CN110756233A - Micro-droplet preparation system, micro-fluidic chip and micro-droplet preparation method - Google Patents

Abstract

The invention relates to a droplet preparation system, a micro-fluidic chip and a droplet preparation method. The micro-fluidic chip comprises a cover plate, a micro-control channel plate and a substrate. When the device is used specifically, for example, a trace quantitative pipette gun is adopted to respectively add quantitative continuous phase liquid into a continuous phase sampling hole and quantitative discrete phase liquid into a discrete phase sampling hole; then the micro-fluidic chip is connected to a micro-droplet preparation system, and micro-droplet preparation is carried out by adjusting time and pressure; in the droplet preparation process, droplets in the droplet outlet holes pass through the first through holes of the cover plate and then are discharged to a storage container (such as a detection test tube and a multi-well plate) along the flow guide tube. So, need not to adopt traditional liquid-transfering gun to carry out liquid-transfering operation to the droplet that prepares, directly outwards discharge the droplet that prepares to the reservoir through the honeycomb duct in, liquid-transfering operation is convenient, can avoid the damage and the loss of droplet betterly to can improve the accuracy of testing result.

Description

Micro-droplet preparation system, micro-fluidic chip and micro-droplet preparation method

Technical Field

The invention relates to the technical field of droplet preparation, in particular to a droplet preparation system, a micro-fluidic chip and a droplet preparation method.

Background

The microdroplet technology is a technology for injecting immiscible liquid into a microfluidic chip and preparing uniform liquid drops meeting various size requirements at an extremely high speed. The micro-fluidic chip technology integrates basic operation units such as sample preparation, reaction, separation, detection and the like in analysis processes such as biology, chemistry, medicine and the like on a micron-scale chip to automatically complete the whole analysis process. The microfluidic chip is generally made of polymer materials and processed by a semiconductor processing technology. The method mainly operates fluid in a micron-scale space, requires a matched liquid path system to be connected, and injects macroscopic fluid into a microscopic microfluidic chip pipeline. However, conventionally, a droplet is prepared by using a single channel, and after the droplet is prepared, the droplet is transported by a pipette one by one, and there is a damage and a loss of the droplet during the transportation, which has a great influence on the final detection result.

Disclosure of Invention

Therefore, it is necessary to overcome the defects of the prior art, and provide a droplet preparation system, a microfluidic chip and a droplet preparation method, which do not require a pipette gun for performing liquid-liquid operation, can facilitate liquid-liquid operation, can better avoid droplet damage and loss, and can improve the accuracy of detection results.

The technical scheme is as follows: a microfluidic chip, comprising: the cover plate is provided with a first through hole and a flow guide pipe which is arranged on the side surface of the cover plate and is communicated with the first through hole, and the flow guide pipe is used for guiding the micro-droplets to a storage container; the micro-control channel plate is stacked on the cover plate, and is provided with a continuous phase hole, a discrete phase hole, a microdrop liquid outlet hole, a first flow channel and a second flow channel, wherein the discrete phase hole is communicated with the microdrop liquid outlet hole through the first flow channel, the continuous phase hole is communicated with the first flow channel through the second flow channel, and the microdrop liquid outlet hole is communicated with the first through hole; and the substrate is superposed on the micro-control channel plate, a continuous phase sample inlet and a discrete phase sample inlet are arranged on the substrate, the continuous phase sample inlet is communicated with the continuous phase hole, and the discrete phase sample inlet is communicated with the discrete phase hole.

When the microfluidic chip is used specifically, for example, a trace quantitative pipette is used to add quantitative continuous phase liquid into the continuous phase sample injection hole and quantitative discrete phase liquid into the discrete phase sample injection hole respectively; then the micro-fluidic chip is connected to a micro-droplet preparation system, and micro-droplet preparation is carried out by adjusting time and pressure; in the droplet preparation process, droplets in the droplet outlet holes pass through the first through holes of the cover plate and then are discharged to a storage container (such as a detection test tube and a multi-well plate) along the flow guide tube. So, need not to adopt traditional liquid-transfering gun to carry out liquid-transfering operation to the droplet that prepares, directly outwards discharge the droplet that prepares to the reservoir through the honeycomb duct in, liquid-transfering operation is convenient, can avoid the damage and the loss of droplet betterly to can improve the accuracy of testing result.

