CN112755935B - Micro-channel structure, micro-fluidic chip and heterogeneous reaction method - Google Patents

Abstract

This application provides a microfluidic channel structure, a microfluidic chip and a heterogeneous reaction method. The microfluidic channel structure includes: a continuous outer triangular expansion focusing unit, an active valve quantitative uniform control unit and a heterogeneous reaction pool unit; continuous The outer triangular expansion focusing unit includes: continuous liquid phase inlet, continuous outer triangular expansion focusing flow channel and continuous liquid phase flow channel; the active valve quantitative and uniform control unit includes: built-in valve plug in the flow channel, gas phase injection port, gas phase channel and Gas buffer chamber; the inner wall of the continuous liquid phase flow channel is equipped with a built-in valve plug; the heterogeneous phase unit includes: reaction liquid phase inlet, reaction liquid phase flow channel, mixed liquid phase flow channel and heterogeneous reaction cell. This application solves how to design a microfluidic device and operating process so that it can achieve rapid and accurate quantitative control on the basis of generating highly dispersed droplets and particles, carry out precise and efficient heterogeneous reactions, and improve the fullness of the reaction. Sexual technical issues.

Description

A microfluidic structure, microfluidic chip and heterogeneous reaction method

Technical field

The present application relates to the field of microfluidic technology, and in particular to a microfluidic channel structure, a microfluidic chip and a heterogeneous reaction method.

Background technique

With the development of science and technology, more and more fields (energy, immunity, biochemistry, etc.) require the use of miniaturized reaction methods for highly dispersed and precise operations. Microfluidic technology can realize many difficult-to-complete micro-processing and micro-operations. received widespread attention. Microfluidics is the use of microchannels and devices to control tiny amounts of particles (or samples) that cannot be achieved by conventional methods. It can integrate biological detection, a series of biochemical reactions and various sample preparations onto tiny chips for special operations, and has broad application prospects in many fields.

At present, the conventional preparation process of droplets or microsphere particles is mainly through large-scale mechanical stirring method, which cannot accurately screen microsphere particles of a specific particle size, and the particle dispersion is low, and the droplets participating in the reaction ( Either too much or too few particles (or particles) cannot guarantee efficient reaction. The droplets (or particles) can be uniformly dispersed through a microfluidic system with a special structure, and effective and sufficient reaction can be carried out after quantitative control, which can effectively improve efficiency and experimental success rate.

There are many methods of using microfluidics to generate (or droplets wrapping particles). The active method requires an external magnetic field and electric field; the passive method usually uses Dean flow, which does not require energy input. The device is simple, easy to maintain, and small in size. Passive Dean flow has become one of the most effective ways to focus droplets (or droplets wrapped around particles) in microfluidics due to its simple, convenient and uniform operation. Through passive Dean flow focusing, disorderly scattered microspheres and droplets can be focused in the microchannel to form an array of microspheres and droplets arranged at equal intervals at specific positions. Although the dispersion of droplets (or particles) can be achieved to a certain extent, a certain length of spiral curved flow channel is required to achieve the goal, and it is difficult to achieve precise quantitative control.

Therefore, how to design a microfluidic device and operating process that can achieve rapid and accurate quantitative control on the basis of generating highly dispersed droplets and particles, conduct precise and efficient heterogeneous reactions, and improve the adequacy of the reaction? It has become one of the problems that need to be solved urgently in this field of technology.

Contents of the invention

The purpose of this application is to provide a microfluidic structure, a microfluidic chip and a heterogeneous reaction method to solve how to design a microfluidic device and operating process so that it can generate highly dispersed droplets and particles. On the basis of this, it is a technical issue to achieve fast and accurate quantitative control for precise and efficient heterogeneous reactions and to improve the adequacy of the reaction.

