Micro-channel structure, micro-fluidic chip and heterogeneous reaction method

文档序号:605714 发布日期:2021-05-07 浏览:16次 中文

阅读说明:本技术 一种微流道结构、微流控芯片以及非均相反应方法 (Micro-channel structure, micro-fluidic chip and heterogeneous reaction method ) 是由 王超 蒋志强 于 2021-01-13 设计创作,主要内容包括:本申请提供了一种微流道结构、微流控芯片以及非均相反应方法,微流道结构包括:连续外三角扩张聚焦单元、主动阀定量均匀控制单元和非均相反应池单元;连续外三角扩张聚焦单元包括:连续液相进样口、连续外三角扩张聚焦流道和连续液相流道;主动阀定量均匀控制单元包括:流道内置阀塞、气相进样口、气相通道和气体缓冲室;连续液相流道内壁设有内置阀塞;非均相单元包括:反应液相进样口、反应液相流道、混合液相流道和非均相反应池。本申请解决了如何设计一种微流控装置和操作工艺,使其能够在生成高分散液滴、颗粒的基础上,实现快速准确的定量控制进行精确高效非均相反应,且提高反应的充分性的技术问题。(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 triangular expansion focusing unit, a driving valve quantitative uniform control unit and a heterogeneous reaction pool unit; the continuous outer triangular expanding focusing unit comprises: the continuous liquid phase sampling port, the continuous outer triangular expansion focusing flow channel and the continuous liquid phase flow channel; the active valve quantitative uniform control unit comprises: a valve plug, a gas phase sample inlet, a gas phase channel and a gas buffer chamber are arranged in the flow channel; the inner wall of the continuous liquid phase flow passage is provided with a built-in valve plug; the heterogeneous unit comprises: a reaction liquid phase sample inlet, a reaction liquid phase flow passage, a mixed liquid phase flow passage and a heterogeneous reaction pool. The application solves the technical problems that how to design a microfluidic device and an operation process to enable the microfluidic device to realize rapid and accurate quantitative control to carry out accurate and efficient heterogeneous reaction on the basis of generating high-dispersion liquid drops and particles and improve the reaction sufficiency.)

1. A micro flow channel structure, comprising: the device comprises a continuous outer triangular expansion focusing unit, a driving valve quantitative uniform control unit and a heterogeneous reaction pool unit;

the continuous outer triangular expanding focusing unit includes: the continuous liquid phase sampling port, the continuous outer triangular expansion focusing flow channel and the continuous liquid phase flow channel;

the continuous liquid phase sample inlet is communicated with the liquid inlet end of the continuous outer triangular expansion focusing flow channel, and the liquid inlet end of the continuous liquid phase flow channel is communicated with the liquid outlet end of the continuous outer triangular expansion focusing flow channel;

the heterogeneous reaction cell unit includes: a reaction liquid phase sample inlet, a reaction liquid phase flow passage, a mixed liquid phase flow passage, a heterogeneous reaction pool, a liquid outlet flow passage and a mixed phase sample outlet;

the liquid inlet end of the reaction liquid phase flow passage is communicated with the reaction liquid phase sample inlet, the liquid outlet end of the reaction liquid phase flow passage is communicated with the liquid inlet end of the mixed liquid phase flow passage, the liquid outlet end of the continuous liquid phase flow passage is communicated with the liquid inlet end of the mixed liquid phase flow passage, the liquid outlet end of the mixed liquid phase flow passage is communicated with the liquid inlet end of the heterogeneous reaction pool, the liquid outlet end of the heterogeneous reaction pool is communicated with the liquid inlet end of the liquid outlet flow passage, and the liquid outlet end of the liquid outlet flow passage is communicated with the mixed phase sample outlet;

the active valve quantitative uniform control unit comprises: the first active valve corresponds to the continuous liquid phase flow channel, and the second active valve corresponds 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 gas buffer chamber;

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.

2. The micro flow channel structure of claim 1, wherein the continuous outer triangularly expanded focusing flow channel is in a spiral shape;

the liquid inlet end of the continuous outer triangular expanding focusing flow channel is positioned at the center of the spiral shape;

the liquid outlet end of the continuous outer triangular expansion focusing flow passage is positioned at the outer side of the spiral shape.

3. The micro flow channel structure of claim 1 wherein at least one of the first active valves is provided.

4. The micro flow channel structure of claim 1, wherein the built-in valve plug comprises a trapezoidal valve block and a rectangular valve block;

the trapezoidal 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 trapezoidal valve block is attached to the inner wall of the continuous liquid phase flow channel;

the rectangle valve block set up in the continuous liquid phase runner inner wall is close to in one side of gas buffer room, the rectangle valve block with trapezoidal valve block staggered distribution, just the rectangle valve block with the corresponding lateral wall of trapezoidal valve block is located on the same cross-section of continuous liquid phase runner.

