CN109622078B - Micro-fluidic chip for single-position enrichment of particles in non-Newtonian fluid - Google Patents
Micro-fluidic chip for single-position enrichment of particles in non-Newtonian fluid Download PDFInfo
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- CN109622078B CN109622078B CN201811511307.2A CN201811511307A CN109622078B CN 109622078 B CN109622078 B CN 109622078B CN 201811511307 A CN201811511307 A CN 201811511307A CN 109622078 B CN109622078 B CN 109622078B
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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- 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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- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
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- 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
- B01L3/502707—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 characterised by the manufacture of the container or its components
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- 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
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- 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
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Abstract
A micro-fluidic chip for single-position enrichment of particles in non-Newtonian fluid consists of a cover plate layer and a slide glass, wherein a particle mixed liquid adding area, a particle enrichment micro-channel, a fluid expansion observation area and a liquid discharging area are arranged on the cover plate layer; the particle mixed liquid enters the particle enrichment microchannel from the particle mixed liquid adding area, passes through the particle enrichment microchannel, enriches particles to a single position, carries out observation and recording through the fluid expansion area, and finally flows out from the liquid discharge area for treatment; the invention can realize single-position enrichment of particles in non-Newtonian fluid, has the advantages of easy processing, simple structure, low cost, convenient carrying and the like, and has important application potential in the fields of biomedicine, food science and the like.
Description
Technical Field
The invention relates to a micro-fluidic chip, in particular to a micro-fluidic chip for single-position enrichment of particles in non-Newtonian fluid.
Background
The micro-fluidic chip is a micro-chip integrating the functions of sample preparation, sample introduction, reaction, separation, detection and the like, has the advantages of small volume of the required sample, high detection efficiency, low use cost, easy integration with other technical equipment, good compatibility and the like, and has important functions in the fields of biomedicine, food and environment monitoring and the like, such as disease diagnosis, food safety detection, water quality monitoring and the like. In the biomedical field, it is often necessary to enrich and extract target cells from whole blood in order to exclude interference from other cells or particles. For example, in the study and diagnosis of cancer, there is a need for the effective enrichment and extraction of malignant cells (commonly referred to as cancer cells) from blood. In the quality safety detection of milk, microorganisms such as bacteria need to be enriched and extracted for subsequent detection. Blood and milk are typical non-newtonian fluids, and have significant differences in rheological properties from newtonian fluids (e.g., water), resulting in different fluid-particle two-phase effects and different enrichment laws of particles in the fluid. At present, few micro-fluidic chips for realizing particle enrichment and extraction in non-Newtonian fluid exist, and the existing work is mainly focused in a straight channel. Generally, the required straight channels are long, which is not conducive to efficient integration of components on the microfluidic chip. In addition, the particles or cells have a plurality of equilibrium positions in the straight channel, which is not favorable for subsequent particle detection and efficient extraction.
Therefore, the micro-fluidic biochip which is small in size, high in efficiency and portable is developed, single-position enrichment and extraction of particles in non-Newtonian fluid are achieved, and the micro-fluidic biochip has important significance in the fields of biomedicine, food safety and the like.
Disclosure of Invention
In order to overcome the problems in the prior art, the invention aims to provide a microfluidic chip for single-position enrichment of particles in non-newtonian fluid, which can realize single-position enrichment of particles or cells in the non-newtonian fluid, has the advantages of easy processing, simple structure, low cost, high efficiency, convenience in carrying and the like, and has good application prospects in the fields of biomedicine, clinical diagnosis, treatment and the like.
In order to achieve the purpose, the invention adopts the following technical scheme:
a micro-fluidic chip for single-position enrichment of particles in non-Newtonian fluid consists of a cover plate layer 5 and a slide 6 arranged below the cover plate layer 5; the cover plate layer 5 is provided with a particle mixed liquid adding area 1, a particle enrichment microchannel 2, a fluid expansion observation area 3, a liquid discharging area 4 and a semi-cylindrical structure 7; the particle-enriched micro-channel 2 is a sin-type curve bending micro-channel, and one side of the micro-channel is provided with a semi-cylindrical structure 7 which is concave towards the particle-enriched micro-channel 2; the inlet of the particle enrichment micro-channel 2 is communicated with the outlet of the particle mixed liquid adding area 1; the outlet of the particle-enriched micro-channel 2 is communicated with the inlet of the fluid expansion observation area 3; the fluid expansion observation area 3 is used for reducing the flow rate of the liquid containing the particles so as to perform observation and recording on the particles; the outlet of the fluid expansion observation area 3 is communicated with the inlet of the liquid drainage area 4; the particle mixed liquid adding area 1 and the liquid discharging area 4 are through holes formed in the cover sheet layer 5, and the particle enrichment micro-channel 2 and the fluid expansion observation area 3 are blind channels formed in the surface, in contact with the slide glass 6, of the cover sheet layer 5.