In order to solve the above problems, this application provides a microfluidic structure, including: a continuous outer triangular expansion focusing unit, an active valve quantitative uniform control unit and a heterogeneous reaction cell unit;

The continuous outer triangular expansion focusing unit includes: a continuous liquid phase inlet, a continuous outer triangular expansion focusing flow channel and a continuous liquid phase flow channel;

The continuous liquid phase sampling inlet is connected to 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 connected to the liquid outlet end of the continuous outer triangular expansion focusing flow channel;

The heterogeneous reaction tank unit includes: reaction liquid phase inlet, reaction liquid phase flow channel, mixed liquid phase flow channel, heterogeneous reaction tank, liquid outlet flow channel and mixed phase sample outlet;

The liquid inlet end of the reaction liquid phase flow channel is connected to the reaction liquid phase sampling inlet, the liquid outlet end is connected to the liquid inlet end of the mixed liquid phase flow channel, and the liquid outlet end of the continuous liquid phase flow channel It is connected to the liquid inlet end of the mixed liquid phase flow channel, and the liquid outlet end of the mixed liquid phase flow channel is connected to the liquid inlet end of the heterogeneous reaction tank. The liquid outlet end of the heterogeneous reaction tank is connected to the liquid inlet end of the mixed liquid phase flow channel. It is connected with the liquid inlet end of the liquid outlet channel, and the liquid outlet end of the liquid outlet channel is connected with the mixed phase sample outlet;

The active valve quantitative and uniform control unit includes: a first active valve corresponding to the continuous liquid phase flow channel, and a second active valve corresponding to the liquid outlet flow channel. ;

The first active valve includes: a built-in valve plug, a gas phase injection port, a gas phase channel and a gas buffer chamber;

A built-in valve plug is provided in the continuous liquid phase flow channel, the gas outlet end of the gas phase channel is connected to the gas buffer chamber, the gas inlet end is connected to the gas phase sampling port, and the gas buffer chamber is connected to the built-in valve plug Corresponding;

The second active valve has the same structure as the first active valve.

Further, the continuous outer triangular expansion focusing flow channel is spiral-shaped;

The liquid inlet end of the continuous outer triangular expansion focusing flow channel is located at the center of the spiral;

The liquid outlet end of the continuous outer triangular expansion focusing flow channel is located outside the spiral shape.

Further, there is at least one first active valve.

Further, the built-in valve plug includes a trapezoidal valve block and a rectangular valve block;

The trapezoidal valve block is disposed on the side of the inner wall of the continuous liquid flow channel away from the gas buffer chamber, and the bottom surface of the trapezoidal valve block is in contact with the inner wall of the continuous liquid flow channel;

The rectangular valve block is disposed on one side of the inner wall of the continuous liquid flow channel close to the gas buffer chamber, the rectangular valve block and the trapezoidal valve block are staggered, and the rectangular valve block and the trapezoidal valve block are The corresponding side walls of the valve block are located on the same cross-section of the continuous liquid phase flow channel.

Further, the gas buffer chamber and the continuous liquid flow channel are made of deformable materials. The gas buffer chamber does not deform in the non-inflated state. The gas buffer chamber expands and interacts with the gas in the inflated state. One side of the continuous liquid phase flow channel is in contact with each other, so that the inner wall of the continuous liquid phase flow channel is in full contact with the built-in valve plug, thereby achieving blocking of the continuous liquid phase flow channel.

Further, the cross-sections of the continuous liquid phase flow channel, the gas phase channel and the reaction liquid phase flow channel are all rectangular, and the heights of the various flow channels are uniform, and the heights are all 100 μm ~ 200 μm.

This application also provides a microfluidic chip, including a chip body and the above-mentioned microfluidic channel structure;

The microfluidic structure is arranged in the chip body.

Further, the chip body includes a substrate and a cover;

The microfluidic 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 sampling port, the gas phase sampling port, the reaction liquid phase sampling port and the mixed phase sampling port all pass through the The cover plate.

Further, it also includes a conveying device and an extraction device;

The delivery device includes a first delivery pump connected to the continuous liquid phase injection port, a second delivery pump connected to the gas phase injection port of the first active valve, and a second delivery pump connected to the reaction liquid phase injection port. A third delivery pump and a fourth delivery pump connected to the gas phase injection port of the second active valve;

The extraction device is connected with the mixed phase sample outlet.

