Microparticle manipulation devices, sorting devices, detection devices, and corresponding methods

Abstract

The application relates to a particle manipulation, sorting and detecting device and method, comprising a special ultrasonic device which comprises two side edges extending from a first end to a second end, the distance between the two side edges gradually shrinks along the extending direction and forms an angle, so that the drag force of the acoustic fluid formed by the side edges gradually decreases along the extending direction, and the second side edge of the two side edges close to the downstream side of the first flow channel is arranged to be inclined to the extending direction of the first flow channel; the special ultrasonic device captures the particles in the first flow channel and moves the particles along the acoustic fluid tunnel of the second side edge towards the second end in the working state, and the particles are separated from the acoustic fluid tunnel of the second side edge at a position where the drag force of the acoustic fluid and the drag force of the fluid in the first flow channel are matched. The application also provides a corresponding method. The application can realize multi-channel particle sorting through one special ultrasonic device, reduces the number of special ultrasonic devices, and is suitable for miniaturization of a micro-fluidic system.

Description

Technical Field

[0001] This application relates to the fields of micro-electro-mechanical systems (MEMS) technology and microfluidics technology, and in particular to a particle manipulation device, sorting device, detection device, manipulation method, sorting method and detection method. Background Technology

[0002] Microfluidic systems are based on microfluidic control chips, supplemented by external driving physical fields and detection systems. They aim to build miniaturized on-chip biochemical laboratories, that is, to integrate the basic operations involved in biological and chemical fields such as sample preparation, reaction, detection, separation, cell culture, screening, and lysis into a micron-scale microchannel network, so as to realize the various functions of biochemical laboratories more efficiently at a lower cost.

[0003] Droplet microfluidics is an important branch of microfluidics. Common droplet manipulation techniques include droplet generation, cutting, fusion, sorting, and laminar mixing and particle enrichment within droplets. Droplet sorting technology refers to droplet manipulation techniques that utilize special flow channel structures, droplet physicochemical properties, or introduce external physical fields to transport and distribute droplets into different downstream sub-channels.

[0004] Droplet sorting technology includes sorting schemes based on electrical, magnetic, acoustic, thermal, and pneumatic technologies. Among these, acoustic droplet sorting has the advantage of good biocompatibility. For example, Chinese patent application CN202311458207.9 discloses a technique for particle sorting using ultrasonic devices. In this patent application, the end of the ultrasonic device is angled, capturing particles flowing through its effective range and releasing them from the end of the ultrasonic device into the target sorting channel. Furthermore, when there are multiple sorting channels (e.g., at least three), multiple ultrasonic devices can be set up. When each target particle is detected sequentially by an optical system, each ultrasonic device is activated to capture the target particle and release it from the end of the ultrasonic device into the corresponding target sorting channel.

[0005] How to reduce the number of ultrasonic devices and miniaturize microfluidic systems with multiple sorting channels is a technical problem that needs to be solved. Summary of the Invention

[0006] In view of the above problems of the prior art, this application provides a particle manipulation device, a sorting device, a detection device, a manipulation method, a sorting method, and a detection method, so as to realize the use of a special ultrasonic device to perform sorting for multiple sorting channels.

[0007] The first aspect of this application provides a particle manipulation device, comprising: A special ultrasonic device includes two sides extending from a first end to a second end, and the distance between the two sides gradually decreases with the extension direction and forms an angle at the second end, so as to make the drag force of the acoustic fluid formed on the sides gradually decrease with the extension direction. The first end includes an arc-shaped edge protruding away from the second end, and the two ends of the arc-shaped edge are connected to the two sides in a smooth transition manner. The second side, which is closer to the downstream side of the first flow channel, is inclined to the extension direction of the first flow channel. The effective range of the ultrasonic device includes the first flow channel, which is used to capture particles in the liquid flowing through the first end in the first flow channel when in operation, and to move the particles toward the second end along the acoustic fluid tunnel on the second side, and to make the particles detach from the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid matches the drag force of the fluid in the first flow channel, so as to flow downstream.

[0008] A second aspect of this application provides a particle sorting apparatus, comprising: A special ultrasonic device includes two sides extending from a first end to a second end, and the distance between the two sides gradually decreases with the extension direction and forms an angle at the second end, so as to make the drag force of the acoustic fluid formed on the sides gradually decrease with the extension direction. The first end includes an arc-shaped edge protruding away from the second end, and the two ends of the arc-shaped edge are connected to the two sides in a smooth transition manner. The second side, which is closer to the downstream side of the first flow channel, is inclined to the extension direction of the first flow channel. The first flow channel is connected to at least two downstream sub-flow channels, and the inlet of each of the downstream sub-flow channels faces a different position on the second side; The effective range of the ultrasonic device includes the first flow channel, which is used to capture particles in the liquid flowing through the first end in the first flow channel when in operation, and to move the particles along the acoustic fluid tunnel on the second side toward the second end, and to make the particles leave the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid and the drag force of the fluid in the first flow channel match, so as to flow to the corresponding downstream flow channel.

[0009] A third aspect of this application provides a particulate detection device, comprising: A special ultrasonic device includes two sides extending from a first end to a second end, and the distance between the two sides gradually decreases with the extension direction and forms an angle at the second end, so as to make the drag force of the acoustic fluid formed on the sides gradually decrease with the extension direction. The first end includes an arc-shaped edge protruding away from the second end, and the two ends of the arc-shaped edge are connected to the two sides in a smooth transition manner. The second side, which is closer to the downstream side of the first flow channel, is inclined to the extension direction of the first flow channel. The effective range of the ultrasonic device includes the first flow channel, which is used to capture particles in the liquid flowing through the first end in the first flow channel when in operation, and to move the particles toward the second end along the acoustic fluid tunnel on the second side, and to make the particles detach from the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid and the drag force of the fluid in the first flow channel match, so as to flow downstream. A detection unit is provided downstream of the first flow channel for generating a detection signal based on the flow of particles through the detection area. The detection signal is related to the particle size and the position of the particles as they flow through the detection area.