In one embodiment, the number of the first through hole, the flow guide tube, the continuous phase hole, the discrete phase hole, the droplet liquid outlet hole, the first flow channel, the second flow channel, the continuous phase sample inlet hole and the discrete phase sample inlet hole is two or more; more than two flow guide pipes are arranged in one-to-one correspondence with more than two first through holes; the more than two first through holes, the more than two discrete phase holes and the more than two first flow channels are respectively arranged corresponding to the more than two micro-droplet liquid outlet holes one by one; the more than two continuous phase holes and the more than two second flow passages are respectively arranged in one-to-one correspondence with the more than two first flow passages.

In one embodiment, the first through hole, the flow guide tube, the continuous phase hole, the discrete phase hole, the droplet liquid outlet hole, the first flow channel, the second flow channel, the continuous phase sample inlet hole and the discrete phase sample inlet hole are all eight, and the eight flow guide tubes are sequentially arranged at intervals and form a row.

In one embodiment, a notch is arranged on the side wall of the liquid outlet end of the draft tube; the height of the honeycomb duct is 3mm-30mm, the outer diameter of the honeycomb duct is 2.5mm-8mm, the inner diameter of the honeycomb duct is 1mm-5mm, and the height of the notch is 1mm-15 mm.

In one embodiment, a continuous phase sampling pipe and a discrete phase sampling pipe are arranged on the substrate, the continuous phase sampling pipe is communicated with the continuous phase sampling hole, and the discrete phase sampling pipe is communicated with the discrete phase sampling hole; the substrate is also provided with a gas blowing hole communicated with the micro-droplet liquid outlet hole; and an air blowing pipe is arranged at the air blowing hole.

In one embodiment, the cover plate and the micro-control channel plate, and the micro-control channel plate and the substrate are bonded, welded, screwed, riveted, pinned or clamped.

In one embodiment, the micro-control channel plate and the cover plate or the base plate are of an integrated structure; or the micro-control channel plate, the cover plate and the base plate are of an integrated structure.

In one embodiment, the micro-control channel plate and the substrate are of an integrated structure, and the cover plate is provided with a plurality of clamping pieces in clamping fit with the substrate.

In one embodiment, the microfluidic chip further includes a sealing plate, a concave portion is disposed on a side surface of the cover plate facing the substrate and corresponding to the first through hole, the sealing plate is adapted to the concave portion, an elastic sleeve is disposed on the sealing plate, and two ends of the elastic sleeve are respectively communicated with the droplet outlet hole and the first through hole.

The utility model provides a microdroplet preparation system, includes the micro-fluidic chip, still include storage container and air supply unit, the honeycomb duct is used for arriving the microdroplet water conservancy diversion in the storage container, the continuous phase gas circuit of air supply unit with continuous phase advances the sample hole and is linked together, the discrete looks gas circuit of air supply unit with discrete looks advance the sample hole and be linked together.

When the microdroplet preparation system is used, for example, a trace quantitative pipette is adopted to respectively add quantitative continuous phase liquid into the continuous phase sample inlet and quantitative discrete phase liquid into the discrete phase sample inlet; then the micro-fluidic chip is connected to a micro-droplet preparation system, and micro-droplet preparation is carried out by adjusting time and pressure; in the droplet preparation process, droplets in the droplet outlet holes pass through the first through holes of the cover plate and then are discharged to a storage container (such as a detection test tube and a multi-well plate) along the flow guide tube. So, need not to adopt traditional liquid-transfering gun to carry out liquid-transfering operation to the droplet that prepares, directly outwards discharge the droplet that prepares to the reservoir through the honeycomb duct in, liquid-transfering operation is convenient, can avoid the damage and the loss of droplet betterly to can improve the accuracy of testing result.

