CN114669335A - Micro-droplet generation method and application method of micro-droplets - Google Patents

Micro-droplet generation method and application method of micro-droplets Download PDF

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Publication number
CN114669335A
CN114669335A CN202011549220.1A CN202011549220A CN114669335A CN 114669335 A CN114669335 A CN 114669335A CN 202011549220 A CN202011549220 A CN 202011549220A CN 114669335 A CN114669335 A CN 114669335A
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layer
droplets
fluid channel
polar plate
micro
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CN114669335B (en
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施苏宝
马汉彬
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Guangdong Aosu Liquid Core Micro Nano Technology Co ltd
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Guangdong Aosu Liquid Core Micro Nano Technology Co ltd
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Priority to CN202011549220.1A priority Critical patent/CN114669335B/en
Application filed by Guangdong Aosu Liquid Core Micro Nano Technology Co ltd filed Critical Guangdong Aosu Liquid Core Micro Nano Technology Co ltd
Priority to JP2023545222A priority patent/JP2024505501A/en
Priority to EP21908985.1A priority patent/EP4268957A1/en
Priority to PCT/CN2021/132216 priority patent/WO2022134986A1/en
Priority to AU2021407922A priority patent/AU2021407922A1/en
Priority to KR1020237025033A priority patent/KR20230123514A/en
Priority to US18/259,197 priority patent/US20240042436A1/en
Priority to CA3203394A priority patent/CA3203394A1/en
Publication of CN114669335A publication Critical patent/CN114669335A/en
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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
    • B01L3/50273Containers 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 means or forces applied to move the fluids

Abstract

The invention provides a method for generating micro-droplets and a method for applying the micro-droplets, wherein the method for generating the micro-droplets comprises the following steps: providing a chip, wherein the chip comprises an upper polar plate and a lower polar plate, an included angle is formed between the plane of the upper polar plate and the plane of the lower polar plate, a fluid channel layer is formed between the upper polar plate and the lower polar plate, the fluid channel layer comprises a first end and a second end which are oppositely arranged, and the height of the first end of the fluid channel layer is smaller than that of the second end of the fluid channel layer; forming a plurality of suction points on at least one of the upper polar plate and the lower polar plate, wherein the suction points are used for adsorbing liquid; by injecting liquid into the first end of the fluid channel layer, the liquid will gradually move from the first end to the second end and form small droplets at the location corresponding to the attraction point. The method for generating the micro-droplets can quickly prepare a large number of small droplets and greatly shorten the generation time of the droplets.

Description

Micro-droplet generation method and application method of micro-droplets
Technical Field
The invention relates to the technical field of microfluidics, in particular to a generation method of micro-droplets capable of quickly preparing micro-droplets in high quantity and application of the micro-droplets.
Background
How to uniformly decompose a certain volume of liquid into a large number of droplets with uniform volumes is one of the key problems to be solved in the microfluidic technology, and is a key link in application fields including digital polymerase chain reaction (ddPCR), digital loop-mediated isothermal amplification (dLAMP), digital enzyme-linked immunosorbent assay (dELISA), unicellular omics and the like. The current technical means for generating nanoliter liquid drops in high flux mainly comprise a micro-droplet micro-fluidic technology and a micro-well micro-fluidic technology. Representative microfluidic droplet flow technologies include Bio-Rad and 10 XMenomics, and the technology is characterized in that a high-precision micropump is used for controlling oil, and a cross-shaped structure is used for continuously extruding sample liquid so as to generate a large number of small droplets from picoliters to nanoliters. The method for generating nano-liter droplets at high flux based on the micro-droplet micro-fluidic technology relies on the accurate control of the pressure of a high-precision micro pump and the high-precision chip processing technology based on MEMS, the generated droplets are still stored in the same container, each droplet needs to be detected one by one through a micro channel during detection, the equipment cost is high, and the system is complex. Micro-well microfluidics, typified by Thermo Fisher, is characterized by mechanically spreading a sample solution over an array of micro-wells, such that the sample is evenly distributed into each micro-well, forming small droplets on the order of picoliters. The technology based on micro-well micro-fluidic usually needs to uniformly coat the reagent on the surface of the micro-well array by mechanical force, and then fill the upper and lower surfaces of the micro-well with inert medium liquid.
