Device, system and method for separating particulate matters in solution

Abstract

The invention relates to a device for separating particulate matters in a solution, and the device comprises a micro-channel which comprises an inlet, a cavity and at least two branch channels which are communicated in sequence, the other end of each branch channel is an outlet, and the at least two branch channels comprise a first branch channel and a second branch channel; the action range of the bulk acoustic wave resonator comprises the cavity, the bulk acoustic wave resonator is used for restraining the position of a first particulate matter in a sample solution flowing through the cavity in the working state of the bulk acoustic wave resonator, and the sample solution comprises the first particulate matter and at least one second particulate matter; pneumatic micro valves covering the branch flow channels are arranged on the first branch flow channel and the second branch flow channel respectively and used for conducting or cutting off the branch flow channels, so that when the bulk acoustic wave resonator is in a working state, a sample solution containing the second particulate matter flowing out of the cavity is discharged through an outlet of the first branch flow channel, and the sample solution containing the second particulate matter flowing out of the cavity is discharged through an outlet of the second branch flow channel. And when the bulk acoustic wave resonator is in a non-working state, the buffer solution flowing through the chamber carries the first particulate matters in the chamber and is discharged from the outlet of the second branch flow channel. The device can be used for separating the first particulate matters from the second particulate matters in the sample solution.

Description

Technical Field

[0001] The present application relates to the field of cell research methodology and medical devices, and in particular to a device, system and method for separating particles in a solution. Background Art

[0002] Effective separation of biological particles is of great significance in drug delivery, disease diagnosis, catalytic reactions and other fields.

[0003] Traditional bioparticle separation technologies mainly include: graded ultracentrifugation, filtration, immunomagnetic beads and other methods, which can be used to separate biological particles (such as cells or microvesicles) and other substances. Among them, size-based graded ultracentrifugation is the most commonly used, but it has problems such as complex operation and long separation time. In addition, the huge fluid shear force generated during ultracentrifugation will damage the activity of biological particles, resulting in a low recovery rate. Other separation technologies based on physical properties such as size, density and surface charge, such as gel exclusion chromatography and filtration, also have problems such as low flux, cumbersomeness, and no standardized methods. Commercial kits that use precipitation separation methods and immunomagnetic beads have problems with later purification because they require the introduction of external reagents.

[0004] In recent years, microfluidics-based bioparticle separation technology has developed rapidly. Microfluidic chips have the characteristics of miniaturization and easy solution operation, and have natural advantages in achieving efficient particle separation, integration of operation steps, and downstream solution dissociation. However, there is currently a lack of mature technical means to separate submicron and nanoscale particles of different sizes in solution. Summary of the invention

[0005] In view of the above problems in the prior art, the present application provides a device, system and method for separating particulate matter in a solution, which can separate particulate matter in a sample solution.

[0006] To achieve the above-mentioned object, the first aspect of the present application provides a device for separating particles in a solution, comprising:

[0007] A microchannel, comprising an inlet, a chamber and at least two branch channels connected in sequence, wherein the other end of the branch channel is an outlet, and the at least two branch channels include a first branch channel and a second branch channel;

[0008] A bulk acoustic wave resonator, whose action range includes the chamber, is used to constrain the position of a first particle in a sample solution flowing through the chamber in its working state, wherein the sample solution includes the first particle and at least one second particle;

[0009] The first branch channel and the second branch channel are respectively provided with pneumatic microvalves covering the branch channels, which are used to open or cut off the branch channels, so that when the BAW resonator is in a working state, the sample solution including the second particle flowing out of the chamber is discharged through the outlet of the first branch channel, and when the BAW resonator is in a non-working state, the buffer solution flowing through the chamber carries the first particle in the chamber and is discharged through the outlet of the second branch channel.

[0010] From the above, the present application proposes a device for separating particles in a solution, which combines a microfluidic channel and a bulk acoustic wave resonator. The bulk acoustic wave resonator can emit bulk acoustic waves to generate an acoustic fluid channel. Through the coordination of the acoustic radiation force and the inertial drag force, the movement position of the first particle and the second particle in the sample solution can be effectively controlled, thereby achieving the separation of the first particle and the second particle in the sample solution.

[0011] To achieve the above object, the second aspect of the present application provides a system for separating particles in a solution, comprising:

[0012] The device for separating particles in a solution provided in the first aspect above;

[0013] a supply device for injecting a solution into an inlet of the device for separating particles from a solution;

[0014] A collecting device for collecting the separated solution from the outlet of the device for separating particles from the solution;

[0015] An image acquisition device, used for acquiring an image of the first particle constrained at a position where the bulk acoustic wave of the device for separating particles in the solution acts;

[0016] A driving device for driving the BAW resonator of the device for separating particles in a solution;

[0017] A control device is used to control the supply device, the collection device, the image acquisition device and the driving device.

