Apparatus and method for achieving particle aggregation within droplets

Abstract

The application relates to a device and a method for realizing particle aggregation in a droplet, which comprises: a microfluid channel for providing a channel for droplet flow; a first bulk acoustic resonator close to the microfluid channel, the working range of the first bulk acoustic resonator including the space in the microfluid channel; the overall shape of the first bulk acoustic resonator is arranged to be narrowed from the front end to the tail end, and the tail end is an outwardly convex arc-shaped end portion, the arc-shaped end portion being used for making particles in the droplet be aggregated at a first position in the droplet during the process that the droplet flows through the first bulk acoustic resonator; and the tail end is located on the downstream side in the microfluid channel relative to the front end. The scheme of the application can realize that particles in the droplet are aggregated at a first position in the droplet, so as to facilitate observation or the interaction of different particles in the droplet after aggregation.

Description

Technical Field

[0001] This application relates to the field of microfluidics, and in particular to a device and method for achieving particle aggregation within droplets. Background Technology

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

[0003] Currently, methods for particle aggregation within droplets include electrical, magnetic, thermal, and acoustic methods. Electrical methods utilize dielectric force to repel particles from the electrode region or attract them to the vicinity of the electrode, resulting in low manipulation precision and poor enrichment. Magnetic methods use magnetic forces to manipulate magnetic particles, arranging them into a linear pattern, but this requires specific particle properties. Thermal methods use electrothermal or photothermal methods to induce thermal surges that manipulate particles, allowing them to arrange into a linear pattern, but this results in poor particle enrichment, low manipulation precision, and poor biocompatibility. Acoustic methods use low-frequency sound waves to form standing wave sound fields, using acoustic radiation to aggregate particles within the droplet at nodes and antinodes, allowing them to arrange into a linear pattern, but the enrichment level is low. Surface acoustic waves (SAWs) can use centrifugal force to aggregate particles within an independent droplet at its center or periphery through rotation, but this results in low droplet flux and long enrichment time. Current techniques typically arrange particles within droplets into a linear pattern. However, in photoelectric detection, the light spot cannot cover all linearly arranged particles, resulting in a dispersed target signal and insufficient enhancement. Therefore, there is an urgent need for a technique targeting the highly aggregated particles within high-throughput droplets.

[0004] How to improve the aggregation effect when manipulating the aggregation of particles within a droplet is a technical problem that this application aims to solve. Summary of the Invention

[0005] In view of the above-mentioned problems of the prior art, this application provides an apparatus and method for realizing particle aggregation within droplets, so as to more effectively improve the aggregation effect of particles within droplets.

[0006] To achieve the above objectives, the first aspect of this application provides an apparatus for achieving particle aggregation within a droplet, characterized in that it comprises: a microchannel for providing a channel for droplet flow; a first bulk acoustic resonator closely attached to the microchannel, the operating range of which includes the space within the microchannel; the overall shape of the first bulk acoustic resonator is narrowed from the front end to the rear end, and the rear end is an outwardly convex arc-shaped end, the arc-shaped end being used to allow particles within the droplet to be aggregated at a first position within the droplet during the flow of the droplet through the first bulk acoustic resonator; the rear end is located downstream of the front end within the microchannel.

[0007] As described above, since the overall shape of the first bulk acoustic resonator of the microchannel is narrowed from the front end to the back end, and the back end is a convex arc-shaped end, the arc-shaped end can form an acoustic energy potential well compared to the shape of the tip. When the droplet flows through the first bulk acoustic resonator, the formed acoustic energy potential well will capture the particle at the back end, and it is easier to keep it at the back end position corresponding to the acoustic energy potential well during the aggregation process, thus improving the aggregation effect.

[0008] As one possible implementation of the first aspect, the front end of the overall shape of the first bulk acoustic resonator is configured as a convex arc-shaped front end.

[0009] As can be seen from the above, the overall profile of the first-body acoustic resonator is composed of continuous, smooth edges of arc and straight lines, which makes the movement of particles in the acoustic tunnel smoother and more stable.

[0010] As one possible implementation of the first aspect, the microchannel has a cross-sectional dimension in the vertical flow direction that allows a single droplet to pass through, and the single droplet is in a state in which it is confined by the microchannel and elongates along the direction of the microchannel.