Digital microfluidics, due to its ability to manipulate each droplet independently, is another technology for high-throughput droplet generation, and WO 2016/170109 Al and US20200061620a1 both describe a method for generating a large number of droplets based on a digital microfluidic platform. However, the method for generating nanoliter droplets at high throughput based on digital microfluidic technology described in the above patent mainly uses digital microfluidic technology to manipulate a large droplet to generate a small droplet, and then transport the small droplet to a corresponding position. The main disadvantage of this method is the slow droplet generation and the long sample preparation time.
Disclosure of Invention
In view of the above, it is desirable to provide a method for generating micro-droplets capable of rapidly generating a large number of micro-droplets and an application of the micro-droplets.
A method of microdroplet generation comprising the steps of:
providing a chip, wherein the chip comprises an upper polar plate and a lower polar plate, an included angle is formed between the plane of the upper polar plate and the plane of the lower polar plate, a fluid channel layer is formed between the upper polar plate and the lower polar plate, the upper polar plate is provided with a plurality of sample injection holes, the sample injection holes are positioned at the edge of the upper polar plate and used for injecting samples, the fluid channel layer comprises a first end and a second end which are oppositely arranged, and the height of the first end of the fluid channel layer is smaller than that of the second end of the fluid channel layer;
forming a plurality of suction points on at least one of the upper plate and the lower plate, the suction points being used for adsorbing liquid;
injecting liquid into the first end of the fluid channel layer through the sample injection hole;
when liquid is injected into the fluid channel layer, the liquid gradually moves from the first end to the second end under the action of surface tension, and the liquid forms small liquid drops at the position corresponding to the attraction point.
In one embodiment, the lower electrode plate comprises an electrode layer, the electrode layer is an n × m electrode array, n and m are positive integers, and the shape of the electrode layer is a hexagon or a square.
In one embodiment, the upper plate comprises an upper cover, a conductive layer and a first hydrophobic layer which are sequentially stacked, the lower plate further comprises a second hydrophobic layer and a dielectric layer, the second hydrophobic layer, the dielectric layer and the electrode layer are sequentially stacked, and the fluid channel layer is formed between the first hydrophobic layer and the second hydrophobic layer.
In one embodiment, forming a plurality of attraction points on at least one of the upper plate and the lower plate is formed by: and a plurality of electrodes of the electrode layer are started, the started electrodes are the attraction points, and the adjacent started electrodes are arranged at intervals through the unopened electrodes.
In one embodiment, the distance between the upper plate and the lower plate at the first end is 0 μm to 20 μm.
In one embodiment, the angle between the upper plate and the lower plate is greater than 0 ° and less than 1 °.
In one embodiment, in the step of injecting the liquid into the first end of the fluid channel layer, the injection speed of the liquid is 1 μ L/s to 10 μ L/s.
In one embodiment, forming a plurality of attraction points on at least one of the upper plate and the lower plate is formed by: hydrophilic points are arranged on the first hydrophobic layer, the hydrophilic points are the attraction points, and the hydrophilic points are arranged at intervals.
In one embodiment, the hydrophilic dots are prepared as follows:
and carrying out hydrophilic modification on the first hydrophobic layer, and damaging the hydrophobic coating at the required position of the first hydrophobic layer by using laser or plasma to obtain the hydrophilic point.
In addition, an application method of the micro-droplets is also provided, which comprises the following steps:
preparing the micro-droplets by adopting the micro-droplet generation method;
and manipulating the micro-droplets through electrodes to complete subsequent application.