[0018] From the above, the system for separating particles in solution proposed in this application can automatically and intelligently separate the first particles and the second particles in the sample solution, while having good biocompatibility, performing particle separation in a contactless manner to avoid destroying the activity of the particles, having a high recovery rate, and can achieve a separation speed of 1-2 ml / h with a short separation time, thereby achieving high-throughput sample solution separation and meeting clinical requirements.

[0019] To achieve the above object, the third aspect of the present application provides a method for separating particles in a solution, comprising:

[0020] Injecting a sample solution into the inlet of the device, so that the sample solution flows through the chamber of the device; wherein the sample solution includes a first particle and at least one second particle;

[0021] The BAW resonator is put into operation to constrain the position of the first particles in the sample solution flowing through the chamber;

[0022] Controlling the pneumatic microvalve of the first branch flow channel of the device to make the first branch flow channel conductive, and controlling the pneumatic microvalve of the second branch flow channel of the device to cut off the second branch flow channel, so that the sample solution including the second particle flowing out of the chamber is discharged through the outlet of the first branch flow channel;

[0023] A buffer solution is injected into the inlet of the device so that the buffer solution flows through the chamber of the device, and the pneumatic microvalve of the first branch channel of the device is controlled to cut off the first branch channel, and the pneumatic microvalve of the second branch channel of the device is controlled to connect the second branch channel, and the bulk acoustic wave resonator is put into a non-working state, so that the buffer solution flowing through the chamber carries the first particle in the chamber and is discharged through the outlet of the second branch channel.

[0024] The present application proposes a method for separating particles in a solution. By coordinating the acoustic radiation force and the inertial drag force, the movement positions of the first particles and the second particles in the sample solution can be effectively controlled, thereby achieving the separation of the first particles and the second particles in the sample solution. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 It is an overall structural diagram of the device for separating particles in a solution provided by the present application;

[0026] Figure 2 is an exploded view of a device for separating particles in a solution provided by the present application;

[0027] Figure 3 is a top view of a device for separating particles in a solution provided by the present application;

[0028] Figure 4 is a partial cross-sectional view of a device for separating particles in a solution provided by the present application;

[0029] Figure 5 This is a simulation diagram of the coupling between ultra-high frequency sound waves and fluid;

[0030] Figure 6 is a schematic diagram of the structure of the ultra-high frequency bulk acoustic wave resonator in this application;

[0031] Figure 7 It is a schematic diagram of the acoustic wave action area and vortex channel of the ultra-high frequency bulk acoustic wave resonator in the present application;

[0032] Figure 8 It is a schematic diagram of the structure of the separation system of submicron and nanometer-sized particles in the solution of the present application;

[0033] Fig. 9 is a flow chart of the method for separating submicron and nanometer-sized particles in a solution of the present application;

[0034] Fig.10 It is a timing diagram of the separation method of submicron and nanometer-sized particles in the solution of the present application;

[0035] It should be understood that the size and shape of each block diagram in the above structural diagram are for reference only and should not constitute an exclusive interpretation of the embodiment of the present invention. The relative position and inclusion relationship between the blocks presented in the structural diagram are only schematic representations of the structural association between the blocks, and do not limit the physical connection method of the embodiment of the present invention. DETAILED DESCRIPTION

[0036] The technical solution provided by the present application is further described below with reference to the accompanying drawings and examples. It should be understood that the system structure and business scenarios provided in the examples of the present application are mainly to illustrate the possible implementation methods of the technical solution of the present application and should not be interpreted as the only limitation on the technical solution of the present application. It is known to those of ordinary skill in the art that with the evolution of the system structure and the emergence of new business scenarios, the technical solution provided by the present application is also applicable to similar technical problems.

[0037] It should be understood that the separation scheme of submicron and nanometer-scale particles in solution provided in the embodiments of the present application includes a separation device, system and method for submicron and nanometer-scale particles in solution. Since the principles of solving the problems in these technical solutions are the same or similar, some repetitions may not be repeated in the introduction of the following specific embodiments, but it should be regarded as that these specific embodiments have been referenced to each other and can be combined with each other.

[0038] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present application. In case of any inconsistency, the meaning described in this specification or the meaning derived from the contents recorded in this specification shall prevail. In addition, the terms used herein are only for the purpose of describing the embodiments of the present application and are not intended to limit the present application.

[0039] The embodiments of the present application can be used to separate and capture particulate matter in a sample solution.