This application also provides a heterogeneous reaction method, applied to the above-mentioned microfluidic structure, including the steps:

The microsphere suspension is evenly and stably dispersed through the continuous outer triangular expansion focusing flow channel and flows into the continuous liquid channel;

The opening and closing of the continuous liquid phase channel is adjusted through the first active valve of the active valve quantitative uniformity control unit;

The reaction liquid enters the mixed liquid phase flow channel through the reaction liquid phase flow channel, and is briefly contacted with the microsphere suspension in the mixed liquid phase flow channel and then enters the heterogeneous reaction tank for reaction;

The second active valve of the active valve quantitative and uniform control unit adjusts the opening and closing of the outlet flow channel, so that the mixed liquid in the heterogeneous reaction tank can fully react and obtain the required micro droplets.

Compared with the existing technology, the advantages of the embodiments of the present application are:

This application provides a microfluidic structure, including: a continuous outer triangular expansion focusing unit, an active valve quantitative uniform control unit and a heterogeneous reaction cell unit; the continuous outer triangular expansion focusing unit includes: a continuous liquid phase injection port , the continuous outer triangular expansion focusing flow channel and the continuous liquid phase flow channel; the continuous liquid phase injection port is connected to the liquid inlet end of the continuous outer triangular expansion focusing flow channel, and the liquid phase inlet end of the continuous liquid phase flow channel is connected to the liquid inlet end of the continuous outer triangular expansion focusing flow channel. The liquid outlet ends of the continuous outer triangular expansion focusing flow channel are connected; the heterogeneous reaction tank unit includes: reaction liquid phase inlet, reaction liquid phase flow channel, mixed liquid phase flow channel, heterogeneous reaction tank, outlet liquid flow channel and mixed phase sample outlet; the liquid inlet end of the reaction liquid phase flow channel is connected to the reaction liquid phase sample inlet, and the liquid outlet end is connected to the liquid inlet end of the mixed liquid phase flow channel, so The liquid outlet end of the continuous liquid phase flow channel is connected to the liquid inlet end of the mixed liquid phase flow channel, and the liquid outlet end of the mixed liquid phase flow channel is connected to the liquid inlet end of the heterogeneous reaction tank, so The liquid outlet end of the heterogeneous reaction tank is connected to the liquid inlet end of the outlet channel, and the liquid outlet end of the outlet channel is connected to the mixed phase sample outlet; the active valve is quantitatively and uniformly controlled The unit includes: a first active valve corresponding to the continuous liquid phase flow channel and a second active valve corresponding to the liquid outlet flow channel; the first active valve It includes: a built-in valve plug, a gas phase sampling port, a gas phase channel and a gas buffer chamber; a built-in valve plug is arranged in the continuous liquid phase flow channel, the gas outlet end of the gas phase channel is connected to the gas buffer chamber, and the gas inlet end is connected to the gas buffer chamber. The gas phase sampling inlet is connected, 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 microfluidic structure provided in this application includes a continuous outer triangular expansion focusing unit, an active valve quantitative uniform control unit and a coaxial flow heterogeneous reaction unit. The continuous outer triangular expansion focusing unit includes a continuous liquid phase inlet, a continuous The outer triangular expanded focusing flow channel and the continuous liquid phase flow channel are used. The continuous liquid phase inlet is used to introduce samples (droplets or particles). The samples are separated layer by layer through the continuous outer triangular structure of the continuous outer triangular expanded focusing flow channel, so that The sample forms microspheres of the same size and equidistantly distributed and enters the continuous liquid channel. The first active valve of the active valve quantitative uniform control unit controls the opening and closing degree of the continuous liquid channel, thereby controlling the flow rate of the microspheres and achieving Quantitative control, and enter the mixed liquid phase flow channel, introduce the reaction liquid through the reaction liquid phase injection port, and make the reaction liquid enter the mixed liquid phase flow channel through the reaction liquid phase flow channel, collect and enter the heterogeneous reaction tank for full reaction, the opening and closing degree of the outlet flow channel is controlled by the second active valve of the active quantitative uniformity control unit, so that the sample and the reaction solution in the heterogeneous reaction tank can fully react to ensure the adequacy of the reaction. After the reaction is completed, it is discharged from the outlet flow channel, thereby achieving fast and accurate quantitative control for precise and efficient heterogeneous reactions, and solving the problem of how to design a microfluidic device and operating process so that it can generate highly dispersed droplets. , particles, to achieve rapid and accurate quantitative control for precise and efficient heterogeneous reactions and to improve the adequacy of the reaction.

