CN110237873B - Sheath-flow-free micro-fluidic chip for particle separation based on surface acoustic wave - Google Patents
Sheath-flow-free micro-fluidic chip for particle separation based on surface acoustic wave Download PDFInfo
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- CN110237873B CN110237873B CN201910349727.3A CN201910349727A CN110237873B CN 110237873 B CN110237873 B CN 110237873B CN 201910349727 A CN201910349727 A CN 201910349727A CN 110237873 B CN110237873 B CN 110237873B
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- 239000002245 particle Substances 0.000 title claims abstract description 56
- 238000000926 separation method Methods 0.000 title claims abstract description 30
- 238000010897 surface acoustic wave method Methods 0.000 title claims abstract description 12
- 239000007788 liquid Substances 0.000 claims abstract description 19
- 239000002699 waste material Substances 0.000 claims abstract description 19
- 239000000758 substrate Substances 0.000 claims abstract description 15
- 230000005855 radiation Effects 0.000 claims abstract description 10
- 230000001133 acceleration Effects 0.000 claims abstract description 8
- GQYHUHYESMUTHG-UHFFFAOYSA-N lithium niobate Chemical compound [Li+].[O-][Nb](=O)=O GQYHUHYESMUTHG-UHFFFAOYSA-N 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 8
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 3
- 229910052782 aluminium Inorganic materials 0.000 claims description 3
- 238000005468 ion implantation Methods 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 238000003491 array Methods 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- CXQXSVUQTKDNFP-UHFFFAOYSA-N octamethyltrisiloxane Chemical group C[Si](C)(C)O[Si](C)(C)O[Si](C)(C)C CXQXSVUQTKDNFP-UHFFFAOYSA-N 0.000 claims 2
- 238000001259 photo etching Methods 0.000 claims 1
- 239000012530 fluid Substances 0.000 abstract description 5
- 230000009471 action Effects 0.000 abstract description 3
- 238000002347 injection Methods 0.000 abstract 1
- 239000007924 injection Substances 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 6
- 238000001514 detection method Methods 0.000 description 4
- 239000004205 dimethyl polysiloxane Substances 0.000 description 3
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 3
- 230000006978 adaptation Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000000206 photolithography Methods 0.000 description 2
- 238000004088 simulation Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000004401 flow injection analysis Methods 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- -1 polydimethylsiloxane structure Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
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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
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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
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
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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
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
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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
- B01L2300/00—Additional constructional details
- B01L2300/12—Specific details about materials
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (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 invention discloses a sheath-flow-free micro-fluidic chip for particle separation based on surface acoustic waves, which comprises an input area, an acceleration area, a focusing area, a sorting area and an output area. The input area realizes sample injection, so that fluid is stable when reaching the acceleration area; the accelerating area is used for accelerating the fluid and pre-concentrating particles; the focusing region enables deflection of particles in the liquid to the middle of the tube; after the same Radio Frequency (RF) driving signals are applied to the interdigital electrodes (IDT) on two sides of the separation area, standing waves are formed on the substrate, so that particles with different sizes in the pipeline can be selectively deflected under the action of acoustic wave radiation force. The output area comprises a waste liquid channel and a collecting channel, which respectively correspond to the waste liquid and the particles which are not effective after separation. The microfluidic chip has the advantages of simple structure, low power, high sample processing efficiency and the like due to the structure without sheath flow and SAW sorting.
Description
Technical Field
The invention relates to the technical field of microfluidic analysis, in particular to a sheath-flow-free microfluidic chip for particle separation based on surface acoustic waves.
Background
In recent years, on-chip laboratory technology based on microfluidic chips has achieved many research results, such as cell culture, sorting, lysis, solution sample preparation, reaction, separation, detection, and the like. The method has the advantages of small reagent demand, closed operation, low system price and the like, and has great application potential in the fields of future biological medicine research and on-site rapid detection (POC).
At present, the principle of realizing cell/particle sorting by using a microfluidic chip is mainly based on different physicochemical properties of particles, such as sorting can be realized under electrophoretic force according to different dielectric properties of particles; the fluorescence activation can realize sorting according to whether the particles are fluorescently labeled or not; sorting can be realized under inertial force according to different masses; sorting can be achieved under lateral sonic radiation forces, depending on the size of the particles. Compared with other separation methods, the particle separation system based on the surface acoustic wave has the following advantages: the structure is simple, and the piezoelectric device mainly comprises a piezoelectric substrate, IDTs and a microfluidic pipeline; the separation effect is easy to control, as long as the RF power applied to the IDTs is adjusted; the biological compatibility is good, and the sorting does not influence the activity of cells.