In one embodiment, the gas source device comprises a pressing connector, a continuous phase connector and a discrete phase connector are arranged on the pressing connector, the continuous phase gas path is correspondingly communicated with the continuous phase sampling hole through the continuous phase connector, and the discrete phase gas path is correspondingly communicated with the discrete phase sampling hole through the discrete phase connector;

pressure gauges are arranged on the continuous phase gas circuit and the discrete phase gas circuit; the air source device further comprises a control module for controlling the pressure of the air source and the air supply time, and the control module is connected with the continuous phase air path, the discrete phase air path and the external air source respectively.

A method for preparing droplets, which adopts the droplet preparation system, comprises the following steps:

adding quantitative continuous phase liquid into the continuous phase sample inlet and quantitative discrete phase liquid into the discrete phase sample inlet;

communicating a continuous phase gas path of a gas source device with a continuous phase sample inlet, communicating a discrete phase gas path with a discrete phase sample inlet, and performing droplet preparation by adjusting time and gas pressure;

in the process of preparing the droplets, the droplets of the droplet liquid outlet holes pass through the first through holes of the cover plate and then are discharged into the storage container along the flow guide pipe.

According to the droplet preparation method, the prepared droplets are directly discharged to the storage container through the guide pipe without adopting the traditional pipetting gun to carry out pipetting operation on the prepared droplets, the pipetting operation is convenient, the damage and the loss of the droplets can be better avoided, and the accuracy of the detection result can be improved.

Drawings

Fig. 1 is a schematic structural diagram of a microfluidic chip installed in a storage container according to an embodiment of the present invention;

fig. 2 is a schematic structural diagram of a microfluidic chip according to an embodiment of the present invention;

fig. 3 is an exploded view of a microfluidic chip according to an embodiment of the present invention;

fig. 4 is a schematic structural diagram of a micro-control channel plate in a micro-fluidic chip according to an embodiment of the present invention;

fig. 5 is an exploded view of a microfluidic chip according to another embodiment of the present invention;

fig. 6 is a schematic structural diagram of a cover plate and a sealing plate in a microfluidic chip according to another embodiment of the present invention;

fig. 7 is a schematic structural diagram of a microfluidic chip and a storage container according to another embodiment of the present invention;

fig. 8 is a first exploded view of a microfluidic chip according to another embodiment of the present invention;

fig. 9 is a second exploded view of a microfluidic chip according to another embodiment of the present invention;

FIG. 10 is a schematic diagram of a gas source device in a droplet preparation system according to an embodiment of the invention;

FIG. 11 is a schematic diagram of a droplet control chip for preparing droplets according to an embodiment of the present invention.

Reference numerals:

10. a microfluidic chip; 11. a cover plate; 111. a first through hole; 112. a flow guide pipe; 1121. cutting; 113. a fastener; 114. a recess; 115. a protrusion; 12. a micro-control channel plate; 121. continuous phase pore; 122. discrete phase holes; 123. a droplet outlet hole; 124. a first flow passage; 125. a second flow passage; 13. a substrate; 14. a continuous phase sample injection pipe; 15. a discrete phase sampling tube; 16. an air blowing pipe; 17. a sealing plate; 171. an elastic sleeve; 20. a storage container; 30. an air supply device; 31. a continuous phase gas circuit; 32. a discrete phase gas circuit; 33. pressing the joint downwards; 331. a continuous phase joint; 332. discrete phase connectors; 34. a pressure gauge; 35. a control module; 36. an external gas source.

Detailed Description

In order to make the aforementioned objects, features and advantages of the present invention comprehensible, embodiments accompanied with figures are described in detail below. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein.

In the description of the present invention, it is to be understood that the terms "first", "second" and the like are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implying any number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one such feature. In the description of the present invention, "a plurality" means at least two, e.g., two, three, etc., unless specifically limited otherwise.

