WO2023108473A1 - 基于声人工结构的微粒分选方法 - Google Patents

基于声人工结构的微粒分选方法 Download PDF

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WO2023108473A1
WO2023108473A1 PCT/CN2021/138307 CN2021138307W WO2023108473A1 WO 2023108473 A1 WO2023108473 A1 WO 2023108473A1 CN 2021138307 W CN2021138307 W CN 2021138307W WO 2023108473 A1 WO2023108473 A1 WO 2023108473A1
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acoustic
artificial structure
particles
radiation force
sample
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PCT/CN2021/138307
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English (en)
French (fr)
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郑海荣
黄来鑫
李飞
蔡飞燕
孟龙
牛丽丽
周伟
林争荣
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中国科学院深圳先进技术研究院
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Priority to PCT/CN2021/138307 priority Critical patent/WO2023108473A1/zh
Publication of WO2023108473A1 publication Critical patent/WO2023108473A1/zh

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B07—SEPARATING SOLIDS FROM SOLIDS; SORTING
    • B07C—POSTAL SORTING; SORTING INDIVIDUAL ARTICLES, OR BULK MATERIAL FIT TO BE SORTED PIECE-MEAL, e.g. BY PICKING
    • B07C5/00—Sorting according to a characteristic or feature of the articles or material being sorted, e.g. by control effected by devices which detect or measure such characteristic or feature; Sorting by manually actuated devices, e.g. switches
    • B07C5/34—Sorting according to other particular properties
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/02—Investigating particle size or size distribution

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  • the present invention relates to the field of acoustic manipulation and microfluid technology, in particular to a particle sorting method, device, equipment and storage medium based on an acoustic artificial structure.
  • microfluidic sorting technology has become a mainstream solution. Its notable advantage is that it can integrate technologies such as sound, electricity, magnetism, light and force with microfluidics, and has the characteristics of high precision, miniaturization and easy manipulation. These methods all rely on the force of the physical field on the particles. In the case of flow, different particles receive different forces, resulting in different motion trajectories, so as to achieve the purpose of separation. Compared with other physical fields, acoustic sorting has the advantages of no contact, no label and high biocompatibility.
  • the particle pairs in the sound field will have a scattering effect on the sound wave, resulting in momentum exchange between the sound propagation medium and the particles, resulting in a steady-state force with a non-zero time average, called the acoustic radiation force.
  • the acoustic radiation force is affected by parameters such as particle size, density and compressibility, so the acoustic radiation force experienced by different particles is usually different, which provides the basis for acoustic separation.
  • the existing acoustic sorting mainly includes body wave sorting and surface wave sorting.
  • Bulk waves usually rely on a piezoelectric transducer attached to one side of a rectangular channel, and a standing wave field propagating in the cavity is formed by reflection from the opposite side wall.
  • a piezoelectric ceramic sheet is pasted on the bottom of the rectangular cavity, so a standing wave field is formed in the vertical direction, which will give the particles a force in the vertical direction.
  • the buffer enters from the top to fill the cavity with liquid, and the sample to be separated flows in from the bottom of the rectangular cavity. Under the action of the acoustic radiation force, the trajectories of the particles are different in the vertical direction, and flow out at different heights of the sample outlets. , to achieve the purpose of sorting.
  • the width of the cavity can be made larger, so it has the characteristics of high throughput.
  • the body wave involves the vibration of the medium inside the entire cavity, higher energy is often required to generate a sufficiently strong radiation force, which is the defect of the body wave.
  • Surface wave devices are mainly composed of piezoelectric crystals and metal interdigitated electrodes covering the surface of the crystals. When an alternating current signal is applied to the electrodes, the piezoelectric crystal vibrates, creating sound waves that travel across the surface.
  • chips that rely on surface waves for sorting use two pairs of interdigitated electrodes, and a standing wave surface wave is formed between the interdigitated electrodes.
  • the slender main channel is buckled on the crystal surface and placed between the electrodes. , the placement direction is perpendicular to the propagation direction of the surface wave.
  • the sample to be separated flows in from the entrance of the main channel, and the sheath flow flows into both sides to make the sample converge on the center line.
  • an embodiment of the present application provides a particle sorting method based on an acoustic artificial structure, the method includes: causing the acoustic artificial structure to resonate through ultrasonic excitation; The acoustic radiation force generated by the sound field captures the sample particles to be separated whose radiation force is greater than the threshold to the acoustic artificial structure; collects the particles flowing out from the flow chamber, and the radiation force of the particles is less than the threshold.
  • the excitation of the acoustic artificial structure to generate resonance through ultrasound includes: generating sound waves through a signal generator, a power amplifier, and an ultrasonic transducer; using the generated sound waves to excite the acoustic artificial structure to generate a resonant sound field.
  • the use of the acoustic radiation force generated by the resonant strong local sound field to capture the sample particles to be separated with a radiation force greater than the threshold to the acoustic artificial structure includes: using the drag force of the incident flow on the particles, the artificial structure The acoustic radiation force of the sound field to the particles and the drag force of the acoustic flow of the artificial structure sound field to the particles separate the sample particles to be separated; the sample particles to be separated whose radiation force is greater than the threshold are captured to the acoustic artificial structure.
  • the top cover of the flow chamber is made of transparent sound-absorbing material.
