CN114669335B - Micro-droplet generation method and micro-droplet application method - Google Patents
Micro-droplet generation method and micro-droplet application method Download PDFInfo
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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 a plane where the upper polar plate is positioned and a plane where the lower polar plate is positioned, 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 in at least one of the upper plate and the lower plate, the suction points being used for adsorbing liquid; liquid is injected into the first end of the fluid channel layer, and the liquid gradually moves from the first end to the second end and forms small liquid drops at positions corresponding to the suction points. The method for generating the micro-droplets can quickly prepare a large number of small droplets and greatly shorten the droplet generation time.
Description
Technical Field
The invention relates to the technical field of microfluidics, in particular to a method for generating micro-droplets capable of rapidly 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 volume is one of the problems to be solved by the microfluidic technology, and is a key link in various application fields including digital polymerase chain reaction (ddPCR), digital loop-mediated isothermal amplification (dLAMP), digital enzyme-linked immunosorbent assay (dELISA), single-cell histology and other application fields. The current technical means for generating nano-liter liquid drops with high flux mainly comprise a micro-droplet microfluidic technology and a micro-well microfluidic technology. Representative of micro-droplet microfluidics include Bio-Rad and 10XGenomics, which is characterized by the use of high-precision micropump control oil, and the continuous extrusion of sample liquid with a cross-shaped structure to generate a large number of picoliter to nanoliter-scale droplets. The method for generating nano-liter liquid drops with high flux based on the micro-droplet microfluidic technology relies on the accurate control of the pressure of a high-precision micro-pump and the processing technology of a high-precision chip based on MEMS, the generated liquid drops are still stored in the same container, each liquid drop needs to be detected one by one through a micro-channel during detection, the equipment cost is high, and the system is complex. The micro-well microfluidic technology is represented by Thermo Fisher, and is characterized in that a sample solution is mechanically coated on a micro-well array, so that the sample is evenly distributed into each micro-well to form small droplets ranging from picoliter to nanoliter. The technology based on micro-well micro-flow control generally needs to uniformly coat reagents on the surface of a micro-well array by means of mechanical force, and then fill the upper surface and the lower surface of the micro-well with inert medium liquid.
Digital microfluidics has another technical approach to high throughput generation of droplets due to its ability to independently manipulate each droplet, patent WO 2016/170109 Al and US20200061620A1 both describe a method of generating a large number of droplets based on a digital microfluidic platform. However, the method for generating nano-liter liquid drops at high flux based on the digital micro-fluidic technology described in the above patent mainly controls large liquid drops to generate small liquid drops through the digital micro-fluidic technology, and then the small liquid drops are transported to corresponding positions. The main disadvantage of this method is the slow speed of droplet generation and long sample preparation time.
Disclosure of Invention
In view of this, it is necessary to provide a method of generating microdroplets and application of microdroplets that can generate a large number of microdroplets quickly.
A method of generating 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 a plane where the upper polar plate is located and a plane where the lower polar plate is located, a fluid channel layer is formed between the upper polar plate and the lower polar plate, a plurality of sample injection holes are formed in the upper polar plate, the sample injection holes are positioned at the edge of the upper polar plate and are 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 in at least one of the upper plate and the lower plate, the suction points being for adsorbing a liquid;
injecting liquid through the sample injection hole to the first end of the fluid channel layer;
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 small liquid drops are formed at positions corresponding to the suction points.
In one embodiment, the lower electrode plate comprises an electrode layer, the electrode layer is an n×m electrode array, n and m are both positive integers, and the shape of the electrode layer is hexagonal or square.
In one embodiment, the upper electrode plate comprises an upper cover, a conductive layer and a first hydrophobic layer which are sequentially stacked, the lower electrode 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 suction points in at least one of the upper plate and the lower plate is formed by: and opening a plurality of electrodes of the electrode layer, wherein the opened electrodes are the suction points, and adjacent opened electrodes are arranged at intervals through the unopened electrodes.
In one embodiment, the distance between the upper plate and the lower plate is 0 μm to 20 μm at the first end.
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 a liquid into the first end of the fluid channel layer, the liquid is injected at a rate of 1 μL/s to 10 μL/s.
In one embodiment, forming a plurality of suction points in 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 suction points, and the adjacent hydrophilic points are arranged at intervals.
In one embodiment, the hydrophilic dot is prepared as follows:
and (3) carrying out hydrophilic modification on the first hydrophobic layer, and destroying the hydrophobic coating at the required position of the first hydrophobic layer by utilizing laser or plasma to obtain the hydrophilic point.
In addition, the application method of the micro-droplet comprises the following steps:
preparing micro-droplets by adopting the generation method of the micro-droplets;
and controlling the micro-droplets through an electrode to finish subsequent application.
