CN113996362B - Liquid drop fusion microfluidic device and method based on focusing surface acoustic wave regulation - Google Patents
Liquid drop fusion microfluidic device and method based on focusing surface acoustic wave regulation Download PDFInfo
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Abstract
The invention discloses a liquid drop fusion microfluidic device and method based on focusing surface acoustic wave regulation, and the device comprises an interdigital transducer, wherein two focusing arc electrodes are arranged on the interdigital transducer, a micro-channel system is bonded on the upper part of the interdigital transducer, the focusing arc electrodes are matched with the micro-channel system, and the micro-channel system is provided with a first collection outlet joint, a first dispersed phase inlet joint, a continuous phase inlet joint, a second dispersed phase inlet joint and a second collection outlet joint. The invention flexibly realizes the fusion control of liquid drops with different sizes in a micro-channel through a focusing surface acoustic wave and a liquid drop micro-channel structure generated by an interdigital transducer; the durability and the repeatability of the microfluidic device are enhanced by adopting a symmetrical structure; the method is not only suitable for the fusion control among micro-droplets, but also suitable for the fusion control among micro-bubbles and between micro-droplets and micro-bubbles; the surface acoustic wave has non-contact and good biocompatibility, and meets the requirements of a liquid drop fusion technology in the fields of biochemical medical treatment and the like.
Description
Technical Field
The invention belongs to the technical field of microfluidics, and particularly relates to a droplet fusion microfluidic device and method based on focusing surface acoustic wave regulation.
Background
With the continuous development of the microfluidic chip technology, the droplet microfluidic technology is developed rapidly from inexistence as an important component in the field of microfluidic technology. The droplet microfluidics aims to construct discrete micro-droplets through incompatible multiphase fluids, and the mutually independent properties of the micro-droplets can ensure that biochemical reactions are carried out in a micro-liquid environment like a compartment, so that the droplet microfluidics technology is also called as a digital microfluidics technology, can realize digitization and programmability, and provides a platform for solving the research problem with great challenges in the aspect of biochemical medical treatment. In view of the advantages of small reagent consumption, good uniformity, higher specific surface area and independent control of the micro-droplet technology, the micro-droplet becomes an important experimental platform in biological, chemical, medical and material preparation and application.
After the micro-droplets are generated, the micro-droplets can be used as a closed biological environment simulation platform to perform researches on PCR micro-reaction, single cell protein analysis, single cell gene analysis, single cell culture, chemical micro-reaction and the like. Complex biochemical research usually involves a series of complex processing processes such as encapsulation, mixing, reaction and measurement of a liquid drop sample, and accurate liquid drop control technologies such as liquid drop sorting, splitting, fusion, capturing and releasing enable the complex processing processes to be more convenient and simpler, wherein liquid drop fusion is the most key technology for liquid drop-based biochemical mixing and reaction.
In order to realize the precise fusion of micro-droplets, scientific researchers at home and abroad propose various micro-droplet fusion methods. At present, the existing microdroplet fusion methods can be mainly divided into the following categories: 1) The fusion of adjacent droplets is achieved by changing the speed of movement of adjacent droplets by design of the shape of the channel structures in the microfluidic Chip (see, in detail, xize Niu, shell Gulati, joshua B. Edel, et al, pillar-induced droplet fusion in microfluidic circuits [ J ]. Lab Chip, 2008, 8, 1837-1841. Sanghyun Lee, hojin Kim, dong-Joon Won, et al, pillar-induced droplet fusion in microfluidic circuits [ J ]. Microfluidic Nanofluid, 2016, 20. 2) Fusion of adjacent droplets is achieved by magnetically inducing the Magnetic droplets with the aid of an applied Magnetic field (see in detail V.B. Varma1, A. Ray, Z.M. Wang, et al, droplet Merging on a Lab-on-a-Chip Platform by Uniform Magnetic Fields [ J ]. Scientific Reports, 2016, 6: 37671). 3) Fusion of adjacent droplets is promoted by an alternating Electric Field with the aid of an applied Electric Field (see for details Adrian J.T. Teo, say Hwa Tan, et al, on-Demand Droplet Merging with an AC Electric Field for Multiple-Volume Droplet Generation [ J ]. Anal. Chem, 2020, 92, 1147-1153).