[0010] In some feasible ways, the position where the particles detach from the acoustic-fluid tunnel on the second side is adjusted by one of the following: Adjust the power driving the ultrasonic device; the greater the power, the closer the position is to the second end. The duration of operation of the ultrasonic device is adjusted; the longer the duration, the closer the position is to the second end. Adjust the fluid flow rate in the first flow channel; the faster the flow rate, the closer the position is to the first end.

[0011] In some feasible implementations, when the particles in the liquid flowing through the first end in the first channel include particles of different sizes, the smaller the particle, the closer its position is to the second end as it leaves the acoustic fluid tunnel on the second side.

[0012] Among the feasible methods, at least one of the following is also included: The first end of the ultrasonic device has a first distance from the sidewall closest to the first flow channel. The first distance causes particles flowing through the first end to be captured by the acoustic-fluid tunnel of the arc-shaped edge of the first end and causes the particles to move toward the acoustic-fluid tunnel of the second side. The second side of the ultrasonic device is inclined at a first angle to the extension direction of the first flow channel. The first angle causes the particle to move a distance along the acoustic-fluid tunnel of the second side to exceed a threshold, and the deviation of the particle from the acoustic-fluid tunnel of the second side to exceed a threshold.

[0013] Among the feasible methods, at least one of the following is also included: The first flow channel is connected upstream to a first upstream sub-flow channel and at least one second upstream sub-flow channel; the outlet of the first upstream sub-flow channel faces a first position towards the inlet of the first flow channel, and the downstream of the first position is directly opposite the first end of the ultrasonic device, so that the first upstream sub-flow channel carries the liquid including the particles to the first end of the ultrasonic device; the outlet of the at least one second upstream sub-flow channel faces the remaining position towards the inlet of the first flow channel, and is used to introduce liquid into the first flow channel to maintain a stable flow direction of the liquid including the particles entering the first flow channel through the first upstream sub-flow channel; A support structure located within the first flow channel, supporting the first flow channel between its bottom and top; A balancing channel is formed by bridging and connecting each of the downstream sub-channels to balance the flow resistance of each of the downstream sub-channels. The cross-sectional dimension of the balancing channel is smaller than that of the sub-channel.

[0014] A fourth aspect of this application provides a method for particle manipulation, characterized in that it uses the apparatus described in any one of the first, second, and third aspects, and the method includes: When the ultrasonic device is in operation, it captures particles in the liquid flowing through the first end of the ultrasonic device in the first flow channel, and causes the particles to move towards the second end along the acoustic fluid tunnel on the second side of the ultrasonic device. The particles detach from the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid matches the drag force of the fluid in the first flow channel, and then flow downstream.

[0015] A fifth aspect of this application provides a method for particle sorting, characterized in that it uses the apparatus described in any one of the first, second, and third aspects, and the method includes: When the ultrasonic device is in operation, it captures particles in the liquid flowing through the first end of the ultrasonic device in the first flow channel, and causes the particles to move towards the second end along the acoustic fluid tunnel on the second side of the ultrasonic device. The particles detach from the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid matches the drag force of the fluid in the first channel, and flow into the corresponding downstream channel.

[0016] A sixth aspect of this application provides a method for detecting particulate matter, characterized in that it uses the apparatus described in any one of the first, second, and third aspects, and the method includes: When the ultrasonic device is in operation, it captures particles in the liquid flowing through the first end of the ultrasonic device in the first flow channel, and causes the particles to move towards the second end along the acoustic fluid tunnel on the second side of the ultrasonic device. The particles detach from the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid matches the drag force of the fluid in the first flow channel, and flow downstream. A detection unit located downstream of the first flow channel generates a detection signal when the particles flow through the detection area. The detection signal is related to the particle size and the position of the particles as they flow through the detection area.

[0017] The particle manipulation, sorting, and detection scheme provided in this application can achieve sorting of multiple channels based on a single ultrasonic device, such as sorting of two, three, or more channels, which can effectively reduce the number of ultrasonic devices and facilitate the miniaturization of microfluidic systems. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the acoustic-fluid tunnel provided in an embodiment of this application; Figure 2 This is a schematic diagram of the particle manipulation device provided in the first embodiment of this application performing particle manipulation; Figure 3 This is a schematic diagram of the ultrasonic device in the embodiments of this application; Figure 4 This is a schematic diagram of the particle sorting device provided in the second embodiment of this application; Figure 5 This is a schematic diagram of the particulate detection device provided in the third embodiment of this application; Figure 6a This is a schematic diagram of the experimental platform for particle sorting provided in the embodiments of this application; Figure 6b This is an experimental result diagram showing the deflection of droplets at different positions within the first flow channel using the ultrasonic device provided in this application embodiment; Figure 6c1 and Figure 6c2 The figure shows the experimental results of manipulating droplets of different sizes with a fixed power of the driving ultrasonic device; Figure 6d1 and Figure 6d2 The figures show the experimental results of using different powers of a driving ultrasonic device to drive droplets of the same size. Figure 6e1 and Figure 6e2 This is a graph showing the results of a droplet sorting experiment applied to a three-channel system; Figure 6f This is a graph showing the results of a droplet sorting experiment applied to a five-channel system; Figure 6g This is a graph showing the results of a droplet sorting experiment applied to a seven-channel system.

[0019] 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

[0020] 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.

