Device for droplet generation and method for droplet preparation, droplet generation control system

Abstract

The disclosure provides a droplet generation device and a droplet preparation method and a droplet generation control system, at least two target sample solutions are introduced into the at least two dispersed phase flow channels; the continuous phase solution is introduced into the continuous phase flow channel; an electric signal is applied to the interdigital electrode to generate a surface acoustic wave on the surface of the piezoelectric substrate, and the at least two target samples are arranged and distributed in the at least two dispersed phase flow channels respectively; the continuous phase solution is driven to converge with the target sample in the dispersed phase flow channel, and the target sample solution is sheared to generate droplets. Compared with the related art, the acoustic field generated by the interdigital electrode acoustic chip acts on the target sample, so that the target sample can be arranged and distributed in the laminar flow of the sample flow channel in a single row; the interdigital electrode acoustic chip can accurately control the arrangement of the target sample in the sample flow channel, and thus the droplet wrapping rate of the target sample can be improved.

Description

TECHNICAL FIELD

[0001] The present disclosure relates to the technical field of cell quantitative analysis, and particularly relates to a droplet generation device, a droplet preparation method and a droplet generation control system. BACKGROUND

[0002] The on-chip laboratory technology based on the microfluidic chip accelerates the research level of quantitative analysis in the single cell field. Using the microfluidic technology, a single cell or a microparticle can be wrapped in a certain micro-volume droplet, each droplet wrapped with a cell or a microparticle is isolated in space from other droplets, and quantitative analysis of a single cell or a microparticle can be achieved. Therefore, the microfluidic technology has been widely applied and developed in the field of single cell analysis in recent years.

[0003] However, in the droplet preparation process, due to the random loading of the number of cells or microparticles, the number of cells or microparticles in each droplet will change. The existing process of wrapping a single cell or a microparticle in a droplet is a typical random process, and the number of cells or microparticles distributed in each droplet is determined by Poisson statistics. Most of the droplets actually do not contain any cells or microparticles, or due to random distribution, a droplet contains more than one microparticle or cell, which ultimately leads to the inability to quantitatively analyze the biological characteristics of a single cell. Therefore, how to improve the wrapping rate of the droplet has become a problem to be solved. SUMMARY

[0004] The present disclosure provides a droplet generation device, a droplet preparation method and a droplet generation control system. The main purpose is to solve the problem of low wrapping rate of the droplet.

[0005] According to a first aspect of the present disclosure, a droplet generation device is provided, comprising: a microfluidic chip, and an interdigital electrode acoustic chip connected with the microfluidic chip.

[0006] The interdigital electrode acoustic chip comprises: a piezoelectric substrate, and interdigital electrodes; wherein,

[0007] The interdigital electrodes are arranged on the piezoelectric substrate, and the interdigital electrodes receive an electrical signal and apply a voltage between the interdigital electrodes to the piezoelectric substrate to generate a surface acoustic wave on the surface of the piezoelectric substrate.

[0008] The microfluidic chip comprises a droplet generation flow channel, a continuous phase flow channel and at least two dispersed phase flow channels packaged on the interdigital electrode acoustic chip, and the at least two dispersed phase flow channels are communicated with the droplet generation flow channel after converging with the continuous phase flow channel.

[0009] The interdigital electrodes are arranged corresponding to the dispersed phase flow channels, and the acoustic energy of the surface acoustic wave arranges and distributes at least two target samples in the dispersed phase flow channels.

[0010] The continuous phase solution in the continuous phase flow channel shears the target sample solution to generate droplets when the target sample solution flows into the continuous phase flow channel.

[0011] Optionally, the interdigital electrodes are arranged on both sides of the at least two dispersed phase flow channels; the surface acoustic wave of the piezoelectric substrate surface forms a standing wave effect in the dispersed phase flow channels, and the standing wave points are located in the dispersed phase flow channels.

[0012] Different interdigital electrodes control different sizes of the target sample arranged and distributed in the dispersed phase flow channels.

[0013] Optionally, the electrical signal applied to the interdigital electrodes is adjustable.

[0014] The electrical signal is adjusted to control the acoustic radiation force and the generated acoustic streaming force of the surface acoustic wave acting on the sample in the dispersed phase flow channel.

[0015] Optionally, the adjustable parameters of the electrical signal include voltage amplitude and / or driving frequency.