However, in the above method for fusing micro droplets, only the method relying on the flow channel structure requires strict flow channel design parameters to meet the requirement of droplet fusion, and the particle size range suitable for droplet fusion is limited, and the flexibility is poor; the method realizes the liquid drop fusion by depending on magnetism, is only suitable for magnetic liquid drops, and has limited application range; although the droplet fusion mode depending on the electric field is simple, the electrode arranged in the flow channel can generate inevitable damage to the biological sample and even inactivate the sample while generating the droplet under the action of the electric field, so that the method can not be widely applied to the requirements of the biomedical microfluidic technology.
Disclosure of Invention
In order to overcome the defects of the technical method and promote the development of the micro-droplet fusion technology, the invention aims to provide a droplet fusion micro-fluidic device and method based on focusing surface acoustic wave regulation, and the focusing surface acoustic wave and droplet micro-channel structure generated by a focusing interdigital transducer can flexibly realize the fusion control of droplets with different sizes in a micro-channel; the symmetrical structure design is adopted, so that the durability and the repeatability of the microfluidic device are enhanced; the method is not only suitable for the fusion control among micro-droplets, but also suitable for the fusion control among micro-bubbles and between micro-droplets and micro-bubbles; and the surface acoustic wave has non-contact and good biocompatibility, and can meet the requirements of a liquid drop fusion technology in the fields of biochemical medical treatment and the like.
The purpose of the invention is realized by the following technical scheme:
the utility model provides a liquid drop fuses micro-fluidic device based on regulation and control of focus surface acoustic wave, includes the interdigital transducer, is provided with two focus formula arc electrodes on the interdigital transducer, and it has micro-channel system to bond on interdigital transducer upper portion, focus formula arc electrode and micro-channel system cooperation, micro-channel system is symmetrical structure, and micro-channel system is equipped with first collection outlet joint, first dispersed phase inlet joint, continuous phase inlet joint, second dispersed phase inlet joint, second and collects outlet joint, and first dispersed phase inlet joint and second dispersed phase inlet joint use continuous phase inlet joint to set up as central symmetry.
The micro-channel system comprises a first dispersed phase channel, a continuous phase channel and a second dispersed phase channel, wherein the inlet end of the first dispersed phase channel is a first dispersed phase inlet, and the outlet end of the first dispersed phase channel is communicated with the continuous phase channel; wherein the first dispersed phase flow channel and the second dispersed phase flow channel are symmetrical structures taking the continuous phase flow channel as a central shaft; the inlet end of the continuous phase flow channel is a continuous phase inlet, the outlet end of the continuous phase flow channel is communicated with the first conveying flow channel and the second conveying flow channel, and the tail end of the continuous phase flow channel is communicated with the outlet end of the first dispersed phase flow channel and the outlet end of the second dispersed phase flow channel; the inlet end of the second dispersed phase flow channel is a second dispersed phase inlet, and the outlet end of the second dispersed phase flow channel is communicated with the continuous phase flow channel at the interval tail end of the flow channel; the inlet end of the first conveying flow channel and the inlet end of the second conveying flow channel are connected and communicated with the continuous phase flow channel, and the outlet end of the first conveying flow channel and the outlet end of the second conveying flow channel are intersected and communicated at the inlet end of the convergence flow channel; the inlet end of the first fusion flow channel and the inlet end of the second fusion flow channel are outlet ends of the convergence flow channel, the outlet end of the first fusion flow channel is a first collection outlet, and the outlet end of the second fusion flow channel is a second collection outlet; the first collecting outlet joint is coaxially matched with the first collecting outlet and is connected and communicated with the first collecting outlet; the first dispersed phase inlet joint is coaxially matched with the first dispersed phase inlet and is connected and communicated with the first dispersed phase inlet; the continuous phase inlet joint is coaxially matched with the continuous phase inlet and is connected and communicated with the continuous phase inlet; the second dispersed phase inlet joint is coaxially matched with and communicated with the second dispersed phase inlet; the second collection outlet connector is coaxially matched with the second collection outlet and is connected and communicated with the second collection outlet.
The liquid drop fusion microfluidic device based on focusing surface acoustic wave regulation is characterized in that the interdigital transducer is a focusing interdigital transducer.
