KR101781499B1 - Apparatus for separation and alignment for particles and method thereof - Google Patents

Apparatus for separation and alignment for particles and method thereof Download PDF

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KR101781499B1
KR101781499B1 KR1020160022725A KR20160022725A KR101781499B1 KR 101781499 B1 KR101781499 B1 KR 101781499B1 KR 1020160022725 A KR1020160022725 A KR 1020160022725A KR 20160022725 A KR20160022725 A KR 20160022725A KR 101781499 B1 KR101781499 B1 KR 101781499B1
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standing wave
fluid
particles
wave
surface acoustic
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KR1020160022725A
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Korean (ko)
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KR20170100311A (en
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이형석
이준석
류찬열
강병준
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연세대학교 산학협력단
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502761—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0647—Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0652—Sorting or classification of particles or molecules
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
    • B01L2400/0436—Moving fluids with specific forces or mechanical means specific forces vibrational forces acoustic forces, e.g. surface acoustic waves [SAW]
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
    • B01L2400/0439—Moving fluids with specific forces or mechanical means specific forces vibrational forces ultrasonic vibrations, vibrating piezo elements

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  • Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Fluid Mechanics (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
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  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
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Abstract

The present invention relates to a particle separating and aligning apparatus for separating and aligning two or more kinds of particles mixed in a fluid, comprising a fluid receiving channel for receiving a fluid containing two or more kinds of particles, And a second standing wave adding means for adding a second standing wave to the fluid receiving channel, wherein the second standing wave has a frequency corresponding to a multiple of the first standing wave . Still further, it may further comprise means for displacing the phase of the first standing wave.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a particle separation and sorting apparatus, and a particle separation and sorting method using the same.

The present invention relates to a device for sorting and sorting particles such as proteins or cells in a flowable substance such as a fluid or a hydrogel, and a method for separating and aligning particles using the same. More particularly, To a device and a method for separating different kinds of particles mixed in a fluid by using a standing wave and aligning them in the fluid.

When an electrode formed of a piezoelectric element is attached to a substrate and an AC voltage is applied, a surface acoustic wave (SAW) is formed on the surface of the substrate. Since the 1990s, RF filters using surface acoustic waves have been widely used in the field of electronics .

When the surface acoustic waves are in contact with the fluid placed on the substrate, the energy of the surface acoustic waves is transmitted to the fluid to generate a flow in the fluid, and a pressure field is formed by the sound waves. You can move.

In particular, when a surface acoustic wave having the same wavelength is simultaneously generated at two points on a substrate, a standing wave is generated due to a surface acoustic wave generated at two points. In the state where the standing wave is generated, It moves. Using this principle, microparticles or cells in the fluid can be aligned as needed.

After the successful use of flow cytometry (FACS) in the separation of cells, methods using microfluidic devices have been developed. Passive methods of separating particles without externally applied force using density or buoyancy differences, and active methods of transferring forces from outside using electric fields, magnetic fields, sound waves, or light waves, The method using the surface acoustic wave has recently been developed as one of the methods of acoustophoresis using a sound wave.

The advantage of particle sorting method using surface acoustic wave is that the device is simple and can be miniaturized, is biocompatible with respect to applying an electromagnetic field, is applicable to a bio field, and can transmit a large force at a high speed through a fluid , And system integration and mass production are easy. Because of these advantages, particle separation and alignment methods using surface acoustic waves have recently attracted attention as a useful tool in the field of lab-on-a-chip.

When a surface acoustic wave in a steady state is used, microparticles or cells can be fixed at a desired position in a fluid, and particles can be moved to a desired position through phase displacement of a surface acoustic wave. Through these devices, different particles or cells can be arranged in a three-dimensional structure or stacked in a layer structure to simulate living tissue, and promotion of growth and differentiation by cell sorting is possible.

FIG. 1 shows a conventional particle aligning apparatus using a surface acoustic wave. An IDT (Interdigital Transducer) electrode 310 for attaching a surface acoustic wave is attached to two points on the substrate, and a microchannel 304 is positioned between the two IDT electrodes 310. In the microchannel 304, a fluid is filled and microparticles 302 are floating in the fluid. In the two IDT electrodes 310, surface acoustic waves of the same frequency are generated, and surface acoustic waves of the same frequency are superposed So that a standing wave occurs. Then, the standing wave is transmitted as energy to the inside of the fluid, and a pressure field is generated in the inside of the fluid, so that the micro particles 302 in the fluid are aligned to the positions corresponding to the nodes of the standing waves as shown in FIG. In this configuration, by changing the phase of the surface acoustic wave or by changing the frequency, the position where the micro particles 302 are aligned can be adjusted.