[0016] Optionally, the microfluidic chip comprises a dispersed phase inlet connected one-to-one with the dispersed phase flow channel, and the dispersed phase inlet is in communication with the outside of the microfluidic chip to receive the target sample.

[0017] The dispersed phase flow channel comprises a guide part in communication with the dispersed phase inlet, and an adjusting part in communication with the guide part, the adjusting part is arranged corresponding to the interdigital electrodes and away from one end of the guide part, and the other end is in communication with the continuous phase flow channel.

[0018] Optionally, the extension direction of the adjusting part is perpendicular to the propagation direction of the surface acoustic wave, and at least the adjusting parts of the at least two dispersed phase flow channels are parallel to each other.

[0019] The distance between the adjusting parts of the at least two dispersed phase flow channels corresponds to the wavelength and the attenuation length of the surface acoustic wave.

[0020] Optionally, the target sample includes any one of a cell suspension and a magnetic bead suspension; and the continuous phase solution is an oil phase.

[0021] According to a second aspect of the present disclosure, a method for generating droplets is provided, comprising:

[0022] Introducing at least two target sample solutions into the at least two dispersed phase flow channels;

[0023] Introducing a continuous phase solution into the continuous phase flow channel;

[0024] applying an electric signal to the interdigital electrodes to generate a surface acoustic wave on the piezoelectric substrate surface, and arranging the at least two target samples in the at least two dispersed phase flow channels respectively;

[0025] driving the continuous phase solution to converge with the target sample in the dispersed phase flow channel and shearing the target sample solution to generate droplets.

[0026] Optionally, the applying an electric signal to the interdigital electrodes to generate a surface acoustic wave on the piezoelectric substrate surface comprises:

[0027] adjusting the electric signal to control the acoustic radiation force and the acoustic streaming force of the surface acoustic wave acting on the sample in the dispersed phase flow channel.

[0028] Optionally, by adjusting the voltage amplitude and / or the driving frequency of the electric signal, in combination with the acoustic contrast coefficient of the surface wave and / or the fluid kinematic viscosity of the sample solution, the monolayer arrangement distribution of the target samples of different sizes in the dispersed phase flow channel is controlled.

[0029] Optionally, the adjusting the electric signal to control the acoustic radiation force and the acoustic streaming force of the surface acoustic wave acting on the sample in the dispersed phase flow channel comprises:

[0030] controlling the frequency of the surface acoustic wave by controlling the width of the fingers of the interdigital electrodes and the interval of the finger repeat distance.

[0031] According to a third aspect of the present disclosure, there is provided a droplet generation control system, comprising:

[0032] a droplet generation device as described in the first aspect above,

[0033] a power supply device electrically connected to the interdigital electrode acoustic chip and a controller connected to the power supply device, the controller driving the power supply device to apply the electric signal to the interdigital electrode acoustic chip and adjust the surface acoustic wave;

[0034] and a pneumatic device connected to the microfluidic chip, the pneumatic device driving the target sample solution and the continuous phase solution to flow towards the droplet generation flow channel.

[0035] The disclosure provides a droplet generation device, a droplet preparation method and a droplet generation control system. At least two target sample solutions are introduced into at least two dispersed phase flow channels; a continuous phase solution is introduced into a continuous phase flow channel; an electrical signal is applied to the interdigital electrode to generate a surface acoustic wave on the surface of the piezoelectric substrate, and the at least two target samples are arranged and distributed in the at least two dispersed phase flow channels respectively; the continuous phase solution and the target sample in the dispersed phase flow channel are driven to converge and the target sample solution is sheared to generate droplets. Compared with the related art, the acoustic field generated by the interdigital electrode acoustic chip acts on the target sample, so that the target sample can be arranged and distributed in the laminar flow of the sample flow channel in a single row; the interdigital electrode acoustic chip can precisely control the arrangement of the target sample in the sample flow channel, and thus the droplet wrapping rate of the target sample can be improved.