[0040] For example, separation and capture of target cells in the blood;

[0041] As another example, vesicles are separated and captured in plasma.

[0042] The particles may be exosomes, Escherichia coli, prostatic bodies, membrane vesicles, etc., and the diameter of the particles is about 0.02-1 μm, preferably about 0.03-0.8 μm, and more preferably about 0.05-0.5 μm.

[0043] For separation of particles in a sample solution, the present application provides a device for separating particles in a solution, such as Figures 1 to 4 The device comprises:

[0044] The microchannel 100 includes an inlet, a chamber 103 and at least two branch channels which are connected in sequence, the other end of the branch channel is an outlet, and the at least two branch channels include a first branch channel 108 and a second branch channel 109;

[0045] A bulk acoustic wave resonator 200, whose action range includes the chamber 103, is used to constrain the position of a first particle in a sample solution flowing through the chamber 103 in its working state, wherein the sample solution includes the first particle and at least one second particle;

[0046] The first branch channel 108 and the second branch channel 109 are respectively provided with pneumatic microvalves covering the branch channels for opening or cutting off the branch channels, so that when the BAW resonator 200 is in a working state, the sample solution including the second particle flowing out of the chamber 103 is discharged through the outlet of the first branch channel 108, and when the BAW resonator 200 is in a non-working state, the buffer solution flowing through the chamber 103 carries the first particle in the chamber 103 and is discharged through the outlet of the second branch channel 109.

[0047] The present application proposes a device for separating particles in a solution. The device combines a microfluidic channel and a bulk acoustic wave resonator. The bulk acoustic wave resonator can emit bulk acoustic waves to generate an acoustic fluid channel. Through the coordination of acoustic radiation force and inertial drag force, the movement position of the first particle and the second particle in the sample solution can be effectively controlled, thereby achieving the separation of the first particle and the second particle in the sample solution.

[0048] In some embodiments, the microfluidic channel 100 is generally closed except for an inlet and an outlet.

[0049] In one aspect of the embodiment of the present application, the cross-section of the fluid channel of the microfluidic channel 100 generally has a size of 0.1-500 μm, and can be in various shapes, including elliptical, rectangular, square, triangular, circular, etc. Among them, the fluid channel can be prepared by various known microfabrication techniques, and its materials include but are not limited to silica, silicon, quartz, glass or polymeric materials (such as PDMS, plastic, etc.).

[0050] In one aspect of the embodiment of the present application, the height of the fluid channel of the microfluidic channel 100 is about 50-300 μm, for example, can be about 60-250 μm, or can be about 100-200 μm.

[0051] In one aspect of the embodiment of the present application, the width of the fluid channel of the microfluidic channel 100 is about 100-3000 μm, for example, can be about 200-2000 μm, or can be about 400-1000 μm.

[0052] In some embodiments, the sample solution is a liquid containing cells to be separated, and may specifically include body fluid, whole blood, any blood fraction containing cells, fragmented tumors, tumor cell suspensions, cell cultures or culture supernatants, tissue fluid, extracellular fluid, lymph fluid, cerebrospinal fluid, aqueous humor, urine, sweat, etc.

[0053] In some embodiments, Figure 2 As shown, the branch channel is provided with the pneumatic microvalve covering the branch channel, and its structure includes: a branch channel layer 303, a deformable film layer 304 and a gas channel layer 305 which are arranged from bottom to top;

[0054] The branch channel layer 303 has the branch channel on its upper surface, the gas channel layer 305 has the gas channel on its lower surface, and the branch channel and the gas channel are arranged in an alternating manner.

[0055] Specifically, Figure 3 and Figure 4 As shown, the upper surface of the branch channel layer 303 has two branch channels, namely a first branch channel 108 and a second branch channel 109;

[0056] The lower surface of the gas channel layer 305 has two gas flow channels, namely a first gas flow channel 110 and a second gas flow channel 111;

[0057] The first branch flow channel 108 is staggered with the first gas flow channel 110 , and the second branch flow channel 109 is staggered with the second gas flow channel 111 .

[0058] In some embodiments, the first branch channel 108 and the second branch channel 109 together form a Y-shaped channel. Figure 2 and Figure 3 shown.

[0059] In some embodiments, the first gas flow channel 110 and the second gas flow channel 111 are rectangular in shape. Figure 2 and Figure 3 shown.

[0060] In some embodiments, the material of the film layer 304 is polydimethylsiloxane, ie, PDMS film layer.

[0061] It should be noted that, combined with Figure 2 and Figure 3 As shown, four through holes are provided on the gas channel layer 305, namely: a first outlet 104 connected to the first branch channel 108, a second outlet 105 connected to the second branch channel 109, a first gas inlet 106 connected to the first gas channel 110, and a second gas inlet 107 connected to the second gas channel 111.