For the existing microfluidic particle sorting system, when particles flow through a sorting area in a microfluidic channel, in order to avoid the influence of turbulence and vortex on the particles, the mixed particles are required to be focused, and a single arranged particle flow is ensured to be formed in the middle of the channel so as to realize: when the function of the sorting area is enabled, the target particles can flow out from the collection port, whereas when the function of the sorting area is not enabled, the particles flow out from the waste port only.
For particle focusing, a common effective method is to inject the sheath flow through multiple input ports, so that the sample flow is focused under the action of the surrounding sheath flow. However, multiple sheath flow input ports means multiple microfluidic pumps, adding to the complexity of the system. Meanwhile, in the existing work adopting sheath flow, the flow speed and the separation effect are often limited, namely, after the separation function is started, the slower the flow speed of particles in the separation area is, the higher the separation effect is, the smaller the number of target particles flowing to the waste liquid port is, and the lower the separation flux is. Therefore, although the method of adding sheath flow overcomes the focusing problem, the flow rate of the sheath flow is often more than twice the flow rate of the sample flow, and the flow rate of the sample flow has to be reduced in order to achieve higher separation efficiency.
Therefore, compared with the design with sheath flow, the design without sheath flow reduces the number of the microfluidic pumps, avoids the mutual limitation of flow speed and separation effect, reduces the time for sample detection, and is more beneficial to the integration and miniaturization of the system.
Disclosure of Invention
In order to solve the problem of releasing contradiction between sample focusing and sample separation efficiency in a microfluidic sorting system in the prior art, the invention provides a design scheme of a microfluidic separation chip without sheath flow based on acoustic wave surface standing waves. Particle focusing is achieved by stokes drag force and savman lift force, and particle separation is achieved based on the relationship that the acoustic radiation force experienced by particles suspended in a microfluidic channel is proportional to the volume of the particles. Thereby reducing the need for a device for the microfluidic pump to drive the sheath flow while reducing the time of detection with equal sample and precision requirements.
In order to achieve the above purpose, the present invention adopts the following technical scheme: particle focusing is achieved by utilizing Shi Tuoke S drag force and Safmann lift force of particles in fluid, and particles with different sizes are separated by utilizing sound wave radiation force. The system can be divided into five areas, namely an input area, an acceleration area, a focusing area, a sorting area and an output area. Wherein the input region pumps ambient liquid into the conduit through the conduit and the disturbance of particles and fluid can stabilize before entering the acceleration region. And an acceleration region, wherein particles which can move along the lower surface are concentrated in the middle region in advance through a series of semicircular protruding structures, the width of the pipeline is 135 mu m at the maximum and 35 mu m at the minimum, so that particles sliding along the pipeline wall are prevented from sliding along the inner wall after entering the focusing region to cause focusing failure, and the particles can have high flow velocity when entering the focusing region. And the focusing area, because the fluid flows in from one vertex of the focusing area and the sectional area of the inlet is far smaller than that of the focusing area, a large speed gradient field is formed near the inlet, and particles move towards the far end of the inlet under the action of inertia force, stirling drag force and Safmann lifting force, so that the focusing effect is realized. And the sorting area is provided with an interdigital transducer (IDTs) at two sides, and the IDTs at two sides are parallel to each other but form an included angle of 10 degrees with the microfluidic pipeline. When a radio frequency power signal is applied to the IDTs, a standing wave is formed on the surface of the lithium niobate substrate. In the microfluidic channel, a traveling wave corresponding to the microfluidic channel is formed in a direction perpendicular to the substrate. Scattering or the like of the traveling wave at the particle surface creates an acoustic wave radiation force that causes the particle to move along the position of the standing wave node. Because of the different radiation forces experienced by different particles, larger volumes of particles will deviate from the focused streamline and move to the collection outlet, while other particles flow out of the waste port. And the output area is arranged at the tail end of the separation area, the main pipeline is divided into two pipelines, namely a waste liquid output pipeline and a collecting pipeline, and the waste liquid and the target sample are respectively collected.