[0011] Therefore, on the one hand, the single droplet, enclosed in the microchannel, is easily driven by positive or negative pressure, making its movement speed and direction easier to control, thus improving the controllability of droplet movement. On the other hand, because the droplet is in an extended state, the time it spends flowing through the first acoustic resonator is prolonged, thereby extending the time the droplet is acted upon by the first acoustic resonator, allowing the first acoustic resonator to fully exert its influence on the particles within the droplet. Furthermore, this also facilitates further integration with another bulk acoustic resonator for manipulating the droplet while the particles within it are enriched by the first acoustic resonator.

[0012] As one possible implementation of the first aspect, it further includes: a detection device, the detection range of which includes the first position.

[0013] Therefore, by detecting the first position, information about the particles gathered at that position can be obtained.

[0014] As one possible implementation of the first aspect, the detection device includes an image detection device, the image acquired by the image detection device including the image at the first location.

[0015] From the above, image information of the aggregated particles can be obtained. This information can be used for image acquisition of fluorescently labeled particles for further image analysis.

[0016] As one possible implementation of the first aspect, a second bulk acoustic resonator is disposed downstream of the first bulk acoustic resonator and at a first distance from the first bulk acoustic resonator, the first distance causing the time of action of the first and second bulk acoustic resonators on the droplet to overlap.

[0017] Therefore, it is possible to manipulate the droplet by using a second bulk acoustic resonator while the droplet is enriched with particles by the first bulk acoustic resonator.

[0018] As one possible implementation of the first aspect, the second bulk acoustic resonator is used to divide the droplet into a first droplet and a second droplet; the first droplet is located downstream of the microchannel relative to the second droplet, and the location of the second droplet includes the first location.

[0019] This demonstrates how aggregated particles can be separated into second droplets. Further applications can be based on this, such as particle purification or liquid purification.

[0020] The second aspect of this application provides a method for achieving particle aggregation within a droplet, and the apparatus for achieving particle aggregation within a droplet as described in the first aspect. The method includes: driving a droplet to flow through a microchannel; driving a first acoustic resonator to operate, such that during the process of the droplet flowing through the first acoustic resonator, particles within the droplet are aggregated at a first position within the droplet, the first position being the position corresponding to the arcuate end of the first acoustic resonator.

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

[0022] As a possible implementation of the second aspect, the first bulk acoustic resonator is driven to operate, and during the process of the particles in the droplet being gathered at a first position in the droplet, the second bulk acoustic resonator is driven to act on the droplet; the second bulk acoustic resonator is located downstream of the first bulk acoustic resonator and at a first distance from the first bulk acoustic resonator. Attached Figure Description

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

[0024] It should be understood that the dimensions and shapes of the blocks in the above structural diagrams are for reference only and should not constitute an exclusive interpretation of the embodiments of the present invention. The relative positions and inclusion relationships between the blocks presented in the structural diagrams are only schematic representations of the structural relationships between the blocks, and are not intended to limit the physical connection methods of the embodiments of the present invention. Detailed Implementation

[0025] The technical solutions provided in this application will be further described below with reference to the accompanying drawings and embodiments. It should be understood that the system architecture and business scenarios provided in the embodiments of this application are mainly for illustrating possible implementations of the technical solutions of this application and should not be construed as the sole limitation on the technical solutions of this application. Those skilled in the art will recognize that the technical solutions provided in this application are equally applicable to similar technical problems as system architectures evolve and new business scenarios emerge.

[0026] It should be understood that the solutions for achieving particle aggregation within droplets provided in the embodiments of this application include apparatus and methods for achieving particle aggregation within droplets. Since these technical solutions solve problems based on the same or similar principles, some repetitions may not be repeated in the following descriptions of specific embodiments, but these specific embodiments should be considered as mutually referencing 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 commonly understood by one of ordinary skill in the art to which this application belongs. In case of any inconsistency, the meaning set forth in this specification or derived from the content described herein shall prevail. Furthermore, the terminology used herein is for the purpose of describing embodiments of this application only and is not intended to limit this application. To accurately describe the technical content of this application and to accurately understand the invention, the following explanations or definitions of the terms used in this specification are provided before describing specific embodiments: 1) Droplets: The volume of droplets in this application can be in the order of femtoliters, picoliters, nanoliters, microliters, etc.