Description of drawings

In order to more clearly explain the specific embodiments of the present application or the technical solutions in the prior art, the drawings needed to be used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings in the following description The drawings illustrate some embodiments of the present application. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without exerting creative efforts.

Figure 1 is a top view of the microfluidic structure provided by the embodiment of the present application;

Figure 2 is a top view of the continuous outer triangular expansion focusing flow channel provided by the embodiment of the present application;

Figure 3 is a control principle diagram of the active valve quantitative and uniform control unit in the application embodiment;

Figure 4 is a top view of the heterogeneous reaction tank unit provided by the embodiment of the present application;

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

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

Detailed ways

The technical solution of the present application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the present application, rather than all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by those of ordinary skill in the art without creative efforts fall within the scope of protection of this application.

In the description of this application, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. The indicated orientation or positional relationship is based on the orientation or positional relationship shown in the drawings. It is only for the convenience of describing the present application and simplifying the description. It does not indicate or imply that the device or element referred to must have a specific orientation or a specific orientation. construction and operation, and therefore should not be construed as limitations on this 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 otherwise clearly stated and limited, the terms "installation", "connection" and "connection" should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection, It can also be an electrical connection; it can be a direct connection, or it can be an indirect connection through an intermediate medium, or it can be an internal connection between two components. For those of ordinary skill in the art, the specific meanings of the above terms in this application can be understood on a case-by-case basis.

For ease of understanding, please refer to Figures 1 to 4. Figure 1 is a top view of the micro-channel structure provided by the embodiment of the present application; Figure 2 is a top view of the continuous outer triangular expansion focusing flow channel provided by the embodiment of the present application; Figure 3 is a control principle diagram of the active valve quantitative and uniform control unit in the embodiment of the application; FIG. 4 is a top view of the heterogeneous reaction tank unit provided in the embodiment of the application.

The embodiment of the present application provides a microfluidic structure, including: a continuous outer triangular expansion focusing unit 1, an active valve quantitative uniform control unit 2 and a heterogeneous reaction tank unit 3;

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

The continuous liquid phase inlet 4 is connected to the liquid inlet end of the continuous outer triangular expansion focusing flow channel 5, and the liquid inlet end of the continuous liquid phase flow channel 6 is connected to the liquid outlet end of the continuous outer triangular expansion focusing flow channel 5;

Heterogeneous reaction tank unit 3 includes: reaction liquid phase inlet 11, reaction liquid phase flow channel 12, mixed liquid phase flow channel 13, heterogeneous reaction tank 28, liquid outlet flow channel 29 and mixed phase sample outlet;

The liquid inlet end of the reaction liquid phase flow channel 12 is connected to the reaction liquid phase inlet 11, the liquid outlet end is connected to the liquid inlet end of the mixed liquid phase flow channel 13, and the liquid outlet end of the continuous liquid phase flow channel 6 is connected to the mixed liquid phase flow channel 13. The liquid inlet end of the flow channel 13 is connected, the liquid outlet end of the mixed liquid phase flow channel 13 is connected with the liquid inlet end of the heterogeneous reaction tank 28, and the liquid outlet end of the heterogeneous reaction tank 28 is connected with the inlet of the outlet flow channel 29. The liquid end is connected, and the liquid outlet end of the liquid outlet channel 29 is connected with the mixed phase sample outlet;

The active valve quantitative and uniform control unit 2 includes: a first active valve 23 and a second active valve 24. The first active valve 23 corresponds to the continuous liquid phase flow channel 6, and the second active valve 24 corresponds to the liquid outlet flow channel 29;

The first active valve 23 includes: a built-in valve plug 7, a gas phase inlet 8, a gas phase channel 9 and a gas buffer chamber 10;

The built-in valve plug 7 is provided in the continuous liquid phase flow channel 6, the gas outlet end of the gas phase channel 9 is connected to the gas buffer chamber 10, the gas inlet end is connected to the gas phase sampling port 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 wall of the continuous outer triangular expansion focusing flow channel 5 is a continuous zigzag shape, and the bird's-eye view is similar to multiple continuous triangles, and the triangles are preferably equilateral triangles, so that the sample can be dispersed equidistantly to form More uniform microsphere particles, the narrowest part of the continuous outer triangular expansion focusing flow channel 5 and the continuous liquid phase flow channel 6 have the same cross-section, so that they can be exactly connected. The bottom surface of the continuous outer triangular expansion focusing flow channel 5 is preferably a smooth wall surface. This is beneficial to the flow of the sample, and the wall surface of the corresponding continuous liquid phase flow channel 6 may also preferably be a smooth wall surface.

