CN109622078A - A kind of micro-fluidic chip for the single position enrichment of particle in non-newtonian fluid - Google Patents

A kind of micro-fluidic chip for the single position enrichment of particle in non-newtonian fluid Download PDF

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Publication number
CN109622078A
CN109622078A CN201811511307.2A CN201811511307A CN109622078A CN 109622078 A CN109622078 A CN 109622078A CN 201811511307 A CN201811511307 A CN 201811511307A CN 109622078 A CN109622078 A CN 109622078A
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particle
micro
microchannel
single position
fluidic chip
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CN201811511307.2A
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CN109622078B (en
Inventor
赵亮
闫庆
范亮亮
张虹
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Xian Jiaotong University
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Xian Jiaotong University
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502707Containers 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 characterised by the manufacture of the container or its components
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/026Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06Fluid handling related problems
    • B01L2200/0647Handling flowable solids, e.g. microscopic beads, cells, particles
    • B01L2200/0652Sorting or classification of particles or molecules
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/10Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0861Configuration of multiple channels and/or chambers in a single devices

Abstract

A kind of micro-fluidic chip for the single position enrichment of particle in non-newtonian fluid, is made of cover plate layer and slide glass, particle mixed liquor liquid feeding area, particle rich microchannel, the fluid expansion area of observation coverage and liquid drainage region is offered on cover plate floor;Particle mixed liquor enters particle rich microchannel by particle mixed liquor liquid feeding area, and by particle rich microchannel, particle rich to single position is observed record through fluid expansion area, and final granule liquid is handled by the outflow of liquid discharge area;The single position enrichment of particle in non-newtonian fluid can be achieved in the present invention, and the present invention has many advantages, such as that handling ease, structure are simple, at low cost, easy to carry, has important application potentiality in fields such as biomedical and Food Sciences.