[0021] It should be understood that the particle sorting schemes provided in the embodiments of this application include particle manipulation devices, sorting devices, detection devices, manipulation methods, sorting methods, and detection methods. Since these technical solutions solve problems based on the same or similar principles, some repetitive details may not be repeated in the following descriptions of specific embodiments. However, it should be considered that these specific embodiments have mutual references and can be combined with each other.

[0022] 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) Ultrasonic Device: A high-frequency resonator, which can be a device that generates mechanical vibration by applying voltage based on the piezoelectric effect. In this application, a piezoelectric resonator that generates ultrasonic waves of not less than 0.5 GHz (GHz is equivalent to gigahertz) during operation is used. Preferably, it is a piezoelectric resonator that generates ultrasonic waves of not less than 1 GHz and not more than 30 GHz during operation, for example, it can be 2 GHz to 2.5 GHz. Such piezoelectric resonators can be, for example, surface acoustic wave (SAW) devices, bulk acoustic wave (BAW) devices, etc. For example, when it is BAW, it can be a thin-film bulk acoustic wave resonator (FBAR), a solid-state assembled resonator (SMR), or a Lamb wave resonator (LWR). For ease of description, the piezoelectric resonator that generates ultrasonic waves of not less than 0.5 GHz will be referred to as an ultrasonic device from now on.

[0023] 2) Acoustic-fluid tunnel: Under the excitation of an input signal, an ultrasonic device generates ultra-high frequency vibrations that emit sound waves. These sound waves propagate through the fluid, inducing directional movement of the fluid and forming fluid vortices. One phenomenon is... Figure 1 As shown, several tiny fluid vortices can be generated at the edge of the chip in a supersonic device. These fluid vortices can trap particles in the liquid. Combined with the positional distribution of these fluid vortices, a phenomenon of the distribution of liquid particles at the edge of the chip in a supersonic device is observed. Since the particles in the fluid flow through these fluid vortices distributed at the edge of the chip, the flow path of these particles formed by the fluid vortices is referred to in this application as an acoustic fluid tunnel.

[0024] 3) Particles: refer to geometric bodies with a specific shape within a certain size range, such as microscopic particles that are located in a liquid environment and can be distinguished from the liquid environment (i.e., insoluble) and can be moved in the liquid environment, which can all be regarded as the particles described in this application.

[0025] In some embodiments, the particle diameter can range from the nanoscale to the millimeter scale, and the particles can include: cells, molecules, molecular polymers, long-chain molecules, DNA nucleic acids, inorganic particles, metal particles, composite particles, magnetic particles, quantum dots, microbeads (or microspheres, used for functional modification, such as modifying proteins, specific substances, etc.), etc. In some embodiments, the particles can also be non-solid, for example, they can be in the form of droplets, such as in the form of droplets in another immiscible liquid medium, such as water droplets (or water beads) in the oil phase of a flow channel, or oil droplets (or oil beads) in the aqueous phase, etc.

[0026] 4) The main forces acting on particles in the fluid include the drag force of the ultrasonic device's acoustic radiation (primarily confining the particles within the acoustic-fluid tunnel) and the downstream drag force of the fluid (primarily driving the particles downstream). The particle escapes the acoustic-fluid tunnel at a critical point where the drag force of the acoustic radiation and the fluid drag force are balanced. In this embodiment, the ultrasonic device can be droplet-shaped, with a gradual change in the distance between the two sides of the droplet tip, causing a gradual change in the drag force of the acoustic-fluid at the sides, thereby allowing particles of different sizes to be released at different positions on the sides.

[0027] 5) Reasonable ranges for parameters, and positive and negative correlations between parameters: A reasonable range refers to the range of parameters that conform to the scheme of this application, such as particle size within a reasonable range, power control within a reasonable range, etc. These ranges can be obtained experimentally. Positive correlation between parameters means that one parameter increases as another parameter increases, and negative correlation means that one parameter increases as another parameter decreases. The parameters mentioned in this application cannot be infinitely small or infinitely large. Therefore, unless otherwise specified, the parameter values ​​mentioned in this application refer to values ​​within a reasonable range. For example, when describing a positive correlation between parameter A and parameter B, it means that within a certain range, parameter A and parameter B are positively correlated, and it can be predicted that beyond this range, parameter B will no longer be positively correlated with parameter A (after parameter A increases to a certain value, B reaches a saturation state, and then parameter B will no longer increase with the increase of parameter A). This range of values ​​is the reasonable range of values.

[0028] Microfluidic particle sorting schemes include acoustic sorting methods, which offer advantages such as low power consumption, minimal cell damage, and high versatility. Acoustic sorting technology can utilize ultrasonic devices to improve screening accuracy. For example, the scheme provided in Chinese patent application CN202311458207.9 employs a two-dimensional sheath flow or other focusing method upstream of the microchannel to arrange the particle sample in a queue within the fluid. When the detection device detects a target particle in the queue, it activates the ultrasonic device, driving the target particles flowing within its effective range to a target sub-channel. When the device is not activated, it directs particles flowing within its effective range to another sub-channel. With more sub-channels, more ultrasonic devices are needed to drive different target particles to different sub-channels.

[0029] This application provides an improved particle sorting scheme that can achieve multi-channel sorting using a single ultrasonic device. That is, a single ultrasonic device is used to drive particles of different sizes in the fluid to different flow channels, reducing the number of ultrasonic devices used.

[0030] The solutions provided in this application will now be described in detail with reference to the accompanying drawings and embodiments.