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

The heterogeneous reaction cell unit consists of the highly dispersed droplets (or microspheres) at the end of the continuous liquid phase flow channel 6 after being quantitatively and uniformly controlled by the first active valve 23, the reaction liquid phase injection channel, and the mixed liquid phase flow channel 13 It is composed of heterogeneous reaction pool 28. Among them, there are preferably two reaction liquid phase inlets 11 and two reaction liquid phase flow channels 12. One reaction liquid phase inlet 11 matches one reaction liquid phase flow channel 12, so that the two reaction liquids can be processed simultaneously. Add to make the micro-channel structure more functional. Preferably, the reaction liquid phase channel 12 includes a first channel 20 and a second channel 21. One end of the first channel 20 is connected to one end of the second channel 21. The other end of the first flow channel 20 is connected to the reaction liquid phase injection port 11, and the other end of the second flow channel 21 is connected to the liquid inlet end of the mixed liquid phase flow channel 13. The first flow channel 20 and the second flow channel 21 are the same. diameter pipe, the first flow channel 20 is in a horizontal direction, and the direction of the second flow channel 21 is at an included angle of 45° with the first flow channel 20. The diameter of the mixed liquid phase flow channel 13 is larger than the diameter of the continuous liquid phase flow channel 6 and the diameter of the reaction liquid phase flow channel 12, so that the mixed liquid phase flow channel 13 can better accommodate microspheres and multiple 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, and the gas phase channel 9 of the second active valve 24 is The gas outlet is connected to the buffer chamber of the second active valve 24, the gas inlet is connected to the gas phase sampling port 8 of the second active valve 24, and the gas buffer chamber 10 of the second active valve 24 is connected to the built-in valve plug of the second active valve 24. 7 corresponds to realize 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, and the bottom of the conical gas buffer chamber 10 corresponds to the flow channel, preferably a conical gas buffer chamber. The distance between 10 and the liquid flow channel wall is 30μm~100μm.

The microfluidic structure provided in this application includes a continuous outer triangular expansion focusing unit 1, an active valve quantitative and uniform control unit 2 and a coaxial flow heterogeneous reaction unit. The continuous outer triangular expansion focusing unit 1 includes continuous liquid phase injection. Port 4, continuous outer triangular expansion focusing flow channel 5 and continuous liquid phase flow channel 6. The continuous liquid phase injection port 4 is used to introduce samples (droplets or particles). The sample passes through the continuous outer triangular expansion focusing flow channel 5. The triangular structure is separated layer by layer, so that the sample forms microspheres of the same size and equidistantly distributed and enters the continuous liquid phase channel. The opening and closing of the continuous liquid phase channel is controlled by the first active valve 23 of the active valve quantitative uniformity control unit 2. degree, thereby controlling the flow rate of the microspheres, achieving quantitative control, and entering the mixed liquid phase flow channel 13. The reaction liquid is introduced into the reaction liquid phase inlet 11, and the reaction liquid enters the mixed liquid phase through the reaction liquid phase flow channel 12. The liquid in the flow channel 13 is collected and enters the heterogeneous reaction tank 28 for full reaction. The opening and closing degree of the outlet flow channel 29 is controlled through the second active valve 24 of the active quantitative and uniform control unit, so that the liquid in the heterogeneous reaction tank 28 The sample and the reaction solution can react completely and fully to ensure the adequacy of the reaction. After the reaction is completed, it is discharged from the outlet flow channel 29, thereby achieving rapid and accurate quantitative control for precise and efficient heterogeneous reaction, and solving the problem of how to It is a technical issue to design a microfluidic device and operating process that can achieve rapid and accurate quantitative control on the basis of generating highly dispersed droplets and particles, conduct precise and efficient heterogeneous reactions, and improve the adequacy of the reaction.

