoustic pressure higher than clinical safety acoustic pressure threshold Value (for four times of the diagnostic ultrasound highest acoustic pressure of FDA approval), thus there are the risks of damage healthy tissues and organ.Although big Acoustic pressure needed for the micro droplets phase transformation of size is lower, but the phase-converted microbubbles size that drop phase transformation generates is often excessive, and excessive ruler Vibration activity of the very little phase-converted microbubbles under ultrasonication is poor, when resulting in the treatment of large scale phase transformation micro droplets assisting ultrasonic Efficiency is lower.

To guarantee high efficiency and safety when the treatment of phase transformation drop assisting ultrasonic, avoid ultrasonic therapy in the process because of acoustic pressure It is excessively high and additional injury is caused to surrounding tissue or organ, how to reduce the phase transformation threshold value of phase transformation nano-liquid droplet and guarantees its correspondence The vibration activity of phase-converted microbubbles becomes mainly studying a question for phase transformation nano-liquid droplet regulation.Studies have shown that in certain concentration model In enclosing, minimum acoustic pressure needed for drop phase transformation is reduced with the raising of concentration, however, the phase transformation nano-liquid droplet meeting of excessive concentrations So that body generates the side effects such as arrhythmia cordis even death.There is scholar to prove, phase transformation micro droplets are right because of its spherical structure Incident acoustic wave has focussing force, so that the sound pressure amplitude of drop internal sound wave focal spot expands several times relative to incident acoustic wave Even decades of times, and the focusing amplification increases with the increase of drop size, therefore phase transformation micro droplets have than receiving The rice lower phase transformation threshold value of drop.Based on this, there is scholar to gather the phase transformation nano-liquid droplet of intravascular dispersion using ultrasonic standing wave field Collection forms the drop aggregation of micron-scale, is focused amplification to incident acoustic wave using drop aggregation, and then significantly reduce The acoustic pressure threshold value of drop phase transformation, while making the phase transformation of the generation of phase transformation nano-liquid droplet and the preceding Similar size distribution of aggregation after aggregation micro- Bubble, to guarantee the vibration activity of phase-converted microbubbles under ultrasonication.

However, the generation of ultrasonic standing wave field needs two symmetrically placed ultrasonic transducers or a ultrasound staggered relatively Energy converter and a sound reflection board, and require to be steered particle between energy converter, therefore significantly limit it in reality Space controllability when border is applied.In addition, the phenomenon that being alternately distributed in ultrasonic standing wave field there are multiple node and antinode, thus Other particles can be captured at random outside target area, and the presence of multiple antinodes will also result in the outer acoustic pressure secondary maximum of target area The appearance of value, and then generate security risk.Therefore, in order to realize that the flexible sound of phase transformation nano-liquid droplet under condition of living body manipulates, promote Into the liquid drop control technology based on ultrasound in clinical application, urgent need develops a kind of safer, flexible phase transformation nano fluid Drop sound manipulates technology.

In particle sound control technique, the sound manipulation based on vortex sound field passes through between the adjacent array element of the ultrasonic vortex energy converter of adjusting Phase be centrally formed intermediate pressure section in a low voice, i.e. momentum trap in vortex sound field, to complete to the spatial manipulation of particle.Relative to super Sound standing wave field, vortex sound field can be generated by the single ultrasonic transducer or transducer array for being located at target area side, thus It has the space operability of height under condition of living body, and the distinctive orbital angular momentum of the sound field that is vortexed may be implemented to sound The rotation manipulation of particle in.However, vortex sound field used is mainly symmetrical uniform of acoustic pressure in sound field in document at present Vortex sound field, and concentrate on the sound manipulation research to particle and microvesicle.In homogeneous vortex sound field central area, particle and microvesicle It will be collected at vortex center intermediate pressure section (i.e. node) and then formation bulk aggregation in a low voice, and phase transformation nano-liquid droplet is due to it The difference of acoustic impedance will be gathered in vortex center periphery high sound pressure region (i.e. antinode), shape under acoustic radiation force effect At larger-diameter cyclic annular aggregation, cause phase transformation nano-liquid droplet aggregation extent under uniform focus vortex sound field reflecting lower, and It is unfavorable for being precisely controlled for the zone of action in the assisted focused ultrasonic therapy of drop.

