CN111659478A - Ultrasonic surface standing wave micro-fluidic chip for micro-particle separation and application - Google Patents

Ultrasonic surface standing wave micro-fluidic chip for micro-particle separation and application Download PDF

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CN111659478A
CN111659478A CN202010548474.5A CN202010548474A CN111659478A CN 111659478 A CN111659478 A CN 111659478A CN 202010548474 A CN202010548474 A CN 202010548474A CN 111659478 A CN111659478 A CN 111659478A
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郭霞生
刘子星
章东
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Nanjing University
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Abstract

The invention discloses an ultrasonic surface standing wave micro-fluidic chip for micro-particle separation and application thereof, belonging to the technical field of micro-fluidic analysis. Aiming at the problems that the micro-fluidic chip in the prior art has low particle separation efficiency and wastes a large amount of time and cost because the parameter design of an ultrasonic surface standing wave action area is judged only according to experience when the micro-fluidic chip separates micro-particles, the invention provides a micro-particle separation method based on the ultrasonic surface standing wave micro-fluidic chip, which is used for determining the size of the cross section area of a channel in a micro-fluidic chip micro-flow cavity, the length of an ultrasonic standing wave action area, the inclination angle of an interdigital transducer, the phase change rate of the interdigital transducer and the aperture size of the interdigital transducer, and the liquid flow speed and the input voltage during working to separate the. The chip design is mainly used for separating the micro-particles, the ultrasonic surface standing wave action area is mainly involved, other areas and a focusing method are not limited, the particle separation operation steps and the device preparation difficulty are reduced, and the particle separation efficiency is improved.

Description

Ultrasonic surface standing wave micro-fluidic chip for micro-particle separation and application
Technical Field
The invention relates to the technical field of microfluidic analysis, in particular to an ultrasonic surface standing wave microfluidic chip for micro-particle separation and application thereof.
Background
In recent years, ultrasonic microfluidics has attracted extensive attention due to its characteristics of non-contact, non-labeling and good biocompatibility. The ultrasonic micro-fluidic chip can be used for manipulating, focusing, arranging, separating and the like the micro-particles or cells. The ultrasonic microfluidic chip can be divided into two types of ultrasonic bulk wave-based chip and ultrasonic surface wave-based chip. Unlike bulk wave based methods, surface acoustic wave based methods do not rely on resonance generated by the channel walls, and have flexible design space and strong application potential. Among the surface wave chips, the standing wave type chip has higher acoustic energy density and is widely applied.
One important application of such chips is in the separation, sorting, purification, etc. of micro-scale particles. When the particle separation type chip works, the two interdigital transducers which are oppositely arranged and have parallel finger strips respectively emit ultrasonic surface waves, and standing wave fields are formed on the surface of the substrate. The standing wave leaks into the fluid in the cavity in the region covered by the cavity, and exerts an ultrasonic radiation force on the particles in the fluid. Due to the property difference (such as size, density or sound velocity difference) of different particles, the stress conditions of the particles under the action of the ultrasonic surface standing wave are also obviously different, and finally different types of particles present different motion tracks. Since the fluid in the chamber generally flows continuously, different types of particles form different flow trajectories in the chamber, and finally can enter different outlets at the downstream of the chamber to realize separation.
In order to realize the particle separation process, the microfluidic cavity of the microfluidic chip needs to include an inlet region, a pre-focusing region, an ultrasonic surface standing wave action region, an outlet region and the like. However, most of the particle separation microfluidic chips published or disclosed at present lack theoretical guidance in the aspect of design parameter selection of the ultrasonic surface standing wave action region, and designers generally can achieve the purpose of particle separation only according to empirical judgment and through multiple chip preparation and experimental tests. The method of empirical judgment and multiple experiments is difficult to optimize the efficiency of particle separation, and wastes a large amount of time and cost. Therefore, a scientific design method is necessary for popularizing the micro-particle separation chip based on the ultrasonic surface standing wave microfluidic technology.
In the prior art, various designs are provided for micro-fluidic chip micro-particle separation application, such as a chip without a sheath flow structure; the liquid realizes particle separation in a mode of carrying out vortex at supersonic speed; dividing the fluid channel into a stepped structure; the first electrode, the second electrode, the interdigital electrode and the third electrode are arranged, and the proportion of the acoustic force and the viscous force is changed. There is no suggestion of any particular design of the principles of chamber size, liquid flow rate and sonication zone, which is significantly different from the method of the present invention.
