Oscillation microbubble chip, separation system and acoustic manipulation method

Abstract

The invention discloses an oscillation microbubble chip, a separation system and an acoustic manipulation method, the device utilizes the acoustic eddy current effect induced by oscillation microbubbles to realize micro-nano particle acoustic manipulation, the chip structure and operation are simple, the biocompatibility is high, and by designing the chip structure, due to the breathable and water-repellent characteristics of PDMS and the surface tension of fluid, the micro-nano particle acoustic manipulation can be realized. Alternatively arranged equilateral triangle column cavities with different sizes are formed on the side wall of the PDMS microfluidic channel to anchor bubbles. Bubble oscillation is driven by bulk acoustic waves generated by exciting a piezoelectric transducer through a signal generator, symmetrical vortexes are formed on the surfaces of the bubbles through secondary acoustic radiation force generated by bubble oscillation, then large-size particles are captured, and small-size particles flow to an outlet along with flowing under the action of drag force. Gradient separation is adopted to separate small particles from a mixed solution and enrich large particles, enrichment, separation and other control of microparticles are achieved through the acoustic vortex field effect of a specific structure, great potential is achieved in biological research, the structure is simple, the equipment cost is low, and integration is easy.

Description

Technical Field

[0001] The invention relates to the field of microfluidic technology, in particular to an oscillating microbubble chip and a separation system and an acoustic manipulation method. Background Art

[0002] Traditional contact methods for cell manipulation involve manual manipulation under a microscope equipped with a micromanipulation system. However, manual methods have problems such as low precision and accuracy, inefficient complex procedures, high labor intensity, risk of contamination, limited scalability, and demanding operating skills. To address these limitations, non-contact methods such as magnetic tweezers, optical tweezers, and acoustophoresis have been widely used. These methods provide flexibility and precise object manipulation, reduce cell damage, and improve repeatability. Among them, acoustofluidic technology for separating cells and particles is an emerging technology that integrates acoustics and microfluidics. It can precisely manipulate biological products such as cells and shows great potential in different biological and biomedical applications. It is composed of a network of microfluidic channels, with controllable microfluidics running through the system, driven by external force fields such as pressure and sound fields, and using the physical properties of the fluid in the microfluidic channel to precisely manipulate and process the microfluidics, thereby completing various complex functions in traditional laboratories, such as solution mixing and particle manipulation.

[0003] Non-contact and precise manipulation are invaluable for biomedicine, bioanalytical chemistry and biophysics. Despite significant progress in acoustic streaming techniques based on bubble oscillation induction, they have mainly been targeted at micrometer-sized objects, such as cells and fluorescent polystyrene particles. Manipulating nanometer-sized biological objects, such as lipids, vesicles, viruses, proteins and molecules, remains challenging. The few previous methods that have used acoustic streaming to capture nanometer-sized particles rely on strong acoustic streaming induced by highly focused traveling surface acoustic waves (TSAWs) in the high-frequency range of 193-636 MHz. However, these high-frequency SAW transducers require complex and expensive manufacturing processes and have limitations such as poor stability, excessive damping losses and insufficient efficiency. Summary of the invention

[0004] In view of this, an object of the present invention is to provide an oscillating microbubble chip and an acoustic manipulation method, which realizes acoustic manipulation of micro-nanoparticles based on the acoustic vortex effect induced by oscillating microbubbles.

[0005] In order to achieve the above object, the present invention provides the following technical solutions: The oscillating microbubble chip provided by the present invention comprises a microchannel structure, wherein the microchannel structure comprises a liquid channel and a plurality of triangular prism cavities arranged on both sides of the liquid channel, wherein the triangular prism cavities are used to form microbubbles in the liquid channel; the openings of the triangular prism cavities are arranged on the side walls of the liquid channel; the openings of the triangular prism cavities are arranged in sequence according to the sizes; the triangular prism cavities of different sizes are used to form bubbles of different diameters, and the bubbles of different diameters are used to capture particles of different sizes.

[0006] Furthermore, the triangular column cavities are alternately arranged on both side walls of the liquid channel.

[0007] Furthermore, the triangular prism cavity is a notch provided on the side wall of the liquid channel, and both sides of the notch are symmetrical to form an isosceles triangular prism cavity.

