CN112755935B - Micro-channel structure, micro-fluidic chip and heterogeneous reaction method - Google Patents
Micro-channel structure, micro-fluidic chip and heterogeneous reaction method Download PDFInfo
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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
- B01L3/502738—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 integrated valves
Abstract
The application provides a micro-channel structure, a micro-fluidic chip and a heterogeneous reaction method, wherein the micro-channel structure comprises: the device comprises a continuous outer triangle expansion focusing unit, an active valve quantitative uniform control unit and a heterogeneous reaction tank unit; the continuous outer triangle expansion focusing unit comprises: a continuous liquid phase sample inlet, a continuous outer triangle expansion focusing flow passage and a continuous liquid phase flow passage; the active valve quantitative and uniform control unit comprises: the flow channel is internally provided with a valve plug, a gas phase sample inlet, a gas phase channel and a gas buffer chamber; the inner wall of the continuous liquid phase runner is provided with a built-in valve plug; heterogeneous units include: the device comprises a reaction liquid phase sample inlet, a reaction liquid phase runner, a mixed liquid phase runner and a heterogeneous reaction tank. The application solves the technical problems of how to design a microfluidic device and an operation process, so that the microfluidic device can realize rapid and accurate quantitative control to perform accurate and efficient heterogeneous reaction and improve the sufficiency of the reaction on the basis of generating high-dispersion liquid drops and particles.
Description
Technical Field
The application relates to the technical field of microfluidics, in particular to a micro-channel structure, a microfluidic chip and a heterogeneous reaction method.
Background
With the development of technology, more and more fields (energy, immunity, biochemistry and the like) need to use miniaturized reaction means to perform highly dispersed micro-precise operation, and the micro-fluidic technology receives a great deal of attention because of being capable of realizing a plurality of micro-processes and micro-operations which are difficult to finish. Microfluidic is the manipulation of tiny particles (or samples) that cannot be achieved by some conventional methods using microchannels and devices. The method can integrate biological detection, a series of biochemical reactions and preparation of various samples on a tiny chip for special operation, and has wide application prospect in multiple fields.
At present, in the conventional preparation process of liquid drops or microsphere particles, a mechanical stirring method under a large scale is mainly adopted, so that microsphere particles with specific particle size cannot be accurately screened, the dispersibility of the particles is low, and the high-efficiency performance of the reaction cannot be ensured because the number of liquid drops (or particles) participating in the reaction is too large or too small. The micro-fluidic system with a special structure can be used for uniformly dispersing liquid drops (or particles), and then carrying out effective and sufficient reaction after quantitative control, so that the efficiency and the experiment success rate can be effectively improved.
There are many methods of generating (or coating droplets of particles) using microfluidics, active application of magnetic field and electric field is required; the passive type is generally a dean flow, no energy input is needed, and the device is simple, convenient and easy to maintain and has small volume. Passive dien flow is one of the most effective ways to focus droplets (or droplets encapsulating particles) by micro-flow control at present due to its simple and convenient operation and uniformity and high efficiency. By passive dien flow focusing, the scattered microspheres and droplets can be focused in the micro-channel to form microspheres and droplet queues which are distributed at specific positions at equal intervals. Although the dispersion of the droplets (or particles) is achieved to some extent, a certain length of spiral-shaped flow path is required to achieve the purpose, and precise quantitative control is difficult.
Therefore, how to design a microfluidic device and an operation process, so that on the basis of generating highly dispersed liquid drops and particles, rapid and accurate quantitative control is realized to perform accurate and efficient heterogeneous reaction, and the sufficiency of the reaction is improved, so that the microfluidic device and the operation process become one of the problems to be solved in the technical urgent need in the art.
Disclosure of Invention
The application aims to provide a micro-flow channel structure, a micro-flow control chip and a heterogeneous reaction method, which are used for solving the technical problems of how to design a micro-flow control device and an operation process, so that the micro-flow control device can realize rapid, accurate and quantitative control to perform accurate and efficient heterogeneous reaction and improve the sufficiency of the reaction on the basis of generating high-dispersion liquid drops and particles.
In order to solve the above problems, the present application provides a micro flow channel structure, comprising: the device comprises a continuous outer triangle expansion focusing unit, an active valve quantitative uniform control unit and a heterogeneous reaction tank unit;
the continuous outer triangle expansion focusing unit includes: a continuous liquid phase sample inlet, a continuous outer triangle expansion focusing flow passage and a continuous liquid phase flow passage;
the continuous liquid phase sample inlet is communicated with the liquid inlet end of the continuous outer triangular expansion focusing flow passage, and the liquid inlet end of the continuous liquid phase flow passage is communicated with the liquid outlet end of the continuous outer triangular expansion focusing flow passage;
the heterogeneous reaction cell unit includes: the device comprises a reaction liquid phase sample inlet, a reaction liquid phase flow channel, a mixed liquid phase flow channel, a heterogeneous reaction tank, a liquid outlet flow channel and a mixed phase sample outlet;
the liquid inlet end of the reaction liquid-phase runner is communicated with the reaction liquid-phase sample inlet, the liquid outlet end of the reaction liquid-phase runner is communicated with the liquid inlet end of the mixed liquid-phase runner, the liquid outlet end of the mixed liquid-phase runner is communicated with the liquid inlet end of the heterogeneous reaction tank, the liquid outlet end of the heterogeneous reaction tank is communicated with the liquid inlet end of the liquid outlet runner, and the liquid outlet end of the liquid outlet runner is communicated with the mixed phase sample outlet;
the active valve quantitative and uniform control unit comprises: a first active valve and a second active valve, the first active valve corresponding to the continuous liquid phase flow channel and the second active valve corresponding to the liquid outlet flow channel;
the first active valve includes: a valve plug, a gas phase sample inlet, a gas phase channel and a gas buffer chamber are arranged in the valve plug;
the built-in valve plug is arranged in the continuous liquid phase flow channel, the gas outlet end of the gas phase channel is communicated with the gas buffer chamber, the gas inlet end of the gas phase channel is communicated with the gas phase sample inlet, and the gas buffer chamber corresponds to the built-in valve plug;
the second active valve has the same structure as the first active valve.
