Device and method for realizing aggregation of particles in liquid drops

Abstract

The invention relates to a device and method for gathering particles in liquid drops, and the device comprises a micro-channel which is used for providing a channel for the flowing of the liquid drops; the first bulk acoustic wave resonator is tightly attached to the micro-channel, and the working action range of the first bulk acoustic wave resonator comprises the space in the micro-channel; the overall shape of the first bulk acoustic wave resonator is narrowed from the front end to the tail end, the tail end is a convex arc-shaped end part, and the arc-shaped end part is used for enabling particles in a liquid drop to be gathered at a first position in the liquid drop in the process that the liquid drop flows through the first bulk acoustic wave resonator; the tip is located on the downstream side in the micro-channel with respect to the tip. According to the scheme provided by the invention, the particles in the liquid drop can be gathered at the first position in the liquid drop, so that the interaction and the like of different particles in the liquid drop after gathering can be conveniently observed.

Description

Technical Field

[0001] The present application relates to the field of microfluidics technology, and in particular to a device and method for achieving particle aggregation in droplets. Background Art

[0002] Microfluidic manipulation technology can be used to manipulate droplets, and in particular can be used to manipulate particles within droplets, such as manipulating the aggregation and mixing of particles within droplets.

[0003] At present, the methods for aggregating particles in droplets include electrical methods, magnetic methods, thermal methods, and acoustic methods. The electrical method uses dielectrophoretic force to repel particles in the droplet to the area outside the electrode or attract them to the vicinity of the electrode. The control precision is low and the enrichment effect is poor. The magnetic method uses magnetic field force to manipulate magnetic particles, and the particles in the droplet can be arranged into a line, but there are requirements for the properties of the particles. The thermal method uses electric heating, photothermal and other methods to induce heat surge to manipulate particles in the droplet. The particles can be arranged in a line, but the particle enrichment effect is poor, the control precision is low, and the biocompatibility is poor. In the acoustic method, low-frequency sound waves form a standing wave sound field and use acoustic radiation force to gather particles in the droplet at the nodes and anti-nodes. The particles can be arranged in a line, but the enrichment degree is low. Surface acoustic waves can rotate independent droplets and use centrifugal action to gather particles in the droplet at the center or periphery of the droplet, but the droplet flux is poor and the enrichment time is long. The current technical methods usually arrange the particles in the droplets into a linear shape, but the light spot cannot cover all the linearly arranged particles during photoelectric detection, resulting in the dispersion of the target signal and insufficient enhancement. Therefore, a technical method for highly aggregated particles in high-throughput droplets is urgently needed.

[0004] When the aggregation of particles in droplets is manipulated, how to improve the aggregation effect is a technical problem to be solved in this application. Summary of the invention

[0005] In view of the above problems in the prior art, the present application provides a device and method for achieving particle aggregation in droplets, so as to more effectively improve the aggregation effect of particles in droplets.

[0006] To achieve the above-mentioned purpose, the first aspect of the present application provides a device for realizing particle aggregation in droplets, characterized in that it includes: a microchannel for providing a channel for droplet flow; a first bulk acoustic wave resonator closely attached to the microchannel, and its effective range during operation includes the space in the microchannel; the overall shape of the first bulk acoustic wave resonator is narrowed from the front end to the end, and the end is an outwardly convex arc end, and the arc end is used to make the particles in the droplet be aggregated at a first position in the droplet during the process of the droplet flowing through the first special acoustic wave resonator; the end is located on the downstream side in the microchannel relative to the front end.

[0007] From the above, since the overall shape of the first bulk acoustic wave resonator of the microchannel is narrowed from the front end to the end, and the end is a convex arc end, the arc end can form an acoustic energy potential well compared to the shape of the tip. When the droplets flow through the first bulk acoustic wave resonator, the formed acoustic energy potential well captures the particles at the end, and during the aggregation process, they are more easily maintained at the end position corresponding to the acoustic energy potential well, thereby improving the aggregation effect.

[0008] As a possible implementation manner of the first aspect, the front end of the overall shape of the first BAW resonator constitutes an outwardly convex arc-shaped front end.