The focusing type interdigital transducer comprises a piezoelectric substrate, wherein a first focusing arc-shaped interdigital electrode and a second focusing arc-shaped interdigital electrode are manufactured on the piezoelectric substrate, the first focusing arc-shaped interdigital electrode and the second focusing arc-shaped interdigital electrode respectively comprise a plurality of pairs of arc-shaped interdigital, the arc-shaped interdigital are arranged in a staggered mode and have a common focusing center, the central angle of the arc-shaped interdigital is 60 degrees, the first focusing arc-shaped interdigital electrode and the second focusing arc-shaped interdigital electrode are respectively provided with two signal input ends, and one signal input end is a common end; the lower surface of the micro-channel system with a channel is bonded on the upper surface of the focusing interdigital transducer with an interdigital electrode; in the horizontal direction, the focusing center of the first focusing arc-shaped interdigital electrode is positioned on the runner wall of one side of the first fusion runner, which is close to the electrode, and the focusing center of the second focusing arc-shaped interdigital electrode is positioned on the runner wall of one side of the second fusion runner, which is close to the electrode; in the vertical direction, the first focusing arc-shaped interdigital electrode and the second focusing arc-shaped interdigital electrode are symmetrically distributed on two sides of the convergence flow channel.
According to the droplet fusion microfluidic device based on focusing surface acoustic wave regulation, the focusing interdigital transducer comprises 10 pairs of interdigital, and the width of the interdigital is 20 micrometers.
According to the droplet fusion microfluidic device based on focusing surface acoustic wave regulation, the piezoelectric substrate 703 is made of single-side polished 128-degree Y lithium niobate.
According to the droplet fusion microfluidic device based on focusing surface acoustic wave regulation, the first focusing arc-shaped interdigital electrode and the second focusing arc-shaped interdigital electrode are of a three-layer structure of chromium at a bottom layer of 40 nanometers, gold at a middle layer of 200 nanometers and silicon dioxide at an upper layer of 50 nanometers.
According to the droplet fusion microfluidic device based on focusing surface acoustic wave regulation, the height of the flow channel of the microfluidic channel system is 90 micrometers, and the first dispersed phase inlet, the continuous phase inlet, the second dispersed phase inlet, the first collection outlet and the second collection outlet are all through holes.
According to the droplet fusion microfluidic device based on focusing acoustic surface wave regulation, the material of the microfluidic channel system is polydimethylsiloxane.
The liquid drop fusion microfluidic control method based on focusing surface acoustic wave regulation comprises the following steps:
1) Firstly, fixing a droplet fusion microfluidic device regulated and controlled by focusing acoustic surface waves on an objective table of a microscope, and observing through an objective lens to ensure that the connecting and penetrating position of the outlet end of a first dispersed phase flow channel and a continuous phase flow channel is positioned in a microscope field of view and has no inclination;
2) Blocking and sealing a second collection outlet joint by using an iron needle, respectively connecting a first dispersed phase inlet joint, a continuous phase inlet joint and a second dispersed phase inlet joint with a first dispersed phase solution storage bottle, a continuous phase solution storage bottle and a second dispersed phase solution storage bottle on a nitrogen pressure injection pump through PEEK pipes, and collecting liquid drops through a Teflon hose by the first collection outlet joint;
3) Starting a nitrogen pressure injection pump, respectively setting corresponding flow rates of a first dispersed phase inlet joint, a continuous phase inlet joint and a second dispersed phase inlet joint, and stably generating micro-droplets at a connection through position of an outlet end of a first dispersed phase flow channel and a continuous phase flow channel and a connection through position of an outlet end of a second dispersed phase flow channel and the continuous phase flow channel;
4) Moving an objective table, observing through an objective lens to ensure that the matching position of a first fusion flow channel and a first focusing arc interdigital electrode is arranged in a microscope view field and has no inclination, observing the connection and communication position of the outlet end of a first dispersed phase flow channel and a continuous phase flow channel, generating two different liquid drops at the connection and communication position of the outlet end of a second dispersed phase flow channel and the continuous phase flow channel, realizing ordered interval arrangement at the convergence flow channel after the two different liquid drops pass through a first conveying flow channel and a second conveying flow channel, and enabling the two different liquid drops to enter the first fusion flow channel in order;
5) Respectively connecting the positive and negative poles of the output signal of the signal generator amplified by the power amplifier with the two poles of the first focusing arc interdigital electrode, and adjusting the output signal of the signal generator to be sine continuous output;
6) Pressing an output button of a signal generator, generating focusing surface acoustic waves by a first focusing arc-shaped interdigital electrode, acting the focusing surface acoustic waves on a first fusion flow channel to form a focusing acoustic pressure field, fusing liquid drops which are orderly arranged at intervals in the first fusion flow channel under the capture action of the focusing surface acoustic waves like light beams to form larger liquid drops, breaking through the constraint of the surface acoustic waves, flowing out along with fluid to a first collection outlet, and finally collecting the liquid drops at a joint of the first collection outlet;
7) Similarly, when the first collection outlet connector is blocked by a stylus, the droplet fusion can also be realized by using the second focusing arc-shaped interdigital electrode and the second fusion flow channel, the steps are the same as (1-6), and finally the droplet is collected at the second collection outlet connector.