Further, the continuous outer triangle expansion focusing flow passage is spiral;
the liquid inlet end of the continuous outer triangle expansion focusing flow passage is positioned at the center of the spiral shape;
the liquid outlet end of the continuous outer triangle expansion focusing flow passage is positioned at the outer side of the spiral shape.
Further, at least one first active valve is arranged.
Further, the built-in valve plug comprises a trapezoid valve block and a rectangular valve block;
the trapezoid valve block is arranged on one side, far away from the gas buffer chamber, of the inner wall of the continuous liquid phase flow channel, and the bottom surface of the trapezoid valve block is attached to the inner wall of the continuous liquid phase flow channel;
the rectangular valve blocks are arranged on one side, close to the gas buffer chamber, of the inner wall of the continuous liquid phase flow channel, the rectangular valve blocks and the trapezoid valve blocks are distributed in a staggered mode, and the side walls, corresponding to the trapezoid valve blocks, of the rectangular valve blocks are located on the same section of the continuous liquid phase flow channel.
Furthermore, the gas buffer chamber and the continuous liquid phase runner are made of deformable materials, the gas buffer chamber is not deformed in a non-inflated state, and the gas buffer chamber expands in an inflated state and is abutted against one side of the continuous liquid phase runner, so that the inner wall of the continuous liquid phase runner is fully contacted with the built-in valve plug, and the continuous liquid phase runner is blocked.
Further, the cross sections of the continuous liquid-phase flow channel, the gas-phase flow channel and the reaction liquid-phase flow channel are rectangular, the heights of the various flow channels are uniform, and the heights are 100-200 mu m.
The application also provides a micro-fluidic chip, which comprises a chip body and the micro-channel structure;
the micro-channel structure is arranged in the chip body.
Further, the chip body comprises a base plate and a cover plate;
the micro-channel structure is arranged on the upper surface of the substrate;
the cover plate covers the upper surface of the substrate, and the continuous liquid phase sample inlet, the gas phase sample inlet, the reaction liquid phase sample inlet and the mixed phase sample outlet are all communicated with the cover plate.
Further, the device also comprises a conveying device and an extracting device;
the conveying device comprises a first conveying pump communicated with the continuous liquid phase sample inlet, a second conveying pump communicated with the gas phase sample inlet of the first driving valve, a third conveying pump communicated with the reaction liquid phase sample inlet and a fourth conveying pump communicated with the gas phase sample inlet of the second driving valve;
the extraction device is communicated with the mixed phase sample outlet.
The application also provides a heterogeneous reaction method which is applied to the micro-channel structure and comprises the following steps:
uniformly and stably dispersing microsphere suspension liquid through a continuous outer triangle expansion focusing flow passage and flowing into a continuous liquid phase passage;
the opening and closing of the continuous liquid phase channel are regulated by a first active valve of the active valve quantitative and uniform control unit;
the reaction liquid enters a mixed liquid flow passage through a reaction liquid flow passage, and enters a heterogeneous reaction tank for reaction after being in short contact with microsphere suspension in the mixed liquid flow passage;
and the opening and closing of the liquid outlet flow channel are regulated by the second active valve of the active valve quantitative uniform control unit, so that the mixed liquid in the heterogeneous reaction tank can fully react, and the required micro-droplets are obtained.
Compared with the prior art, the embodiment of the application has the advantages that:
the application provides a micro-channel structure, comprising: the device comprises a continuous outer triangle expansion focusing unit, an active valve quantitative uniform control unit and a heterogeneous reaction tank unit; the continuous outer triangle expansion focusing unit includes: a continuous liquid phase sample inlet, a continuous outer triangle expansion focusing flow passage and a continuous liquid phase flow passage; the continuous liquid phase sample inlet is communicated with the liquid inlet end of the continuous outer triangular expansion focusing flow passage, and the liquid inlet end of the continuous liquid phase flow passage is communicated with the liquid outlet end of the continuous outer triangular expansion focusing flow passage; the heterogeneous reaction cell unit includes: the device comprises a reaction liquid phase sample inlet, a reaction liquid phase flow channel, a mixed liquid phase flow channel, a heterogeneous reaction tank, a liquid outlet flow channel and a mixed phase sample outlet; the liquid inlet end of the reaction liquid-phase runner is communicated with the reaction liquid-phase sample inlet, the liquid outlet end of the reaction liquid-phase runner is communicated with the liquid inlet end of the mixed liquid-phase runner, the liquid outlet end of the mixed liquid-phase runner is communicated with the liquid inlet end of the heterogeneous reaction tank, the liquid outlet end of the heterogeneous reaction tank is communicated with the liquid inlet end of the liquid outlet runner, and the liquid outlet end of the liquid outlet runner is communicated with the mixed phase sample outlet; the active valve quantitative and uniform control unit comprises: a first active valve and a second active valve, the first active valve corresponding to the continuous liquid phase flow channel and the second active valve corresponding to the liquid outlet flow channel; the first active valve includes: a valve plug, a gas phase sample inlet, a gas phase channel and a gas buffer chamber are arranged in the valve plug; the built-in valve plug is arranged in the continuous liquid phase flow channel, the gas outlet end of the gas phase channel is communicated with the gas buffer chamber, the gas inlet end of the gas phase channel is communicated with the gas phase sample inlet, and the gas buffer chamber corresponds to the built-in valve plug; the second active valve has the same structure as the first active valve.