[0008] Furthermore, the cross-sectional shape of the triangular prism cavity perpendicular to the side wall of the liquid channel is an equilateral triangle, forming an equilateral triangular prism cavity.

[0009] Furthermore, the triangular prism cavity includes a large-sized triangular prism cavity, a medium-sized triangular prism cavity, and a small-sized triangular prism cavity; the large-sized triangular prism cavity is used to form large bubbles; the radius of the large bubbles is 45-35μm; the medium-sized triangular prism cavity is used to form medium bubbles; the radius of the medium bubbles is 35-25μm; the small-sized triangular prism cavity is used to form small bubbles; the radius of the small bubbles is 25-15μm.

[0010] Furthermore, the microchannel structure is made of polydimethylsiloxane.

[0011] Furthermore, the microchannel structure is also provided with a liquid input port and a liquid output port; the liquid input port is provided at one end of the liquid channel, and the liquid output port is provided at the other end of the liquid channel.

[0012] Furthermore, it also includes a piezoelectric transducer and a glass slide; the microchannel structure and the piezoelectric transducer are connected to the glass slide.

[0013] The separation system provided by the present invention, which is formed by using the above-mentioned oscillating microbubble chip, comprises a signal generator, a syringe pump, a fluorescent inverted microscope, an image acquisition system and an oscillating microbubble chip; The signal generator is used to provide a driving signal of a specific frequency or intensity to the oscillating microbubble chip, thereby causing the microbubbles to oscillate; The injection pump is used to connect with the oscillating microbubble chip to deliver the substance to be injected to the liquid channel in the oscillating microbubble chip; The fluorescent inverted microscope is used to observe the microscopic process inside the oscillating microbubble chip. The image acquisition system is connected to the fluorescence inverted microscope and is used to receive and process the optical image signal transmitted by the fluorescence inverted microscope; The oscillating microbubble chip is connected to a signal generator and a syringe pump to achieve particle separation.

[0014] The acoustic manipulation method using the oscillating microbubble chip provided by the present invention comprises the following steps: When the solution enters the liquid microchannel, once the microbubbles are trapped in the triangular column cavity through the surface tension effect, the signal generator is turned on to output a square wave to excite the piezoelectric transducer; large particles are captured by the acoustic vortex formed by the oscillation of large-sized bubbles, and the remaining mixed solution flows to the downstream area; medium-sized particles are captured by using medium-sized bubbles, and the remaining solution containing small particles continues to flow; small particles are captured by small-sized bubbles close to the output port and then flow to the outlet for collection; ultimately, the separation of micro- and nano-sized particles is achieved.

[0015] The beneficial effects of the present invention are: The present invention provides an oscillating microbubble chip, a separation system and an acoustic manipulation method. The device uses the acoustic vortex effect induced by oscillating microbubbles to realize acoustic manipulation of micro-nano particles. The chip structure and operation are simple and biocompatible. By designing the chip structure, due to the air permeability and water repellency of polydimethylsiloxane (PDMS) and the surface tension of the fluid, equilateral triangular column cavities of different sizes are formed on the side walls of the PDMS microfluidic channel to anchor the bubbles. The bubble oscillation is driven by the bulk acoustic wave (BAW) generated by the piezoelectric transducer excited by the signal generator, and the secondary acoustic radiation force generated by the oscillating bubbles forms a symmetrical vortex on the bubble surface to capture larger particles, while the small particles follow the flow to the outlet due to the drag force, and the gradient separation is used to separate the small particles from the mixed solution and enrich the large particles.

[0016] The present invention utilizes the acoustic eddy current field effect of a specific structural device to achieve enrichment, separation and other manipulations of microparticles, and has great potential in biological research, such as non-contact manipulation of vesicles or exosomes in a microfluidic system, avoiding secondary contamination, having a simple structure, low equipment cost, and easy integration.