The sin-type curved micro-channel structure satisfies y 10sin (pi x/50), wherein x refers to the flow direction, and y refers to the direction perpendicular to the flow direction.
The radius of the semi-cylindrical structures 7 recessed on one side of the particle enrichment microchannel 2 is 10-40 μm, and the center distance of the adjacent semi-cylindrical structures 7 in the flow direction is 100 μm; the number of the semi-cylindrical structures 7 recessed in the particle-enriched microchannel 2 is 60 to 120.
The fluid expansion observation area 3 is a symmetrical gradually-expanding structure, and the angle between the expansion wall surface and the horizontal direction is 5-30 degrees.
The cover sheet layer 5 and the slide 6 are bonded together by plasma treatment.
The particle-enriched microchannel 2 and the fluid expansion observation zone 3 are located at the central position where the cover sheet layer 5 and the slide 6 are combined.
The semi-cylindrical structures 7 are part of a particle-enriched microchannel 2.
The particle mixed liquid adding area 1 and the liquid discharging area 4 are both cylindrical holes.
The particle mixed liquid adding area 1 is used for injecting the mixed liquid into the microfluidic chip at a certain flow rate.
The cover plate layer 5 is made of polymethyl methacrylate (PMMA) or Polydimethylsiloxane (PDMS);
the material of the slide 6 is glass or silicon.
Compared with the prior art, the invention has the following advantages:
1) and realizing single-position enrichment of particles in the non-Newtonian fluid. The invention introduces the concave cylinder in the sin-type micro-channel, and finally realizes the single-position enrichment of the particles by utilizing the combined action of the elastic force caused by the non-Newtonian fluid, the dean vortex force caused by the concave cylinder and the inertia force of the particles in the micro-channel. The invention can realize single-position enrichment (less than 30 microliter per minute and as low as 5 microliter per minute) of particles in the non-Newtonian fluid under the conditions of shorter channel length and lower fluid shearing action, and lays an important foundation for the accurate detection of subsequent particles.
2) The channel has small size, is convenient to integrate with other components, is easy to carry, and can be conveniently applied to the aspects of on-site first aid, family medical treatment, personal health care and the like.
3) Low cost and easy manufacture. The micro-fluidic chip can be processed and manufactured by a simple standard soft lithography technology, so that the micro-fluidic chip is suitable for large-scale production and market popularization.
4) Simple structure, easy operation, no risk of sheath flow pollution.
Drawings
FIG. 1 is a top view of a microfluidic chip for single-site enrichment of particles in non-Newtonian fluids according to the present invention.
Fig. 2 is a sectional view taken along a-a of fig. 1.
FIG. 3 is a three-dimensional schematic diagram of a microfluidic chip for single-site enrichment of particles in non-Newtonian fluids according to the present invention.
FIG. 4 is a partial enlarged view of a particle-enriched microchannel.
FIG. 5 is a graph showing experimental results of the present invention for single site enrichment of particles in a non-Newtonian fluid.
