Oscillating microbubble chip, separation system, and acoustic manipulation method

Abstract

The present invention discloses an oscillating microbubble chip, a separation system, and an acoustic manipulation method. The device utilizes the acoustic vortex effect induced by oscillating microbubbles to achieve acoustic manipulation of micro-nanoparticles. The chip features simple structure and operation, and high biocompatibility. By designing the chip structure, equilateral triangular columns of varying sizes are formed on the sidewalls of the PDMS microfluidic channel, anchoring the bubbles due to the air-permeable and water-repellent properties of PDMS and the surface tension of the fluid. The bubble oscillation is driven by bulk acoustic waves generated by a piezoelectric transducer excited by a signal generator. The secondary acoustic radiation force generated by the oscillating bubbles forms symmetrical vortices on the bubble surface, capturing larger particles. Smaller particles, due to drag force, follow the flow toward the outlet. Gradient separation is used to separate small particles from a mixed solution and enrich larger particles. The acoustic vortex field effect of a specific structure is utilized to achieve enrichment, separation, and other manipulations of microparticles. This device has great potential in biological research, with a simple structure, low equipment cost, and ease of integration.

Description

Technical Field

[0001] The present invention relates to the field of microfluidic technology, in particular to an oscillating microbubble chip, 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, these manual methods suffer from low precision and accuracy, complex procedures with low efficiency, high labor intensity, risk of contamination, limited scalability, and demanding operational skills. To address these limitations, non-contact methods such as magnetic tweezers, optical tweezers, and acoustophoresis have been widely used. These methods offer flexibility and precise object manipulation, reducing cell damage and improving reproducibility. Among them, acoustophoresis 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 various biological and biomedical applications. It consists of a network of microfluidic channels with controllable microfluidics running through the system. Driven by external forces such as pressure and acoustic fields, the system utilizes the physical properties of the fluid within the microfluidic channels to precisely manipulate and process the microfluidics, thereby completing various complex functions in traditional laboratories, such as solution mixing and particle manipulation.

[0003] Contactless and precise manipulation is invaluable for biomedicine, bioanalytical chemistry, and biophysics. Despite significant progress in bubble-oscillation-induced acoustic streaming, this has primarily been limited to micrometer-sized objects, such as cells and fluorescent polystyrene particles. Manipulating nanoscale biological objects, such as lipids, vesicles, viruses, proteins, and molecules, remains challenging. Previous studies have employed acoustic streaming to capture nanoscale particles, with the few approaches relying on intense 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 fabrication processes and suffer from limitations such as poor stability, excessive damping losses, and insufficient efficiency. Summary of the Invention

[0004] In view of this, the object of the present invention is to provide an oscillating microbubble chip and an acoustic manipulation method, which realizes the 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:

[0006] The oscillating microbubble chip provided by the present invention includes a microchannel structure, which includes a liquid channel and a plurality of triangular prism cavities arranged on both sides of the liquid channel. 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 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.

[0007] Furthermore, the triangular prism cavities are alternately arranged on both side walls of the liquid channel.

[0008] 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.

[0009] Furthermore, 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.

[0010] 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.

[0011] Furthermore, the microchannel structure is made of polydimethylsiloxane.

[0012] Furthermore, the 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.

[0013] Furthermore, it also includes a piezoelectric transducer and a glass slide; the microchannel structure and the piezoelectric transducer are connected to the glass slide.

[0014] The separation system provided by the present invention, which is composed of the above-mentioned oscillating microbubble chip, comprises a signal generator, a syringe pump, a fluorescence inverted microscope, an image acquisition system and the oscillating microbubble chip;

[0015] 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;

[0016] The injection pump is connected to the oscillating microbubble chip to deliver the substance to be injected into the liquid channel of the oscillating microbubble chip;

[0017] The fluorescent inverted microscope is used to observe the microscopic process inside the oscillating microbubble chip.

[0018] 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;

[0019] The oscillating microbubble chip is connected to a signal generator and a syringe pump to achieve particle separation.