[0017] The present invention provides a method for acoustic manipulation of micro-nano particles. Equilateral triangular column cavities are alternately made on the side walls of a PDMS microfluidic channel. Microbubbles are formed thereon due to the hydrophobicity of the polydimethylsiloxane PDMS surface and the air permeability caused by the porosity and the surface tension of the fluid. When the traveling sound wave interacts with the bubbles in the microfluidic channel, the gas-liquid interface amplifies the vibration displacement and significantly affects the surrounding medium, generating a strong circulating flow pattern near the bubble, which is called bubble-induced acoustic streaming. When the bubble is excited at the resonant frequency, the effect of the acoustic streaming is the greatest. During the movement, the particles are subjected to the combined action of the acoustic radiation force and the drag force to form a vortex pattern. The drag force drives the particles to move along the streamline, and the acoustic radiation force is the force that pulls the particles toward the bubble. The bubble oscillation is driven by the bulk acoustic wave (BAW) generated by the ceramic transducer. Compared with SAW, the low-frequency BAW sensor is simpler, easier to manufacture, more flexible to deploy, and cost-effective for application.

[0018] In addition, the microfluidic channel uses the secondary acoustic radiation force generated by the alternating arrangement of oscillating microbubbles to capture particles within the liquid channel of the microfluidic channel. This method achieves the stable rotation of large particles or particle clusters near the gas-liquid interface and is captured in the center of the vortex, while smaller particles may escape from the vortex and flow downward. Different bubble sizes are used to separate micro- and nanoparticles, and significant results have been obtained.

[0019] Other advantages, objectives and features of the present invention will be described in the following description to some extent, and to some extent, will be obvious to those skilled in the art based on the following examination and study, or can be taught from the practice of the present invention. The objectives and other advantages of the present invention can be realized and obtained through the following description. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to make the purpose, technical solution and beneficial effects of the present invention clearer, the present invention provides the following drawings for explanation.

[0021] Figure 1 Schematic diagram of the structure of the oscillating microbubble chip.

[0022] Figure 2 It is a transverse cross-sectional view of the oscillating microbubble chip along the horizontal plane.

[0023] Figure 3 for Figure 2 A partial enlarged view of .

[0024] Figure 4 Schematic diagram of the movement trajectories of large and small particles in the vortex of the acoustic field.

[0025] Figure 5 A simulation diagram of separating nanoscale particles.

[0026] In the figure, 1 is a piezoelectric transducer; 2 is a PDMS microchannel structure; 3 is a liquid input port of the liquid channel; 4 is a triangular prism cavity; 5 is a liquid output port of the liquid channel; 6 is a horizontal liquid channel; and 7 is a glass slide. DETAILED DESCRIPTION

[0027] The present invention is further described below in conjunction with the accompanying drawings and specific embodiments so that those skilled in the art can better understand the present invention and implement it, but the embodiments are not intended to limit the present invention.

[0028] Example 1 like Figure 1 As shown, Figure 1 The schematic diagram of the structure of the oscillating microbubble chip shows a triangular prism cavity notch structure (only a part of the number is shown in the schematic diagram); the oscillating microbubble chip provided in this embodiment comprises a PDMS microchannel structure disposed on a glass slide, the PDMS microchannel structure comprises a horizontal liquid channel, and a plurality of triangular prism cavities disposed on both sides of the liquid channel, the triangular prism cavities are used to form microbubbles in the liquid channel; the triangular prism cavities are arranged in a V-shape, and the openings of the triangular prism cavities are arranged on the side walls of the liquid channel; the openings of the triangular prism cavities are arranged in sequence from the input port to the output port according to the size; the triangular prism cavities of different sizes are used to form bubbles of different diameters, and the bubbles of different diameters are used to capture particles of different sizes; like Figure 2 As shown, the triangular prism cavity includes a large-sized triangular prism cavity, a medium-sized triangular prism cavity, and a small-sized triangular prism cavity; the large-sized triangular prism cavity is used to form large bubbles; the radius of the large bubbles is 45-35 μm; the medium-sized triangular prism cavity is used to form medium bubbles; the radius of the medium bubbles is 35-25 μm; the small-sized triangular prism cavity is used to form small bubbles; the radius of the small bubbles is 25-15 μm; In this embodiment, the diameter of the microbubble is set to the side length of the microchannel notch (i.e., the opening length), and the resonance frequency is estimated according to the Rayleigh-Plessett equation. The calculated bubble radius and resonance frequency can be used for simulation. In the experimental operation, because the resonance frequency of the microbubble is highly dependent on its size and shape, there is a certain error with the theoretical calculation. The resonance frequency of the simulation can be used as a reference to appropriately adjust the excitation frequency in a small range for experimentation.