Compared with the prior art, the invention has the following beneficial technical effects:
(1) The invention can orderly arrange different liquid drops, thereby realizing flexible and accurate liquid drop fusion.
(2) The invention can realize effective fusion among micro-droplets, micro-bubbles and between micro-droplets and micro-bubbles with the same size and different sizes, and has wide applicability.
(3) The invention adopts the comprehensive design of the flow channel spacing structure, and can effectively solve the problem of unstable frequency caused by mutual interference when different liquid drops are generated.
(4) The invention adopts a symmetrical flow channel structure and a double-focusing arc interdigital transducer structure, the whole structure is also symmetrical, each focusing arc interdigital electrode can realize the liquid drop fusion function, even if one focusing arc interdigital electrode or fusion flow channel is damaged, the other half can be continuously used, and the durability and the repeatability of the microfluidic device are enhanced.
(5) The surface acoustic wave has non-contact and good biocompatibility, and can meet the requirements of a liquid drop fusion technology in the fields of biochemical medical treatment and the like.
Drawings
Fig. 1 is an isometric view of a focused surface acoustic wave modulated droplet fusion microfluidic device of the present invention.
Fig. 2 is an isometric view of the microchannel system 100.
Fig. 3 is a rear view of the micro flow channel system 100.
Fig. 4 is an isometric view of a focused interdigital transducer 700.
Fig. 5 is a schematic diagram of droplet fusion for a focused surface acoustic wave modulated droplet fusion microfluidic device.
FIG. 6 is a diagram of a droplet fusion experiment before (left) and after (right) focusing of SAW.
Detailed Description
The invention is described in detail with reference to the accompanying figures 1-6 of the specification.
A liquid drop fusion microfluidic device based on focusing surface acoustic wave regulation comprises an interdigital transducer 700, wherein two focusing arc electrodes are arranged on the interdigital transducer 700, a micro-channel system 100 is bonded on the upper portion of the interdigital transducer, the focusing arc electrodes are matched with the micro-channel system 100, and the micro-channel system 100 is provided with a first collection outlet connector 200, a first dispersed phase inlet connector 300, a continuous phase inlet connector 400, a second dispersed phase inlet connector 500 and a second collection outlet connector 600. The microchannel system has a symmetrical structure, and the first dispersed phase inlet connector 300 and the second dispersed phase inlet connector 500 are symmetrically arranged with the continuous phase inlet connector 400 as the center.
The specific structure of the micro-channel system 100 of the droplet fusion micro-fluidic device based on the regulation and control of the focusing surface acoustic wave is shown in fig. 2, 3 and 5, the micro-channel system 100 comprises a first dispersed phase channel 102, a continuous phase channel 104 and a second dispersed phase channel 106, the inlet end of the first dispersed phase channel 102 is a first dispersed phase inlet 101, and the outlet end of the first dispersed phase channel 102 is communicated with the continuous phase channel 104; wherein the first dispersed phase flow channel 102 and the second dispersed phase flow channel 106 are symmetrically arranged with the continuous phase flow channel 104 as a central axis; the inlet end of the continuous phase flow channel 104 is a continuous phase inlet 103, the outlet end of the continuous phase flow channel 104 is communicated with the first conveying flow channel 107 and the second conveying flow channel 113, and the tail end of the continuous phase flow channel 104 is communicated with the outlet end of the first dispersed phase flow channel 102 and the outlet end of the second dispersed phase flow channel 106; the inlet end of the second dispersed phase flow channel 106 is a second dispersed phase inlet 105, and the outlet end of the second dispersed phase flow channel 106 is communicated with the continuous phase flow channel 104 at the tail end of the flow channel interval 114; the inlet end of the first conveying flow channel 107 and the inlet end of the second conveying flow channel 113 are communicated with the continuous phase flow channel 104, and the outlet end of the first conveying flow channel 107 and the outlet end of the second conveying flow channel 113 are intersected and communicated at the inlet end of the convergence flow channel 112; the inlet end of the first fusion flow channel 110 and the inlet end of the second fusion flow channel 109 are outlet ends of a convergence flow channel 112, the outlet end of the first fusion flow channel 110 is a first collection outlet 111, and the outlet end of the second fusion flow channel 109 is a second collection outlet 108; the first collection outlet connector 200 is coaxially matched with and communicated with the first collection outlet 111; the first dispersed phase inlet joint 300 is coaxially matched with and communicated with the first dispersed phase inlet 101; the continuous phase inlet connector 400 is coaxially matched with and communicated with the continuous phase inlet 103; the second dispersed phase inlet joint 500 is coaxially matched with and communicated with the second dispersed phase inlet 105; the second collection outlet connection 600 is coaxially engaged with and connected to the second collection outlet 108.
