CN113304790A - Three-dimensional microfluidic chip for realizing high-throughput preparation of micro-droplets by parallelization design - Google Patents
Three-dimensional microfluidic chip for realizing high-throughput preparation of micro-droplets by parallelization design Download PDFInfo
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- B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
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- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
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- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502769—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements
- B01L3/502784—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
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- B—PERFORMING OPERATIONS; TRANSPORTING
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- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
Abstract
The invention discloses a three-dimensional microfluidic chip for realizing high-throughput preparation of micro-droplets through parallelization design, which comprises a micro-droplet unit generation layer, a substrate layer and a liquid distribution layer, wherein the substrate layer is bonded on the lower surface of the micro-droplet unit generation layer, the liquid distribution layer is bonded on the upper surface of the micro-droplet unit generation layer, the lower surface of the micro-droplet unit generation layer is provided with a plurality of droplet generation units which are arranged in parallelization, each droplet generation unit is used for generating micro-droplets, the lower surface of the liquid distribution layer is provided with a continuous phase distribution flow channel and a disperse phase distribution flow channel, the continuous phase flow channel is used for enabling continuous phase fluid to respectively enter each droplet generation unit, and the disperse phase flow channel enables corresponding disperse phase fluid to respectively enter each droplet generation unit. The three-dimensional microfluidic chip device provided by the invention has the advantages that the yield of micro liquid drops can be improved by multiple times in the same time by paralleling a plurality of micro liquid drop generating units.
Description
Technical Field
The invention belongs to the technical field of microfluidics, and particularly relates to a three-dimensional microfluidic chip and a method for realizing high-throughput preparation of micro-droplets through parallelization design.
Background
The droplet microfluidics technology is a technology which forms monodisperse droplets by multiphase flow shearing in a micro-channel and controls the droplets. The technique benefits from the ability to precisely control surface tension, viscous forces, etc. between multiphase fluids in a microscale flow channelThe velocity of each fluid can be precisely adjusted to produce monodisperse, highly uniform microdroplets. The micro-droplet prepared by the micro-fluidic technology has proved to have potential application prospect in the fields of chemical reaction, material synthesis, biological analysis and the like. Nevertheless, microfluidic droplets have low yields (< 10mL h)-1) Has been a barrier to the transition of this technology from the laboratory phase to commercial large-scale applications. The yield of one micro-droplet generation unit is limited, but the micro-droplet generation units can be arranged in parallel in a ladder-shaped design, so that the yield of micro-droplets can be improved by multiple times in the same time. The N micro-droplet generating units have N continuous phase inlets, N dispersed phase inlets and N collecting outlets, and in principle, N + N liquid inlet devices are required, which is obviously time-consuming, labor-consuming and will greatly increase the cost. Most of the droplet microfluidic devices commonly used at present are two-dimensional fluid flow channels, and no matter how designed, the generation rate of micro droplets has certain limitation, and the generation of high-flux micro droplets is not satisfied. Chinese patent No. ZL201911031393.1 discloses a three-dimensional microfluidic device and method for high-throughput droplet generation, which relates to a method for distributing liquid using a dendritic microfluidic channel, but the fluid branch in this design occupies a larger space, and compared with the ladder-shaped channel distribution design used in the present invention, fewer droplet generation units are accommodated, and if one of the channels in the fluid branch is blocked, the fluid distribution in the symmetrical channel is affected to some extent. Chinese patent (publication number CN109908983A) discloses a micro-fluidic chip with a three-dimensional conical structure and used for micro-droplet high-proportion splitting extraction, and relates to a micro-fluidic chip with a three-dimensional conical structure. Chinese patent (publication number CN206492517U) discloses an embedded three-dimensional flow channel type microfluidic chip based on PMMA material. Chinese patent (publication No. CN209144161U) discloses a microfluidic chip system, which includes a micro-droplet generating device, a power generating device, a collecting bottle, and a connecting device for connecting the micro-droplet generating device, the power generating device, and the collecting bottle. However, in the above method, the production rate of the micro-droplets is limitedAnd the production scale required for preparing micro-droplets in high flux cannot be met.
Disclosure of Invention
The purpose of the invention is as follows: the invention aims to provide a three-dimensional microfluidic chip which can convey continuous phase fluid and disperse phase fluid to each micro-droplet generation unit through respective distribution flow channels and realize high-throughput production of micro-droplets by means of parallelization design; it is another object of the present invention to provide a method for preparing microdroplets using the above chip.