  • the embodiment of the present application also provides a particle sorting device based on an acoustic artificial structure
  • the device includes: a resonance unit, used to make the acoustic artificial structure resonate through ultrasonic excitation; a separation unit, used to separate the The sample is injected into the flow chamber, and the acoustic radiation force generated by the resonant strong local acoustic field is used to trap the sample particles to be separated whose radiation force is greater than the threshold to the acoustic artificial structure; the collection unit is used to collect the particles flowing out of the flow chamber. The radiation force is less than the threshold.
  • the excitation of the acoustic artificial structure to generate resonance through ultrasound includes: generating sound waves through a signal generator, a power amplifier, and an ultrasonic transducer; using the generated sound waves to excite the acoustic artificial structure to generate a resonant sound field.
  • the use of the acoustic radiation force generated by the resonant strong local sound field to capture the sample particles to be separated with a radiation force greater than the threshold to the acoustic artificial structure includes: using the drag force of the incident flow on the particles, the artificial structure The acoustic radiation force of the sound field to the particles and the drag force of the acoustic flow of the artificial structure sound field to the particles separate the sample particles to be separated; the sample particles to be separated whose radiation force is greater than the threshold are captured to the acoustic artificial structure.
  • the top cover of the flow chamber is made of transparent sound-absorbing material.
  • the embodiment of the present application also provides a computer device, including a memory, a processor, and a computer program stored in the memory and operable on the processor.
  • the processor executes the program, it implements the The method described in any one of the descriptions of the examples.
  • the embodiment of the present application also provides a computer device, a computer-readable storage medium, on which a computer program is stored, and the computer program is used for: when the computer program is executed by a processor, the computer program according to the present application is implemented.
  • a computer device a computer-readable storage medium, on which a computer program is stored, and the computer program is used for: when the computer program is executed by a processor, the computer program according to the present application is implemented.
  • the particle sorting method based on the acoustic artificial structure provided by the present invention does not need to use sheath flow or other methods to focus the sample, so the channel can be wider and the processing throughput is higher; compared with the surface wave device, the device used in this solution has a low manufacturing cost .
  • the artificial structure can be replaced freely, which is flexible and convenient.
  • Fig. 1 shows a schematic flow diagram of a particle sorting method based on an acoustic artificial structure provided by an embodiment of the present application
  • Fig. 2 shows an exemplary structural block diagram of a particle sorting device 200 based on an acoustic artificial structure according to an embodiment of the present application
  • FIG. 3 shows a schematic structural diagram of a computer system suitable for implementing a terminal device according to an embodiment of the present application
  • Fig. 4 shows the schematic diagram of the sorting system provided by the embodiment of the present application.
  • Figure 5 shows a schematic diagram of the sorting process provided by the embodiment of the present application.
  • Figure 6 shows a schematic diagram of the transmission spectrum of the artificial structure provided by the embodiment of the present application.
  • Figure 7 is a schematic diagram of the distribution of acoustic radiation force received by Escherichia coli
  • Figure 8 is a schematic diagram of the trajectory of particles of different sizes
  • Fig. 9 is a schematic diagram of the relationship between the capture efficiency of particle A and particle B and the incident sound pressure at different flow rates
  • Figure 10 is a schematic diagram of cascade sorting.
  • first and second are used for descriptive purposes only, and cannot be interpreted as indicating or implying relative importance or implicitly specifying the quantity of indicated technical features.
  • the features defined as “first” and “second” may explicitly or implicitly include at least one of these features.
  • “plurality” means at least two, such as two, three, etc., unless otherwise specifically defined.
  • the first feature may be in direct contact with the first feature or the first and second feature may be in direct contact with the second feature through an intermediary. touch.
  • “above”, “above” and “above” the first feature on the second feature may mean that the first feature is directly above or obliquely above the second feature, or simply means that the first feature is higher in level than the second feature.
  • “Below”, “beneath” and “beneath” the first feature may mean that the first feature is directly below or obliquely below the second feature, or simply means that the first feature is less horizontally than the second feature.
  • FIG. 1 shows a schematic flowchart of a particle sorting method based on an acoustic artificial structure provided in an embodiment of the present application.
  • the method includes:
  • Step 110 making the acoustic artificial structure resonate through ultrasonic excitation
  • step 120 the sample to be separated is injected into the flow chamber, and the acoustic radiation force generated by the resonant strong local sound field is used to capture the sample particles to be separated whose radiation force is greater than the threshold to the acoustic artificial structure;
  • Step 130 collecting particles effluent from the flow chamber, the particles having a radiation force less than a threshold.
  • the channel can be wider and the processing throughput is higher; compared with the surface wave device, the device used in this solution has a lower manufacturing cost.
  • the artificial structure can be replaced freely, which is flexible and convenient.
  • exciting the acoustic artificial structure to generate resonance through ultrasound includes: generating sound waves through a signal generator, a power amplifier, and an ultrasonic transducer; using the generated sound waves to excite the acoustic artificial structure to generate a resonant sound field.
  • the acoustic radiation force generated by the resonant strong local acoustic field is used to capture the sample particles to be separated whose radiation force is greater than the threshold to the acoustic artificial structure, including: using the drag force of the incident flow on the particles, artificial The acoustic radiation force of the structural acoustic field on the particles and the drag force of the acoustic flow of the artificial structure acoustic field on the particles separate the sample particles to be separated; the sample particles to be separated whose radiation force is greater than the threshold are captured to the acoustic artificial structure.
  • the top cover of the flow chamber of the present application is a transparent sound-absorbing material.