The Chinese invention patent micro-nano particle micro-fluidic chip based on surface acoustic waves (application number: CN201822216199.8) discloses a particle separation chip based on acoustic surface standing waves, wherein an interdigital transducer and a main channel are provided with a preset included angle q. The setting of the angle is random, and is not theoretically optimized according to the dynamics of ultrasonic radiation force, fluid flow velocity and particle motion; in addition, the invention does not relate to the optimization of the size of the cavity and the caliber of the interdigital transducer. Therefore, the device is significantly different from the optimization proposed in the present invention.
Disclosure of Invention
1. Technical problem to be solved
The invention provides an ultrasonic surface standing wave micro-fluidic chip for micro-particle separation and application, aiming at the problems that the parameter design of an ultrasonic surface standing wave action area is judged only according to experience when the micro-fluidic chip separates micro-particles, the particle separation efficiency is not high, and a large amount of time and cost are wasted in the prior art.
2. Technical scheme
The invention provides an ultrasonic surface standing wave microfluidic chip for micro-particle separation and application thereof, and the ultrasonic surface standing wave microfluidic chip is determined for micro-particle separation, so that the particle separation efficiency of the microfluidic chip is improved, and the parameter design conforms to a clear theoretical basis.
In a first aspect, the invention provides an ultrasonic surface standing wave microfluidic chip for micro-particle separation, which comprises a piezoelectric substrate, an interdigital transducer and a micro-flow cavity, wherein the interdigital transducer is attached to the piezoelectric substrate, and the micro-flow cavity is bonded or adhered to the piezoelectric substrate; the inside channel cross-section of micro-fluidic chamber is the rectangle, interdigital transducer includes two relative interdigital transducers, and interdigital transducer preparation is in micro-fluidic chamber channel both sides, and the surface wave that interdigital transducer produced spreads the fluid that gets into the micro-fluidic intracavity along piezoelectric substrate.
The related parameters are determined by the micro-particle separation parameters during the preparation of the micro-fluidic chip, and the separation parameters of the two micro-particles 1 and 2 comprise the radius a of the micro-particle1And a2Density rhop1And ρp2Compressibility ratio κp1And kappap2In (1). Determining the minimum separation distance of the micro-particles according to the radius of the micro-particles to be separated and the target separation purity; and determining the width and height of the section in the microfluidic cavity and the sectional area of the channel in the microfluidic cavity according to the minimum separation distance and the radius.
Furthermore, the micro-fluidic cavity comprises an inlet area, a pre-focusing area, an ultrasonic surface standing wave action area and an outlet area, the pre-focusing area focuses fluid and micro-particles, the ultrasonic surface standing wave action area performs micro-particle separation under the action of the interdigital transducer, and the interdigital transducer is optimized by the micro-fluidic chip which is divided into two types according to the inclination angle and the phase change rate of the interdigital transducer. And optimizing the speed of the input signals and phase differences of the interdigital transducer along with the change of time and the included angle between the finger direction of the interdigital transducer and the microfluidic channel by calculating the parameters of the micro-particles, and determining the length of the ultrasonic surface standing wave action area, the minimum caliber of the interdigital transducer, the shortest distance between the interdigital transducer and a liquid flow channel and the minimum distance between the interdigital transducer.
Furthermore, the chip is of a TaSSAW or PM-SSAW type, the chip is of the TaSSAW type when the phase change rate of the interdigital transducer is zero, the chip is of the PM-SSAW type when the inclination angle of the interdigital transducer is zero, and different formulas are selected to optimize parameters of the interdigital transducer according to different chip types. When the time-varying rates of the input signals and the phase difference of the interdigital transducer are zero or the included angle between the finger direction of the interdigital transducer and the microfluidic channel is zero, the optimization formulas of the interdigital transducer are different, if the chip preparation process limits and the angle is difficult to accurately set, a PM-SSAW type chip optimization mode is selected, and the phase-varying rate parameter optimization process required by the mode is not directly related to the flow rate; if the chip preparation process is mature, the actual separation distance of two types of micro-particles needs to be as large as possible, then a TaSSAW type chip optimization mode is selected, but after the micro-fluidic chip is prepared, the inclination angle of the interdigital transducer cannot be changed.
Furthermore, the chip further comprises a driving circuit, and the driving circuit drives the interdigital transducer to work to generate ultrasonic surface standing waves. The driving circuit comprises a signal source and a power amplifying circuit.
Furthermore, the piezoelectric substrate is made of piezoelectric ceramics, piezoelectric crystals or solid materials with piezoelectric films attached to the surfaces; the material of the micro-channel is glass or polydimethylsiloxane; the interdigital transducer fingers on two sides of the microfluidic cavity channel are parallel, have the same width and length. Such as lead zirconate titanate, piezoelectric crystals such as lithium niobate, piezoelectric films such as zinc oxide, fixing materials such as quartz glass, and the interdigital transducer is produced by a chemical method or a physical method.