[0009] From the above, it can be formed that the overall outline of the first bulk acoustic wave resonator is composed of a continuous, smooth edge design of arcs and straight lines, which makes the movement of particles in the acoustic flow tunnel smoother and more stable.

[0010] As a possible implementation of the first aspect, the cross-sectional dimensions of the microfluidic channel in the vertical direction of flow accommodate the passage of a single droplet, and the single droplet is restricted by the microfluidic channel and extended along the direction of the microfluidic channel.

[0011] From the above, on the one hand, a single droplet is wrapped by a microfluidic channel and can be easily driven by positive or negative pressure, so the movement speed and direction of the single droplet are in a state that is easier to control, thereby improving the controllability of the droplet movement. On the other hand, since the droplet is in an extended state, the time it takes to flow through the first special acoustic wave resonator is extended, thereby extending the time that the droplet is acted upon by the first special acoustic wave resonator, which can achieve the full effect of the first special acoustic wave resonator on the particles in the droplet. On the other hand, it is also convenient to further combine with another bulk acoustic wave resonator to manipulate the droplet when the first special acoustic wave resonator enriches the particles in the droplet.

[0012] As a possible implementation manner of the first aspect, it also includes: a detection device, wherein a detection range includes the first position.

[0013] From the above, by detecting the first position, the information of the particles gathered at the position can be obtained.

[0014] As a possible implementation manner of the first aspect, the detection device includes an image detection device, and the image collected by the image detection device includes an image of the first position.

[0015] From the above, the image information of the aggregated particles can be obtained, which can be used to collect images of fluorescently labeled particles to further analyze the images.

[0016] As a possible implementation manner of the first aspect, a second BAW resonator is disposed downstream of the first BAW resonator and at a first distance from the first BAW resonator, and the first distance causes the first SAR resonator and the second SAR resonator to act on the droplet in overlapping time.

[0017] From the above, it can be achieved that when the first bulk acoustic wave resonator enriches the particles in the droplet, the droplet can be manipulated through the second bulk acoustic wave resonator.

[0018] As a possible implementation manner of the first aspect, the second BAW resonator is used to split the droplet into a first droplet and a second droplet; the first droplet is located on the downstream side of the microchannel relative to the second droplet, and the position of the second droplet includes the first position.

[0019] As described above, the aggregated particles are separated into the second droplet, and other further applications can be performed based on this, such as particle purification or liquid purification.

[0020] The second aspect of the present application provides a method for achieving particle aggregation in a droplet. The device for achieving particle aggregation in a droplet as described in the first aspect comprises: driving the droplet to flow through a microchannel; driving a first special acoustic wave resonator to work, so that during the process of the droplet flowing through the first special acoustic wave resonator, the particles in the droplet are aggregated at a first position in the droplet, and the first position is a position corresponding to the arc-shaped end of the first special acoustic wave resonator.

[0021] As a possible implementation manner of the second aspect, the method further includes: detecting the first position by a detection device.

[0022] As a possible implementation manner of the second aspect, the first BAW resonator is driven to work, and during the process of particles in the droplet being gathered at a first position in the droplet, the second BAW resonator is driven to act on the droplet; the second BAW resonator is located downstream of the first BAW resonator and is set at a first distance from the first BAW resonator. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 is a schematic diagram of a device for achieving particle aggregation in a droplet provided in the first embodiment of the present application; Figure 2 is a schematic diagram of a device for achieving particle aggregation in a droplet provided in the second embodiment of the present application; Figure 3 is a first schematic diagram of a particle aggregation process of a droplet flowing through a first bulk acoustic wave resonator provided by the first embodiment of the present application; Figure 4is a second schematic diagram of a particle aggregation process of a droplet flowing through a first bulk acoustic wave resonator provided by the first embodiment of the present application; Figure 5 is a schematic diagram of the image detection device provided in the first embodiment of the present application detecting modified fluorescent particles; Figure 6 is a schematic diagram of brightness data obtained by an image detection device provided in the first embodiment of the present application; Figure 7 This is a flow chart of a method for achieving particle aggregation in droplets provided in the first embodiment of the present application.