  • FIG. 4 shows the sorting system of the present invention, including an ultrasonic excitation module, a sample delivery and collection module, and a sorting module.
  • the ultrasonic excitation module includes a signal generator, a power amplifier and an ultrasonic transducer, and the acoustic waves generated by the transducer are used to excite the acoustic artificial structure to generate a resonant sound field;
  • the sample delivery and collection module includes a syringe pump and a collection device, a syringe pump and a flow chamber, The collection devices are connected by hoses.
  • the sorting module After injecting the sample into the flow chamber by the syringe pump, part of the separated samples stay on the surface of the acoustic artificial structure and part of the separated sample enters the collection device under the action of the acoustic radiation force; the sorting module includes the acoustic artificial structure and the flow chamber, are the areas where the sorting takes place, and the process is shown in Figure 5.
  • Figure 5 is a schematic diagram of the sorting process.
  • t is the plate thickness
  • a is the period of the structure
  • w is the width of the grid
  • h is the height of the grid.
  • Fig. 6 is the transmission spectrum of the artificial structure of the above-mentioned size, and its resonant frequency is 4 MHz.
  • the flow chamber adopted in this patent has an outlet and an inlet, and the incident flow is pumped in from the inlet by a microfluidic pump and flows out from the outlet.
  • the relative magnitudes of the three forces are adjusted, so as to realize the High-throughput sorting of particles of different sizes.
  • the top cover of the flow chamber in this patent is made of a transparent sound-absorbing material such as PDMS, which can effectively absorb incident waves and prevent boundary reflections from affecting the sound field of artificial structures.
  • the flow drag force and acoustic radiation force produced by the superimposed flow field of incident flow and acoustic flow on particles in the flow chamber are calculated by using numerical methods, ignoring gravity and buoyancy.
  • the governing equation of the sound field is
  • ⁇ 0 and ⁇ 1 are the density and first-order perturbation of water
  • p 1 and u 1 are the first-order sound pressure and velocity, respectively
  • ⁇ and ⁇ are the bulk viscosity and shear viscosity of water
  • k th is the thermal conductivity of water
  • T is the temperature.
  • the diameter of the sorted particles is usually much smaller than this wavelength, and the scattering effect on the sound field is very small, so we use Gorkov's theory to calculate the acoustic radiation force F R that the particles with a radius of r experience in the sound field
  • ⁇ > is the time average operator.
  • ⁇ p and c p are the particle density and the longitudinal wave velocity.
  • u f is the velocity of the flow field
  • p is the pressure of the flow field
  • F is the body force.
  • the sound field further induces a steady-state flow of the liquid, known as acoustic streaming.
  • acoustic streaming For smaller particles, several works have shown that acoustic flow, rather than radiation forces, dominate particle motion. In order to consider this effect, this paper calculates the second-order acoustic flow effect from the first-order sound field, and adds the body force term to the flow field
  • e 1 and e 2 Define e 1 and e 2 as the proportion of small particles in the outflow particles and the proportion of large particles in the particles trapped on the surface of the acoustic artificial structure, respectively.
  • the most ideal situation is that e 1 and e 2 are both 1, and complete separation is achieved at this time, but due to the influence of laminar flow, the initial velocity and position of different particles are different, which is difficult to achieve.
  • FIG. 10 By combining phononic crystal plates with different resonance frequencies, a cascade sorting of various particles can be performed, as shown in Figure 10.
  • This device can also be used to sort cells and microvesicles or vesicle-containing bacteria.
  • the principle is that the acoustic contrast factors of the two are quite different, and the radiation force they receive is very different.
  • FIG. 2 shows an exemplary structural block diagram of an acoustic artificial structure-based particle sorting apparatus 200 according to an embodiment of the present application.
  • the device includes:
  • a resonance unit 210 configured to cause the acoustic artificial structure to resonate through ultrasonic excitation
  • the separation unit 220 is used to inject the sample to be separated into the flow chamber, and use the acoustic radiation force generated by the resonant strong local acoustic field to capture the sample particles to be separated with a radiation force greater than the threshold value to the acoustic artificial structure;
  • the collecting unit 230 is used for collecting particles flowing out from the flow chamber, and the radiation force of the particles is less than a threshold.
  • the units or modules recorded in the device 200 correspond to the steps in the method described with reference to FIG. 1 . Therefore, the operations and features described above for the method are also applicable to the device 200 and the units contained therein, and will not be repeated here.
  • the apparatus 200 may be pre-implemented in the browser of the electronic device or other security applications, and may also be loaded into the browser of the electronic device or its security applications by downloading or other means.
  • the corresponding units in the apparatus 200 may cooperate with the units in the electronic device to implement the solutions of the embodiments of the present application.
  • FIG. 3 shows a schematic structural diagram of a computer system 300 suitable for implementing a terminal device or a server according to an embodiment of the present application.
  • a computer system 300 includes a central processing unit (CPU) 301 that can operate according to a program stored in a read-only memory (ROM) 302 or a program loaded from a storage section 308 into a random-access memory (RAM) 303 Instead, various appropriate actions and processes are performed.
  • ROM read-only memory
  • RAM random-access memory
  • various programs and data necessary for the operation of the system 300 are also stored.
  • the CPU 301 , ROM 302 , and RAM 303 are connected to each other via a bus 304 .
  • An input/output (I/O) interface 305 is also connected to the bus 304 .