Chinese patent: a kind of generation device and method (CN109261472A) of space-focusing vortex sound field utilize ball Face energy converter generate sound pressure amplitude show center press in a low voice, the focusing vortex sound field of peripheral annular high sound pressure characteristic distributions, can So that the contrast microbubbles of full entire imitative body blood vessel are gathered in rapidly vortex sound field center intermediate pressure section in a low voice.But it has not yet to see Utilize the report for focusing vortex sound field manipulation phase transformation nano-liquid droplet.

Summary of the invention

For phase transformation nano-liquid droplet phase transformation threshold value is excessively high and the existing particle sound manipulation technology based on ultrasonic standing wave field Limitation, the purpose of the present invention is to provide a kind of phase transformation nano-liquid droplet regulation sides that vortex sound field is focused based on spatial non-uniform Method, to realize to the flexible, accurate, efficient of phase transformation nano-liquid droplet spatial distribution in the histoorgans such as blood vessel and phase transformation threshold value Tone control.

In order to achieve the above object, the invention adopts the following technical scheme:

A kind of phase transformation nano-liquid droplet regulation device focusing vortex sound field based on spatial non-uniform, the regulation device include coke Domain can be overlapped ultrasonic cavitation energy converter and spherical focusing ultrasonic transducer (focus ultrasound division battle array spherical surface energy converter), The phase difference of the driving signal of the adjacent division array element of the spherical focusing ultrasonic transducer is consistent, and there are n (n >=1) is a It is different from other division array element power, acoustic pressure maximum point is generated in vortex sound field focal regions inner annular antinodes for making to focus Divide array element.

Preferably, the division array element of the spherical focusing ultrasonic transducer is divided into A class division array element and B class division array element (position is adjacent or disperses), the quantity that A class divides array element are greater than B class and divide array element, and the power W that two class of A, B divides array element expires Foot: W_B=aW_A, wherein 0 < a < 1.

Preferably, the phase difference of the driving signal of the spherical focusing ultrasonic transducer division array element is that (N is array element to 2 π/N Number) non-zero integer multiples.

Preferably, the ultrasonic cavitation energy converter emits single Microsecond grade short pulse by certain frequency (for example, 2-10MHz) Ultrasound.

Preferably, the regulation device further includes imitative body, the water tank for placing imitative body and imitative for observing and recording The high speed micro imaging system of intracorporal phase transformation nano-liquid droplet and phase-converted microbubbles.

It is a kind of based on spatial non-uniform focus vortex sound field phase transformation nano-liquid droplet regulate and control method, the regulation method include with Lower step:

1) pass through the driving electricity of the above-mentioned spherical focusing ultrasonic transducer of adjusting (focusing ultrasound division battle array spherical surface energy converter) Road is consistent the phase difference of the driving signal of the adjacent division array element of the spherical focusing ultrasonic transducer, and there are one Above division array elements different from other division array element power, so that the spherical focusing ultrasonic transducer be made to generate in one The heart is pressed in a low voice, peripheral annular high sound pressure is distributed and has the non-homogeneous focusing vortex sound of acoustic pressure maximum point on loud pressure area ；

2) phase transformation in the vortex sound field (vortex sound field central area) is made to receive using the non-homogeneous focusing vortex sound field Rice drop aggregation；

3) it after stopping non-homogeneous focusing vortex sound field described in step 2), is induced using above-mentioned ultrasonic cavitation energy converter poly- The phase transformation nano-liquid droplet of collection forms phase-converted microbubbles.

Preferably, in the step 2), phase transformation nano-liquid droplet is gathered in acoustic pressure pole in the non-homogeneous focusing vortex sound field Acoustic pressure large area where big value point.In the step 3), ultrasonic cavitation energy converter (3) is by certain frequency (for example, 2- 10MHz) emit single Microsecond grade short pulse ultrasound, makes the aggregation being located in the above-mentioned non-homogeneous focal regions position for focusing vortex sound field Drop phase transformation.