[0024] It should be understood that the size and shape of each block diagram in the above structural diagram are for reference only and should not constitute an exclusive interpretation of the embodiment of the present invention. The relative position and inclusion relationship between the blocks presented in the structural diagram are only schematic representations of the structural association between the blocks, and do not limit the physical connection method of the embodiment of the present invention. DETAILED DESCRIPTION

[0025] The technical solution provided by the present application is further described below with reference to the accompanying drawings and examples. It should be understood that the system structure and business scenarios provided in the examples of the present application are mainly to illustrate the possible implementation methods of the technical solution of the present application and should not be interpreted as the only limitation on the technical solution of the present application. It is known to those of ordinary skill in the art that with the evolution of the system structure and the emergence of new business scenarios, the technical solution provided by the present application is also applicable to similar technical problems.

[0026] It should be understood that the solution for achieving particle aggregation in droplets provided in the embodiments of the present application includes a device and method for achieving particle aggregation in droplets. Since the principles of solving the problems in these technical solutions are the same or similar, some repetitions may not be repeated in the introduction of the following specific embodiments, but it should be regarded as that these specific embodiments have been referenced to each other and can be combined with each other.

[0027] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by technicians in the technical field of this application. In the event of any inconsistency, the meaning described in this specification or the meaning derived from the contents recorded in this specification shall prevail. In addition, the terms used herein are only for the purpose of describing the embodiments of the present application and are not intended to limit the present application. In order to accurately describe the technical content in this application and to accurately understand the present invention, the following explanations or definitions are given to the terms used in this specification before describing the specific embodiments: 1) Droplets: The volume of the droplets in the present application can be in the order of femtoliter, picoliter, nanoliter, microliter, etc.

[0028] 2) UHF BAW resonator: Its frequency is usually greater than 1GHz. Under the stimulation of the input signal, it generates UHF vibration and emits BAW. The BAW propagates in the fluid and induces the directional movement of the fluid, forming a fluid vortex. One of the phenomena is that a number of tiny fluid vortices can be generated in the fluid at the edge of the UHF BAW resonator chip. These fluid vortices can capture particles in the liquid. Combined with the position distribution of these fluid vortices, the particles in the liquid are distributed at the edge of the UHF BAW resonator chip.

[0029] 3) Potential well: refers to the movement of particles in a certain force field. The potential energy function curve has the minimum potential energy in a limited range of space, which is like a trap. The kinetic energy of particles in the potential well is less than the potential energy, and they are in a relatively stable position and are not easy to escape from this position. Acoustic energy potential well, in this article, refers to the potential well formed under the acoustic energy of ultra-high frequency body sound waves.

[0030] In a droplet manipulation method based on an ultra-high frequency bulk acoustic wave resonator, when the boundary of a bulk acoustic wave chip is placed in a microfluidic channel, the boundary can capture particles in droplets flowing through the bulk acoustic wave chip, and when the droplets move downstream in the microfluidic channel, the droplets or particles can gather along the boundary, especially at the end of the downstream side of the bulk acoustic wave chip, and then move out of the active area of ​​the bulk acoustic wave chip with the droplets. This phenomenon is disclosed in the patent with patent application number CN202111538154.2. The downstream end of the bulk acoustic wave chip used in this patent is pointed, and the particle aggregation is not stable, and the particles gathered at the tip can easily be released from the aggregation position to other positions in the droplet.

[0031] The present application provides another solution for achieving particle aggregation in droplets. For a first bulk acoustic wave resonator that is set close to the microfluidic channel, its overall shape is narrowed from the front end to the end, and the end is an outwardly convex arc end. Compared with the shape of the tip, the arc end can form an acoustic energy potential well. When the droplets flow through the first bulk acoustic wave resonator, the formed acoustic energy potential well captures the particles at the end, and during the aggregation process, the particles are more easily maintained at the end position corresponding to the acoustic energy potential well.

