Cell cluster stretching and compression method and device based on surface acoustic wave harmonic regulation

Abstract

The application discloses a kind of cell cluster stretching and compression method and device based on surface acoustic wave harmonic regulation, and the application includes central processing unit, power amplifier, signal generator, microfluidic cavity module and surface acoustic wave driving chip;The application utilizes harmonic multiplexing interdigital transducer, through the collocation of different frequency excitation signals and amplitude, to realize the construction of adjustable acoustic field in microfluidic cavity, and then realize the stimulation of cell aggregation, stretching and compression of cell cluster;Due to the influence of dynamic excitation on cell cluster, it accelerates the entry of drug into cell interior, thereby promoting drug screening for cells;Harmonic multiplexing interdigital transducer is optimized by finite element simulation, and the required acoustic field is excited under the condition of matching excitation frequency, power, the size of interdigital electrode and microfluidic cavity boundary condition;The excitation power of surface acoustic wave can be selectively regulated to excite different forms of acoustic field for excitation.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of analytical instruments, in particular to a cell cluster stretching and compression method and device based on surface acoustic wave harmonic regulation. BACKGROUND

[0002] Tumor is a serious threat to human health, and there is still a great challenge in finding more effective anti-tumor drugs. Traditional drug screening methods often provide limited information and cannot fully simulate the response of tumor spheres in complex physiological environments. Therefore, seeking new drug screening methods is an important topic in current tumor research.

[0003] In recent years, artificially stimulating tumor spheres in an anti-tumor drug environment has become an attractive drug screening method. By applying different degrees of dynamic stimulation, such as dynamic stretching or compression, the behavior of tumor spheres in different tissue environments can be simulated, and the effect of drugs on tumor growth, invasion and metastasis can be evaluated. In order to more truly reflect the mechanism of drugs in the body and provide more accurate efficacy evaluation data, researchers have developed various techniques for dynamically stimulating tumor spheres, such as atomic force microscopy, electrical excitation, magnetic excitation, and micro-pipette loading. However, although these methods can apply mechanical stimulation to some extent, they also have many limitations, such as low processing throughput, cumbersome processing procedures, and the need for special markers, which can have a significant impact on cell activity.

[0004] Ultrasound-assisted drug screening research has been verified in multiple application fields, and these systems can process biological samples with high throughput and non-invasively, while maintaining cell activity. Similar to other contact methods, sound waves can also apply acoustic radiation force stimulation to cell clusters composed of tumor spheres, but it requires the design of an acoustic field with sufficiently high precision and a stable and specified form of force field. Therefore, developing a stretching and compression stimulation method for tumor cell clusters with the aid of sound waves to achieve a biologically friendly and contactless high-throughput screening of tumor drugs is a challenging task. SUMMARY

[0005] In view of the above problems existing in the prior art, the present application provides a cell cluster stretching and compression method and device based on surface acoustic wave harmonic regulation, which can well realize the stretching and compression stimulation of cell clusters and accelerate drug screening.

[0006] One object of the present application is to provide a cell cluster stretching and compression device based on surface acoustic wave harmonic regulation.

[0007] The cell cluster stretching and compression device based on surface acoustic wave harmonic regulation of the application comprises a central processing unit, a power amplifier, a signal generator, a microfluidic cavity module and a surface acoustic wave driving chip; wherein the microfluidic cavity module is located below the surface acoustic wave driving chip; the surface acoustic wave driving chip is connected to the power amplifier, the power amplifier is connected to the signal generator, and the signal generator is connected to the central processing unit;

[0008] The microfluidic cavity module comprises a liquid inlet, a liquid outlet and a microfluidic cavity; the surface of the microfluidic cavity is open, the inside is a cavity, and the liquid inlet and the liquid outlet are respectively arranged on the opposite sides of the microfluidic cavity;

[0009] The surface acoustic wave driving chip comprises a substrate and a harmonic multiplexing interdigital transducer, the harmonic multiplexing interdigital transducer comprises a plurality of series-connected interdigital electrodes; a plurality of interdigital electrodes are respectively arranged on the substrate, and the plurality of interdigital electrodes are connected in series to the output end of the power amplifier; each interdigital electrode has a different finger width, different finger widths correspond to different center frequencies of the interdigital electrodes, and the center frequencies of the interdigital electrodes are adjusted by the finger width; the surface acoustic wave driving chip is inverted on the microfluidic cavity module, that is, the harmonic multiplexing interdigital transducer directly faces the microfluidic cavity of the microfluidic cavity module.