[0028] 2) Ultra-high frequency bulk acoustic wave resonator: Its frequency is typically greater than 1 GHz. Excited by an input signal, it generates ultra-high frequency vibrations, emitting bulk acoustic waves. These waves propagate through the fluid, inducing directional motion and forming fluid vortices. One phenomenon is that several tiny fluid vortices can be generated at the edge of the ultra-high frequency bulk acoustic wave resonator chip. These vortices can trap particles in the liquid, and combined with the positional distribution of these vortices, it presents the phenomenon of particles in the liquid being distributed at the edge of the ultra-high frequency bulk acoustic wave resonator chip.

[0029] 3) Potential well: This refers to a potential well formed when a particle moves in a force field, and the potential energy function curve reaches its minimum within a certain finite range of space, resembling a trap. Particles within a potential well have less kinetic energy than potential energy, are in a relatively stable position, and are not easily escaped. In this paper, an acoustic energy potential well refers to the potential well formed under the acoustic energy of ultra-high frequency bulk sound waves.

[0030] In a method for manipulating droplets based on an ultra-high frequency bulk acoustic wave (UAS) resonator, when the boundary of the bulk acoustic wave chip is placed in a microchannel, the boundary can capture particles in the droplets flowing through the chip. Furthermore, as the droplet moves downstream in the microchannel, the droplets or particles can aggregate along the boundary, particularly at the downstream end of the chip, and then move out of the chip's operating area with the droplet. This phenomenon is disclosed in patent application CN202111538154.2. However, the downstream end of the bulk acoustic wave chip used in this patent is pointed, making particle aggregation unstable, and particles aggregated at the pointed end can easily be released from that aggregation point to other locations within the droplet.

[0031] This application provides another scheme for achieving particle aggregation within droplets. For the first bulk acoustic resonator that is closely attached to the microchannel, its overall shape is narrowed from the front end to the rear end, and the rear end is an outwardly convex arc-shaped end. Compared with the shape of the tip, the arc-shaped end can form an acoustic energy potential well. When the droplet flows through the first bulk acoustic resonator, the formed acoustic energy potential well captures the particles at the rear end, and during the aggregation process, the particles are more easily maintained at the rear position corresponding to the acoustic energy potential well.

[0032] This application can be used for the detection of particles contained in droplets. For example, when particles pass through a fluorescent label, the aggregation of particles can lead to an increase in the intensity of the fluorescence signal, thereby amplifying the signal, improving the signal-to-noise ratio, and increasing the detection limit. The intensity of fluorescence can reflect the amount of target particles. For example, a small number of dispersed particles within a droplet are difficult to detect. This application, due to the enhanced fluorescence signal after enrichment, can detect the presence of particles within the droplet. Another application of this application is for the combination of different particles. For example, injecting two or more different types of particles into a droplet, or a droplet containing two different types of particles (one droplet or two droplets fused into one droplet), can allow these two particles to be enriched in one place, increasing the probability of the two types of particles combining. The same principle applies to the combination of a first particle with multiple second particles, or the separate combination of multiple second particles with multiple second particles. This application can also be applied to applications such as particle purification and liquid purification, as detailed in the embodiments described later.

[0033] The present application will now be described in detail with reference to the accompanying drawings and specific embodiments.

[0034] The first embodiment of this application provides a device for realizing particle aggregation within droplets, which can be applied to the control of particle aggregation within droplets, such as... Figure 1 As shown, the device includes: Microchannels are used to provide channels for droplet flow; The first bulk acoustic resonator, which is closely attached to the microchannel, has an operating range that includes the space within the microchannel. The overall shape of the first bulk acoustic resonator is narrowed from the front end to the rear end, and the rear end is a convex arc-shaped end. The arc-shaped end is used to allow the particles in the droplet to be gathered at a first position in the droplet during the process of the droplet flowing through the first bulk acoustic resonator. The first position is the position corresponding to the arc-shaped end. The end is located on the downstream side of the microchannel relative to the front end.

[0035] Figure 2 The second embodiment of this application illustrates a device for achieving particle aggregation within a droplet. Figure 2 In, with Figure 1 In contrast, the microchannel does not cover the entire first-body acoustic resonator, but it does cover the end of the first-body acoustic resonator.