In the description of the present invention, it should be understood that when an element is referred to as being "connected" to another element, it can be directly connected to the other element or intervening elements may also be present. In contrast, when an element is referred to as being "directly connected" to another element, there are no intervening elements present.

In one embodiment, referring to fig. 1 to 4, a microfluidic chip 10 includes: a cover plate 11, a micro-control channel plate 12 and a substrate 13. The cover plate 11 is provided with a first through hole 111 and a flow guide tube 112 disposed on a side surface of the cover plate 11 and communicating with the first through hole 111. The flow conduit 112 is used to direct the droplets into the storage container 20. The storage vessel may be either a 96-well PCR plate as illustrated in FIG. 1 or an eight-row PCR tube as illustrated in FIG. 7.

The micro-control channel plate 12 is stacked on the cover plate 11, and the micro-control channel plate 12 is provided with a continuous phase hole 121, a discrete phase hole 122, a droplet liquid outlet hole 123, a first flow channel 124 and a second flow channel 125. The discrete phase hole 122 is communicated with the droplet outlet hole 123 through the first flow channel 124, and the continuous phase hole 121 is communicated with the first flow channel 124 through the second flow channel 125. The droplet outlet 123 is in communication with the first through hole 111. The substrate 13 is stacked on the micro-control channel plate 12, the substrate 13 is provided with a continuous phase sample inlet and a discrete phase sample inlet, the continuous phase sample inlet is communicated with the continuous phase hole 121, and the discrete phase sample inlet is communicated with the discrete phase hole 122.

When the microfluidic chip 10 is used specifically, for example, a trace quantitative pipette is used to add quantitative continuous phase liquid into the continuous phase sample hole and quantitative discrete phase liquid into the discrete phase sample hole respectively; then the micro-fluidic chip 10 is connected to a micro-droplet preparation system, and micro-droplet preparation is carried out by adjusting time and pressure; in the droplet preparation process, droplets from the droplet outlet 123 pass through the first through hole 111 of the cover plate 11 and then are discharged along the flow guide tube 112 into the storage container 20 (e.g., test tubes and multi-well plates). Therefore, the prepared droplets are directly discharged to the storage container 20 through the guide pipe 112 without adopting the traditional pipetting gun to perform pipetting operation on the prepared droplets, the pipetting operation is convenient, the damage and the loss of the droplets can be better avoided, and the accuracy of the detection result can be improved.

In one embodiment, referring to fig. 1 to 4 again, the number of the first through holes 111, the flow guiding pipe 112, the continuous phase hole 121, the discrete phase hole 122, the droplet liquid outlet hole 123, the first flow channel 124, the second flow channel 125, the continuous phase sample inlet hole and the discrete phase sample inlet hole is two or more. The two or more flow guide pipes 112 are arranged in one-to-one correspondence with the two or more first through holes 111. The two or more first through holes 111, the two or more discrete phase holes 122, and the two or more first channels 124 are respectively disposed in one-to-one correspondence with the two or more droplet outlet holes 123. The two or more continuous phase holes 121 and the two or more second flow channels 125 are respectively disposed in one-to-one correspondence with the two or more first flow channels 124. Thus, when the continuous phase hole 121, the discrete phase hole 122, the droplet outlet hole 123, the first flow channel 124 and the second flow channel 125 are one, they are equivalent to one droplet preparation channel; when the number is two or more, it corresponds to two or more droplet preparing channels. When more than two droplet preparation channels work synchronously, more droplets can be prepared more efficiently, and the production efficiency is higher; furthermore, two or more droplets may be prepared simultaneously. Optionally, the first through hole 111, the flow guiding tube 112, the continuous phase hole 121, the discrete phase hole 122, the droplet outlet hole 123, the first flow channel 124, the second flow channel 125, the continuous phase sampling hole, and the discrete phase sampling hole are all one.