[0020] The acoustic manipulation method using the oscillating microbubble chip provided by the present invention comprises the following steps:

[0021] 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 near the output port and then flow to the outlet for collection; ultimately, the separation of micro- and nano-sized particles is achieved.

[0022] The beneficial effects of the present invention are:

[0023] The present invention provides an oscillating microbubble chip, separation system, and acoustic manipulation method. This device utilizes the acoustic vortex effect induced by oscillating microbubbles to achieve acoustic manipulation of micro- and nanoparticles. The chip features simple structure and operation, as well as high biocompatibility. By designing the chip structure, the air-permeable and water-repellent properties of polydimethylsiloxane (PDMS) and the surface tension of the fluid enable alternating equilateral triangular columns of varying sizes to form on the sidewalls of the PDMS microfluidic channel to anchor the bubbles. Bubble oscillation is driven by bulk acoustic waves (BAWs) generated by a piezoelectric transducer excited by a signal generator. The secondary acoustic radiation force generated by the oscillating bubbles creates symmetrical vortices on the bubble surface, capturing larger particles. Smaller particles, driven by drag, follow the flow toward the outlet. Gradient separation is used to separate small particles from a mixed solution and enrich larger particles.

[0024] 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. For example, it can enable non-contact manipulation of vesicles or exosomes in microfluidic systems, avoid secondary contamination, have a simple structure, low equipment cost, and be easy to integrate.

[0025] The present invention provides a method for acoustic manipulation of micro- and nanoparticles. Equilateral triangular cavities are alternately fabricated on the sidewalls of a PDMS microfluidic channel. Microbubbles form on the cavities due to the hydrophobicity of the polydimethylsiloxane (PDMS) surface, its gas permeability due to its porosity, and the surface tension of the fluid. When traveling acoustic waves interact with bubbles within the microfluidic channel, the gas-liquid interface amplifies the vibrational displacement and significantly affects the surrounding medium, generating a powerful circulating flow pattern near the bubbles, known as bubble-induced acoustic streaming. The acoustic streaming effect is greatest when the bubbles are excited at their resonant frequency. During their motion, particles are subjected to the combined effects of acoustic radiation force and drag force, forming vortex patterns. The drag force drives the particles along streamlines, while the acoustic radiation force pulls the particles toward the bubbles. The bubble oscillations are driven by bulk acoustic waves (BAW) generated by a ceramic transducer. Compared to SAW sensors, low-frequency BAW sensors are simpler, easier to manufacture, more flexible to deploy, and cost-effective for applications.

[0026] Furthermore, the microfluidic channel uses the secondary acoustic radiation force generated by alternating oscillating microbubbles to capture particles within the microfluidic channel's liquid channel. This method allows large particles or particle clusters near the gas-liquid interface to rotate stably and be captured at the center of the vortex, while smaller particles may escape from the vortex and flow downward. Using different bubble sizes to separate micro- and nanoparticles has yielded remarkable results.

[0027] Other advantages, objects, and features of the present invention will be described in part in the following description and, in part, will be apparent to those skilled in the art upon examination of the following description or may be learned from practice of the present invention. The objects and other advantages of the present invention may be realized and obtained through the following description. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to make the purpose, technical solutions and beneficial effects of the present invention more clear, the present invention provides the following drawings for illustration.

[0029] Figure 1 Schematic diagram of the structure of the oscillating microbubble chip.

[0030] Figure 2 This is a transverse cross-sectional view of the oscillating microbubble chip along the horizontal plane.

[0031] Figure 3 for Figure 2 A partial enlarged view of .

[0032] Figure 4 Schematic diagram of the motion trajectories of large and small particles in the vortex of the acoustic field.

[0033] Figure 5 A simulation diagram of separating nanoscale particles.

[0034] 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

[0035] The present invention will be further described below with reference to the accompanying drawings and specific embodiments so that those skilled in the art can better understand the present invention and implement it. However, the embodiments are not intended to limit the present invention.