And (3) carrying out hydrophilic modification on the first hydrophobic layer, and destroying the hydrophobic coating at the required position of the first hydrophobic layer by utilizing laser or plasma to obtain the hydrophilic point.
According to the method for generating the micro-droplets, the 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 gradually moves from the first end to the second end, and when the liquid passes through the suction points, the small droplets are left at positions corresponding to the suction points in the fluid channel layer due to the suction effect of the suction points. Compared with the traditional method for generating micro-droplets, which needs to separate out the droplets and then convey the droplets to the designated positions, the method for generating the micro-droplets can quickly finish the separation of the micro-droplets at the required positions, prepare a large number of small droplets, greatly shorten the droplet generation time, improve the efficiency and simplify the operation flow. And equipment such as a high-precision micropump is not needed, and the system cost is reduced. And the expansion capability is strong, and more small liquid drops can be separated 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 flow chart of a method for generating micro-droplets according to an embodiment.
Fig. 3 is a schematic cross-sectional structure of a chip according to an embodiment.
Fig. 4 is a schematic diagram of the structure of one state of the chip of fig. 3 for preparing droplets.
Fig. 5 is a schematic diagram of the structure of another state of the chip shown in fig. 3 for preparing small droplets.
Fig. 6 is a top view of the chip of fig. 3 in a series of steps for preparing droplets.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. It will be apparent that the described embodiments are some, but not all, embodiments of the invention. The components of the 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 invention, as 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 made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
It should be noted that: like reference numerals and letters denote like items in the following figures, and thus once an item is defined in one figure, no further definition or explanation thereof is necessary in the following figures.
In the description of the present invention, it should be understood that, for the convenience of description and simplification of the description, it is not necessary to indicate or imply that the apparatus or elements referred to have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be construed as limiting the invention, it is that the relation of orientation or position indicated as "upper" is based on the orientation or position relation shown in the drawings, or the orientation or position relation that is conventionally put when the inventive product is used, or the orientation or position relation that is conventionally understood by those skilled in the art.
Furthermore, the terms "first," "second," and the like, are used merely to distinguish between descriptions and should not be construed as indicating or implying relative importance.
The following describes specific embodiments of the present invention in detail with reference to the 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 a plane where the upper polar plate is located and a plane where the lower polar plate is located. A fluid channel layer is formed between the upper polar plate and the lower polar plate, a plurality of sample injection holes are formed in the upper polar plate, the sample injection holes are located 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.
S20, forming a plurality of sucking points on at least one of the upper polar plate and the lower polar plate, wherein the sucking points are used for sucking liquid.
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 small liquid drops are formed at positions corresponding to the suction points.
And S40, after the liquid is injected into the fluid channel layer, the upper polar plate and the lower polar plate are gradually closed, the liquid gradually moves from the first end to the second end under the action of surface tension, and small liquid drops are formed at positions corresponding to the suction points.
It is understood that the order of S20 and S30 is not limited to proceeding with S20 first and then S30. In a specific case, S30 may be performed before S20.
According to the method for generating the micro-droplets, the 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 gradually moves from the first end to the second end, and when the liquid passes through the suction points, the small droplets are left at positions corresponding to the suction points in the fluid channel layer due to the suction effect of the suction 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. And equipment such as a high-precision micropump is not needed, and the system cost is reduced. And the expansion capability is strong, and more small liquid drops can be separated or multiple groups of samples can be separated by expanding the chip size.
The height of the first end of the fluid channel layer being smaller than the height of the second end of the fluid channel layer means that: at the first end, the distance between the upper plate and the lower plate is smallest, and at the second end, the distance between the upper plate and the lower plate is largest.
In one embodiment, the suction points may be formed on the upper plate or the lower plate. Or suction points are formed on the upper polar plate and the lower polar plate at the same time.
In particular, the suction points may be formed by different methods.
In one embodiment, the lower plate includes an electrode layer including a plurality of electrodes arranged in an array. The shape of the electrode may be hexagonal or square, of course, the shape of the electrode is not limited to hexagonal or square. Specifically, the electrode layer is an electrode array of n×m, where n and m are both positive integers. The forming of the plurality of suction points in at least one of the upper plate and the lower plate is performed by: and opening a plurality of electrodes of the electrode layer, wherein the opened electrodes are suction points, and adjacent opened electrodes are arranged at intervals through unopened electrodes.
The method for preparing the micro-droplet using the start electrode is 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 comprises an upper polar plate and a lower polar plate, wherein an included angle is formed between a plane where the upper polar plate is located and a plane where the lower polar plate is located. The upper polar plate comprises an upper cover 1, a conductive layer 3 and a first hydrophobic layer 4 which are sequentially stacked, the lower polar 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) is formed between the first hydrophobic layer 4 and the second hydrophobic layer 6. The fluid channel layer includes oppositely disposed first and second ends, the first end of the fluid channel layer having a height that is less than the height 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.