[0062] The working principle of the pneumatic microvalve is described in detail as follows:

[0063] A gas of a certain pressure is introduced into the first gas inlet 106. After the gas passes through the first gas flow channel 110, the film layer 304 is deformed under the driving of the gas pressure and bends toward the first branch flow channel 108. As the pressure increases, the deformation of the film layer 304 gradually increases until the first branch flow channel 108 is completely blocked, and the sample solution cannot flow out from the first outlet 104. When the gas pressure gradually decreases, the film layer 304 itself has elastic force, and it returns to its original state under the driving of the elastic force. At this time, the first branch flow channel 108 is opened, and the sample solution flows out from the first outlet 104. In this way, the blocking and opening of the first branch flow channel 108 by the pneumatic microvalve is realized;

[0064] Similarly, when a certain pressure of gas is introduced into the second gas inlet 107, after the gas passes through the second gas flow channel 111, the film layer 304 is deformed under the driving of the gas pressure and bends toward the second branch flow channel 109. As the pressure increases, the deformation of the film layer 304 gradually increases until the second branch flow channel 109 is completely blocked, and the sample solution cannot flow out from the second outlet 105. When the gas pressure gradually decreases, the film layer 304 itself has elastic force, and the elastic force drives the film layer 304 to restore the original state, and at this time the second branch flow channel 109 is opened, and the sample solution flows out from the second outlet 105. In this way, the blocking and opening of the second branch flow channel 109 by the pneumatic microvalve is realized.

[0065] In some embodiments, Figure 3 As shown, the inlet of the microfluidic channel 100 includes a first inlet 101 for injecting the sample solution and a second inlet 102 for injecting the buffer solution.

[0066] In some embodiments, Figure 2 As shown, the structure of the inlet of the microchannel 100 includes: an inlet receiving layer 302 and an inlet channel layer 301 which are arranged adjacent to each other from bottom to top;

[0067] The lower surface of the inlet channel layer 301 has an inlet channel.

[0068] Combination Figure 2 As shown, the shape of the inlet flow channel on the lower surface of the inlet flow channel layer 301 is Y-shaped, which can be called a Y-shaped inlet flow channel.

[0069] Thus, the sample solution flows into the Y-shaped inlet channel from the first inlet 101, and the buffer solution flows into the Y-shaped inlet channel from the second inlet 102. After passing through the inlet receiving layer 302, the sample solution and the buffer solution finally enter the chamber 103 for subsequent separation operations.

[0070] In some embodiments, the BAW resonator 200 is located at the bottom of the chamber 103 , and is 50-300 μm away from the top of the chamber;

[0071] The frequency of the bulk acoustic wave generated by the bulk acoustic wave resonator includes 0.5-50 GHz;

[0072] The speed at which the sample solution flows through the active area of ​​the BAW resonator is 0.1-100 μL / min.

[0073] In some embodiments, one or more BAW resonators 200 are disposed in the chamber 103, and the BAW resonator 200 is a BAW generating component that can generate BAW with a frequency of about 0.5-50 GHz, and generates a vortex channel (i.e., an acoustic fluid channel) defined by the boundary of the BAW generating region of the BAW resonator 200 in the sample solution. Under the conditions of suitable flow rate and BAW power, the particles in the sample solution enter the vortex channel and move along the vortex channel. At a certain position (positions) in the vortex channel, the particles in the sample solution will leave the BAW action region and move downstream, i.e., be released, i.e., leave the vortex channel at a set position (i.e., a release point). Since one of the important factors for the particles in the sample solution to leave the vortex channel is the influence of the laminar flow along the direction of the fluid channel, the release point is usually located in the most downstream area of ​​the vortex channel.

[0074] The multiple BAW resonators can be the same, set to the same frequency, and produce the same BAW action area. The multiple BAW resonators can also be different, set to different frequencies, and produce different BAW action areas.

[0075] In addition, multiple BAW resonators can form a BAW resonator array. For details, see Figure 1 and Figure 3 shown.

[0076] It is worth noting that the principle of the BAW resonator 200 combined with the chamber 103 to generate an acoustic fluid channel is as follows: ultra-high frequency sound waves exist in the fluid in the form of pressure waves, that is, they propagate in the liquid in the form of regular vibration changes in density and pressure, and produce two effects in the liquid: acoustic pressure effect and acoustic fluid effect. Due to its ultra-high frequency characteristics, hypersonic sound waves can complete energy conversion within a very short distance from the device surface and generate more than 10 10 m / s 2 When the fluid is ejected upward from the device surface, due to the boundary restriction, a stable high-speed rotating microscale acoustic flow vortex is formed. Figure 5 .