  • the following components are connected to the I/O interface 305: an input section 306 including a keyboard, a mouse, etc.; an output section 307 including a cathode ray tube (CRT), a liquid crystal display (LCD), etc., and a speaker; a storage section 308 including a hard disk, etc. and a communication section 309 including a network interface card such as a LAN card, a modem, or the like.
  • the communication section 309 performs communication processing via a network such as the Internet.
  • a drive 310 is also connected to the I/O interface 305 as needed.
  • a removable medium 311, such as a magnetic disk, an optical disk, a magneto-optical disk, a semiconductor memory, etc., is mounted on the drive 310 as necessary so that a computer program read therefrom is installed into the storage section 308 as necessary.
  • the process described above with reference to FIG. 1 may be implemented as a computer software program.
  • embodiments of the present disclosure include a method for particle sorting based on acoustic artificial structures, comprising a computer program tangibly embodied on a machine-readable medium, the computer program comprising program code for performing the method of FIG. 1 .
  • the computer program may be downloaded and installed from a network via communication portion 309 and/or installed from removable media 311 .
  • each block in a flowchart or block diagram may represent a module, program segment, or part of code that includes one or more logical functions for implementing specified executable instructions.
  • the functions noted in the block may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or they may sometimes be executed in the reverse order, depending upon the functionality involved.
  • each block of the block diagrams and/or flowchart illustrations, and combinations of blocks in the block diagrams and/or flowchart illustrations can be implemented by a dedicated hardware-based system that performs the specified functions or operations , or may be implemented by a combination of dedicated hardware and computer instructions.
  • the units or modules involved in the embodiments described in the present application may be implemented by means of software or by means of hardware.
  • the described units or modules may also be set in a processor.
  • a processor includes a first sub-region generating unit, a second sub-region generating unit, and a display region generating unit.
  • the names of these units or modules do not constitute limitations on the units or modules themselves in some cases, for example, the display area generation unit can also be described as "used to generate The cell of the display area of the text".
