CN115041245B - Method and device for capturing and separating particles based on ultra-high frequency bulk acoustic wave acoustic flow potential well - Google Patents

Abstract

The invention discloses a method and a device for capturing and separating particles based on an ultrahigh frequency bulk acoustic wave sound current potential well, comprising a central processing unit, a power source module and a particle separating module, wherein the central processing unit is used for sending instruction information to the power source module; the power adjusting module is used for converting the received instruction information into a power signal; the micro-fluidic chip is positioned above the ultrahigh frequency bulk acoustic wave resonator and used for controlling the sample to directionally pass through the micro-channel; the ultrahigh frequency bulk acoustic resonator is characterized in that a microstructure array is processed on the top electrode, and each microstructure unit in the microstructure array penetrates through the top electrode and the adhesion layer to reach the surface of the piezoelectric layer; high-speed acoustic fluid vortex generated by fluid is excited by the peripheral acoustic pressure field of the microstructure units, so that a stagnation region, namely an acoustic flow potential well field, is created in the middle of the fluid vortex, and particles with different sizes are captured and separated. The method and the device can capture and separate particles with different sizes and materials and have better effect.

Description

Method and device for trapping and separating particles based on UHF bulk acoustic wave potential well

technical field

The invention belongs to the field of analytical instruments, in particular to a method and device for capturing and separating particles based on ultra-high frequency bulk acoustic waves.

Background technique

With the development of science and technology, people pay more and more attention to molecules related to biomedicine, and it is of great significance to develop fast and easy methods to detect multiple biological samples simultaneously. Particle manipulation technology, including particle capture, enrichment, separation, dispersion, and patterning technologies, plays an important role in the fields of biomedicine, industry, and the environment. Appropriate particle manipulation tools will enable size-based sorting and filtering for the study of downstream behaviors such as multiplexed diagnostics and drug delivery. There are many ways to manipulate and separate particles such as cells or microvesicles. Traditional passive sorting techniques are based on different densities and sizes, such as ultracentrifugation, ultrafiltration, and inertial microfluidics. Law.

Active technologies include manipulation methods such as electricity, magnetism, optics, acoustics, and fluid dynamics. Each method has a specific scope of application, and the separation resolution of passive sorting technology is low; the application of electrophoresis technology with strong electric field and heat generation has limitations, and can only work in solutions with specific electrical properties; magnetoelectrophoresis technology Involves magnetic beads, requiring additional incubation times and elution steps to remove beads from isolated microparticles or cells; both optical and hydrodynamic techniques can damage cells, surface acoustic waves and acoustophoresis based on standing waves in fluids have both been used For the separation, extraction and manipulation of microparticles and cells.

The Chinese patent with publication number CN114112826A discloses an acousto-optic interconnected microfluidic detection system and detection method for fluorescent particles. The detection system includes: a microfluidic chip, an ultra-high frequency sound source, a fluorescence detection device, and a data analysis device. Including fluorescent particles of at least two sizes: The ultra-high frequency sound source is used to provide an acoustic pressure field environment for the sample to be tested in the micro-channel, so that the fluorescent particles in the sample to be tested can decelerate and pass through the micro-channel in a single line: Fluorescence detection module It is used to provide excitation light to make the sample to be tested in the microfluidic channel emit fluorescence, and is also used to collect the fluorescence flowing through the sample to be tested and then convert it into an electrical signal and send it to the data analysis device: the data analysis device is used for analysis based on the electrical signal As a result, the analysis results include concentrations of fluorescent particles of multiple sizes.

However, these existing manipulation tools have the problems of high cost, low throughput, low efficiency, and sample damage, and cannot deal with particle agglomeration, resulting in reduced sensitivity of sample capture and separation, and single particle analysis cannot be achieved.

Therefore, there is an urgent need for a fast, accurate, and scalable manipulation device and method that can simultaneously manipulate the positions of particles of different sizes in space to achieve discrete separation and prepare for the next step of analysis.

Contents of the invention

The invention provides a method and device for trapping and separating particles based on an ultra-high frequency bulk acoustic flow potential well, and the method and device can better separate and trap particles.