S120, injecting liquid 9 into the first end of the fluid channel layer.
In one embodiment, the liquid 9 is injected through the injection well to the first end of the fluid channel layer.
S130, a plurality of electrodes of the electrode layer 8 are started, and adjacent started electrodes 22 are arranged at intervals through non-started electrodes 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 at positions corresponding to the suction points by the liquid 9.
It is understood that S120 and S130 are not limited in order, and S120 may be performed first and S130 may be performed again. S130 may be performed first, and S120 may be performed again.
In the method for generating micro-droplets, the liquid is injected into the first end of the fluid channel layer, and when the upper electrode plate and the lower electrode plate are gradually moved close to each other, the liquid 9 gradually moves from the first end to the second end, and when the liquid passes through the plurality of opened electrodes 22, the liquid 9 forms a plurality of small droplets 10 in the fluid channel layer at positions corresponding to the plurality of opened 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 simple and convenient operation flow. And equipment such as a high-precision micropump is not needed, and the system cost is reduced. And the expansion capability is strong, more droplets 10 can be separated or multiple groups of samples can be separated by expanding the chip size.
It will be appreciated that in preparing the droplet 10, the electrodes of the electrode layer 8 are not all on, including the on electrode 22 and the off electrode 24. To avoid binding of droplets 10 to each other, adjacent activated electrodes 22 are spaced apart by unopened electrodes 24. It will be appreciated that adjacent activated electrodes 22 are spaced apart from one another by at least one unopened electrode 24. Preferably, adjacent activated electrodes 22 are separated from each other by 2 unopened electrodes 24.
In one embodiment, the distance between the upper and lower plates is 0 μm-20 μm at the first end.
In one embodiment, the angle between the upper and lower plates 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 has an injection rate of 1 μL/s to 10 μL/s.
In one embodiment, the electrode is square in shape, with a side length in the range: 50 μm to 2000 μm. It is understood that the shape of the electrode may be any shape or combination of shapes.
The volume of the small droplet can be precisely adjusted by adjusting the electrode size, the gap distance of the electrodes, and the like. By controlling the dimensions of the different electrodes, single droplets of different volumes can be rapidly generated.
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 1.1mm.
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 150nm.
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-100nm.
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-100nm.
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-400nm.
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 400nm.
In another embodiment, forming a plurality of suction points in 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 suction points, and the adjacent hydrophilic points are arranged at intervals.
In one embodiment, the hydrophilic dot is prepared as follows:
and carrying out hydrophilic modification on the first hydrophobic layer, and destroying the hydrophobic coating on the required position on the first hydrophobic layer by utilizing laser or plasma to obtain a hydrophilic dot array.
In one embodiment, the hydrophilic dots are arranged in an array. I.e. the first hydrophobic layer is provided with an array of hydrophilic spots.
According to the method for generating the micro-droplets, the 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 small droplets are left at positions corresponding to the hydrophilic points in the fluid channel layer due to the hydrophilic effect of the hydrophilic points when large droplets pass through 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. According to the method for generating the micro-droplets, the micro-droplets can be separated without a control electrode, so that the operation is simpler and more convenient. And equipment such as a high-precision micropump is not needed, and the system cost is reduced. And the expansion capability is strong, and more small liquid drops can be separated or multiple groups of samples can be separated by expanding the chip size.
In addition, the application method of the micro-droplet comprises the following steps:
s210, preparing micro-droplets by adopting the micro-droplet generation method.
The method for generating the micro-droplets is described above and will not be described here again.
S220, controlling the micro-droplets through the electrodes to finish subsequent application.
According to the application method of the micro-droplet, after a large number of micro-droplets are generated, the micro-droplets can be controlled to move by controlling the opening of the electrode, and the on-chip experiment is completed by controlling the droplets through electrowetting. Can be applied to a plurality of biochemical applications based on micro-droplets.
The following is a detailed description of embodiments.
Example 1
Referring to fig. 3, a chip is provided, the chip including 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 by 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 a droplet is injected onto a chip from the right side, the liquid 9 will move to a large gap, i.e. move from the right side to the left side, and a voltage is applied to the electrode layer 8 to make the surface of the corresponding electrode hydrophilic, so that when the liquid 9 flows over the electrode with the applied voltage, a plurality of droplets 10 with a single electrode size will be torn out, and a plurality of electrodes with open intervals between the droplets 10 will avoid fusion between the droplets 10. The faster the liquid is injected, the higher the success rate of tearing out the droplet. Fig. 6 is a top view of the movement of the droplet 9, from steps S1 to S6, a rapid large number of small droplets 10 can be generated, and according to the calculation, a large number of small droplets of different volumes can be generated, facilitating the preparation of samples of different concentrations.