However, in the particle aligning apparatus using the conventional surface acoustic wave, it is possible to arrange the particles at specific positions, but when two or more particles are mixed, it is impossible to separate them.

U.S. Patent Publication No. 8,573,060 (Nov. Korean Patent Publication No. 10-2014-0005488 (Jul.

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made keeping in mind the above problems occurring in the prior art, and an object of the present invention is to provide an apparatus and a method for sorting and sorting different kinds of particles when two or more different kinds of particles are mixed in a fluid The purpose.

The present invention relates to a particle separating and aligning apparatus for separating and aligning two or more kinds of particles mixed in a fluid, comprising a fluid receiving channel for receiving a fluid containing two or more kinds of particles, And a second standing wave adding means for adding a second standing wave to the fluid receiving channel, wherein the second standing wave has a frequency corresponding to a multiple of the first standing wave . Here, the particles may be cells or proteins, and the shape of the particles is not particularly limited, and the present invention can be applied to any type of particles.

Furthermore, in the present invention, the first standing wave adding means or the second standing wave adding means may be a surface acoustic wave generating means or an ultrasonic transducer. Preferably, the first standing wave adding means and the second standing wave adding means may be surface acoustic wave generating means including a substrate and a pair of IDT electrodes formed on the substrate.

And the first standing wave adding means or the second standing wave adding means may further comprise means for displacing the phase of the standing wave.

The present invention provides a method for particle sorting and sorting for separating and aligning two or more types of particles mixed in a fluid, comprising the steps of preparing a fluid containing two or more kinds of particles, adding a first standing wave to the fluid, And adding a second standing wave to the fluid, wherein the second standing wave has a frequency corresponding to a multiple of the first normal.

Still further, the method may further include shifting the phase of the first standing wave between the step of adding the first standing wave to the fluid and the step of adding the second standing wave.

As another embodiment, it is possible to stop the generation of the first standing wave before the step of adding the second standing wave, and to shift the phase of the second standing wave after the step of adding the second standing wave. In the above embodiments, the first standing wave or the second standing wave can be formed by overlapping two surface acoustic waves.

Even when two or more different kinds of fine particles are mixed in the fluid, it is possible to separate and sort these different types of fine particles by type.

1 is a perspective view of a conventional particle aligning apparatus using SAW.
Fig. 2 shows a state in which particles are aligned by surface acoustic waves having normal fines.
3 is a plan view of a particle aligning apparatus according to an embodiment of the present invention.
4 is a side view of a particle aligning apparatus according to an embodiment of the present invention.
5 is a plan view of an IDT electrode used for generating a surface acoustic wave.
FIG. 6 is a block diagram illustrating a particle sorting process according to the first embodiment.
FIG. 7 is a conceptual diagram illustrating a particle sorting process according to the first embodiment.
8 is a block diagram illustrating a particle sorting process according to the second embodiment.
FIG. 9 is a conceptual diagram illustrating a particle aligning process according to the second embodiment.

FIG. 3 is a plan view of a particle separation and alignment apparatus 100 according to an embodiment of the present invention, and FIG. 4 is a side view of a particle separation and alignment apparatus 100 according to the above embodiment.

The particle separation and alignment apparatus 100 includes a substrate 110, IDT electrodes 120L, 120R, 130L, and 130R formed on the substrate 110, and a fluid receiving channel 150 formed between the IDT electrodes .

The substrate 110 can be mainly made of lithium niobate (LiNbO 3 ), quartz (Quartz), or lithium tantalite (LiTaO 3 ), but the material is not particularly limited as long as it can generate surface acoustic waves.

On the substrate 110, a fluid receiving channel 150 capable of accommodating a fluid is formed, which is mainly made of PDMS (Polydimethylsiloxane). However, the material of the fluid receiving channel 150 may be any material capable of storing the fluid therein, and the material of the fluid receiving channel 150 is not particularly limited.

First IDT electrodes 120L and 120R and second IDT electrodes 130L and 130R are formed on both sides of the fluid receiving channel 150 with the fluid receiving channel 150 therebetween. The IDT electrode is formed by attaching a piezoelectric material to the substrate 110. When an AC power source is applied to the IDT electrode, the IDT electrode generates a surface acoustic wave on the substrate 110. [

Here, the first IDT electrodes 120L and 120R and the second IDT electrodes 130L and 130R are disposed symmetrically with respect to one another with a fluid receiving channel 150 therebetween. First, the first IDT electrodes 120L and 120R generate surface acoustic waves having the same frequency, respectively. The first IDT electrode 120R on the right side and the first IDT electrode 120L on the left side with respect to the fluid receiving channel 150 generate surface acoustic waves having the same frequency. (Standing Wave).