The invention mainly aims at the parameters of the ultrasonic action area of the chip, the ultrasonic action parameters are determined by the separation parameters of the micro-particles, and a definite theoretical basis is compounded. The invention is not limited to the design method of the inlet area, the pre-focusing area and the outlet area of the microfluidic cavity, nor is the specific particle pre-focusing method limited, and the design of other areas of the chip can be carried out according to the known method in the field.
In a second aspect, the invention provides a method for separating micro-particles based on an ultrasonic surface standing wave microfluidic chip, which is used for separating the micro-particles, and the method is used for determining the cross-sectional dimension of an inner channel of a microfluidic cavity of the microfluidic chip, the length of an ultrasonic standing wave action area of the microfluidic chip, the inclination angle of an interdigital transducer, the phase change rate of the interdigital transducer and the aperture dimension of the interdigital transducer, and the liquid flow rate and the input voltage of the microfluidic chip during the operation of the microfluidic chip to separate the particles. The particles enter a microfluidic cavity of the microfluidic chip by utilizing a sheath flow technology known in the art, under the action of ultrasonic surface standing waves, different types of particles present different flow tracks and finally enter different outlets at the downstream of the cavity to realize separation.
Furthermore, the flow rate of the liquid for separating the particles is determined by the area of the cross section in the microfluidic of the chip, the required micro-particle separation flux and the volume concentration of the target particles.
Further, the input voltage of the interdigital transducer when separating particles is determined by a typical driving voltage and a voltage conversion coefficient. The method comprises the steps of determining a standing wave boosting amplitude value in a micro-fluid cavity through a typical driving voltage and a voltage conversion coefficient, determining an input voltage peak value of an interdigital transducer by combining an electroacoustic conversion coefficient of a sound wave radiated into a fluid by the interdigital transducer, and further setting the input voltage of the interdigital transducer.
Furthermore, the particles to be separated are focused with the fluid in the pre-focusing area, the viscous layer thickness of the fluid is calculated and verified when the fluid carrying the particles is determined, and the viscous layer thickness of the fluid is determined by the driving frequency of the interdigital transducer. Determining the driving frequency of the interdigital transducer, obtaining the wavelength of the ultrasonic surface wave, determining the thickness of a viscous layer of the fluid carrying micro-particles, and determining that the fluid and the particles are biocompatible and chemically compatible. And comparing the thickness of the viscous layer of the fluid with the radius of one tenth of the micro-particle, and determining that the viscous layer meets the standard.
Furthermore, the time-varying phase difference of two columns of surface acoustic waves in the PM-SSAW type chip is realized by increasing or decreasing the driving frequency of the interdigital transducer.
When the particles are separated, the parameters such as the width and the height of a micro-flow cavity, the length of an ultrasonic surface standing wave action area, the caliber of an interdigital transducer, the minimum distance of an interdigital transducer, the distance between the interdigital transducer and a micro-channel, the inclination angle of the interdigital transducer and the like are determined before the chip is prepared. The minimum separation distance, the liquid flow rate, the input voltage peak value and the phase difference time-varying rate can be determined after the chip preparation is completed, and for the prepared chip, the parameters can be optimized according to the steps in the design method so as to realize better separation effect and separation purity.
3. Advantageous effects
Compared with the prior art, the invention has the advantages that:
the structure and the driving frequency of a chip are determined according to the micro-particle separation parameters, and then the sound pressure amplitude in the micro-channel and the excitation voltage of the chip are determined according to the chip structure and the peripheral circuit design; further determining the flow velocity of the fluid in the microfluidic channel according to parameters such as the micro-particle separation flux; then determining the optimized inclination angle or phase difference change rate of the interdigital transducer according to a theoretical formula; and finally, determining the aperture size of the required interdigital transducer according to theoretical analysis. The chip used in the separation of the microparticles only has requirements on the parameters of the ultrasonic wave action area, and partial design parameters can be determined before the chip is prepared. For example, separation distance Deltay and flow velocity vfThe parameters such as the input voltage peak value and the like can be determined after the chip preparation is finished, and for the prepared chip, the parameters can be optimized according to the steps in the design method, so that the better separation effect and the separation purity are realized, and the preparation efficiency is improved.