[0029] like Figure 3 As shown, the triangular prism cavities in this embodiment are alternately arranged on the two side walls of the liquid channel; the triangular prism cavities are equal-sided triangular prism cavities; the triangular prism cavities are notches arranged on the side walls of the liquid channel, and the notch angle ranges from 55° to 65°; in this embodiment, the optimal notch angle is 60 degrees; The two sides of the notch are symmetrical, forming an isosceles triangular prism cavity; the cross-section of the triangular prism cavity perpendicular to the side wall of the liquid channel is an equilateral triangle, forming an equilateral triangular prism cavity; The triangular prism in this embodiment is set as an equilateral triangle, wherein the large-sized, medium-sized, and small-sized triangular prism cavities correspond to the bubbles with radii of about 40, 30, and 20 μm (the diameters are 80, 60, and 40 μm, and the radius is used because the variables of all formulas include the radius), that is, Figure 2 The cavities of the three triangular prisms of different sizes are shown, and the side lengths of the triangles in the top view correspond to the diameters of the three bubbles, namely 80, 60, and 40 μm; The PDMS plate in this embodiment is made of polydimethylsiloxane; In this embodiment, the PDMS microchannel structure is further provided with a liquid input port and a liquid output port; the liquid input port is provided at one end of the liquid channel, and the liquid output port is provided at the other end of the liquid channel; The oscillating microbubble chip provided in this embodiment also includes a piezoelectric transducer and a glass slide; The PDMS microchannel structure and the piezoelectric transducer are connected to a glass slide; like Figure 4 As shown, a schematic diagram of the motion trajectory of large-sized and small-sized particles in the vortex of the acoustic field is shown. The oscillating microbubble chip provided in this embodiment is composed of a PDMS microchannel structure, an output end of a vibration source (a piezoelectric transducer) and a glass slide. The interior of the PDMS microchannel structure is a horizontal liquid channel, and the liquid input port and the liquid output port of the liquid channel are located on both sides of the PDMS microchannel structure. Except for the liquid input port and the liquid output port of the liquid channel, the other parts of the structure are closed structures, and there are equilateral triangular prism cavity notch structures on the side walls on both sides of the liquid channel. The PDMS microchannel structure is air permeable and water repellent.

[0030] The oscillating microbubble chip provided in this embodiment is separated based on the body acoustic wave acoustic vortex technology. Compared with the strong acoustic flow induced by highly focused surface acoustic waves to enrich and separate nanoparticles, the device has a simple structure, mature manufacturing process and low cost. Through the structural design of the chip, multiple alternating microscale bubbles of different sizes are used, and gradient separation is adopted, that is: three cavity sizes are selected for different gradient separation, namely, bubbles with radii of 40μm, 30μm, and 20μm, respectively, and different gradient separation is adopted by using the secondary acoustic radiation force caused by the acoustic vortex. First, large-sized bubbles are used to capture large particles, and the mixed solution flows to the outlet for collection; then intermediate-sized bubbles are further used to capture medium-sized particles, and the remaining solution containing small particles is captured by small-sized bubbles and flows to the outlet for collection, and finally the separation of micro-nano-sized particles is achieved. Larger particles are trapped in the vortex, while smaller particles are washed toward the outlet due to the larger drag force and collected in a waste liquid bottle, thereby achieving the separation of large and small particles in the mixed solution; and improving the separation effect and separation accuracy. Compared with most methods based on bulk acoustic wave separation of micron-sized particles, this oscillating microbubble chip can enrich and separate nano-sized particles through small bubble size, achieving a difference of one order of magnitude reduction in enrichment and separation size.

[0031] like Figure 5 As shown, Figure 5 This is a simulation diagram of separating nano-scale particles. In the figure, when the microbubble radius is 20μm, the microbubble captures 300nm particles (red), and the remaining 100nm particles (blue) in the channel are rarely affected by the oscillating microbubbles and are almost not captured by the microbubbles. They will flow to the outlet along the flow channel.