The technical scheme is as follows: the invention relates to a three-dimensional microfluidic chip for realizing micro-droplet high-throughput preparation through parallelization design, which comprises a micro-droplet unit generation layer, a substrate layer and a liquid distribution layer, wherein the substrate layer is bonded on the lower surface of the micro-droplet unit generation layer, the liquid distribution layer is bonded on the upper surface of the micro-droplet unit generation layer, the lower surface of the micro-droplet unit generation layer is provided with a plurality of micro-droplet generation units which are arranged in parallelization, each micro-droplet generation unit is used for generating a micro-droplet, the lower surface of the liquid distribution layer is provided with a continuous phase distribution flow channel and a disperse phase distribution flow channel, the continuous phase flow channel is used for enabling continuous phase fluid to respectively enter each droplet generation unit, and the disperse phase flow channel enables corresponding disperse phase fluid to respectively enter each droplet generation unit. The invention introduces the design of multilayer micro-fluid flow channels, and conveys continuous phase fluid and disperse phase fluid to each micro-droplet generation unit through respective distribution flow channels, thereby realizing parallel production, obviously reducing the use number of injection pumps, and reducing the number of injection pumps from N + N to two.
Furthermore, the upper surface of the liquid distribution layer is provided with a plurality of liquid inlet joints and a plurality of collection port joints, each liquid inlet joint comprises a continuous phase inlet joint and a plurality of disperse phase inlet joints, the liquid distribution layer is provided with a continuous phase distribution flow channel communicated with the continuous phase inlet joints and a plurality of disperse phase distribution flow channels communicated with the disperse phase inlet joints in a one-to-one correspondence manner, and the collection port joints are used for collecting micro-droplets generated by the droplet generation unit.
Furthermore, the micro-droplet unit generation layer comprises a plurality of micro-droplet generation units and a main micro-droplet collection flow channel, each micro-droplet generation unit comprises a continuous phase inlet communicated with the continuous phase distribution flow channel, a continuous phase flow channel communicated with the continuous phase inlet, a dispersed phase inlet communicated with the dispersed phase distribution flow channels in a one-to-one correspondence manner, and a dispersed phase flow channel communicated with the dispersed phase inlets in a one-to-one correspondence manner, micro-droplets are generated by shearing at the position of the intersection of the continuous phase fluid and the mixed dispersed phase fluid under the action of surface tension, the generated micro-droplets are converged into the main micro-droplet collection flow channel, and a micro-droplet outlet is arranged at the tail end of the main micro-droplet collection flow channel.
Furthermore, the upper surface of the liquid distribution layer is provided with three liquid inlet joints and a collection port joint, the liquid inlet joints comprise a continuous phase inlet joint, a first dispersed phase inlet joint and a second dispersed phase inlet joint, and the liquid distribution layer is provided with a continuous phase distribution flow channel communicated with the continuous phase inlet joint, a first dispersed phase distribution flow channel communicated with the first dispersed phase inlet joint and a second dispersed phase distribution flow channel communicated with the second dispersed phase inlet joint.
Further, the micro-droplet unit generation layer comprises a plurality of micro-droplet generation units and a main micro-droplet collection flow channel, each micro-droplet generation unit comprises a continuous phase inlet communicated with the continuous phase distribution flow channel, a continuous phase flow channel, a first dispersed phase inlet communicated with the first dispersed phase distribution flow channel, a second dispersed phase inlet communicated with the second dispersed phase distribution flow channel, a first dispersed phase flow channel, a second dispersed phase flow channel and a delivery flow channel, the front end of the continuous phase flow channel is communicated with the continuous phase inlet, the rear end of the continuous phase flow channel is communicated with the delivery flow channel, the front end of the first dispersed phase flow channel is communicated with the first dispersed phase inlet, the rear end of the first dispersed phase flow channel is communicated with the delivery flow channel, two dispersed phase fluids are collected firstly in the delivery flow channel and then meet with the continuous phase fluid, and at the meeting position, under the action of surface tension, and the tail end of the conveying flow channel is communicated with a main micro-droplet collecting flow channel, and a micro-droplet outlet is arranged at the tail end of the main micro-droplet collecting flow channel.