The design parameters of the micro-fluidic chip such as the size of the cavity, the working frequency, the width of the ultrasonic action area and the like accord with definite theoretical basis. Compared with the ultrasonic surface standing wave microfluidic chip for particle separation, which is designed according to other experiences, the chip designed by the invention has better separation efficiency and separation purity under similar other conditions. The micro-fluidic design method does not need to limit a specific micro-channel inlet and outlet structure and a pre-focusing method, only has requirements on parameters of an ultrasonic wave action area, does not limit a specific driving circuit structure, and reduces the difficulty of device preparation.
Drawings
FIG. 1 is a process for preparing an ultrasonic surface standing wave microfluidic chip according to the present invention;
fig. 2 is a schematic diagram of a structure of an ultrasonic surface standing wave microfluidic chip in embodiment 1 of the present invention;
FIG. 3 is a particle motion trajectory of an ultrasonic surface standing wave action region in a TaSSAW type chip in example 1 of the present invention;
fig. 4 is a schematic diagram of a structure of an ultrasonic surface standing wave microfluidic chip in embodiment 2 of the present invention;
FIG. 5 shows the particle motion trajectory in the ultrasonic surface standing wave action region of the PM-SSAW type chip in example 2 of the present invention.
Detailed Description
The invention is described in detail below with reference to the drawings and specific examples.
Example 1
The embodiment specifically describes an ultrasonic surface standing wave microfluidic chip which comprises a piezoelectric substrate, an interdigital transducer, a microfluidic cavity and a driving circuit, wherein the interdigital transducer is attached to the piezoelectric substrate and emits ultrasonic surface waves, a standing wave is formed on the surface of the substrate, and ultrasonic radiation force is applied to fluid particles in a cavity of the microfluidic cavity; the micro-flow cavity is bonded or adhered to the piezoelectric substrate, and the section of the inner channel of the micro-flow cavity is rectangular; the driving circuit drives the interdigital transducer to work. The particles enter a microfluidic cavity of the microfluidic chip by utilizing a sheath flow technology known in the art, under the action of ultrasonic surface standing waves, different types of particles present different flow tracks and finally enter different outlets at the downstream of the cavity to realize separation.
The substrate of the micro-fluidic chip is a piezoelectric ceramic chip, a piezoelectric crystal chip or any solid sheet with a piezoelectric film on the surface. Two opposite interdigital transducers I and II are prepared on two sides of the micro-flow cavity, and all the finger strips are parallel, have the same width and have the same length; the generated surface wave propagates along the substrate into the fluid in the cavity. As shown in fig. 2 to 3, the present example selects the tassaww type chip as the microfluidic chip.
The microfluidic chip separates Polystyrene (PS) microspheres with the radius of 3 μm and 5 μm. The polystyrene microsphere is a high molecular polymer, and the monodisperse polystyrene microsphere has the characteristics of uniform particle size distribution, high mechanical strength, large specific surface area, good solvent resistance and the like. The separation purity d >0.95 and the particle flux P of 100/s are required.
According to the parameters of the particles to be separated, the parameters of the microfluidic chip such as the size of the cavity of the microfluidic cavity of the chip, the flow velocity of the particle fluid, the width of an ultrasonic action area and the like are calculated, and the parameters of the chip and the separation parameters of the microparticles are confirmed. The preparation process of the microfluidic chip for separating particles and the parameter flow for separating the particles are shown in figure 1.
Firstly, determining the structural composition of a chip and the separation parameters of the chip to two types of micro-particles:
a128-degree Y-tangential lithium niobate crystal sheet with the thickness of 0.5mm is selected to prepare a piezoelectric substrate of the microfluidic chip, and PDMS is selected as a material of a channel wall of a microfluidic cavity of the chip. The microparticle pre-focusing is performed by using the sheath flow technique known in the art, as shown in fig. 2, the number of inlets is three, the second inlet in the middle is the particle inlet, the first inlet and the third inlet on both sides are the sheath flow inlets, and the number of outlets is two. The microfluidic chip is a TaSSAW type chip, and the interdigital transducer forms an angle theta with the microfluidic cavity.
Secondly, calculating the size of the cavity of the micro-flow cavity according to the target separation purity:
the target separation purity d was 0.95, and the minimum separation distance Δ y was calculated to be not less than 2 × (a)1+a2) × tan (π d/2), substituting the radii a of the two particles to be separated13 μm and a2The separation distance Δ y needs to be larger than 203 μm, 5 μm. Calculating the width W of the inner section of the micro-flow cavity to be more than or equal to 2 delta y and the height H of the inner section of the micro-flow cavity to be more than or equal to 5 (a)1+a2) In this embodiment, the cross-sectional width W of the microfluidic cavity is 1000 μm and the height H is 80 μm.