The liquid drop fusion micro-fluidic device based on focusing surface acoustic wave regulation is characterized in that the interdigital transducer is a focusing interdigital transducer. As shown in fig. 4, the focusing interdigital transducer 700 includes a piezoelectric substrate 703, a first focusing arc-shaped interdigital electrode 701 and a second focusing arc-shaped interdigital electrode 702 are fabricated on the piezoelectric substrate 703, and each of the first focusing arc-shaped interdigital electrode and the second focusing arc-shaped interdigital electrode includes a plurality of pairs of arc-shaped interdigital, and the arc-shaped interdigital are arranged in a staggered manner and have a common focusing center, the central angle of the arc-shaped interdigital is 60 °, and the first focusing arc-shaped interdigital electrode 701 and the second focusing arc-shaped interdigital electrode 702 respectively have two signal input terminals, one of which is a common terminal; the lower surface of the micro-channel system 100 with channels is bonded on the upper surface of the focusing interdigital transducer 700 with interdigital electrodes; in the horizontal direction, the focusing center of the first focusing arc-shaped interdigital electrode 701 is positioned on the runner wall on the side of the first fusion runner 110 close to the electrode, and the focusing center of the second focusing arc-shaped interdigital electrode 702 is positioned on the runner wall on the side of the second fusion runner 109 close to the electrode; in the vertical direction, the first focusing arc-shaped interdigital electrode 701 and the second focusing arc-shaped interdigital electrode 702 are symmetrically distributed on both sides of the convergence channel 112.
The focusing interdigital transducer 700 of the present invention comprises 10 pairs of interdigital, the width of the finger is 20 microns; the piezoelectric substrate 703 is made of lithium niobate with a single polished surface of 128 degrees; the first focusing arc-shaped interdigital electrode 701 and the second focusing arc-shaped interdigital electrode 702 adopt a three-layer structure of chromium at the bottom layer of 40 nanometers, gold at the middle layer of 200 nanometers and silicon dioxide at the upper layer of 50 nanometers.
The liquid drop fusion microfluidic device based on focusing surface acoustic wave regulation and control is characterized in that the height of a flow channel of the microfluidic channel system 100 is 90 micrometers, a first dispersed phase inlet 101, a continuous phase inlet 103, a second dispersed phase inlet 105, a first collection outlet 111 and a second collection outlet 108 are all through holes, and the microfluidic channel system 100 is made of polydimethylsiloxane.
The symmetrical flow channel structure and the structure of the double-focusing arc interdigital transducer are also symmetrical integrally, each focusing arc interdigital electrode can realize a liquid drop fusion function, and even if one focusing arc interdigital electrode or fusion flow channel is damaged, the other half can be continuously used, so that the durability and the repeatability of a microfluidic device are enhanced.
A liquid drop fusion microfluidic control method based on focusing surface acoustic wave regulation comprises the following steps:
1) Firstly, fixing a droplet fusion microfluidic device regulated and controlled by focusing surface acoustic waves on an objective table of a microscope, and observing through an objective lens to ensure that the connecting through position of the outlet end of a first dispersed phase flow channel 102 and a continuous phase flow channel 104 is positioned in a microscope field of view and has no inclination;
2) The second collection outlet joint 600 is blocked and closed by an iron needle, the first dispersed phase inlet joint 300, the continuous phase inlet joint 400 and the second dispersed phase inlet joint 500 are respectively connected with a first dispersed phase solution storage bottle, a continuous phase solution storage bottle and a second dispersed phase solution storage bottle on a nitrogen pressure injection pump through PEEK pipes, and the first collection outlet joint 200 is used for collecting liquid drops through a Teflon hose;
3) Starting a nitrogen pressure injection pump, setting corresponding flow rates of the first dispersed phase inlet joint 300, the continuous phase inlet joint 400 and the second dispersed phase inlet joint 500 respectively, and stably generating micro-droplets at the connecting and communicating part of the outlet end of the first dispersed phase flow channel 102 and the continuous phase flow channel 104 and the connecting and communicating part of the outlet end of the second dispersed phase flow channel 106 and the continuous phase flow channel 104;