[0036] Example 1

[0037] like Figure 1 As shown, Figure 1 This is a schematic diagram of the structure of an oscillating microbubble chip, showing a triangular prism cavity notch structure (only a portion of the structure is shown in the schematic diagram). The oscillating microbubble chip provided in this embodiment includes a PDMS microchannel structure disposed on a glass slide. The PDMS microchannel structure includes 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, with the openings of the triangular prism cavities disposed on the sidewalls of the liquid channel. The openings of the triangular prism cavities are arranged in order of size from the input port to the output port. The triangular prism cavities of different sizes are used to form bubbles of different diameters, which are used to capture particles of different sizes.

[0038] 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;

[0039] In this example, the desired microbubble diameter is set to the side length of the microchannel opening (i.e., the opening length). The resonant frequency is estimated using the Rayleigh-Plesset equation. The calculated bubble radius and resonant frequency can be used for simulation. In experimental operations, because the resonant frequency of microbubbles is highly dependent on their size and shape, there may be some error from theoretical calculations. The simulated resonant frequency can be used as a reference to adjust the excitation frequency appropriately within a small range for experimental purposes.

[0040] like Figure 3As shown, the triangular prism cavities in this embodiment are alternately arranged on both 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;

[0041] 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;

[0042] In this embodiment, the triangular prism is configured as an equilateral triangle, wherein the large, medium, and small triangular prism cavities correspond to the bubbles with radii of approximately 40, 30, and 20 μm, respectively (the diameters are 80, 60, and 40 μm, expressed as radius because all formula variables include the radius), that is, Figure 2 The three triangular prism cavities of different sizes are shown. The side lengths of the triangles in the top view correspond to the diameters of the three bubbles, namely 80, 60, and 40 μm;

[0043] The PDMS plate in this embodiment is made of polydimethylsiloxane;

[0044] 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;

[0045] The oscillating microbubble chip provided in this embodiment further includes a piezoelectric transducer and a glass slide;

[0046] The PDMS microchannel structure and the piezoelectric transducer are connected to a glass slide;

[0047] like Figure 4 As shown in the figure, a schematic diagram of the motion trajectory of large and small 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, the output end of the vibration source (piezoelectric transducer) and a glass slide. The interior of the PDMS microchannel structure is a horizontal liquid channel, and the liquid input and liquid output of the liquid channel are located on both sides of the PDMS microchannel structure. Except for the liquid input and liquid output of the liquid channel, the rest of the structure is a closed structure, and there are equilateral triangular prism cavity notch structures on the side walls of both sides of the liquid channel. The PDMS microchannel structure is breathable and water repellent.

[0048] The oscillating microbubble chip provided in this embodiment is based on the separation of bulk acoustic wave 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. 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 intermediate-sized particles. The remaining solution containing small particles is captured by small-sized bubbles and flows to the outlet for collection, finally achieving the separation of micro-nano-sized particles. Larger particles are trapped in the vortex, while smaller particles are swept toward the outlet due to the larger drag force and collected in a waste 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 waves to separate 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 in enrichment and separation size reduction.

[0049] like Figure 5 As shown, Figure 5 This is a simulation diagram of separating nanoscale particles. In the figure, when the microbubble radius is 20μm, the microbubble captures 300nm particles (red). 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.

[0050] This example prepares an oscillating microbubble chip according to the following steps. The specific process is as follows:

[0051] S1: A mold with a preset microchannel structure is fabricated on a substrate by photolithography;

[0052] Substrate preparation: Clean and treat the substrate surface to ensure it is suitable for adhesive coating;

[0053] Glue coating: evenly coating photoresist on the substrate;

[0054] Pre-baking: remove the solvent in the photoresist and bake to enhance adhesion;

[0055] Exposure: Use a mask to expose the photoresist to form the desired pattern;

[0056] Post-exposure bake: For certain types of photoresists, a baking process is performed after exposure;

[0057] Development: dissolve the soluble areas on the photoresist to form a pattern;

[0058] Post-baking: improve the adhesion of photoresist to substrate and complete pattern transfer;

[0059] S2: The prepared solution is cast onto a customized mold and processed to obtain a PDMS microchannel structure;

[0060] Glue preparation: Dow Corning Sylgard 184 silicone base and Sylgard curing agent are evenly mixed in a weight ratio of 10:1.