Then determining the working frequency of the chip and the liquid flow parameters:
selecting the driving frequency f of the interdigital transducer according to the sizes of the two particles, wherein f is 20MHz, and calculating the wavelength lambda of the corresponding surface acoustic wave according to the driving frequency fs,λs=cs/f,csFor the surface acoustic wave propagation velocity in the substrate, the substrate material used in this example is lithium niobate, which has a surface acoustic wave propagation velocity of approximately 3500m/s to 3700m/s, in relation to the specified substrate material of the microfluidic chip. The corresponding surface acoustic wave wavelength is about lambdasAbout 200 μm, the wavelength λ of the surface wavesSatisfies the condition of not less than 10a1Is not less than 10a2The requirements of (1).
Depending on the size and nature of the particles and the frequency of the interdigital transducer driving, this example selects water as the fluid carrying the polystyrene microspheres, the viscous layer thickness of which is (η/pi ρ)0f)1/2Where η is the dynamic viscosity coefficient of water, ρ0Is the density of water. Calculated to be approximately equal to 0.12 mu m, which satisfies the condition that the diameter is less than 0.1a1Also less than 0.1a2100 particles per second and a target particle concentration n (-1 × 10) in the microfluidic chamber, depending on the desired flux of separated particles P12One/cubic meter), determining the fluid flow velocity v in the microfluidic cavityfP/(n × S) ≈ 1.5mm/S, wherein S is the sectional area in the micro-flow cavity, and S W × H0.08 mm2
Then, calculating the cavity standing wave boosting amplitude required by particle separation:
calculating parameter psi of polystyrene microsphere with two radii1And Ψ2,Ψi=Φiai 2(i ═ 1,2) where Φ isiAcoustic contrast factor for particle i, Φi=f1i/3+Re(f2i)(2c0 2-cs 2)/2cs 2,c0Is the speed of sound in the fluid. f. of1iIs the acoustic monopole scattering coefficient, f, of the particle i2iIs the acoustic dipole scattering coefficient, f, of the particle i1i=(κpi0)/κpi,f2i=2(ρpif)/(2ρpi0),ρpiIs the density of the particles, p0Is the density of the fluid, κpiIs the compressibility of the particle, κ0Is the compressible rate of the fluid.
The parameter psi of the microspheres with a radius of 3 μm1=1.2×10-12m2Parameter psi of microspheres with radius of 5 μm2=3.4×10-12m2The electroacoustic conversion coefficient ζ was 5.66 × 10 according to the previous measurement in the same chip5Pa/V, drive power supplied by typical peripheral circuitsPressure range V00.5-50V, and the sound pressure amplitude p of standing wave in the micro-flow cavity0=ζV0≈200kPa。
Further utilizing a theoretical formula to optimize parameters of the interdigital transducer, and calculating the minimum caliber of the interdigital transducer:
the micro-fluidic chip is a TaSSAW type chip, the angle theta can be accurately set, and the actual separation distance of two types of particles is as large as possible when the parameters of the device are optimized. Standing ultrasonic surface waves with a wavefront at an angle θ to the direction of the liquid stream are generated by placing an interdigital transducer tilted with respect to the microfluidic chamber. Calculating the angle between the interdigital transducer and the micro-flow cavity according to a formula, namely the angle theta between the wave front of the generated ultrasonic surface wave and the liquid flow direction,
Figure BDA0002541590050000061
wherein k isy=2π/λsFor the surface acoustic wave number, θ ≈ 14 ° is obtained. Then, the minimum caliber L of the interdigital transducer is determined according to the minimum caliber LIDT=Δycosθ/(b1 2-b2 2)1/20.9mm, definition b1=sinθ,b2=kyp0 2Ψ1/(6ηρ0c0 2). Therefore, in the present embodiment, the length L of the selected SAW region is 2mm ≧ LIDT
And finally, determining the preparation parameters of the micro-flow cavity, preparing the chip, setting the flow rate of liquid and the input voltage, and separating particles:
according to the driving frequency f of the interdigital transducer, the width W of the section in the micro-flow cavity, the height H of the section in the micro-flow cavity, the inclination angle theta of the interdigital transducer and the minimum caliber L of the interdigital transducerIDTThe length L of the ultrasonic surface wave action area of the micro-flow cavity, the finger strip width of the interdigital transducer, and the distance d between the interdigital transducer and the micro-flow cavityICAnd minimum distance d between interdigital transducersIIAnd preparing the microfluidic chip according to the equal parameters. Shortest distance d between each interdigital transducer and the flow channelICNot less than lambdas/4, and twoMinimum distance d between interdigital transducersIIIs λsInteger multiple of/4, finger width being acoustic surface wave wavelength lambdasOne fourth of (a).