Further, referring to fig. 1 to 4 and 7, the first through hole 111, the flow guide tube 112, the continuous phase hole 121, the discrete phase hole 122, the droplet liquid outlet hole 123, the first flow channel 124, the second flow channel 125, the continuous phase sample inlet hole and the discrete phase sample inlet hole are all eight, and the eight flow guide tubes 112 are sequentially arranged at intervals to form a row. Thus, corresponding to eight droplet preparation channels, the storage container is, for example, eight rows of PCR tubes or 96-well PCR plates, and the eight flow-guide tubes 112 arranged in a row can be inserted into the respective test tubes of the eight rows of PCR tubes or into one of the rows of wells of the 96-well PCR plate.

In one embodiment, please refer to fig. 2 or fig. 3, a notch 1121 is formed on a sidewall of the liquid outlet end of the flow guiding tube 112. So, can avoid the microdroplet of preparation because surface tension acts on the inner wall of honeycomb duct 112 and the inner wall of self stickness adhesion honeycomb duct 112 and be not convenient for drop to the storage container in, play the surface tension who reduces the microdroplet and act on the pipe wall and reduce the adhesive force to the inner wall of honeycomb duct 112 to the microdroplet of being convenient for drops.

In one embodiment, referring to fig. 2 and 3, the height of the flow guide tube 112 is 3mm to 30mm, the outer diameter of the flow guide tube 112 is 2.5mm to 8mm, the inner diameter of the flow guide tube 112 is 1mm to 5mm, and the height of the notch 1121 is 1mm to 15 mm.

In one embodiment, referring to fig. 2 and 3, the substrate 13 is provided with a continuous phase sample inlet 14 and a discrete phase sample inlet 15. The continuous phase sampling pipe 14 is communicated with the continuous phase sampling hole, and the discrete phase sampling pipe 15 is communicated with the discrete phase sampling hole. Therefore, the continuous phase sampling pipe 14 is convenient to connect the continuous phase gas path 31 on one hand, and can be used for storing the continuous phase liquid on the other hand, and the continuous phase gas path 31 exerts pressure to press the continuous phase liquid stored in the continuous phase sampling pipe 14 into the continuous phase hole 121 during operation. In a similar way, the discrete phase sampling tube 15 is connected with the discrete phase gas path 32 on the one hand, and on the other hand can be used for storing discrete phase liquid, and the discrete phase gas path 32 is used for applying pressure to press the discrete phase liquid stored in the discrete phase sampling tube 15 into the discrete phase hole 122 during operation.

In one embodiment, referring to fig. 2 and fig. 3, the substrate 13 further has a gas blowing hole communicating with the droplet outlet hole 123. Specifically, an air blowing pipe 16 is arranged at the air blowing hole. Thus, if the prepared droplets are not convenient to fall into the storage container due to the fact that the surface tension acts on the inner wall of the guide pipe 112 and the inner wall of the guide pipe 112 is adhered to the viscosity of the droplets, the droplets can be blown through the blowing holes, and the droplets are separated from the guide pipe 112 and enter the storage container.

In one embodiment, referring to fig. 1 to 4, the cover plate 11 and the micro-control channel plate 12, and the micro-control channel plate 12 and the base plate 13 are bonded, welded, screwed, riveted, pinned, or clamped. Specifically, the adhesive connection may be a connection by using an adhesive, a connection by using a thermal compression bonding, or a connection by using a chemical agent. Furthermore, the welded connection may be a laser welded or ultrasonic welded connection. The cover plate 11, the micro-control channel plate 12 and the substrate 13 may be made of PMMA, PC, COC or POM, but not limited thereto.

In one embodiment, the micro control channel plate 12 is integrated with the cover plate 11 or the base plate 13; alternatively, the micro-control channel plate 12, the cover plate 11 and the substrate 13 are integrated.

Further, referring to fig. 5 to 9, the micro-control channel plate 12 and the substrate 13 are integrated, and the cover plate 11 is provided with a plurality of fasteners 113 that are snap-fit with the substrate 13. Specifically, the cover plate 11 is provided with a plurality of fasteners 113 on opposite sides thereof, and the cover plate 11 is provided with protrusions 115 corresponding to the opposite sides of the substrate 13 and abutting against the substrate in a limiting manner.