[0036] It should be understood that the content described in this part is not intended to identify key or important features of the embodiments of the application, nor to limit the scope of the application. Other features of the application will become apparent from the following description. BRIEF DESCRIPTION OF DRAWINGS

[0037] The accompanying drawings are used to better understand the present scheme and do not limit the disclosure. Among them:

[0038] Figure 1 A schematic diagram of a droplet generation device provided by an embodiment of the disclosure;

[0039] Figure 2 A schematic diagram of bonding of an interdigital electrode acoustic chip and a microfluidic chip provided by an embodiment of the disclosure;

[0040] Figure 3 A schematic diagram of the working principle of a droplet generation device provided by an embodiment of the disclosure;

[0041] Figure 4 A schematic diagram of a system using a droplet generation device according to an embodiment of the disclosure;

[0042] Figure 5 A flowchart of a droplet generation method provided by an embodiment of the disclosure;

[0043] Figure 6 A flowchart of another droplet generation method provided by an embodiment of the disclosure. DETAILED DESCRIPTION

[0044] Exemplary embodiments of the present disclosure are described herein with reference to the accompanying drawings, which are meant to be exemplary in nature, and include various details intended to facilitate understanding of the present disclosure. Thus, it should be apparent to those skilled in the art that various modifications and changes can be made in the embodiments described herein without departing from the scope and spirit of the present disclosure. Likewise, the description is not to be construed to limit the present disclosure to the features described herein. Rather, it is the intent to cover all modifications and changes that fall within the scope and spirit of the present disclosure.

[0045] A droplet generation device and a droplet preparation method, and a droplet generation control system are described below with reference to the accompanying drawings.

[0046] Figure 1 A schematic diagram of a droplet generation device according to an embodiment of the present disclosure is shown in FIG. 1. As shown in FIG. 1, the droplet generation device includes a microfluidic chip 12 and an interdigital acoustic chip 11 connected to the microfluidic chip. Figure 1

[0047] The interdigital acoustic chip 11 includes a piezoelectric substrate 111 and interdigital electrodes 112.

[0048] The interdigital electrodes 112 are disposed on the piezoelectric substrate 111. The interdigital electrodes 112 receive an electrical signal and apply a voltage between the interdigital electrodes 112 to the piezoelectric substrate 111 to generate a surface acoustic wave on the surface of the piezoelectric substrate 111.

[0049] The microfluidic chip 12 includes a droplet generation flow channel 125, a continuous phase flow channel 122, and at least two dispersed phase flow channels 121 encapsulated on the interdigital acoustic chip. The at least two dispersed phase flow channels 121 converge with the continuous phase flow channel 122 and communicate with the droplet generation flow channel 125.

[0050] The interdigital electrodes 112 are disposed corresponding to the dispersed phase flow channels 121. The acoustic energy of the surface acoustic wave arranges and distributes at least two target samples in the dispersed phase flow channels 121.

[0051] The continuous phase solution in the continuous phase flow channel 122 shears the target sample solution to generate droplets when the target sample solution converges with the target sample in the dispersed phase flow channels 121.

[0052] In particular embodiments of the present disclosure, please refer to Figure 1 ​The interdigital electrode 112 is coated on the upper surface of the piezoelectric substrate 111 to form an interdigital electrode acoustic chip 11. The material of the interdigital electrode 112 can be, but is not limited to, metal materials such as gold, aluminum, silver, copper, etc. The piezoelectric substrate 111 is made of piezoelectric material. When an electrical signal is applied to the interdigital electrode 112, a surface acoustic wave is generated on the surface layer of the piezoelectric substrate 111. The surface acoustic wave is used to arrange the target sample in the dispersed phase flow channel 121 in rows and columns. The particles in the two different target samples change from a free dispersion state in the respective target sample solution fluid to a single layer, ordered spatial arrangement and are maintained in a certain specific laminar flow.

[0053] The microfluidic chip 12 is packaged on the interdigital electrode acoustic chip 11 and is used to shear the target sample solution to generate droplets through the continuous phase solution in the continuous phase flow channel 122.

[0054] In order to more clearly understand the embodiments of the present disclosure, the present disclosure provides a schematic diagram of the bonding of the interdigital electrode acoustic chip and the microfluidic chip, as shown in Figure 2 The packaging and bonding between the interdigital electrode acoustic chip 11 and the microfluidic chip 12 can be, but is not limited to, thermal compression bonding, chemical bond modification bonding, or plasma bonding, etc.

[0055] The present disclosure provides a droplet generation device. At least two target sample solutions are introduced into the at least two dispersed phase flow channels. A continuous phase solution is introduced into the continuous phase flow channel. An electrical signal is applied to the interdigital electrode to generate a surface acoustic wave on the surface of the piezoelectric substrate. The at least two target samples are arranged and distributed in the at least two dispersed phase flow channels, respectively. The continuous phase solution and the target sample in the dispersed phase flow channel are driven to flow together and the target sample solution is sheared to generate droplets. Compared with the related art, the acoustic field generated by the interdigital electrode acoustic chip acts on the target sample, so that the target sample can be arranged and distributed in a single row in the laminar flow of the sample flow channel. The interdigital electrode acoustic chip can be used to accurately control the arrangement of the target sample in the sample flow channel, thereby improving the droplet wrapping rate of the target sample.