The micro-channel structure provided by the application comprises a continuous outer triangle expansion focusing unit, an active valve quantitative uniform control unit and a coaxial flow heterogeneous reaction unit, wherein the continuous outer triangle expansion focusing unit comprises a continuous liquid phase sample inlet, a continuous outer triangle expansion focusing channel and a continuous liquid phase channel, the continuous liquid phase sample inlet is used for leading in samples (liquid drops or particles), the samples are separated layer by layer through the continuous outer triangle structure of the continuous outer triangle expansion focusing channel, so that the samples form microspheres which are identical in size and distributed at equal intervals and enter the continuous liquid phase channel, the opening and closing degree of the continuous liquid phase channel is controlled through the first active valve of the active valve quantitative uniform control unit, the flow rate of the microspheres is controlled, the quantitative control is realized, the mixed liquid phase channel is entered, the reaction liquid is led into the mixed liquid phase channel through the reaction liquid phase sample inlet, the reaction liquid is led into the mixed liquid phase channel through the reaction liquid phase channel, and the opening and closing degree of the liquid phase channel is controlled through the second active valve of the active quantitative uniform control unit, the samples and the reaction liquid in the heterogeneous reaction channel can be fully reacted, the reaction is ensured, the reaction is fully carried out, the microspheres are distributed from the liquid drops after the reaction channel is completely and discharged from the liquid phase channel, the high-speed uniform reaction channel is realized, the accurate and the quantitative control is realized, and the high-accuracy and the accuracy is realized, and the high-speed accuracy is realized, and the quantitative control is realized, and the problem is realized, and the high-speed and the quantitative and the uniform.
Drawings
In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described, and it is obvious that the drawings in the description below are some embodiments of the present application, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art.
Fig. 1 is a top view of a micro flow channel structure according to an embodiment of the present application;
FIG. 2 is a top view of a continuous outer triangular expanded focused runner provided by an embodiment of the present application;
FIG. 3 is a control schematic diagram of an active valve quantitative and uniform control unit in an embodiment of the application;
FIG. 4 is a top view of a heterogeneous reaction cell unit provided by an embodiment of the present application;
fig. 5 is an overall structure diagram of a microfluidic chip according to an embodiment of the present application.
Wherein, the reference numerals are as follows: the device comprises a continuous outer triangle expansion focusing unit 1, an active valve quantitative uniform control unit 2, a heterogeneous reaction tank unit 3, a continuous liquid phase sample inlet 4, a continuous outer triangle expansion focusing flow passage 5, a continuous liquid phase flow passage 6, a built-in valve plug 7, a gas phase sample inlet 8, a gas phase passage 9, a gas buffer chamber 10, a reaction liquid phase sample inlet 11, a reaction liquid phase flow passage 12, a mixed liquid phase flow passage 13, a base plate 14, a cover plate 15, a first conveying pump 16, a second conveying pump 17, a third conveying pump 18, an extraction device 19, a first flow passage 20, a second flow passage 21, a mixed phase sample outlet 22, a first active valve 23, a second active valve 24, a trapezoid valve block 25, a rectangular valve block 26, a fourth conveying pump 27, a heterogeneous reaction tank 28 and a liquid outlet flow passage 29.
Detailed Description
The following description of the embodiments of the present application will be made apparent and fully in view of the accompanying drawings, in which some, but not all embodiments of the application are shown. All other embodiments, which can be made by those skilled in the art based on the embodiments of the application without making any inventive effort, are intended to be within the scope of the application.
In the description of the present application, it should be noted that the directions or positional relationships indicated by the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. are based on the directions or positional relationships shown in the drawings, are merely for convenience of describing the present application and simplifying the description, and do not indicate or imply that the devices or elements referred to must have a specific orientation, be configured and operated in a specific orientation, and thus should not be construed as limiting the present application. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.
Unless specifically stated or limited otherwise, the terms "mounted," "connected," and "coupled" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; can be directly connected or indirectly connected through an intermediate medium, and can be communication between two elements. The specific meaning of the above terms in the present application will be understood in specific cases by those of ordinary skill in the art.
For easy understanding, please refer to fig. 1 to 4, fig. 1 is a top view of a micro flow channel structure provided in an embodiment of the present application; FIG. 2 is a top view of a continuous outer triangular expanded focused runner provided by an embodiment of the present application; FIG. 3 is a control schematic diagram of an active valve quantitative and uniform control unit in an embodiment of the application; fig. 4 is a top view of a heterogeneous reaction cell unit provided by an embodiment of the present application.