4) Moving an object stage, observing through an objective lens to ensure that the matching position of the first fusion flow channel 110 and the first focusing arc-shaped interdigital electrode 701 is arranged in a microscope field of view and has no inclination, observing the connecting and penetrating position of the outlet end of the first dispersed phase flow channel 102 and the continuous phase flow channel 104, generating two different liquid drops at the connecting and penetrating position of the outlet end of the second dispersed phase flow channel 106 and the continuous phase flow channel 104, and after the two different liquid drops pass through the first conveying flow channel 107 and the second conveying flow channel 113, realizing ordered interval arrangement at the converging flow channel 112 and orderly entering the first fusion flow channel 110;
5) Respectively connecting the positive and negative poles of the output signal of the signal generator amplified by the power amplifier with the two poles of the first focusing arc-shaped interdigital electrode 701, and adjusting the output signal of the signal generator to be sine-shaped continuous output;
6) Pressing an output button of a signal generator, generating focusing surface acoustic waves by the first focusing arc-shaped interdigital electrode 701, acting the focusing surface acoustic waves on the first fusion flow channel 110 to form a focusing acoustic pressure field, fusing the droplets orderly arranged at intervals in the first fusion flow channel 110 under the capturing action of the focusing surface acoustic waves like light beams to form larger droplets, breaking the constraint of the surface acoustic waves, flowing out along with the fluid to the first collection outlet 111, and finally collecting the droplets at the first collection outlet joint 200;
7) Similarly, when the first collection outlet connector 200 is plugged with a stylus, droplet fusion can also be achieved using the second focusing arc-shaped interdigital electrode 702 and the second fusion flow channel 109, in the same steps as (1-6), and finally collected at the second collection outlet connector 600.
Referring to fig. 1, 2, 3, 4, 5 and 6, the process of the micro-droplet fusion in the droplet fusion microfluidic device regulated by the focused surface acoustic wave is as follows: blocking and sealing the second collection outlet joint 600 by using an iron needle, enabling the first dispersed phase solution to pass through the first dispersed phase inlet joint 300 and the first dispersed phase inlet 101, enabling the first dispersed phase solution to fill the first dispersed phase flow channel 102, enabling the continuous phase solution to pass through the continuous phase inlet joint 400 and the continuous phase inlet 103, enabling the continuous phase solution to fill the continuous phase flow channel 104, the first conveying flow channel 107, the second conveying flow channel 113, the converging flow channel 112, the first fusing flow channel 110 and the second fusing flow channel 109, enabling the second dispersed phase solution to pass through the second dispersed phase inlet joint 500 and the second dispersed phase inlet 105, enabling the second dispersed phase solution to fill the second dispersed phase flow channel 106, adjusting the input pressure of the first dispersed phase solution, the second dispersed phase solution and the continuous phase solution by using a nitrogen pressure injection pump to adjust the flow rates of the first dispersed phase solution, the second dispersed phase solution and the continuous phase solution to the corresponding flow channels, and accordingly achieving the effect that the continuous phase solution shears the first dispersed phase solution and the first dispersed phase solution to generate droplets, the droplets of the continuous phase solution and the continuous phase solution at the outlet end, enabling the first dispersed phase solution to be connected with the continuous phase flow channel 104 to be communicated with the continuous phase flow channel 106A, and the continuous phase flow channel 104, and the continuous phase flow channel 106 to generate stable droplet discharge end, and the continuous phase flow channel 104, so as to generate droplets of the continuous phase solution; the micro liquid drops A and the micro liquid drops B are respectively conveyed to the converging flow channel 112 through the first conveying flow channel 107 and the second conveying flow channel 113 along with the continuous phase, the two micro liquid drops are orderly arranged at intervals at the converging flow channel 112, and then flow into the first fusion flow channel 110; then, an 'output' button of a signal generator is pressed, the first focusing arc-shaped interdigital electrode 701 generates focusing surface acoustic waves, the focusing surface acoustic waves act on the first fusion flow channel 110 to form a focusing acoustic pressure field, when the proper input voltage peak value and input frequency are adjusted, the micro liquid drops A and the micro liquid drops B which are arranged at intervals are captured and fused under the focusing surface acoustic wave acoustic radiation force like light beams, so that large liquid drops are formed, the large liquid drops break through the constraint of the surface acoustic waves under the pushing of the fluid force and flow out along with the fluid to the first collection outlet 111, and are finally collected at the first collection outlet connector 200, and the liquid drop fusion experiment process is shown in fig. 6.