[0056] Further, in a possible implementation manner of the present embodiment, as shown in Figure 3 The interdigital electrode 112 is arranged on both sides of the at least two dispersed phase flow channels 121. The surface acoustic wave on the surface of the piezoelectric substrate 111 forms a standing wave effect in the dispersed phase flow channel 121, and the standing wave point is located in the dispersed phase flow channel 121.

[0057] The different interdigital electrodes 112 control different sizes of the target samples arranged and distributed in the dispersed phase flow channel 121.

[0058] Specifically in the embodiments of the present disclosure, the target sample solution flowing through the dispersed phase flow channel 121 is excited to act on the target sample by the acoustic streaming force generated by the acoustic wave signal generated by the piezoelectric substrate 111; at the same time, the target sample solution flows through the working area of the interdigital electrode 112, and the target sample is subjected to the acoustic radiation force generated by the surface acoustic wave. The interdigital electrode acoustic chip 11 utilizes the combined action of the acoustic streaming force and the acoustic radiation force acting on the target sample to control the single-layer arrangement distribution of the target sample in the laminar flow of the fluid in the dispersed phase flow channel 121. Figure 3 The dashed part represents the surface acoustic wave, and the black dot and the white dot at the intersection of the dashed line represent two different target samples. The position of the target sample is the standing wave point generated by the surface acoustic wave.

[0059] In some embodiments of the present disclosure, the interdigital electrode 112 can have various forms, including but not limited to parallel, widening, focusing, and oblique interdigital electrode, etc. The acoustic radiation force generated by the interdigital electrode 112 of different sizes is different, and therefore the size and form of the interdigital electrode 112 can be changed to adapt to target samples of different sizes.

[0060] Further, in a possible implementation manner of the present embodiment, as shown in Figure 4 The electrical signal applied to the interdigital electrode 112 is adjustable.

[0061] The electrical signal is adjusted to control the acoustic radiation force and the acoustic streaming force of the surface acoustic wave acting on the sample in the dispersed phase flow channel 121. The adjustable parameters of the electrical signal include the voltage amplitude and / or the driving frequency.

[0062] Specifically in the embodiments of the present disclosure, the piezoelectric substrate 111 can accept any suitable voltage signal. The voltage signal can be a periodic input signal such as a sine wave, a square wave, a triangular wave, a sawtooth wave, etc. The working frequency can be a single frequency in the range of tens of Hz to GHz, or a combination of specific frequencies. It should be noted that the present disclosure does not limit the form of the electrical signal selected for the piezoelectric substrate.

[0063] Further, in a possible implementation manner of the present embodiment, as shown in Figure 2 The microfluidic chip 12 includes a dispersed phase inlet 124 connected one-to-one with the dispersed phase flow channel 121. The dispersed phase inlet 124 is in communication with the outside of the microfluidic chip 12 to receive the target sample.

[0064] The dispersed phase flow channel 121 includes a guide part 1211 in communication with the dispersed phase inlet 124, and an adjusting part 1212 in communication with the guide part 1211. The adjusting part 1212 is arranged corresponding to the interdigital electrode 112 and is away from one end of the guide part 1211. The other end of the adjusting part 1212 is in confluence with the continuous phase flow channel 122.

[0065] In particular in the embodiments of the present disclosure, please refer to Figure 2 With Figure 3 After the target sample solution passes through the dispersed phase inlet 124, the target sample solution flows through the guiding part 1211 and the adjusting part 1212 in sequence, and the continuous phase solution in the continuous phase flow channel 122 shears the target sample solution to generate droplets.

[0066] Further, in a possible implementation manner of the present embodiment, the extending direction of the adjusting part 1212 is perpendicular to the surface acoustic wave propagation direction, and the adjusting parts of the at least two dispersed phase flow channels 121 are parallel to each other.

[0067] The distance between the adjusting parts 1212 of the at least two dispersed phase flow channels 121 corresponds to the wavelength and the attenuation length of the surface acoustic wave.