The embodiment of the application provides a micro-channel structure, which comprises the following components: the device comprises a continuous outer triangle expansion focusing unit 1, an active valve quantitative uniform control unit 2 and a heterogeneous reaction tank unit 3;
the continuous outer triangle expansion focusing unit 1 includes: a continuous liquid phase sample inlet 4, a continuous outer triangle expansion focusing flow passage 5 and a continuous liquid phase flow passage 6;
the continuous liquid phase sample inlet 4 is communicated with the liquid inlet end of the continuous outer triangle expansion focusing flow passage 5, and the liquid inlet end of the continuous liquid phase flow passage 6 is communicated with the liquid outlet end of the continuous outer triangle expansion focusing flow passage 5;
the heterogeneous reaction tank unit 3 includes: the reaction liquid phase sample inlet 11, the reaction liquid phase flow channel 12, the mixed liquid phase flow channel 13, the heterogeneous reaction tank 28, the liquid outlet flow channel 29 and the mixed phase sample outlet;
the liquid inlet end of the reaction liquid-phase runner 12 is communicated with the reaction liquid-phase sample inlet 11, the liquid outlet end is communicated with the liquid inlet end of the mixed liquid-phase runner 13, the liquid outlet end of the continuous liquid-phase runner 6 is communicated with the liquid inlet end of the mixed liquid-phase runner 13, the liquid outlet end of the mixed liquid-phase runner 13 is communicated with the liquid inlet end of the heterogeneous reaction tank 28, the liquid outlet end of the heterogeneous reaction tank 28 is communicated with the liquid inlet end of the liquid outlet runner 29, and the liquid outlet end of the liquid outlet runner 29 is communicated with the mixed phase sample outlet;
the active valve quantitative uniformity control unit 2 includes: a first active valve 23 and a second active valve 24, the first active valve 23 corresponding to the continuous liquid flow channel 6 and the second active valve 24 corresponding to the liquid flow channel 29;
the first active valve 23 includes: a built-in valve plug 7, a gas phase sample inlet 8, a gas phase channel 9 and a gas buffer chamber 10;
the built-in valve plug 7 is arranged in the continuous liquid-phase flow channel 6, the gas outlet end of the gas-phase channel 9 is communicated with the gas buffer chamber 10, the gas inlet end is communicated with the gas-phase sample inlet 8, and the gas buffer chamber 10 corresponds to the built-in valve plug 7;
the second active valve 24 is identical in structure to the first active valve 23.
It should be noted that, the inner side wall of the continuous outer triangle expansion focusing flow passage 5 is continuous zigzag, the overlook angle is similar to a plurality of continuous triangles, and the triangle is preferably equilateral triangle, so as to realize equally dispersing the sample and form more uniform microsphere particles, the narrowest part of the continuous outer triangle expansion focusing flow passage 5 is the same as the cross section of the continuous liquid phase flow passage 6, so that butt joint can be just performed, the bottom surface of the continuous outer triangle expansion focusing flow passage 5 is preferably a smooth wall surface, thus being beneficial to the flow of the sample, and the wall surface of the corresponding continuous liquid phase flow passage 6 can also be preferably a smooth wall surface.
Preferably, in order to avoid damage to the wall surface caused by excessive pressure at the contact point of the gas phase channel 9 and the wall surface of the continuous liquid phase channel 6 due to direct contact, a gas buffer chamber 10 is arranged to separate the gas phase channel 9 from the wall surface of the liquid phase channel, and the buffer chamber is kept at a certain distance from the wall surface of the liquid phase channel.
The heterogeneous reaction tank unit consists of a tail end of a continuous liquid-phase flow channel 6 of highly dispersed liquid drops (or microspheres), a reaction liquid-phase sample injection flow channel, a mixed liquid-phase flow channel 13 and a heterogeneous reaction tank 28, wherein the tail end of the continuous liquid-phase flow channel is quantitatively and uniformly controlled through a first active valve 23. The two reaction liquid phase sample inlets 11 and the two reaction liquid phase flow channels 12 are preferably two, one reaction liquid phase sample inlet 11 is matched with one reaction liquid phase flow channel 12, so that two reaction liquids can be added simultaneously, the functionality of the micro-channel structure is stronger, preferably, the reaction liquid phase flow channel 12 comprises a first flow channel 20 and a second flow channel 21, one end of the first flow channel 20 is communicated with one end of the second flow channel 21, the other end of the first flow channel 20 is communicated with the reaction liquid phase sample inlet 11, the other end of the second flow channel 21 is communicated with the liquid inlet end of the mixed liquid phase flow channel 13, the first flow channel 20 and the second flow channel 21 are in the same-diameter pipeline, the first flow channel 20 is in the horizontal trend, and the trend of the second flow channel 21 and the first flow channel 20 form a 45-degree included angle. The caliber of the mixed liquid flow channel 13 is larger than that of the continuous liquid flow channel 6 and that of the reaction liquid flow channel 12, so that the mixed liquid flow channel 13 can better accommodate microspheres and various reaction liquids at the same time.