[0036] Among them, such as Figure 3 and Figure 4The diagram illustrates the particle aggregation process of a droplet flowing through a first-body acoustic resonator. When the droplet flows above the first-body acoustic resonator within the microchannel, the acoustofluid within the resonator gathers the particles within the droplet to the edge of the device. At this point, the particles only aggregate at the edge, exhibiting linear aggregation. As the droplet moves downstream, the droplet tail interface, located above the edge of the first-body acoustic resonator, moves downstream. The force exerted by the droplet tail interface acts on the particles at the edge of the first-body acoustic resonator below the droplet tail, driving the particles gathered at the edge downstream. As the droplet continues to move downstream, these particles are driven and aggregate at the downstream end of the first-body acoustic resonator, achieving point-like aggregation. It is evident that the particle aggregation process is accomplished through the interaction between the moving droplet and the first-body acoustic resonator.

[0037] The overall shape of the first-body acoustic resonator, which narrows from the front to the back, is more conducive to driving particles at the left and right edges of the first-body acoustic resonator to move towards the back. The back of the first-body acoustic resonator is designed as an arc shape, rather than a pointed structure, which is more conducive to forming an acoustic energy potential well, so as to capture and gather the moving particles at the back of the first-body acoustic resonator, making it less likely for the particles to be released at this back.

[0038] In some embodiments, the first bulk acoustic resonator is located at the bottom of the microchannel, and its width (measured as the dimension of the first bulk acoustic resonator in the direction perpendicular to the flow direction of the microchannel in a top view) is smaller than the width of the microchannel. In other embodiments, the first bulk acoustic resonator is located at the top or side of the microchannel. In still other embodiments, the widest portion of the width of the first bulk acoustic resonator may be greater than the width of the microchannel.

[0039] In some embodiments, the cross-sectional dimensions of the microchannel in the vertical flow direction are large enough to accommodate a single droplet.

[0040] In some embodiments, the microchannel has a cross-sectional dimension in the vertical flow direction that can accommodate a single droplet, and the single droplet is confined within the microchannel and elongated along the microchannel direction. In this case, on the one hand, the single droplet is enclosed by the microchannel and is easily driven by positive or negative pressure, thus making the droplet's movement speed (including the special case of zero speed) and movement direction (forward or backward) easier to control. On the other hand, because the droplet is in an elongated state, the time it takes to flow through the first acoustic resonator is extended, thereby extending the time the droplet is acted upon by the first acoustic resonator, allowing the first acoustic resonator to fully exert its effect on the particles within the droplet. In some embodiments, a device capable of generating air pressure, such as an air pump, a manual pipette, or a squeezed rubber ball, can be provided to connect to the inlet or outlet of the microchannel to control the droplet's movement speed and direction.

[0041] In other embodiments, the cross-sectional dimensions of the microchannel in the vertical flow direction are large enough to accommodate two or more droplets passing side-by-side simultaneously. In one case, two or more first-volume acoustic resonators can be arranged side-by-side in the vertical flow direction within the microchannel to aggregate particles from the passing droplets. In another case, a single first-volume acoustic resonator is maintained within the microchannel, but its effective range can extend to all droplets, including those passing side-by-side or alternating left and right. For each droplet, particles can still be aggregated along the edge of the first-volume acoustic resonator (here referring to the edge the liquid can pass through) towards the end, with the final aggregation point including the staggered points where the droplets are about to leave the range of the first-volume acoustic resonator.

[0042] In some embodiments, in addition to the above-described overall shape, the front end of the first bulk acoustic resonator may be configured as a convex arc-shaped front end. In some embodiments, the edges of the first bulk acoustic resonator located on both sides between the front and rear ends may be straight lines. The continuous, smooth edge design of the arc and straight lines described above makes the movement of particles in the acoustic tunnel smoother and more stable.

[0043] In some embodiments, a detection device is further included, the detection range of which includes the first location. This allows for the detection of aggregated particles at the first location. The point-like enrichment of particles described in this application facilitates the amplification of the target detection signal, improves the signal-to-noise ratio, and increases 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, which can acquire an image including the first location. In some embodiments, such as Figure 3 As shown in the schematic diagram, the camera of the image detection device can be positioned directly facing the first location. In some embodiments, fluorescent labeling can be performed by modifying the detected object (i.e., particles) with fluorescence, thereby enabling the image detection device to obtain, for example, [further details needed]. Figure 6 The brightness data shown may include the brightness or range of the detected fluorescence at the first location, enabling analysis of particle quantity, concentration, etc. Figure 6 The peak corresponds to the fluorescence intensity and range of the first detected position. The lines from top to bottom at the peak represent the locations of the droplet. Figure 5 The brightness at the 2nd time, the 1st time, and the initial time.