Further, referring to fig. 5 and 6, the microfluidic chip 10 further includes a sealing plate 17. A concave portion 114 is disposed on a side surface of the cover plate 11 facing the substrate 13 corresponding to the first through hole 111, the sealing plate 17 is adapted to the concave portion 114, an elastic sleeve 171 is disposed on the sealing plate 17, and two ends of the elastic sleeve 171 are respectively communicated with the droplet outlet hole 123 and the first through hole 111. Thus, the sealing plate 17 ensures the sealing property between the base plate 13 and the cover plate 11.

In one embodiment, referring to fig. 2, 3 and 10, a droplet preparation system includes the microfluidic chip 10 according to any of the above embodiments, and further includes a storage container and a gas source device 30. The flow conduit 112 is used to direct droplets into the storage container 20. The continuous phase gas path 31 of the gas source device 30 is communicated with the continuous phase sample inlet, and the discrete phase gas path 32 of the gas source device 30 is communicated with the discrete phase sample inlet.

When the microdroplet preparation system is used, for example, a trace quantitative pipette is adopted to respectively add quantitative continuous phase liquid into the continuous phase sample inlet and quantitative discrete phase liquid into the discrete phase sample inlet; then the micro-fluidic chip 10 is connected to a micro-droplet preparation system, and micro-droplet preparation is carried out by adjusting time and pressure; in the droplet preparation process, droplets from the droplet outlet 123 pass through the first through hole 111 of the cover plate 11 and then are discharged along the flow guide tube 112 into the storage container 20 (e.g., test tubes and multi-well plates). Therefore, the prepared droplets are directly discharged to the storage container 20 through the guide pipe 112 without adopting the traditional pipetting gun to perform pipetting operation on the prepared droplets, the pipetting operation is convenient, the damage and the loss of the droplets can be better avoided, and the accuracy of the detection result can be improved.

In one embodiment, referring to fig. 2, 3 and 10, the air supply device 30 includes a lower pressure connector 33. The pressing connector 33 is provided with a continuous connector 331 and a discrete connector 332. The continuous phase gas path 31 is communicated with the continuous phase sample inlet through the continuous phase joint 331, and the discrete phase gas path 32 is communicated with the discrete phase sample inlet through the discrete phase joint 332.

Further, pressure gauges 34 are arranged on the continuous phase air path 31 and the discrete phase air path 32. The air source device 30 further comprises a control module 35 for controlling the pressure of the air source and the air supply time, wherein the control module 35 is connected to the continuous phase air path 31, the discrete phase air path 32 and the external air source 36 respectively.

Specifically, when a plurality of continuous phase sampling holes are provided, the number of the continuous phase connectors 331 is correspondingly large, and when the plurality of continuous phase connectors 331 are correspondingly communicated with the plurality of continuous phase sampling holes, gas can be synchronously introduced into the plurality of continuous phase sampling holes; when the looks of discretizing advance the hole for a plurality of, the looks of discretizing connects 332 correspondingly for a plurality of, and when a plurality of looks of discretizing connect 332 correspond a plurality of looks of discrete advance the hole of intercommunication, can let in gas for a plurality of looks of discretizing in step.

In one embodiment, referring to fig. 2, 3 and 10, a droplet preparation method using the droplet preparation system of the above embodiment includes the following steps:

adding quantitative continuous phase liquid into the continuous phase sample inlet and quantitative discrete phase liquid into the discrete phase sample inlet;

communicating a continuous phase gas path 31 of a gas source device 30 with a continuous phase sample inlet, communicating a discrete phase gas path 32 with the discrete phase sample inlet, and performing droplet preparation by adjusting time and gas pressure;

during the droplet preparation process, droplets from the droplet outlet 123 pass through the first through hole 111 of the cover plate 11 and then are discharged along the flow guide tube 112 to the storage container 20.