And measuring the electroacoustic conversion coefficient based on a known method to obtain an input voltage. According to p0And the actual electroacoustic conversion coefficient ζ of the acoustic wave radiated by the interdigital transducer j into the fluidj(j ═ I, II, the electroacoustic transfer coefficient can be determined experimentally according to a known method) to determine the peak value V of the input voltagep,j=p0j. Setting the fluid flow velocity vf1.5mm/s, the input voltages of the interdigital transducers are respectively set to
Figure BDA0002541590050000071
And
Figure BDA0002541590050000072
wherein t is a time period in which,
Figure BDA0002541590050000073
and separating the polystyrene microspheres by using the device for any phase value.
The movement locus of the particles after being separated by the microfluidic chip is shown in fig. 3, the x axis shown in fig. 3 is the movement distance of the particles, the y axis is the separation distance of two types of particles, and the final actual separation distance of the two types of microsphere particles in the embodiment is 452 μm and the separation purity is 97.4% which is better than the preset separation distance index 203 μm.
The microfluidic chip only has requirements on parameters of an ultrasonic action area, does not limit an inlet and an outlet of a microfluidic cavity, does not limit a specific particle pre-focusing method, does not limit a specific driving circuit structure, and reduces the difficulty of device preparation. Before the chip is prepared, some design parameters, such as separation distance delta y and flow speed v, can be determinedfAnd the input voltage peak value and other parameters are optimized, and the preparation efficiency is improved.
Example 2
This example is substantially the same as example 1, except that it separates Polystyrene (PS) microspheres with radii of 3 μm and 3.8 μm, and requires a separation purity d >0.95, a particle flux P of 100 particles/sec, and the microfluidic chip of this example is a PM-SSAW type chip.
And calculating the cavity size, the particle fluid flow rate and the ultrasonic action area width of the micro-flow cavity of the chip according to the parameters of the particles to be separated, manufacturing the chip and separating micro-particles. The method comprises the following specific steps:
firstly, determining the structural composition of a chip and the separation parameters of the chip to two types of micro-particles:
a128-degree Y-tangential lithium niobate crystal sheet with the thickness of 0.5mm is selected to prepare a piezoelectric substrate of the microfluidic chip, and PDMS is selected as a material of a channel wall of a microfluidic cavity of the chip. The microparticle pre-focusing is performed by using a sheath flow technique known in the art, and as shown in fig. 4, the number of inlets is three, the second inlet in the middle is a particle inlet, the first inlet and the third inlet on both sides are sheath inlets, and the number of outlets is two. The microfluidic chip is a PM-SSAW type chip, and the interdigital transducer is parallel to the microfluidic cavity.
Secondly, calculating the size of the cavity of the micro-flow cavity according to the target separation purity:
according to the target separation purity d is 0.95, the radius a of two kinds of particles to be separated13 μm and a2Calculated separation distance Δ y ≧ 2 × (a) at 3.8 μm1+a2) × tan (pi d/2), the separation distance delta y is required to be larger than 173 mu m, the width W of the inner section of the micro-flow cavity is calculated to be larger than or equal to 2 delta y according to the minimum separation distance, and the height H of the inner section of the micro-flow cavity is larger than or equal to 5 (a)1+a2) In this embodiment, the width W of the cross section in the microfluidic cavity is 600 μm and the height H is 80 μm.
Then determining the working frequency of the chip and the liquid flow parameters:
selecting the driving frequency f of the interdigital transducer according to the sizes of the two particles, wherein f is 13.4MHz, and calculating the wavelength lambda of the corresponding surface acoustic waves,λs=cs/f, in this case cs4000 m/s. The corresponding surface acoustic wave wavelength is about lambdasAbout 300 μm, the wavelength λ of the surface wavesSatisfies the condition of not less than 10a1Is not less than 10a2The requirements of (1).