Preferably, the regulation method is further comprising the steps of: using high speed micro imaging system to imitating intracorporal phase transformation Nano-liquid droplet is positioned at this and imitates and intracorporal non-homogeneous focus accumulation process under vortex sound field reflecting and observed, remember in focal regions Record.

Preferably, the regulation method is further comprising the steps of: using high speed micro imaging system to the phase transformation after aggregation The phase transformation of nano-liquid droplet and the evanishment for being formed by phase-converted microbubbles are observed, are recorded.

The beneficial effects of the present invention are embodied in:

The present invention is produced by relative power and phase between adjusting ultrasonic transducer (spherical focusing ultrasonic transducer) array element It is non-homogeneous using this there are the non-homogeneous focusing vortex sound field of acoustic pressure maximum in raw acoustic pressure asymmetric distribution, cyclic annular antinode Vortex sound field is focused, the phase transformation nano-liquid droplet of dispersion is collected as to the bulk drop aggregation of micron-scale, drop in aggregation Nano-scale distribution ensure the vibration activity of phase-converted microbubbles, to significantly reduce the phase transformation threshold value of phase transformation nano-liquid droplet, this Invention can be realized by the ultrasonic transducer (spherical focusing ultrasonic transducer, ultrasonic cavitation energy converter) for being located at target area side The tone control of phase transformation nano-liquid droplet, and liquid drop control region can be limited only to vortex sound field focal regions, relative to based on ultrasonic standing wave The drop tone control of field has higher flexibility ratio and safety (especially under condition of living body).

Further, the present invention acts on the phase transformation nano-liquid droplet of aggregation using single Microsecond grade short pulse, avoids phase transformation Microvesicle generates biggish fusion under ultrasonication, avoids phase-converted microbubbles oversized and influences vibration activity and (also avoid imitative The judgement to microvesicle initial radium is influenced in body experiment).

Detailed description of the invention

Fig. 1 is to regulate and control experimental system based on the non-homogeneous phase transformation nano-liquid droplet for focusing vortex sound field in the embodiment of the present invention Schematic diagram；Wherein: 1. focus vortex sound field driving circuit, 2. high speed micro imaging systems, 3. ultrasonic cavitation energy converters, 4. blood vessels Imitative body, 5. focus ultrasonic vortex energy converter, 6. water tanks.

Fig. 2 is the dimension measurement result of phase transformation nano-liquid droplet obtained in experiment；Wherein: being (a) volume basis of drop It is (b) the number percent profile of drop than distribution.

Fig. 3 is the optical imagery of phase transformation nano-liquid droplet accumulation process in non-uniform focus vortex sound field.

Fig. 4 is acoustic pressure distribution map in non-uniform focus vortex acoustic field focus transverse plane.

Fig. 5 is the vector distribution map of acoustic radiation force suffered by phase transformation nano-liquid droplet in non-uniform focus vortex sound field；Wherein (a) It is (b) the details distribution of acoustic radiation force suffered by acoustic pressure non-uniform Distribution region (dotted line frame in a) interior drop for overall situation distribution.

Fig. 6 is the simulation result of non-uniform focus vortex sound field；Wherein: (a) being distributed for the acoustic pressure of sound field, (b) be sound field The vector of interior phase transformation nano-liquid droplet stress is distributed.

Fig. 7 is the optics picture of phase transformation nano-liquid droplet aggregation phase transformation and phase-converted microbubbles evanishment.

Fig. 8 is variation relation of the various concentration phase transformation nano-liquid droplet aggregation front and back phase transformation threshold value with drop initial concentration.

The optical imagery of phase-converted microbubbles when Fig. 9 is 5.35s after ultrasonic phase conversion pulse acts on；Wherein: (not gathering for dispersion (a) Collection) phase transformation nano-liquid droplet generate phase-converted microbubbles, (b), (c), (d) be different initial concentrations under drop aggregation generate phase Become microvesicle, (a), (b), (c), phase transformation nano-liquid droplet initial concentration is respectively 1.64 × 10 in (d)¹⁰droplets /ml、4.1× 10⁹droplets/ml、8.2×10⁹droplets/ml、1.64×10¹⁰droplets/ml。

Figure 10 is the initial radium distribution situation of the corresponding phase-converted microbubbles generated in the case of four kinds in Fig. 9.