[0031] The first embodiment of this application provides a particle manipulation device, referring to... Figure 2 As shown, the control device includes: Special ultrasonic devices, such as Figure 3 An embodiment of the ultrasonic device shown includes two sides extending from a first end to a second end, the distance between the two sides gradually narrows with the extension direction and forms an angle at the second end, so that the drag force of the acoustic fluid formed on the sides gradually decreases with the extension direction. The first end includes an arc-shaped edge protruding away from the second end, and the two ends of the arc-shaped edge are smoothly connected to the two sides. The two sides include a first side and a second side, wherein the second side is closer to the downstream channel, forming that the second side of the two sides that is closer to the downstream side of the first channel is inclined to the extension direction of the first channel. The effective range of the ultrasonic device includes the first flow channel, which is used to capture particles in the liquid flowing through the first end in the first flow channel when in operation, and to move the particles toward the second end along the acoustic fluid tunnel on the second side, and to make the particles detach from the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid matches the drag force of the fluid in the first flow channel, so as to flow downstream.

[0032] like Figure 2 As shown, a particle capture zone is illustrated, in which particles in the liquid flowing through the first end in the first channel are captured and enter the acoustic fluid tunnel on the arc-shaped side. A release zone is also shown, corresponding to the acoustic fluid tunnel distribution area on the second side.

[0033] The width of the ultrasonic device is designed to decrease from the first end to the second end by the particle manipulation device. This allows the acoustic fluid drag force distribution on the second side of the ultrasonic device to gradually decrease from the first end to the second end. Under the action of fluid drag force and acoustic fluid drag force, particles of different sizes will detach from the acoustic fluid tunnel at different positions on the second side. Specifically, the smaller the particle size, the closer the detachment position is to the second end. Thus, when particles of different sizes flow through the ultrasonic device, they can be manipulated to flow downstream to their corresponding positions, thereby achieving particle manipulation.

[0034] A second embodiment of this application provides a particle sorting device, including the particle manipulation device described in the first embodiment, such as... Figure 3 As shown, the particle sorting device specifically includes: A special ultrasonic device includes two sides extending from a first end to a second end, and the distance between the two sides gradually decreases with the extension direction and forms an angle at the second end, so as to make the drag force of the acoustic fluid formed on the sides gradually decrease with the extension direction. The first end includes an arc-shaped edge protruding away from the second end, and the two ends of the arc-shaped edge are connected to the two sides in a smooth transition manner. The two sides include a first side and a second side, wherein the second side is closer to the downstream channel, forming that the second side of the two sides that is closer to the downstream side of the first channel is inclined to the extension direction of the first channel. The first flow channel is connected to at least two downstream sub-flow channels, and the inlet of each of the downstream sub-flow channels faces a different position on the second side; The effective range of the ultrasonic device includes the first flow channel, which is used to capture particles in the liquid flowing through the first end in the first flow channel when in operation, and to move the particles along the acoustic fluid tunnel on the second side toward the second end, and to make the particles leave the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid and the drag force of the fluid in the first flow channel match, so as to flow to the corresponding downstream flow channel.

[0035] As shown above, when there are multiple downstream sub-channels in parallel downstream of the first channel, particles of different sizes can be directed to different downstream sub-channels, thus achieving particle sorting.

[0036] The third embodiment of this application provides a particulate detection device, including the particulate manipulation device described in the first embodiment, with reference to... Figure 5 The diagram shown illustrates a particle detection device, which includes: A special ultrasonic device includes two sides extending from a first end to a second end, and the distance between the two sides gradually decreases with the extension direction and forms an angle at the second end, so as to make the drag force of the acoustic fluid formed on the sides gradually decrease with the extension direction. The first end includes an arc-shaped edge protruding away from the second end, and the two ends of the arc-shaped edge are connected to the two sides in a smooth transition manner. The two sides include a first side and a second side, wherein the second side is closer to the downstream channel, forming that the second side of the two sides that is closer to the downstream side of the first channel is inclined to the extension direction of the first channel. The effective range of the ultrasonic device includes the first flow channel, which is used to capture particles in the liquid flowing through the first end in the first flow channel when in operation, and to move the particles toward the second end along the acoustic fluid tunnel on the second side, and to make the particles detach from the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid and the drag force of the fluid in the first flow channel match, so as to flow downstream. A detection unit is provided downstream of the first flow channel for generating a detection signal based on the flow of particles through the detection area. The detection signal is related to the particle size and the position of the particles as they flow through the detection area.

[0037] Therefore, when there is a detection unit downstream of the first flow channel, the detection of particles can be achieved by combining the detection signals related to particle size and the position of the flow through the detection area.

[0038] In some embodiments, when the detection unit can detect the fluorescence intensity of particles (the particles are pre-modified with fluorescence), it can not only detect the fluorescence intensity based on the particle size, but also determine the particle size based on the position of the fluorescence flowing through the detection area. The two signals enhance the judgment of particle size.

[0039] In some embodiments, when the detection unit can detect the electrical signal of particles, it can not only detect the strength of the electrical signal based on the particle size, but also determine the strength of the particle's electrical signal based on the position of the particle flowing through the detection area. These two signals enhance the judgment of particle size. The principle behind increasing the differentiation in detecting different particle electrical properties is further explained below: Ultrasonic devices can capture particles in fluids. The captured particles move towards the end of the device through an acoustic-fluid tunnel. During this movement, the drag force from the acoustic radiation gradually decreases, causing particles of different sizes to detach from the acoustic-fluid tunnel at different locations. This allows particles of different sizes to be distributed into different laminar flows (referring to laminar flows distributed from the side of the flow channel to the center). Based on this, the differences in the detected electrical parameters of different particles can be increased, thereby improving the accuracy of particle identification, sorting, and detection. Specific details are as follows: In one experiment, such as Figure 5 In the schematic diagram, when the electrical detection area is a coplanar electrode located on one side of the flow channel, particles of the same size are closer to that side of the flow channel, and thus closer to the electrode, resulting in a larger detected impedance signal. Conversely, when the electrical detection area is an array electrode located on one side of the flow channel, particles are further away from the electrode the closer they are to the opposite side of the flow channel, resulting in a smaller detected impedance signal. Therefore, the location of the electrical detection area can be designed to achieve a positive or negative correlation between the magnitude of the detected particle's electrical signal and its laminar position within the flow channel; this is referred to as the first correlation.