According to the particlesThe size, nature and driving frequency of the interdigital transducer, water is selected as the fluid for bearing the polystyrene microspheres, and the thickness of the viscous layer of the water is (η/pi rho)0f)1/20.17 μm, where η is the dynamic viscosity coefficient of water, ρ0Is the density of water. Satisfies both less than 0.1a1Also less than 0.1a2100 particles per second and a target particle concentration n (-1 × 10) in the microfluidic chamber, depending on the desired flux of separated particles P12One/cubic meter), determining the fluid flow velocity v in the microfluidic cavityfP/(n × S) ≈ 2mm/S, wherein S is the sectional area in the micro-flow cavity, and S W × H0.048 mm2
Then, calculating the cavity standing wave boosting amplitude required by particle separation:
calculating parameter psi of polystyrene microsphere with two radii1And Ψ2。Ψi=Φiai 2(i ═ 1,2) where Φ isiAcoustic contrast factor for particle i, Φi=f1i/3+Re(f2i)(2c0 2-cs 2)/2cs 2,c0At the speed of sound in the fluid, f1iIs the acoustic monopole scattering coefficient, f, of the particle i2iIs the acoustic dipole scattering coefficient, f, of the particle i1i=(κpi0)/κpi,f2i=2(ρpif)/(2ρpi0),ρpiIs the density of the particles, p0Is the density of the fluid, κpiIs the compressibility of the particle, κ0Is the compressible rate of the fluid.
The parameter psi of the microspheres with a radius of 3 μm1=1.2×10-12m2Parameter psi of microspheres with radius of 3.8 μm2=2.0×10-12m2The electroacoustic conversion coefficient ζ was 5.66 × 10 according to the previous measurement in the same chip5Pa/V, the range of drive voltages V provided by typical peripheral circuits00.5-50V, and the sound pressure amplitude p of standing wave in the micro-flow cavity0=ζV0≈340kPa。
Further utilizing a theoretical formula to optimize parameters of the interdigital transducer and calculating the minimum caliber of the interdigital transducer;
the micro-fluidic chip is a PM-SSAW type chip, and two input signals are adjusted during parameter optimization design, so that the phase difference of the two input signals changes along with time, and the time-varying rate is s. Calculating the phase difference time-varying rate of the input signals of the two interdigital transducers as s according to a formula,
Figure BDA0002541590050000081
wherein k isy=2π/λsFor surface acoustic wave number, s is obtained to be approximately equal to 17.7s-1Optimization process and flow velocity v of s parameter required by PM-SSAW chipfAre not directly related. Then, the minimum caliber L of the interdigital transducer is determined according to the minimum caliber LIDT=Δycosθ/(b1 2-b2 2)1/21.1mm, definition b1=s/(2kyvf),b2=kyp0 2Ψ1/(6ηρ0c0 2). In a PM-SSAW type chip, cos theta is 1, and the length L of an ultrasonic surface wave action region of a micro-flow cavity is not to bear the caliber L of an interdigital transducerIDTSelecting the length L of the ultrasonic surface wave action area to be 2mm ≥ LIDT
Finally, determining the preparation parameters of the micro-flow cavity, preparing a chip, setting the flow speed and the input voltage, and separating particles;
according to the driving frequency f of the interdigital transducer, the width W of the section in the micro-flow cavity, the height H of the section in the micro-flow cavity, the inclination angle theta of the interdigital transducer and the minimum caliber L of the interdigital transducerIDTThe length L of the ultrasonic surface wave action area of the micro-flow cavity, the finger strip width of the interdigital transducer, and the distance d between the interdigital transducer and the micro-flow cavityICAnd minimum distance d between interdigital transducersIIAnd preparing the microfluidic chip according to the equal parameters. Shortest distance d between each interdigital transducer and the flow channelICNot less than lambdas/4, and the minimum distance d between two interdigital transducersIIIs λsInteger multiple of/4, finger width being acoustic surface wave wavelength lambdasOne fourth of (a).
And measuring the electroacoustic conversion coefficient based on a known method to obtain an input voltage. The time-varying phase difference of two rows of surface acoustic waves in a PM-SSAW type chip can be realized by increasing or decreasing the driving frequency of one interdigital transducer by delta f, and the time-varying speed s of the phase difference is 2 pi delta f. After setting the fluid flow rate to 2mm/s, the input voltages of the interdigital transducers are set to
Figure BDA0002541590050000091
And
Figure BDA0002541590050000092
wherein t is a time period in which,
Figure BDA0002541590050000093
and separating the polystyrene microspheres by using the device for any phase value.
The movement locus of the particles after being separated by the microfluidic chip is shown in fig. 5, and the final actual separation distance of the two microsphere particles in the embodiment is 274 μm and the separation purity is 96.8% which is better than the preset design index 173 μm. In this embodiment, part of the design parameters, such as separation distance Δ y and flow velocity v, can be determined before chip preparationfThe peak value of the input voltage, the phase difference time varying rate s in the PM-SSAW type chip and other parameters are optimized, and the preparation efficiency is improved.