And carrying out hydrophilic modification on the first hydrophobic layer, and damaging the hydrophobic coating at the required position of the first hydrophobic layer by using laser or plasma to obtain the hydrophilic point.
In the method for generating the micro-droplets, liquid is injected into the first end of the fluid channel layer, when the upper polar plate and the lower polar plate are gradually close to each other, the liquid is gradually moved from the first end to the second end, and when the liquid passes through the attraction point, the small droplets are left in the position, corresponding to the attraction point, in the fluid channel layer due to the attraction effect of the attraction point. Compared with the traditional micro-droplet generation method which needs to separate droplets and then convey the droplets to a specified position, the micro-droplet generation method can quickly separate the micro-droplets at the required position, prepare a large amount of small droplets, greatly shorten the droplet generation time, improve the efficiency and simplify the operation flow. And equipment such as a high-precision micro pump and the like is not needed, so that the system cost is reduced. And the expansion capability is strong, and more small droplets or multiple groups of samples can be separated by expanding the chip size.
Drawings
Fig. 1 is a schematic flow chart of a method for generating micro droplets according to an embodiment.
Fig. 2 is a schematic flow chart of a method for generating micro droplets according to an embodiment.
Fig. 3 is a schematic cross-sectional view of a chip according to an embodiment.
FIG. 4 is a schematic diagram of a state of the chip of FIG. 3 in which droplets are prepared.
FIG. 5 is a schematic diagram of another state of the chip of FIG. 3 for preparing small droplets.
FIG. 6 is a top view of a chip showing the successive steps of preparing small droplets shown in FIG. 3.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention. It is to be understood that the embodiments described are only a few embodiments of the present invention, and not all embodiments. The components of embodiments of the present invention generally described and illustrated in the figures herein may be arranged and designed in a wide variety of different configurations.
Thus, the following detailed description of the embodiments of the present invention, presented in the figures, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
It should be noted that: like reference numbers and letters refer to like items in the following figures, and thus, once an item is defined in one figure, it need not be further defined and explained in subsequent figures.
In the description of the present invention, it should be understood that the relation indicating the orientation or position such as "above" is based on the orientation or position relation shown in the drawings, or the orientation or position relation which the product of the present invention is usually put into use, or the orientation or position relation which is usually understood by those skilled in the art, and is only for convenience of describing the present invention and simplifying the description, but does not indicate or imply that the device or element to be referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus, cannot be construed as limiting the present invention.
Furthermore, the terms "first," "second," and the like are used merely to distinguish one description from another, and are not to be construed as indicating or implying relative importance.
The following detailed description of embodiments of the invention refers to the accompanying drawings.
Referring to fig. 1, a method for generating micro-droplets according to an embodiment includes the following steps:
s10, providing a chip, wherein the chip comprises an upper polar plate and a lower polar plate, and an included angle is formed between the plane of the upper polar plate and the plane of the lower polar plate. The fluid channel layer is formed between the upper polar plate and the lower polar plate, the upper polar plate is provided with a plurality of sample injection holes, the sample injection holes are located on the edge of the upper polar plate and used for injecting samples, the fluid channel layer comprises a first end and a second end which are oppositely arranged, and the height of the first end of the fluid channel layer is smaller than that of the second end of the fluid channel layer.
And S20, forming a plurality of suction points on at least one of the upper polar plate and the lower polar plate, wherein the suction points are used for absorbing liquid.
And S30, injecting liquid into the first end of the fluid channel layer through the sample injection hole.
And S40, when the liquid is injected into the fluid channel layer, the liquid gradually moves from the first end to the second end under the action of surface tension, and the liquid forms small liquid drops at the position corresponding to the attraction point.
S40 is specifically that, after the liquid is injected into the fluid channel layer, the upper plate and the lower plate are gradually closed, and the liquid gradually moves from the first end to the second end under the action of surface tension, and the liquid forms small droplets at the position corresponding to the attraction point.
