A microfluidic chip

By designing the liquid separation flow channel and self-heating layer in the microfluidic chip, reaction uniformity and full mixing of reagents at a specific temperature are achieved, and the problems of uneven reactions and insufficient mixing in the prior art are solved, and the accuracy of the detection results is improved.

CN119702103BActive Publication Date: 2025-07-11FUZHOU AGENMIC BIOTECHNOLOGY CO LTD

Patent Information

Application Number
CN202510247086.6
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2025-03-04
Publication Date
2025-07-11
Estimated Expiration
2045-03-04

AI Technical Summary

Technical Problem

The existing microfluidic chips react unevenly under specific temperature conditions and lack flexibility, resulting in inaccurate detection results and insufficient mixing of reagents in the prior art.

Method used

A microfluidic chip is designed, including a sample loading channel, a shunt chamber and a reaction chamber, which is divided into several quantitative sections using a liquid separation flow channel, and the flow and temperature of the solution are controlled through a heat-sensitive valve and a self-heating layer to achieve reactions and intermittent addition of reagents at specific temperatures.

Benefits of technology

在特定温度下实现反应的均匀性和试剂的充分混合,提高了检测结果的准确性,操作简便且适用于户外使用。

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention relates to a microfluidic chip, comprising a chip body, wherein a sample loading channel, a shunt chamber and a reaction chamber are provided in the chip body; a heat transfer layer, a self-heating layer and a base layer are sequentially arranged on one side of the chip body; the liquid separation flow channel is divided into a number of independent quantitative segments along its trajectory direction, and adjacent two groups of quantitative segments are connected by a thermosensitive valve; the present invention does not need to use heating devices, and the heating structure is adopted to realize reaction under specific temperature conditions, which is more conducive to outdoor operation and is easy to operate; the liquid separation flow channel is separated into a plurality of quantitative segments, and there is only an equal amount of solution in each quantitative segment, and the solutions in each quantitative segment flow into the reaction chamber at equal time intervals for reaction, which is beneficial to improving the mixing of different reagents and improving the reaction uniformity, thereby improving the accuracy of the detection result.
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Description

Technical Field

[0001] The present invention relates to the technical field of microfluidic detection, and particularly relates to a microfluidic chip. Background Art

[0002] A laboratory on a chip, abbreviated as LOC, is an important detection technology in the fields of medicine, analytical chemistry, etc. for detecting analytes in equipment. A microfluidic chip is one of the more important detection devices in LOC detection technology. In existing microfluidic chips, the channel diameter is usually only 100 nanometers to 100 micrometers, and the analyte needs to flow through the channel into a small shunt cavity, and then very precise instruments are required to generate a certain driving force on the analyte to promote the flow of the analyte.

[0003] For example, the "microfluidic chip for analyte detection" disclosed in the patent publication number CN117654653A can directly complete the injection of the sample liquid into the reaction cavity by using a pressing member without using an additional pipette or pipettor to transfer the liquid in the reaction cavity.

[0004] Since many chemical and biological reactions and detections in the application process of microfluidic chips often need to be carried out under specific temperature conditions, heating control is of extremely important significance in the application of microfluidic chips.

[0005] For example, the "self-heating microfluidic chip" disclosed in the patent publication number CN103301891A injects water into the self-heating layer, and the exothermic reaction between water and calcium oxide obtains a self-heating effect to provide heat for subsequent reactions;

[0006] Some chemical and biological reactions and detections need to be carried out under specific temperature conditions, and in the prior art, all reagents are usually added at one time, lacking flexibility; after adding all reagents at one time, due to the laminar flow characteristics of the fluid inside the microfluidic chip, the mixing between different reagents may not be sufficient, resulting in uneven reactions and affecting the accuracy of detection results;

[0007] Therefore, there is a need for a device that can provide a specific reaction temperature and intermittently add reagents to control the microfluidic chip. Summary of the Invention

[0008] In view of the deficiencies of the prior art, the present invention provides a microfluidic chip to solve the above problems.

[0009] The present invention provides the following technical solutions:

[0010] A microfluidic chip, comprising a chip body, wherein a sample loading channel, a shunt cavity and a reaction cavity are provided in the chip body, one end of the sample loading channel communicates with the shunt cavity, the shunt cavity communicates with the reaction cavity through a liquid distribution channel, and a heat transfer layer, a self-heating layer and a base layer are sequentially arranged on one side of the chip body;

[0011] The liquid distribution channel is divided into a number of mutually independent quantitative segments along its track direction, and adjacent two groups of quantitative segments are connected by a thermal valve;

[0012] The self-heating layer includes a liquid area, a reaction cavity solid area, a plurality of mutually independent thermal valve solid areas, a liquid discharge channel and a partition valve. The reaction cavity solid area is aligned with the position of the reaction cavity, the thermal valve solid areas are aligned with the corresponding thermal valves one by one, the liquid discharge channel is connected with the liquid area through the partition valve, a plurality of liquid discharge ports are arranged on the liquid discharge channel, the reaction cavity solid area and the plurality of thermal valve solid areas are respectively aligned with one liquid discharge port, a water melting film is arranged in the liquid discharge port, and the number of water melting films in the liquid discharge port decreases sequentially along the flowing direction of the liquid in the liquid distribution channel.