[0040] In another experiment, when particles of different sizes flowed through the electrical detection zone along the same path (i.e., arranged in a line), the magnitude of the detected electrical signal was positively or negatively correlated with the particle size; this is called the second correlation. Whether it is a positive or negative correlation depends on the electrical parameters of the particles and the fluid. For example, if the conductivity of the particles is lower than that of the fluid, then the particle size is positively correlated with the measured impedance signal; if the conductivity of the particles is higher than that of the fluid, then the particle size is negatively correlated with the measured impedance signal.

[0041] Based on the correlation revealed by the two experiments above, the position of the electrical detection zone is set so that the combination of the first and second correlations can enhance the difference in electrical parameters of the detected different particles: the first correlation is the correlation between the electrical parameters detected when the particle flows through the electrical detection zone and the particle's laminar flow within the channel (from one side of the channel to the other); the second correlation is the correlation between the electrical parameters detected when the particle flows through the electrical detection zone and the particle size. That is, the position of the electrical detection zone on the microchannel side can be set based on this principle, so that when particles of different sizes flow through the electrical detection zone via different laminar flow paths, the difference in detected electrical signals is enhanced. An example is given below: For example, in some embodiments, when the particle size of each measured particle is positively correlated with the measured impedance signal, the electrical detection area can be set as a coplanar electrode located on the side of the first end of the ultrasonic device corresponding to the flow channel. Thus, the larger the particle size of the measured particle, the closer the particle is to the side of the flow channel, and the larger the detected impedance signal will be. These two positive correlations enhance the difference in detection results of particles with different sizes, which is beneficial to improving detection sensitivity and accuracy.

[0042] For example, in other embodiments, when the particle size of each measured particle is negatively correlated with the measured impedance signal, the electrical detection area can be set as a coplanar electrode located on the side of the second end of the ultrasonic device corresponding to the flow channel. Thus, the larger the particle size, the farther the particle is from the coplanar electrode, and the smaller the detected impedance signal will be. These two negative correlations enhance the difference in detection results for particles of different sizes, which is beneficial to improving detection sensitivity and accuracy.

[0043] For the apparatus described in the first, second, or third embodiment above, in some embodiments, the position where the particles detach from the acoustic-fluid tunnel on the second side is adjusted by one of the following: Adjust the power driving the ultrasonic device; the greater the power, the closer the position is to the second end. The duration of operation of the ultrasonic device is adjusted; the longer the duration, the closer the position is to the second end. Adjust the fluid flow rate in the first flow channel; the faster the flow rate, the closer the position is to the first end.

[0044] The greater the power driving the ultrasonic device, the greater the drag force of the generated acoustic fluid, the stronger the binding effect on the particles, allowing the particles to move a longer distance within the acoustic fluid tunnel, and bringing the release point closer to the second end. Conversely, the faster the liquid flow velocity in the first channel, the greater the fluid drag force on the particles, the shorter the distance they move within the tunnel, and the closer the release point is to the first end of the ultrasonic device. Furthermore, the longer the ultrasonic device is in operation, the longer it acts on the particles, the longer the particles move within the acoustic fluid tunnel, and the closer the release point is to the second end of the ultrasonic device. Therefore, based on the above methods, the position of the particles detaching from the acoustic fluid tunnel on the second side can be adjusted to allow them to flow towards the downstream sub-channel of the target.

[0045] In some embodiments of the apparatus described in the first, second, or third embodiments, when the particles in the liquid flowing through the first end in the first channel include particles of different sizes, the smaller the particle, the closer its position is to the second end as it detaches from the acoustic-fluid tunnel on the second side. Accordingly, particles of different sizes can flow to their corresponding downstream sub-channels.

[0046] For the apparatus described in the first, second, or third embodiments above, in some embodiments, reference may be made to, as follows: Figure 2 The schematic diagram also includes: the first end of the ultrasonic device has a first distance d from the sidewall closest to the first flow channel. This first distance d causes particles flowing through the first end to be captured by the acoustic-fluid tunnel of the arc-shaped edge of the first end, and causes the particles to move towards the acoustic-fluid tunnel of the second side. A suitable first distance d allows particles to flow through the arc-shaped edge of the first end, be captured by the corresponding acoustic-fluid tunnel, and gradually change their direction of movement to the acoustic-fluid tunnel of the second side based on the arc-shaped acoustic-fluid tunnel. If the first distance is too large, some particles will not flow through the first end of the ultrasonic device and will flow downstream. If the first distance is too small, some particles will not be captured by the first end and will directly rush towards the acoustic-fluid tunnel of the second side. Thus, because the particles lack the process of gradually changing direction, they cannot be captured by the acoustic-fluid tunnel of the second side and will flow downstream.

[0047] For the apparatus described in the first, second, or third embodiments above, in some embodiments, reference may be made to, as follows: Figure 2The schematic diagram also includes: the second side of the ultrasonic device is inclined at a first angle θ to the extension direction of the first flow channel. The first angle θ causes the distance the particle moves along the acoustic-fluid tunnel of the second side to exceed a threshold, and the deviation of the position of the particle from the acoustic-fluid tunnel of the second side relative to the initial moving position exceeds a threshold. If the first angle is too small, the release position of particles of any size will be too concentrated in the laminar flow (referring to laminar flow from one side of the first flow channel to the other side) (the deviation of the release position from the initial moving position will be too concentrated). If the first angle is too large, the fluid force cannot be used to move the particles along the second side to the second end. Therefore, a suitable first angle θ can make different particles flow more dispersed downstream in the laminar flow, which is more conducive to particle sorting.