According to the droplet preparation method, the prepared droplets are directly discharged to the storage container 20 through the guide pipe 112 without adopting the traditional pipetting gun to perform pipetting operation on the prepared droplets, so that the pipetting operation is convenient, the damage and the loss of the droplets can be better avoided, and the accuracy of the detection result can be improved.

Further, the droplet preparation method further comprises the steps of: the gas source device 30 includes a lower pressure joint 33, a continuous phase joint 331 and a discrete phase joint 332 are provided on the lower pressure joint 33, the continuous phase gas path 31 is correspondingly communicated with the continuous phase sample inlet through the continuous phase joint 331, and the discrete phase gas path 32 is correspondingly communicated with the discrete phase sample inlet through the discrete phase joint 332; the continuous phase sampling holes and the discrete phase sampling holes are multiple, and the continuous phase connectors 331 and the discrete phase connectors 332 are multiple correspondingly; when connecting a plurality of continuous phase connectors 331 with a plurality of continuous phase sampling holes of corresponding intercommunication, let in gas for a plurality of continuous phase sampling holes in step to and connect a plurality of discrete phase sampling holes with a plurality of discrete phase connectors 332 with a plurality of discrete phase sampling holes of corresponding intercommunication, let in gas for a plurality of discrete phase sampling holes in step.

It should be noted that the principle of generating droplets by the microfluidic chip is to introduce two immiscible fluids into a flow channel of the microfluidic chip, wherein one of the fluids is a discrete phase and serves as a sheared phase fluid, and the other fluid is a continuous phase and serves as a shearing fluid, and the discrete phase fluid is separated into discrete droplets by the continuous phase fluid in an intersection region of the two fluids.

Specifically, referring to fig. 11, after the continuous phase fluid and the discrete phase fluid respectively enter the corresponding channels in the microfluidic chip, interfaces of the continuous phase fluid and the discrete phase fluid are formed at the junctions of different channels. The discrete phase fluid moves forward synchronously with the continuous phase fluid under the pushing of external force and the shearing force of the continuous phase fluid. When the interfacial tension at the interface is insufficient to maintain the shear force applied to the discrete phase fluid by the continuous phase fluid, the discrete phase fluid breaks to create individual microscopic volume elements, i.e., droplets, surrounded by the continuous phase fluid.

For example, in the case where the continuous phase fluid is oil and the discrete phase fluid is water, an oil/water interface is formed at the oil-water junction, the aqueous phase moves forward in synchronization with the oil phase under the urging of an external force and the shearing force of the oil phase, and the aqueous phase breaks to form individual droplets surrounded by the oil phase when the interfacial tension at the oil/water interface is insufficient to maintain the shearing force applied to the aqueous phase by the oil phase.

The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.

Claims (12)

1. A microfluidic chip, comprising:

the cover plate is provided with a first through hole and a flow guide pipe which is arranged on the side surface of the cover plate and is communicated with the first through hole, and the flow guide pipe is used for guiding the micro-droplets to a storage container;

the micro-control channel plate is stacked on the cover plate, and is provided with a continuous phase hole, a discrete phase hole, a microdrop liquid outlet hole, a first flow channel and a second flow channel, wherein the discrete phase hole is communicated with the microdrop liquid outlet hole through the first flow channel, the continuous phase hole is communicated with the first flow channel through the second flow channel, and the microdrop liquid outlet hole is communicated with the first through hole; and

the substrate, the substrate stack is located on the micro-control channel board, be equipped with continuous phase sample inlet and discrete looks sample inlet on the substrate, continuous phase sample inlet with continuous phase hole is linked together, discrete looks sample inlet with discrete looks hole intercommunication.