A device for trapping and separating particles based on UHF bulk acoustic flow potential well, including:

The central processing unit is used to send instruction information to the power source module;

The power adjustment module is used to convert the received instruction information into a power signal, and control the bulk acoustic wave generated by the UHF bulk acoustic wave resonator through the power signal;

A microfluidic chip, located above the UHF bulk acoustic resonator, including a sample inlet, a sample outlet, and a microfluidic channel for controlling the orientation of the sample through the microfluidic channel, the sample including particles of at least one size; and

The ultra-high frequency bulk acoustic wave resonator includes a Bragg reflection layer, a bottom electrode, a piezoelectric layer, an adhesion layer and a top electrode arranged in sequence from bottom to top, and a microstructure array is arranged on the top electrode, and each microstructure array in the microstructure array A microstructure unit penetrates the top electrode and the adhesion layer to reach the surface of the piezoelectric layer;

The micro-fluid vortex is generated by exciting the micro-liquid through the resonance area around the micro-structure unit, and a stagnation zone is formed in the middle of the acousto-fluid vortex, that is, the acoustic fluid potential well field. The particles are dragged by the Stokes drag force and the acoustic radiation force of the fluid vortex. Drag it onto the acoustic flow potential well field on the microstructure unit to achieve stable capture and separation of particles of different sizes.

It also includes a fluorescence microscope and a CCD camera; wherein, a CCD camera is arranged on the fluorescence microscope, and the CCD camera is connected to the central controller, and the particle distribution information is obtained through the CCD camera on the fluorescence microscope, and the particle distribution information is input to the central controller, through The central controller displays the particle distribution.

The power adjustment module includes a signal generator and a power amplifier. The signal generator receives instruction information to generate a high-frequency signal, which is amplified by the power amplifier and drives the ultra-high frequency bulk acoustic wave resonator to generate bulk acoustic waves.

The speed of injecting the sample into the micro-channel is 0.5-5 μl/min, the height of the micro-channel is 200 nm-100 μm, and the width of the micro-channel is 100-300 μm.

The power applied to the UHF bulk acoustic wave resonator is 100-800mW, the distance between the microstructure units is 100nm-50μm, and the shape of the microstructure units is circular, elliptical, rectangular or polygonal.

The particle size is 100 nm-30 μm, and the particles are silica, magnetic iron oxide, gold, silver, carbon, polystyrene, polylactic acid, polyacrylic acid, polyamides, polyaniline, gelatin, calcium carbonate, barium carbonate , cellulose, pectin, starch, albumin, chitosan, cells, exosomes, microvesicles, vesicles, membrane vesicles, viruses or bacteria.

Multiple UHF bulk acoustic wave resonators are arranged on the inner wall of the microfluidic chip, and each ultrahigh frequency bulk acoustic wave resonator is arranged with a microstructure array of one size, from the inlet to the outlet. The corresponding UHF bulk acoustic wave resonators are arranged according to the size of the microstructure array from small to large to capture particles of different sizes.

The gap between the sizes of the microstructure units in the microstructure array arranged on each UHF bulk acoustic resonator is at least 100nm, and the optimal difference is 1-2 times the size of the smallest microstructure unit.

Multiple microstructure arrays of different sizes are arranged on the UHF BAW resonator, and the microstructure arrays are arranged from small to large along the flow direction of the sample to capture particles of different sizes.

The gap between the sizes of the microstructure units in the microstructure array on a single UHF BAW resonator is at least 100nm, and the optimal difference is 1-2 times the size of the smallest microstructure unit. Preferably, three kinds of microstructure arrays are arranged on a single UHF BAW resonator, the sizes of the microstructure units in the microstructure array are respectively 300nm, 500nm and 800nm, or the sizes of the microstructure units in the microstructure array are respectively 5 μm, 10μm and 15μm.

A method for preparing an ultrahigh frequency bulk acoustic wave resonator, comprising:

(1) Obtain the initial UHF BAW resonator with substrate, Bragg reflection layer, bottom electrode, piezoelectric layer, adhesion layer and top electrode layer from bottom to top;

(2) Coating a methyl methacrylate film on the top electrode layer, sequentially performing electron beam exposure and development on the methyl methacrylate film based on the microstructure array parameters, removing excess developer, and drying to obtain a methyl methacrylate based film. Microstructural arrays of methyl acrylate films;

(3) On the microstructure array based on methyl methacrylate film obtained in step (2), etch the top electrode layer with the first etching solution, after drying the first etching solution, pass the The second etching solution etches the adhesion layer, and then removes the methyl methacrylate film with acetone to obtain the final microstructure array UHF bulk acoustic wave resonator. The materials of the bottom electrode, the adhesion layer and the top electrode are all metals, and the metals include aluminum, molybdenum, gold, chromium, titanium, copper and alloys thereof. The first etching solution is potassium iodide, and the second etching solution is hydrogen peroxide.