Furthermore, the height of the flow channels in the liquid distribution layer is equal, the height range is 10-1000 microns, the height of the flow channels in the liquid distribution layer is equal, and the height range is 10-1000 microns.
Further, the liquid distribution layer is provided with through holes at positions of the respective joints, and the micro droplet unit generation layer is provided with through holes at positions of the respective inlets and the respective outlets.
Furthermore, the structure of the flow channel is a rectangular flow channel, the continuous phase flow channel and the dispersed phase flow channel are symmetrically designed, and the continuous phase fluid and the collected dispersed phase fluid are cut at the intersection of the flow channels in a flow focusing manner to generate micro-droplets.
A method for preparing micro-droplets by using the three-dimensional microfluidic chip comprises the following steps:
(1) fixing a three-dimensional microfluidic chip for preparing micro-droplets in a high flux manner on a microfluidic operation platform, observing through a microscope, and ensuring that each group of micro-droplet generation units in the micro-droplet unit generation layer are positioned in the field of view of the microscope and no inclination is caused;
(2) respectively connecting a continuous phase inlet joint, a first dispersed phase inlet joint and a second dispersed phase inlet joint with an injector filled with continuous phase fluid, an injector filled with first dispersed phase fluid and an injector filled with second dispersed phase fluid through conduits, wherein each injector is respectively connected with an injection pump, and a micro-droplet collection port joint is also connected with a collection container through a conduit;
(3) and starting the injection pump, adjusting the continuous phase fluid and the disperse phase fluid to corresponding flow rates through the injection pump, generating the micro-droplets through each group of micro-droplet generation units, and finally finishing the collection.
Has the advantages that: the three-dimensional microfluidic chip can overcome the defects of low micro-droplet generation speed, low yield and the like of the conventional two-dimensional microfluidic chip, the three-dimensional microfluidic chip device can realize that the yield of micro-droplets is improved by multiple times in the same time by paralleling a plurality of micro-droplet generation units, and similarly, the three-dimensional microfluidic chip device can also paralleling a plurality of micro-droplet generation units to manufacture a chip with more layers of complex structures by combining an upper distribution flow channel so as to realize that the yield of micro-droplets reaches a high-flux scale. Secondly, the micro-droplet unit generation layer and the liquid distribution layer are made of PDMS, the substrate layer, the micro-droplet unit generation layer and the liquid distribution layer are mutually bonded and then are very firm, the pressure caused by the sample injection fluid can be borne, the cracking phenomenon caused by overlarge pressure can be avoided, and the PDMS is transparent in the whole body and convenient to observe. The chip of the invention can realize the generation of micro-droplets containing one or two dispersed phases, and can also realize the high-flux production of micro-bubbles when the dispersed phases are changed into gas.
Drawings
Fig. 1 is an isometric view of a three-dimensional microfluidic chip for high-throughput production of microdroplets according to the present invention;
fig. 2 (a) is an isometric top view of a microdroplet-unit-generating layer, and (b) is an isometric side view of a microdroplet-unit-generating layer;
FIG. 3 (a) is a top isometric view of a liquid distribution layer and (b) is a side isometric view of the liquid distribution layer;
fig. 4 (a) is an isometric top view of a schematic diagram of the generation of micro-droplets of a three-dimensional microfluidic chip device for high-throughput micro-droplet generation, and (b) is an isometric side view of a schematic diagram of the generation of micro-droplets of a three-dimensional microfluidic chip device for high-throughput micro-droplet generation;
fig. 5 (a) is an isometric top view of a three-dimensional microfluidic chip for high-throughput preparation of microdroplets, which has forty sets of microdroplet generation units in parallel, and (b) is an isometric side view of a three-dimensional microfluidic chip for high-throughput preparation of microdroplets, which has forty sets of microdroplet generation units in parallel.
Detailed Description
For a further understanding of the present invention, reference will now be made in detail to the embodiments illustrated in the drawings.
In this embodiment, a three-dimensional microfluidic chip for realizing high-throughput preparation of micro droplets through a parallelization design is a closed flow channel structure formed by bonding and forming a substrate layer 700, a micro droplet unit generation layer 600 (the micro droplet unit generation layer includes five groups of micro droplet generation units), and a liquid distribution layer 500, and the closed flow channel structure is provided with a continuous phase inlet joint 100, a first dispersed phase inlet joint 200, a second dispersed phase inlet joint 300, and a collection joint 400.