It is understood that the order of S20 and S30 is not limited to S20 followed by S30. In a specific case, S30 may be performed first, and then S20 may be performed.
In the method for generating the micro-droplets, liquid is injected into the first end of the fluid channel layer, when the upper polar plate and the lower polar plate are gradually close to each other, the liquid is gradually moved from the first end to the second end, and when the liquid passes through the attraction point, the small droplets are left in the position, corresponding to the attraction point, in the fluid channel layer due to the attraction effect of the attraction point. The method for generating the micro-droplets can quickly prepare a large number of small droplets, greatly shortens the droplet generation time and has simple and convenient operation flow. And equipment such as a high-precision micro pump and the like is not needed, so that the system cost is reduced. And the expansion capability is strong, and more small droplets or multiple groups of samples can be separated by expanding the chip size.
The height of the first end of the fluid channel layer is smaller than the height of the second end of the fluid channel layer, which means that: the distance between the upper plate and the lower plate is smallest at the first end and largest at the second end.
In one embodiment, the attraction points may be formed on the upper plate or the lower plate. Or forming attraction points on the upper polar plate and the lower polar plate simultaneously.
In particular, the attraction points may be formed by different methods.
In one embodiment, the lower plate comprises an electrode layer comprising a plurality of electrodes arranged in an array. The shape of the electrodes may be hexagonal or square, although the shape of the electrodes is not limited to hexagonal or square. Specifically, the electrode layer is an n × m electrode array, where n and m are positive integers. Forming a plurality of attraction points on at least one of the upper plate and the lower plate is formed by: and a plurality of electrodes of the electrode layer are started, the started electrodes are attraction points, and the adjacent started electrodes are arranged at intervals through the unopened electrodes.
The method for preparing the micro-droplets using the open electrodes will be described in detail below.
Referring to fig. 2 to 5, a method for generating micro droplets according to an embodiment includes the following steps:
s110, providing a chip, referring to fig. 3, the chip includes an upper plate and a lower plate, and an included angle is formed between a plane of the upper plate and a plane of the lower plate. The upper plate comprises an upper cover 1, a conducting layer 3 and a first hydrophobic layer 4 which are sequentially stacked, the lower plate comprises a second hydrophobic layer 6, a dielectric layer 7 and an electrode layer 8 which are sequentially stacked, the electrode layer comprises a plurality of electrodes which are arranged in an array, and a fluid channel layer (not shown in the figure) is formed between the first hydrophobic layer 4 and the second hydrophobic layer 6. The fluid channel layer comprises a first end and a second end which are oppositely arranged, and the height of the first end of the fluid channel layer is smaller than that of the second end of the fluid channel layer.
In one embodiment, the upper plate is provided with a plurality of sample injection holes, the sample injection holes are positioned at the edge of the upper plate, and the sample injection holes are used for injecting samples.
And S120, injecting liquid 9 into the first end of the fluid channel layer.
In one embodiment, the liquid 9 is injected into said first end of the fluid channel layer through the injection holes.
S130, a plurality of electrodes of the electrode layer 8 are turned on, and adjacent turned-on electrodes 22 are spaced apart from each other by the turned-off electrode 24.
And S140, gradually approaching the upper polar plate and the lower polar plate, gradually moving the liquid 9 from the first end to the second end, and forming small liquid drops 10 on the liquid 9 at positions corresponding to the attraction points.
It is understood that S120 and S130 are not limited to be in sequence, and S120 may be performed first, and then S130 may be performed. S130 may be performed first, and then S120 may be performed.
In the method for forming micro-droplets, the liquid 9 is gradually moved from the first end to the second end when the liquid is injected into the first end of the fluid channel layer and the upper plate and the lower plate are gradually brought close to each other, and when the liquid passes through the plurality of open electrodes 22, the liquid 9 forms a plurality of small droplets 10 in the fluid channel layer at positions corresponding to the plurality of open electrodes 22. The method for generating the micro-droplets can quickly prepare a large number of small droplets 10, greatly shortens the droplet generation time, and has a simple operation process. And equipment such as a high-precision micro pump and the like is not needed, so that the system cost is reduced. And the expansion capability is strong, more droplets 10 can be separated or a plurality of groups of samples can be separated by expanding the chip size.