The piezoelectric layer material is a piezoelectric material, including aluminum nitride, lead zirconate titanate, zinc oxide and doped materials.

The Bragg reflective layer is composed of two materials alternately stacked, including aluminum nitride/molybdenum, aluminum nitride/silicon dioxide or molybdenum/silicon dioxide.

The shape of the UHF bulk acoustic wave resonator is triangle, circle, shuttle, rhombus or pentagon.

A method for trapping and separating particles based on an ultra-high-frequency bulk acoustic wave potential well, using an ultra-high-frequency bulk acoustic wave potential well for trapping and separating particles, comprising the following steps:

Inject the sample into the inlet of the microfluidic channel, start the microfluidic chip to control the flow of the sample through the microfluidic channel and then flow out from the sample outlet. The size of the microfluidic channel is: 100-300 μm wide and 200nm-100 μm high , the parameters of the sample are: the concentration of the sample is 1×10 ⁷ -1×10 ¹⁰ /ml, the flow rate of the sample is 0.5-5 μl/min, and the particle size of the sample is 100-30 μm;

Start the power adjustment module through the central processing unit, and apply a power of 100-800 mW to the UHF BAW resonator. The size of the microstructure array on the UHF BAW resonator is: the spacing between the microstructure units is 100-50 μm, The size of the microstructure unit is 100-50 μm, and the depth is 100-400 nm. The CCD camera can detect that the fluorescent sample particles passing above the UHF bulk acoustic wave resonator are trapped in the microstructure unit, presenting an array distribution state.

Compared with prior art, the beneficial effect of the present invention is:

(1) In the present invention, the microstructure array is set on the UHF bulk acoustic resonator, and each microstructure unit penetrates the top electrode and the adhesion layer, so that no resonance occurs at the microstructure unit, and then the microstructure The acoustic fluid potential well is formed at the unit, and the acoustic flow effect is generated in the fluid due to the action of the bulk acoustic pressure field around it, forming a fluid vortex. Finally, the Stokes drag force and the acoustic radiation force of the fluid vortex will While the particles are separated, the separated particles are dragged to the acoustic fluid potential well, that is, the microstructure unit, to achieve the technical effect of capturing and separating the particles.

(2) The microstructure can make the UHF BAW resonator produce a spatially localized, non-periodic, and non-uniform sound field, or form a sound field that is not directly related to the size and position of the resonator, and can selectively control the vibration size and position, and can accommodate the motion of the surrounding fluid without affecting the expected acoustofluidic potential well effect. In general, the height of the micro-channel matches the spacing of the micro-structure units, which can be operated better. The spacing of the micro-structure units is generally set to 1-2 times the unit size, and the corresponding micro-channel height is 1-2 times. The unit size of the microchannel is the best, and the width of the microchannel mainly matches the width of the microstructure array. In order to ensure that all particles flowing through the microchannel can pass above the microstructure array, the width of the microchannel is usually set slightly larger than the width of the microstructure array. The optimal distance between one side of the inner wall of the microchannel and one side of the microstructure array is the width of one microstructure unit.

Description of drawings

Fig. 1 is a diagram of a particle capture and separation device based on ultra-high frequency bulk acoustic wave provided by a specific embodiment;

Fig. 2 is a flow chart of a method for preparing a UHF bulk acoustic resonator provided in a specific embodiment;

Fig. 3 is a physical diagram of the circular hole array of the UHF bulk acoustic resonator provided in the specific embodiment, wherein Fig. 3a is a plane physical diagram of the circular hole array, and Fig. 3b is a circular hole depth diagram of the circular hole array;

FIG. 4 is a physical diagram of fluorescent particles captured by the UHF BAW resonator prepared in Example 1;

FIG. 5 is a physical diagram of fluorescent particles captured by the UHF BAW resonator prepared in Example 2;

6 is a schematic diagram of fluorescent particles captured by the UHF BAW resonator prepared in Example 3;