[0032] This embodiment prepares the oscillating microbubble chip according to the following steps, and the specific process is as follows: S1: fabricating a mold with a preset microchannel structure on a substrate by photolithography; Substrate preparation: Clean and treat the substrate surface to ensure it is suitable for glue coating; Gluing: evenly coating photoresist on the substrate; Pre-baking: remove the solvent in the photoresist and bake to enhance adhesion; Exposure: Use a mask to expose the photoresist to form the desired pattern; Post-exposure baking: For certain types of photoresists, baking is performed after exposure; Development: dissolve the soluble area on the photoresist to form a pattern; Post-baking: improve the adhesion of photoresist to substrate and complete pattern transfer; S2: The prepared solution is cast onto a customized mold and processed to obtain a PDMS microchannel structure; Glue preparation: Dow Corning Sylgard 184 silicone base and Sylgard curing agent are evenly mixed in a weight ratio of 10:1.

[0033] Defoaming: Put the mixed PDMS glue into a vacuum drying oven to remove bubbles.

[0034] Molding: After eliminating bubbles, pour the PDMS into the mold and put it into the vacuum drying oven to evacuate the air.

[0035] Pre-bake: The temperature was set to about 80 °C for 2 hours to cure the PDMS.

[0036] Demolding: Gently peel the cured PDMS from the mold.

[0037] Post-baking: Bake at 65°C for 3 hours to enhance its stability.

[0038] S3: The PDMS microchannel structure is processed and bonded to a glass slide to obtain an oscillating microbubble chip; Punching: Use a handheld punch to make input and output ports.

[0039] Cutting: PDMS is cut into desired sizes.

[0040] Bonding and assembly: Use a plasma gun to bond with the glass slide and connect the steel needle and hose at the output and inlet.

[0041] The detailed process of making the PDMS microchannel structure in this embodiment is as follows: The molds were fabricated using standard soft lithography techniques.

[0042] First, the substrate surface was cleaned using a 7:3 mixture of 98% H2SO4 and 30% H2O2 to promote uniform coating of the photoresist.

[0043] The substrate is a silicon wafer, which acts as a base in the photolithography process, and the mold is made on this base using photoresist; A small amount of edge bead removal solvent is then used to remove edge burrs to enhance adhesion, and a mask is used to expose the photoresist to form the desired microfluidic channel pattern.

[0044] After exposure, the mask pattern on the SU-82000 photoresist coating is exposed by baking at 95°C for 1 minute. The unexposed areas of the photoresist are dissolved using a developer to form a microstructure pattern. Finally, bake at 150°C for at least 5 minutes to improve the adhesion between the photoresist and the substrate, and immerse the photoresist in a special photoresist stripper and heat it to 50°C for 30 minutes to complete the 3D pattern transfer.

[0045] Evenly mix Dow Corning Sylgard 184A silicone elastomer base material and Sylgard 184B curing agent at a weight ratio of 10:1 until an opaque white mixture appears; Then, degassing was performed in a vacuum oven at a pressure of 0.09 MPa for 30 min to remove air bubbles; It is then cast onto a custom mold; A second vacuum degassing cycle was performed at a pressure of 0.09 MPa for 1 h until all bubbles were removed; After degassing, the temperature was set to about 80°C for 2 hours of pre-baking to cure the polydimethylsiloxane PDMS; The cured polydimethylsiloxane (PDMS) was then gently removed from the mold and baked at 65 °C for 3 h to enhance its stability.

[0046] Afterwards, the polydimethylsiloxane (PDMS) was cut into the desired size.

[0047] The inlet and outlet ports are made using a hand-held punch, and then the glass sheets are bonded to them using a plasma gun.

[0048] After assembly, use a steel needle and a hose to connect the inlet and outlet of the injection pump and the waste collection bottle respectively.

[0049] The oscillating microfluidic chip is composed of a microfluidic channel made of polydimethylsiloxane (PDMS) and a piezoelectric transducer connected to a glass slide. The PDMS microchannel structure and the glass slide are bonded together by a plasma gun; The process of preparing the solution in this embodiment is as follows: The (5 μm, 1 μm, 300 nm and 100 nm) polystyrene microsphere stock solutions were shaken on a vortex mixer for 1 minute to ensure uniform dispersion, and then 100 μL of the solution was transferred to a 1.5 mL centrifuge tube using a pipette, to which 900 μL of deionized water and 880 μL of 0.1% Tween 20 solution were added. Finally, the centrifuge tube was placed on a vortex mixer again to completely disperse the polystyrene microspheres to obtain a preliminary solution.