[0068] In particular in the embodiments of the present disclosure, please refer to Figure 3 In order to enable the standing wave points generated by the surface acoustic wave to be gathered in each dispersed phase flow channel 121, the distance between each adjusting part 1212 (i.e. the thickness of the dispersed phase flow channel wall) needs to be set in consideration of the width of each adjusting part 1212 and the wavelength of the surface acoustic wave. Due to the attenuation of the surface acoustic wave energy in the propagation path, the distance between different numbers of adjusting parts 1212 is not the same; for example, when the number of adjusting parts 1212 increases from two to three, the distance between the adjusting parts 1212 needs to be re-set in consideration of the increase in the attenuation of the surface acoustic wave energy in the propagation path. In some optional embodiments, the distance between each adjusting part 1212 can be about several microns to several hundred microns in consideration of factors such as the sealing of the dispersed phase flow channel 121, the attenuation wavelength of the surface acoustic wave, the manufacturing process, and the like. It should be noted that the present embodiments do not constitute a limitation on the distance between the adjusting parts.

[0069] Further, in a possible implementation manner of the present embodiment, the target sample includes any one of a cell suspension and a magnetic bead suspension; and the continuous phase solution is an oil phase.

[0070] In particular in the embodiments of the present disclosure, the target sample includes any one of a cell suspension and a magnetic bead suspension; it should be noted that the cell suspension and the magnetic bead suspension in the present embodiments are not limited to a specific type of cells and a specific type of magnetic bead combined microparticles; similarly, the continuous phase solution is an oil phase, and the present embodiments are not limited to a specific type of oil phase solution.

[0071] Figure 4A schematic diagram of a system using a droplet generation device according to an embodiment of the present application is shown in Figure 4 The system comprises:

[0072] A droplet generation device as described in the foregoing embodiments,

[0073] a power supply device electrically connected to the interdigital acoustic chip 11 and a controller 16 connected to the power supply device, the controller 16 driving the power supply device to apply the electrical signal to the interdigital acoustic chip 11 and adjust the surface acoustic wave;

[0074] and a pneumatic device (e.g. mechanical pump devices P1, P2) connected to the microfluidic chip 12, the mechanical pump devices P1, P2 driving the target sample solution and the continuous phase solution to flow into the droplet generation flow channel 125.

[0075] In particular in the embodiments of the present disclosure, in combination with Figures 2-4 , the mechanical pump device P2 acts on the dispersed phase inlet 124 to input different target sample solutions into the dispersed phase flow channels 121a-121b, respectively, and flow through the guide part 1211 and the adjustment part 1212 of the dispersed phase flow channels 121a-121b in sequence; when flowing through the adjustment part 1212, the target sample in the target sample solution is arranged in a single layer in the dispersed phase flow channel 121 by the combined action of the acoustic streaming force and the acoustic radiation force generated by the interdigital acoustic chip 11; after intersecting with the continuous phase flow channel 122, the continuous phase solution in the continuous phase flow channel 122 shears the target sample solution to generate droplets. The continuous phase inlet 1220 of the continuous phase flow channel 122 is connected to the mechanical pump device P1, and the mechanical pump device P1 pumps the oil phase liquid at the continuous phase inlet 1220 into the continuous phase flow channel 122 to provide power for shearing the droplets. The generated droplets flow through the droplet generation flow channel 125 and are collected by the sample recovery tube 13.

[0076] The computer 17 is used for implementation monitoring, biological sample visual recognition, and trajectory tracking of the sample, etc. The controller 16 provides a control signal. The power supply device includes a power amplifier 14 and a signal source 15.

[0077] Corresponding to the above-described droplet generation device, the present application further provides a droplet generation method.

[0078] Figure 5 A flowchart of a droplet preparation method according to an embodiment of the present disclosure is shown in

[0079] As shown in Figure 5 , the method comprises the following steps:

[0080] Step 201, introducing at least two target sample solutions into the at least two dispersed phase flow channels.

[0081] Specifically in the embodiments of the present disclosure, different target sample solutions are respectively conveyed into different dispersed phase flow channels, to prepare for subsequent control of target sample arrangement and distribution. The sizes of the at least two dispersed phase flow channels can be the same or different, for example, the widths of the plurality of dispersed phase flow channels can be the same specific width or length, or have different widths or lengths. The fluid samples in the at least two dispersed phase flow channels can be samples of the same property or samples of different properties. For example, organic particles, inorganic particles, biological cells, microbial spheres, etc.