5. The micro flow channel structure of claim 4,

the gas buffer chamber and the continuous liquid phase flow channel are both made of deformable materials, the gas buffer chamber does not deform in a non-inflation state, the gas buffer chamber expands in an inflation 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.

6. The micro flow channel structure of claim 1, wherein the continuous liquid phase flow channel, the gas phase channel and the reaction liquid phase flow channel are rectangular in cross section, and the height of each flow channel is uniform and is 100 μm to 200 μm.

7. A microfluidic chip comprising a chip body and the micro flow channel structure of any of claims 1 to 6;

the micro-channel structure is arranged in the chip body.

8. The microfluidic chip according to claim 7, 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 apron cover in the upper surface of base plate, just continuous liquid phase introduction port the gas phase introduction port reaction liquid phase introduction port with mixed phase appearance mouth all link up in the apron.

9. The microfluidic chip according to claim 7, 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 active 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 active valve;

the extraction device is communicated with the mixed phase sample outlet.

10. A heterogeneous reaction method applied to the micro flow channel structure according to any one of claims 1 to 6, comprising the steps of:

uniformly and stably dispersing the microsphere suspension liquid through a continuous external triangular expansion focusing flow channel and flowing the microsphere suspension liquid into a continuous liquid phase channel;

the opening and closing of the continuous liquid phase channel are adjusted through a first active valve of the active valve quantitative uniform control unit;

enabling the reaction liquid to enter a mixed liquid phase flow channel through a reaction liquid phase flow channel, enabling the reaction liquid to be in short contact with the microsphere suspension in the mixed liquid phase flow channel, and enabling the reaction liquid to enter a heterogeneous reaction tank for reaction;

the opening and closing of the liquid outlet flow channel are adjusted 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 liquid drops are obtained.

Technical Field

The application relates to the technical field of microfluidics, in particular to a micro-channel structure, a micro-fluidic chip and a heterogeneous reaction method.

Background

With the development of science and technology, more and more fields (energy, immunity, biochemistry, and the like) need to use a miniaturized reaction means to perform highly dispersed micro precise operations, and the micro-fluidic technology has attracted extensive attention because of being capable of realizing a lot of micro-processing and micro-operation which are difficult to be completed. Microfluidics is a manipulation of minute 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, the conventional preparation process of liquid drops or microsphere particles mainly adopts a large-scale mechanical stirring method, so that the microsphere particles with specific particle size cannot be accurately screened, the particle dispersibility is low, and the high-efficiency reaction cannot be ensured when the number of liquid drops (or particles) participating in the reaction is too large or too small. The liquid drops (or particles) can be uniformly dispersed by a micro-fluidic system with a special structure, effective and sufficient reaction is carried out after quantitative control, and the efficiency and the success rate of experiments can be effectively improved.

There are many methods of generating (or wrapping droplets of particles) using microfluidics, which actively require an external magnetic field and an electric field; the passive mode usually adopts dean flow, does not need energy input, and the device is simple and convenient, easy to maintain and small in size. Passive dean flow is currently one of the most effective means for microfluidic focusing of droplets (or particle-encapsulated droplets) due to its simplicity and convenience of operation, uniformity and high efficiency. By passive dean flow focusing, the micro-ball and liquid drop scattered in disorder can be focused to form micro-ball and liquid drop queue arranged at equal intervals at specific positions in the micro-channel. Although the dispersion of the liquid drops (or particles) is achieved to a certain extent, a spiral bent flow channel with a certain length is required to achieve the purpose, and accurate quantitative control is difficult to perform.

Therefore, how to design a microfluidic device and an operation process to realize fast and accurate quantitative control to perform accurate and efficient heterogeneous reaction on the basis of generating highly dispersed droplets and particles and improve the sufficiency of the reaction is one of the problems to be solved in the art.

Disclosure of Invention

The application aims to provide a micro-channel structure, a micro-fluidic chip and a heterogeneous reaction method, which are used for solving the technical problems that how to design a micro-fluidic device and an operation process, the micro-fluidic device and the operation process can realize rapid and accurate quantitative control to carry out accurate and efficient heterogeneous reaction on the basis of generating highly dispersed liquid drops and particles, and the reaction sufficiency is improved.