[0048] Regarding the apparatus described in the first, second, or third embodiments above, in some embodiments, such as Figure 2 , Figure 4 or Figure 5 As shown, the first flow channel is connected to a first upstream sub-flow channel and at least one second upstream sub-flow channel upstream; the outlet of the first upstream sub-flow channel faces a first position towards the inlet of the first flow channel, and the downstream of the first position is directly opposite the first end of the ultrasonic device, so that the first upstream sub-flow channel carries the liquid including the particles to the first end of the ultrasonic device; the outlet of the at least one second upstream sub-flow channel faces the remaining position towards the inlet of the first flow channel, and is used to introduce liquid into the first flow channel to maintain a stable flow direction of the liquid including the particles entering the first flow channel through the first upstream sub-flow channel.

[0049] Regarding the apparatus described in the first, second, or third embodiments above, in some embodiments, such as Figure 2 , Figure 4 or Figure 5 As shown, it also includes a support structure located within the first flow channel, supporting the flow channel between its bottom and top to prevent collapse. The support structure can also be located at the junction of the second upstream sub-flow channel and the first flow channel, or at the inlet of each downstream sub-flow channel, etc.

[0050] Regarding the particle sorting device described in the second embodiment above, in some embodiments, such as Figure 4 As shown, it also includes a balancing channel that spans and connects each of the downstream sub-channels to balance the flow resistance of each of the downstream sub-channels, wherein the cross-sectional dimension of the balancing channel is smaller than that of the sub-channel.

[0051] In some embodiments of the first, second, or third embodiment of the device described above, the first ultrasonic device is located at the bottom of the microchannel or on the substrate supporting the microchannel, and is disposed in close contact with the bottom of the microchannel or the surface of the substrate.

[0052] The fourth embodiment of this application provides a particle manipulation method using the particle manipulation device described in the first embodiment or any optional embodiment thereof. The manipulation method includes: When the ultrasonic device is in operation, it captures particles in the liquid flowing through the first end of the ultrasonic device in the first flow channel, and causes the particles to move towards the second end along the acoustic fluid tunnel on the second side of the ultrasonic device. The particles detach from the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid matches the drag force of the fluid in the first flow channel, and flow downstream.

[0053] The fifth embodiment of this application provides a particle sorting method using the particle sorting apparatus described in the second embodiment or any optional embodiment thereof. The sorting method includes: When the ultrasonic device is in operation, it captures particles in the liquid flowing through the first end of the ultrasonic device in the first flow channel, and causes the particles to move towards the second end along the acoustic fluid tunnel on the second side of the ultrasonic device. The particles detach from the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid matches the drag force of the fluid in the first channel, and flow into the corresponding downstream channel.

[0054] The sixth embodiment of this application provides a particulate detection method using the particulate detection device described in the third embodiment or any optional embodiment thereof. The detection method includes: When the ultrasonic device is in operation, it captures particles in the liquid flowing through the first end of the ultrasonic device in the first flow channel, and causes the particles to move towards the second end along the acoustic fluid tunnel on the second side of the ultrasonic device. The particles detach from the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid matches the drag force of the fluid in the first flow channel, and flow downstream. A detection unit located downstream of the first flow channel generates a detection signal when the particles flow through the detection area. The detection signal is related to the particle size and the position of the particles as they flow through the detection area.

[0055] In some embodiments, the methods described in the first, second, or third embodiments described above further include at least one of the following: Adjust the power driving the ultrasonic device to adjust the position of the detached particles so that they flow into a downstream sub-channel that serves as the target channel. The duration of operation of the ultrasonic device is adjusted to adjust the position of the detached particles so that they flow into a downstream sub-channel that serves as the target channel. Adjust the inlet flow rate to adjust the fluid flow rate in the first flow channel, thereby adjusting the position where the particles detach, so that they flow to a downstream sub-flow channel that serves as the target flow channel.

[0056] To further understand this application, the following section will introduce it in conjunction with some specific experiments.

[0057] like Figure 6a The experimental setup for droplet sorting is shown, including a droplet generation device. The generated droplets (water droplets separated by an oil phase) enter the first flow channel through a first upstream sub-channel. A biased oil phase enters the first flow channel through a second upstream sub-channel to prevent the droplets from drifting towards the center of the wider first flow channel. The droplets are sorted by ultrasonic devices in the first flow channel and enter their corresponding downstream sub-channels. Each downstream sub-channel achieves flow resistance balance through a balancing channel to prevent the flow resistance balance between different downstream sub-channels from being disrupted by a previous droplet entering a particular downstream sub-channel. To prevent crosstalk between droplets in adjacent downstream sub-channels, the size of the balancing channel is designed to be 1 / 5 or less than 1 / 2 the size of the downstream sub-channel. In this example, the width of the first flow channel is approximately 190 μm and its length is approximately 280 μm.

[0058] like Figure 6b The experimental results of droplet deflection at different positions of the ultrasonic device are shown in the figure. These results are used to determine reasonable values ​​for the first distance *d* between the first end of the ultrasonic device and the sidewall closest to the first flow channel, and the first angle *θ* between the second side of the ultrasonic device and the direction of extension of the first flow channel. The experiment shows that... Figure 6b Position 3 cannot deflect the droplet, while positions 1, 4, and 5 can only deflect the droplet over short distances. Figure 6b Position 2 allows the droplet to deviate significantly from its original flow direction, with a first distance d of 46 μm and a first angle θ of 67°. The ultrasonic device was placed at this position in subsequent experiments.