A standing wave is a concept that contrasts with a progressive wave, which is a wave traveling in an arbitrary direction. It refers to a wave whose node of a vibration is fixed at a certain position. The waves of the same amplitude and vibration move in opposite directions It is caused by the synthesis of waves.

Like the first IDT electrodes 120L and 120R, the second IDT electrodes 130L and 130R are disposed symmetrically with respect to the fluid receiving channel 150. The second IDT electrodes are also arranged at the same frequency The surface acoustic waves of the surface acoustic waves are generated and overlapped to form a standing wave. Here, the surface acoustic waves generated from the second IDT electrodes 130L and 130R and the standing waves formed by the second IDT electrodes 130L and 130R have a frequency corresponding to a surface acoustic wave generated by the first IDT electrodes 120L and 120R, The specific reason will be described later.

FIG. 5 shows a basic structure of the first IDT electrode or the second IDT electrode. The IDT electrode is formed by forming a piezoelectric material on a substrate by a method such as evaporation. The IDT electrode is formed in a state in which the upper electrode having a plurality of branches and the lower electrodes having a plurality of branches are alternately arranged so that the wavelengths or frequencies of the surface acoustic waves generated by adjusting the widths of the branches and the spacing between adjacent branches. (The width and spacing of the electrodes are determined to be 1/4 of the wavelength (? / 4)).

Referring to FIG. 6, the particle separating and aligning apparatus 100 separates and aligns the particles. First, the fluid containing the fine particles or cells is accommodated in the fluid receiving channel 150 (S100). Fig. 7 (a) shows two particles of different sizes. The blue second particles 300 are large particles and the red first particles 200 are small particles.

Next, an AC power is supplied to the pair of first IDT electrodes 120R and 120L to generate a first standing wave (S200). Illustratively, a standing wave having a frequency of 14 MHz is generated. For convenience of explanation, the wavelength of a surface acoustic wave generated by each of the first IDT electrodes 120R and 120L is denoted by "? &Quot;.

As described above, the standing wave is a wave whose vibration does not move its nodal point but remains in a certain region, and the upper node is formed at intervals of? / 2.

A pressure field is created inside the fluid due to the standing wave, and both the first particle 200 and the second particle 300 are moved by the pressure field to move to the vicinity of the node of the standing wave to be aligned (refer to FIG. 7 (a) ). Here, it can be seen that both the first particle 200 and the second particle 300 are aligned in the vicinity of the node of the standing wave.

In this state, when the phase of the AC power supplied to the first IDT electrodes 120R and 120L generating the first standing wave is changed, the positions of the standing waves are changed (S400). When a node position of the standing wave is changed, a new pressure field is formed. As a result, a force directed toward the position of the new node is applied to the first particle 200 and the second particle 300, The second particles 300 larger in size than the first particles 200 move first and thus the first particles 200 and the second particles 300 are somewhat different from each other in alignment (See Fig. That is, the first particle 200 having a small size stays at the node of the first standing wave, and the second particle 300 having a large size is collected at a position slightly deviated from the node position of the first standing wave.

When AC power is supplied to the second IDT electrodes 130R and 130L generating the second standing wave again (S500), the second standing wave is applied to the fluid receiving channel 150. The principle of generating the standing waves is the first Is the same as the principle in which the first standing wave is generated by the IDT electrodes 120R and 120L. However, the superficial acoustic waves generated by the second IDT electrodes 130R and 130L have a frequency corresponding to a multiple of the surface acoustic wave frequency generated by the first IDT electrodes 120R and 120L, And the node of the second standing wave are matched with each other. In this embodiment, since the first standing wave has a frequency of 14 MHz and the second standing wave has a frequency of 28 MHz, the second standing wave has twice the node as the first standing wave.

The position of the second particle 300 is shifted to a position slightly shifted from the node of the first standing wave by displacing the phase of the first standing wave (S400). In this state, When the standing wave is applied, the second particle 300 moves to the node of the second standing wave by the pressure field formed by the second standing wave.

Here, since the wavelengths of the first standing wave and the second standing wave correspond to a multiple relation, all the nodes of the first standing wave coincide with the node positions of the second standing wave. However, since the second standing wave has a multiple of the first standing wave, that is, twice the frequency of the first standing wave, the second standing wave has twice the number of nodes compared to the first standing wave, and the additional node I have. That is, the interval between nodes of the first standing wave is? / 2 while the interval between nodes of the second standing wave is? / 4.

Since the first particle 200 is located at a common node between the first standing wave and the standing wave when the second standing wave is added, a force for moving the first particle 200 acts on the first particle 200 even if the second standing wave is applied And remain in place.

On the other hand, since the second particle 300 is shifted to a position deviated from the common node between the first standing wave and the second standing wave when the phase of the standing wave is displaced (S400), the pressure field generated when the second standing wave is added (See Fig. 7 (d)).