In order to solve the above problems, the present application provides a micro flow channel structure comprising: the device comprises a continuous outer triangular expansion focusing unit, a driving valve quantitative uniform control unit and a heterogeneous reaction pool unit;

the continuous outer triangular expanding focusing unit includes: the continuous liquid phase sampling port, the continuous outer triangular expansion focusing flow channel and the continuous liquid phase flow channel;

the continuous liquid phase sample inlet is communicated with the liquid inlet end of the continuous outer triangular expansion focusing flow channel, and the liquid inlet end of the continuous liquid phase flow channel is communicated with the liquid outlet end of the continuous outer triangular expansion focusing flow channel;

the heterogeneous reaction cell unit includes: a reaction liquid phase sample inlet, a reaction liquid phase flow passage, a mixed liquid phase flow passage, a heterogeneous reaction pool, a liquid outlet flow passage and a mixed phase sample outlet;

the liquid inlet end of the reaction liquid phase flow passage is communicated with the reaction liquid phase sample inlet, the liquid outlet end of the reaction liquid phase flow passage is communicated with the liquid inlet end of the mixed liquid phase flow passage, the liquid outlet end of the continuous liquid phase flow passage is communicated with the liquid inlet end of the mixed liquid phase flow passage, the liquid outlet end of the mixed liquid phase flow passage is communicated with the liquid inlet end of the heterogeneous reaction pool, the liquid outlet end of the heterogeneous reaction pool is communicated with the liquid inlet end of the liquid outlet flow passage, and the liquid outlet end of the liquid outlet flow passage is communicated with the mixed phase sample outlet;

the active valve quantitative uniform control unit comprises: the first active valve corresponds to the continuous liquid phase flow channel, and the second active valve corresponds 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 gas buffer chamber;

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.

Furthermore, the continuous outer triangular expanding focusing flow channel is spiral;

the liquid inlet end of the continuous outer triangular expanding focusing flow channel is positioned at the center of the spiral shape;

the liquid outlet end of the continuous outer triangular expansion focusing flow passage is positioned at the outer side of the spiral shape.

Further, at least one of the first active valves is provided.

Further, the built-in valve plug comprises a trapezoid valve block and a rectangular valve block;

the trapezoidal 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 trapezoidal valve block is attached to the inner wall of the continuous liquid phase flow channel;

the rectangle valve block set up in the continuous liquid phase runner inner wall is close to in one side of gas buffer room, the rectangle valve block with trapezoidal valve block staggered distribution, just the rectangle valve block with the corresponding lateral wall of trapezoidal valve block is located on the same cross-section of continuous liquid phase runner.

Furthermore, the gas buffer chamber and the continuous liquid phase flow channel are both made of deformable materials, the gas buffer chamber does not deform in a non-inflation state, the gas buffer chamber expands in an inflation state and abuts against one side of the continuous liquid phase flow channel, so that the inner wall of the continuous liquid phase flow channel is in full contact with the built-in valve plug, and the continuous liquid phase flow channel is blocked.

Furthermore, the cross sections of the continuous liquid phase flow channel, the gas phase channel and the reaction liquid phase flow channel are rectangular, the heights of the various flow channels are uniform, and the heights of the various flow channels are all 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 substrate and a cover plate;

the micro-channel structure is arranged on the upper surface of the substrate;

the apron cover in the upper surface of base plate, just continuous liquid phase introduction port the gas phase introduction port reaction liquid phase introduction port with mixed phase appearance mouth all link up in the apron.

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 active 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 active valve;

the extraction device is communicated with the mixed phase sample outlet.

The application also provides a heterogeneous reaction method applied to the micro-channel structure, which comprises the following steps:

uniformly and stably dispersing the microsphere suspension liquid through a continuous external triangular expansion focusing flow channel and flowing the microsphere suspension liquid into a continuous liquid phase channel;

the opening and closing of the continuous liquid phase channel are adjusted through a first active valve of the active valve quantitative uniform control unit;

enabling the reaction liquid to enter a mixed liquid phase flow channel through a reaction liquid phase flow channel, enabling the reaction liquid to be in short contact with the microsphere suspension in the mixed liquid phase flow channel, and enabling the reaction liquid to enter a heterogeneous reaction tank for reaction;

the opening and closing of the liquid outlet flow channel are adjusted 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 liquid drops are obtained.

Compared with the prior art, the embodiment of the application has the advantages that:

the application provides a micro flow channel structure, includes: the device comprises a continuous outer triangular expansion focusing unit, a driving valve quantitative uniform control unit and a heterogeneous reaction pool unit; the continuous outer triangular expanding focusing unit includes: the continuous liquid phase sampling port, the continuous outer triangular expansion focusing flow channel and the continuous liquid phase flow channel; the continuous liquid phase sample inlet is communicated with the liquid inlet end of the continuous outer triangular expansion focusing flow channel, and the liquid inlet end of the continuous liquid phase flow channel is communicated with the liquid outlet end of the continuous outer triangular expansion focusing flow channel; the heterogeneous reaction cell unit includes: a reaction liquid phase sample inlet, a reaction liquid phase flow passage, a mixed liquid phase flow passage, a heterogeneous reaction pool, a liquid outlet flow passage and a mixed phase sample outlet; the liquid inlet end of the reaction liquid phase flow passage is communicated with the reaction liquid phase sample inlet, the liquid outlet end of the reaction liquid phase flow passage is communicated with the liquid inlet end of the mixed liquid phase flow passage, the liquid outlet end of the continuous liquid phase flow passage is communicated with the liquid inlet end of the mixed liquid phase flow passage, the liquid outlet end of the mixed liquid phase flow passage is communicated with the liquid inlet end of the heterogeneous reaction pool, the liquid outlet end of the heterogeneous reaction pool is communicated with the liquid inlet end of the liquid outlet flow passage, and the liquid outlet end of the liquid outlet flow passage is communicated with the mixed phase sample outlet; the active valve quantitative uniform control unit comprises: the first active valve corresponds to the continuous liquid phase flow channel, and the second active valve corresponds 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 gas buffer chamber; 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 comprises a continuous outer triangular expansion focusing unit, an active valve quantitative uniform control unit and a coaxial flow non-homogeneous reaction unit, wherein the continuous outer triangular expansion focusing unit comprises a continuous liquid phase injection port, a continuous outer triangular expansion focusing flow channel and a continuous liquid phase flow channel, the continuous liquid phase injection port is used for introducing samples (liquid drops or particles), the samples are separated layer by layer through the continuous outer triangular structure of the continuous outer triangular expansion focusing flow channel, so that the samples form microspheres which are same in size and distributed equidistantly and enter a continuous liquid phase channel, the opening and closing degree of the continuous liquid phase channel is controlled through a first active valve of the active valve quantitative uniform control unit, the flow of the microspheres is controlled, the quantitative control is realized, the microspheres enter a mixed liquid phase flow channel, reaction liquid is introduced into the reaction liquid phase injection port, and the reaction liquid enters the mixed liquid phase flow channel through the reaction liquid phase flow channel to be converged and enter a non-homogeneous reaction pool for full reaction, the second driving valve of the uniform quantitative control unit is used for controlling the opening and closing degree of the liquid outlet channel, so that a sample and a reaction liquid in the heterogeneous reaction tank can be fully reacted, the reaction sufficiency is ensured, the liquid outlet channel is discharged after the reaction is completed, the accurate quantitative control is realized to carry out the accurate and high-efficiency heterogeneous reaction, and the technical problems of how to design a microfluidic device and an operation process are solved, the microfluidic device can generate high-dispersion liquid drops and particles, the accurate and high-efficiency heterogeneous reaction is carried out by the accurate and high-speed quantitative control, and the reaction sufficiency is improved.

Drawings

In order to more clearly illustrate the detailed description of the present application or the technical solutions in the prior art, the drawings needed to be used in the detailed description of the present application or the prior art description will be briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative efforts.

FIG. 1 is a plan view of a micro flow channel structure according to an embodiment of the present invention;

FIG. 2 is a top view of a continuous outer triangular expanding focusing flow channel provided in an embodiment of the present application;

FIG. 3 is a control schematic diagram of an active valve quantitative uniformity control unit in an embodiment of the application;

FIG. 4 is a top view of a heterogeneous reaction cell unit provided in an embodiment of the present application;

fig. 5 is an overall structural diagram of a microfluidic chip provided in an embodiment of the present application.

Wherein the reference numerals are: the device comprises a continuous outer triangular expansion focusing unit 1, an active valve quantitative uniformity control unit 2, a heterogeneous reaction cell unit 3, a continuous liquid phase sample inlet 4, a continuous outer triangular expansion focusing flow channel 5, a continuous liquid phase flow channel 6, a built-in valve plug 7, a gas phase sample inlet 8, a gas phase channel 9, a gas buffer chamber 10, a reaction liquid phase sample inlet 11, a reaction liquid phase flow channel 12, a mixed liquid phase flow channel 13, a substrate 14, a cover plate 15, a first delivery pump 16, a second delivery pump 17, a third delivery pump 18, an extraction device 19, a first flow channel 20, a second flow channel 21, a mixed phase sample outlet 22, a first active valve 23, a second active valve 24, a trapezoidal valve block 25, a rectangular valve block 26, a fourth delivery pump 27, a heterogeneous reaction cell 28 and a liquid outlet flow channel 29.

Detailed Description

The technical solutions of the present application will be described clearly and completely with reference to the accompanying drawings, and it should be understood that the described embodiments are only some embodiments of the present application, but not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.