[0077] When particles are in a fluid field, they are simultaneously acted upon by multiple forces, including acoustic radiation force, fluid drag force, and other negligible forces that cancel each other out. These two forces are the key to particle manipulation in an acoustofluidic channel.

[0078] In some embodiments, Figure 6 As shown, the BAW resonator 200 includes an acoustic wave reflecting layer 206, a bottom electrode layer 205, a piezoelectric layer 204 and a top electrode layer 203 arranged in sequence from bottom to top. The overlapping area of ​​the bottom electrode layer, the piezoelectric layer, the top electrode layer and the acoustic wave reflecting layer constitutes a BAW generating area. The top surface of the BAW resonator 200 is arranged on the wall of the fluid channel, and generates a BAW with a propagation direction perpendicular to the wall to the opposite wall; generally speaking, the area formed by the top surface of the BAW resonator 200 is the BAW generating area, also referred to as the BAW area or the BAW action area in this application. In one aspect of the present application, the area of ​​the acoustic wave action area is about 500-200000μm 2 , preferably about 5000-50000 μm 2 , most preferably about 10000-25000 μm 2 The side length of the bulk acoustic wave generating region is about 30-500 μm, preferably about 40-300 μm, and most preferably about 50-200 μm.

[0079] In some embodiments, the shape of the body acoustic wave action area includes at least one of the following: a circle, an ellipse, a semicircle, a parabola, a polygon with an acute angle or an obtuse angle at the vertex, a polygon with a vertex replaced by an arc, a polygon with a vertex of any combination of an acute angle, a semicircle or a parabola, or a square array or a circular array of the same shape that is repeatedly arranged. The present application provides the acoustic wave action areas of the above shapes, but other acoustic wave action areas of any shape are also within the protection scope of the present application.

[0080] In some embodiments, Figure 7As shown, the body acoustic wave emitted by the body acoustic wave resonator 200, the volume force generated by the attenuation of the sound wave in the fluid causes an acoustic jet to appear in the solution flowing through, resulting in a local three-dimensional vortex 401 in the liquid in the fluid channel, and the continuous vortex caused by the body acoustic wave forms an acoustic fluid vortex channel. Since the vortex is generated by the volume force caused by the attenuation of the sound wave, the central axis of the vortex is above the boundary of the body acoustic wave action, so the shape of the vortex channel is basically the same as the shape of the body acoustic wave action area, and is located above the boundary of the body acoustic wave action area. The acoustic fluid vortex is caused by the nonlinearity of the propagation of the sound wave in the liquid medium. The strength of the amplitude of the sound wave directly determines the intensity of the acoustic fluid vortex. The amplitude of the super ultrasonic device, that is, the amplitude of the sound wave, can be adjusted by adjusting the applied power, thereby controlling the flow rate of the acoustic fluid vortex. The forces on the particles in the vortex (including larger particles 402 and smaller particles 403) include the fluid drag force (Stokes drag force) generated by the vortex, the inertial lift force (inertial lift force) generated by the laminar flow, and the acoustic radiation force (acoustic radiation force) caused by the attenuation of sound waves. Since the magnitude of the fluid drag force is positively correlated with the particle, such as the particle diameter, and the magnitude of the acoustic radiation force is positively correlated with the square of the particle size. As the particles grow larger, the forces they are subjected to will change from being dominated by fluid drag to being dominated by acoustic radiation force, and the acoustic radiation force will push the particles toward the center of the vortex. The larger particles 402 are subjected to a greater acoustic radiation force and thus move to the center of the vortex; while the smaller particles 403 rotate on the periphery under the action of the vortex drag force, and further move downstream to the area of ​​action of the body sound wave under the action of the lateral drag force generated by the laminar flow.

[0081] In some embodiments, the BAW resonator may be an ultra-high frequency BAW resonator, which may be a thin film BAW resonator or a solid-state assembly resonator, such as an acoustic wave resonator in a thickness stretching vibration mode, made by growing a piezoelectric material thin film layer in a vertical direction, and exciting vibration by coupling a vertical electric field through a d33 piezoelectric coefficient. The ultra-high frequency acoustic wave resonator used in the present invention can generate a localized acoustic flow at the interface between the device and the liquid without the help of a coupling medium or structure.