As a further improvement, the continuous outer triangular expansion focused flow channel 5 of the microchannel structure provided by the embodiment of the present application is spiral-shaped;

The liquid inlet end of the continuous outer triangular expansion focusing flow channel 5 is located at the center of the spiral;

The liquid outlet end of the continuous outer triangular expansion focusing flow channel 5 is located outside the spiral.

Specifically, the use of a spiral structure is conducive to minimizing the length of the continuous outer triangular expansion flow channel while occupying the smallest possible area, so that the separation and dispersion effect of the sample is better, and the introduced sample can be the focusing liquid Relatively turbulent fluids such as droplets or droplets wrapping particles, after entering the continuous outer triangular expanded focusing flow channel, the turbulent fluid containing particles will flow along the inner wall of the triangle due to the simultaneous action of centrifugal force and Dean flow force, and finally Achieving high dispersion and stable arrangement can effectively increase the focusing process and improve dispersion stability. .

As a further improvement, the active valve quantitative and uniform control unit of the microfluidic structure provided by the embodiment of the present application has at least one first active valve 23 . Preferably there are two. By arranging two first active valves 23, it is conducive to perform hierarchical control of the flow rate in the continuous liquid phase flow channel 6, so that the flow rate in the continuous liquid phase flow channel 6 is gradually reduced, which is beneficial to To control the final flow rate more accurately, specifically, the two first active valves 23 are arranged in parallel and arranged front and back.

As a further improvement, the built-in valve plug 7 provided by 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 the side of the inner wall of the continuous liquid phase flow channel 6 away from the gas buffer chamber 10, and the bottom surface of the trapezoidal valve block 25 is in contact with the inner wall of the continuous liquid phase flow channel 6;

The rectangular valve block 26 is disposed on one side of the inner wall of the continuous liquid flow channel 6 close to the gas buffer chamber 10. The rectangular valve block 26 and the trapezoidal valve block 25 are staggered, and the side walls of the rectangular valve block 26 and the trapezoidal valve block 25 correspond to each other. 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 can be the continuous liquid phase flow channel 6 or the liquid outlet flow channel 29 ) is squeezed through the bottom of the gas buffer chamber 10 , causing the flow channel to deform and drive the rectangular valve. The block 26 moves and approaches the trapezoidal valve block 25, so that the flow opening of the flow channel gradually becomes smaller, thereby controlling the flow rate. When the rectangular valve block 26 and the trapezoidal valve block 25 are in close contact, the flow channel is closed.

As a further improvement, the materials of the gas buffer chamber 10 and the continuous liquid flow channel 6 provided in the embodiment of the present application are both deformable materials. The gas buffer chamber 10 does not deform in the non-inflated state, and the gas buffer chamber 10 does not deform when inflated. state, it expands and abuts one side of the continuous liquid phase flow channel 6 , so that the inner wall of the continuous liquid phase flow channel 6 fully contacts the built-in valve plug 7 , thereby achieving the blocking of the continuous liquid phase flow channel 6 . Specifically, the gas source in the gas phase channel 9 comes from the gas introduced through the gas phase sampling port 8. The gas phase sampling port 8 can be externally connected to equipment such as a gas pump.

As a further improvement, the continuous liquid phase flow channel 6, gas phase channel 9, reaction liquid phase flow channel 12, mixed liquid phase flow channel 13 and liquid outlet flow channel 29 provided in the embodiment of the present application are all rectangular in cross section, and each The flow channels are highly uniform and have a height of 100μm~200μm.

Preferably, the total length of the continuous outer triangular expansion focusing flow channel 5 is 200 mm ~ 2000 mm; the width of the continuous outer triangular expansion focusing flow channel 5 is 100 μm ~ 200 μm; the adjacent two adjacent outer triangular expansion focusing flow channels 5 The spacing of the flow channels is 100 μm~400 μm; the curvature radius of the innermost flow channel of the continuous outer triangular expansion focused flow channel 5 is 20 mm~50 mm.

Referring to Figures 1 to 5, this application also provides a microfluidic chip, which includes a chip body and the microfluidic structure in the above embodiment; the microfluidic structure is disposed in the chip body.

Optionally, the material of the chip body is preferably transparent PDMS as the chip material, which can be directly observed, photographed and recorded 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 microfluidic channel structure is provided 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 sampling port 4, the gas phase sampling port 8, the reaction liquid phase sampling port 11 and the mixed phase sampling port 22 all penetrate the cover plate 15.

