CN110923127A - Micro-fluidic chip - Google Patents
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- CN110923127A CN110923127A CN201811098968.7A CN201811098968A CN110923127A CN 110923127 A CN110923127 A CN 110923127A CN 201811098968 A CN201811098968 A CN 201811098968A CN 110923127 A CN110923127 A CN 110923127A
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M23/00—Constructional details, e.g. recesses, hinges
- C12M23/02—Form or structure of the vessel
- C12M23/16—Microfluidic devices; Capillary tubes
Abstract
The invention relates to the field of microfluidics, in particular to a microfluidic chip. The microfluidic chip is provided with a special cap-shaped cavity structure, each cavity is a micro detection analysis chamber, the length of the longitudinal section of each cavity is larger than that of a target liquid drop (or cell), and the length of the longitudinal section of each cavity is 1.3 times larger than the diameter of the target liquid drop (or cell) and 2 times smaller than the diameter of the target liquid drop (or cell), and the length is optimal (1.3< d < 2). The micro-fluidic chip provided by the invention can be used for a water phase and oil phase system, single water phase droplets (or single droplets coated with single/multiple cells) are captured in the oil phase system, and single cells and microorganisms are captured in the water phase system.
Description
Technical Field
The invention relates to the field of microfluidics, in particular to a microfluidic chip.
Background
Microfluidic chip technology (Microfluidics), also known as Lab-on-a-chip, is capable of integrating the basic functions of conventional biological and chemical laboratories, including sample separation, preparation, chemical reactions, detection, etc., on a few square centimeters microchip.
The micro-fluidic chip has the characteristics of controllable liquid flow, extremely less consumption of samples and reagents, ten-fold or hundred-fold improvement of analysis speed and the like, can simultaneously analyze hundreds of samples in a few minutes or even shorter time, and can realize the whole processes of pretreatment and analysis of the samples on line. Droplet microfluidics is an important branch of microfluidic chip technology. Droplet microfluidic technology was developed over the traditional single-phase microfluidic chip technology, and the three-inlet T-type microfluidic chip design was first proposed by professor runtemf. Compared with a single-phase micro-fluidic system, the system has the advantages of less consumption of samples and reagents, higher mixing speed, difficulty in causing cross contamination, easiness in operation and the like due to the characteristic of water/oil two-phase separation. Therefore, the method has important application in the fields of rapid high-flux detection of pollutants, separation and cultivation of biological samples, observation of chemical reaction progress and the like. The micro-droplets have the advantages of high flux, no cross contamination and the like, and have great application potential in the fields of ink-jet printing, micro-mixing, DNA analysis, material synthesis, protein crystallization and the like.
In the process of observing and image analyzing cells, bacteria and microorganisms, a group is usually targeted for observation, so that the observation is roughly summarized, and if a single change is especially found, the observation cannot be found at all, so that the problem that the observation and image analysis of the cells, the bacteria and the microorganisms can be carried out independently is needed to be solved urgently.
Disclosure of Invention
In view of the above, the present invention provides a microfluidic chip. The chip can capture single individuals, and requirements of image analysis, fluorescence reaction analysis and the like through microscopic observation can be met conveniently.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a micro-fluidic chip, which comprises a substrate 1, wherein the substrate 1 is provided with a sample inlet 4, a sample outlet 5, a micro-channel 2 and a cap-shaped cavity 3;
the cap type cavity 3 is arranged between the sample inlet 4 and the sample outlet 5, and the opening of the cap type cavity 3 is communicated with the micro-channel 2.
Preferably, the opening length of the longitudinal section of the cap-shaped chamber 3 is not less than the diameter of the target droplet and/or cell.
More preferably, the ratio of the opening length of the longitudinal section of the cap-shaped chamber 3 to the diameter of the target droplet and/or cell is not less than 1.3: 1.
More preferably, the ratio of the opening length of the longitudinal section of the cap-shaped chamber 3 to the diameter of the target droplet and/or cell is 1.3-2: 1.
Preferably, the cap-shaped chamber 3 has a rectangular, arched or trapezoidal longitudinal section.
Preferably, the number of the cap-shaped chambers 3 is not less than 1.
Based on the technical scheme, the invention also provides the application of the microfluidic chip in capturing a single target; the target includes liquid drops, cells, microorganisms.