[0059] Here, for Figure 6bThe specific analysis is as follows: For position 1, because the ultrasonic device is too close to the lower channel wall, the acoustic vortex at the droplet capture location is compressed, making it impossible to capture a droplet of this size at that point. As the droplet moves forward, the acoustic vortex first increases and then decreases, exhibiting a small deflection at its maximum position. However, due to the lack of the preceding capture process, the droplet velocity remains high at this point, causing it to immediately detach, thus preventing a large-distance deflection. For position 3, because the ultrasonic device is too far from the lower channel wall, the droplet is outside the effective range of the acoustic flow, preventing droplet capture. As the droplet moves forward, the distance increases, so deflection is never achieved. For position 4, the droplet can be captured, but because the angle between the ultrasonic device's deflection boundary (second side) and the lower channel wall is too large, the component of the laminar drag force perpendicular to the deflection boundary exceeds the binding force of the acoustic-fluid tunnel, causing the droplet to immediately detach, thus only achieving a small-distance deflection. For position 5, the droplet undergoes the complete process of capture, deflection, and release. However, due to the small angle of placement, the projection distance of the deflection boundary in the longitudinal direction of the flow channel is small, resulting in a small longitudinal distance for the droplet to deflect along this boundary. For position 2, a suitable placement distance can achieve droplet capture, and a suitable placement angle can achieve a large deflection distance. Therefore, this placement method is suitable for multi-channel droplet sorting.

[0060] Figure 6c1 In the experiment, the power driving the ultrasonic device was fixed, and experiments were conducted on droplets of different sizes. Figure 6c1 It can be seen that for small droplets of 5.6 pL and 8.7 pL, although a large-distance deflection can be achieved, they will be captured on the device. Only after the subsequent droplet enters the acoustic flow tunnel will the preceding droplet be released. In this case, the several droplets captured simultaneously will be deflected into the same sub-channel, which is an undesirable result in droplet sorting. Therefore, multi-channel sorting is not suitable for droplets that are too small. For droplets of 12.3–65.7 pL, single droplet capture and large-distance deflection can be achieved, making it suitable for multi-channel sorting. However, for droplets that are too large, the binding force of the acoustic flow tunnel decreases, while the drag force of the laminar flow increases, causing them to detach earlier and preventing large-distance deflection. Therefore, multi-channel droplet sorting in this system is also unsuitable. Thus, the droplet size range of 12.3–65.7 pL was chosen for subsequent experiments.

[0061] on the other hand, Figure 6c2The experimental results show that when the droplet size is selected in the range of 12.3-65.7 pL, the droplet release offset increases with the increase of droplet size, that is, the release position is lower in the longitudinal distance of the flow channel. Therefore, it can be seen that within a reasonable range, the ultrasonic device can sort droplets of different sizes into different downstream sub-channels.

[0062] Figure 6d1 In the experiment, droplets of the same size were used, and different powers were applied to drive the ultrasonic device. As shown in the figure, as the driving power increases, the droplet trajectory gradually deviates upwards. When the power increases to a certain level, multiple droplets are simultaneously trapped in the acoustic tunnel. Under these experimental conditions, Figure 6d2 The experimental results show that when the power is below 1260mW, the longitudinal deflection displacement of the droplet gradually increases with increasing power. However, when the power continues to increase, the deflection displacement stops increasing because the droplet release position has reached the uppermost corner of the ultrasonic device. These experimental results demonstrate that within a reasonable power range, the longitudinal deflection displacement of the droplet can be controlled by adjusting the power, thereby achieving multi-channel droplet sorting.

[0063] Figure 6e1 This is a diagram applied to a three-channel sorting experiment. Figure 6e2 These are experimental results; the downstream sub-channel dimensions are all 50 μm. As can be seen from the figure, three-channel sorting can be achieved. Figure 6e2 The longitudinal displacement refers to the distance the droplet moves longitudinally from its initial position. A five-channel sorting experiment was also conducted; the results are shown in [link to experimental data]. Figure 6f A seven-channel sorting experiment was conducted, and the results are shown in [link to results]. Figure 6g These experiments validated the feasibility of this application, demonstrating that droplet sorting can be achieved by controlling power.

[0064] 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.

[0065] 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.

[0066] 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.

[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 particle manipulation device, characterized in that, include: A special ultrasonic device includes two sides extending from a first end to a second end, and the distance between the two sides gradually decreases with the extension direction and forms an angle at the second end, so as to make the drag force of the acoustic fluid formed on the sides gradually decrease with the extension direction. The first end includes an arc-shaped edge protruding away from the second end, and the two ends of the arc-shaped edge are connected to the two sides in a smooth transition manner. The second side, which is closer to the downstream side of the first flow channel, is inclined at a first angle to the extension direction of the first flow channel. The first angle causes the particle to move a distance along the acoustic-fluid tunnel of the second side to exceed a threshold, and the deviation of the particle from the acoustic-fluid tunnel of the second side to exceed a threshold. The effective range of the ultrasonic device includes the first flow channel, which is used to capture particles in the liquid flowing through the first end in the first flow channel when in operation, and to move the particles toward the second end along the acoustic fluid tunnel on the second side, and to make the particles detach from the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid matches the drag force of the fluid in the first flow channel, so as to flow downstream.