[0046] Optical detection units include devices such as microscopes. Photoelectric detection units typically include lasers and spectrometers, or a combination of optical detection units and image acquisition and analysis units. Electrical detection units are used to detect the strength of the target's polarity. The choice of detection device can be flexible, depending on the needs and particle characteristics. For example, image detection is suitable for observing and judging targets; it can involve continuous imaging with a high-speed camera, then extracting fluorescence intensity from the images to calculate concentration. Photoelectric detection, on the other hand, can be directly used to detect parameters such as the concentration and quantity of a target.

[0047] In some embodiments, a second bulk acoustic resonator is disposed downstream of the first bulk acoustic resonator at a first distance from the first bulk acoustic resonator, the first distance causing the time of action of the first and second bulk acoustic resonators on the droplet to overlap. Thus, it is possible to further manipulate the droplet in a state where particles in the droplet have gathered at the tail of the droplet using the second bulk acoustic resonator.

[0048] In some embodiments, when the second bulk acoustic resonator is provided, at least the microchannel covers the second bulk acoustic resonator, or the portion of the microchannel covering the first and second bulk acoustic resonators may have a cross-section smaller than other portions of the microchannel, so that the droplet flowing through this portion becomes longer along the direction of the microchannel under the constraint of this portion of the microchannel, which is more conducive to the second bulk acoustic resonator's control over the droplet.

[0049] In some embodiments, the manipulation of the second volume acoustic resonator is used to divide the droplet into a first droplet and a second droplet; wherein the first droplet is located downstream of the second droplet within the microchannel, the location of the second droplet includes the first location, that is, the second droplet includes the tail of the original droplet, and the second droplet includes the aggregated particles. In this way, based on the aggregation of particles towards the distant droplet tail, the droplet is further divided into a second droplet including the aggregated particles and a first droplet excluding the aggregated particles. In some embodiments, when the power of the second volume acoustic resonator is greater than a preset first power, and the droplet flow rate is controlled to be lower than a preset first flow rate, the manipulation effect is the cutting of the droplet, wherein the first power and the first flow rate can be experimentally determined based on the specific liquid type of the droplet. Furthermore, since the first resonator also acts on the droplet, the power of the first resonator and the experimentally determined first power and first flow rate can be combined simultaneously.

[0050] In some embodiments, after a continuous droplet passes through the first and second bulk acoustic resonators, a continuous second droplet can be obtained. The continuous second droplet can then merge and pass through the first and second bulk acoustic resonators again in a droplet manner. This process can be repeated multiple times to obtain a liquid containing a high concentration of particles, which can be applied to the detection or purification of the second particles.

[0051] In some embodiments, after continuous droplets pass through the first and second bulk acoustic resonators, continuous first droplets can be obtained. These continuous first droplets can then merge and pass through the first and second bulk acoustic resonators again in a droplet manner. This process can be repeated multiple times to obtain a liquid containing a low number of particles, which can be applied to the purification process of liquids.

[0052] In some embodiments, a third bulk acoustic resonator is disposed downstream of the first bulk acoustic resonator at a second distance from the first bulk acoustic resonator. This second distance ensures that the time at which the first and third bulk acoustic resonators act on the droplet does not overlap. Therefore, since the time at which the first and third bulk acoustic resonators act on the droplet does not overlap, it can be considered that the third bulk acoustic resonator acts independently on the droplet flowing through it. Thus, the shape, relative position, and angle of the third bulk acoustic resonator to the microchannel can be set according to downstream needs to achieve the desired function.

[0053] In some embodiments, the third acoustic resonator can be used for mixing particles within a droplet. In some embodiments, one edge of the third acoustic resonator is located below the microchannel along the microchannel direction, so that microvortices generated by this edge mix the particles within the flowing droplet, restoring them to their original mixed state.