The invention and its embodiments have been described above schematically, without limitation, and the invention can be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The representation in the drawings is only one of the embodiments of the invention, the actual construction is not limited thereto, and any reference signs in the claims shall not limit the claims concerned. Therefore, if a person skilled in the art receives the teachings of the present invention, without inventive design, a similar structure and an embodiment to the above technical solution should be covered by the protection scope of the present patent. Furthermore, the word "comprising" does not exclude other elements or steps, and the word "a" or "an" preceding an element does not exclude the presence of a plurality of such elements. Several of the elements recited in the product claims may also be implemented by one element in software or hardware. The terms first, second, etc. are used to denote names, but not any particular order.

Claims (10)

1. An ultrasonic surface standing wave micro-fluidic chip for micro-particle separation is characterized by comprising a piezoelectric substrate, an interdigital transducer and a micro-fluidic cavity, wherein the interdigital transducer is attached to the piezoelectric substrate, and the micro-fluidic cavity is bonded or adhered to the piezoelectric substrate; the inside channel cross-section of micro-fluidic chamber is the rectangle, interdigital transducer includes two relative interdigital transducers, and interdigital transducer preparation is in micro-fluidic chamber channel both sides, and the surface wave that interdigital transducer produced spreads the fluid that gets into the micro-fluidic intracavity along piezoelectric substrate.
2. The ultrasonic surface standing wave microfluidic chip for micro-particle separation of claim 1, wherein the microfluidic cavity comprises an inlet region, a pre-focusing region, an ultrasonic surface standing wave action region and an outlet region, the pre-focusing region focuses fluid and micro-particles, the ultrasonic surface standing wave action region performs micro-particle separation under the action of the interdigital transducer, and the interdigital transducer is optimized according to the two types of microfluidic chips based on the tilt angle and the phase change rate of the interdigital transducer.
3. The ultrasonic surface standing wave microfluidic chip for separating the micro-particles as claimed in claim 2, wherein the chip is of a TaSSAW or PM-SSAW type, the chip when the phase change rate of the interdigital transducer is zero is of the TaSSAW type, the chip when the tilt angle of the interdigital transducer is zero is of the PM-SSAW type, and different formulas are selected according to different chip types to optimize parameters of the interdigital transducer.
4. The ultrasonic surface standing wave microfluidic chip for separating fine particles according to claim 1, wherein the chip further comprises a driving circuit, and the driving circuit drives the interdigital transducer to operate to generate the ultrasonic surface standing wave.
5. The ultrasonic surface standing wave microfluidic chip for micro-particle separation according to claim 1, wherein the piezoelectric substrate is made of piezoelectric ceramics, piezoelectric crystals or solid materials with piezoelectric films attached on the surfaces; the material of the micro-channel is glass or polydimethylsiloxane; the interdigital transducer fingers on two sides of the microfluidic cavity channel are parallel, have the same width and length.
6. A method for separating micro-particles based on an ultrasonic surface standing wave micro-fluidic chip is characterized in that the ultrasonic surface standing wave micro-fluidic chip for separating the micro-particles is used according to any one of claims 1 to 5, the cross section size of a channel in a micro-fluidic cavity of the micro-fluidic chip, the length of an ultrasonic standing wave action area of the micro-fluidic chip, the inclination angle of an interdigital transducer, the phase change rate of the interdigital transducer and the aperture size of the interdigital transducer are determined, and the particle separation is carried out by the liquid flow speed and the input voltage of the micro-fluidic chip when the micro-fluidic chip works.
7. The method for separating the micro-particles based on the ultrasonic surface standing wave microfluidic chip as claimed in claim 6, wherein the liquid flow rate of the particles to be separated is determined by the area of the microfluidic internal cross section of the chip, the required micro-particle separation flux and the volume concentration of the target particles.
8. The method for separating the micro-particles based on the ultrasonic surface standing wave microfluidic chip as claimed in claim 6, wherein the input voltage of the interdigital transducer when separating the particles is determined by a typical driving voltage and a voltage conversion coefficient.
9. The method for separating the micro-particles based on the ultrasonic surface standing wave microfluidic chip as claimed in claim 6, wherein the particles to be separated are focused with the fluid in the pre-focusing area, and the thickness of the viscous layer of the fluid is determined and verified when the fluid carrying the particles is determined, and the thickness of the viscous layer of the fluid is determined by the driving frequency of the interdigital transducer.
10. The method for separating the micro-particles based on the ultrasonic surface standing wave microfluidic chip as claimed in claim 8, wherein the time-varying phase difference of two rows of surface acoustic waves in the PM-SSAW type chip is realized by increasing or decreasing the driving frequency of an interdigital transducer.
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