[0050] To prevent particles from adhering to the microfluidic channel walls, the microfluidic channels were first flushed and lubricated with Tween 20 solution.

[0051] The oscillating microfluidic chip was fixed on the stage of a fluorescence inverted microscope equipped with a CMOS camera, and a precision syringe pump containing the prepared solution was connected to the inlet of the oscillating microfluidic chip through a syringe.

[0052] When the solution enters the liquid channel, once the microbubbles are trapped in the triangular column cavity through the surface tension effect, the piezoelectric transducer is connected to the signal generator, and the square wave generated by the signal generator at a driving voltage of 10Vpp controls the opening of the acoustic field and the activation of the microbubbles.

[0053] The prepared solution in a 1 mL syringe was then injected into the liquid channel using a syringe pump.

[0054] The bubbles generate vibrations. Since the resonant frequency of microbubbles is highly dependent on their size and shape, the excitation frequency of the piezoelectric transducer is adjusted according to the most significant bubble oscillations observed under a microscope. When the output frequency is the same as the natural frequency of the bubbles, significant acoustic field vortices appear in the liquid channel.

[0055] Three cavity sizes were selected for different gradient separation, namely bubbles with radii of 40μm, 30μm, and 20μm. Different gradient separation was adopted by using the secondary acoustic radiation force caused by acoustic vortex. Large-sized bubbles were first used to capture large particles, and the mixed solution flowed to the outlet for collection; then intermediate-sized bubbles were further used to capture medium-sized particles, and the remaining solution containing small particles was captured by small-sized bubbles and flowed to the outlet for collection, finally achieving the separation of micro-nano sized particles. Larger particles were trapped in the vortex, and smaller particles were rushed to the outlet due to the larger drag force and collected in a waste liquid bottle, thus achieving the separation of large and small particles.

[0056] Example 2 This embodiment uses the above-mentioned oscillating microbubble chip to construct a separation system to realize the process of micro-nano particle separation, and the separation system includes a signal generator, a syringe pump, a fluorescent inverted microscope, an image acquisition system and an oscillating microbubble chip; the signal generator is used to provide a driving signal of a specific frequency or intensity for the oscillating microbubble chip, so that the microbubble produces an oscillation phenomenon; the syringe pump is used to connect with the oscillating microbubble chip to deliver the substance to be injected to the liquid channel in the oscillating microbubble chip; the fluorescent inverted microscope is used to observe the microscopic process inside the oscillating microbubble chip; in particular, the situation when the microbubble and the microbubble interact with other substances is observed by fluorescent imaging; the image acquisition system is connected to the fluorescent inverted microscope, and is used to receive and process the optical image signal transmitted by the fluorescent inverted microscope; the oscillating microbubble chip is connected to the signal generator and the syringe pump to realize particle separation; the oscillating microbubble chip is the core component of the entire separation system, where the oscillation of the microbubble and the separation process of the substance occur. The microbubble is driven by the signal of the signal generator inside the oscillating microbubble chip and oscillates, interacts with the substance injected by the syringe pump, and realizes the functions of separation of specific substances.

[0057] The principle of using the oscillating microbubble chip for acoustic manipulation of micro-nano particles is as follows: The resonant frequency of microbubbles on the sidewalls of a polydimethylsiloxane microfluidic channel can be estimated using the Rayleigh-Plesset equation: in, is the fluid density, n is the bubble variability index, is the bubble radius, σ is the surface tension of the liquid; Indicates the liquid pressure; represents the resonance frequency of the microbubble; The motion trajectory of particles has two mechanisms: resistance and acoustic radiation force.

[0058] At low Reynolds numbers, the drag force F acting on a spherical particle is d The following formula represents: in, is the dynamic viscosity of the liquid, is the particle radius, and U is the relative velocity between the fluid and the particle.