7 is a schematic diagram of fluorescent particles captured by the UHF BAW resonator prepared in Example 5;

Fig. 8 is a schematic diagram of the fluorescent particles captured by the conventional UHF bulk acoustic resonator prepared in Comparative Example 1. Fig. 8a is the sound pressure propagation diagram of the conventional UHF bulk acoustic resonator, and Fig. 8b is the conventional is the sound pressure amplitude diagram of the UHF BAW resonator;

Figure 9 is a schematic diagram of the principle of fluorescent particles captured by the microstructure array UHF bulk acoustic resonator prepared in Example 1, Figure 9a is the sound pressure propagation diagram of the microstructure array UHF bulk acoustic resonator, and Figure 9b is the microstructure The sound pressure amplitude diagram of the array UHF BAW resonator;

FIG. 10 is a schematic diagram of the UHF BAW resonator prepared in Example 1 to generate a fluid vortex to trap particles.

Detailed ways

In order to make the object, technical solution and advantages of the present invention clearer, the present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described here are only used to explain the present invention, and do not limit the protection scope of the present invention.

The present invention provides a device for trapping and separating particles based on UHF bulk acoustic flow potential well, as shown in Figure 1, specifically including:

The central processing unit is used to send instruction information to the power source module;

The power adjustment module is used to convert the received instruction information into a power signal, and control the bulk acoustic wave generated by the UHF bulk acoustic wave resonator through the power signal; the power adjustment module includes a signal generator and a power amplifier, and the signal generator receives the instruction information to generate The high-frequency signal is amplified by the power amplifier and drives the ultra-high frequency bulk acoustic wave resonator to generate bulk acoustic waves;

A microfluidic chip, located above the UHF bulk acoustic resonator, including a sample inlet, a sample outlet, and a microfluidic channel for controlling the orientation of the sample through the microfluidic channel, the sample including particles of at least one size; and

The ultra-high frequency bulk acoustic wave resonator includes a Bragg reflection layer, a bottom electrode, a piezoelectric layer, an adhesion layer and a top electrode arranged in sequence from bottom to top, and a microstructure array is arranged on the top electrode, and each microstructure array in the microstructure array A microstructure unit penetrates the top electrode and the adhesion layer to reach the surface of the piezoelectric layer;

The acoustic fluid vortex generated by exciting the liquid around the microstructure unit creates a stagnation zone in the middle of the fluid vortex, the acoustic fluid potential well field, to capture and separate particles of different sizes. The particles can be Stokes by the fluid vortex The drag force and the acoustic radiation force are dragged to the acoustic fluid potential well on the microstructure unit to generate stable capture. After the particle is captured, the potential well is filled, and the next particle will not be captured again, thus completing the separation .

Fluorescence microscope and CCD camera; among them, a CCD camera is arranged on the fluorescence microscope, and the CCD camera is connected to the central controller, and the particle distribution information is obtained through the CCD camera on the fluorescence microscope, and the particle distribution information is input to the central controller. The monitor shows the distribution of particles.

The present invention also provides a method for preparing an ultra-high frequency bulk acoustic wave resonator, including:

In this case, for the first time, electron beam exposure technology and wet etching technology were used to prepare a circular gold nanohole array on the surface of a regular pentagonal UHF bulk acoustic wave resonator. The schematic diagram of the process flow is shown in Figure 2:

(1) Obtain the initial UHF with silicon substrate, aluminum nitride/silicon dioxide Bragg reflector layer, gold bottom electrode, aluminum nitride piezoelectric layer, titanium-tungsten adhesion layer and gold top electrode layer from bottom to top Bulk acoustic wave resonator;

(2) Preparation of nanopore array mask layer: first clean the gold-top electrode with acetone and isopropanol, then evenly coat polymethyl methacrylate on its surface with a homogenizer, and set the speed of the homogenizer at 200- 500 rpm for 30-60s and 4000-6000 rpm for 60-90s, optimal for 500 rpm for 30 s and 5000 rpm for 60s. After heating at 150-200°C for 60-120s, preferably at 180°C for 90s, a polymethyl methacrylate film with a thickness of 500-1000 nm, preferably 800 nm is obtained, and then exposed by electron beam exposure technology, introduced For microstructure array parameters, set the current intensity to 0.05-0.15 nA, preferably 0.111nA, the exposure agent intensity to 500-800 μC/cm ² , preferably 600 μC/cm ² , and then develop, the development time is 3-5min, The preferred developing time is 4min, washed with water and dried to obtain a microstructure array based on methyl methacrylate film;