It will be appreciated that in the preparation of the droplets 10, the electrodes of the electrode layer 8 are not all on, including the electrode 22 which is on and the electrode 24 which is not on. To avoid binding of the droplets 10 to each other, adjacent activated electrodes 22 are spaced apart by an unactivated electrode 24. It will be appreciated that adjacent activated electrodes 22 are spaced apart from each other by at least one non-activated electrode 24. Preferably, adjacent activated electrodes 22 are spaced apart from each other by 2 non-activated electrodes 24.
In one embodiment, the distance between the upper plate and the lower plate at the first end is 0 μm-20 μm.
In one embodiment, the angle between the upper plate and the lower plate is greater than 0 ° and less than 1 °.
In one embodiment, the step of injecting the liquid into the first end of the fluid channel layer is performed at a rate of 1 μ L/s to 10 μ L/s.
In one embodiment, the shape of the electrodes is square with side lengths ranging from: 50-2000 μm. It will be appreciated that the shape of the electrodes may be any shape or combination of shapes.
The volume of the droplets can be precisely adjusted by adjusting the size of the electrodes, the gap distance of the electrodes, and the like. By controlling the size of the different electrodes, single droplets of different volumes can be generated quickly.
In one embodiment, the material of the upper cover 1 may be a glass substrate. The thickness of the upper cover 1 may be 0.7mm to 1.1 mm.
In one embodiment, the material of the conductive layer 3 may be an ITO conductive layer. The thickness of the conductive layer 3 may be 50nm to 150 nm.
In one embodiment, the material of the first hydrophobic layer 4 may be a fluorine-containing hydrophobic coating. The thickness of the first hydrophobic layer 4 may be 10nm-100 nm.
In one embodiment, the material of the second hydrophobic layer 6 may be a Teflon coating. The thickness of the second hydrophobic layer 6 may be 10nm-100 nm.
In one embodiment, the material of the dielectric layer 7 may be an organic or inorganic insulating layer. The thickness of the dielectric layer 7 may be 100nm to 400 nm.
In one embodiment, the material of the electrode layer 8 may be transparent conductive glass or metal. The thickness of the electrode layer 8 may be 100nm to 400 nm.
In another embodiment, forming a plurality of attraction points on at least one of the upper plate and the lower plate is formed by: hydrophilic points are arranged on the first hydrophobic layer, the hydrophilic points are the attraction points, and the hydrophilic points are arranged at intervals.
In one embodiment, the hydrophilic dots are prepared as follows:
and carrying out hydrophilic modification on the first hydrophobic layer, and damaging the hydrophobic coating on the required position on the first hydrophobic layer by using laser or plasma to obtain a hydrophilic dot array.
In one embodiment, the hydrophilic dots are arranged in an array. Namely, the first hydrophobic layer is provided with a hydrophilic dot array.
According to the method for generating the micro-droplets, liquid is injected into the first end of the fluid channel layer, the upper polar plate and the lower polar plate are gradually close to each other, the liquid gradually moves from the first end to the second end, and when the large droplets pass through the hydrophilic points, the small droplets are left in the positions, corresponding to the hydrophilic points, in the fluid channel layer due to the hydrophilic action of the hydrophilic points. The method for generating the micro-droplets can quickly prepare a large number of small droplets, greatly shortens the droplet generation time and has simple and convenient operation flow. The method for generating the micro-droplets can separate the small droplets without controlling electrodes, so that the operation is simpler and more convenient. And equipment such as a high-precision micro pump and the like is not needed, so that the system cost is reduced. And the expansion capability is strong, and more small droplets or multiple groups of samples can be separated by expanding the chip size.