[0032] The application scenario of the present application may be the detection of particles contained in the droplets. For example, when the particles are fluorescently labeled, the aggregation of the particles can lead to an increase in the intensity of the fluorescence signal, thereby achieving signal amplification, improving the signal-to-noise ratio, and increasing the detection limit. The intensity of the fluorescence can reflect the amount of the target particles. For example, a small amount of particles dispersed in a droplet is not easy to detect. Due to the enhancement of the fluorescence signal after enrichment, the present application can detect the presence of particles in the droplet. Another application scenario of the present application can be used for the combination of different particles. For example, two or more particles of different types are injected into a droplet, or a droplet mixed with two different types of particles (a droplet, or two droplets fused into a droplet) can be enriched in one place through the present application, increasing the probability of the two particles combining. The same principle applies to the combination of a first particle with multiple second particles, or the combination of multiple second particles with multiple second particles. The present application can also be applied to application scenarios such as particle purification and liquid purification. For details, please refer to the embodiments described below.

[0033] Below, the present application is described in detail with reference to specific drawings and specific embodiments.

[0034] The first embodiment of the present application provides a device for realizing particle aggregation in a droplet, which can be applied to control the aggregation of particles in a droplet, such as Figure 1 As shown, the device comprises: Microfluidic channel, used to provide a channel for droplet flow; A first bulk acoustic wave resonator closely attached to the microchannel, wherein the working range of the first bulk acoustic wave resonator includes the space in the microchannel; The overall shape of the first BAW resonator is narrowed from the front end to the rear end, and the rear end is an outwardly convex arc end, and the arc end is used to make the particles in the droplet be gathered at a first position in the droplet during the process of the droplet flowing through the first BAW resonator, and the first position is the position corresponding to the arc end; The terminal end is located on a downstream side in the microchannel relative to the front end.

[0035] Figure 2 The second embodiment of the present application provides a device for realizing particle aggregation in droplets. Figure 2 In, with Figure 1 In contrast, the microchannel does not cover the entire first BAW resonator, but covers the end of the first BAW resonator.

[0036] Among them, Figure 3 and Figure 4The schematic diagram of the particle aggregation process of a droplet flowing through the first BAW resonator is shown. When the droplet flows through the top of the first BAW resonator in the microchannel, the acoustic fluid of the first BAW resonator will gather the particles in the droplet to the edge of the device of the first BAW resonator. At this time, the particles are only gathered at the edge of the device, which belongs to linear aggregation. As the droplet moves downstream, the interface of the droplet tail is located above the edge of the first BAW resonator of the device and moves downstream. The force of the droplet tail interface acts on the particles at the edge of the first BAW resonator below the droplet tail, driving the particles gathered at the edge of the first BAW resonator downstream. As the droplet continues to move downstream, these particles are driven and gathered at the downstream end of the first BAW resonator, achieving point aggregation. It can be seen that the particle aggregation process is completed by the interaction between the moving droplet and the first BAW resonator.

[0037] The overall shape of the first BAW resonator narrows from the front end to the end, which is more conducive to driving the particles at the left and right edges of the first BAW resonator to move to the end of the first BAW resonator. The end of the first BAW resonator is designed to be an arc rather than a tip structure, which is more conducive to forming an acoustic energy potential well to capture and gather the moving particles at the end of the first BAW resonator, and the particles are less likely to be released at this end.

[0038] In some embodiments, the first BAW resonator is located at the bottom of the microfluidic channel, and its width (the dimension of the first BAW resonator perpendicular to the flow direction of the flow channel in the top view is taken as the width) is smaller than the width of the microfluidic channel. In other embodiments, the first BAW resonator is located at the top or side of the microfluidic channel. In other embodiments, the widest part of the width of the first BAW resonator can be larger than the width of the microfluidic channel.

[0039] In some embodiments, the cross-sectional dimension of the microfluidic channel in the direction perpendicular to the flow direction can accommodate a single droplet passing through.

[0040] In some embodiments, the cross-sectional dimensions of the microfluidic channel perpendicular to the flow direction can accommodate the passage of a single droplet, and the single droplet is restricted by the microfluidic channel and extended along the direction of the microfluidic channel. In this case, on the one hand, the single droplet is wrapped by the microfluidic channel and can be easily driven by positive or negative pressure, so the movement speed (including the special case of 0 speed) and movement direction (forward or backward) of the single droplet are in a state that is easier to control. On the other hand, since the droplet is in an extended state, the time it takes to flow through the first special acoustic wave resonator is extended, so that the time the droplet is acted on by the first special acoustic wave resonator is extended, and the first special acoustic wave resonator can fully act on the particles in the droplet. In some embodiments, a device that can generate air pressure, such as an air pump, a manual pipette, a hand-squeezed rubber ball, etc., connected to the inlet or outlet of the microfluidic channel can be provided to control the speed and direction of the droplet movement.