(3) To prepare gold nanopores, use the gold etching solution potassium iodide to etch the gold top electrode for 5-10s, the preferred etching time is 8s, and dry it with an air gun after etching to prevent the excess solution from reacting with gold. To generate side engraving, at a heating temperature of 40-50°C, etch the titanium-tungsten adhesion layer by hydrogen peroxide for 4-6 minutes, and then soak in acetone for 2-6 minutes to remove the uppermost methyl methacrylate film and obtain The microstructure array of the UHF BAW resonator, as shown in Figure 3a, has a neat and uniform array of gold nanoholes etched on the surface of the UHF BAW resonator, and the diameter of a single gold nanohole is measured to be about 550nm , with a hole spacing of 1 μm. Figure 3b shows the depth of the circular gold nanohole, which is measured to be 240nm, which is just the sum of the thickness of the gold top electrode and the titanium-tungsten adhesion layer of the UHF BAW resonator. By adjusting the process parameters, the processing of circular holes with an aperture size of 100nm-50μm can be realized.

Example 1

In this case, a regular pentagonal UHF bulk acoustic wave resonator with a microstructure array is used to verify the trapping effect of particles. Figure 4 is a picture of the ultrahigh frequency bulk acoustic wave resonator engraved with gold nanohole arrays capturing 300nm fluorescent particles. The fluorescent particles are solid polystyrene microspheres doped with fluorescein isothiocyanate (FITC) dyes inside. The etched nanopore size is 550nm, the depth is 240nm, the hole spacing is 800nm, the straight microchannel width is 100-300μm, the optimum is 200μm, the height is 200nm-100um, the optimum is 1.1μm, and the concentration of the prepared 300nm sample is 1*10 ⁷ -1*10 ¹⁰ cells/ml, the optimum is 1*10 ⁸ cells/ml. Use a syringe pump or a peristaltic pump to inject into the microchannel at a speed of 0.5-5 μl/min, the optimum is 2 μl/min. Turn on the resonator, set the power to 100-800mW, and the optimal value is 700mW. Under the CCD camera, it can be seen that the fluorescent particles passing above the resonator are quickly captured in the fluid vortex, and will eventually be pushed to the sound pressure potential well area. That is, inside the nanopore, it is in an array distribution state.

Example 2

Figure 5 is a picture of 15 μm fluorescent particles captured by UHF bulk acoustic wave resonators engraved with nanohole arrays. The fluorescent particles are solid polystyrene microspheres doped with fluorescein isothiocyanate (FITC) dyes inside. The etched nanopore size is 20μm, the depth is 240nm, the width of the microfluidic chip microchannel is 100-300μm, the optimum is 200μm, the height is 200nm-100μm, the optimum is 25μm, and the concentration of 15μm fluorescent particles is prepared to be 1x10 ⁷ -1x10 ¹⁰ /ml, optimally 1*10 ⁷ /ml. The speed of injecting into the microchannel with a syringe pump or a peristaltic pump is 0.5-5μl/min, and the optimum is 2μl/min. Turn on the resonator, set the power to 100-800mW, and the optimal value is 400mW. Under the CCD camera, it can be seen that 15μm fluorescent particles are trapped inside the nanopores, and each hole only captures a single particle, which has a good dispersion effect.

Example 3

This case proposes a solution for the simultaneous capture and separation of multi-size particles. One or more UHF bulk acoustic wave resonators with microstructure arrays are placed inside the microchannel. The structure of the microchannel can be designed as linear, serpentine, spiral, telescopic-extending, etc. The inlet and outlet One or more microstructure arrays of different sizes or shapes are prepared in different regions on the same UHF BAW resonator, and different combination types and quantities are realized by adjusting the unit size, spacing and shape. Figure 6 is a schematic diagram of a circular nanohole array structure with three sizes on the surface of a single regular pentagonal UHF resonator. The combination of the three sizes of the circular nanohole array structure is 300nm, 500nm, 800nm, each size The array spacing is 100nm-50μm, which is optimally 1-2 times the size of the microstructure unit, and the captured nanoparticles are solid microspheres with a density between 1-3g/ml. The power setting is 600mW (applied to 300nm, 500nm, 800nm combination). Due to the different acoustofluidic potential wells of array units of different sizes, when a mixed sample with multi-sized particles enters the acoustic pressure region, the particles will enter the matching acoustofluidic potential wells respectively to realize the capture and separation of particles of various sizes.