[0010] According to the required acoustic field, the corresponding frequency and power of the required acoustic field are obtained; the central processing unit sends a digital signal to the signal generator, controls the signal generator to correspondingly send excitation signals of different frequencies and corresponding powers from different output channels according to the parameterized scanning results; the signal generator converts the digital signal into an electrical signal, and transmits the superimposed excitation signals of different frequencies from each output channel to the power amplifier; the power amplifier converts the electrical signal into an amplified power signal and transmits it to the harmonic multiplexing interdigital transducer; the interdigital electrode with the same center frequency as the frequency of the excitation signal generates a surface acoustic wave through the inverse piezoelectric effect, and the surface acoustic wave is transferred to the flow field in the set region to form the required acoustic field; by designing different forms of harmonic multiplexing interdigital transducers, the frequency and power of the excitation signal are changed to generate a specified acoustic field, so that the acoustic field respectively produces the effects of gathering into a cluster, positioning, stretching and compression on the cells in turn.

[0011] The microfluidic cavity module is used for culturing cells and storing the required nutrient solution for the cells, and maintaining the required environment for the survival of the cells. The height of the microfluidic cavity is 50-1000 μm, and the length and width are 5-20 mm. A flow valve is arranged on the microfluidic cavity inlet or outlet through an external catheter. After the valve is closed, the liquid in the catheter and the microfluidic cavity will no longer flow. The liquid inlet of the microfluidic cavity is injected with a drug, and the drug is paclitaxel, cisplatin or 5-fluorouracil, etc., and the concentration is 0-1000 μM. The material property of the microfluidic cavity is polydimethylsiloxane (PDMS).

[0012] Further, the micro-observation device includes a fluorescence microscope and a CCD camera, and the micro-fluid cavity module is placed on a sample stage of the fluorescence microscope; wherein, a charge coupled device (CCD) camera is arranged on the fluorescence microscope, and the CCD camera is connected to the central processing unit.

[0013] The harmonic multiplexing interdigital transducer on the surface acoustic wave driving chip includes a plurality of interdigital electrodes, each interdigital electrode has different finger width, the finger width is 20-100 mu m, the index is 10-30 pairs, the center frequency range is 10-50 MHz, and the applied power range is 100-1000 mW. The center frequency is determined by the finger width, and the relationship between the finger width and the center frequency is w=c / (4f0), w is the finger width, c is the substrate wave speed, generally 3960 m / s in lithium niobate substrate, and f0 is the center frequency.

[0014] Generally, in order to generate different forms of stimulation with appropriate precision of the acoustic field, the frequency of the interdigital transducer is generally 10-50 MHz, the corresponding interdigital width is 20-100 mu m, the height of the micro-channel cavity is generally 2-5 times the size of the cell cluster, and the width of the micro-channel cavity is mainly matched with the action size of the substrate acoustic field.

[0015] Another object of the present application is to provide a cell cluster stretching and compression method based on harmonic control of surface acoustic waves.

[0016] The cell cluster stretching and compression method based on harmonic control of surface acoustic waves of the present application includes the following steps:

[0017] 1) injecting cells into the micro-channel cavity;

[0018] 2) according to the required converging acoustic field, obtaining the corresponding frequency and power, the central processing unit controlling the signal generator to output the excitation signal of the corresponding frequency and power to the power amplifier for amplification and transmission to the harmonic multiplexing interdigital transducer; the interdigital electrode with the same frequency as the center frequency of the excitation signal generates surface acoustic waves through the inverse piezoelectric effect, and the surface acoustic waves are transferred to the flow field in the set area to form a converging acoustic field and make the cell cluster converge;

[0019] 3) Wait for the cell crosslinking to form cell clusters;

[0020] 4) According to the required converging acoustic field, the corresponding frequency and power are obtained, the central processing unit controls the signal generator to output the excitation signal of the corresponding frequency and power to the power amplifier for amplification and transmission to the harmonic multiplexing interdigital transducer; the interdigital electrode with the same frequency as the center frequency of the excitation signal generates an acoustic surface wave through the inverse piezoelectric effect, and the acoustic surface wave is transferred to the flow field in the set area to form a converging acoustic field, so that the initial cell clusters are recaptured at the acoustic pressure node position;