In the description of the present application, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", and the like indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, and are only for convenience of description and simplicity of description, and do not indicate or imply that the device or element being referred to must have a particular orientation, be constructed and operated in a particular 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 expressly stated or limited otherwise, the terms "mounted," "connected," and "connected" are intended to be inclusive and mean, for example, that they may be fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meaning of the above terms in the present application can be understood in a specific case 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 according to an embodiment of the present disclosure; FIG. 2 is a top view of a continuous outer triangular expanding focusing flow channel provided in an embodiment of the present application; FIG. 3 is a control schematic diagram of an active valve quantitative uniformity control unit in an embodiment of the application; fig. 4 is a top view of a heterogeneous reaction cell unit provided in an embodiment of the present application.

The embodiment of the present application provides a micro flow channel structure, includes: the device comprises a continuous outer triangular expansion focusing unit 1, a driving valve quantitative uniform control unit 2 and a heterogeneous reaction pool unit 3;

the continuous outer triangular expanding focusing unit 1 includes: a continuous liquid phase sample inlet 4, a continuous outer triangular expansion focusing flow channel 5 and a continuous liquid phase flow channel 6;

the continuous liquid phase sample inlet 4 is communicated with the liquid inlet end of the continuous external triangular expanding focusing flow channel 5, and the liquid inlet end of the continuous liquid phase flow channel 6 is communicated with the liquid outlet end of the continuous external triangular expanding focusing flow channel 5;

the heterogeneous reaction cell unit 3 includes: a reaction liquid phase sample inlet 11, a reaction liquid phase flow channel 12, a mixed liquid phase flow channel 13, a heterogeneous reaction pool 28, a liquid outlet flow channel 29 and a mixed phase sample outlet;

the liquid inlet end of the reaction liquid phase flow channel 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 flow channel 13, the liquid outlet end of the continuous liquid phase flow channel 6 is communicated with the liquid inlet end of the mixed liquid phase flow channel 13, the liquid outlet end of the mixed liquid phase flow channel 13 is communicated with the liquid inlet end of the non-homogeneous reaction pool 28, the liquid outlet end of the heterogeneous reaction pool 28 is communicated with the liquid inlet end of the liquid outlet flow channel 29, and the liquid outlet end of the liquid outlet flow channel 29 is communicated with the mixed phase;

the active valve quantitative uniformity control unit 2 includes: a first active valve 23 and a second active valve 24, wherein the first active valve 23 corresponds to the continuous liquid phase flow passage 6, and the second active valve 24 corresponds to the liquid outlet flow passage 29;

the first active valve 23 includes: the device comprises an internal 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 has the same structure as the first active valve 23.

It should be noted that the inner side wall of the continuous outer triangular expanding focusing flow channel 5 is a continuous zigzag shape, the overlooking angle is similar to a plurality of continuous triangles, and the triangle is preferably an equilateral triangle, so as to realize that samples are equally dispersed to form more uniform microsphere particles, the narrowest part of the continuous outer triangular expanding focusing flow channel 5 is the same as the cross section of the continuous liquid phase flow channel 6, so that the continuous outer triangular expanding focusing flow channel can be just butted, the bottom surface of the continuous outer triangular expanding focusing flow channel 5 is preferably a smooth wall surface, so as to be beneficial to the flow of the samples, and the wall surface of the corresponding continuous liquid phase flow channel 6 can also be preferably.

Preferably, in order to avoid the damage to the wall surface caused by the excessive pressure at the contact point of the wall surface of the continuous liquid phase flow channel 6 due to the direct contact between the gas phase channel 9 and the wall surface of the continuous liquid phase flow channel 6, a gas buffer chamber 10 is arranged to separate the gas phase channel 9 and the liquid phase flow channel wall, and the buffer chamber is kept at a certain distance from the wall surface of the liquid phase flow channel.

The heterogeneous reaction cell unit consists of a highly dispersed liquid drop (or microsphere) continuous liquid phase flow channel 6 tail end, a reaction liquid phase sample injection flow channel, a mixed liquid phase flow channel 13 and a heterogeneous reaction cell 28 which are quantitatively and uniformly controlled through a first active valve 23. Preferably, the reaction liquid phase injection port 11 and the reaction liquid phase flow channel 12 are both preferably two, and one reaction liquid phase injection port 11 is matched with one reaction liquid phase flow channel 12, so that simultaneous addition of two reaction liquids can be realized, and the micro flow channel structure has stronger functionality, and 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 injection port 11, the other end of the second flow channel 21 is communicated with a liquid inlet end of the mixed liquid phase flow channel 13, the first flow channel 20 and the second flow channel 21 are same-diameter pipes, the first flow channel 20 is in a horizontal direction, and the direction of the second flow channel 21 and the first flow channel 20 form an included angle of 45 degrees. The aperture of the mixed liquid phase flow channel 13 is larger than the apertures of the continuous liquid phase flow channel 6 and the reaction liquid phase flow channel 12, so that the mixed liquid phase flow channel 13 can better accommodate the microspheres and various reaction liquids simultaneously.

