Micro-droplet preparation system, micro-fluidic chip and micro-droplet preparation method
阅读说明:本技术 微滴制备系统、微流控芯片及微滴制备方法 (Micro-droplet preparation system, micro-fluidic chip and micro-droplet preparation method ) 是由 梁帅 何关金 罗杵添 张慧儒 林计良 何霖 李晶 王帅超 于 2019-10-28 设计创作,主要内容包括:本发明涉及一种微滴制备系统、微流控芯片及微滴制备方法。微流控芯片,包括盖板、微控通道板及基板。具体使用时,例如采用微量定量移液枪分别将定量的连续相液体加入到连续相进样孔中,以及将定量的离散相液体加入到离散相进样孔中;然后将微流控芯片接入到微滴制备系统,通过调节时间和压力进行微滴制备;微滴制备过程中,微滴出液孔的微滴经过盖板的第一通孔后沿着导流管排放到储存容器中(例如检测试管及多孔板)。如此,无需采用传统的移液枪对制备好的微滴进行移液操作,直接将制备好的微滴通过导流管向外排放到储存容器中,移液操作方便,能较好地避免微滴的破损和损失,从而能提高检测结果的准确性。(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.)
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.
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
The micro-control channel plate 12 is stacked on the
When the
In one embodiment, referring to fig. 1 to 4 again, the number of the first through
Further, referring to fig. 1 to 4 and 7, the first through
In one embodiment, please refer to fig. 2 or fig. 3, a
In one embodiment, referring to fig. 2 and 3, the height of the
In one embodiment, referring to fig. 2 and 3, the
In one embodiment, referring to fig. 2 and fig. 3, the
In one embodiment, referring to fig. 1 to 4, the
In one embodiment, the micro control channel plate 12 is integrated with the
Further, referring to fig. 5 to 9, the micro-control channel plate 12 and the
Further, referring to fig. 5 and 6, the
In one embodiment, referring to fig. 2, 3 and 10, a droplet preparation system includes the
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
In one embodiment, referring to fig. 2, 3 and 10, the
Further, pressure gauges 34 are arranged on the continuous
Specifically, when a plurality of continuous phase sampling holes are provided, the number of the
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
during the droplet preparation process, droplets from the
According to the droplet preparation method, the prepared droplets are directly discharged to the
Further, the droplet preparation method further comprises the steps of: the
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.
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