  • the present application also provides a computer-readable storage medium, which may be the computer-readable storage medium contained in the aforementioned devices in the above-mentioned embodiments; computer-readable storage media stored in the device.
  • the computer-readable storage medium stores one or more programs, and the aforementioned programs are used by one or more processors to execute the text generation method applied to transparent window envelopes described in this application.

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Abstract

本申请公开了一种基于声人工结构的微粒分选方法、装置、设备及其存储介质，该方法包括：通过超声激励使得声人工结构发生共振；将待分离样品注入到流动室，利用共振强局域声场产生的声辐射力将辐射力大于阈值的待分离样品粒子捕获至声人工结构；收集从流动室中的流出的粒子，该粒子的辐射力小于阈值。本申请提供的上述方案，无需使用鞘流或其它方式聚焦样品，因此通道可以更宽，处理通量更高；相对于表面波器件，本方案使用的器件制作成本低。人工结构可以自由更换，灵活方便。

Description

基于声人工结构的微粒分选方法 技术领域
本发明涉及声操控、微流体技术领域，具体涉及一种基于声人工结构的微粒分选方法、装置、设备及其存储介质。
背景技术
从混合样品中分离特定颗粒或细胞对于许多研究是重要的，包括生物医学研究，化学分析和水处理等。微流控分选技术经过一定时间的发展，已经成为一种主流的解决方案。其显著优点是能够将声、电、磁、光和力等技术与微流体集成，具备高精度、小型化和易操控等特点。这些方法都依赖于物理场对粒子的力的作用，在流动情况下，不同粒子受到的力不同，产生了不同的运动轨迹，从而达到分离的目的。相比于其他物理场，声分选具备无接触，无标记和高度生物相容性的优点。声场中的微粒对会对声波产生散射效应，导致声传播介质与微粒产生动量交换，产生一种时间平均不为零的稳态力，称为声辐射力。声辐射力受到粒子尺寸、密度和压缩性等参数的影响，因此不同粒子受到的声辐射力通常是不同的，这为声分选提供了基础。现有的声分选主要包括体波分选和表面波分选。
体波通常依靠在矩形通道一侧贴上压电换能器，通过对侧壁面反射形成在腔内传播的驻波场。现有的体波分选装置，在矩形腔的底部贴上压电陶瓷片，因此竖直方向上形成驻波场，会给予粒子竖直方向 的力。缓冲液从顶部进入，使腔内充满液体，待分离样品从矩形腔的底部流入，在声辐射力的作用下粒子的轨迹在竖直方向上产生差异，分别在不同的高度的出样口流出，达到分选的目的。由于是在垂直方向上分选，腔的宽度可以做的较大，因此具有高通量的特点。但由于体波涉及到整个腔体内部介质的振动，因此为了产生足够强的辐射力，往往需要较高的能量，这是体波的缺陷所在。
表面波器件主要由压电晶体和覆盖在晶体表面的金属叉指电极构成。当给电极施加交流电信号时，压电晶体会产生振动，形成在表面传播的声波。现有的方案中依赖表面波进行分选的芯片，使用了两对叉指电极，在叉指电极之间形成了驻波表面波，细长主通道扣置晶体表面，放置在在电极之间，摆放方向与表面波传输方向垂直。待分离样品从主通道入口流入，两侧汇入鞘流使样品汇集在中心线，流过表面波区域时，不同粒子轨迹发生偏移，流入不同通道完成分选。这种方法精度较高也便于观察，但由于是水平方向分选且需要鞘流聚焦，通道不能太高也不能太宽，因此在通量上存在限制。
发明内容
鉴于现有技术中的上述缺陷或不足，期望提供一种基于声人工结构的微粒分选方法、装置、设备及其存储介质。
第一方面，本申请实施例提供了一种基于声人工结构的微粒分选方法，该方法包括：通过超声激励使得声人工结构发生共振；将待分离样品注入到流动室，利用共振强局域声场产生的声辐射力将辐射力大于阈值的待分离样品粒子捕获至声人工结构；收集从流动室中的流出的粒子，该粒子的辐射力小于阈值。
在其中一个实施例中，所述通过超声激励声人工结构发生共振，包括：通过信号发生器、功率放大器以及超声换能器产生声波；利用 产生的声波激发声人工结构发生共振声场。
在其中一个实施例中，所述利用共振强局域声场产生的声辐射力将辐射力大于阈值的待分离样品粒子捕获至声人工结构，包括：利用入射流对颗粒的拖拽力、人工结构声场对颗粒的声辐射力以及人工结构声场的声流对颗粒的拖拽力对待分离样品粒子进行分离；将辐射力大于阈值的待分离样品粒子捕获至声人工结构。
在其中一个实施例中，所述流动室的顶盖为透明吸声材料。
第二方面，本申请实施例还提供了一种基于声人工结构的微粒分选装置，该装置包括：共振单元，用于通过超声激励使得声人工结构发生共振；分离单元，用于将待分离样品注入到流动室，利用共振强局域声场产生的声辐射力将辐射力大于阈值的待分离样品粒子捕获至声人工结构；收集单元，用于收集从流动室中的流出的粒子，该粒子的辐射力小于阈值。
在其中一个实施例中，所述通过超声激励声人工结构发生共振，包括：通过信号发生器、功率放大器以及超声换能器产生声波；利用产生的声波激发声人工结构发生共振声场。
在其中一个实施例中，所述利用共振强局域声场产生的声辐射力将辐射力大于阈值的待分离样品粒子捕获至声人工结构，包括：利用入射流对颗粒的拖拽力、人工结构声场对颗粒的声辐射力以及人工结构声场的声流对颗粒的拖拽力对待分离样品粒子进行分离；将辐射力大于阈值的待分离样品粒子捕获至声人工结构。
在其中一个实施例中，所述流动室的顶盖为透明吸声材料。
第三方面，本申请实施例还提供了一种计算机设备，包括存储器、处理器以及存储在存储器上并可在处理器上运行的计算机程序，所述处理器执行所述程序时实现如本申请实施例描述中任一所述的方法。