Preferably, the structure of the second active valve 24 is the same as that of the first active valve 23, specifically, the built-in valve plug 7 of the second active valve 24 is disposed in the liquid outlet channel 29, the gas outlet end of the gas phase channel 9 of the second active valve 24 is communicated with the buffer chamber of the second active valve 24, the gas inlet end is communicated with the gas phase inlet 8 of the second active valve 24, and the gas buffer chamber 10 of the second active valve 24 corresponds to the built-in valve plug 7 of the second active valve 24, thereby realizing the opening and closing control of the liquid outlet channel. The gas buffer chamber 10 of the first active valve 23 and the gas buffer chamber 10 of the second active valve 24 are preferably conical gas buffer chambers 10, the bottoms of the conical gas buffer chambers 10 correspond to the flow channels, and the distance between the conical gas buffer chambers 10 and the walls of the liquid-phase flow channels is preferably 30-100 μm.
The micro-channel structure provided by the application comprises a continuous outer triangle expansion focusing unit 1, an active valve quantitative uniform control unit 2 and a coaxial flow non-uniform reaction unit, wherein the continuous outer triangle expansion focusing unit 1 comprises a continuous liquid phase sample inlet 4, a continuous outer triangle expansion focusing channel 5 and a continuous liquid phase channel 6, the continuous liquid phase sample inlet 4 is used for introducing samples (liquid drops or particles), the samples are separated layer by layer through the continuous outer triangle structure of the continuous outer triangle expansion focusing channel 5, so that the samples form microspheres which are identical in size and are distributed at equal intervals and enter the continuous liquid phase channel, the opening and closing degree of the continuous liquid phase channel is controlled through a first active valve 23 of the active valve quantitative uniform control unit 2, thereby controlling the flow rate of the microspheres, realizing quantitative control, entering a mixed liquid phase channel 13, introducing reaction liquid through a reaction liquid phase sample inlet 11, and the reaction liquid enters the mixed liquid flow channel 13 through the reaction liquid flow channel 12 and is converged and enters the heterogeneous reaction tank 28 to carry out full reaction, the opening and closing degree of the liquid flow channel 29 is controlled through the second active valve 24 of the active quantitative uniform control unit, so that the sample in the heterogeneous reaction tank 28 and the reaction liquid can fully react, the sufficiency of the reaction is ensured, and the reaction liquid is discharged from the liquid flow channel 29 after the reaction is finished, thereby realizing the rapid and accurate quantitative control to carry out the precise and efficient heterogeneous reaction, solving the technical problems of how to design a microfluidic device and an operation process, realizing the rapid and accurate quantitative control to carry out the precise and efficient heterogeneous reaction on the basis of generating high-dispersion liquid drops and particles, and improving the sufficiency of the reaction.
As a further improvement, the continuous outer triangle expansion focusing flow passage 5 of the micro flow passage structure provided by the embodiment of the application is spiral;
the liquid inlet end of the continuous outer triangle expansion focusing flow passage 5 is positioned at the center of the spiral shape;
the liquid outlet end of the continuous outer triangular expansion focusing flow passage 5 is positioned at the outer side of the spiral shape.
Specifically, the spiral structure is beneficial to the fact that the length of the continuous outer triangle expansion flow channel is the largest under the condition of occupying area as small as possible, so that the separation and dispersion effects on samples are better, the introduced samples can be relatively turbulent fluids such as focused liquid drops or liquid drops wrapping particles, after entering the continuous outer triangle expansion focusing flow channel, turbulent fluids containing particles flow along the inner wall surface of the triangle under the simultaneous action of centrifugal force and Dien flow force, and finally high-dispersion and stable arrangement is realized, so that the focusing flow can be effectively increased, and the dispersion stability is improved. .
As a further improvement, at least one first active valve 23 of the active valve quantitative and uniform control unit of the micro-channel structure provided by the embodiment of the application is provided. Preferably, two first driving valves 23 are arranged, so that the flow in the continuous liquid phase flow channel 6 is controlled in a grading manner, the flow in the continuous liquid phase flow channel 6 is reduced step by step, the final flow is controlled more accurately, and specifically, the two first driving valves 23 are arranged in a front-back parallel manner.
As a further improvement, the built-in valve plug 7 provided by the embodiment of the present application includes a trapezoid valve block 25 and a rectangular valve block 26;
the trapezoid valve block 25 is arranged on one side of the inner wall of the continuous liquid-phase flow channel 6 far away from the gas buffer chamber 10, and the bottom surface of the trapezoid valve block 25 is attached to the inner wall of the continuous liquid-phase flow channel 6;
the rectangular valve block 26 is arranged on one side of the inner wall of the continuous liquid phase flow channel 6 close to the gas buffer chamber 10, the rectangular valve block 26 and the trapezoid valve block 25 are distributed in a staggered mode, and the side walls of the rectangular valve block 26 corresponding to the trapezoid valve block 25 are located on the same section of the continuous liquid phase flow channel 6.
Specifically, when the gas buffer chamber 10 is inflated, the flow channel (which may be the continuous liquid flow channel 6 or the liquid flow channel 29) is extruded through the bottom of the gas buffer chamber 10, so that the flow channel is deformed and drives the rectangular valve block 26 to move and approach the trapezoid valve block 25, so that the flow port of the flow channel is gradually reduced, the flow rate can be controlled, and when the rectangular valve block 26 is tightly attached to the trapezoid valve block 25, the flow channel is closed.
As a further improvement, the materials of the gas buffer chamber 10 and the continuous liquid-phase flow channel 6 provided by the embodiment of the application are deformable materials, the gas buffer chamber 10 does not deform in a non-inflated state, the gas buffer chamber 10 expands in an inflated state and is abutted against one side of the continuous liquid-phase flow channel 6, and the inner wall of the continuous liquid-phase flow channel 6 is fully contacted with the built-in valve plug 7, so that the blocking of the continuous liquid-phase flow channel 6 is realized. Specifically, the gas source in the gas phase channel 9 is from the gas introduced by the gas phase inlet 8, and the gas phase inlet 8 can be externally connected with a gas pump and other devices.