[0061] Defoaming: Place the mixed PDMS glue in a vacuum drying oven to remove bubbles.

[0062] Molding: Pour the PDMS after eliminating bubbles into the mold and place it in a vacuum drying oven to evacuate the mold again.

[0063] Pre-bake: The temperature was set to about 80°C for 2 hours to cure the PDMS.

[0064] Demolding: Gently peel the cured PDMS from the mold.

[0065] Post-baking: Bake at 65°C for 3 hours to enhance its stability.

[0066] S3: The PDMS microchannel structure is processed and bonded to a glass slide to obtain an oscillating microbubble chip;

[0067] Punching: Use a handheld punch to make input and output ports.

[0068] Cutting: PDMS is cut into desired sizes.

[0069] Bonding and assembly: Use a plasma gun to bond to the glass slide and connect the steel needle and hose at the output and inlet.

[0070] The detailed process of making the PDMS microchannel structure in this embodiment is as follows:

[0071] Standard soft lithography techniques were used to fabricate the molds.

[0072] First, the substrate surface was cleaned using a 7:3 mixture of 98% H2SO4 and 30% H2O2 to promote uniform coating of the photoresist.

[0073] The substrate is a silicon wafer, which acts as a base in the photolithography process, and the mold is made on this substrate using photoresist;

[0074] 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.

[0075] After exposure, the mask pattern on the SU-82000 photoresist coating is exposed by baking at 95°C for 1 minute. A developer is used to dissolve the unexposed areas of the photoresist to form a microstructure pattern.

[0076] Finally, bake at 150°C for at least 5 minutes to improve the adhesion of the photoresist to 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.

[0077] Mix Dow Corning Sylgard 184A silicone elastomer base and Sylgard 184B curing agent in a weight ratio of 10:1 until an opaque white mixture appears;

[0078] Then, the mixture was degassed in a vacuum oven at a pressure of 0.09 MPa for 30 min to remove air bubbles;

[0079] It is then cast onto a custom mold;

[0080] A second vacuum degassing cycle was performed at a pressure of 0.09 MPa for 1 h until all bubbles were removed;

[0081] After degassing, the temperature was set to about 80°C for 2 hours of pre-baking to cure the polydimethylsiloxane (PDMS).

[0082] The cured polydimethylsiloxane (PDMS) was then gently removed from the mold and baked at 65 °C for 3 h to enhance its stability.

[0083] Afterwards, the polydimethylsiloxane (PDMS) was cut into the desired size.

[0084] A handheld punch is used to create the inlets and outlets, and then a plasma gun is used to bond the glass sheets to them.

[0085] After assembly is completed, use a steel needle and a hose to connect the inlet and outlet to the injection pump and the waste collection bottle respectively.

[0086] The oscillating microfluidic chip consists 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 using a plasma gun;

[0087] The solution preparation process in this embodiment is as follows:

[0088] The stock solutions of polystyrene microspheres (5 μm, 1 μm, 300 nm, and 100 nm) were shaken on a vortex mixer for 1 minute to ensure uniform dispersion. Then, 100 μL of the solution was transferred to a 1.5 mL centrifuge tube using a pipette. 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 the stock solution.

[0089] To prevent particles from adhering to the microfluidic channel walls, the microfluidic channels were first flushed and lubricated with Tween 20 solution.

[0090] 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.

[0091] When the solution enters the liquid channel, once the microbubbles are trapped in the triangular cylindrical cavity through the surface tension effect, the piezoelectric transducer is connected to the signal generator, which generates a square wave at a driving voltage of 10Vpp to control the opening of the acoustic field and the activation of the microbubbles.

[0092] The prepared solution in a 1 mL syringe was then injected into the liquid channel using a syringe pump.

[0093] The bubbles generate vibrations. Because 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.