Specific embodiment

The present invention is described in further details with reference to the accompanying drawings and examples.

It is proposed by the present invention that method is regulated and controled suitable for non-free based on the non-homogeneous phase transformation nano-liquid droplet for focusing vortex sound field The regulation of the spatial distribution of phase transformation nano-liquid droplet and its phase transformation threshold value in field flow body.The present invention is using the ultrasonic vortex energy converter of focusing The non-homogeneous focusing vortex sound field generated, in the imitative regulation completed in vivo to phase transformation nano-liquid droplet of blood vessel, comprising the following steps:

Step 1: placement focuses ultrasonic vortex energy converter, transparent blood vessel is imitated body, high speed microscope camera and ultrasonic cavitation and changed Can device, the relative tertiary location between accurate adjusting.

Referring to Fig. 1, the transparent blood vessel of production being made of acrylamide gel is imitated into stream of the body 4 as phase transformation nano-liquid droplet Circulation passage, and transparent blood vessel is imitated the y-axis direction along Fig. 1 of body 4 and is placed in the water tank 6 for filling degassed water；Ultrasound vortex is focused to change Energy device 5 is fixed on water tank 6, axially along the x-axis direction；The high speed microscope camera of high speed micro imaging system 2 is along the x-axis direction It places, optical path reaches pick-up lens via the central hole for focusing ultrasonic vortex energy converter 5, records optical data；Ultrasonic cavitation Energy converter 3 is placed along the z-axis direction.In order to be received using the ultrasonic vortex energy converter 5 of focusing and the realization of ultrasonic cavitation energy converter 3 to phase transformation The regulation of rice drop, ultrasonic cavitation energy converter 3 is connected with corresponding transducer drive device.Meanwhile it establishing and focusing vortex sound Field generation system generates multi-channel drive signal and input focus ultrasound vortex energy converter 5 by focusing vortex sound field driving circuit 1 (16 division battle array spherical surface energy converters etc. specifically can be used and focus ultrasound division battle array spherical surface energy converter)；Focus vortex sound field driving electricity Road 1 includes power supply, signal generator (timing control), power amplifier module and impedance matching circuit, and wherein power supply is used for letter Number generator and power amplifier module provide energy, and signal generator generates multichannel phase and (wanted according to vortex sound field to phase Ask), frequency (according to ultrasound division battle array spherical surface transducer frequency is focused) adjustable square-wave signal, through a passive low-pass filter It filters off signal high frequency components and converts sine wave for square wave approximation, and then by power amplifier module to multiple paths of sine wave signals Amplitude amplify, finally by impedance matching circuit will by amplification sine wave signal and focus ultrasound division battle array spherical surface Each fan-shaped array element of energy converter carries out precision tuning matching, while adjusting to the amplitude of each sine wave signal by amplification It is whole.

Adjusting imitative 4 position of body of transparent blood vessel imitates the focal regions for focusing ultrasonic vortex energy converter 5 in body 4 in transparent blood vessel Portion.By 16 division battle array spherical surface energy converters for, opening diameter and focal length are 12cm, calculate known to vortex sound field focal regions away from From transducer face 10.4cm.Transparent blood vessel is adjusted using three-dimensional motion device and imitates 4 position of body, and transparent blood vessel is made to imitate body 4 It is contour with 16 division battle array spherical surface energy converter centers, and transparent blood vessel is imitated 4 center of body and is being changed with 16 division battle array spherical surface energy converters Energy device axial direction distance is 10.4cm, so that it is guaranteed that vortex sound field focal regions, which are located at blood vessel, imitates internal portion.

Step 2: the normal saline solution for being mixed with a certain concentration phase transformation nano-liquid droplet is pumped into transparent blood vessel using jerk pump Inside imitative body 4, utilizes focusing vortex sound field generation system to imitate 4 center of body in transparent blood vessel after solution stand and generate non-homogeneous gather Burnt vortex sound field.