As shown in fig. 2 and 3, three distribution flow channels, namely a continuous phase distribution flow channel 519, a first dispersed phase distribution flow channel 520 and a second dispersed phase distribution flow channel 521, are arranged on the lower surface of the liquid distribution layer 500, and four joint positions in fig. 1 are respectively provided with a continuous phase inlet 501, a first dispersed phase inlet 507, a second dispersed phase inlet 513 and a micro-droplet collection outlet a522 which are in one-to-one correspondence and are communicated; continuous phase fluid enters a continuous phase distribution flow channel 519 from the continuous phase inlet connector 100 through a continuous phase inlet 501, the flow resistance in the distribution flow channel is far smaller than that in each micro-droplet generation unit in the micro-droplet unit generation layer, and the continuous phase fluid can uniformly flow into a continuous phase first inlet A502 and a continuous phase second inlet A503, a continuous phase third inlet A504, a continuous phase fourth inlet A505 and a continuous phase fifth inlet A506; similarly, the first dispersed phase fluid enters the first dispersed phase distribution flow channel 520 from the first dispersed phase inlet joint 200 through the first dispersed phase inlet 507, and the first dispersed phase fluid uniformly flows into the first dispersed phase first inlet a508, the first dispersed phase second inlet a509, the first dispersed phase third inlet a510, the first dispersed phase fourth inlet a511, and the first dispersed phase fifth inlet a 512; the second dispersed phase fluid enters the second dispersed phase distribution flow channel 521 from the second dispersed phase inlet joint 300 through the second dispersed phase inlet 513, and the second dispersed phase fluid uniformly flows into the second dispersed phase first inlet a514, the second dispersed phase second inlet a515, the second dispersed phase third inlet a516, the second dispersed phase fourth inlet a517 and the second dispersed phase fifth inlet a 518; each distribution flow channel in the liquid distribution layer uniformly conveys the continuous phase fluid and the disperse phase fluid to the corresponding continuous phase inlet and disperse phase inlet in each micro-droplet generation unit, and the fluid flows into each micro-droplet generation unit.
The flow channels of the closed flow channel structure in the liquid distribution layer are all equal in height, the height range is 10-1000 microns, and the continuous phase inlet 501, the first dispersed phase inlet 507, the second dispersed phase inlet 513 and the micro-droplet collection outlet A522 are all through holes penetrating through the upper surface. The heights of the flow channels in the micro-droplet unit generation layer (600) are all equal and are in the range of 10-1000 microns, wherein the continuous phase first inlet A502, the continuous phase second inlet A503, the continuous phase third inlet A504, the continuous phase fourth inlet A505, the continuous phase fifth inlet A506, the first dispersed phase first inlet A508, the first dispersed phase second inlet A509, the first dispersed phase third inlet A510, the first dispersed phase fourth inlet A511, the first dispersed phase fifth inlet A512, the second dispersed phase first inlet A514, the second dispersed phase second inlet A515, the second dispersed phase third inlet A516, the second dispersed phase fourth inlet A517 and the second dispersed phase fifth inlet A518 are all through holes, and the diameters of the through holes are all the same.