第四方面，本申请实施例还提供了一种计算机设备一种计算机可 读存储介质，其上存储有计算机程序，所述计算机程序用于：所述计算机程序被处理器执行时实现如本申请实施例描述中任一所述的方法。
本发明的有益效果：
本发明提供的基于声人工结构的微粒分选方法，无需使用鞘流或其它方式聚焦样品，因此通道可以更宽，处理通量更高；相对于表面波器件，本方案使用的器件制作成本低。人工结构可以自由更换，灵活方便。
附图说明
通过阅读参照以下附图所作的对非限制性实施例所作的详细描述，本申请的其它特征、目的和优点将会变得更明显：
图1示出了本申请实施例提供的基于声人工结构的微粒分选方法的流程示意图；
图2示出了根据本申请一个实施例的基于声人工结构的微粒分选装置200的示例性结构框图；
图3示出了适于用来实现本申请实施例的终端设备的计算机系统的结构示意图；
图4示出了本申请实施例提供的分选系统示意图；
图5示出了本申请实施例提供的分选流程示意图；
图6示出了本申请实施例提供的人工结构的透射谱示意图；
图7为大肠杆菌受到的声辐射力分布示意图；
图8为大小不同的粒子的运动轨迹示意图；
图9为不同流速下粒子A和粒子B的捕获效率与入射声压的关系示意图；
图10为级联式分选示意图。
具体实施方式
为使本发明的上述目的、特征和优点能够更加明显易懂，下面结合附图对本发明的具体实施方式做详细的说明。在下面的描述中阐述了很多具体细节以便于充分理解本发明。但是本发明能够以很多不同于在此描述的其它方式来实施，本领域技术人员可以在不违背本发明内涵的情况下做类似改进，因此本发明不受下面公开的具体实施例的限制。
在本发明的描述中，需要理解的是，术语“中心”、“纵向”、“横向”、“长度”、“宽度”、“厚度”、“上”、“下”、“前”、“后”、“左”、“右”、“竖直”、“水平”、“顶”、“底”、“内”、“外”、“顺时针”、“逆时针”、“轴向”、“径向”、“周向”等指示的方位或位置关系为基于附图所示的方位或位置关系，仅是为了便于描述本发明和简化描述，而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作，因此不能理解为对本发明的限制。
此外，术语“第一”、“第二”仅用于描述目的，而不能理解为指示或暗示相对重要性或者隐含指明所指示的技术特征的数量。由此，限定有“第一”、“第二”的特征可以明示或者隐含地包括至少一个该特征。在本发明的描述中，“多个”的含义是至少两个，例如两个，三个等，除非另有明确具体的限定。
在本发明中，除非另有明确的规定和限定，术语“安装”、“相连”、“连接”、“固定”等术语应做广义理解，例如，可以是固定连接，也可以是可拆卸连接，或成一体；可以是机械连接，也可以是电连接；可以是直接相连，也可以通过中间媒介间接相连，可以是两个元件内部的连通或两个元件的相互作用关系，除非另有明确的限定。对于本领域的普通技术人员而言，可以根据具体情况理解上述术语在本发明 中的具体含义。
在本发明中，除非另有明确的规定和限定，第一特征在第二特征“上”或“下”可以是第一和第二特征直接接触，或第一和第二特征通过中间媒介间接接触。而且，第一特征在第二特征“之上”、“上方”和“上面”可是第一特征在第二特征正上方或斜上方，或仅仅表示第一特征水平高度高于第二特征。第一特征在第二特征“之下”、“下方”和“下面”可以是第一特征在第二特征正下方或斜下方，或仅仅表示第一特征水平高度小于第二特征。
需要说明的是，当元件被称为“固定于”或“设置于”另一个元件，它可以直接在另一个元件上或者也可以存在居中的元件。当一个元件被认为是“连接”另一个元件，它可以是直接连接到另一个元件或者可能同时存在居中元件。本文所使用的术语“垂直的”、“水平的”、“上”、“下”、“左”、“右”以及类似的表述只是为了说明的目的，并不表示是唯一的实施方式。
请参考图1，图1示出了本申请实施例提供的基于声人工结构的微粒分选方法的流程示意图。
如图1所示，该方法包括：
步骤110，通过超声激励使得声人工结构发生共振；
步骤120，将待分离样品注入到流动室，利用共振强局域声场产生的声辐射力将辐射力大于阈值的待分离样品粒子捕获至声人工结构；
步骤130，收集从流动室中的流出的粒子，该粒子的辐射力小于阈值。
采用上述技术方案，无需使用鞘流或其它方式聚焦样品，因此通道可以更宽，处理通量更高；相对于表面波器件，本方案使用的器件制作成本低。人工结构可以自由更换，灵活方便。
在一些实施例中，本申请中的通过超声激励声人工结构发生共振， 包括：通过信号发生器、功率放大器以及超声换能器产生声波；利用产生的声波激发声人工结构发生共振声场。
在一些实施例中，本申请中的利用共振强局域声场产生的声辐射力将辐射力大于阈值的待分离样品粒子捕获至声人工结构，包括：利用入射流对颗粒的拖拽力、人工结构声场对颗粒的声辐射力以及人工结构声场的声流对颗粒的拖拽力对待分离样品粒子进行分离；将辐射力大于阈值的待分离样品粒子捕获至声人工结构。
在一些实施例中，本申请中的流动室的顶盖为透明吸声材料。
综上所述，参考图4，图4为本发明的分选系统，包括超声激励模块、样品递送与收集模块和分选模块。超声激励模块包括信号发生器、功率放大器和超声换能器，换能器产生的声波用来激发声人工结构产生共振声场；样品递送与收集模块包括注射泵和收集装置，注射泵和流动室、收集装置之间用软管连接，注射泵向流动室注入样品后，经过声辐射力的作用，分离后的样品一部分留在声人工结构的表面，一部分进入收集装置；分选模块包括声人工结构和流动室，是分选发生的区域，过程如图5所示。
图5为分选过程的示意图，声人工结构中的t为板厚，a为结构的周期，w为栅格的宽度，h为栅格的高度。材料为不锈钢，参数为t＝50μm，h＝50μm，w＝50μm，a＝300μm。图6为上述尺寸人工结构的透射谱，其共振频率为4MHz。
由于以前的研究主要是在无入射流条件下，在微腔或者水槽内的静止流体环境中，仅利用声人工结构产生的声辐射力实现对颗粒的捕获、分选、输运等操控。本专利中采用的流动室，有出口和入口，入射流从入口由微流体泵泵入，并从出口流出。通过综合考虑入射流对颗粒的拖拽力，人工结构声场对颗粒的声辐射力和人工结构声场的声流对颗粒的拖拽力的合力作用，调控三种作用力的相对大小，从而实 现对不同大小颗粒的高通量分选。另外，本专利中的流动室的顶盖为透明吸声材料如PDMS，可以有效吸收入射波，防止边界反射对人工结构声场的影响。