Example 4

The difference from Example 3 is that the combination of the three sizes of the circular nanohole array structure is 5 μm, 10 μm, and 15 μm, and the power is set to 300 mW.

Example 5

This embodiment provides that different microstructures are respectively prepared on multiple UHF BAW resonators. Fig. 7 is a schematic diagram of the arrangement and combination of three nanohole array UHF bulk acoustic wave resonators with different sizes, which are placed in the same micro flow channel. The microstructure sizes on the three UHF BAW resonators are 300nm, 500nm, and 800nm respectively, and the array spacing of each size is 100nm-50μm, which is optimally 1-2 times the size of the microstructure unit. The captured nanoparticles are solid microspheres with a density between 1-3 g/ml. Set the power of 700mW, 600mW, and 500mW on the three resonators (applied to the combination of 300nm, 500nm, and 800nm). The power of the bulk acoustic wave resonator can adjust the size of the acoustic fluid potential well to realize the capture and separation of particles of various sizes.

Example 6

The difference from Example 5 is that the combination of the three sizes of the circular nanohole array structure is 5 μm, 10 μm, and 15 μm, and the power setting is 350 mW, 300 mW, and 200 mW.

Embodiments 3, 4, 5, and 6 all have the advantages of fast, efficient, multi-channel and precise separation.

Comparative example 1

The difference from Embodiment 1 is that there is no microstructure array on the UHF BAW resonator.

The principle of microstructure array trapping particles on the UHF BAW resonator provided by the present invention is as follows:

First, the change of the sound pressure distribution area of the UHF BAW resonator with and without the microstructure array was compared, and the schematic diagram is shown in Fig. 8 . A microfluidic chip is provided, which is placed directly above the ultra-high frequency bulk acoustic wave resonator, and the contact position is closely attached, and the ultra-high frequency bulk acoustic wave resonator can generate exponentially attenuated Bulk acoustic waves form a sound pressure gradient region. Figure 8a is a cross-sectional view of a UHF BAW resonator without a microstructure array, and its sound pressure area is continuously and uniformly distributed in the horizontal direction and exponentially vertically upwards to the inside of the microchannel, and Figure 8b is a UHF BAW resonator without a microstructure array The sound pressure amplitude of the bulk acoustic wave resonator is large. Since the entire area of the resonator can resonate, the values of the high-sound potential energy zone and the low-sound potential energy zone are relatively high and the difference is small, and particles cannot be effectively captured.

Figure 9a is a cross-sectional view of a UHF BAW resonator with a microstructure array. In the microstructure region, due to the lack of a top electrode, resonance will not occur, so an acoustic pressure potential well will be formed, and an acoustic pressure potential well will be formed when coupled into the fluid. Fluid potential well. Figure 9b shows the magnitude of the sound pressure of the UHF BAW resonator with a microstructure array. The value of the low acoustic potential energy region is almost zero, and the difference between the high acoustic potential energy region and the low acoustic potential energy region is large. Therefore, in the low acoustic potential energy region , that is, the position of the microstructure can form a stable capture site, which can effectively trap particles.

The principle of particle capture by the microstructure array is explained in detail below. As shown in Figure 10, the sound pressure zone 1 and the sound pressure zone 2 around the microstructure can generate exponentially decaying bulk acoustic waves upward. Due to the acoustic flow effect, the fluid vortex, vortex The direction of vortex 1 is clockwise, and the direction of vortex 2 is counterclockwise. The contact area of the two vortexes is the acoustofluid area, that is, the position of the microstructure, and the directions are all downward. Therefore, when a particle passes by, it will be quickly trapped inside the microstructure by the force of acoustic radiation and the Stokes drag force of the fluid vortex. The acoustic radiation force is expressed by the following formula:

(1)

(1)

(2)

(2)

(3)

(3)