Description

A kind of micro-fluidic chip for the single position enrichment of particle in non-newtonian fluid
Technical field
The present invention relates to a kind of micro-fluidic chips, and in particular to one kind is for the single position enrichment of particle in non-newtonian fluid Micro-fluidic chip.
Background technique
Micro-fluidic chip is the functions such as preparation, sample introduction, reaction, separation, the detection for realizing sample in the minicore of one Piece, has that required sample volume is small, detection efficiency is high, use cost is low and is easy to and other technologies integration of equipments, good simultaneous The advantages that capacitive, plays an important role in the fields such as biomedical, food and environmental monitoring, such as medical diagnosis on disease, food safety detection With water quality monitoring etc..In field of biomedicine, it usually needs target cell is enriched with and is extracted from whole blood, to arrange Except the interference of other cells or particle.Such as it in the research and diagnosis of cancer, needs malignant cell (it is thin to be commonly called as cancer Born of the same parents) effective enrichment is carried out from blood and is extracted.In the quality safety detection of milk, need to micro- life such as contained bacterium Object is enriched with and is extracted, so as to subsequent detection.Blood and milk are typical non-newtonian fluids, with Newtonian fluid (such as water) There are significant differences for rheological behavior, cause two phase separation of Fluid-Particle different, the enrichment discipline of particle in a fluid is different.Mesh The micro-fluidic chip of particle rich and extraction is less in preceding realization non-newtonian fluid, has work and is concentrated mainly in straight channel. In general, required straight channel is longer, it is unfavorable for the efficient of each component on micro-fluidic chip and integrates.In addition to this, particle or cell There are multiple equilbrium positions in straight channel, is unfavorable for subsequent particle detections and high efficiency extraction.
Therefore, small, high-efficient, the portable microflow controlled biochip of research and development size, realizes the list of particle in non-newtonian fluid The enrichment of one position and extraction, have great significance for fields such as biomedical and food safeties.
Summary of the invention
In order to overcome the above-mentioned problems of the prior art, the purpose of the present invention is to provide one kind to be used for non-newtonian fluid The micro-fluidic chip of the middle single position enrichment of particle, can be to the particle or the single position richness of cell realization in non-newtonian fluid Collection has many advantages, such as handling ease, simple structure, low cost, high efficiency, easy to carry, in biomedicine, clinical diagnosis and controls The fields such as treatment, have a good application prospect.
In order to achieve the above object, the present invention adopts the following technical scheme:
A kind of micro-fluidic chip for the single position enrichment of particle in non-newtonian fluid, by cover plate layer 5 and is placed in cover plate Slide glass 6 under layer 5 forms;Particle mixed liquor liquid feeding area 1, particle rich microchannel 2, fluid expansion are offered on the cover plate floor 5 Open observation area 3, liquid drainage region 4 and semi-cylindrical in configuration 7;The particle rich microchannel 2 is sin type curved microchannel, Wherein side has the semi-cylindrical in configuration 7 to 2 indent of particle rich microchannel;2 entrance of particle rich microchannel and particle 1 outlet of mixed liquor liquid feeding area;The outlet of particle rich microchannel 2 is connected to 3 entrance of the fluid expansion area of observation coverage;Fluid expands The area of observation coverage 3 is opened for reducing the flow rate of liquid containing particle, to be observed record to particle;The fluid expansion area of observation coverage 3 goes out Mouth is connected with 4 entrance of liquid drainage region;The particle mixed liquor liquid feeding area 1 and liquid drainage region 4 are to open up on cover plate floor 5 Through-hole, the particle rich microchannel 2 and the fluid expansion area of observation coverage 3 are to open on the surface that cover plate layer 5 is in contact with slide glass 6 If blind way.
The sin type curved microchannel structure meets y=10sin (π x/50), and x refers to flow direction, and y refers to Be perpendicular to flow direction.
The radius of the recessed semi-cylindrical in configuration 7 in 2 side of particle rich microchannel is 10-40 μm, adjacent semicolumn The center of structure 7 in the flowing direction is away from being 100 μm;The quantity for the semi-cylindrical in configuration 7 being recessed in the particle rich microchannel 2 It is 60-120.
The fluid extension area of observation coverage 3 is symmetrical divergent structure, and the angle for extending wall surface and horizontal direction is 5 ° -30 °.
The cover plate layer 5 and slide glass 6 are combined together by plasma treatment.
The particle rich microchannel 2 and the fluid expansion area of observation coverage 3 are located at cover plate layer 5 and slide glass 6 combines the center at place Position.
The semi-cylindrical in configuration 7 is to belong to a part of particle rich microchannel 2.
The particle mixed liquor liquid feeding area 1 and liquid drainage region 4 are cylindrical hole.
The particle mixed liquor liquid feeding area 1 is to inject in micro-fluidic chip mixed liquor with certain flow.
The material of the cover plate layer 5 is polymetylmethacrylate or polydimethylsiloxane;
The material of the slide glass 6 is glass or silicon.
The present invention is compared to the prior art compared with having the advantages that
1) the single position enrichment of particle in non-newtonian fluid is realized.The present invention is by introducing indent in sin type microchannel Cylinder, using particle in microchannel by dien vertex power caused by elastic force caused by non-newtonian fluid, interior fluted column with And the collective effect of inertia force, finally realize the single position enrichment of particle.The present invention can be in shorter passage length, lower fluid Realize that the single position enrichment of particle in non-newtonian fluid (per minute less than 30 microlitres, minimum can be to 5 micro- under the conditions of shear action Liter Per Minute), it is accurately detected for subsequent particle and establishes important foundation.