[0021] 5) After observing that the cell clusters grow well through the microscopic observation module, inject the drug from the liquid inlet of the microchannel cavity;

[0022] 6) According to the required stretching acoustic field, the required frequency and power are obtained, the central processing unit controls the signal generator to output the excitation signal of the corresponding frequency and power to the power amplifier for amplification, and gradually increases the applied power from low to high, and transmits to the harmonic multiplexing interdigital transducer; the harmonic multiplexing interdigital transducer generates an acoustic surface wave that is transferred to the flow field in the set area, the harmonic multiplexing interdigital transducer generates an acoustic surface wave that is transferred to the flow field in the set area, the acoustic pressure node in the set area migrates to both sides, and the cell clusters are subjected to acoustic radiation force towards both sides, thereby stretching the cell clusters;

[0023] 7) According to the required compression acoustic field, the required acoustic field corresponding frequency and power are obtained, the central processing unit controls the signal generator to output the excitation signal of the corresponding frequency and power to the power amplifier for amplification, and transmits to the harmonic multiplexing interdigital transducer; the harmonic multiplexing interdigital transducer generates an acoustic surface wave that is transferred to the flow field in the set area, forming a converging acoustic field, the acoustic pressure node in the set area will migrate to the inside, and the cell clusters will be subjected to acoustic radiation force towards the inside, thereby producing compression loading on the cell clusters;

[0024] 8) Repeat 6) and 7), repeatedly stretch and compress the cell clusters to achieve repeated dynamic stimulation of the cell clusters; the dynamic stimulation can produce stretching and compression traction on the cell membrane of the cells, accelerate the entry of the drug into the cells; at the same time, it can make the drug penetrate into the cells inside the cell clusters, and accelerate the action on the entire cell clusters;

[0025] 9) Capture image signals and fluorescence signals through a CCD camera and a fluorescence microscope;

[0026] 10) The image signals represent the deformation state of the cell clusters after stretching and compression stimulation, and the fluorescence signals represent the drug treatment state of the cell clusters after stimulation, and the central processing unit analyzes the image signals and the fluorescence signals.

[0027] In step 1), the size of the cells is 10-30 mu m, and the flow rate of the cells injected into the microfluidic cavity is 0.5-10 mu l / min.

[0028] In step 2), the applied frequency is 10-50 MHz, the applied power is 100-500 mW, and the excitation time is 30-60 s.

[0029] In step 3), the waiting time is 6-24 hours.

[0030] In step 4), the applied frequency is 10-50 MHz, the applied power is 100-500 mW, and the excitation time is until the cell cluster is recaptured at the acoustic pressure node position.

[0031] In step 5), the drug is paclitaxel, cisplatin or 5-fluorouracil, etc., and the concentration is 0-1000 mu M.

[0032] In step 6), the applied frequency is 10-50 MHz, the applied power is slowly increased from low to high in the range of 0-1000 mW, the step length of the applied power is 5-20 s, and the excitation time is 10-30 s.

[0033] In step 7), the applied frequency is 10-50 MHz, the applied power is 100-1000 mW, and the excitation time is 10-30 s.

[0034] In steps 2), 4), 6) and 7), according to the required acoustic field, the frequency and power are parameterized scanned by finite elements to obtain the corresponding frequency and power of the required acoustic field. The signal generator converts the digital signal into an electric signal, and the excitation signals of different frequencies are superimposed and output from each output channel to a power amplifier; the power amplifier converts the electric signal into an amplified power signal and transmits it to the harmonic multiplexing interdigital transducer;

[0035] Advantages of the application:

[0036] (1) The application utilizes the harmonic multiplexing interdigital transducer, designs the interdigital electrodes with multiple center frequencies, and realizes the construction of an adjustable acoustic field in the microfluidic cavity by matching the excitation signals and power of different frequencies, so as to realize the convergence of cells, and the stretching and compression stimulation of the cell cluster; due to the influence of dynamic excitation on the cell cluster, the drug enters the cell interior, thereby promoting the drug screening for cells;