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 sample 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, so as to realize the open and close 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 tapered gas buffer chambers 10, the bottom of the tapered gas buffer chambers 10 correspond to the flow channel, and the distance between the tapered gas buffer chambers 10 and the wall of the liquid phase flow channel is preferably 30 to 100 μm.

The micro flow channel structure provided in the application comprises a continuous outer triangular expansion focusing unit 1, an active valve quantitative uniform control unit 2 and a coaxial flow heterogeneous reaction unit, wherein the continuous outer triangular expansion focusing unit 1 comprises a continuous liquid phase sample inlet 4, a continuous outer triangular expansion focusing flow channel 5 and a continuous liquid phase flow 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 triangular structure of the continuous outer triangular expansion focusing flow channel 5, so that the samples form microspheres which are same in size and distributed equidistantly and enter a 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 of the microspheres, realizing quantitative control, entering a mixed liquid phase flow channel 13, and introducing reaction liquid through a reaction liquid phase sample inlet 11, the reaction liquid enters the mixed liquid phase flow channel 13 through the reaction liquid phase flow channel 12 to be collected and enter the heterogeneous reaction tank 28 to be fully reacted, the opening and closing degree of the liquid outlet flow channel 29 is controlled through the second active valve 24 of the active quantitative uniform control unit, so that a sample and the reaction liquid in the heterogeneous reaction tank 28 can be fully and fully reacted, the reaction sufficiency is ensured, and the sample and the reaction liquid are discharged from the liquid outlet flow channel 29 after the reaction is finished, so that the rapid and accurate quantitative control and the accurate and high-efficiency heterogeneous reaction are realized, and the technical problems of how to design a microfluidic device and an operation process, realizing the rapid and accurate quantitative control and the accurate and high-efficiency heterogeneous reaction on the basis of generating high-dispersion liquid drops and particles and improving the reaction sufficiency are solved.

As a further improvement, the continuous outer triangular expanding focusing flow channel 5 of the micro flow channel structure provided by the embodiment of the application is spiral;

the liquid inlet end of the continuous outer triangular expansion focusing flow channel 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.

Particularly, the spiral structure is favorable for reducing the maximum length of the continuous outer triangular expansion flow channel under the condition of occupying area as small as possible, so that the separation and dispersion effects on the sample are better, the introduced sample can be relatively disordered fluid such as focused liquid drops or liquid drops wrapping particles, after entering the continuous outer triangular expansion focusing flow channel, the disordered fluid containing the particles is acted by centrifugal force and dean flow force and flows along the inner wall surface of the triangle, and finally high dispersion and stable arrangement are realized, so that the focusing flow can be effectively increased, and the dispersion stability is improved. .

As a further improvement, the active valve quantitative uniform control unit of the micro flow channel structure provided by the embodiment of the present application has at least one first active valve 23. Preferably, two first driving valves 23 are arranged, so that the flow in the continuous liquid phase flow channel 6 can be controlled in a grading manner, the flow in the continuous liquid phase flow channel 6 can be reduced step by step, the final flow can be controlled more accurately, and specifically, the two first driving valves 23 are arranged in parallel in the front-back direction.

As a further improvement, the built-in valve plug 7 provided in the embodiment of the present application includes a trapezoidal valve block 25 and a rectangular valve block 26;

the trapezoidal valve block 25 is arranged on one side of the inner wall of the continuous liquid phase flow channel 6, which is far away from the gas buffer chamber 10, and the bottom surface of the trapezoidal 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 trapezoidal valve block 25 are distributed in a staggered mode, and the corresponding side walls of the rectangular valve block 26 and the trapezoidal valve block 25 are located on the same cross section of the continuous liquid phase flow channel 6.

Specifically, when the gas buffer chamber 10 is inflated, deformed and expanded, the flow channel (which may be the continuous liquid phase flow channel 6 or the liquid outlet 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 trapezoidal valve block 25, and thus the flow opening of the flow channel is gradually reduced, the flow rate can be controlled, and when the rectangular valve block 26 and the trapezoidal valve block 25 are attached tightly, the flow channel is closed.

As a further improvement, the gas buffer chamber 10 and the continuous liquid phase flow channel 6 provided in the embodiment of the present application are both made of 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 abuts against one side of the continuous liquid phase flow channel 6, and the inner wall of the continuous liquid phase flow channel 6 is in full contact with the built-in valve plug 7, so that the continuous liquid phase flow channel 6 is blocked. Specifically, the gas source in the gas phase channel 9 is gas introduced from the gas phase sample inlet 8, and the gas phase sample inlet 8 can be externally connected with devices such as a gas pump.