2. The microfluidic chip according to claim 1, wherein the number of the first through hole, the flow guide tube, the continuous phase hole, the discrete phase hole, the droplet outlet hole, the first flow channel, the second flow channel, the continuous phase sample inlet hole, and the discrete phase sample inlet hole is two or more; more than two flow guide pipes are arranged in one-to-one correspondence with more than two first through holes; the more than two first through holes, the more than two discrete phase holes and the more than two first flow channels are respectively arranged corresponding to the more than two micro-droplet liquid outlet holes one by one; the more than two continuous phase holes and the more than two second flow passages are respectively arranged in one-to-one correspondence with the more than two first flow passages.

3. The microfluidic chip according to claim 2, wherein the first through hole, the flow guide tube, the continuous phase hole, the discrete phase hole, the droplet liquid outlet hole, the first flow channel, the second flow channel, the continuous phase sample inlet hole and the discrete phase sample inlet hole are eight, and the eight flow guide tubes are sequentially arranged at intervals to form a row.

4. The microfluidic chip according to claim 1, wherein a notch is formed on a sidewall of the liquid outlet end of the flow guide tube; the height of the honeycomb duct is 3mm-30mm, the outer diameter of the honeycomb duct is 2.5mm-8mm, the inner diameter of the honeycomb duct is 1mm-5mm, and the height of the notch is 1mm-15 mm.

5. The microfluidic chip according to claim 1, wherein the substrate is provided with a continuous phase sampling tube and a discrete phase sampling tube, the continuous phase sampling tube is communicated with the continuous phase sampling hole, and the discrete phase sampling tube is communicated with the discrete phase sampling hole; the substrate is also provided with a gas blowing hole communicated with the micro-droplet liquid outlet hole; and an air blowing pipe is arranged at the air blowing hole.

6. The microfluidic chip according to claim 1, wherein the cover plate and the micro control channel plate and the substrate are bonded, welded, screwed, riveted, pinned or clamped.

7. The microfluidic chip according to claim 1, wherein the micro control channel plate is integrated with the cover plate or the substrate; or the micro-control channel plate, the cover plate and the base plate are of an integrated structure.

8. The microfluidic chip according to claim 7, wherein the micro control channel plate and the substrate are integrated, and the cover plate is provided with a plurality of fasteners that are engaged with the substrate.

9. The microfluidic chip according to claim 8, further comprising a sealing plate, wherein a recess is formed on a side surface of the cover plate facing the substrate corresponding to the first through hole, the sealing plate is adapted to the recess, and an elastic sleeve is disposed on the sealing plate, and two ends of the elastic sleeve are respectively connected to the droplet outlet hole and the first through hole.

10. A droplet preparation system, comprising the microfluidic chip according to any one of claims 1 to 9, further comprising a storage container and an air source device, wherein the flow guide tube is used for guiding the droplets to the storage container, the continuous phase air path of the air source device is communicated with the continuous phase sample inlet, and the discrete phase air path of the air source device is communicated with the discrete phase sample inlet.

11. The droplet preparation system of claim 10, wherein the gas source device includes a pressure connector, the pressure connector having a continuous phase connector and a discrete phase connector, the continuous phase gas path being in communication with the continuous phase sample inlet via the continuous phase connector, and the discrete phase gas path being in communication with the discrete phase sample inlet via the discrete phase connector;

pressure gauges are arranged on the continuous phase gas circuit and the discrete phase gas circuit; the air source device further comprises a control module for controlling the pressure of the air source and the air supply time, and the control module is connected with the continuous phase air path, the discrete phase air path and the external air source respectively.

12. A method of droplet preparation using the droplet preparation system of claim 10, comprising the steps of:

adding quantitative continuous phase liquid into the continuous phase sample inlet and quantitative discrete phase liquid into the discrete phase sample inlet;

communicating a continuous phase gas path of a gas source device with a continuous phase sample inlet, communicating a discrete phase gas path with a discrete phase sample inlet, and performing droplet preparation by adjusting time and gas pressure;

in the process of preparing the droplets, the droplets of the droplet liquid outlet holes pass through the first through holes of the cover plate and then are discharged into the storage container along the flow guide pipe.

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