[0037] (2) The harmonic multiplexing interdigital transducer can be optimized through COMSOL finite element simulation, and in the case of matching the excitation frequency, power, size of the interdigital electrode and the boundary conditions of the micro-channel cavity, the required acoustic field is excited; the surface acoustic wave excitation power can be selectively regulated to excite different forms of acoustic field for excitation. BRIEF DESCRIPTION OF DRAWINGS

[0038] Figure 1 A schematic diagram of a cell cluster stretching and compression device based on the harmonic regulation of the surface acoustic wave of the application Figure 1 A schematic diagram of an embodiment;

[0039] Figure 2 A dynamic regulation simulation effect diagram of a cell cluster stretching and compression device based on the harmonic regulation of the surface acoustic wave of the application for an embodiment thereof;

[0040] Figure 3 A parameter diagram of the series interdigital electrode of a cell cluster stretching and compression device based on the harmonic regulation of the surface acoustic wave of the application for an embodiment thereof. DETAILED DESCRIPTION

[0041] The application will be further described below with reference to the accompanying drawings and specific embodiments.

[0042] As shown in the drawings, Figure 1 The cell cluster stretching and compression device based on the harmonic regulation of the surface acoustic wave of the embodiment includes a central processing unit 1, a signal generator 2, a power amplifier 3, a surface acoustic wave driving chip 4, a microfluidic cavity module 5, a fluorescence microscope 6 and a CCD camera 7; wherein the microfluidic cavity module 5 is located below the surface acoustic wave driving chip 4; the surface acoustic wave driving chip 4 is connected to the power amplifier 3, the power amplifier 3 is connected to the signal generator 2, and the signal generator 2 is connected to the central processing unit 1;

[0043] The microfluidic cavity module 5 includes a liquid inlet, a liquid outlet and a microfluidic cavity; the surface of the microfluidic cavity is open and the inside is a cavity; the liquid inlet and the liquid outlet are respectively arranged on the opposite sides of the microfluidic cavity;

[0044] The surface acoustic wave driving chip 4 includes a substrate and a harmonic multiplexing interdigital transducer, and the harmonic multiplexing interdigital transducer includes a plurality of series interdigital electrodes; a plurality of interdigital electrodes are respectively arranged on the substrate, and the plurality of interdigital electrodes are connected in series to the output end of the power amplifier 3; each interdigital electrode has a different finger width, and the different finger widths correspond to different center frequencies of the interdigital electrodes; the center frequency of the interdigital electrode is adjusted by adjusting the finger width; the surface acoustic wave driving chip 4 is inverted on the microfluidic cavity module 5, that is, the harmonic multiplexing interdigital transducer is opposite to the microfluidic cavity of the microfluidic cavity module 5;

[0045] A CCD camera 7 is arranged on the fluorescence microscope 6, and the CCD camera 7 is connected to the central processing unit 1.

[0046] In the embodiment, the substrate is lithium niobate, the wave velocity in the lithium niobate is 3960 m / s, the material of the micro-fluidic cavity is polydimethylsiloxane (PDMS), the harmonic multiplexing interdigital transducer includes two interdigital electrodes in series, the finger width is 50 μm and 100 μm respectively, the interdigital spacing is 50 μm, and the index is 13 pairs, corresponding to the center frequencies 20 MHz and 10 MHz. Figure 2 The finite element simulation results of the harmonic mixed 10 MHz and 20 MHz signal excitation and the single-frequency 20 MHz signal excitation are shown in Figure 3 .

[0047] The principle of the harmonic acoustic surface wave acoustic field regulation for realizing the cell cluster manipulation provided by the application is as follows:

[0048] When in a far-field liquid environment, the particles will mainly be subjected to the action of the acoustic radiation force, the size and direction of the action of the acoustic radiation force are related to the gradient of the Gor'kov potential energy, at the extreme value point of the Gor'kov potential energy, the acoustic radiation force is 0, and the particles will converge to the position of the Gor'kov potential well under the action of the acoustic radiation force, so the particle manipulation can be realized by designing the position of the Gor'kov potential well.

[0049]

[0050] Wherein, F rad is the acoustic radiation force, U is the Gor'kov potential energy, and <> represents the time average in a period.