[0094] Three cavity sizes were selected for different gradient separations: bubbles with radii of 40μm, 30μm, and 20μm, respectively. Different gradient separations were employed using the secondary acoustic radiation force induced by acoustic vortexes. Larger bubbles were first used to capture larger particles, and the mixed solution flowed to the outlet for collection. Intermediate-sized bubbles were then used to capture intermediate-sized particles. The remaining solution containing small particles was captured by the small bubbles and then flowed to the outlet for collection, ultimately achieving the separation of micro- and nano-sized particles. Larger particles were trapped in the vortex, while smaller particles, due to the greater drag force, were swept toward the outlet with the flow and collected in a waste bottle, achieving the separation of large and small particles.

[0095] Example 2

[0096] This embodiment utilizes 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 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 syringe pump is used to connect to the oscillating microbubble chip and deliver the substance to be injected to the liquid channel in the oscillating microbubble chip; the fluorescence inverted microscope is used to observe the microscopic process inside the oscillating microbubble chip; in particular, fluorescence imaging is performed to observe the microbubbles and the interaction between the microbubbles and other substances; the image acquisition system is connected to the fluorescence inverted microscope to receive and process the optical image signal transmitted by the fluorescence 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 microbubbles and the separation process of the substances occur. The microbubbles are driven by the signal of the signal generator inside the oscillating microbubble chip and interact with the substances injected by the syringe pump to realize the functions of separating specific substances.

[0097] The principle of the oscillating microbubble chip for micro-nanoparticle acoustic manipulation is as follows:

[0098] The resonant frequency of microbubbles on the sidewalls of polydimethylsiloxane microfluidic channels can be estimated using the Rayleigh-Plesset equation:

[0099]

[0100] in, is the fluid density, n is the bubble variability index, is the bubble radius, σ is the surface tension of the liquid;

[0101] Indicates liquid pressure; represents the resonance frequency of the microbubble;

[0102] The motion trajectory of particles has two mechanisms: resistance and acoustic radiation force.

[0103] At low Reynolds numbers, the drag force F acting on a spherical particle is d The following formula represents:

[0104]

[0105] in, is the dynamic viscosity of the liquid, is the particle radius, and U is the relative velocity between the fluid and the particle.

[0106] However, it is difficult to determine U in the flow, so its maximum value is used Estimate the upper limit of particle velocity in the vortex, where is the radial vibration velocity of the bubble wall;

[0107] Indicates the maximum velocity between the fluid and the particles; represents the angular frequency of bubble oscillation; represents the center-to-center distance between bubbles and particles;

[0108] Acoustic radiation force exerted on spherical particles by microbubbles oscillating in an acoustic field Expressed as:

[0109]

[0110] 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 fluid density; represents a constant;

[0111] At a fixed operating frequency, larger particles experience stronger acoustic radiation forces than smaller particles, resulting in efficient separation.

[0112] Secondary radiation force between vibrating bodies and particles Expressed as:

[0113]

[0114] Where, represents the center-to-center distance between bubbles and particles, R b is the bubble radius. are the frequency and amplitude of the bubble vibration, respectively.

[0115] The magnitude of the secondary radiation force depends on the particle geometry and the amplitude and frequency of the bubble's excitation. Furthermore, the sign of the force, attractive or repulsive, depends on the ratio of the particle and fluid densities.

[0116] When particles are subjected to different radiation forces and drag forces, they will have different types of particle motion trajectories.

[0117] and The ratio is expressed as follows:

[0118]

[0119] in, Represents the secondary radiation force between the vibrating body and the particle;

[0120] 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.

[0121] The larger the particle size, the greater the secondary acoustic radiation force it receives, the smaller the vortex trajectory, and the easier it is to be captured by bubbles; while smaller particles are subject to stronger drag force and will be flushed out by the buffer solution.