[0041] In other embodiments, the cross-sectional dimensions of the microfluidic channel in the direction perpendicular to the flow direction can accommodate two or more droplets passing side by side at the same time. In one case, two or more first BAW resonators can be arranged side by side in the direction perpendicular to the flow direction in the microfluidic channel to respectively gather particles in the passing droplets. In another case, a single first BAW resonator is still maintained in the microfluidic channel, but the action range of the first BAW resonator may involve the droplets, including droplets passing side by side, or droplets passing alternately left and right. For each droplet, the particles in each droplet can still be gathered along the edge of the first BAW resonator (here, the edge through which the liquid can pass) toward the end, and the final gathered points include the staggered points when the droplets are about to move out of the range of the first BAW resonator.

[0042] In some embodiments, in addition to the above, the first BAW resonator may have a front end that is convexly curved. In some embodiments, the edges of the first BAW resonator on both sides between the front end and the end may be straight lines. The above continuous and smooth edge design of the arc and straight line makes the movement of particles in the acoustic flow tunnel smoother and more stable.

[0043] In some embodiments, a detection device is also included, and the detection range of the detection device includes the first position. Thus, the aggregated particles at the first position can be detected. Among them, the point-like enrichment of particles in the present application can facilitate the amplification of the target detection signal, improve the signal-to-noise ratio, and increase the detection limit.

[0044] In some embodiments, the detection device includes at least one of the following: an optical system detection unit, a photoelectric detection unit, an electrical detection unit, or an image detection unit.

[0045] The image detection unit may be an image detection device, and the image detection device may acquire an image including the first position. Figure 3 As shown in the schematic diagram, the camera of the image detection device can be set directly at the first position. In some embodiments, the detected object (i.e., particle) can be fluorescently marked by modifying the fluorescence, and then the image detection device can be used to obtain the image. Figure 6 The brightness data shown may include the brightness or range of the fluorescence detected at the first position to analyze the number and concentration of particles. Figure 6 The peak of the wave corresponds to the fluorescence brightness and range of the first position detected, and the lines from top to bottom at the peak respectively represent the locations of the droplet at Figure 5 The brightness at the 2nd moment, 1st moment, and initial moment.

[0046] Among them, the optical system detection unit is a device such as a microscope. The photoelectric detection unit generally includes a laser and a spectrometer, or an optical system detection unit combined with an image acquisition unit and an analysis unit. The electrical detection unit is used to detect the strength of the polarity of the target. The detection device can be used flexibly according to the needs and particle characteristics. For example, image detection can be used for observing and judging the target, such as a high-speed camera for continuous photography or photography, and then extracting the fluorescence intensity from the image to calculate the concentration. Photoelectric detection can be directly used to detect parameters such as the concentration and quantity of the target.

[0047] In some embodiments, a second BAW resonator is disposed downstream of the first BAW resonator and at a first distance from the first BAW resonator, and the first distance causes the first and second BAW resonators to overlap in time when acting on the droplet. Thus, when particles in the droplet are aggregated to the tail of the droplet, the droplet in this state can be further manipulated through the second BAW resonator.

[0048] In some embodiments, when the second BAW resonator is set, at least the microchannel covers the second BAW resonator, or the part of the microchannel covering the first and second BAW resonators can be set with a cross-section smaller than other parts of the microchannel, so that a droplet flowing through this part becomes longer along the direction of the microchannel under the restriction of this part of the microchannel, so as to be more conducive to the manipulation of the droplet by the second BAW resonator.