2) channel size is smaller, convenient for integrated and portable with other assemblies, be applied to can be convenient field first aid, Domestic medicine and individual health care etc..
3) at low cost, it is easy to make.Micro-fluidic chip of the invention is achieved that by simple standard soft lithography technology Processing and fabricating, thus the present invention is suitable for large-scale production and marketing.
4) structure is simple, and operation is easy, the risk of no sheath stream pollution.
Detailed description of the invention
Fig. 1 is micro-fluidic chip top view of the present invention for the single position enrichment of particle in non-newtonian fluid.
Fig. 2 be Fig. 1 along A-A to cross-sectional view.
Fig. 3 is schematic three dimensional views of the present invention for the micro-fluidic chip of the single position enrichment of particle in non-newtonian fluid.
Fig. 4 is the partial enlarged view of particle rich microchannel.
Fig. 5 is experimental result picture of the present invention for the single position enrichment of particle in non-newtonian fluid.
Specific embodiment
The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments:
As shown in Figure 1, Figure 2, Figure 3 and Figure 4, the present invention is a kind of for the micro- of the single position enrichment of particle in non-newtonian fluid Fluidic chip, the chip are process by standard soft lithography technology, and the micro-fluidic chip is by cover plate layer 5 and is placed in cover plate layer 5 Under slide glass 6 form;Particle mixed liquor liquid feeding area 1, particle rich microchannel 2, fluid expansion sight are offered on the cover plate floor 5 Examine area 3, liquid drainage region 4 and semi-cylindrical in configuration 7;The particle rich microchannel 2 is the microchannel of sin type curved, Middle side has the semi-cylindrical in configuration 7 to 2 indent of particle rich microchannel;2 entrance of particle rich microchannel and particle are mixed 1 outlet of He Ye liquid feeding area;The outlet of particle rich microchannel 2 is connected to 3 entrance of the fluid expansion area of observation coverage;Fluid expansion The area of observation coverage 3 is for reducing the flow rate of liquid containing particle, to be observed record to particle;The fluid expansion area of observation coverage 3 exports It is connected with 4 entrance of liquid drainage region;The particle mixed liquor liquid feeding area 1 and liquid drainage region 4 open up on cover plate floor 5 Through-hole, the particle rich microchannel 2 and the fluid expansion area of observation coverage 3 are to open up on the surface that cover plate layer 5 is in contact with slide glass 6 Blind way.The diameter of the present embodiment particle mixed liquor liquid feeding area 1 and 4 cavity of liquid drainage region is all 1-2mm, highly with cover plate layer 5 height are consistent.Particle mixed liquor liquid feeding area 1, particle rich microchannel 2, fluid extension observation area 3, liquid drainage region 4 and semicircle The microchannel that rod structure 7 is formed is located at the central location that cover plate layer 5 is combined with slide glass 6.2 width of particle rich microchannel is 40 μm, depth is 40 μm, and front end connects the outlet in particle mixed liquor liquid feeding area 2.The particle rich microchannel 2 is sin type curve Bending micro, mathematic(al) structure model are y=asin (π x/50), and the value of a is 5-30um, and x refers to flow direction, and y refers to Be perpendicular to flow direction, as the preferred embodiment of the present invention, a value is 10.The particle rich microchannel 2 is most wide The width at place is 40 μm, including 60-120 indent half cylindrical structure 7 be located at bending channel side, as of the invention preferred Embodiment, semicolumn number are 100.The radius of the circle of the recessed semi-cylindrical in configuration 7 of the microchannel is 10-40 μm, As the preferred embodiment of the present invention, the radius of the circle of semi-cylindrical in configuration 7 is 20um, the particle rich at semi-cylindrical in configuration 7 The most narrow place's width in microchannel 2 is 20 μm, and the distance of adjacent semi-cylindrical in configuration in the flowing direction is 100 μm.Fluid extension observation Area 3 is symmetrical divergent structure, and specific width can be according to specific flow rates demand flexible design, as preferred implementation side of the invention Formula, the angle for extending wall surface and horizontal direction is 6 °.
As the preferred embodiment of the present invention, micro-fluidic chip is processed using standard soft lithography technology in the present invention, institute It states cover plate layer 5 and slide glass 6 is combined together by plasma treatment.Also other materials or method can be used, such as dry method, wet process Etching etc. processes microchannel of the invention on the materials such as silicon wafer.
As the preferred embodiment of the present invention, the particle mixed liquor liquid feeding area 1 and liquid drainage region 4 are cylinder Hole.
As the preferred embodiment of the present invention, the material of the cover plate layer 5 is polymetylmethacrylate or gathers Dimethyl siloxane PDMS.
As the preferred embodiment of the present invention, the material of the slide glass 6 is glass or silicon.
Illustrate implementation process of the invention with an embodiment below:
The concrete operations of single position enrichment are as follows to be realized to the haemocyte in blood using micro-fluidic chip of the present invention, it will Blood containing haemocyte injects micro-fluidic chip by particle mixed liquor liquid feeding area 1 with certain flow.Haemocyte enters particle It is enriched with microchannel 2, by the sin type curved microchannel with semi- cylindrical, by caused by blood class non-newtonian fluid Dien vertex power and inertia force caused by elastic force, interior fluted column realize the single position of particle under the collective effect of three power Enrichment.The area of observation coverage 3 is extended through fluid after and, speed is further slack-off, can combine with detection means such as optics, realizes to blood The accurate detection of middle haemocyte.Mixed liquor after detection and analysis is carried out useless by the discharge micro-fluidic chip of liquid discharge area 4 Liquid processing.Fig. 5 is that flow is 5 microlitres per minute, and fluid extends the particle in the area of observation coverage 3 and arranges experimental result picture.Experimental verification The present invention can be achieved to be enriched with the single position of particle in non-newtonian fluid, in biomedical, analytical chemistry and Food Science etc. Field has important application potentiality.