In addition, an application method of the micro-droplets is also provided, which comprises the following steps:
s210, preparing the micro-droplets by adopting the micro-droplet generation method.
The method for generating the micro-droplets is as described above, and will not be described herein again.
And S220, controlling the micro-droplets through the electrodes to finish subsequent application.
According to the application method of the micro-droplets, after a large number of micro-droplets are generated, the micro-droplets can be controlled to move by controlling the opening of the electrodes, and the on-chip experiment is completed by controlling the droplets through electrowetting. May be suitable for a variety of droplet-based biochemical applications.
The following is a detailed description of the embodiments.
Example 1
Referring to fig. 3, a chip is provided, which includes an upper plate and a lower plate. The upper plate comprises a glass substrate 1, an ITO conductive layer 3 and a first hydrophobic layer 4. The lower plate comprises a second hydrophobic layer 6, a dielectric layer 7 and an electrode layer 8. One side of the upper polar plate is padded up by using a gasket, and a certain angle is formed between the upper polar plate and the lower polar plate, so that the distance 5 between the upper polar plate and the lower polar plate is changed. The distance between the upper polar plate and the lower polar plate is gradually increased from right to left. Referring to fig. 4-5, when the liquid drops are injected onto the chip from the right side, the liquid 9 will move to the place with large gap, i.e. from the right side to the left side, and at this time, a voltage is applied to the electrode layer 8, so that the corresponding electrode surface becomes hydrophilic, when the liquid 9 flows over the electrode with applied voltage, a plurality of small liquid drops 10 with single electrode size will be torn off, and a plurality of electrodes which are turned on are arranged among the small liquid drops 10 to avoid the fusion among the small liquid drops 10. The faster the liquid is injected, the higher the success rate of tearing out small droplets. Fig. 6 is a top view of the movement of the droplets 9, and from steps S1 to S6, a rapid large number of small droplets 10 can be generated, and according to calculation, a large number of small droplets of different volumes can be generated, facilitating the preparation of samples of different concentrations.
Conventional digital microfluidics generate a small droplet by manipulating a large droplet and then transport the small droplet to a corresponding location. According to the method for generating the micro-droplets, the liquid is injected into the first end of the fluid channel layer, the injected liquid is subjected to the action of the surface tension 2, the liquid can gradually move from the first end to the second end, and the small droplets are left in the position, corresponding to the attraction point, in the fluid channel layer, so that the time for generating the droplets is greatly shortened.
In the later experiments, the required amount of the liquid drops can be selected to complete the experiment. After the separation of the high-throughput nanoliter droplets is completed, corresponding experiments and detection can be carried out on the chip, such as ddPCR, dLAMP, dELISA single cell experiments and the like. Can be applied to other nucleic acid detection such as isothermal amplification. Meanwhile, any small liquid drop in the chip can be screened or independently tested, and more small liquid drops or a plurality of groups of samples can be separated by expanding the size of the chip.
According to the method for generating the micro-droplets, the gap between the upper polar plate and the lower polar plate is changed to be combined with electrowetting, so that a plurality of small droplets can be generated rapidly at the same time, the volume of the small droplets can be controlled by adjusting the gap between the upper polar plate and the lower polar plate and the size of the electrode, the operation process is simple, and the controllability is high. Meanwhile, the liquid drops can be controlled to move automatically to leave small liquid drops at a designated position or area, the small liquid drops can be controlled to move by controlling the opening of the electrode, and the liquid drops are controlled by electrowetting to complete an on-chip experiment. May be suitable for a variety of droplet-based biochemical applications.
Through practical tests, the micro-droplet generation method can tear a large amount of droplets quickly, can control the movement of the torn droplets, and improves the tearing efficiency.