As shown in fig. 2, the microdroplet unit generation layer 600 includes five groups of microdroplet generation units, wherein the first group of microdroplet generation units includes a continuous phase first inlet B601, a first dispersed phase first inlet B602, a second dispersed phase first inlet B605, a continuous phase flow channel 603, a first dispersed phase flow channel 604, a second dispersed phase flow channel 606, and a delivery flow channel 608, the continuous phase fluid flows through the continuous phase distribution flow channel 519 in the liquid distribution layer, flows through the continuous phase first inlet a502, the continuous phase first inlet a502 is communicated with the continuous phase first inlet B601, the continuous phase fluid flows into the symmetrical and intercommunicated flow channel 603, and the continuous phase fluid can uniformly divide into two sub-streams to flow in the flow channel 603; the first dispersed phase fluid flows through a first dispersed phase distribution flow channel 520 in the liquid distribution layer and flows through a first dispersed phase first inlet A508, the first dispersed phase first inlet A508 is communicated with a first dispersed phase first inlet B602, the first dispersed phase fluid flows into symmetrical and communicated first dispersed phase flow channels 604, and the first dispersed phase fluid is uniformly divided into two branch flows to flow in the flow channels 604; the second dispersed phase fluid flows through the second dispersed phase distribution flow channel 521 in the liquid distribution layer, through the second dispersed phase first inlet a514, the second dispersed phase first inlet a514 communicating with the second dispersed phase first inlet B605, the second dispersed phase fluid entering the second dispersed phase flow channel 606, the second dispersed phase fluid flowing in the flow channel 606; the continuous phase fluid meets the first and second dispersed phase fluids at the channel position 607, and under the action of surface tension, the continuous phase fluid is sheared into micro-droplets, and the micro-droplets pass through the delivery channel 608 having a curved structure and flow into the main micro-droplet collection channel 622; the second group, the third group, the fourth group and the fifth group of micro-droplet generation units have the same structure as the first group and are designed in parallel. The five groups of micro-droplet collecting channels are converged into the main micro-droplet collecting channel 622, and pass through the micro-droplet collecting outlet B621, the micro-droplet collecting outlet B621 in the droplet unit production layer is vertically communicated with the micro-droplet collecting outlet A522 in the liquid distribution layer, and the generated micro-droplets are collected by connecting the micro-droplet collecting connector 400 through a capillary pipeline.
The flow channels of the closed flow channel structure in the droplet generation layer are all equal in height, the height ranges from 10 micrometers to 1000 micrometers, and the continuous phase first inlet B601, the continuous phase second inlet B609, the continuous phase third inlet B612, the continuous phase fourth inlet B615, the continuous phase fifth inlet B618, the first dispersed phase first inlet B602, the first dispersed phase second inlet B610, the first dispersed phase third inlet B613, the first dispersed phase fourth inlet B616, the first dispersed phase fifth inlet B619, the second dispersed phase first inlet B605, the second dispersed phase second inlet B611, the third dispersed phase first inlet B614, the fourth dispersed phase first inlet B617, the second dispersed phase fifth inlet B620 and the flow channel outlet B621 which are included in the droplet generation layer are all through holes penetrating through the upper surface of the droplet generation layer, and the hole diameters are all the same.
The closed micro-channel system is made of Polydimethylsiloxane (PDMS) with good biocompatibility and good light transmission performance, and other organic polymer materials or glass or quartz can be adopted as a manufacturing material, wherein the organic polymer materials can be: cyclic Olefin Copolymer (COC), polymethyl methacrylate (PMMA), Polystyrene (PS) and the like, and is convenient for monitoring and recording the generation process of the micro-droplets.
The relative positional relationship among the substrate layer 700, the micro droplet unit generation layer 600, and the liquid distribution layer 500 is as follows: the micro-droplet unit generation layer 600 has a lower surface key of the flow channel and is on the surface of the substrate layer 700; the liquid distribution layer 500 has a lower surface key of the flow channel and an upper surface without the flow channel in the micro droplet unit generation layer 600; the continuous phase first inlet a502 is communicated with the continuous phase first inlet B601, the continuous phase second inlet a503 is communicated with the continuous phase second inlet B609, the continuous phase third inlet a504 is communicated with the continuous phase third inlet B612, the continuous phase fourth inlet a505 is communicated with the continuous phase fourth inlet B615, the continuous phase fifth inlet a506 is communicated with the continuous phase fifth inlet B618, the first dispersed phase first inlet a508 is communicated with the first dispersed phase first inlet B602, the first dispersed phase second inlet a509 is communicated with the first dispersed phase second inlet B610, the first dispersed phase third inlet a510 is communicated with the first dispersed phase third inlet B613, the first dispersed phase fourth inlet a511 is communicated with the first dispersed phase fourth inlet B616, the first dispersed phase fifth inlet a512 is communicated with the first dispersed phase fifth inlet B619, the second dispersed phase first inlet a514 is communicated with the continuous phase first dispersed phase first inlet B605, the second dispersed phase second inlet a515 and the second dispersed phase second inlet B611 are communicated with each other, the second dispersed phase third inlet a516 and the second dispersed phase third inlet B614 are communicated with each other, the second dispersed phase fourth inlet and the second dispersed phase fourth inlet B617 are communicated with each other, the second dispersed phase fifth inlet a518 and the second dispersed phase fifth inlet B620 are communicated with each other, and the micro droplet collection outlet B621 and the micro droplet collection outlet a522 are communicated with each other.