[0082] Based on the same concept, the present application also provides a system for separating particles in a solution, such as Figure 8 As shown, including:

[0083] The above-mentioned device for separating particles in a solution;

[0084] A supply device 501, used to inject a solution into the inlet of the device for separating particles from the solution;

[0085] A collecting device 504, used to collect the separated solution from the outlet of the device for separating particles from the solution;

[0086] An image acquisition device 509, used for acquiring an image of the first particle constrained at a position where the bulk acoustic wave of the device for separating particles in the solution acts;

[0087] A driving device 500, used to drive the BAW resonator of the device for separating particles in the solution;

[0088] The control device 510 is used to control the supply device 501 , the collection device 504 , the image acquisition device 509 and the driving device 500 .

[0089] From the above, the system provided by the embodiment of the present application can intelligently and automatically separate the first particles and the second particles in the sample solution, and at the same time has good biocompatibility, performs particle separation in a contactless manner, avoids destroying the activity of the particles, has a high recovery rate, and can achieve a separation speed of 1-2 ml / h with a short separation time, thereby achieving high-throughput sample solution separation and meeting clinical requirements.

[0090] In some embodiments, the supply device 501 may include a liquid injection and flow rate regulating device (not shown) for controlling the liquid injection and the flow rate of the control liquid. The flow rate of the injected liquid can be controlled by an external pressure source, an internal pressure source, electronic dynamics or a magnetic field dynamics method. The external pressure source and the internal pressure source can be pumps, such as peristaltic pumps, syringe pumps or pneumatic pumps. In the present embodiment, the supply device 501 adopts a solution injection pump 502 finely adjusted by a computer to control the flow rate of the sample solution injection and a buffer injection pump 503 to control the flow rate of the buffer injection. The flow rate range of the solution and the buffer is preferably set according to actual conditions.

[0091] The speed at which the sample solution flows through the bulk acoustic wave region is about 0.1-100 μL / min, preferably about 5-60 μL / min, and more preferably about 20-50 μL / min.

[0092] In some embodiments, the collecting device 504 includes a small-sized particle collecting tube 505 and a large-sized particle collecting tube 506 , the small-sized particle collecting tube 505 is connected to the first outlet 104 , and the large-sized particle collecting tube 506 is connected to the second outlet 105 .

[0093] In some embodiments, the system further includes a first control pump 507 and a second control pump 508 . The first control pump 507 is used to control the gas pressure in the first gas flow channel 110 , and the second control pump 508 is used to control the gas pressure in the second gas flow channel 111 .

[0094] Specifically, the first control pump 507 includes a solenoid valve and a micro air pump. The solenoid valve is connected to one end of the micro air pump, and the other end of the micro air pump is connected to the first gas inlet 106 through a thin tube. The main purpose of the micro air pump is to pass a certain pressure of gas from the first gas inlet 106 to the first gas flow channel 110. The purpose of the solenoid valve is to act as a switch. When the gas filled in the first gas flow channel 110 needs to be released, the solenoid valve is opened to discharge the gas.

[0095] Similarly, the second control pump 508 includes a solenoid valve and a micro air pump. The solenoid valve is connected to one end of the micro air pump, and the other end of the micro air pump is connected to the second gas inlet 107 through a thin tube. The main purpose of the micro air pump is to pass gas of a certain pressure from the second gas inlet 107 to the second gas flow channel 111. The purpose of the solenoid valve is to act as a switch. When the gas filled in the second gas flow channel 111 needs to be released, the solenoid valve is opened to discharge the gas.

[0096] In some embodiments, the image acquisition device 509 includes but is not limited to a microscope, a high-speed camera, etc. The image acquisition device 509 is used to observe the saturation degree of the bottom bulk acoustic wave resonator capturing particles, thereby controlling the switching actions of the driving device 500, the supply device 501, the first control pump 507 and the second control pump 508.

[0097] In some embodiments, the control device 510 is electrically connected to the driving device 500, the supply device 501, the first control pump 507, and the second control pump 508. The control device 510 can be a set of logical relationships embedded in hardware or firmware, or a series of programs written in a programming language and stored in a memory or other firmware. The control device 510 and the image acquisition device 509 make comprehensive decisions to control the working mode of the driving device 500, the supply device 501, the first control pump 507, and the second control pump 508, so that the device for separating particles in the solution automatically separates the first particles and the second particles in the sample solution.

[0098] In some embodiments, the separation system further includes a power supply device 511, which supplies power to the entire system for separating particles in a solution to ensure that the system can operate normally.

[0099] In some embodiments, the driving device 500 includes a high-frequency signal generator, a power amplifier, and a power distributor;

[0100] The high frequency signal generator is electrically connected to the power amplifier, and the power amplifier is connected to the power distributor via an impedance matching signal line;

[0101] The high-frequency signal generator is used to make the ultra-high frequency bulk acoustic wave resonator emit a high-frequency signal;

[0102] The power amplifier is used to amplify the high-frequency signal emitted by the ultra-high frequency bulk acoustic wave resonator.