[0059] However, it is difficult to determine U in the flow, so its maximum value is used Estimate the upper limit of the particle velocity in the vortex, where, is the radial vibration velocity of the bubble wall; Indicates the maximum velocity between the fluid and the particles; represents the angular frequency of the bubble oscillation; represents the center-to-center distance between bubbles and particles; Acoustic radiation force exerted on spherical particles by microbubbles oscillating in an acoustic field It is expressed as: in, is the particle density, A is the velocity potential complex amplitude, k is the wave number of the acoustic radiation, and 2 ; The wavelength of the sound wave; represents the density of the fluid; represents a constant; At a fixed operating frequency, larger particles experience stronger acoustic radiation forces than smaller particles, resulting in efficient separation.

[0060] Secondary radiation force between vibrating bodies and particles It is expressed as: In the formula, represents the center-to-center distance between the bubble and the particle, R bis the bubble radius. are the frequency and amplitude of the bubble vibration, respectively.

[0061] The magnitude of the secondary radiation force depends on the geometry of the particle and the amplitude and frequency of the vibrations when the bubble is excited. The sign of the force direction, attractive or repulsive, also depends on the ratio of the density of the particle to the density of the fluid.

[0062] When particles are subjected to different radiation forces and drag forces, they will have different types of particle motion trajectories.

[0063] and The ratio is expressed as follows: in, Represents the secondary radiation force between the vibrating body and the particle; When the particle mixed solution is introduced, particles of different sizes are simultaneously introduced into the acoustic field vortex. Due to different forces, the movement trajectories of particles of different sizes are different.

[0064] The larger the particle size, the greater the secondary acoustic radiation force it receives, and the smaller the vortex trajectory, making it easier for the particle to be captured by bubbles. Smaller particles are subject to stronger drag and will be flushed out by the buffer solution.

[0065] This embodiment provides an acoustic manipulation method using the above-mentioned oscillating microbubble chip, the acoustic manipulation method is used to achieve particle separation, and includes the following steps: When the solution enters the liquid microchannel, once the microbubbles are trapped in the triangular column cavity through the surface tension effect, the signal generator is turned on to output a square wave to excite the piezoelectric transducer; The large particles are captured by the acoustic vortex formed by the oscillation of large-sized bubbles, and the remaining mixed solution flows to the downstream area; By using medium-sized bubbles to capture medium-sized particles, the remaining solution containing small particles continues to flow; Small particles are captured by small bubbles near the output port and then flow toward the outlet for collection; Finally, the separation of micro-nano sized particles in the mixed solution is achieved; In this embodiment, since larger particles are subjected to stronger secondary acoustic radiation force, they are gradually trapped in the vortex generated by larger bubbles, and smaller particles are washed toward the outlet along with the flow due to stronger drag force and collected in a waste liquid bottle, thereby achieving separation of large and small particles.

[0066] The oscillating microwave chip provided in this embodiment uses the acoustic vortex effect induced by oscillating microbubbles to realize the acoustic manipulation of micro-nanoparticles. Equilateral triangular column cavities are alternately made on the side walls of the polydimethylsiloxane (PDMS) liquid channel. Microbubbles are formed on the surface of polydimethylsiloxane (PDMS) due to its hydrophobicity and air permeability due to its porosity and the surface tension of the fluid. When the traveling sound wave interacts with the bubbles in the liquid channel, the gas-liquid interface amplifies the vibration displacement and significantly affects the surrounding medium, generating a strong circulating flow pattern near the bubble, which is called bubble-induced acoustic streaming.

[0067] The effect of acoustic streaming is greatest when the bubbles are excited at the resonant frequency. During the movement of particles, the particles are subjected to the combined effects of acoustic radiation force and drag force to form vortex patterns. The drag force drives the particles to move along the streamline, and the acoustic radiation force is the force that pulls the particles toward the bubbles. The bubble oscillation is driven by bulk acoustic waves (BAW) generated by the piezoelectric transducer excited by the signal generator. Compared with SAW, low-frequency BAW sensors are simpler, easier to manufacture, more flexible in deployment, and cost-effective for applications.