分别表示微球位置处的 一阶声压和声速。

和

分别为微球和液体的压缩系数，

和

分别为微球和液体 的密度，f ₁ 和f ₂ 分别表示单极散射系数和偶极散射系数，

为哈密顿算子。 in,frepresents the sound radiation force,urepresents the acoustic potential energy,arepresents the particle radius,pand

respectively represent the position of the microsphere First-order sound pressure and sound velocity.

and

are the compressibility coefficients of microspheres and liquid, respectively,

and

microspheres and liquid density of,f ₁ andf ₂ are the monopole and dipole scattering coefficients, respectively,

is the Hamiltonian.

f ₁ indicates that the acoustic radiation force is related to the volume modulus ratio of particles and liquids, and f ₂ indicates that the acoustic radiation force is related to the density of particles and liquids. The fluid drag force is expressed by the formula:

（4）

(4)

Among them, a is the radius of the particle, 𝜈 _d is the relative velocity between the fluid and the particle, and 𝜇 is the viscosity of the liquid. When a particle is captured, the potential well is filled and the next particle will not be captured again, thus completing the separation. As particles agglomerate, complex interactions take place in the vortex, and they are eventually dispersed and driven into the acoustofluidic potential well region. UHF bulk acoustic wave resonator capture ability and microstructure depth, microstructure unit spacing, unit size, unit shape, microchannel height, bulk acoustic wave with different power applied, different sample flow rates, capture target particle size, Captures the target particle material, or a combination thereof. The magnitude of the drag force is proportional to the velocity difference (𝜈 _d ) between the fluid and the particle, so the higher the velocity of the flow field, the smaller the size of the particles that can be manipulated, so the injection velocity into the microchannel is usually set at 0.5-5μl /min. Both the height of the microchannel and the power applied to the bulk acoustic resonator will affect the size of the vortex, the flow channel is reduced, the outer layer of the vortex will be limited, and only the inner small vortex exists; the power applied to the bulk acoustic resonator increases Larger, the vortex will also increase. Therefore, the channel height is generally set to 200nm-100μm, the channel width is set to 100-300μm, and the applied power is generally set to 100-800mW. The spacing between microstructure units will affect the distance between vortex 1 and vortex 2. When the distance between vortex 1 and vortex 2 is too large, the acoustic radiation force and fluid drag force are too small to capture particles; when the two vortexes overlap When , it will lead to the reduction of the area of the acoustic fluid potential well, which will also reduce the ability to capture particles. Therefore, the microstructure array spacing is usually set to 100nm-50μm, and the optimum is 1-2 times the size of the microstructure unit. The size of the capture target particle is usually 100nm-30μm, and the material of the capture target particle is usually silicon dioxide, magnetic iron oxide, gold, silver, carbon, polystyrene, polylactic acid, polyacrylic acid, polyamide, polyaniline, gelatin, Calcium carbonate, barium carbonate, cellulose, pectin, starch, albumin, chitosan, cells, exosomes, microvesicles, vesicles, membrane vesicles, viruses or bacteria.

Claims (9)