使用数值方法计算了粒子在流动室内受到的入射流和声流叠加后的流场产生的流动曳力和声辐射力，忽略了重力和浮力。首先计算了水中的一阶声场。声场的控制方程为
Figure PCTCN2021138307-appb-000001
Figure PCTCN2021138307-appb-000002
Figure PCTCN2021138307-appb-000003
其中ρ 0和ρ 1为水的密度和一阶摄动量，p 1和u 1分别为一阶声压和速度，η和μ为水的体积粘度和剪切粘度。k th为水的热传导系数，T为温度。
本文计算的声人工结构的共振频率为f＝4Mhz，水中的波长为
Figure PCTCN2021138307-appb-000004
其中c 0为水的声速设为1500m/s。分选的粒子直径通常远远小于该波长，对声场的散射作用很小，因此我们使用了Gorkov的理论计算了半径为r的粒子在声场中受到的声辐射力F R
Figure PCTCN2021138307-appb-000005
Figure PCTCN2021138307-appb-000006
Figure PCTCN2021138307-appb-000007
Figure PCTCN2021138307-appb-000008
其中ω＝2πf为波的角频率。<·>为时间平均算子。ρ p和c p为粒子的密度和纵波波速。半径为r＝1.15μm，ρ p＝1160kg/m^3，c p＝ 1600m/s的大肠杆菌受到的声辐射力分布如图7所示。从公式可以看出，半径较大的粒子所受辐射力较大。
由于流速很低，腔室的尺寸很小，雷诺数很小，所以使用如下方程计算腔道内的流动，不可压缩假设下，忽略惯性项后的控制方程为
Figure PCTCN2021138307-appb-000009
Figure PCTCN2021138307-appb-000010
其中，u f为流场速度，p为流场压力，F为体积力。入口和出口均设为充分发展的速度边界条件，速度大小设为u 0，上壁面设为无滑移边界。
声场会进一步引发液体的稳态流动，称为声流。对于尺寸较小的粒子，已有多项工作表明声流而非辐射力会主导粒子的运动。为了考虑这种影响，本文由一阶声场计算了二阶的声流效应，在流场中添加了体积力项
Figure PCTCN2021138307-appb-000011
在流场中，球形粒子受到的流动曳力F D为
F D＝6πμr(u f-u p)
其中u p为粒子运动速度。粒子的运动由牛顿第二定律描述
Figure PCTCN2021138307-appb-000012
其中m p为粒子的质量。
图8为u 0＝5mm/s，p 0＝50kPa条件下半径为1.15μm和5.75μm的两种粒子在流动室内的运动轨迹，所有粒子均匀地从左侧入口进入。可以看出大的粒子全部被捕获，而小的粒子大部分流出了通道，只有少量被捕获。因此从原理上来说分选是可行的。
定义e 1和e 2分别为流出的粒子中小粒子所占的比例和捕获至声人工结构表面的粒子中大粒子所占的比例。最理想的情况是e 1和e 2均为1，此时达到完全的分离，但由于层流的影响，不同粒子的初 始速度和位置都不同，这是难以达到的。进一步计算了不同流速和不同入射电压下的分选效率，研究了流速和入射声压对效率的影响，结果如图9所示。可以看出，随着入射声压的增加，大粒子被捕获的数量逐渐增加，当全部被捕获时，e 1达到了1，在u 0＝5mm/s和u 0＝10mm/s的条件下，此时e 2接近于0.8，分选的效果较好。
另外，将具有不同共振频率的声子晶体板组合，可以对多种粒子进行级联式分选，如图10所示。此器件也可以用来分选细胞和微泡或者含泡细菌，原理是两者的声学对比因子差距较大，所受辐射力差距很大。
进一步地，参考图2，图2示出了根据本申请一个实施例的基于声人工结构的微粒分选装置200的示例性结构框图。
如图2所示，该装置包括：
共振单元210，用于通过超声激励使得声人工结构发生共振；
分离单元220，用于将待分离样品注入到流动室，利用共振强局域声场产生的声辐射力将辐射力大于阈值的待分离样品粒子捕获至声人工结构；
收集单元230，用于收集从流动室中的流出的粒子，该粒子的辐射力小于阈值。
应当理解，装置200中记载的诸单元或模块与参考图1描述的方法中的各个步骤相对应。由此，上文针对方法描述的操作和特征同样适用于装置200及其中包含的单元，在此不再赘述。装置200可以预先实现在电子设备的浏览器或其他安全应用中，也可以通过下载等方式而加载到电子设备的浏览器或其安全应用中。装置200中的相应单元可以与电子设备中的单元相互配合以实现本申请实施例的方案。
下面参考图3，其示出了适于用来实现本申请实施例的终端设备或服务器的计算机系统300的结构示意图。
如图3所示，计算机系统300包括中央处理单元(CPU)301，其可以根据存储在只读存储器(ROM)302中的程序或者从存储部分308加载到随机访问存储器(RAM)303中的程序而执行各种适当的动作和处理。在RAM303中，还存储有系统300操作所需的各种程序和数据。CPU301、ROM302以及RAM303通过总线304彼此相连。输入/输出(I/O)接口305也连接至总线304。
以下部件连接至I/O接口305：包括键盘、鼠标等的输入部分306；包括诸如阴极射线管(CRT)、液晶显示器(LCD)等以及扬声器等的输出部分307；包括硬盘等的存储部分308；以及包括诸如LAN卡、调制解调器等的网络接口卡的通信部分309。通信部分309经由诸如因特网的网络执行通信处理。驱动器310也根据需要连接至I/O接口305。可拆卸介质311，诸如磁盘、光盘、磁光盘、半导体存储器等等，根据需要安装在驱动器310上，以便于从其上读出的计算机程序根据需要被安装入存储部分308。
特别地，根据本公开的实施例，上文参考图1描述的过程可以被实现为计算机软件程序。例如，本公开的实施例包括一种基于声人工结构的微粒分选方法，其包括有形地包含在机器可读介质上的计算机程序，所述计算机程序包含用于执行图1的方法的程序代码。在这样的实施例中，该计算机程序可以通过通信部分309从网络上被下载和安装，和/或从可拆卸介质311被安装。