[0049] In some embodiments, the manipulation of the second BAW resonator is used to split the droplet into a first droplet and a second droplet; wherein, the first droplet is located on the downstream side of the microchannel relative to the second droplet, and the position of the second droplet includes the first position, that is, the second droplet includes the tail of the original droplet, and the second droplet includes the aggregated particles. In this way, on the basis of achieving the aggregation of particles to the far tail of the droplet, the droplet is further split into a second droplet including the aggregated particles, and a first droplet not including the aggregated particles. In some embodiments, when the power of the second BAW resonator is greater than the preset first power, and the flow rate of the droplet is controlled to be lower than the preset first flow rate, the effect of the manipulation is the cutting of the droplet, wherein the first power and the first flow rate can be experimentally determined according to the specific liquid type of the droplet. In addition, since the first resonator acts on the droplet at the same time, the first power and the first flow rate can be experimentally determined in combination with the power of the first resonator.

[0050] In some embodiments, after continuous droplets pass through the first BAW resonator and the second BAW resonator, continuous second droplets can be obtained, and the continuous second droplets can be merged and continuously pass through the first BAW resonator and the second BAW resonator again in a droplet manner. This can be repeated many times to obtain a liquid containing a higher concentration of particles, which can be used for the detection or purification process of the second particles.

[0051] In some embodiments, after continuous droplets pass through the first BAW resonator and the second BAW resonator, continuous first droplets can be obtained, and the continuous first droplets can be merged and continuously pass through the first BAW resonator and the second BAW resonator again in a droplet manner. This can be repeated many times to obtain a liquid containing a low number of particles, which can be used in the liquid purification process.

[0052] In some embodiments, a third BAW resonator is disposed downstream of the first BAW resonator and at a second distance from the first BAW resonator, and the second distance makes the time when the first BAW resonator and the third BAW resonator act on the droplet non-overlap. From the above, since the time when the first BAW resonator and the third BAW resonator act on the droplet does not overlap, it can be regarded that the third BAW resonator acts independently on the droplet flowing through the third BAW resonator. Therefore, the shape of the third BAW resonator, its relative position and angle with the microchannel can be set according to the needs of the downstream to achieve the desired function.

[0053] In some embodiments, the third special acoustic wave resonator can be used to mix particles in a droplet. In some embodiments, an edge of the third special acoustic wave resonator is located below the microchannel along the direction of the microchannel, so that the particles in the droplet flowing through are mixed in the droplet through the micro-vortex generated by the edge to restore the original mixing state.

[0054] In some embodiments, the third special acoustic wave resonator is located downstream of the second bulk acoustic wave resonator and can be used to control the flow direction of the droplet. Correspondingly, there are at least two microchannel branches on the downstream side of the third special acoustic wave resonator, and the first droplet and the second droplet generated by the second bulk acoustic wave resonator can be driven to flow to two different branches through the third special acoustic wave resonator. In some embodiments, the first branch is located in the direction of normal flow of the microchannel (such as being arranged in a manner extending along the microchannel), the second branch can be perpendicular to or at an angle to the microchannel, and the third special acoustic wave resonator is arranged on the opposite side of the microchannel directly opposite to the position of the second branch. When the third special acoustic wave resonator is not started, the first droplet flowing through the third special acoustic wave resonator will continue to flow to the first branch downstream. When the third special acoustic wave resonator is started, the second droplet flowing through the third special acoustic wave resonator can be driven into the second branch by controlling the third special acoustic wave resonator to generate a jet driving force. In some other embodiments, two third special acoustic wave resonators corresponding to the first branch and the second branch respectively may be provided to drive the first liquid droplet and the second liquid droplet to flow toward the first branch and the second branch respectively.

[0055] In some embodiments, a droplet injection device is also included, which can inject at least one droplet into the microchannel. If multiple droplets are present, they can be injected continuously at intervals.

[0056] In some embodiments, the driving device also includes a driving device for driving the droplet to move downstream in the microfluidic channel. In some embodiments, the driving device can be arranged as a whole with the droplet injection device, that is, the droplet injection device itself can generate the driving force for driving the droplet to move. In other embodiments, the driving device can be a device independent of the droplet injection device, for example, it can be a controllable air pump, a handheld rubber ball, and these devices are connected to the microfluidic channel front end. In other embodiments, the driving device can also be connected to the microfluidic channel outlet with a pump, and the pump can be a micropump based on the siphon principle, such as a capillary pump consisting of a capillary, or a conventional micropump.