Based on the technical scheme, the invention also provides a device for capturing the single target, which comprises the microfluidic chip; the target includes liquid drops, cells, microorganisms.
Based on the technical scheme, the invention also provides a method for capturing the single target, wherein a sample, a water phase and/or an oil phase are introduced into the microfluidic chip, and the density of the water phase and/or the oil phase is adjusted, so that the single target enters the cap-shaped cavity 3; the target includes liquid drops, cells, microorganisms.
Preferably, the method further comprises the step of turning over the microfluidic chip after the single droplet and/or cell enters the cap-shaped chamber 3, so that the single target object leaves the cap-shaped chamber 3, enters the microchannel 2, and is collected.
The microfluidic chip provided by the invention has a special cap-shaped cavity structure, each cavity is a micro detection analysis chamber, the length of the longitudinal section of each cavity is larger than that of a target liquid drop (or cell), and the length of the longitudinal section of each cavity is 1.3 times larger than the diameter of the target liquid drop (or cell) and 2 times smaller than the diameter of the target liquid drop (or cell) to be optimal (1.3< d < 2). The micro-fluidic chip provided by the invention can be used for a water phase and oil phase system, single water phase droplets (or single droplets coated with single/multiple cells) are captured in the oil phase system, and single cells and microorganisms are captured in the water phase system.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below.
FIG. 1 shows a microfluidic chip provided by the present invention; wherein FIG. 1A shows a top view; FIG. 1B shows a side view;
FIG. 2 is a schematic diagram of a microfluidic chip for capturing a single droplet provided by the present invention; wherein, fig. 2A shows that the microfluidic chip provided by the present invention captures a single droplet; FIG. 2B shows microscopic observation and analysis in a cap-shaped chamber; FIG. 2C shows the microfluidic chip provided by the present invention inverted so that droplets enter the microchannel from the cap-shaped chamber to be collected at the sample outlet;
FIG. 3 shows the results of single droplets and single droplets coated with single cells captured by a cap-type chamber;
FIG. 4 is a schematic diagram showing the capture of a single droplet using the inverted structure of FIG. 1 when the droplet density is greater than the solution density;
FIG. 5 shows different cell separations performed by adjusting the density of the solution between the target and non-target to be separated;
wherein, 1-a substrate; 2-micro flow channel; 3-a cap-shaped chamber; 4-sample inlet; 5-sample outlet.
Detailed Description
The invention discloses a microfluidic chip, which can be realized by appropriately improving process parameters by referring to the content in the text by the technical personnel in the field. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention.
The parts, raw materials and reagents used in the microfluidic chip provided by the invention can be purchased from the market.
The invention provides a micro-fluidic chip, which comprises a substrate 1, wherein the substrate 1 is provided with a sample inlet 4, a sample outlet 5, a micro-channel 2 and a cap-shaped cavity 3;
the cap type cavity 3 is arranged between the sample inlet 4 and the sample outlet 5, and the opening of the cap type cavity 3 is communicated with the micro-channel 2.
In some embodiments of the invention, the length of the opening of the longitudinal section of the cap-shaped chamber 3 is not less than the diameter of the target droplet and/or cell. Preferably, the ratio of the opening length of the longitudinal section of the cap-shaped chamber 3 to the diameter of the target droplet and/or cell is not less than 1.3: 1. More preferably, the ratio of the opening length of the longitudinal section of the cap-shaped chamber 3 to the diameter of the target droplet and/or cell is 1.3-2: 1.
In some embodiments of the invention, the cap-shaped chamber 3 has a rectangular, arched or trapezoidal longitudinal section.
In some embodiments of the invention, the number of cap-shaped chambers 3 is not less than 1.
The length of the longitudinal section of the cap-shaped chamber can be changed (1.3< d <2) according to the diameter of the analyzed target (for example, bacteria, cells, microorganisms) or the diameter of the generated liquid drop, so that the capture of various targets can be realized. It is easy for those skilled in the art to change the size of the cap-shaped chamber, the shape of the longitudinal section, and the number of the cap-shaped chambers, and the present invention is not described herein, and the length of the longitudinal section of the cap-shaped chamber, the structure and the number of the cap-shaped chambers suitable for the target object are all within the protection scope of the present invention.