附图中的流程图和框图，图示了按照本发明各种实施例的系统、方法和计算机程序产品的可能实现的体系架构、功能和操作。在这点上，流程图或框图中的每个方框可以代表一个模块、程序段、或代码的一部分，前述模块、程序段、或代码的一部分包含一个或多个用于实现规定的逻辑功能的可执行指令。也应当注意，在有些作为替换的实现中，方框中所标注的功能也可以以不同于附图中所标注的顺序发 生。例如，两个接连地表示的方框实际上可以基本并行地执行，它们有时也可以按相反的顺序执行，这依所涉及的功能而定。也要注意的是，框图和/或流程图中的每个方框、以及框图和/或流程图中的方框的组合，可以用执行规定的功能或操作的专用的基于硬件的系统来实现，或者可以用专用硬件与计算机指令的组合来实现。
描述于本申请实施例中所涉及到的单元或模块可以通过软件的方式实现，也可以通过硬件的方式来实现。所描述的单元或模块也可以设置在处理器中，例如，可以描述为：一种处理器包括第一子区域生成单元、第二子区域生成单元以及显示区域生成单元。其中，这些单元或模块的名称在某种情况下并不构成对该单元或模块本身的限定，例如，显示区域生成单元还可以被描述为“用于根据第一子区域和第二子区域生成文本的显示区域的单元”。
作为另一方面，本申请还提供了一种计算机可读存储介质，该计算机可读存储介质可以是上述实施例中前述装置中所包含的计算机可读存储介质；也可以是单独存在，未装配入设备中的计算机可读存储介质。计算机可读存储介质存储有一个或者一个以上程序，前述程序被一个或者一个以上的处理器用来执行描述于本申请的应用于透明窗口信封的文本生成方法。
以上描述仅为本申请的较佳实施例以及对所运用技术原理的说明。本领域技术人员应当理解，本申请中所涉及的发明范围，并不限于上述技术特征的特定组合而成的技术方案，同时也应涵盖在不脱离前述发明构思的情况下，由上述技术特征或其等同特征进行任意组合而形成的其它技术方案。例如上述特征与本申请中公开的(但不限于)具有类似功能的技术特征进行互相替换而形成的技术方案。

Claims (10)

  1. 一种基于声人工结构的微粒分选方法，其特征在于，该方法包括：
    通过超声激励使得声人工结构发生共振；
    将待分离样品注入到流动室，利用共振强局域声场产生的声辐射力将辐射力大于阈值的待分离样品粒子捕获至声人工结构；
    收集从流动室中的流出的粒子，该粒子的辐射力小于阈值。
  2. 根据权利要求1所述的基于声人工结构的微粒分选方法，其特征在于，所述通过超声激励声人工结构发生共振，包括：
    通过信号发生器、功率放大器以及超声换能器产生声波；
    利用产生的声波激发声人工结构发生共振声场。
  3. 根据权利要求2所述的基于声人工结构的微粒分选方法，其特征在于，所述利用共振强局域声场产生的声辐射力将辐射力大于阈值的待分离样品粒子捕获至声人工结构，包括：
    利用入射流对颗粒的拖拽力、人工结构声场对颗粒的声辐射力以及人工结构声场的声流对颗粒的拖拽力对待分离样品粒子进行分离；
    将辐射力大于阈值的待分离样品粒子捕获至声人工结构。
  4. 根据权利要求3所述的基于声人工结构的微粒分选方法，其特征在于，所述流动室的顶盖为透明吸声材料。
  5. 一种基于声人工结构的微粒分选装置，其特征在于，该装置包括：
    共振单元，用于通过超声激励使得声人工结构发生共振；
    分离单元，用于将待分离样品注入到流动室，利用共振强局域声场产生的声辐射力将辐射力大于阈值的待分离样品粒子捕获至声人工结构；
    收集单元，用于收集从流动室中的流出的粒子，该粒子的辐射力小于阈值。
  6. 根据权利要求5所述的基于声人工结构的微粒分选装置，其特征在于，所述通过超声激励声人工结构发生共振，包括：
    通过信号发生器、功率放大器以及超声换能器产生声波；
    利用产生的声波激发声人工结构发生共振声场。
  7. 根据权利要求6所述的基于声人工结构的微粒分选装置，其特征在于，所述利用共振强局域声场产生的声辐射力将辐射力大于阈值的待分离样品粒子捕获至声人工结构，包括：
    利用入射流对颗粒的拖拽力、人工结构声场对颗粒的声辐射力以及人工结构声场的声流对颗粒的拖拽力对待分离样品粒子进行分离；
    将辐射力大于阈值的待分离样品粒子捕获至声人工结构。
  8. 根据权利要求7所述的基于声人工结构的微粒分选装置，其特征在于，所述流动室的顶盖为透明吸声材料。
  9. 一种计算机设备，包括存储器、处理器以及存储在存储器上并可在处理器上运行的计算机程序，其特征在于，所述处理器执行所述程序时实现如权利要求1－4中任一所述的方法。
  10. 一种计算机可读存储介质，其上存储有计算机程序，所述计算机程序用于：
    所述计算机程序被处理器执行时实现如权利要求1－4中任一所述的方法。
PCT/CN2021/138307 2021-12-15 2021-12-15 基于声人工结构的微粒分选方法 WO2023108473A1 (zh)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103203328A (zh) * 2013-03-14 2013-07-17 深圳先进技术研究院 基于结构声场操控和筛选颗粒的系统及方法
CN109946217A (zh) * 2017-12-21 2019-06-28 深圳先进技术研究院 一种声驱动的流式细胞检测装置
CN111773177A (zh) * 2020-07-16 2020-10-16 南京大学 一种利用声辐射力实现药物粒子定点释放方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103203328A (zh) * 2013-03-14 2013-07-17 深圳先进技术研究院 基于结构声场操控和筛选颗粒的系统及方法
CN109946217A (zh) * 2017-12-21 2019-06-28 深圳先进技术研究院 一种声驱动的流式细胞检测装置
CN111773177A (zh) * 2020-07-16 2020-10-16 南京大学 一种利用声辐射力实现药物粒子定点释放方法

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