The droplet generation method of the three-dimensional microfluidic chip for realizing the high-throughput preparation of the micro droplets through the parallelization design comprises the following steps:
(1) the three-dimensional microfluidic chip for preparing the micro-droplets in a high-flux manner is fixed on a microfluidic operation platform, and observation is carried out by a microscope, so that five groups of micro-droplet generation units in the micro-droplet unit generation layer 500 are ensured to be positioned in the field of view of the microscope and no inclination is ensured.
(2) The continuous phase inlet connector 100, the first dispersed phase inlet connector 200 and the second dispersed phase inlet connector 300 are respectively connected with a syringe filled with continuous phase fluid, a syringe filled with first dispersed phase fluid and a syringe filled with second dispersed phase fluid through conduits, the syringes are respectively connected with an injection pump, and the micro-droplet collection port connector A522 is also connected with a collection container through a conduit.
(3) And starting the injection pump, adjusting the continuous phase fluid and the disperse phase fluid to corresponding flow rates through the injection pump, and generating and collecting the micro-droplets through the five micro-droplet generation units.
Referring to fig. 4, the generation process of micro-droplets in the three-dimensional microfluidic chip device for high-throughput micro-droplet generation is as follows: the principle of droplet generation in the five groups of droplet generation units is the same, in the first group of droplet generation units, the continuous phase fluid enters the first continuous phase flow channel 603 from the continuous phase first inlet B601, the first dispersed phase fluid enters the first dispersed phase flow channel 604 from the first dispersed phase first inlet B602, the second dispersed phase fluid enters the second dispersed phase flow channel 606 from the second dispersed phase first inlet B605, the continuous phase fluid and the mixed first dispersed phase and second dispersed phase fluid meet at the flow channel position 607, droplets are generated by shearing under the action of surface tension, and the generated droplets flow into the conveying device 608 and join the droplet main collection flow channel 622 to collect the generated droplets. The flow rate of the continuous phase fluid and the dispersed phase fluid is adjusted through the injection pump, so that the size of the generated micro-droplets is changed, and the high-flux generation of the micro-droplets is realized by paralleling five groups of micro-droplet generation units.
Example 2
Referring to fig. 5, the difference from embodiment 1 is: the three-dimensional microfluidic chip for preparing the micro-droplets in a high-flux manner by paralleling forty groups of micro-droplet generation units comprises a substrate layer, a micro-droplet generation layer and a plurality of liquid distribution layers, and also comprises a continuous phase inlet joint 101, a first dispersed phase inlet joint 102, a second dispersed phase inlet joint 103 and a collection port joint 104.
Claims (10)
1. The three-dimensional microfluidic chip is characterized by comprising a micro-droplet unit generation layer (600), a substrate layer (700) bonded on the lower surface of the micro-droplet unit generation layer (600), and a liquid distribution layer (500) bonded on the upper surface of the micro-droplet unit generation layer (600), wherein the lower surface of the micro-droplet unit generation layer (600) is provided with a plurality of droplet generation units which are arranged in parallel, each droplet generation unit is used for generating a micro-droplet, the lower surface of the liquid distribution layer (500) is provided with a continuous phase distribution flow channel and a disperse phase distribution flow channel, the continuous phase flow channel is used for enabling continuous phase fluid to respectively enter each droplet generation unit, and the disperse phase distribution flow channel enables corresponding disperse phase fluid to respectively enter each droplet generation unit.
2. The three-dimensional microfluidic chip according to claim 1, wherein the three-dimensional microfluidic chip is provided with a plurality of liquid inlet joints and a plurality of collecting port joints (400), the liquid inlet joints comprise a continuous phase inlet joint (100) and a plurality of disperse phase inlet joints, the continuous phase distribution flow channels of the liquid distribution layer (500) are communicated with the continuous phase inlet joints, the liquid distribution layer is provided with a plurality of disperse phase distribution flow channels which are communicated with the disperse phase inlet joints in a one-to-one correspondence manner, and the collecting port joints are used for collecting micro-droplets generated by the droplet generation unit.