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. A method of producing microdroplets, comprising the steps of:
providing a chip, wherein the chip comprises an upper polar plate and a lower polar plate, an included angle is formed between the plane of the upper polar plate and the plane of the lower polar plate, a fluid channel layer is formed between the upper polar plate and the lower polar plate, the upper polar plate is provided with a plurality of sample injection holes, the sample injection holes are positioned at the edge of the upper polar plate and used for injecting samples, the fluid channel layer comprises a first end and a second end which are oppositely arranged, and the height of the first end of the fluid channel layer is smaller than that of the second end of the fluid channel layer;
forming a plurality of suction points on at least one of the upper plate and the lower plate, the suction points being used for adsorbing liquid;
injecting liquid into the first end of the fluid channel layer through the sample injection hole;
when the liquid is injected into the fluid channel layer, the liquid gradually moves from the first end to the second end under the action of surface tension, and the liquid forms small liquid drops at the position corresponding to the attraction point.
2. The method of claim 1, wherein the bottom plate comprises an electrode layer, the shape of the electrode layer is hexagonal or square, the electrode layer is an n x m electrode array, and n and m are positive integers.
3. The method of claim 2, wherein the upper plate comprises an upper cover, a conductive layer and a first hydrophobic layer, the lower plate further comprises a second hydrophobic layer and a dielectric layer, the second hydrophobic layer, the dielectric layer and the electrode layer are sequentially stacked, and the first hydrophobic layer and the second hydrophobic layer form the fluid channel layer therebetween.
4. A method of producing microdroplets as claimed in claim 2 or 3 wherein the forming of a plurality of attraction points on at least one of the upper and lower plates is by: and a plurality of electrodes of the electrode layer are started, the started electrodes are the attraction points, and the adjacent started electrodes are arranged at intervals through the unopened electrodes.
5. The method of any of claims 1-3, wherein the distance between the upper plate and the lower plate at the first end is between 0 μm and 20 μm.
6. The method of any of claims 1-3, wherein the angle between the upper plate and the lower plate is greater than 0 ° and less than 1 °.
7. The method of any of claims 1-3, wherein the step of injecting the liquid into the first end of the fluid channel layer is performed at a rate of from 1 μ L/s to 10 μ L/s.
8. The method of claim 3, wherein forming a plurality of suction points on at least one of the upper plate and the lower plate is performed by: hydrophilic points are arranged on the first hydrophobic layer, the hydrophilic points are the attraction points, and the hydrophilic points are arranged at intervals.
9. The method of forming microdroplets according to claim 8, wherein the hydrophilic dots are prepared by the following method:
and carrying out hydrophilic modification on the first hydrophobic layer, and damaging the hydrophobic coating at the required position of the first hydrophobic layer by using laser or plasma to obtain the hydrophilic point.
10. A method of applying microdroplets, comprising the steps of:
preparing microdroplets using the method of microdroplet generation as claimed in any one of claims 1 to 9;
and manipulating the micro-droplets through electrodes to complete subsequent application.
CN202011549220.1A 2020-12-24 2020-12-24 Micro-droplet generation method and micro-droplet application method Active CN114669335B (en)

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Application Number Priority Date Filing Date Title
CN202011549220.1A CN114669335B (en) 2020-12-24 2020-12-24 Micro-droplet generation method and micro-droplet application method
EP21908985.1A EP4268957A1 (en) 2020-12-24 2021-11-23 Micro-droplet generation method and generation system
PCT/CN2021/132216 WO2022134986A1 (en) 2020-12-24 2021-11-23 Micro-droplet generation method and generation system
AU2021407922A AU2021407922A1 (en) 2020-12-24 2021-11-23 Micro-droplet generation method and generation system
JP2023545222A JP2024505501A (en) 2020-12-24 2021-11-23 Micro droplet generation method and generation system
KR1020237025033A KR20230123514A (en) 2020-12-24 2021-11-23 Micro droplet generation method and generation system
US18/259,197 US20240042436A1 (en) 2020-12-24 2021-11-23 Micro-droplet generation method and generation system
CA3203394A CA3203394A1 (en) 2020-12-24 2021-11-23 Micro-droplet generation method and generation system

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