Detailed Description
The invention is described in further detail below with reference to the following figures and detailed description:
as shown in fig. 1, fig. 2, fig. 3 and fig. 4, the microfluidic chip for single-position particle enrichment in non-newtonian fluid according to the present invention is manufactured by a standard soft lithography technique, and comprises a cover sheet layer 5 and a slide 6 disposed under the cover sheet layer 5; the cover plate layer 5 is provided with a particle mixed liquid adding area 1, a particle enrichment microchannel 2, a fluid expansion observation area 3, a liquid discharging area 4 and a semi-cylindrical structure 7; the particle-enriched micro-channel 2 is a sin-type curved micro-channel, and one side of the micro-channel is provided with a semi-cylindrical structure 7 which is concave towards the particle-enriched micro-channel 2; the inlet of the particle enrichment micro-channel 2 is communicated with the outlet of the particle mixed liquid adding area 1; the outlet of the particle-enriched micro-channel 2 is communicated with the inlet of the fluid expansion observation area 3; the fluid expansion observation area 3 is used for reducing the flow rate of the liquid containing the particles so as to perform observation and recording on the particles; the outlet of the fluid expansion observation area 3 is communicated with the inlet of the liquid drainage area 4; the particle mixed liquid adding area 1 and the liquid discharging area 4 are through holes formed in the cover sheet layer 5, and the particle enrichment micro-channel 2 and the fluid expansion observation area 3 are blind channels formed in the surface, in contact with the slide glass 6, of the cover sheet layer 5. In this embodiment, the diameter of the cavities of the particle mixture liquid adding region 1 and the liquid discharging region 4 is 1-2mm, and the height is the same as that of the cover sheet layer 5. The micro-channel formed by the particle mixed liquid adding area 1, the particle enrichment micro-channel 2, the fluid expansion observation area 3, the liquid discharging area 4 and the semi-cylindrical structure 7 is positioned in the central position where the cover plate layer 5 is combined with the slide glass 6. The width of the particle enrichment micro-channel 2 is 40 μm, the depth is 40 μm, and the front end is connected with the outlet of the particle mixed liquid adding area 2. The particle enrichment microchannel 2 is a sin-type curve bending microchannel, the mathematical structure model of the particle enrichment microchannel is that y is asin (pi x/50), the value of a is 5-30um, x refers to the flow direction, y refers to the direction perpendicular to the flow direction, and as a preferred embodiment of the invention, the value of a is 10. The widest part of the particle-enriched microchannel 2 has a width of 40 μm, and comprises 60 to 120 concave semicylindrical structures 7 at one side of the curved channel, and the number of the semicylindrical structures is 100 as a preferred embodiment of the present invention. The radius of the circle of the concave semi-cylindrical structure 7 of the microchannel is 10-40 μm, as a preferred embodiment of the invention, the radius of the circle of the semi-cylindrical structure 7 is 20um, the width of the narrowest part of the particle-enriched microchannel 2 at the semi-cylindrical structure 7 is 20 μm, and the distance between the adjacent semi-cylindrical structures in the flow direction is 100 μm. The fluid expansion observation area 3 is a symmetrical gradually-expanding structure, the specific width can be flexibly designed according to the specific flow velocity requirement, and as a preferred embodiment of the invention, the angle between the expansion wall surface and the horizontal direction is 6 degrees.
As a preferred embodiment of the invention, the microfluidic chip of the invention is processed using standard soft lithography techniques, and the cover sheet layer 5 and the slide 6 are bonded together by plasma treatment. Other materials or methods, such as dry etching, wet etching, etc., may also be used to fabricate the microchannels of the present invention in materials such as silicon wafers.
In a preferred embodiment of the present invention, the particle mixture liquid addition region 1 and the liquid discharge region 4 are both cylindrical holes.
In a preferred embodiment of the present invention, the material of the cover sheet layer 5 is polymethyl methacrylate (PMMA) or Polydimethylsiloxane (PDMS).
As a preferred embodiment of the present invention, the material of the carrier sheet 6 is glass or silicon.
The following describes the implementation of the present invention in one embodiment:
the specific operation of the microfluidic chip for realizing single-position enrichment of the blood cells in the blood is as follows, the blood containing the blood cells is injected into the microfluidic chip at a certain flow rate from the particle mixed liquid adding area 1. Blood cells enter the particle enrichment microchannel 2, pass through the sin-type curve curved microchannel with the semi-cylindrical shape, and are subjected to elastic force caused by blood non-Newtonian fluid, dean vortex force and inertia force caused by concave cylinders, and under the combined action of the three forces, single-position enrichment of particles is realized. Then, the speed is further slowed down through the fluid expansion observation area 3, and the blood cell detection device can be combined with detection means such as optics and the like to realize accurate detection of blood cells in blood. The detected and analyzed mixed liquid is discharged out of the microfluidic chip through the liquid discharge area 4 to be subjected to waste liquid treatment. Fig. 5 is a graph showing the results of an experiment of particle alignment in the fluid expansion observation zone 3 at a flow rate of 5 microliters per minute. Experiments prove that the method can realize single-position enrichment of particles in the non-Newtonian fluid, and has important application potential in the fields of biomedicine, analytical chemistry, food science and the like.