[0057] Accordingly, the present application also provides a method for achieving particle aggregation in a droplet, using the above-mentioned device for achieving particle aggregation in a droplet, the method comprising: S10: driving droplets to flow through the microfluidic channel; S20: driving the first special acoustic wave resonator to operate, so that during the process of the droplet flowing through the first special acoustic wave resonator, particles in the droplet are gathered at a first position in the droplet, and the first position is a position corresponding to the arc-shaped end of the first special acoustic wave resonator.

[0058] In some embodiments, the method further includes: detecting the first position by a detection device. For details, please refer to the corresponding examples in the first embodiment, such as detecting the fluorescently labeled particles at the first position and determining the amount of the particles accordingly, which will not be repeated here.

[0059] In some embodiments, the method further includes: in the process of driving the first special acoustic wave resonator to work and the particles in the droplet are gathered at the first position in the droplet, driving the second special acoustic wave resonator to act on the droplet. For details, please refer to the corresponding examples in the first embodiment, such as splitting the droplet into the first droplet and the second droplet, purifying the droplet or purifying the particles in the droplet, etc., which will not be repeated here.

[0060] In some embodiments, the method further includes: driving the third special acoustic wave resonator to work, and when the third special acoustic wave resonator is used for mixing, mixing the particles in the droplet in the droplet. For details, please refer to the above corresponding examples, which will not be repeated here.

[0061] In some embodiments, the method further includes: driving the third special acoustic wave resonator to work, and when the third special acoustic wave resonator is used for driving based on the jet effect, controlling the flow directions of the first droplets and the second droplets generated by the segmentation in different branches. For details, please refer to the corresponding examples above, which will not be repeated here.

[0062] In addition, the applicant verified the effect of the particle aggregation scheme in the droplet provided by the present application through experiments, and compared the particle aggregation effect in the droplet when the particle aggregation device in the droplet adopts the first BAW resonator of the shape described in the present application and the first BAW resonator with a pointed tip (such as a shuttle-shaped or leaf-shaped tip). In the experiment, the particles were fluorescently labeled, and then a video was formed by continuous shooting with a high-speed camera. From the obtained video, it can be clearly observed that when the scheme of the present application is adopted, in the process of the droplet passing through the first BAW resonator, the particles gradually gather along the edge of the first BAW resonator to the arc-shaped end of the end of the first BAW resonator, forming a bright fluorescent spot. In the case of a first BAW resonator with a pointed tip, although the particles will move along the edge of the first BAW resonator to the tip of the end, they will quickly diffuse into the droplet when they reach the tip or near the tip, and it is difficult to stably gather at the tip of the end. It is verified that the end of the first BAW resonator of the shape described in the present application can generate an energy potential well, which can be more stably captured at the end to form bright fluorescence gathered at the point, thereby enhancing the detection limit of particles in the droplet.

[0063] In the several embodiments provided in the present application, it should be understood that the disclosed devices and methods are not limited to the above embodiments, and can also be implemented in other ways. For example, the device embodiments described above are only schematic. For example, the division of the units is only a logical function division. There may be other division methods in actual implementation, such as multiple units or components can be combined or integrated into another system, or some features can be ignored or not executed. Another point is that the mutual coupling or direct coupling or communication connection shown or discussed can be through some interfaces, indirect coupling or communication connection of devices or units, which can be electrical, mechanical or other forms.

[0064] The units described as separate components may or may not be physically separated, and the components shown as units may or may not be physical units, that is, they may be located in one place or distributed on multiple network units. Some or all of the units may be selected according to actual needs to achieve the purpose of the solution of this embodiment.

[0065] In addition, the words "first, second, third, etc." or module A, module B, module C and other similar terms in the specification and claims are only used to distinguish similar objects and do not represent a specific ordering of the objects. It can be understood that the specific order or sequence can be interchanged where permitted so that the embodiments of the present application described herein can be implemented in an order other than that illustrated or described herein.