[0051] The traditional particle / cell manipulation based on the acoustic surface wave is mainly for the fixed form interdigital transducer, which is usually designed to be arranged at equal intervals and has only one center frequency, and the acoustic field distribution mode is single. Through the superposition of the multi-frequency harmonic acoustic field and the regulation of the acoustic pressure amplitude and phase distribution of the acoustic surface wave substrate, the regulation of various radiation acoustic field potential wells can be realized, and the manipulation of the pattern or trajectory of the particles / cells can be realized. Therefore, the specified acoustic field form can be set to realize the stretching and compression stimulation effect for the cell cluster.

[0052] The relationship between the excitation amplitude of a single electrical signal and time is as follows:

[0053] F1(t)=V1sin(2πf1t)

[0054] wherein V1 is a first amplitude peak-to-peak value, and f1 is a first frequency.

[0055] When there are multiple electrical signals in the circuit, the relationship between the superimposed signal and time is obtained by superimposing the excitation signal waveform:

[0056] F(t) = F1(t) + F2(t) + … = V1sin(2p f1t) + V2sin(2p f2t) + …

[0057] wherein V2 is a second amplitude peak-to-peak value, and f2 is a second frequency.

[0058] The signal of the voltage with respect to time is sent out by the signal generator 2, and the voltage is amplified by the power amplifier 3; however, since the impedance (resistance) of each device is different, the power will be different. In the experiment, the output power of the power amplifier 3 is usually measured, and the voltage size of the signal generator 2 is adjusted to match the actual power size.

[0059] The cell cluster stretching and compression method based on the surface acoustic wave harmonic regulation of the embodiment comprises the following steps:

[0060] 1) Injecting a tumor single cell sample into a micro-channel cavity;

[0061] 2) According to the required converging acoustic field, parameterize the frequency and power by COMSOL finite element simulation to obtain the excitation signal of 10MHz and 20MHz superposition with an applied power of 300mW; the signal generator 2 converts the digital signal into an electrical signal, and the central processing unit 1 controls the signal generator 2 to output the excitation signal of the corresponding frequency and power to the power amplifier 3 for amplification; the power amplifier 3 converts the electrical signal into an amplified power signal and transmits it to the harmonic multiplexing interdigital transducer; the interdigital electrode with the same frequency as the excitation signal generates a corresponding power surface acoustic wave through the inverse piezoelectric effect, and the surface acoustic wave is transferred to the flow field in the set area; the excitation time is 30-60s, a converging acoustic field is formed, and cell clusters are formed;

[0062] 3) Wait for about 24h for the cells to crosslink and form cell clusters;

[0063] 4) According to the required converging acoustic field, obtain the excitation signal of 10MHz and 20MHz superposition with an applied power of 100-500mW by finite element simulation; the harmonic multiplexing interdigital transducer generates a surface acoustic wave through the inverse piezoelectric effect, and the surface acoustic wave is transferred to the flow field in the set area to form a converging acoustic field, so that the initial cell cluster is recaptured at the acoustic pressure node position;

[0064] 5) After the tumor cell spheroids grow well, inject the anti-tumor drugs from the liquid inlet of the micro-channel cavity, and the drugs act on the outer cells of the cell group first, and then penetrate into the interior of the cells layer by layer;

[0065] 6) According to the required tensile acoustic field, use single frequency 20MHz as the excitation signal, and slowly increase the applied power from low to high, but cannot apply power in pulses, the step is 5-20s, the acoustic pressure nodes in the set area migrate to both sides, the corresponding cell group is subjected to acoustic radiation force towards both sides, thereby producing tensile loading on the cell group;

[0066] 7) According to the required compression acoustic field, use 10MHz and 20MHz superposition as the excitation signal, and the applied power is 300-1000mW, forming a converging acoustic field, the acoustic pressure nodes in the set area will migrate to the inside, and the corresponding tumor cell group will be subjected to acoustic radiation force towards the inside, thereby producing compression loading on the cell group;

[0067] 8) Repeat 6) and 7), repeatedly stretch and compress the cell group to achieve repeated dynamic stimulation on the cell group; dynamic stimulation can produce tensile and compressive traction on the cell membrane of tumor cells, accelerate drug entry into cells; at the same time, it can make the drug penetrate into the cells inside the cell group and accelerate the action on the whole cell group;

[0068] 9) Collect image signals and fluorescence signals through the CCD camera 7 and the fluorescence microscope 6 for analysis;

[0069] 10) The image signals represent the deformation state of the cell group after tensile and compression stimulation, and the fluorescence signals represent the drug treatment state of the cell group after stimulation, and the central processing unit 1 analyzes the image signals and fluorescence signals.