As a further improvement, the microfluidic chip provided in the embodiment of the present application also includes a delivery device and an extraction device 19; the delivery device includes a first delivery pump 16 connected to the continuous liquid phase inlet 4, and a first active valve 23 The second delivery pump 17 communicated with the gas phase sampling port 8, the third delivery pump 18 communicated with the reaction liquid phase sampling port 11, and the fourth delivery pump 27 communicated with the gas phase sampling port 8 of the second active valve 24; The extraction device 19 is connected to the mixed phase sample outlet 22. Among them, the first delivery pump 16 is used to deliver the sample into the continuous liquid phase sampling inlet 4; the second delivery pump 17 is used to deliver gas into the gas phase sampling inlet 8 of the first active valve 23; and the third delivery pump 18 is used to deliver The reaction liquid enters the reaction liquid phase sampling port 11, and the fourth delivery pump 27 is used to transport gas into the gas phase sampling port 8 of the second active valve 24. Specifically, due to the reaction liquid phase sampling port 11 and the reaction liquid phase flow channel 12 is preferably two, and one reaction liquid phase inlet 11 matches a reaction liquid phase flow channel 12. Therefore, the number of the third delivery pump 18 can be preferably two, and each third delivery pump 18 can be connected to a reaction liquid phase channel 12. The liquid phase inlets 11 are connected and used to deliver the same or different reaction liquids to respective corresponding reaction liquid phase inlets 11 . Preferably, since the number of the first active valves 23 is preferably two, the number of the second delivery pumps is also preferably two, and is matched with the two first active valves 23 respectively, thereby realizing the control of the two first active valves 23 independent control. .

The microfluidic chip of the present application is highly integrated, and the entire chip area is small, only a few cubic centimeters; the microfluidic chip has low cost, simple structure, and is easy to be mass-produced.

The microfluidic chip provided by this application has the following advantages:

1. Miniaturization of device structure. The entire chip device has a small area and a large specific surface area. The coordinated operation of the conveying device and the extraction device 19 can achieve high throughput.

2. High dispersion stability. The continuous outer triangular expansion focusing flow channel 5 is more conducive to passive Dean flow inertial focusing and increases particle dispersion stability.

3. Accurate quantitative control. The microspheres that have passed through the focusing curve have uniform height and spacing values. By adjusting the pneumatic pump, the number of particles (or droplets) in the continuous liquid phase can be quickly and accurately controlled to achieve precise and controllable quantitative control.

4. The reaction is uniform and sufficient. Through the cooperation between the heterogeneous reaction tank, the first active valve and the second active valve, it can be ensured that the heterogeneous reaction proceeds evenly and fully in the reaction tank.

5. Environmentally friendly and low cost. The chip material used is non-toxic and harmless, and only fewer particles and reaction solutions are needed during the operation to achieve reaction effects that are difficult to achieve with conventional operations.

6. Easy to observe. This device can use transparent PDMS as the chip material, and can be directly observed, photographed and recorded using a microscope.

7. Wide adaptability. Since the gas phase channel 9 is separated from the liquid phase flow channel, the gas will not react to the particles in the reaction liquid, and is suitable for many heterogeneous reactions.

8. Safe and reliable, the reaction chip is sealed and will not cause contamination or leakage of reactants. Using polymers such as PDMS as chip materials can ensure that the chip has certain mechanical properties.

9. The process flow is fast, and rapid and mass production can be achieved using photolithography, etching, etc. The device materials are highly replaceable, and commonly used PDMS can be replaced by glass, metal, etc.

This application also provides a heterogeneous reaction method, applied to any microfluidic structure, which is characterized by including the steps:

S1. Disperse the microsphere suspension evenly and stably through the continuous outer triangular expansion focusing flow channel 5 and flow into the continuous liquid channel;

S2. Adjust the opening and closing of the continuous liquid channel through the first active valve of the active valve quantitative and uniform control unit to accurately control the number of microspheres in the microsphere suspension flowing into the coaxial flow heterogeneous reaction unit;

S3. The reaction liquid enters the mixed liquid phase flow channel 13 through the reaction liquid phase flow channel 12, and is briefly mixed with the microsphere suspension in the mixed liquid phase flow channel 13 before entering the heterogeneous reaction tank for reaction. S4. Adjust the opening and closing of the outlet flow channel through the second active valve of the active valve quantitative uniformity control unit, so that the mixed liquid in the heterogeneous reaction tank can fully react and obtain the required micro droplets.