Further, the interdigital transducer is directly manufactured on the lithium niobate substrate by a photolithography process and an aluminum ion implantation method.
Further, polydimethylsiloxane structure (PDMS) with microfluidic channel grooves and lithium niobate substrate were bonded after plasma cleaning.
Compared with the prior art, the invention has the following beneficial effects: compared with the traditional pipeline with sheath flow, fewer micro-flow injection pumps are needed, and the total separation time is reduced under the condition of ensuring that the similar target separation precision is achieved under the same volume of sample.
Drawings
Fig. 1 is a 3D structure of a microfluidic chip of the present invention;
FIG. 2 is a top view of a microfluidic chip of the present invention;
FIG. 3 is a block diagram of a microfluidic channel;
fig. 4 is a schematic view of a focusing trajectory of particles of a sheath-free flow microfluidic channel under a Comsol simulation.
Detailed Description
The invention is further described below with reference to the accompanying drawings.
As shown in fig. 1-3, the surface acoustic wave-based sheath-flow-free microfluidic chip for particle separation comprises a microfluidic pipeline and an interdigital transducer, wherein the microfluidic chip is divided into an input area, an acceleration area, a focusing area, a sorting area and an output area. The structure of each region is as follows.
Input area: the radius of the circular hole of the conduit inlet 7 is 700 μm, the length of the conduit is 1300 μm, the minimum width of the conduit is 135 μm, and the conduit inlet 7 is connected to the sample input conduit 1.
Acceleration region: the tubing length was 1600 μm, the minimum tubing width was 35 μm, the maximum tubing width was 135 μm, comprising six half semi-circular protrusion arrays 8, the radius was 100 μm, and the minimum spacing between the semi-circles was 50 μm.
Focal region: the length of the tube was 2780. Mu.m, and the width of the tube was 800. Mu.m. At the left border a 60 deg. sharp angle is provided, which area is provided with a positioning point 9.
Sorting area: the length of the tube is 7220 μm and the width of the tube is 800 μm, and an interdigital transducer 2 is provided.
Output area: the cross-sectional area ratio of the waste liquid channel 10 to the collecting channel 11 is 3:1, an included angle of 60 degrees is formed between the waste liquid channel 10 and the collecting channel 11, the lengths of the waste liquid channel 10 and the collecting channel 11 are 2500 mu m, and the tail ends of the waste liquid channel 10 and the collecting channel 11 are respectively provided with a waste liquid outlet 12 and a collecting outlet 13 with the radius of 700 mu m and are respectively used for being connected into the waste liquid conduit 3 and the collecting conduit 4.
And the micro-fluidic pipeline is formed on the PDMS structure 5, the PDMS structure 5 and the lithium niobate substrate 6 are cleaned by using plasma and then bonded to form a sheath-flow-free micro-fluidic chip, and particles can realize focusing under the driving of no surface acoustic wave.
The interdigital transducer 2 (IDTs) is directly manufactured on a lithium niobate substrate by a photolithography process and an aluminum ion implantation method, and the piezoelectric substrate material is 128 DEG Y-cut lithium niobate. Each IDTs has 25 pairs of fingers and 6 reflective strips, the spacing between the fingers being 40 μm and the wavelength being 160 μm. The IDTs are 5mm in length and form an included angle of 10 DEG with the microfluidic pipeline. By applying the same radio frequency power signals on the IDTs on the two sides, standing waves can be formed on the substrate between the IDTs, and then acoustic wave radiation force is formed on the particles, and the particles deflect to the collecting outlet from the focusing streamline under the acoustic wave radiation force, so that particle sorting is realized.
As shown in fig. 4, the sheath-free flow microfluidic pipeline focuses on the trajectories of particles under the Comsol simulation.
The foregoing is only a preferred embodiment of the present invention. It should be noted that: it will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the principles of the present invention, and such modifications and adaptations are intended to be comprehended within the scope of the invention.