As a further improvement, the cross sections of the continuous liquid-phase flow channel 6, the gas-phase flow channel 9, the reaction liquid-phase flow channel 12, the mixed liquid-phase flow channel 13 and the liquid outlet flow channel 29 provided by the embodiment of the application are rectangular, the heights of the various flow channels are uniform, and the heights are 100-200 mu m.
Preferably, the total length of the continuous outer triangular expansion focusing runner 5 is 200 mm-2000 mm; the width of the continuous outer triangular expansion focusing flow passage 5 is 100-200 mu m; the distance between two adjacent channels of the continuous outer triangular expansion focusing channel 5 is 100-400 μm; the radius of curvature of the innermost runner of the continuous outer triangular expansion focusing runner 5 is 20 mm-50 mm.
Referring to fig. 1 to 5, the present application further provides a microfluidic chip, which includes a chip body and a micro flow channel structure in the above embodiment; the micro-channel structure is arranged in the chip body.
Alternatively, the material of the chip body is preferably PDMS made of transparent material, and the chip body can be directly observed and photographed by using a microscope.
As a further improvement, the chip body of the microfluidic chip provided by the embodiment of the application comprises a substrate 14 and a cover plate 15; the micro-channel structure is arranged on the upper surface of the substrate 14; the cover 15 covers the upper surface of the substrate 14, and the continuous liquid phase sample inlet 4, the gas phase sample inlet 8, the reaction liquid phase sample inlet 11 and the mixed phase sample outlet 22 are all penetrated through the cover 15.
As a further improvement, the microfluidic chip provided by the embodiment of the present application further includes a conveying device and an extracting device 19; the conveying device comprises a first conveying pump 16 communicated with the continuous liquid phase sample inlet 4, a second conveying pump 17 communicated with the gas phase sample inlet 8 of a first active valve 23, a third conveying pump 18 communicated with the reaction liquid phase sample inlet 11 and a fourth conveying pump 27 communicated with the gas phase sample inlet 8 of a second active valve 24; the extraction device 19 is communicated with the mixed phase sample outlet 22. Wherein, the first delivery pump 16 is used for delivering the sample into the continuous liquid phase sample inlet 4; the second transfer pump 17 is used for transferring gas into the gas phase sample inlet 8 of the first active valve 23; the third transfer pump 18 is used for transferring the reaction liquid into the reaction liquid phase sample inlet 11, the fourth transfer pump 27 is used for transferring the gas into the gas phase sample inlet 8 of the second active valve 24, specifically, since the reaction liquid phase sample inlet 11 and the reaction liquid phase flow channel 12 are preferably two, one reaction liquid phase sample inlet 11 is matched with one reaction liquid phase flow channel 12, the number of the third transfer pumps 18 can be preferably two, and each third transfer pump 18 can be respectively communicated with one reaction liquid phase sample inlet 11 and is used for transferring the same or different reaction liquid into the corresponding reaction liquid phase sample inlet 11. Preferably, since the number of the first active valves 23 is preferably two, the number of the second transfer pumps is also preferably two, and the two first active valves 23 are respectively matched, so that independent control of the two first active valves 23 is realized. .
The micro-fluidic chip is highly integrated, and the whole chip area is small and only has a plurality of cubic centimeters; the microfluidic chip has low cost and simple structure, and is easy for mass production.
The microfluidic chip provided by the application has the following advantages:
1. the device structure is miniaturized. The whole chip device has small area and large specific surface area. The coordinated operation of the conveyor and the extraction device 19 allows for high throughput.
2. High dispersion stability. The continuous outer triangle expansion focusing flow passage 5 is more beneficial to passive diun flow inertial focusing, and particle dispersion stability is increased.
3. And the quantitative control is accurate. The microspheres passing through the focusing curve have uniform height and interval values, and the quantity of particles (or liquid drops) in the continuous liquid phase can be rapidly and accurately controlled by adjusting the pneumatic pump, so that precise and controllable quantitative control is realized.
4. The reaction is uniform and full. By matching the heterogeneous reaction tank, the first active valve and the second active valve, the heterogeneous reaction can be ensured to be uniformly and fully carried out in the reaction tank.
5. Is environment-friendly and low in cost. The used chip materials are nontoxic and harmless, and the reaction effect can be hardly achieved by the conventional operation only by less particles and reaction liquid in the operation process.
6. Is easy to observe. The device can select PDMS of transparent material as the chip material, can directly use the microscope to observe, record of shooing.
7. The application field is wide. Due to the separation between the gas phase channel 9 and the liquid phase channel, the gas will not react with particles in the reaction liquid, and is suitable for many heterogeneous reactions.
8. The reaction chip is sealed, and the reactant is not polluted or leaked. And the polymer such as PDMS is used as a chip material, so that the chip can be ensured to have certain mechanical properties.
9. The process flow is fast, and rapid and batch production can be realized by adopting a photoetching method, an etching method and the like. The device material has strong substitutability, and the common PDMS can be replaced by glass, metal and the like.