As a result, the first particles 200 and the second particles 300 are separated at intervals of? / 4 and arranged in a line-like shape. Therefore, it can be confirmed that the mixed particles can be separated and arranged by the surface acoustic wave generating means for adding the frequencies in the drain relation to each other.

Further, in the above-described embodiment, the first particle 200 and the second particle 300 are separated by displacing the phase of the first standing wave, but in some cases, as shown in FIGS. 8 and 9, It is also possible to separate particles by displacing the phase. In this case, when the first standing wave is generated, the first particles 200 and the second particles 300 having a size larger than that of the first particles 200 are collected at the nodal portions of the first standing waves (S200 '), (I.e., the same steps up to step (b) of FIG. 7).

However, unlike the embodiment of FIG. 7, instead of shifting the phase of the first standing wave, the first standing wave generating device is stopped (S400 ') and a second standing wave is generated, So that a new node is formed (S500 '). When the second standing wave is further phase-shifted (S600 '), only the second particle 300, which receives a larger pressure field due to the standing wave, is moved first, and the above-mentioned new node (the first standing wave and the second standing wave (See Fig. 8d), the first particles 200 and the second particles 300 are separated from each other.

In this embodiment, the two kinds of particles are mutually separated by a surface acoustic wave having a frequency relationship of two times. However, when the frequency of the surface acoustic wave to be added corresponds to a multiple relation, It will be apparent to those of ordinary skill in the art that separation and alignment of particles will be possible.

Further, in the present embodiment, the SAW generated by the IDT electrode is used as a source for generating a standing wave added to the fluid. However, if it is a means for adding a standing wave to the fluid, such as an ultrasonic transducer, It will also be obvious to a person skilled in the art that it can be used to implement technical ideas.

100: Particle separation and alignment device 110:
120R and 120L: first IDT electrodes 130R and 130L: IDT electrodes
150: fluid receiving channel

Claims (10)

The present invention relates to a particle separating and aligning apparatus for separating and aligning two or more kinds of particles mixed in a fluid,
A fluid receiving channel for receiving a fluid containing two or more kinds of particles;
First standing wave adding means for adding a first standing wave to the fluid receiving channel; And
And second standing wave adding means for adding a second standing wave to the fluid receiving channel,
Wherein the second standing wave has a frequency corresponding to a multiple of the first standing wave,
One of the first stationary wave and the second stationary wave has a fixed frequency and the other has a phase shift of the frequency
Wherein the first standing wave adding means or the second standing wave adding means further comprises means for displacing the phase of the standing wave.
The particle separation and alignment apparatus according to claim 1, wherein the first standing wave adding means or the second standing wave adding means is a surface acoustic wave generating means or an ultrasonic transducer.
3. The particle separation and alignment apparatus according to claim 2, wherein the first standing wave adding means or the second standing wave adding means are surface acoustic wave generating means including a substrate and a pair of IDT electrodes formed on the substrate.
delete 4. The apparatus of claim 3, wherein each of the pair of first IDT electrodes or the pair of second IDT electrodes is symmetrically disposed on both sides of the fluid receiving channel.
The apparatus of claim 1, wherein the particles are proteins or cells.
delete The present invention relates to a method for separating and aligning two or more kinds of particles mixed in a fluid,
Preparing a fluid containing two or more kinds of particles;
Adding a first standing wave to the fluid;
Shifting the phase of the first standing wave; And
Adding a second standing wave to the fluid; , ≪ / RTI &
Wherein the second standing wave has a frequency corresponding to a multiple of the first normal.
The present invention relates to a method for separating and aligning two or more kinds of particles mixed in a fluid,
Preparing a fluid containing two or more kinds of particles;
Adding a first standing wave to the fluid;
Stopping the first stationary wave generation;
Adding a second standing wave to the fluid; And
Shifting the phase of the second standing wave; , ≪ / RTI &
Wherein the second standing wave has a frequency corresponding to a multiple of the first normal.
The method of claim 8 or 9, wherein the first standing wave or the second standing wave is formed by superimposing two surface acoustic waves.
KR1020160022725A 2016-02-25 2016-02-25 Apparatus for separation and alignment for particles and method thereof KR101781499B1 (en)

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KR102226368B1 (en) * 2019-11-18 2021-03-11 한국생산기술연구원 TDLAS gas detection apparatus comprising sonic standing wave

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KR102569747B1 (en) * 2020-04-27 2023-08-25 고려대학교 산학협력단 Flow channel and device for separation of particles in bodyfluid
CN113941379B (en) * 2021-10-15 2023-02-17 重庆大学 Micro-fluidic chip and method for sorting, enriching and detecting bacteria and fungi

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