[0103] Based on the same concept, the present application also provides a method for separating particles in a solution, such as Fig. 9 As shown, including:

[0104] S101, injecting a sample solution into the inlet of the device, so that the sample solution flows through the chamber of the device; wherein the sample solution includes a first particle and at least one second particle;

[0105] S102, putting the BAW resonator into a working state, and performing position constraints on the first particles in the sample solution flowing through the chamber;

[0106] S103, controlling the pneumatic microvalve of the first branch flow channel of the device to make the first branch flow channel conductive, and controlling the pneumatic microvalve of the second branch flow channel of the device to cut off the second branch flow channel, so that the sample solution including the second particle flowing out of the chamber is discharged through the outlet of the first branch flow channel;

[0107] S104, injecting a buffer solution into the inlet of the device so that the buffer solution flows through the chamber of the device, and controlling the pneumatic microvalve of the first branch channel of the device to cut off the first branch channel, and controlling the pneumatic microvalve of the second branch channel of the device to connect the second branch channel, and placing the BAW resonator in a non-working state, so that the buffer solution flowing through the chamber carries the first particulate matter in the chamber and is discharged through the outlet of the second branch channel.

[0108] In some embodiments, constraining the position of the first particles in the sample solution flowing through the chamber, and causing the sample solution including the second particles flowing out of the chamber to be discharged through the outlet of the first branch flow channel, comprises:

[0109] Based on the acoustic radiation force of the BAW resonator, the first particle is confined at the top position of the chamber;

[0110] Based on the inertial drag force generated by the laminar flow of the sample solution, the second particles are discharged along with the sample solution through the outlet of the first branch flow channel.

[0111] In some embodiments, the first particles are larger in size than the second particles.

[0112] In some embodiments, when the BAW resonator enters the working state, it further includes:

[0113] An image of the position is acquired, and it is determined according to the image that the first particle constrained in position has reached saturation.

[0114] In addition, an embodiment of the present application also provides a timing diagram of a method for separating particles in a solution.

[0115] like Fig.10 As shown, the whole process is mainly divided into two stages: capture and release;

[0116] Capture stage: the sample solution is introduced into the first inlet, the driving device drives the BAW resonator to generate BAW, the first particles are captured in the chamber based on the acoustic radiation force of the BAW resonator, and the second particles are discharged through the outlet of the first branch channel based on the inertial drag force generated by the laminar flow of the sample solution;

[0117] Release stage: When the captured first particles reach saturation, the sample solution is stopped from being introduced into the first inlet, and a buffer solution is introduced into the second inlet, and the buffer solution carries the first particles in the chamber and is discharged through the outlet of the second branch channel.

[0118] By repeating the above two stages, a larger volume of sample solution can be separated and processed.

[0119] In addition, the words "first, second, third, etc." or module A, module B, module C and other similar terms in the specification and claims are only used to distinguish similar objects and do not represent a specific ordering of the objects. It can be understood that the specific order or sequence can be interchanged where permitted so that the embodiments of the present application described herein can be implemented in an order other than that illustrated or described herein.

[0120] In the above description, the numbers representing the steps, such as S110, S120, etc., do not necessarily mean that the steps will be executed in this manner. If permitted, the order of the steps can be interchanged or they can be executed simultaneously.

[0121] The term "comprising" as used in the description and claims should not be interpreted as being limited to what is listed thereafter; it does not exclude other elements or steps. Therefore, it should be interpreted as specifying the presence of the features, integers, steps or components mentioned, but does not exclude the presence or addition of one or more other features, integers, steps or components and groups thereof. Therefore, the expression "a device comprising means A and B" should not be limited to a device consisting of components A and B only.

[0122] References to "one embodiment" or "an embodiment" in this specification mean that a particular feature, structure, or characteristic described in conjunction with the embodiment is included in at least one embodiment of the present application. Therefore, the phrases "in one embodiment" or "in an embodiment" appearing in various places in this specification do not necessarily refer to the same embodiment, but may refer to the same embodiment. In addition, in one or more embodiments, the particular features, structures, or characteristics can be combined in any appropriate manner, as would be apparent to one of ordinary skill in the art from this disclosure.

[0123] Note that the above are only preferred embodiments of the present application and the technical principles used. Those skilled in the art will understand that the present application is not limited to the specific embodiments described herein, and that various obvious changes, readjustments and substitutions can be made by those skilled in the art without departing from the scope of protection of the present application. Therefore, although the present application is described in more detail through the above embodiments, the present application is not limited to the above embodiments, and may also include more other equivalent embodiments without departing from the concept of the present application, all of which belong to the scope of protection of the present application.