[0082] In step 202, the continuous phase solution is introduced into the continuous phase flow channel.

[0083] Specifically in the embodiments of the present disclosure, the continuous phase solution is introduced into the continuous phase flow channel by a mechanical pump device. The mechanical pump device pumps the continuous phase solution to generate a certain shear force, which shears the target sample solution into droplets. The speed of the mechanical pump device pumping the continuous phase solution affects the size of the generated droplets and the coating rate. It should be noted that the embodiments of the present disclosure do not limit the speed of the mechanical pump device pumping the continuous phase solution.

[0084] In step 203, an electrical signal is applied to the interdigital electrode to generate a surface acoustic wave on the surface of the piezoelectric substrate, and the at least two target samples are respectively arranged and distributed in the at least two dispersed phase flow channels.

[0085] Specifically in the embodiments of the present disclosure, when the interdigital electrode acoustic chip is applied with a voltage signal, a surface acoustic wave is generated. The target sample is arranged in rows and columns in the dispersed phase flow channel by the surface acoustic wave, and the particles in the target sample change from a free dispersed state in the target sample solution fluid to a single-layer, ordered spatial arrangement and are kept in a certain specific laminar flow.

[0086] In step 204, the continuous phase solution is driven to converge with the target sample in the dispersed phase flow channel and shear the target sample solution to generate droplets.

[0087] Specifically in the embodiments of the present disclosure, the oil phase solution with a certain flow rate wraps at least two single target samples and then shears to form droplets with uniform size of at least two target sample pairs. The flow rate of the oil phase solution determines the size of the cut droplets.

[0088] The present disclosure provides a droplet preparation method, at least two target sample solutions are introduced into the at least two dispersed phase flow channels; a continuous phase solution is introduced into the continuous phase flow channel; an electrical signal is applied to the interdigital electrode to generate a surface acoustic wave on the surface of the piezoelectric substrate, and the at least two target samples are arranged and distributed in the at least two dispersed phase flow channels respectively; and the continuous phase solution is driven to converge with the target samples in the dispersed phase flow channel, and the target sample solution is sheared to generate droplets. Compared with the related art, the acoustic field generated by the interdigital electrode acoustic chip acts on the target sample, so that the target sample can be arranged and distributed in the laminar flow of the sample flow channel in a single row; the interdigital electrode acoustic chip can be used to accurately control the arrangement of the target sample in the sample flow channel, thereby improving the droplet wrapping rate of the target sample.

[0089] In order to more clearly illustrate the embodiments of the present disclosure, Figure 6 A flowchart of another droplet preparation method is provided for the embodiments of the present disclosure, as shown in Figure 6 The method comprises the following steps:

[0090] Step 301, at least two target sample solutions are introduced into the at least two dispersed phase flow channels, and a continuous phase solution is introduced into the continuous phase flow channel.

[0091] Step 302, adjust the electrical signal to control the acoustic radiation force and acoustic streaming force of the surface acoustic wave acting on the sample in the dispersed phase flow channel.

[0092] As a refinement of the embodiments of the present disclosure, the frequency of the surface acoustic wave is controlled by controlling the width of the fingers of the interdigital electrode and the interval of the finger repetition distance.

[0093] In some embodiments of the present disclosure, by adjusting the voltage amplitude and / or driving frequency of the electrical signal, in combination with the acoustic contrast coefficient of the surface wave and / or the fluid motion viscosity of the sample solution, the single-layer arrangement and distribution of the target samples of different sizes in the dispersed phase flow channel is controlled.

[0094] Step 303, drive the continuous phase solution to converge with the target sample in the dispersed phase flow channel, and shear the target sample solution to generate droplets.

[0095] For the description of steps 301 to 303, please refer to the above embodiments, and the embodiments of the present disclosure will not be described one by one.

[0096] It should be noted that the above explanation and description of the method embodiments also apply to the device of the present embodiment, and the principle is the same, which will not be limited in the present embodiment.

[0097] It has to be noted that, in the present document, relational terms are intended only to convey a possible relationship between elements or

[0098] The above detailed description does not limit the scope of the disclosure. Various modifications, combinations, sub-combinations, and alternatives can be made to the details of the disclosure within the scope of the disclosure. Any modification, equivalent replacement or improvement made without departing from the spirit and principles of the disclosure should be included in the scope of the disclosure.