[0070] Through the introduction of anti-tumor drugs, the drug response of tumor cells subjected to mechanical stimulation can be studied, and by evaluating the effect of drugs on tumor cells, more effective anti-tumor drugs can be selected, and individualized treatment plans can be further developed. Therefore, when the frequency is switched, the tumor cell group in the position does not change, so it does not affect the tumor cell group subjected to excitation, and thus can be used as a control group for comparison with the tumor cell group subjected to excitation.

[0071] Finally, it should be noted that the purpose of publishing the embodiments is to help further understand the present application, but those skilled in the art can understand that various substitutions and modifications are possible without departing from the spirit and scope of the present application and the appended claims. Therefore, the present application should not be limited to the disclosed content of the embodiments, and the scope of protection claimed by the present application is defined by the scope of the claims.

Claims

1. A device for stretching and compressing cell clusters based on surface acoustic wave harmonic control, characterized in that, The cell cluster stretching and compressing device comprises a central processing unit, a power amplifier, a signal generator, a micro-fluidic cavity module and a surface acoustic wave driving chip; the micro-fluidic cavity module is located below the surface acoustic wave driving chip; the surface acoustic wave driving chip is connected to the power amplifier, the power amplifier is connected to the signal generator, and the signal generator is connected to the central processing unit; The micro-fluidic cavity module comprises a liquid inlet, a liquid outlet and a micro-fluid channel cavity; the surface of the micro-fluid channel cavity is open, and the inside is a cavity; the liquid inlet and the liquid outlet are arranged on opposite sides of the micro-fluid channel cavity; The surface acoustic wave driving chip comprises a substrate and a harmonic multiplexing interdigital transducer; the harmonic multiplexing interdigital transducer comprises a plurality of interdigital electrodes connected in series; a plurality of interdigital electrodes are arranged on the substrate; the plurality of interdigital electrodes are connected in series to the output end of the power amplifier; each interdigital electrode has a different finger width; different finger widths correspond to different center frequencies of the interdigital electrodes; the center frequency of the interdigital electrode is adjusted by the finger width; the surface acoustic wave driving chip is inverted on the micro-fluidic cavity module, i.e. the harmonic multiplexing interdigital transducer faces the micro-fluid channel cavity of the micro-fluidic cavity module; According to the required acoustic field, the corresponding frequency and power of the required acoustic field are obtained; the central processing unit sends a digital signal to the signal generator; the signal generator emits excitation signals of different frequencies and corresponding powers according to the parameterized scanning results; the signal generator converts the digital signal into an electrical signal, and outputs the excitation signals of different frequencies from each output channel; the power amplifier converts the electrical signal into an amplified power signal and transmits it to the harmonic multiplexing interdigital transducer; the interdigital electrode with the same center frequency as the frequency of the excitation signal generates a surface acoustic wave through the inverse piezoelectric effect; the surface acoustic wave is transmitted to the flow field in the set region to form the required acoustic field; by designing different forms of harmonic multiplexing interdigital transducers, the frequency and power of the excitation signal are changed to generate a specified acoustic field, so that the acoustic field respectively generates the effects of gathering into clusters, positioning, stretching and compressing on the cells in turn.

2. The cell cluster stretching and compressing device of claim 1, wherein, The height of the micro-fluid channel cavity is 50-1000 μm, and the length and width are 5-20 mm.

3. The cell cluster stretching and compressing device of claim 1, wherein, The micro observation device comprises a fluorescence microscope and a charge coupled device (CCD) camera; the micro-fluid channel cavity module is placed on the sample stage of the fluorescence microscope; the CCD camera is arranged on the fluorescence microscope and connected to the central processing unit.

4. The cell cluster stretching and compressing device of claim 1, wherein, The finger width of the interdigital electrode is 20-100 μm, the number of interdigital electrodes is 10-30, the center frequency range is 10-50 MHz, and the applied power range is 100-1000 mW.