Claims (5)
1. The utility model provides a no sheath flow micro-fluidic chip for particle separation based on surface acoustic wave, includes micro-fluidic pipeline, interdigital transducer and lithium niobate substrate (6), micro-fluidic chip divide into input region, acceleration region, focus region, separation region, output region, its characterized in that:
The input area is provided with a conduit inlet (7), the radius of a round hole of the conduit inlet (7) is 700 mu m, the length of the pipeline is 1300 mu m, the minimum width of the pipeline is 135 mu m, and the conduit inlet (7) is connected into the sample input pipeline (1); the accelerating area is provided with six semicircular protrusion arrays (8) with the radius of 100 mu m, the minimum interval between the semicircles is 50 mu m, the maximum width of the pipeline is 135 mu m, and the minimum width of the pipeline is 35 mu m; the focusing area is provided with a 60-degree sharp angle at the left side boundary, the focusing area is provided with a positioning point (9), the length of the pipeline is 2780 mu m, and the width of the pipeline is 800 mu m; the sorting area is provided with two interdigital transducers (2) distributed on two sides of the microfluidic pipeline; the output area is provided with a waste liquid channel (10) and a collecting channel (11), the cross-sectional area ratio of the waste liquid channel (10) to the collecting channel (11) is 3:1, the included angle is 60 degrees, the tail ends of the waste liquid channel (10) and the collecting channel (11) are respectively provided with a waste liquid outlet (12) and a collecting outlet (13), and the waste liquid outlet (12) and the collecting outlet (13) are respectively used for being connected into the waste liquid guide pipe (3) and the collecting guide pipe (4).
2. The surface acoustic wave-based sheath-flow-free microfluidic chip for particle separation of claim 1, wherein: the microfluidic pipeline is formed on a PDMS structure (5), and the PDMS structure (5) is bonded with a lithium niobate substrate (6).
3. The surface acoustic wave-based sheath-flow-free microfluidic chip for particle separation of claim 2, wherein: the interdigital transducer (2) is directly formed on a lithium niobate substrate through a photoetching process and aluminum ion implantation, and the material of the lithium niobate substrate is 128-degree Y-cut lithium niobate.
4. The surface acoustic wave-based sheath-flow-free microfluidic chip for particle separation of claim 1, wherein: each interdigital transducer (2) has 25 pairs of interdigital transducers and 6 reflection strips, the interval between the interdigital transducers is 40 mu m, the wavelength is 160 mu m, and an included angle of 10 degrees is formed between the interdigital transducers and the microfluidic pipeline.
5. The surface acoustic wave-based sheath-flow-free microfluidic chip for particle separation according to claim 4, wherein: by applying the same radio frequency power signals to the interdigital transducers on two sides, standing waves are formed on the substrate between the interdigital transducers, and then acoustic wave radiation force is formed on the particles, and the particles deflect to the collecting outlet from the focusing streamline under the acoustic wave radiation force, so that particle sorting is realized.
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| CN201910349727.3A CN110237873B (en) | 2019-04-28 | 2019-04-28 | Sheath-flow-free micro-fluidic chip for particle separation based on surface acoustic wave |
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| CN110237873B true CN110237873B (en) | 2024-05-07 |
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Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110653014B (en) * | 2019-10-28 | 2020-08-25 | 西安交通大学 | Particle multilayer film structure generating device based on surface acoustic wave |
| CN112973986B (en) * | 2019-12-14 | 2023-07-14 | 深圳先进技术研究院 | Centrifugal device |
| CN111157616A (en) * | 2020-01-21 | 2020-05-15 | 杭州电子科技大学 | Detection platform integrating acoustic surface standing wave cell sorting and lensless imaging |
| CN113736649A (en) * | 2021-09-03 | 2021-12-03 | 中国科学院深圳先进技术研究院 | Apparatus and method for screening particles within a fluid sample |
| CN115382590A (en) * | 2022-08-19 | 2022-11-25 | 南京理工大学 | Sheath-flow-free particle sorting micro-fluidic chip based on surface acoustic waves |
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| CN105283753A (en) * | 2013-03-14 | 2016-01-27 | 塞通诺米/St有限责任公司 | Hydrodynamic focusing apparatus and methods |
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| CN105283753A (en) * | 2013-03-14 | 2016-01-27 | 塞通诺米/St有限责任公司 | Hydrodynamic focusing apparatus and methods |
| CN103341372A (en) * | 2013-07-05 | 2013-10-09 | 西北工业大学 | Micro-fluidic chip structure for flow cytometer, and preparation method of micro-fluidic chip |
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