Based on the technical scheme, the invention also provides the application of the microfluidic chip in capturing a single target; the target includes liquid drops, cells, microorganisms.
Based on the technical scheme, the invention also provides a device for capturing the single target, which comprises the microfluidic chip; the target includes liquid drops, cells, microorganisms.
Based on the technical scheme, the invention also provides a method for capturing the single target, wherein a sample, a water phase and/or an oil phase are introduced into the microfluidic chip, and the density of the water phase and/or the oil phase is adjusted to enable the single target to enter the cap-shaped chamber 3; the target includes liquid drop, cell, microorganism. In other embodiments of the present invention, after the single droplet and/or cell enters the cap-shaped chamber 3, the method further comprises the step of inverting the microfluidic chip to allow the single target to leave the cap-shaped chamber 3, enter the microchannel 2, and be collected.
As shown in fig. 1, the microfluidic chip provided by the present invention achieves the goal that a single sample droplet can only enter a single cap-type chamber by matching the structure of the cap-type chamber with the density of oil and water, and the structure design is based on a cap, and a plurality of protrusion structures (cavities) are arranged on the surface of the micro flow channel, and the protrusion structures are used for capturing, observing and analyzing each target. As can be seen from the side view of fig. 1, the cap-shaped chamber 3 is connected to the micro flow channel 2, and when a sample enters, the density of oil and water is different (when the liquid drops flow through the cap-shaped chamber 3, the liquid drops enter the cap-shaped chamber 3 (fig. 2A), the cell types can be observed under a microscope, fluorescence analysis, immunofluorescence staining analysis and the like (fig. 2B), or automatic fluorescence analysis related instruments are used for assisting automatic analysis, and after the observation and analysis are finished, the sample can be taken out to facilitate subsequent further reaction, analysis or culture use or further downstream analysis, the micro flow control chip is turned over, the liquid drops can leave the cap-shaped chamber 3, and then the micro flow control chip is carried out by matching with an experiment buffer solution (fig. 2C).
The microfluidic chip provided by the invention enables liquid drops to float upwards and stay and be captured in the cap-shaped cavity when flowing under the condition that the cap-shaped cavity structure and the density of oil and water are different (taking the situation as an example, water is lighter than oil). If the density of the droplets is greater than that of the oil phase, the reversed structure of fig. 1 can be used for trapping, so that the droplets sink and are trapped in the micro-cavities while flowing. If the droplets are denser than the oil phase, capture can be achieved using the structure of FIG. 4.
When the detection and analysis are finished and the target object needs to be taken out, the micro-fluidic chip is only required to be turned over to be taken out. The selective capture of targets (single cell, single droplet, single microorganism, or single/multiple cell coating within single droplet) can be performed depending on the density of the aqueous phase or the oil phase.
In addition, on the basis of the microfluidic chip provided by the invention, selective capture can be carried out according to different target objects with different sizes, so that micro particles (or biological particles) larger than the micro-pores are filtered, and only micro particles (or biological particles) smaller than the micro-pores are captured.
The micro-fluidic chip provided by the invention can adjust the density of the water phase and/or the oil phase in a combined manner, so as to achieve the purpose of capturing a single target object.
In the water phase, the density of the water phase is adjusted to enable the cells to float above the solution (the density of the cells is less than that of the solution), and therefore the characteristics of the solution are combined with the cap-shaped chamber structure of the microfluidic chip provided by the invention to enable the cells to float in the cap-shaped chamber for observation.
On the basis, the solutions with different densities can be adjusted to separate the target objects. The density of the solution is adjusted according to the different volumes and densities of different cells, so that the density of the solution is between the target object and the non-target object to be separated, and different cell separation is performed. Such as red and white blood cells, red blood cells and circulating tumor cells, etc. The density of the solution is adjusted according to the basic characteristics (volume and density) of different cells, so that the non-target object cannot be influenced (or sink) by the solution, and the non-target object floats in the cap-shaped chamber due to the solution, thereby achieving the separation effect (fig. 5).