Claims (10)

1. a kind of micro-fluidic chip for the single position enrichment of particle in non-newtonian fluid, by cover plate layer (5) and is placed in cover plate Layer 5) under slide glass (6) composition;It is characterized by: offering particle mixed liquor liquid feeding area (1), particle on the cover plate floor (5) It is enriched with microchannel (2), fluid expansion observation area (3), liquid drainage region (4) and semi-cylindrical in configuration (7);The particle rich is micro- logical Road (2) is sin type curved microchannel, and wherein side has the semi-cylindrical in configuration to particle rich microchannel (2) indent (7);Particle rich microchannel (2) entrance and particle mixed liquor liquid feeding area (1) outlet;The particle rich microchannel (2) outlet is connected to the fluid expansion area of observation coverage (3) entrance;The fluid expansion area of observation coverage (3) is for reducing the liquid flow containing particle Speed, to be observed record to particle;The fluid expansion area of observation coverage (3) outlet is connected with liquid drainage region (4) entrance;It is described Particle mixed liquor liquid feeding area (1) and liquid drainage region (4) are the through-hole opened up on cover plate floor (5), and the particle rich is micro- logical Road (2) and the fluid expansion area of observation coverage (3) are the blind way opened up on the surface that cover plate layer (5) is in contact with slide glass (6).
2. a kind of micro-fluidic chip for the single position enrichment of particle in non-newtonian fluid according to claim 1, Be characterized in that: the sin type curved microchannel structure meets y=10sin (π x/50), and x refers to flow direction, and y refers to Be perpendicular to flow direction.
3. a kind of micro-fluidic chip for the single position enrichment of particle in non-newtonian fluid according to claim 1, Be characterized in that: the radius of the recessed semi-cylindrical in configuration (7) in particle rich microchannel (2) side is 10-40 μm, adjacent half The center of cylindrical structure (7) in the flowing direction is away from being 100 μm;The semicolumn knot being recessed in the particle rich microchannel (2) The quantity of structure (7) is 60-120.
4. a kind of micro-fluidic chip for the single position enrichment of particle in non-newtonian fluid according to claim 1, Be characterized in that: the described fluid extension area of observation coverage (3) is symmetrical divergent structure, the angle for extending wall surface and horizontal direction is 5 °- 30°。
5. a kind of micro-fluidic chip for the single position enrichment of particle in non-newtonian fluid according to claim 1, Be characterized in that: the cover plate layer (5) and slide glass (6) are combined together by plasma treatment.
6. a kind of micro-fluidic chip for the single position enrichment of particle in non-newtonian fluid according to claim 1, It is characterized in that: the particle rich microchannel (2) and the fluid expansion area of observation coverage (3) is located at cover plate layer (5) and slide glass (6) combines The central location at place.
7. a kind of micro-fluidic chip for the single position enrichment of particle in non-newtonian fluid according to claim 1, Be characterized in that: the semi-cylindrical in configuration (7) is a part for belonging to particle rich microchannel (2).
8. a kind of micro-fluidic chip for the single position enrichment of particle in non-newtonian fluid according to claim 1, Be characterized in that: the particle mixed liquor liquid feeding area (1) and liquid drainage region (4) are cylindrical hole.
9. a kind of micro-fluidic chip for the single position enrichment of particle in non-newtonian fluid according to claim 1, Be characterized in that: the material of the cover plate layer (5) is polymetylmethacrylate or polydimethylsiloxane.
10. a kind of micro-fluidic chip for the single position enrichment of particle in non-newtonian fluid according to claim 1, Be characterized in that: the material of the slide glass (6) is glass or silicon.
CN201811511307.2A 2018-12-11 2018-12-11 Micro-fluidic chip for single-position enrichment of particles in non-Newtonian fluid Active CN109622078B (en)

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CN113893892A (en) * 2021-11-10 2022-01-07 大连海事大学 Nanopore based on microfluidic chip and preparation method thereof
CN114152132A (en) * 2021-11-22 2022-03-08 南京理工大学 Micro-channel heat exchanger based on dean vortex

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CN113042120A (en) * 2021-03-24 2021-06-29 西安交通大学 Micro-fluidic device for efficiently separating particles in viscoelastic fluid
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CN114152132A (en) * 2021-11-22 2022-03-08 南京理工大学 Micro-channel heat exchanger based on dean vortex
CN114152132B (en) * 2021-11-22 2024-02-20 南京理工大学 Micro-channel heat exchanger based on Dien vortex

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