The above is the first embodiment provided by this application, and the following is the second embodiment provided by this application, specifically:

The material of the chip body is PDMS (polydimethylsiloxane). The length of the continuous outer triangular expansion focusing channel is 800mm. The distance between two adjacent vortex focusing channels is 120μm. The radius of curvature of the innermost channel is 30mm. The gas phase The width of the flow channel, reaction liquid phase flow channel, and continuous liquid phase flow channel is 60 μm, the width of the mixed liquid phase flow channel and the outlet flow channel is 120 μm, and the distance between the gas buffer chamber and the continuous liquid phase flow channel in the non-working state is 50μm, all channel heights are 100μm. Nitrogen was used as the gas phase, containing polystyrene microspheres with a particle size of 30 μm and a methyl blue aqueous solution as the sample liquid. At the same time, an external light source was set directly above the heterogeneous reaction cell to perform continuous illumination treatment on the heterogeneous reaction cell. A polytetrafluoroethylene capillary hose was used to inject the fluid into the chip body, and a second delivery pump was used to control the gas phase fluid. The sample liquid flow rate is 30 μl/min, the gas phase flow rate is 60 μl/min, and the reaction liquid phase flow rate is 30 μl/min. Adjusting the gas phase and continuous phase liquid flow rates can allow the quantitative titanium dioxide microspheres in the microsphere suspension to pass through the methyl blue aqueous solution. Enter the heterogeneous reaction tank, close the first active valve and the second active valve before and after the heterogeneous reaction tank, so that the methyl blue aqueous solution and titanium dioxide microspheres can carry out precise, efficient and sufficient heterogeneous reaction under light conditions. , to obtain methylene blue or methylene blue.

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

The material of the chip body is PDMS. The length of the continuous outer triangular expansion focusing channel is 500mm. The distance between two adjacent vortex focusing channels is 180μm. The radius of curvature of the innermost channel is 40mm. The gas phase flow channel, reaction liquid phase flow channel and The width of the continuous liquid phase flow channel is 80 μm, the width of the mixed liquid phase flow channel and the outlet flow channel is 160 μm, the gas buffer chamber maintains a certain distance from the liquid phase flow channel wall in the non-working state, which is 60 μm, and the height of all flow channels is 100 μm. . Nitrogen is selected as the gas phase, and a magnesium hydroxide [Mg(OH)2] solution containing carbon spheres with a particle size of 30 μm, that is, a carbon sphere suspension, is used as the microsphere suspension (carbon spheres do not react with magnesium hydroxide) as the sample liquid. The focusing fan of the outer triangular expansion focusing flow channel forms a dispersed phase, and a certain concentration of ammonium carbonate solution is used as the reaction liquid to form a continuous liquid phase. The carbon ball suspension and ammonium carbonate solution were respectively injected into the chip using a polytetrafluoroethylene capillary hose, and a second delivery pump was used to control the gas phase fluid. The flow rate of the microsphere suspension injected into the first liquid phase channel is 50 μL/min, the gas phase flow rate is 60 μl/min, and the flow rate of the ammonium carbonate solution injected into the second liquid phase channel and the third liquid phase channel is 60 μL/min. By adjusting the flow rate of the gas phase and microsphere suspension, microsphere suspensions with various quantitative carbon ball contents can be obtained. Through coaxial flow, they enter the heterogeneous reaction tank together with the ammonium carbonate continuous phase, and can be fully mixed for precise and precise heterogeneous reaction. Efficient reaction, magnesium carbonate [MgCO3] precipitates on the surface of the carbon spheres and evenly wraps the carbon spheres. At the same time, the heterogeneous reaction is uniform, and micro-particle droplets with quantitative carbon sphere content can be obtained.

The above embodiments are only used to illustrate the technical solutions of the present application, but not to limit them. Although the present application has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still implement the foregoing implementations. The technical solutions described in the examples are modified, or some or all of the technical features are equivalently replaced; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions in the embodiments of the present 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.