Claims

1. A droplet generating device, characterized in that, include: A microfluidic chip, and an interdigital electrode acoustic chip connected to the microfluidic chip; The interdigitated electrode acoustic chip includes: a piezoelectric substrate and interdigitated electrodes; wherein... The interdigitated electrodes are disposed on the piezoelectric substrate. The interdigitated electrodes receive electrical signals and apply the voltage between the interdigitated electrodes to the piezoelectric substrate to generate surface acoustic waves on the surface of the piezoelectric substrate. The microfluidic chip includes a droplet generation channel, a continuous phase channel, and at least two dispersed phase channels encapsulated on the interdigitated electrode acoustic chip. The at least two dispersed phase channels and the continuous phase channel merge and communicate with the droplet generation channel. The interdigitated electrodes are correspondingly arranged with the dispersed phase flow channel, and the acoustic energy of the surface acoustic wave arranges at least two target samples in the dispersed phase flow channel. When the continuous phase solution in the continuous phase channel merges with the target sample solution in the dispersed phase channel, it shears the target sample solution to generate droplets. The interdigitated electrodes are disposed on both sides of the at least two dispersed phase channels; the surface acoustic wave on the surface of the piezoelectric substrate forms a standing wave effect in the dispersed phase channels, and the standing wave point is located within the dispersed phase channels. Different interdigitated electrodes control target samples of different sizes to be arranged and distributed in different dispersed phase channels; The microfluidic chip includes a dispersed phase inlet connected to the dispersed phase channel in a one-to-one manner, and the dispersed phase inlet is connected to the outside of the microfluidic chip to receive the target sample; The dispersed phase flow channel includes a guide section communicating with the dispersed phase inlet and an adjustment section communicating with the guide section. The adjustment section is disposed corresponding to the interdigitated electrode and its end away from the guide section merges with the continuous phase flow channel. The extension direction of the adjustment section is perpendicular to the propagation direction of the surface acoustic wave, and at least the adjustment section is parallel to each other between the at least two dispersed phase flow channels; The distance between the adjustment sections of the at least two dispersed phase channels corresponds to the wavelength and attenuation length of the surface acoustic wave; The electrical signal applied to the interdigital electrodes is adjustable; The adjustable parameters of the electrical signal include: voltage amplitude and / or driving frequency; by adjusting the voltage amplitude and / or driving frequency of the electrical signal, combined with the acoustic contrast coefficient of the surface acoustic wave and the fluid kinematic viscosity of the target sample solution, the monolayer arrangement distribution of the target samples of different sizes in the dispersed phase channel is controlled.

2. The droplet generating device according to claim 1, characterized in that, The target sample solution includes either a cell suspension or a magnetic bead suspension; the continuous phase solution is an oil phase.

3. A method for preparing droplets using the droplet generating apparatus as described in any one of claims 1-2, characterized in that, include: At least two target sample solutions are introduced into the at least two dispersed phase channels; A continuous phase solution is introduced into the continuous phase flow channel; An electrical signal is applied to the interdigitated electrodes to generate surface acoustic waves on the surface of the piezoelectric substrate, and the at least two target samples are respectively arranged and distributed in the at least two dispersed phase channels; The continuous phase solution is driven to merge with the target sample solution in the dispersed phase channel, and the target sample solution is sheared to form droplets.

4. The droplet preparation method according to claim 3, characterized in that, Applying an electrical signal to the interdigitated electrodes to generate surface acoustic waves on the piezoelectric substrate includes: The electrical signal is adjusted to control the acoustic radiation force and acoustic flow force of the surface acoustic wave acting on the target sample in the dispersed phase channel.

5. The droplet preparation method according to claim 4, characterized in that, The adjustment of the electrical signal to control the acoustic radiation force and acoustic flow force of the surface acoustic wave acting on the target sample in the dispersed phase channel includes: The frequency of surface acoustic waves is controlled by adjusting the width of the interdigitated electrodes and the interval of the repeating distance of the interdigitated electrodes.

6. A droplet generation control system, characterized in that, include: The droplet generating apparatus according to any one of claims 1-2, A power supply device electrically connected to the interdigital electrode acoustic chip and a controller connected to the power supply device, wherein the controller drives the power supply device to apply the electrical signal to the interdigital electrode acoustic chip and adjust the surface acoustic wave; And a pneumatic device connected to the microfluidic chip, the pneumatic device driving the target sample solution and the continuous phase solution to flow toward the droplet generation channel.

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