[0054] In some embodiments, the third acoustic resonator is located downstream of the second bulk acoustic resonator and can be used to control the flow direction of the droplets. Correspondingly, a branch with at least two microchannels is located downstream of the third acoustic resonator. The third acoustic resonator can drive the first and second droplets generated by the second bulk acoustic resonator to flow into two different branches. In some embodiments, the first branch is located in the normal flow direction of the microchannel (e.g., arranged along the microchannel), and the second branch can be perpendicular to or at an angle to the microchannel. The third acoustic resonator is located on the opposite side of the microchannel, directly opposite the location connecting the second branch. When the third acoustic resonator is not activated, the first droplet flowing through it continues to flow downstream into the first branch. When the third acoustic resonator is activated, by controlling the third acoustic resonator to generate a jet driving force, the second droplet flowing through it can be driven into the second branch. In other embodiments, two third acoustic resonators corresponding to the first branch and the second branch respectively can be provided to drive the first droplet and the second droplet to flow to 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, and when there are multiple droplets, they can be injected continuously at intervals.

[0056] In some embodiments, the system further includes a driving device for moving droplets downstream within the microchannel. In some embodiments, the driving device may be integrated with the droplet injection device, meaning the droplet injection device itself generates the driving force to move the droplets. In other embodiments, the driving device may be a device independent of the droplet injection device, such as a controllable air pump or a handheld rubber ball connected to the front end of the microchannel. In still other embodiments, the driving device may be a pump connected to the outlet of the microchannel; this pump may be a micropump based on the siphon principle, such as a capillary pump consisting of capillaries, or a conventional micropump.

[0057] Accordingly, this application also provides a method for achieving particle aggregation within a droplet, using the aforementioned apparatus for achieving particle aggregation within a droplet, the method comprising: S10: Drives droplets to flow through the microchannel; S20: Drive the first acoustic resonator to work, so that during the process of the droplet flowing through the first acoustic resonator, the particles in the droplet are gathered at a first position in the droplet, the first position being the position corresponding to the arc-shaped end of the first acoustic resonator.

[0058] In some embodiments, the method further includes detecting the first position using a detection device. Specific examples can be found in the corresponding examples of the first embodiment, such as detecting fluorescently labeled particles at the first position and determining the quantity of particles accordingly, which will not be elaborated upon here.

[0059] In some embodiments, the method further includes: driving the first ultrasonic resonator to operate, during the process of the particles in the droplet being gathered at a first position within the droplet, driving the second ultrasonic resonator to act on the droplet. Specific examples can be found in the corresponding examples of the first embodiment, such as splitting the droplet into a first droplet and a second droplet, droplet purification, or particle purification in the droplet, etc., which will not be elaborated further here.

[0060] In some embodiments, the method further includes: driving the third acoustic resonator to operate, wherein when the third acoustic resonator is used for mixing, the particles within the droplet are mixed within the droplet. See the foregoing examples for details, which will not be repeated here.

[0061] In some embodiments, the method further includes: driving the third acoustic resonator to operate, wherein when the third acoustic resonator is used for jet-effect-based driving, the flow direction of the first and second droplets generated by the segmentation is controlled in different branches. See the foregoing examples for details, which will not be repeated here.

[0062] Furthermore, the applicant conducted experiments to verify the effectiveness of the droplet particle aggregation scheme provided in this application, and compared the particle aggregation effects when the droplet particle aggregation device uses a first bulk acoustic resonator of the shape described in this application, and when the first bulk acoustic resonator has a pointed end (such as a spindle-shaped or leaf-shaped tip). In the experiment, the particles were fluorescently labeled, and then a video was generated by continuous shooting with a high-speed camera. From the obtained video, it can be clearly observed that when using the scheme of this application, as the droplet passes through the first bulk acoustic resonator, the particles gradually aggregate along the edge of the first bulk acoustic resonator to the arc-shaped end of the first bulk acoustic resonator, forming a bright fluorescent spot. However, when using a first bulk acoustic resonator with a pointed end, although the particles will move along the edge of the first bulk acoustic resonator towards the pointed end, they will quickly diffuse into the droplet when they reach or are near the pointed end, making it difficult to stably aggregate at the pointed end. This study verifies that the first bulk acoustic resonator of the shape described in this application can generate an energy potential well at its end, which can more stably capture particles at the end, forming a bright fluorescence focused at that point, thus enhancing the detection limit of particles within the droplet.