Claims (7)
1. A micro-fluidic chip for single-position enrichment of particles in non-Newtonian fluid is composed of a cover plate layer (5) and a slide glass (6) arranged below the cover plate layer (5); the method is characterized in that: the cover plate layer (5) is provided with a particle mixed liquid adding area (1), a particle enrichment micro-channel (2), a fluid expansion observation area (3), a liquid discharging area (4) and a semi-cylindrical structure (7); the particle-enriched micro-channel (2) is a sin-type curve curved micro-channel satisfying y 10sin (pi x/50), wherein x refers to the flow direction, y refers to the direction perpendicular to the flow direction, one side of the micro-channel is provided with a semi-cylindrical structure (7) which is concave towards the particle-enriched micro-channel (2), the radius of the semi-cylindrical structure (7) is 10-40 mu m, the center distance of the adjacent semi-cylindrical structures (7) in the flow direction is 100 mu m, and the number of the semi-cylindrical structures is 60-120; the inlet of the particle enrichment micro-channel (2) is communicated with the outlet of the particle mixed liquid adding area (1); the outlet of the particle enrichment micro-channel (2) is communicated with the inlet of the fluid expansion observation area (3); the fluid expansion observation area (3) is used for reducing the flow rate of the liquid containing the particles so as to perform observation and recording on the particles; the outlet of the fluid expansion observation area (3) is communicated with the inlet of the liquid discharge area (4); the particle mixed liquid feeding area (1) and the liquid discharging area (4) are through holes formed in the cover sheet layer (5), and the particle enrichment micro-channel (2) and the fluid expansion observation area (3) are blind channels formed in the surface, in contact with the slide glass (6), of the cover sheet layer (5).
2. The microfluidic chip according to claim 1, wherein the microfluidic chip comprises: the fluid expansion observation area (3) is of a symmetrical gradually-expanding structure, and the angle between the expansion wall surface and the horizontal direction is 5-30 degrees.
3. The microfluidic chip according to claim 1, wherein the microfluidic chip comprises: the cover sheet layer (5) and the slide (6) are combined together by plasma treatment.
4. The microfluidic chip according to claim 1, wherein the microfluidic chip comprises: the particle enrichment microchannel (2) and the fluid expansion observation area (3) are positioned in the central position of the combination of the cover sheet layer (5) and the slide glass (6).
5. The microfluidic chip according to claim 1, wherein the microfluidic chip comprises: the particle mixed liquid adding area (1) and the liquid discharging area (4) are both cylindrical holes.
6. The microfluidic chip according to claim 1, wherein the microfluidic chip comprises: the cover plate layer (5) is made of polymethyl methacrylate (PMMA) or Polydimethylsiloxane (PDMS).
7. The microfluidic chip according to claim 1, wherein the microfluidic chip comprises: the material of the slide glass or silicon is used as the slide glass or silicon.
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CN113042120B (en) * | 2021-03-24 | 2022-03-01 | 西安交通大学 | Micro-fluidic device for efficiently separating particles in viscoelastic fluid |
CN113893892B (en) * | 2021-11-10 | 2023-02-10 | 大连海事大学 | Nanopore based on microfluidic chip and preparation method thereof |
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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WO2010102335A1 (en) * | 2009-03-10 | 2010-09-16 | Monash University | Platelet aggregation using a microfluidics device |
CN105980057A (en) * | 2013-11-19 | 2016-09-28 | 普拉托德公司 | Fluidic device for producing platelets |
CN107020164A (en) * | 2017-04-12 | 2017-08-08 | 东南大学 | A kind of high flux micro particles circulation sorting and enrichment facility and preparation method thereof |
CN107488582A (en) * | 2017-08-08 | 2017-12-19 | 上海交通大学 | Micro fluidic device |
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WO2010102335A1 (en) * | 2009-03-10 | 2010-09-16 | Monash University | Platelet aggregation using a microfluidics device |
CN105980057A (en) * | 2013-11-19 | 2016-09-28 | 普拉托德公司 | Fluidic device for producing platelets |
CN107020164A (en) * | 2017-04-12 | 2017-08-08 | 东南大学 | A kind of high flux micro particles circulation sorting and enrichment facility and preparation method thereof |
CN107488582A (en) * | 2017-08-08 | 2017-12-19 | 上海交通大学 | Micro fluidic device |
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