Claims

1. A device for separating particles in a solution, characterized in that: include: A microchannel, comprising an inlet, a chamber and at least two branch channels connected in sequence, wherein the other end of the branch channel is an outlet, and the at least two branch channels include a first branch channel and a second branch channel; A bulk acoustic wave resonator, whose action range includes the chamber, is used to constrain the position of a first particle in a sample solution flowing through the chamber in its working state, wherein the sample solution includes the first particle and at least one second particle; The first branch channel and the second branch channel are respectively provided with pneumatic microvalves covering the branch channels, which are used to open or cut off the branch channels, so that when the BAW resonator is in a working state, the sample solution including the second particle flowing out of the chamber is discharged through the outlet of the first branch channel, and when the BAW resonator is in a non-working state, the buffer solution flowing through the chamber carries the first particle in the chamber and is discharged through the outlet of the second branch channel.

2. The device according to claim 1, characterized in that The branch channel is provided with the pneumatic microvalve covering the branch channel, and the structure thereof comprises: a branch channel layer, a deformable film layer and a gas channel layer which are arranged adjacent to each other from bottom to top; The branch channel layer has the branch channel on its upper surface, the gas channel layer has the gas channel on its lower surface, and the branch channel and the gas channel are arranged in an alternating manner.

3. The device according to claim 1, characterized in that The inlet of the microfluidic channel includes a first inlet for injecting the sample solution and a second inlet for injecting the buffer solution.

4. The device according to claim 1 or 3, characterized in that The structure of the inlet of the microchannel includes: an inlet receiving layer and an inlet flow channel layer arranged adjacent to each other from bottom to top; Wherein, the lower surface of the inlet flow channel layer has an inlet flow channel.

5. The device according to claim 1, characterized in that Include at least one of the following: The BAW resonator is located at the bottom of the chamber, and is 50-300 μm away from the top of the chamber; The frequency of the bulk acoustic wave generated by the bulk acoustic wave resonator includes 0.5-50 GHz; The speed at which the sample solution flows through the active area of ​​the BAW resonator is 0.1-100 μL / min.

6. A system for separating particles in a solution, characterized in that: include: The device for separating particles in a solution according to any one of claims 1 to 5; a supply device for injecting a solution into an inlet of the device for separating particles from a solution; A collecting device for collecting the separated solution from the outlet of the device for separating particles from the solution; An image acquisition device, used for acquiring an image of the first particle constrained at a position where the bulk acoustic wave of the device for separating particles in the solution acts; A driving device for driving the BAW resonator of the device for separating particles in a solution; A control device is used to control the supply device, the collection device, the image acquisition device and the driving device.

7. A method for separating particulate matter in a solution using the device for separating particulate matter in a solution according to any one of claims 1 to 5, characterized in that: include: Injecting a sample solution into the inlet of the device, so that the sample solution flows through the chamber of the device; wherein the sample solution includes a first particle and at least one second particle; The BAW resonator is put into operation to constrain the position of the first particles in the sample solution flowing through the chamber; Controlling the pneumatic microvalve of the first branch flow channel of the device to make the first branch flow channel conductive, and controlling the pneumatic microvalve of the second branch flow channel of the device to cut off the second branch flow channel, so that the sample solution including the second particle flowing out of the chamber is discharged through the outlet of the first branch flow channel; A buffer solution is injected into the inlet of the device so that the buffer solution flows through the chamber of the device, and the pneumatic microvalve of the first branch channel of the device is controlled to cut off the first branch channel, and the pneumatic microvalve of the second branch channel of the device is controlled to connect the second branch channel, and the bulk acoustic wave resonator is put into a non-working state, so that the buffer solution flowing through the chamber carries the first particle in the chamber and is discharged through the outlet of the second branch channel.

8. The method according to claim 7, characterized in that Positionally constraining the first particles in the sample solution flowing through the chamber, and causing the sample solution including the second particles flowing out of the chamber to be discharged through the outlet of the first branch flow channel, comprises: Based on the acoustic radiation force of the BAW resonator, the first particle is confined at the top position of the chamber; Based on the inertial drag force generated by the laminar flow of the sample solution, the second particles are discharged along with the sample solution through the outlet of the first branch flow channel.

9. The method according to claim 8, characterized in that The first particles are larger in size than the second particles.

10. The method according to claim 7, characterized in that When the BAW resonator enters the working state, it also includes: An image of the position where the bulk acoustic wave acts is acquired, and it is determined according to the image that the first particle constrained in position has reached saturation.

Images