2. A particle sorting device, characterized in that, include: A special ultrasonic device includes two sides extending from a first end to a second end, and the distance between the two sides gradually decreases with the extension direction and forms an angle at the second end, so as to make the drag force of the acoustic fluid formed on the sides gradually decrease with the extension direction. The first end includes an arc-shaped edge protruding away from the second end, and the two ends of the arc-shaped edge are connected to the two sides in a smooth transition manner. The second side, which is closer to the downstream side of the first flow channel, is inclined at a first angle to the extension direction of the first flow channel. The first angle causes the particle to move a distance along the acoustic-fluid tunnel of the second side to exceed a threshold, and the deviation of the particle from the acoustic-fluid tunnel of the second side to exceed a threshold. The first flow channel is connected to at least two downstream sub-flow channels, and the inlet of each of the downstream sub-flow channels faces a different position on the second side; The effective range of the ultrasonic device includes the first flow channel, which is used to capture particles in the liquid flowing through the first end in the first flow channel when in operation, and to move the particles along the acoustic fluid tunnel on the second side toward the second end, and to make the particles leave the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid and the drag force of the fluid in the first flow channel match, so as to flow to the corresponding downstream flow channel.

3. A particulate detection device, characterized in that, include: A special ultrasonic device includes two sides extending from a first end to a second end, and the distance between the two sides gradually decreases with the extension direction and forms an angle at the second end, so as to make the drag force of the acoustic fluid formed on the sides gradually decrease with the extension direction. The first end includes an arc-shaped edge protruding away from the second end, and the two ends of the arc-shaped edge are connected to the two sides in a smooth transition manner. The second side, which is closer to the downstream side of the first flow channel, is inclined at a first angle to the extension direction of the first flow channel. The first angle causes the particle to move a distance along the acoustic-fluid tunnel of the second side to exceed a threshold, and the deviation of the particle from the acoustic-fluid tunnel of the second side to exceed a threshold. The effective range of the ultrasonic device includes the first flow channel, which is used to capture particles in the liquid flowing through the first end in the first flow channel when in operation, and to move the particles toward the second end along the acoustic fluid tunnel on the second side, and to make the particles detach from the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid and the drag force of the fluid in the first flow channel match, so as to flow downstream. A detection unit is provided downstream of the first flow channel for generating a detection signal based on the flow of particles through the detection area. The detection signal is related to the particle size and the position of the particles as they flow through the detection area.

4. The apparatus according to any one of claims 1-3, characterized in that, The position where the particles detach from the acoustic-fluid tunnel on the second side is adjusted by one of the following: Adjust the power driving the ultrasonic device; the greater the power, the closer the position is to the second end. The duration of operation of the ultrasonic device is adjusted; the longer the duration, the closer the position is to the second end. Adjust the fluid velocity in the first flow channel; the faster the velocity, the closer the position is to the first end.

5. The apparatus according to any one of claims 1-3, characterized in that, When the particles in the liquid flowing through the first end in the first flow channel include particles of different sizes, the smaller the particle, the closer its position is to the second end as it leaves the acoustic fluid tunnel on the second side.

6. The apparatus according to any one of claims 1-3, characterized in that, It also includes at least one of the following: The first end of the ultrasonic device has a first distance from the sidewall closest to the first flow channel. The first distance causes particles flowing through the first end to be captured by the acoustic-fluid tunnel of the arc-shaped edge of the first end and to move the particles toward the acoustic-fluid tunnel of the second side.

7. The apparatus according to claim 2, characterized in that, It also includes at least one of the following: The first flow channel is connected upstream to a first upstream sub-flow channel and at least one second upstream sub-flow channel; the outlet of the first upstream sub-flow channel faces a first position towards the inlet of the first flow channel, and the downstream of the first position is directly opposite the first end of the ultrasonic device, so that the first upstream sub-flow channel carries the liquid including the particles to the first end of the ultrasonic device; the outlet of the at least one second upstream sub-flow channel faces the remaining position towards the inlet of the first flow channel, and is used to introduce liquid into the first flow channel to maintain a stable flow direction of the liquid including the particles entering the first flow channel through the first upstream sub-flow channel; A support structure located within the first flow channel, supporting the bottom and top of the first flow channel; A balancing channel is formed by bridging and connecting each of the downstream sub-channels to balance the flow resistance of each of the downstream sub-channels. The cross-sectional dimension of the balancing channel is smaller than that of the downstream sub-channel.

8. A method for manipulating particles, characterized in that, Using the apparatus of any one of claims 1-7, the method comprises: When the ultrasonic device is in operation, it captures particles in the liquid flowing through the first end of the ultrasonic device in the first flow channel, and causes the particles to move towards the second end along the acoustic fluid tunnel on the second side of the ultrasonic device. The particles detach from the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid matches the drag force of the fluid in the first flow channel, and then flow downstream.

9. A method for sorting particles, characterized in that, Using the apparatus according to any one of claims 1-7, the method comprises: When the ultrasonic device is in operation, it captures particles in the liquid flowing through the first end of the ultrasonic device in the first flow channel, and causes the particles to move towards the second end along the acoustic fluid tunnel on the second side of the ultrasonic device. The particles detach from the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid matches the drag force of the fluid in the first channel, and flow into the corresponding downstream channel.

10. A method for detecting particulate matter, characterized in that, Using the apparatus according to any one of claims 1-7, the method comprises: When the ultrasonic device is in operation, it captures particles in the liquid flowing through the first end of the ultrasonic device in the first flow channel, and causes the particles to move towards the second end along the acoustic fluid tunnel on the second side of the ultrasonic device. The particles detach from the acoustic fluid tunnel on the second side at a position where the drag force of the acoustic fluid matches the drag force of the fluid in the first flow channel, and flow downstream. A detection unit located downstream of the first flow channel generates a detection signal when the particles flow through the detection area. The detection signal is related to the particle size and the position of the particles as they flow through the detection area.

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