As a further improvement, the continuous liquid phase flow channel 6, the gas phase channel 9, the reaction liquid phase flow channel 12, the mixed liquid phase flow channel 13 and the liquid outlet flow channel 29 provided in the embodiment of the present application have rectangular cross sections, and the heights of the various flow channels are uniform and are all 100 μm to 200 μm.

Preferably, the total length of the continuous external triangular expanding focusing flow channel 5 is 200 mm-2000 mm; the width of the continuous outer triangular expansion focusing flow channel 5 is 100-200 μm; the distance between two adjacent channels of the continuous outer triangular expanding focusing channel 5 is 100-400 μm; the curvature radius of the innermost flow passage of the continuous outer triangular expanding focusing flow passage 5 is 20 mm-50 mm.

Referring to fig. 1 to 5, the present application further provides a microfluidic chip including a chip body and a micro channel structure in the above embodiments; the micro-channel structure is arranged in the chip body.

Optionally, the material of the chip body is preferably PDMS which is a transparent material, and the PDMS can be directly observed and photographed by using a microscope.

As a further improvement, the chip body of the microfluidic chip provided in the embodiment of the present application includes a substrate 14 and a cover plate 15; the micro flow channel structure is arranged on the upper surface of the substrate 14; the cover plate 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 communicated with the cover plate 15.

As a further improvement, the microfluidic chip provided in 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 the 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 the second active valve 24; the extraction device 19 communicates with the mixed phase outlet 22. Wherein, the first delivery pump 16 is used for delivering the sample into the continuous liquid phase sample inlet 4; the second delivery pump 17 is used for delivering gas into the gas phase sample inlet 8 of the first active valve 23; the third transfer pump 18 is configured to transfer the reaction liquid into the reaction liquid phase sample inlet 11, and the fourth transfer pump 27 is configured to transfer 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 both preferably two, and one reaction liquid phase sample inlet 11 is matched with one reaction liquid phase flow channel 12, the third transfer pump 18 is preferably two, and each third transfer pump 18 can be respectively communicated with one reaction liquid phase sample inlet 11, and is configured to transfer the same or different reaction liquids to the corresponding reaction liquid phase sample inlets 11. Preferably, since the first active valves 23 are preferably two, the number of the second delivery pumps is also preferably two, and the two first active valves 23 are respectively matched, so that the two first active valves 23 can be independently controlled. .

The microfluidic chip is highly integrated, the whole chip area is small, and the chip area is only several cubic centimeters; the microfluidic chip has low cost and simple structure and is easy for batch production.

The micro-fluidic 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 delivery device and the extraction device 19 work in concert to achieve high throughput.

2. High dispersion stability. The continuous external triangle expansion focusing flow passage 5 is more beneficial to passive dean flow inertial focusing, and the particle dispersion stability is increased.

3. The quantitative control is accurate. The microspheres passing through the focusing curve have uniform height and spacing values, and the quantity of particles (or liquid drops) in a continuous liquid phase can be quickly and accurately controlled by adjusting the pneumatic pump, so that accurate and controllable quantitative control is realized.

4. The reaction is uniform and sufficient. Through the cooperation between heterogeneous reaction pond, first initiative valve and the second initiative valve, can guarantee that heterogeneous reaction is even, carried out fully in the reaction pond.

5. Environment-friendly and low in cost. The used chip material is non-toxic and harmless, and the reaction effect which is difficult to achieve by conventional operation can be achieved only by less particles and reaction liquid in the operation process.

6. Easy to observe. The device can select PDMS of transparent material for use as the chip material, can directly use the microscope to observe, take a picture the record.

7. The application field is wide. Due to the spacing between the gas phase channel 9 and the liquid phase flow channel, the gas does not react any more on the particles in the reaction liquid, which is suitable for many heterogeneous reactions.

8. Safe and reliable, the reaction chip is closed, and the pollution and leakage of reactants can not be caused. The use of PDMS and other polymers as chip materials can ensure that the chip has certain mechanical properties.

9. The process flow has high speed, and the rapid and batch production can be realized by adopting a photoetching method, an etching method and the like. The device material can be replaced by strong material, and the common PDMS can be replaced by glass, metal and the like.