Technical means disclosed in the technical solution of the present invention are not limited to the technical means disclosed in the above embodiments, and include technical solutions formed by arbitrary combinations of the above technical features. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principle of the present invention, and such improvements and modifications are also considered to be within the scope of the present invention.
Claims (8)
1. A liquid drop fusion microfluidic device based on focusing surface acoustic wave regulation comprises an interdigital transducer (700), and is characterized in that two focusing arc electrodes are arranged on the interdigital transducer (700), a microchannel system (100) is bonded on the upper portion of the interdigital transducer, the focusing arc electrodes are matched with the microchannel system (100), the microchannel system is of a symmetrical structure, the microchannel system (100) is provided with a first collection outlet connector (200), a first dispersed phase inlet connector (300), a continuous phase inlet connector (400), a second dispersed phase inlet connector (500) and a second collection outlet connector (600), the first dispersed phase inlet connector (300) and the second dispersed phase inlet connector (500) are symmetrically arranged by taking the continuous phase inlet connector (400) as the center, the microchannel system (100) comprises a first dispersed phase channel (102), a continuous phase channel (104) and a second dispersed phase channel (106), wherein the first dispersed phase channel (102) and the second dispersed phase channel (106) are of a symmetrical structure with the continuous phase channel (104) as the central axis, the inlet end of the first dispersed phase channel (102) is connected with the continuous phase channel (102), and the outlet end of the first dispersed phase channel (102) is connected with the continuous phase channel (101); the inlet end of the continuous phase flow channel (104) is a continuous phase inlet (103), the outlet end of the continuous phase flow channel (104) is communicated with the first conveying flow channel (107) and the second conveying flow channel (113), and the tail end of the continuous phase flow channel (104) is communicated with the outlet end of the first dispersed phase flow channel (102) and the outlet end of the second dispersed phase flow channel (106); the inlet end of the second dispersed phase flow channel (106) is a second dispersed phase inlet (105), and the outlet end of the second dispersed phase flow channel (106) is communicated with the continuous phase flow channel (104) at the tail end of the flow channel interval (114); the inlet end of the first conveying flow channel (107) and the inlet end of the second conveying flow channel (113) are connected and communicated with the continuous phase flow channel (104), and the outlet end of the first conveying flow channel (107) and the outlet end of the second conveying flow channel (113) are intersected and communicated at the inlet end of the convergence flow channel (112); the inlet end of the first fusion flow channel (110) and the inlet end of the second fusion flow channel (109) are outlet ends of a convergence flow channel (112), the outlet end of the first fusion flow channel (110) is a first collection outlet (111), and the outlet end of the second fusion flow channel (109) is a second collection outlet (108); the first collection outlet connector (200) is coaxially matched with the first collection outlet (111) and is connected and communicated with the first collection outlet; the first dispersed phase inlet joint (300) is coaxially matched with and communicated with the first dispersed phase inlet (101); the continuous phase inlet connector (400) is coaxially matched with the continuous phase inlet (103) and is connected and communicated with the continuous phase inlet; the second dispersed phase inlet joint (500) is coaxially matched with and communicated with the second dispersed phase inlet (105); the second collection outlet joint (600) is coaxially matched with the second collection outlet (108) and is connected and communicated with the second collection outlet;
the liquid drop fusion microfluidic control method based on the liquid drop fusion microfluidic control device regulated and controlled by the focusing surface acoustic wave comprises the following steps:
1) Firstly, fixing a droplet fusion microfluidic device regulated by focusing surface acoustic waves on an objective table of a microscope, and ensuring that the connection through position of the outlet end of a first dispersed phase flow channel (102) and a continuous phase flow channel (104) is ensured through objective observation, and the connection through position of the outlet end of a second dispersed phase flow channel (106) and the continuous phase flow channel (104) is positioned in the field of view of the microscope and has no inclination;
2) Blocking and sealing a second collection outlet connector (600) by using an iron needle, respectively connecting a first dispersed phase inlet connector (300), a continuous phase inlet connector (400) and a second dispersed phase inlet connector (500) with a first dispersed phase solution storage bottle, a continuous phase solution storage bottle and a second dispersed phase solution storage bottle on a nitrogen pressure injection pump through PEEK pipes, and collecting liquid drops by using a first collection outlet connector (200) through a Teflon hose;