5. The stretching and compressing method of the cell cluster stretching and compressing device based on surface acoustic wave harmonic regulation according to claim 1, characterized in that, The stretching and compressing method comprises the following steps: 1) injecting cells into the micro-fluid channel cavity; 2) According to the required converging acoustic field, the corresponding frequency and power are obtained, the central processing unit controls the signal generator to output the excitation signal of the corresponding frequency and power to the power amplifier for amplification and transmission to the harmonic multiplexing interdigital transducer; the interdigital electrode with the same frequency as the center frequency of the excitation signal generates the surface acoustic wave through the inverse piezoelectric effect, and the surface acoustic wave is transferred to the flow field in the set area to form a converging acoustic field, so that the cells are aggregated; 3) Wait for the cells to crosslink to form cell clusters; 4) According to the required converging acoustic field, the corresponding frequency and power are obtained, the central processing unit controls the signal generator to output the excitation signal of the corresponding frequency and power to the power amplifier for amplification and transmission to the harmonic multiplexing interdigital transducer; the interdigital electrode with the same frequency as the center frequency of the excitation signal generates the surface acoustic wave through the inverse piezoelectric effect, and the surface acoustic wave is transferred to the flow field in the set area to form a converging acoustic field, so that the initial cell clusters are recaptured at the acoustic pressure node position; 5) After observing that the cell clusters grow well through the microscopic observation module, the drug is injected from the liquid inlet of the microchannel cavity; 6) According to the required stretching acoustic field, the required frequency and power are obtained, the central processing unit controls the signal generator to output the excitation signal of the corresponding frequency and power to the power amplifier for amplification, and gradually increases the applied power from low to high, and transmits to the harmonic multiplexing interdigital transducer; the surface acoustic wave generated by the excitation harmonic multiplexing interdigital transducer is transferred to the flow field in the set area, the surface acoustic wave generated by the excitation harmonic multiplexing interdigital transducer is transferred to the flow field in the set area, and the acoustic pressure node in the set area migrates to both sides, and the corresponding cell clusters are subjected to the action of the acoustic radiation force towards both sides, thereby stretching the cell clusters; 7) According to the required compression acoustic field, the required acoustic field corresponding frequency and power are obtained, the central processing unit controls the signal generator to output the excitation signal of the corresponding frequency and power to the power amplifier for amplification and transmission to the harmonic multiplexing interdigital transducer; the surface acoustic wave generated by the excitation harmonic multiplexing interdigital transducer is transferred to the flow field in the set area to form a converging acoustic field, and the acoustic pressure node in the set area will migrate to the inside, and the corresponding cell clusters will be subjected to the action of the acoustic radiation force towards the inside, thereby producing compression loading to the cell clusters; 8) Repeat 6) and 7), repeatedly stretch and compress the cell clusters to realize repeated dynamic stimulation of the cell clusters; the dynamic stimulation can produce stretching and compression traction on the cell membrane of the cells, accelerate the entry of the drug into the cells; at the same time, it can make the drug penetrate into the cells inside the cell clusters, and accelerate the action on the whole cell clusters; 9) Image signals and fluorescence signals are collected through a charge coupled device (CCD) camera and a fluorescence microscope; 10) The image signals represent the deformation state of the cell clusters after stretching and compression stimulation, and the fluorescence signals represent the drug treatment state of the cell clusters after stimulation, and the central processing unit analyzes the image signals and the fluorescence signals.

6. The stretch and compression method of claim 5, wherein, In step 1), the size of the cells is 10 μm-30 μm, and the flow rate of the cells injected into the microchannel cavity is 0.5-10 μl / min.

7. The stretch and compression method of claim 5, wherein, In step 2), the frequency applied is 10-50 MHz, the power applied is 100-500 mW, and the excitation time is 30-60 s.

8. The stretch and compression method of claim 5, wherein, In step 4), the frequency applied is 10-50 MHz, and the power applied is 100-500 mW.

9. The stretch and compression method of claim 5, wherein, In step 6), the frequency applied is 10-50 MHz, the power applied ranges from 0 to 1000 mW, and the excitation time is 10-30 s.

10. The stretch and compression method of claim 5, wherein, In step 7), the frequency applied is 10-50 MHz, the power applied is 100-1000 mW, and the excitation time is 10-30 s.

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