Production has obtained the phase transformation nano-liquid droplet being made of perflexane and fluorocarbon surfactant and has utilized in experiment Zetasizer nanoparticle measuring system measures the size distribution of phase transformation nano-liquid droplet, and Fig. 2 illustrates utilization The size distribution results for the phase transformation nano-liquid droplet that Zetasizer nanoparticle measuring system obtains: phase transformation nano-liquid droplet is average straight Diameter is 400~420nm, and diameter distribution is 100~1000nm；The initial concentration of corresponding drop is about 1.64 × 10¹² Droplets/ml (is respectively diluted phase transformation nano-liquid droplet solution using physiological saline in experimentation with normal saline dilution 100 times, 200 times and 400 times.) after phase transformation nano-liquid droplet solution be pumped into transparent blood vessel imitate body 4 in.

It opens and focuses vortex sound field generation system, adjust the relative power and phase between focusing ultrasonic 5 array element of vortex energy converter Place value, by taking 16 division battle array spherical surface energy converters as an example, the phase difference between adjustable adjacent ultrasonic transducer array element is fixed as π/8, The power for adjusting 9~No. 12 four transducer array elements is 0.25 times of other array element power.Focusing ultrasound is input in control While the phase difference of the driving signal of the adjacent division array element of division battle array spherical surface energy converter is consistent, there is difference by control The quantity of the division array element of power and position, make to focus ultrasonic vortex energy converter 5 generate there is center press in a low voice, peripheral annular height The vortex sound field central area (focusing the focal regions of vortex) of acoustic pressure characteristic distributions, and on antinode (the loud pressure area of peripheral annular) Non-homogeneous focusing vortex sound field with acoustic pressure extreme point (acoustic pressure is bigger relative to sound pressure level at surrounding point).

Vortex ultrasonic transducer is focused in experimentation and uses continuous operation mode, utilizes non-homogeneous focusing vortex sound field pair Phase transformation nano-liquid droplet is assembled, assemble index 3min, using high speed micro imaging system 2 to non-homogeneous focusing vortex sound field The accumulation process of interior phase transformation nano-liquid droplet is observed, and analysis of the droplet aggregation radius and area change with time situation.Ginseng See Fig. 3, it is non-homogeneous to focus the detailed process that phase transformation nano-liquid droplet is assembled under vortex sound field reflecting are as follows: to carve at the beginning, phase transformation is received Rice drop is evenly distributed on blood vessel and imitates internal portion, optical characteristics and lesser ruler as having with water phase nano-liquid droplet Very little, the phase transformation nano-liquid droplet of dispersion is invisible in optical imagery.At the 0s moment, opens and focus vortex sound field generation system, In Blood vessel is imitative to generate non-homogeneous focusing vortex sound field in vivo, and under the action of its acoustic radiation force, the phase transformation nano-liquid droplet of dispersion starts Aggregation, in 30s, optical imagery center is observed that the aggregation zone of phase transformation nano-liquid droplet, shows as pixel in the region The decline of point gray value.With the increase of sound field reflecting time, phase transformation nano-liquid droplet is further mobile to vortex center region, Vortex sound field central area initially forms a bulk drop aggregation when 50s, the aggregation base of phase transformation nano-liquid droplet in 180s This completion, drop aggregation are rendered as approximate circle in the picture.

Acoustic pressure distribution of the non-homogeneous focusing vortex sound field generated in experiment in focus transverse plane is referring to fig. 4.Fig. 4 In, focusing vortex sound field ring-type antinode upper left side, there are an acoustic pressure large areas, are vortexed to demonstrate non-homogeneous focusing The generation of sound field (there are acoustic pressure maximum in acoustic pressure asymmetric distribution, cyclic annular antinode), thus it is speculated that exactly because acoustic pressure is non-homogeneous Property distribution so that phase transformation nano-liquid droplet is gathered into bulk drop aggregation under the action of acoustic radiation force.