3. The three-dimensional microfluidic chip of claim 2, wherein the droplet generation layer (600) comprises a plurality of droplet generation units and a main droplet collection channel (622), each of the droplet generation units comprises a continuous phase inlet communicated with the continuous phase distribution channel, a continuous phase channel communicated with the continuous phase inlet, a dispersed phase inlet communicated with the dispersed phase distribution channels in a one-to-one correspondence, and a dispersed phase channel communicated with the dispersed phase inlets in a one-to-one correspondence, and the continuous phase fluid and the mixed dispersed phase fluid flow in the respective channels, and at the intersection position of the continuous phase channel and the dispersed phase channel, the droplets are sheared and generated under the action of surface tension and merge into the main droplet collection channel (622), and a droplet outlet is arranged at the end of the main droplet collection channel.
4. The three-dimensional microfluidic chip according to claim 1, wherein the upper surface of the three-dimensional microfluidic chip is provided with three liquid inlet joints and one collection port joint, the liquid inlet joints comprise a continuous phase inlet joint (100), a first dispersed phase inlet joint (200) and a second dispersed phase inlet joint (300), and the liquid distribution layer (500) is provided with a continuous phase distribution flow channel (519) communicated with the continuous phase inlet joint (100), a first dispersed phase distribution flow channel (520) communicated with the first dispersed phase inlet joint (200), and a second dispersed phase distribution flow channel (521) communicated with the second dispersed phase inlet joint (300).
5. The three-dimensional microfluidic chip according to claim 4, wherein the droplet generation layer (600) comprises a plurality of droplet generation units and a main droplet collection channel (622), each of the droplet generation units comprises a continuous phase inlet communicating with the continuous phase distribution channel, a continuous phase channel, a first dispersed phase inlet communicating with the first dispersed phase distribution channel, a second dispersed phase inlet communicating with the second dispersed phase distribution channel, a first dispersed phase channel, a second dispersed phase channel, and a transport channel, the continuous phase channel has a front end communicating with the continuous phase inlet and a rear end communicating with the transport channel, the first dispersed phase channel has a front end communicating with the first dispersed phase inlet and a rear end communicating with the transport channel, the second dispersed phase channel has a front end communicating with the second dispersed phase inlet and a rear end communicating with the transport channel, and two dispersed phase fluids are collected in the transport channel, and then the continuous phase fluid is intersected, micro liquid drops are generated by shearing under the action of surface tension at the intersection position, the tail end of the conveying flow channel is communicated with a main micro liquid drop collecting flow channel, and an outlet is arranged at the tail end of the main micro liquid drop collecting flow channel.
6. The three-dimensional microfluidic chip according to claim 1, wherein the flow channels in the liquid distribution layer are all equal in height, ranging from 10 to 1000 microns, and the flow channels in the micro-droplet unit generation layer (600) are all equal in height, ranging from 10 to 1000 microns.
7. The three-dimensional microfluidic chip according to claim 1, wherein the material of the droplet generation layer and the material of the liquid distribution layer are both PDMS.
8. The three-dimensional microfluidic chip according to claim 3 or 5, wherein the liquid distribution layer (500) is provided with through holes at each joint position, and the micro-droplet unit generation layer is provided with through holes at each channel inlet position and channel outlet position.
9. The three-dimensional microfluidic chip according to claim 3 or claim 5, wherein the flow channels are rectangular in structure, the continuous phase flow channel and the dispersed phase flow channel of the droplet unit generation layer (600) are symmetrically designed, and the dispersed phase fluid is converged and then converged with the continuous phase fluid, and is sheared into droplets in a flow focusing manner.
10. A method for preparing micro-droplets by the three-dimensional microfluidic chip according to any one of claims 1 to 9, comprising the steps of:
(1) fixing a three-dimensional microfluidic chip for preparing micro-droplets in a high flux manner on a microfluidic operation platform, observing through a microscope, and ensuring that each group of micro-droplet generation units in the micro-droplet unit generation layer are positioned in the field of view of the microscope and no inclination is caused;
(2) respectively connecting a continuous phase inlet joint (100), a first dispersed phase inlet joint (200) and a second dispersed phase inlet joint (300) with an injector filled with continuous phase fluid, an injector filled with first dispersed phase fluid and an injector filled with second dispersed phase fluid through conduits, wherein each injector is respectively connected with an injection pump, and a micro-droplet collection port joint is also connected with a collection container through a conduit;
(3) and starting the injection pump, adjusting the continuous phase fluid and the disperse phase fluid to corresponding flow rates through the injection pump, generating the micro-droplets through each group of micro-droplet generation units, and finally finishing the collection.
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