[0068] In addition, the liquid channel uses the secondary acoustic radiation force generated by the alternating arrangement of oscillating microbubbles to capture particles in the liquid channel. This method achieves stable rotation of large particles or particle clusters near the gas-liquid interface and is captured in the center of the vortex, while smaller particles may escape from the vortex and flow downward. Different bubble sizes are used to separate micro- and nanoparticles, and significant results are obtained.

[0069] The above-described embodiments are only preferred embodiments for fully illustrating the present invention, and the protection scope of the present invention is not limited thereto. Equivalent substitutions or changes made by those skilled in the art based on the present invention are within the protection scope of the present invention. The protection scope of the present invention shall be subject to the claims.

Claims

1. Oscillating microbubble chip, characterized in that: The invention comprises a microchannel structure, wherein the microchannel structure comprises a liquid channel and a plurality of triangular prism cavities arranged on both sides of the liquid channel, wherein the triangular prism cavities are used to form microbubbles in the liquid channel; openings of the triangular prism cavities are arranged on the side walls of the liquid channel; the openings of the triangular prism cavities are arranged in sequence according to sizes; the triangular prism cavities of different sizes are used to form bubbles of different diameters, and the bubbles of different diameters are used to capture particles of different sizes.

2. The oscillating microbubble chip according to claim 1, characterized in that: The triangular column cavities are alternately arranged on the two side walls of the liquid channel.

3. The oscillating microbubble chip according to claim 1, characterized in that: The triangular prism cavity is a notch arranged on the side wall of the liquid channel, and the two sides of the notch are symmetrical to form an isosceles triangular prism cavity.

4. The oscillating microbubble chip according to claim 1, characterized in that: The cross-sectional shape of the triangular prism cavity perpendicular to the side wall of the liquid channel is an equilateral triangle, forming an equilateral triangular prism cavity.

5. The oscillating microbubble chip according to claim 1, characterized in that: The triangular prism cavity includes a large-sized triangular prism cavity, a medium-sized triangular prism cavity and a small-sized triangular prism cavity; the large-sized triangular prism cavity is used to form a large bubble; the radius of the large bubble is 45-35 μm; The medium-sized triangular prism cavity is used to form medium bubbles, the radius of which is 35-25 μm. The small-sized triangular prism cavity is used to form small bubbles, the radius of which is 25-15 μm.

6. The oscillating microbubble chip according to claim 1, characterized in that: The microchannel structure is made of polydimethylsiloxane.

7. The oscillating microbubble chip according to claim 1, characterized in that: The microchannel structure is also provided with a liquid input port and a liquid output port; the liquid input port is provided at one end of the liquid channel, and the liquid output port is provided at the other end of the liquid channel.

8. The oscillating microbubble chip according to claim 1, characterized in that: It also includes a piezoelectric transducer and a glass slide; the microchannel structure and the piezoelectric transducer are connected to the glass slide.

9. A separation system using the oscillating microbubble chip according to any one of claims 1 to 8, characterized in that: It includes a signal generator, a syringe pump, a fluorescence inverted microscope, an image acquisition system and an oscillating microbubble chip; The signal generator is used to provide a driving signal of a specific frequency or intensity to the oscillating microbubble chip, thereby causing the microbubbles to oscillate; The injection pump is used to connect with the oscillating microbubble chip to deliver the substance to be injected to the liquid channel in the oscillating microbubble chip; the fluorescent inverted microscope is used to observe the microscopic process inside the oscillating microbubble chip; the image acquisition system is connected with the fluorescent inverted microscope to receive and process the optical image signal transmitted by the fluorescent inverted microscope; the oscillating microbubble chip is connected with the signal generator and the injection pump to achieve particle separation.

10. An acoustic manipulation method using the oscillating microbubble chip according to any one of claims 1 to 8, characterized in that: The following steps are involved: When the solution enters the liquid microchannel and the microbubbles are trapped in the triangular column cavity through the surface tension effect, the signal generator is turned on to output a square wave to excite the piezoelectric transducer; large particles are captured by the acoustic vortex formed by the oscillation of large-sized bubbles, and the remaining mixed solution flows to the downstream area; medium-sized particles are captured by using medium-sized bubbles, and the remaining solution containing small particles continues to flow; small particles are captured by small-sized bubbles close to the output port and then flow to the outlet for collection; ultimately, the separation of micro- and nano-sized particles is achieved.

Images