The application also provides a heterogeneous reaction method which is applied to any micro-channel structure and is characterized by comprising the following steps:
s1, uniformly and stably dispersing microsphere suspension liquid through a continuous outer triangle expansion focusing flow passage 5 and flowing into a continuous liquid phase passage;
s2, adjusting the opening and closing of the continuous liquid phase channel through a first active valve of the active valve quantitative uniform control unit, and accurately controlling the quantity of microspheres in microsphere suspension flowing into the same axial flow non-uniform reaction unit;
s3, enabling the reaction liquid to enter a mixed liquid flow channel 13 through a reaction liquid flow channel 12, and enabling the reaction liquid to enter a heterogeneous reaction tank for reaction after being mixed with microsphere suspension in the mixed liquid flow channel 13 for a short time. S4, the opening and closing of the liquid outlet channel are regulated through a second active valve of the active valve quantitative uniform control unit, so that the mixed liquid in the heterogeneous reaction tank can fully react, and the required micro-droplets are obtained.
The first embodiment provided by the present application is the second embodiment provided by the present application, specifically:
the chip body is made of PDMS (polydimethylsiloxane), wherein the length of the continuous outer triangle expansion focusing flow passage is 800mm, the distance between two adjacent vortex focusing flow passages is 120 mu m, the radius of curvature of the innermost flow passage is 30mm, the widths of the gas phase flow passage, the reaction liquid phase flow passage and the continuous liquid phase flow passage are 60 mu m, the widths of the mixed liquid phase flow passage and the liquid outlet flow passage are 120 mu m, the distance between the gas buffer chamber and the continuous liquid phase flow passage is 50 mu m when the gas buffer chamber is in a non-working state, and the heights of all flow passages are 100 mu m. Nitrogen is selected as a gas phase, polystyrene microspheres with the particle size of 30 mu m and methyl blue aqueous solution are used as sample liquid, and an external light source is arranged right above the heterogeneous reaction tank to correspond to the heterogeneous reaction tank for continuous illumination treatment. Fluid is injected into the chip body by using a polytetrafluoroethylene capillary hose, and the gas-phase fluid is controlled by using a second delivery pump. The flow rate of the sample liquid is 30 mu l/min, the flow rate of the gas phase is 60 mu l/min, the flow rate of the reaction liquid phase is 30 mu l/min, quantitative titanium dioxide microspheres in microsphere suspension liquid and methyl blue aqueous solution are enabled to enter a heterogeneous reaction tank through adjustment of the flow rates of the gas phase and continuous phase liquid phase, a first active valve and a second active valve in front of and behind the heterogeneous reaction tank are closed, and the methyl blue aqueous solution and the titanium dioxide microspheres are enabled to carry out precise, efficient and sufficient heterogeneous reaction under the illumination condition, so that methylene blue or methylene blue is obtained.
The second embodiment provided by the present application is the third embodiment provided by the present application, and specifically, the following is:
the chip body is made of PDMS, wherein the length of the continuous outer triangle expansion focusing flow passage is 500mm, the distance between two adjacent vortex focusing flow passages is 180 mu m, the radius of curvature of the innermost flow passage is 40mm, the widths of the gas phase flow passage, the reaction liquid phase flow passage and the continuous liquid phase flow passage are 80 mu m, the widths of the mixed liquid phase flow passage and the liquid phase flow passage are 160 mu m, the gas buffer chamber keeps a certain distance from the wall of the liquid phase flow passage in a non-working state, the distance is 60 mu m, and the heights of all flow passages are 100 mu m. Nitrogen is selected as a gas phase, magnesium hydroxide [ Mg (OH) 2] solution containing carbon spheres with the particle size of 30 mu m, namely carbon sphere suspension liquid is selected as a microsphere suspension liquid (the carbon spheres and the magnesium hydroxide do not react) as a sample liquid, a dispersed phase is formed by a focusing fan of a continuous external triangular expansion focusing flow passage, and ammonium carbonate solution with certain concentration is selected as a reaction liquid to form a continuous liquid phase. Carbon sphere suspension and ammonium carbonate solution were injected into the chip using polytetrafluoroethylene capillary hoses, respectively, and the gas phase fluid was controlled by a second transfer pump. The flow rate of the microsphere suspension injected into the first liquid flow channel is 50 mu L/min, the flow rate of the gas phase is 60 mu L/min, the flow rates of the ammonium carbonate solution injected into the second liquid flow channel and the third liquid flow channel are 60 mu L/min, microsphere suspension with various quantitative carbon sphere contents can be obtained by regulating the flow rates of the gas phase and the microsphere suspension, and the microsphere suspension and the ammonium carbonate continuous phase enter a heterogeneous reaction tank together through the same axial flow so as to fully mix and carry out heterogeneous accurate and efficient reaction, and magnesium carbonate [ MgCO3] precipitate is precipitated on the surface of the carbon sphere to uniformly wrap the carbon sphere, and meanwhile, the heterogeneous reaction is uniform, so that the microparticle liquid drops with the quantitative carbon sphere contents can be obtained.
The above embodiments are only for illustrating the technical solution of the present application, and not for limiting the same; although the application has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some or all of the technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit of the application.