1. A device based on ultra-high frequency bulk acoustic flow potential well trapping and separating particles, characterized in that it comprises: The central processing unit is used to send instruction information to the power source module; The power adjustment module is used to convert the received instruction information into a power signal, and control the bulk acoustic wave generated by the UHF bulk acoustic wave resonator through the power signal; A microfluidic chip, located above the UHF bulk acoustic resonator, including a sample inlet, a sample outlet, and a microfluidic channel, used to control the orientation of the sample through the microfluidic channel, and the sample includes particles of at least one size; And the ultra-high frequency bulk acoustic wave resonator, including the Bragg reflection layer, the bottom electrode, the piezoelectric layer, the adhesion layer and the top electrode arranged in sequence from bottom to top, the microstructure array is processed on the top electrode, each microstructure array A microstructure unit penetrates the top electrode and the adhesion layer to reach the surface of the piezoelectric layer; The micro-fluid vortex is generated by exciting the micro-liquid through the resonance area around the micro-structure unit, and a stagnation zone is formed in the middle of the acousto-fluid vortex, that is, the acoustic fluid potential well field. The particles are dragged by the Stokes drag force and the acoustic radiation force of the fluid vortex. Drag to the acoustofluidic potential well field located on the microstructure unit to achieve the effect of stably capturing and separating particles of different sizes; The particle size is 100 nm-30 μm, and the particles are silica, magnetic iron oxide, gold, silver, carbon, polystyrene, polylactic acid, polyacrylic acid, polyamides, polyaniline, gelatin, calcium carbonate, barium carbonate , cellulose, pectin, starch, albumin, chitosan, cells, exosomes, microvesicles, vesicles, membrane vesicles, viruses or bacteria. 2. The UHF BAW potential trap trapping and separating particle device according to claim 1 is characterized in that it also includes a fluorescence microscope and a CCD camera; wherein a CCD camera is arranged on the fluorescence microscope, and the CCD camera and the central The controller is connected, and the particle distribution information is obtained through the CCD camera on the fluorescence microscope, and the particle distribution information is input to the central controller, and the distribution of the particles is displayed through the central controller. 3. The ultra-high frequency bulk acoustic flow potential well capture and separation particle device according to claim 1, wherein the power adjustment module includes a signal generator and a power amplifier, and the signal generator receives instruction information to generate a high-frequency signal, After being amplified by the power amplifier, the ultra-high frequency bulk acoustic wave resonator is driven to generate ultra-high frequency bulk acoustic waves. 4. The ultra-high frequency bulk acoustic flow potential trap device for trapping and separating particles according to claim 1, wherein the speed at which the sample is injected into the micro-channel is 0.5-5 μl/min, and the height of the micro-channel is 200nm -100 μm, the width of the microchannel is 100-300 μm. 5. The UHF BAW potential well capture and separation particle device according to claim 1, characterized in that the power applied to the UHF BAW resonator is 100-800mW, and the microstructure unit spacing is 100nm -50μm, the shape of the microstructure unit is circular, elliptical, rectangular or polygonal. 6. The ultrahigh frequency bulk acoustic wave potential well trapping and separating particle device according to claim 1, characterized in that, a plurality of ultrahigh frequency bulk acoustic wave resonators are arranged on one side of the microfluidic channel inner wall of the microfluidic chip , a microstructure array of one size is etched on each UHF BAW resonator, and the corresponding UHF BAW resonators are arranged from small to large according to the size of the microstructure array from the sample inlet to the sample outlet. Capture particles of different sizes. 7. The UHF BAW potential trap device for trapping and separating particles according to claim 1, wherein a plurality of microstructure arrays of different sizes are arranged on the UHF BAW resonator, along the sample The flow direction of the microstructure array is arranged from small to large to capture particles of different sizes. 8. The UHF BAW potential well trapping and separating particle device according to claim 1, characterized in that the preparation method of the microstructure array UHF BAW resonator comprises: (1) Obtain the initial UHF BAW resonator with substrate, Bragg reflection layer, bottom electrode, piezoelectric layer, adhesion layer and top electrode layer from bottom to top; (2) Coating a methyl methacrylate film on the top electrode layer, sequentially performing electron beam exposure and development on the methyl methacrylate film based on the microstructure array parameters, removing excess developer, and drying to obtain a methyl methacrylate based film. Microstructural arrays of methyl acrylate films; (3) On the microstructure array based on methyl methacrylate film obtained in step (2), etch the top electrode layer with the first etching solution, after drying the first etching solution, pass the The second etching solution etches the adhesion layer, and then removes the methyl methacrylate film with acetone to obtain the final microstructure array UHF bulk acoustic wave resonator. 9. A method for capturing and separating particles based on UHF BAW potential well, characterized in that, using the UHF BAW potential well described in any one of claims 1-8 to capture and separate particles device, comprising the steps of: Inject the sample into the inlet of the microfluidic channel, start the microfluidic chip to control the flow of the sample through the microfluidic channel and then flow out from the sample outlet. The size of the microfluidic channel is: 100-300 μm wide and 200nm-100 μm high , the parameters of the sample are: the concentration of the sample is 1×10 ⁷ -1×10 ¹⁰ /ml, the flow rate of the sample is 0.5-5 μl/min, and the particle size of the sample is 100 nm-30 μm; The power adjustment module is activated by the central processing unit, and a power of 100-800 mW is applied to the UHF bulk acoustic wave resonator. The size of the microstructure array on the UHF bulk acoustic wave resonator is: The size of the structural unit is 100nm-50μm, and the depth is 100nm-400nm. The CCD camera can detect that the fluorescent sample particles passing above the UHF bulk acoustic wave resonator are trapped in the microstructural unit, presenting an array distribution state.

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