The present application also provides a heterogeneous reaction method applied to the micro flow channel structure of any one of claims 1 to 6, comprising the steps of:

s1, uniformly and stably dispersing the microsphere suspension liquid through the continuous outer triangular expansion focusing flow channel 5 and flowing the microsphere suspension liquid into a continuous liquid phase channel;

s2, adjusting the opening and closing of the continuous liquid phase channel through a first active valve of the active valve quantitative and uniform control unit, and accurately controlling the quantity of microspheres in the microsphere suspension flowing into the coaxial flow heterogeneous reaction unit;

and S3, allowing the reaction liquid to enter the mixed liquid phase flow channel 13 through the reaction liquid phase flow channel 12, mixing the reaction liquid with the microsphere suspension in the mixed liquid phase flow channel 13 for a short time, and allowing the mixture to enter a heterogeneous reaction tank for reaction. And S4, adjusting the opening and closing of the liquid outlet flow channel 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 liquid drops are obtained.

The above is the first embodiment provided by the present application, and the following 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 triangular expansion focusing flow channel is 800mm, the distance between two adjacent vortex focusing flow channels is 120 mu m, the curvature radius of the innermost flow channel is 30mm, the widths of the gas phase flow channel, the reaction liquid phase flow channel and the continuous liquid phase flow channel are 60 mu m, the widths of the mixed liquid phase flow channel and the liquid outlet flow channel are 120 mu m, the distance between the gas buffer chamber and the continuous liquid phase flow channel is 50 mu m in a non-working state, and the heights of all the flow channels are 100 mu m. Selecting nitrogen as a gas phase, using polystyrene microspheres with the particle size of 30 micrometers and methyl blue aqueous solution as sample liquid, and simultaneously arranging an external light source right above the heterogeneous reaction tank to perform continuous illumination treatment corresponding to the heterogeneous reaction tank. The fluid was injected into the chip body using a teflon capillary hose, and the gas phase fluid was controlled using a second delivery pump. The flow rate of a sample liquid is 30 mul/min, the flow rate of a gas phase is 60 mul/min, the flow rate of a reaction liquid phase is 30 mul/min, the flow rate of the gas phase and the continuous phase liquid phase can be adjusted to enable quantitative titanium dioxide microspheres and a methyl blue aqueous solution in a microsphere suspension to enter a heterogeneous reaction tank, a first active valve and a second active valve in front of and behind the heterogeneous reaction tank are closed, so that the methyl blue aqueous solution and the titanium dioxide microspheres can carry out accurate, efficient and sufficient heterogeneous reaction under the illumination condition, and methylene blue or methylene blue is obtained.

The above is the second embodiment provided by the present application, and the following is the third embodiment provided by the present application, specifically:

the chip body is made of PDMS, wherein the length of the continuous outer triangular expansion focusing flow channel is 500mm, the distance between two adjacent vortex focusing flow channels is 180 micrometers, the curvature radius of the innermost flow channel is 40mm, the widths of the gas phase flow channel, the reaction liquid phase flow channel and the continuous liquid phase flow channel are 80 micrometers, the widths of the mixed liquid phase flow channel and the liquid outlet flow channel are 160 micrometers, the gas buffer chamber keeps a certain distance with the liquid phase flow channel wall in a non-working state, the gas buffer chamber is 60 micrometers, and the heights of all the flow channels are 100 micrometers. Selecting nitrogen as gas phase, using magnesium hydroxide [ Mg (OH)2] solution containing carbon spheres with the particle size of 30 mu m, namely carbon sphere suspension as microsphere suspension (the carbon spheres do not react with the magnesium hydroxide) as sample solution, forming dispersion phase by a focusing fan of a continuous external triangular expansion focusing flow channel, and using ammonium carbonate solution with certain concentration as reaction solution to form continuous liquid phase. The carbon ball suspension and the ammonium carbonate solution were injected into the chip using teflon capillary hoses, respectively, and the gas phase fluid was controlled using a second transfer pump. The flow of injecting the microsphere suspension into the first liquid phase flow channel is 50 mu L/min, the flow of gas phase is 60 mu L/min, the flow of injecting the ammonium carbonate solution into the second liquid phase flow channel and the third liquid phase flow channel is 60 mu L/min, the microsphere suspension with various quantitative carbon sphere contents can be obtained by adjusting the flow of the gas phase and the microsphere suspension, the microsphere suspension and the ammonium carbonate solution enter a heterogeneous reaction tank together through coaxial flow and ammonium carbonate continuous phase, can be fully mixed to carry out heterogeneous accurate and efficient reaction, magnesium carbonate [ MgCO3] precipitates are separated out on the surfaces of carbon spheres to uniformly wrap the carbon spheres, and meanwhile, the heterogeneous reaction is uniform, and microparticle liquid drops with quantitative carbon sphere contents can be obtained.

The above embodiments are only used for illustrating the technical solutions of the present application, and not for limiting the same; although the present application has been described in detail with reference to the foregoing embodiments, it should be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present application.

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