[0063] In the several embodiments provided in this application, it should be understood that the disclosed apparatus and methods are not limited to the above embodiments and can be implemented in other ways. For example, the apparatus embodiments described above are merely illustrative. For instance, the division of units is only a logical functional division, and in actual implementation, there may be other division methods. For example, multiple units or components may be combined or integrated into another system, or some features may be ignored or not executed. Furthermore, the coupling or direct coupling or communication connection shown or discussed may be through some interfaces; the indirect coupling or communication connection between apparatuses or units may be electrical, mechanical, or other forms.

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

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

[0066] In the above description, the labels of the steps involved, such as S110, S120, etc., do not mean that the steps will necessarily be executed. The order of the steps can be interchanged or executed simultaneously if permitted.

[0067] The term "comprising" as used in the specification and claims should not be construed as limiting itself to what follows; it does not exclude other elements or steps. Therefore, it should be interpreted as specifying the presence of the mentioned feature, integral, step, or component, but does not exclude the presence or addition of one or more other features, integrals, steps, or components, or groups thereof. Thus, the statement "device comprising means A and B" should not be limited to a device consisting solely of components A and B.

[0068] The terms "an embodiment" or "an embodiment" as used in this specification mean that a particular feature, structure, or characteristic described in conjunction with that embodiment is included in at least one embodiment of this application. Therefore, the terms "in one embodiment" or "in an embodiment" appearing throughout this specification do not necessarily refer to the same embodiment, but may refer to the same embodiment. Furthermore, in one or more embodiments, the particular features, structures, or characteristics can be combined in any suitable manner, as will be apparent to those skilled in the art from this disclosure.

[0069] Note that the above are merely preferred embodiments and the technical principles employed in this application. Those skilled in the art will understand that this application is not limited to the specific embodiments described herein, and various obvious changes, readjustments, and substitutions can be made without departing from the scope of protection of this application. Therefore, although this application has been described in detail through the above embodiments, this application is not limited to the above embodiments, and may include many other equivalent embodiments without departing from the concept of this application, all of which fall within the scope of protection of this application.

Claims

1. A device for achieving particle aggregation within a droplet, characterized in that, include: Microchannels are used to provide channels for droplet flow; The first bulk acoustic resonator, which is closely attached to the microchannel, has an operating range that includes the space within the microchannel. The overall shape of the first bulk acoustic resonator is narrowed from the front end to the rear end, and the rear end is a convex arc-shaped end. The arc-shaped end is used to allow the particles in the droplet to be gathered at a first position in the droplet as the droplet flows through the first bulk acoustic resonator. The first position is the position corresponding to the arc-shaped end of the first bulk acoustic resonator; The end is located on the downstream side of the microchannel relative to the front end.

2. The apparatus according to claim 1, characterized in that, The front end of the first bulk acoustic resonator has an outwardly convex arc shape.

3. The apparatus according to claim 1 or 2, characterized in that, The microchannel has a cross-sectional dimension in the vertical flow direction that allows a single droplet to pass through, and the single droplet is in a state where it is confined by the microchannel and elongates along the direction of the microchannel.

4. The apparatus according to claim 1, characterized in that, Also includes: The detection device has a detection range including the first position.

5. The apparatus 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 apparatus according to claim 1, 2, 4 or 5, characterized in that, A second bulk acoustic resonator is located downstream of the first bulk acoustic resonator and at a first distance from the first bulk acoustic resonator. The first distance causes the time of action of the first bulk acoustic resonator and the second bulk acoustic resonator on the droplet to overlap.

7. The apparatus according to claim 6, characterized in that, The second bulk acoustic resonator is used to divide the droplet into a first droplet and a second droplet; the first droplet is located downstream of the microchannel relative to the second droplet, and the location of the second droplet includes the first location.

8. A method for achieving particle aggregation within a droplet, using the apparatus for achieving particle aggregation within a droplet as described in any one of claims 1-7, characterized in that, The method includes: Drive droplets through microchannels; When the first bulk acoustic resonator is driven to work, the droplet flows through the first bulk acoustic resonator and the particles in the droplet are gathered at a first position in the droplet. The first position is the position corresponding to the arc-shaped end of the first bulk acoustic 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, The process of driving the first bulk acoustic resonator to work, and during the process of the particles in the droplet being gathered at the first position in the droplet, drives the second bulk acoustic resonator to act on the droplet. The second bulk acoustic resonator is located downstream of the first bulk acoustic resonator and at a first distance from the first bulk acoustic resonator.

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