Claims (8)
1. A micro flow channel structure, characterized by comprising: the device comprises a continuous outer triangle expansion focusing unit, an active valve quantitative uniform control unit and a heterogeneous reaction tank unit;
the continuous outer triangle expansion focusing unit includes: a continuous liquid phase sample inlet, a continuous outer triangle expansion focusing flow passage and a continuous liquid phase flow passage;
the inner side wall of the continuous outer triangular expansion focusing runner is continuous zigzag;
the continuous liquid phase sample inlet is communicated with the liquid inlet end of the continuous outer triangular expansion focusing flow passage, and the liquid inlet end of the continuous liquid phase flow passage is communicated with the liquid outlet end of the continuous outer triangular expansion focusing flow passage;
the heterogeneous reaction cell unit includes: the device comprises a reaction liquid phase sample inlet, a reaction liquid phase flow channel, a mixed liquid phase flow channel, a heterogeneous reaction tank, a liquid outlet flow channel and a mixed phase sample outlet;
the liquid inlet end of the reaction liquid-phase runner is communicated with the reaction liquid-phase sample inlet, the liquid outlet end of the reaction liquid-phase runner is communicated with the liquid inlet end of the mixed liquid-phase runner, the liquid outlet end of the mixed liquid-phase runner is communicated with the liquid inlet end of the heterogeneous reaction tank, the liquid outlet end of the heterogeneous reaction tank is communicated with the liquid inlet end of the liquid outlet runner, and the liquid outlet end of the liquid outlet runner is communicated with the mixed phase sample outlet;
the active valve quantitative and uniform control unit comprises: a first active valve and a second active valve, the first active valve corresponding to the continuous liquid phase flow channel and the second active valve corresponding to the liquid outlet flow channel;
the first active valve includes: a valve plug, a gas phase sample inlet, a gas phase channel and a gas buffer chamber are arranged in the valve plug;
the built-in valve plug is arranged in the continuous liquid phase flow channel, the gas outlet end of the gas phase channel is communicated with the gas buffer chamber, the gas inlet end of the gas phase channel is communicated with the gas phase sample inlet, and the gas buffer chamber corresponds to the built-in valve plug;
the built-in valve plug comprises a trapezoid valve block and a rectangular valve block;
the trapezoid valve block is arranged on one side, far away from the gas buffer chamber, of the inner wall of the continuous liquid phase flow channel, and the bottom surface of the trapezoid valve block is attached to the inner wall of the continuous liquid phase flow channel;
the rectangular valve blocks are arranged on one side, close to the gas buffer chamber, of the inner wall of the continuous liquid phase flow channel, the rectangular valve blocks and the trapezoid valve blocks are distributed in a staggered mode, and the side walls of the rectangular valve blocks and the trapezoid valve blocks, which correspond to each other, are positioned on the same section of the continuous liquid phase flow channel;
the gas buffer chamber and the continuous liquid phase flow channel are made of deformable materials, the gas buffer chamber does not deform in a non-inflated state, and the gas buffer chamber expands in an inflated state and is abutted against one side of the continuous liquid phase flow channel, so that the inner wall of the continuous liquid phase flow channel is fully contacted with the built-in valve plug, and the continuous liquid phase flow channel is blocked;
the second active valve has the same structure as the first active valve.
2. The micro flow channel structure according to claim 1, wherein the continuous outer triangular expansion focusing flow channel is spiral;
the liquid inlet end of the continuous outer triangle expansion focusing flow passage is positioned at the center of the spiral shape;
the liquid outlet end of the continuous outer triangle expansion focusing flow passage is positioned at the outer side of the spiral shape.
3. The microchannel structure of claim 1, wherein the first active valve comprises at least one.
4. The micro flow channel structure according to claim 1, wherein the cross sections of the continuous liquid flow channel, the gas phase flow channel and the reaction liquid flow channel are rectangular, the heights of the various flow channels are uniform, and the heights are 100-200 μm.
5. A microfluidic chip comprising a chip body and the microchannel structure of any one of claims 1-4;
the micro-channel structure is arranged in the chip body.
6. The microfluidic chip according to claim 5, wherein the chip body comprises a substrate and a cover plate;
the micro-channel structure is arranged on the upper surface of the substrate;
the cover plate covers the upper surface of the substrate, and the continuous liquid phase sample inlet, the gas phase sample inlet, the reaction liquid phase sample inlet and the mixed phase sample outlet are all communicated with the cover plate.
7. The microfluidic chip according to claim 6, further comprising a delivery device and an extraction device;
the conveying device comprises a first conveying pump communicated with the continuous liquid phase sample inlet, a second conveying pump communicated with the gas phase sample inlet of the first driving valve, a third conveying pump communicated with the reaction liquid phase sample inlet and a fourth conveying pump communicated with the gas phase sample inlet of the second driving valve;
the extraction device is communicated with the mixed phase sample outlet.
8. A heterogeneous reaction method applied to the micro flow channel structure as claimed in any one of claims 1 to 4, comprising the steps of:
uniformly and stably dispersing microsphere suspension liquid through a continuous outer triangle expansion focusing flow passage and flowing into a continuous liquid phase passage;
the opening and closing of the continuous liquid phase channel are regulated by a first active valve of the active valve quantitative and uniform control unit;
the reaction liquid enters a mixed liquid flow passage through a reaction liquid flow passage, and enters a heterogeneous reaction tank for reaction after being in short contact with microsphere suspension in the mixed liquid flow passage;
and the opening and closing of the liquid outlet flow channel are regulated by the second active valve of the active valve quantitative uniform control unit, so that the mixed liquid in the heterogeneous reaction tank can fully react, and the required micro-droplets are obtained.
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