[0066] In the above description, the numbers representing the steps, such as S110, S120, etc., do not necessarily mean that the steps will be executed in this manner. If permitted, the order of the steps can be interchanged or they can be executed simultaneously.

[0067] The term "comprising" as used in the description and claims should not be interpreted as being limited to what is listed thereafter; it does not exclude other elements or steps. Therefore, it should be interpreted as specifying the presence of the features, integers, steps or components mentioned, but does not exclude the presence or addition of one or more other features, integers, steps or components and groups thereof. Therefore, the expression "a device comprising means A and B" should not be limited to a device consisting of components A and B only.

[0068] References to "one embodiment" or "an embodiment" in this specification mean that a particular feature, structure, or characteristic described in conjunction with the embodiment is included in at least one embodiment of the present application. Therefore, the phrases "in one embodiment" or "in an embodiment" appearing in various places in this specification do not necessarily refer to the same embodiment, but may refer to the same embodiment. In addition, in one or more embodiments, the particular features, structures, or characteristics can be combined in any appropriate manner, as would be apparent to one of ordinary skill in the art from this disclosure.

[0069] Note that the above are only preferred embodiments of the present application and the technical principles used. Those skilled in the art will understand that the present application is not limited to the specific embodiments described herein, and that various obvious changes, readjustments and substitutions can be made by those skilled in the art without departing from the scope of protection of the present application. Therefore, although the present application is described in more detail through the above embodiments, the present application is not limited to the above embodiments, and may also include more other equivalent embodiments without departing from the concept of the present application, all of which belong to the scope of protection of the present application.

Claims

1. A device for achieving particle aggregation in droplets, characterized in that: include: Microfluidic channel, used to provide a channel for droplet flow; A first bulk acoustic wave resonator closely attached to the microchannel, wherein the working range of the first bulk acoustic wave resonator includes the space in the microchannel; The overall shape of the first BAW resonator is narrowed from the front end to the rear end, and the rear end is an outwardly convex arc end, and the arc end is used to make the particles in the droplet be gathered at a first position in the droplet when the droplet flows through the first BAW resonator; The terminal end is located on a downstream side in the microchannel relative to the front end.

2. The device according to claim 1, characterized in that The front end of the overall shape of the first bulk acoustic wave resonator forms an outwardly convex arc-shaped front end.

3. The device according to claim 1 or 2, characterized in that: The cross-sectional dimension of the microfluidic channel in the vertical direction of the flow accommodates the passage of a single droplet, and enables the single droplet in the microfluidic channel to be restricted by the microfluidic channel and extend along the direction of the microfluidic channel.

4. The device according to any one of claims 1 to 3, characterized in that: Also includes: A detection device having a detection range including the first position.

5. The device according to claim 4, characterized in that The detection device includes at least one of the following: an optical system detection unit, a photoelectric detection unit, an electrical detection unit or an image detection unit.

6. The device according to any one of claims 1 to 5, characterized in that: A second BAW resonator is disposed downstream of the first BAW resonator and at a first distance from the first BAW resonator, and the first distance enables the first and second BAW resonators to act on the droplet in overlapping times.

7. The device according to claim 6, characterized in that The second BAW resonator is used to split the droplet into a first droplet and a second droplet; the first droplet is located at a downstream side in the microchannel relative to the second droplet, and the position of the second droplet includes the first position.

8. A method for achieving particle aggregation in a droplet, using the device for achieving particle aggregation in a droplet according to any one of claims 1 to 7, characterized in that: The method comprises: Driving droplets to flow through microfluidic channels; The first special acoustic wave resonator is driven to work, so that during the process of the droplet flowing through the first special acoustic wave resonator, particles in the droplet are gathered at a first position in the droplet, and the first position is a position corresponding to the arc end of the first special acoustic wave resonator.

9. The method according to claim 8, characterized in that Also includes: The first position is detected by a detection device.

10. The method according to claim 8 or 9, characterized in that: In the process of driving the first special acoustic wave resonator to work and causing particles in the droplet to be gathered at a first position in the droplet, the second special acoustic wave resonator is driven to act on the droplet; The second BAW resonator is located downstream of the first BAW resonator and is disposed a first distance from the first BAW resonator.

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