By the vector distribution situation for focusing phase transformation nano-liquid droplet stress in vortex sound field non-homogeneous in Fig. 5 (a) it is found that at this time Phase transformation nano-liquid droplet stress condition is that vortex center region drop is forced away from vortex center, and outer region drop stress is directed toward whirlpool Rotation center, and at the vortex sound field ring-type antinode upper left side non-homogeneous place of acoustic pressure, drop Impact direction deflects, no longer backwards to whirlpool Rotation center.By phase transformation nano-liquid droplet is distributed it is found that liquid in the region by force vector in acoustic pressure non-uniform Distribution region in Fig. 5 (b) It drips stress to be directed toward a bit, therefore predicts that phase transformation nano-liquid droplet will be gathered in herein under non-homogeneous vortex sound field reflecting, form one A bulk drop aggregation.

Due to the limitation of sound field scanning device spatial accuracy, the minimum range of adjacent point-to-point transmission is when sound field scans 0.25mm, so that sound field scan data is to focus can not be clear when particle in vortex sound field carries out force analysis in using Fig. 4 Ground reflects further details.For the aggregation machine more clearly to phase transformation nano-liquid droplet in non-homogeneous focusing vortex sound field System is inquired into, and has carried out simulation calculation to the distribution of acoustic pressure in non-homogeneous focusing vortex sound field.

The physics analysis of phase transformation nano-liquid droplet accumulation process is as follows:

For liquid particle, volume does not change substantially in sound field, when the radius of particle is much smaller than ultrasonic wavelength When, consider sharp keen scattering, in Single Medium, the potential energy of particle can be expressed from the next in sound field:

In formula: r is the radius of particle, ρ₀For the density of medium, p_inFor the acoustic pressure of incident acoustic wave, c₀In the medium for ultrasound Spread speed, v_inFor the speed of particle position,WithIt respectively indicates flat to the time of acoustic pressure and velocity squared value , f₁And f₂Calculation expression it is as follows:

In formula: c is the spread speed of ultrasound in the particle；ρ is the density of particle.V in formula (1)_inIt can be by velocity potential V Gradient acquire, velocity potential V is given by:

For the particle in the medium of suspending, suffered by acoustic radiation force can be calculated by the gradient of potential energy, i.e. sound Radiant force

Parameter setting is as follows when simulation calculation: the radius of phase transformation nano-liquid droplet is 200nm, and the density of phase transformation nano-liquid droplet is 1680kg/m³, acoustic wave propagation velocity is 520m/s in drop, focuses ultrasonic vortex energy converter (16 division battle array spherical surface energy converter) Centre frequency be 645KHz, radius of curvature 120mm, opening radius 120mm, central small hole radius is 60mm, array element Number is 16, and the phase difference between adjacent array element is π/8, and the power of 9~No. 12 array elements is respectively 0.1875W, remaining array element power Respectively 0.75W.The density of medium (water) is 1000kg/m³, the velocity of sound in medium (water) is 1540m/s.

The distributed data importing of acoustic pressure in the non-homogeneous focusing vortex acoustic field focus cross section that experiment measurement is obtained MATLAB software carries out simulation calculation to the stress condition of phase transformation nano-liquid droplet in non-homogeneous focusing vortex sound field.It focuses and is vortexed By adjusting the corresponding division array element of the ultrasonic vortex energy converter of focusing (16 division battle array spherical surface energy converter) when sound field simulation calculation Power can form a biggish region of acoustic pressure on sound field center upper left side, as shown in Fig. 6 (a).Utilize emulation in Fig. 6 (a) The distributed data of acoustic pressure in the non-homogeneous focusing vortex sound field being calculated, it is non-homogeneous to acoustic pressure in non-homogeneous focusing vortex sound field The distribution of force situation of phase transformation nano-liquid droplet carries out simulation calculation in region, as a result as shown in Fig. 6 (b).By Fig. 6 (b) it is found that In Under non-homogeneous focusing vortex sound field reflecting, the acoustic pressure Nonuniform Domain Simulation of Reservoir in cyclic annular antinode, along vortex sound field radial direction, phase transformation is received Rice drop stress is directed in acoustic pressure Nonuniform Domain Simulation of Reservoir a bit, i.e. circled positions in figure, and the ring-type in vortex center periphery is high On acoustic pressure band, phase transformation nano-liquid droplet Impact direction is clockwise on the left of the point, and right side phase transformation nano-liquid droplet Impact direction is then inverse Hour hands, this shows that the phase transformation nano-liquid droplet on vortex sound field ring-type high sound pressure band also can gradually be assembled to the point, therefore most last phase Becoming nano-liquid droplet will assemble to form bulk aggregation at this point, i.e. the Heterogeneous distribution of acoustic pressure makes phase transformation nano-liquid droplet exist Bulk drop aggregation is gathered under the action of acoustic radiation force.