[0122] This embodiment provides an acoustic manipulation method using the above-mentioned oscillating microbubble chip, which is used to achieve particle separation and includes the following steps:

[0123] When the solution enters the liquid microchannel, once the microbubbles are trapped in the triangular cylindrical cavity through the surface tension effect, the signal generator is turned on to output a square wave to excite the piezoelectric transducer;

[0124] 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;

[0125] By using medium-sized bubbles to capture medium-sized particles, the remaining solution containing small particles continues to flow;

[0126] Small particles are captured by small bubbles near the output port and then flow to the outlet for collection;

[0127] Finally, the separation of micro- and nano-sized particles in the mixed solution is achieved;

[0128] In this embodiment, larger particles are subjected to stronger secondary acoustic radiation forces and are gradually trapped in the vortexes generated by larger bubbles. Smaller particles are swept toward the outlet due to stronger drag forces and collected in a waste liquid bottle, thus achieving separation of large and small particles.

[0129] The oscillating microwave chip provided in this embodiment utilizes the acoustic vortex effect induced by oscillating microbubbles to achieve acoustic manipulation of micro- and nanoparticles. Equilateral triangular cavities are alternately fabricated on the sidewalls of a polydimethylsiloxane (PDMS) liquid channel. Microbubbles form on the PDMS surface due to its hydrophobicity, gas permeability due to its porosity, and the surface tension of the fluid. When traveling sound waves interact with the bubbles within the liquid channel, the air-liquid interface amplifies the vibrational displacement and significantly affects the surrounding medium, generating a strong circulating flow pattern near the bubbles, known as bubble-induced acoustic streaming.

[0130] Acoustic streaming is most effective when bubbles are excited at their resonant frequency. During particle motion, the combined effects of acoustic radiation force and drag force form vortex patterns. The drag force propels the particles along streamlines, while the acoustic radiation force pulls the particles toward the bubble. Bubble oscillations are driven by bulk acoustic waves (BAW) generated by a piezoelectric transducer excited by a signal generator. Compared to SAW sensors, low-frequency BAW sensors are simpler, easier to manufacture, offer more flexible deployment, and are cost-effective for applications.

[0131] Furthermore, the liquid channel uses the secondary acoustic radiation force generated by alternating oscillating microbubbles to capture particles within the liquid channel. This method allows large particles or particle clusters near the gas-liquid interface to rotate stably and be captured at the center of the vortex, while smaller particles may escape from the vortex and flow downward. Using different bubble sizes to separate micro- and nanoparticles has achieved remarkable results.

[0132] The above embodiments are merely preferred embodiments for the purpose of fully illustrating the present invention, and the scope of protection of the present invention is not limited thereto. Equivalent substitutions or modifications made by those skilled in the art based on the present invention are within the scope of protection of the present invention. The scope of protection of the present invention shall be subject to the claims.

Claims

1. Oscillating microbubble chip, characterized by: The microchannel structure includes a liquid channel and a plurality of triangular prism cavities arranged on both sides of the liquid channel. 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 order of size from the upstream direction to the downstream direction of the liquid. 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. The triangular prism cavities are alternately arranged on both side walls of the liquid channel; The microchannel structure is made of air-permeable and water-repellent polydimethylsiloxane; It also includes a piezoelectric transducer and a glass slide; the microchannel structure and the piezoelectric transducer are connected to the glass slide.

2. The oscillating microbubble chip according to claim 1, wherein: 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.

3. The oscillating microbubble chip according to claim 1, wherein: 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.

4. The oscillating microbubble chip according to claim 1, wherein: 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 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.

5. The oscillating microbubble chip according to claim 1, wherein: The 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.

6. A separation system comprising the oscillating microbubble chip according to any one of claims 1 to 5, 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 to the oscillating microbubble chip to transport the substance to be injected into the liquid channel of 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 fluorescent inverted microscope 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 injection pump to achieve particle separation.

7. An acoustic manipulation method for a separation system using the oscillating microbubble chip according to claim 6, characterized in that: The following steps are involved: When the solution enters the liquid microchannel and the microbubbles are anchored 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 near the output port and then flow to the outlet for collection; ultimately, the separation of micro- and nano-sized particles is achieved.

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