Conventional digital microfluidics generates a small droplet by manipulating a large droplet and then transports 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 acted by the surface tension 2, the liquid gradually moves from the first end to the second end, and small droplets are left at positions corresponding to the suction points in the fluid channel layer, so that the time for generating the droplets is greatly shortened.
In the later experiments, the experiments can be completed by selecting the required droplet amount. After the high-throughput nano-liter droplet separation is completed, corresponding experiments and detection can be performed on a chip, such as ddPCR, dLAMP, dELISA single-cell experiments and the like. It can be applied to other nucleic acid detection such as isothermal amplification. Meanwhile, screening or independent experiments can be carried out on any small liquid drop in the chip, and more small liquid drops can be separated or multiple groups of samples can be separated by expanding the size of the chip.
According to the method for generating the micro-droplets, the size of the gap between the upper polar plate and the lower polar plate is changed to be combined with electrowetting, a plurality of small droplets can be generated at the same time, the volume of the small droplets can be controlled by adjusting the size of the gap between the upper polar plate and the lower polar plate and the size of the electrode, the operation flow is simple, and the controllability is high. Meanwhile, the movement of the liquid drop can be controlled to leave small liquid drops on a designated position or area, the small liquid drops can be controlled to move through the opening of the control electrode, and the on-chip experiment is completed through electrowetting control liquid drops. Can be applied to a plurality of biochemical applications based on micro-droplets.
Through practical tests, the generation method of the micro liquid drops can tear out liquid drops in a large quantity and rapidly, and can control the movement of the torn liquid drops, so that the tearing efficiency is improved.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (10)
1. A method of generating 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 a plane where the upper polar plate is located and a plane where the lower polar plate is located, a fluid channel layer is formed between the upper polar plate and the lower polar plate, a plurality of sample injection holes are formed in the upper polar plate, the sample injection holes are positioned at the edge of the upper polar plate and are 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 in at least one of the upper plate and the lower plate, the suction points being for adsorbing a liquid;
injecting liquid through the sample injection hole to the first end of the fluid channel layer;
when the liquid is injected into the fluid channel layer, the upper polar plate and the lower polar plate are gradually closed, the liquid is under the action of surface tension, the liquid gradually moves from the first end to the second end, and small liquid drops are formed at positions corresponding to the suction points.
2. The method of generating droplets according to claim 1, wherein the lower electrode plate includes an electrode layer, the electrode of the electrode layer has a hexagonal or square shape, and the electrode layer has an n x m electrode array, where n and m are positive integers.
3. The method of generating droplets according to claim 2, wherein the upper plate comprises an upper cover, a conductive layer, and a first hydrophobic layer stacked in this order, 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 stacked in this order, and the fluid channel layer is formed between the first hydrophobic layer and the second hydrophobic layer.
4. The method of generating droplets according to claim 2 or 3, wherein forming a plurality of attraction points in at least one of the upper plate and the lower plate is performed by: and opening a plurality of electrodes of the electrode layer, wherein the opened electrodes are the suction points, and adjacent opened electrodes are arranged at intervals through the unopened electrodes.
5. A method of generating droplets according to any one of claims 1 to 3, characterized in that the distance between the upper plate and the lower plate at the first end is 0 μm to 20 μm.
6. The method of generating droplets according to any one of claims 1 to 3, wherein an angle between the upper plate and the lower plate is greater than 0 ° and less than 1 °.
7. The method of producing micro-droplets according to any one of claims 1 to 3, wherein in the step of injecting a liquid into the first end of the fluid channel layer, the liquid is injected at a rate of 1 μl/s to 10 μl/s.
8. The method of generating droplets according to claim 3, wherein forming a plurality of attraction points in 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 suction points, and the adjacent hydrophilic points are arranged at intervals.
9. The method of generating droplets according to claim 8, wherein the hydrophilic dot is prepared by:
and (3) carrying out hydrophilic modification on the first hydrophobic layer, and destroying the hydrophobic coating at the required position of the first hydrophobic layer by utilizing laser or plasma to obtain the hydrophilic point.
10. A method of applying microdroplets comprising the steps of:
preparing microdroplets using the method of generating microdroplets as defined in any one of claims 1-9;
and controlling the micro-droplets through an electrode to finish subsequent application.
Priority Applications (8)
| 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 |
| PCT/CN2021/132216 WO2022134986A1 (en) | 2020-12-24 | 2021-11-23 | Micro-droplet generation method and generation system |
| EP21908985.1A EP4268957A1 (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 |
| US18/259,197 US20240042436A1 (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 |
| KR1020237025033A KR20230123514A (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 |
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| GB202012504D0 (en) * | 2020-08-11 | 2020-09-23 | Univ Of Hertfordshire Higher Education Corporation | Droplet generation system |
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| JP2010524002A (en) * | 2007-04-10 | 2010-07-15 | アドヴァンスト リキッド ロジック インコーポレイテッド | Droplet dispensing apparatus and method |
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