Step 3: being utilized respectively high speed micro imaging system 2 and active cavitation detection technique determines that phase transformation nano-liquid droplet is poly- The position of collective and ultrasonic cavitation energy converter focal regions, and 3 position of ultrasonic cavitation energy converter is adjusted by three-dimensional motion device, so that The focal regions of ultrasonic cavitation energy converter 3 are accurately be overlapped on spatial position with the focal regions for focusing ultrasonic vortex energy converter 5, utilize ultrasound Cavitation energy converter 3 emits ultrasonic pulse, induces the phase transformation nano-liquid droplet inside drop aggregation to generate phase transformation, and aobvious using high speed Micro- imaging system 2 carries out observation in real time and record to the phase transformation of drop and the evanishment of phase-converted microbubbles.

Only emit a phase conversion pulse every time in ultrasonic cavitation energy converter (centre frequency=5MHz), and pulse length is 20 periods, when corresponding under the ultrasonication of a length of 4 μ s, the phase transformation for the phase transformation nano-liquid droplet that high speed micro imaging system 2 records And the evanishment of phase-converted microbubbles is referring to Fig. 7.(0s moment) closes poly- before ultrasonic cavitation energy converter 3 emits ultrasonic pulse Burnt vortex sound field generation system, phase transformation nano-liquid droplet aggregation falls under the effect of gravity at this time, and drop the morphology of the aggregate is also sent out Changing, shown in optical imagery when such as 0.25s.In 0.26s, ultrasonic cavitation energy converter 3 emits ultrasonic pulse, in ultrasonic arteries and veins Under the action of punching drop aggregation occur accelerate suddenly move downward, in 2.2s phase transformation nano-liquid droplet aggregation substantially away from The optical observation visual field can observe the appearance of phase-converted microbubbles in 2.7s, later phase transformation under the action of buoyancy in the picture Microvesicle gradually floats, and since the Convention diffusion of air in phase-converted microbubbles and physiological saline acts on, phase transformation is micro- in floating-upward process Foam product becomes larger.

Step 4: the optics picture obtained under analysis different condition according to step 3, show that identical phase transformation nano-liquid droplet is dense Under the conditions of degree, drop is assembling the initial radium distribution with phase transformation threshold value and phase-converted microbubbles under dispersion two states, and complete At the comparative analysis between the two.

Referring to Fig. 8, under identical phase transformation nano-liquid droplet concentration conditions, with/without non-homogeneous focusing vortex sound field (without being vortexed/have Be vortexed) when drop phase transformation threshold value it is different with drop initial concentration and change.As shown in Figure 8, when phase transformation nano-liquid droplet concentration is protected When holding constant, after forming phase transformation nano-liquid droplet aggregation using non-homogeneous focusing vortex sound field, the phase of drop in drop aggregation Variable threshold value significantly reduces (p < 0.01) relative to the phase transformation nano-liquid droplet of dispersion, and with the increase of drop initial concentration, and two kinds Under the conditions of (without be vortexed/have vortex) the phase transformation threshold value of phase transformation nano-liquid droplet is all gradually reduced.

Referring to Fig. 9, after ultrasonic pulse effect when 5.35s, from the light of phase-converted microbubbles in the case of (a), (b), (c), four kinds of (d) Image comparison is learned it is found that synchronization after drop phase transformation, (phase transformation is micro- for the radius distribution for the phase-converted microbubbles that phase transformation nano-liquid droplet generates The size of bubble) without significant change.

Referring to Figure 10, when four kinds of (a), (b), (c), (d) in Fig. 9, the radius mean value of phase-converted microbubbles is all 12 In~16 μ ms, this shows significantly reducing drop phase by the phase transformation nano-liquid droplet of non-homogeneous focusing vortex sound field aggregation The size of the phase-converted microbubbles of its generation can't be significantly increased while variable threshold value.