In the oil phase, the density of the oil phase is adjusted between the target object to be separated (solution with different density or particles containing solution) and other non-target objects (solution with different density or particles with different density coated in the same solution), so as to separate the liquid (micro-droplets) with different density or separate the selective capture of the particles (or biological particles) coated with different density in the same micro-liquid. The microfluidic chip provided by the invention can be applied to a magnetic bead immunocapture cell system, and the magnetic bead group immunologically combined with specific cells and single tiny magnetic bead not combined with cells are selectively filtered and/or selectively captured.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (10)
1. The microfluidic chip is characterized by comprising a substrate (1), wherein the substrate is provided with a sample inlet (4), a sample outlet (5), a micro-channel (2) and a cap-shaped chamber (3);
the cap type cavity (3) is arranged between the sample inlet (4) and the sample outlet (5), and the opening of the cap type cavity (3) is communicated with the micro-channel (2).
2. The microfluidic chip according to claim 1, wherein the opening length of the longitudinal section of the cap-shaped chamber (3) is not less than the diameter of the target droplet and/or cell.
3. The microfluidic chip according to claim 2, wherein the ratio of the opening length of the longitudinal section of the cap-shaped chamber (3) to the diameter of the target droplet and/or cell is not less than 1.3: 1.
4. The microfluidic chip according to claim 3, wherein the ratio of the opening length of the longitudinal section of the cap-shaped chamber (3) to the diameter of the target droplet and/or cell is (1.3-2): 1.
5. Microfluidic chip according to claim 4, characterized in that the cap-shaped chamber (3) has a rectangular, arched or trapezoidal longitudinal section.
6. Microfluidic chip according to claim 5, characterized in that the number of cap-shaped chambers (3) is not less than 1.
7. Use of a microfluidic chip according to any one of claims 1 to 6 for capturing a single target; the target includes liquid drops, cells, microorganisms.
8. A device for capturing a single target, comprising the microfluidic chip according to any one of claims 1 to 6; the target includes liquid drops, cells, microorganisms.
9. A method for capturing a single target, characterized in that a sample, an aqueous phase and/or an oil phase is introduced into the microfluidic chip according to any one of claims 1 to 6, and the density of the aqueous phase and/or the oil phase is adjusted to allow the single target to enter the cap-shaped chamber (3); the target includes liquid drops, cells, microorganisms.
10. The method according to claim 9, wherein the step of inverting the microfluidic chip after the single droplet and/or cell enters the cap chamber (3) to allow the single target to leave the cap chamber (3) and enter the microchannel (2) for collection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811098968.7A CN110923127A (en) | 2018-09-20 | 2018-09-20 | Micro-fluidic chip |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811098968.7A CN110923127A (en) | 2018-09-20 | 2018-09-20 | Micro-fluidic chip |
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| CN110923127A true CN110923127A (en) | 2020-03-27 |
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| CN201811098968.7A Pending CN110923127A (en) | 2018-09-20 | 2018-09-20 | Micro-fluidic chip |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113755332A (en) * | 2021-10-08 | 2021-12-07 | 临沂大学 | Single drop replacement capture microchip system with high time resolution and applications thereof |
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| CN104877899A (en) * | 2014-02-28 | 2015-09-02 | 中国科学院青岛生物能源与过程研究所 | System for rapidly, directly, absolutely and quantitatively detecting microbes based on liquid drop, and method thereof |
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| CN107828651A (en) * | 2017-09-27 | 2018-03-23 | 江汉大学 | A kind of micro-fluidic chip for unicellular microlayer model sample preparation |
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2018
- 2018-09-20 CN CN201811098968.7A patent/CN110923127A/en active Pending
Patent Citations (4)
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| CN104877898A (en) * | 2014-02-27 | 2015-09-02 | 中国科学院青岛生物能源与过程研究所 | System and method for low-cost and efficient separation and obtaining of single cell |
| CN104877899A (en) * | 2014-02-28 | 2015-09-02 | 中国科学院青岛生物能源与过程研究所 | System for rapidly, directly, absolutely and quantitatively detecting microbes based on liquid drop, and method thereof |
| KR101631940B1 (en) * | 2015-07-10 | 2016-06-20 | 충남대학교산학협력단 | Microfluidic Chip for Concurrent Monitoring of Susceptibility in Different Types of Cells to Samples |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113755332A (en) * | 2021-10-08 | 2021-12-07 | 临沂大学 | Single drop replacement capture microchip system with high time resolution and applications thereof |
| CN113755332B (en) * | 2021-10-08 | 2023-10-31 | 临沂大学 | Single drop replacement capture microchip system with high time resolution and application thereof |
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