3) Starting a nitrogen pressure injection pump, setting corresponding flow rates of a first dispersed phase inlet connector (300), a continuous phase inlet connector (400) and a second dispersed phase inlet connector (500) respectively, and stably generating micro-droplets at a connection through position of an outlet end of a first dispersed phase flow channel (102) and a continuous phase flow channel (104) and a connection through position of an outlet end of a second dispersed phase flow channel (106) and the continuous phase flow channel (104);
4) The objective lens observation is carried out to ensure that the first fusion flow channel (110) and the first focusing arc-shaped interdigital electrode (701) are matched and arranged in a microscope field of view and have no inclination, the connection through part of the outlet end of the first dispersed phase flow channel (102) and the continuous phase flow channel (104) is observed, two different liquid drops are generated at the connection through part of the outlet end of the second dispersed phase flow channel (106) and the continuous phase flow channel (104), and the two different liquid drops are orderly arranged at the convergence flow channel (112) at intervals after passing through the first conveying flow channel (107) and the second conveying flow channel (113) and orderly enter the first fusion flow channel (110);
5) Respectively connecting the positive pole and the negative pole of an output signal of the signal generator amplified by the power amplifier with the two poles of a first focusing arc interdigital electrode (701), and adjusting the output signal of the signal generator to be sine continuous output;
6) Pressing an output button of a signal generator, generating focusing surface acoustic waves by a first focusing arc interdigital electrode (701), acting the focusing surface acoustic waves on a first fusion flow channel (110) to form a focusing acoustic pressure field, fusing liquid drops which are sequentially arranged at intervals in the first fusion flow channel (110) under the capture action of the focusing surface acoustic waves like light beams to form larger liquid drops, breaking through the constraint of the surface acoustic waves, flowing out along with fluid to a first collection outlet (111), and finally collecting the liquid drops at a first collection outlet joint (200);
7) Similarly, when the first collection outlet (200) is sealed with a stylus, droplet fusion is achieved with the second focusing arc interdigital electrode (702) and the second fusion flow channel (109), the steps are the same as (1-6), and finally the droplet is collected at the second collection outlet (600).
2. The focused surface acoustic wave regulation-based droplet fusion microfluidic device of claim 1, wherein the interdigital transducer is a focused interdigital transducer.
3. The microfluidic device for droplet fusion based on focused surface acoustic wave regulation according to claim 2, wherein the focused interdigital transducer (700) comprises a piezoelectric substrate (703), a first focused arc-shaped interdigital electrode (701) and a second focused arc-shaped interdigital electrode (702) are formed on the piezoelectric substrate (703), the first focused arc-shaped interdigital electrode and the second focused arc-shaped interdigital electrode each comprise a plurality of pairs of arc-shaped interdigital electrodes, the arc-shaped interdigital electrodes are arranged in a staggered manner and have a common focusing center, the central angle of the arc-shaped interdigital electrodes is 60 °, and the first focused arc-shaped interdigital electrode (701) and the second focused arc-shaped interdigital electrode 702 respectively have two signal input ends, one of which is a common end; the lower surface of the micro-channel system (100) with a channel is bonded on the upper surface of the focusing interdigital transducer (700) with an interdigital electrode; in the horizontal direction, the focusing center of the first focusing arc-shaped interdigital electrode (701) is positioned on the runner wall of the first fusion runner (110) on the side close to the electrode, and the focusing center of the second focusing arc-shaped interdigital electrode (702) is positioned on the runner wall of the second fusion runner (109) on the side close to the electrode; in the vertical direction, the first focusing arc-shaped interdigital electrode (701) and the second focusing arc-shaped interdigital electrode (702) are symmetrically distributed on two sides of the convergence flow channel (112).
4. The microfluidic device for droplet fusion based on focused surface acoustic wave regulation according to claim 3, wherein the focused interdigital transducer (700) comprises 10 pairs of fingers, and the width of the finger is 20 μm.
5. The microfluidic device according to claim 3, wherein the piezoelectric substrate (703) is made of lithium niobate with a single polished surface of 128 ° Y.
6. The microfluidic device according to claim 3, wherein the first focusing arc-shaped interdigital electrode (701) and the second focusing arc-shaped interdigital electrode (702) have a three-layer structure of a bottom layer of 40 nm, a middle layer of (200) nm of gold, and an upper layer of 50 nm of silicon dioxide.
7. The microfluidic device for droplet fusion based on focused surface acoustic wave regulation according to claim 1, wherein the height of the flow channel of the microchannel system (100) is 90 μm, and the first dispersed phase inlet (101), the continuous phase inlet (103), the second dispersed phase inlet (105), the first collection outlet (111), and the second collection outlet (108) are all through holes.
8. The microfluidic device for droplet fusion based on focused surface acoustic wave regulation according to claim 1, wherein the material of the micro channel system (100) is polydimethylsiloxane.
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