[0013] Preferably, a reaction cavity heat conduction area is arranged at the position of the heat transfer layer corresponding to the reaction cavity, a plurality of mutually independent thermal valve heat conduction areas are arranged at the position of the heat transfer layer corresponding to the liquid distribution channel, and the thermal valve heat conduction areas are in one-to-one correspondence with the positions of the thermal valves.

[0014] Preferably, calcium oxide particles with a particle size of 0.1-100 microns are filled in the reaction cavity solid area and the thermal valve solid areas; water is filled in the liquid area.

[0015] Preferably, a sample part is arranged on the chip body, the sample loading channel communicates with the sample part, and a pressing cover body for opening and closing the opening of the sample part is further included.

[0016] Preferably, an airbag is arranged on the pressing cover body, and an exhaust flow channel is arranged in the chip body; one end of the exhaust flow channel communicates with the reaction cavity, the other end is provided with an exhaust hole, and an exhaust liquid blocking film is arranged in the exhaust hole.

[0017] Preferably, the pressing cover body is in threaded connection with the sample part.

[0018] Preferably, the liquid distribution channel includes a first branch channel and a second branch channel; one end of the first branch channel communicates with the shunt cavity, and the other end is closed; one end of the second branch channel communicates with the reaction cavity; the thermal valve is of a three-way valve structure, the first end and the second end of the thermal valve of the three-way valve structure communicate with the second branch channel, a quantitative segment is formed at the part of the second branch channel between adjacent two groups of the thermal valves, and the third end of the thermal valve communicates with the first branch channel.

[0019] Preferably, a bimetal sheet is built in the thermal valve with a three-way valve structure, and the thermal valve has two states;

[0020] In the first state, when the bimetal sheet is not heated, the first end and the third end of the thermal valve are connected, and the second end is closed;

[0021] In the second state, when the bimetal sheet is heated, the first end and the second end of the thermal valve are connected, and the third end is closed.

[0022] Preferably, the other end of the second branch channel away from the reaction cavity is communicated with the shunt cavity, and the first end of the thermal valve with a three-way valve structure is located on the side close to the shunt cavity.

[0023] Preferably, the end of the second branch channel and the shunt cavity are connected by a group of thermal valves, and the first end of this thermal valve is built with a corresponding exhaust liquid-blocking film.

[0024] The present invention has the following beneficial technical effects:

[0025] The present invention does not need to use heating devices. With a heating structure, realizing the reaction under specific temperature conditions is more conducive to outdoor operation, and the operation is simple;

[0026] The present invention divides the liquid separation flow channel into multiple quantitative segments. Only an equal amount of solution is in each quantitative segment, and the solutions in each quantitative segment flow into the reaction cavity at equal time intervals for reaction, which is beneficial to improving the mixing of different reagents and the reaction uniformity, thereby improving the accuracy of the detection result. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 is an exploded three-dimensional schematic diagram of the present invention;

[0028] Figure 2 is a three-dimensional schematic diagram of the chip body and its cooperating components of the present invention;

[0029] Figure 3 is a schematic diagram of the heat transfer layer structure of the present invention;

[0030] Figure 4 is a schematic diagram of the self-heating layer structure of the present invention;

[0031] Figure 5 is an exploded three-dimensional schematic diagram of the cooperation of the drain channel, the solid area of the reaction cavity, the solid area of the thermal valve, etc. of the present invention;

[0032] Figure 6 is a cross-sectional view of the drain port of the present invention;

[0033] Figure 7 is a schematic diagram of the liquid separation flow channel of the present invention;

[0034] Figure 8It is a schematic diagram of the first state of the thermal valve of the present invention;

[0035] Figure 9 It is a schematic diagram of the second state of the thermal valve of the present invention.

[0036] The reference numerals in the figure are:

[0037] 1. Chip body; 11. Sampling channel; 12. Shunt cavity; 13. Liquid distribution channel; 131. First branch channel; 132. Second branch channel; 133. Thermal valve; 1331. Bimetallic strip; 14. Reaction cavity; 15. Exhaust channel; 16. Exhaust hole; 2. Sample part; 3. Pressing cover body; 4. Heat transfer layer; 41. Reaction cavity heat conduction area; 42. Thermal valve heat conduction area; 5. Self-heating layer; 51. Liquid area; 52. Reaction cavity solid area; 53. Thermal valve solid area; 54. Drainage channel; 55. Isolation valve; 56. Drainage port; 561. Melting water film; 6. Base layer. Specific embodiments

[0038] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0039] Embodiment:

[0040] A microfluidic chip, as Figures 1-9 shown, includes a chip body 1, and a heat transfer layer 4, a self-heating layer 5, and a base layer 6 that are sequentially pasted on one side of the chip body 1.

[0041] A sample part 2 is provided on the chip body 1. The chip body 1 has a sampling channel 11, a shunt cavity 12, a liquid distribution channel 13, a reaction cavity 14, an exhaust channel 15, and an exhaust hole 16. One end of the sampling channel 11 is communicated with the inner cavity of the sample part 2, and the other end of the sampling channel 11 is communicated with the shunt cavity 12; multiple groups of reaction cavities 14 are evenly arranged, and each reaction cavity 14 is communicated with the shunt cavity 12 through a corresponding liquid distribution channel 13; the reaction cavity 14 is communicated with the exhaust hole 16 through a corresponding exhaust channel 15; an exhaust liquid-blocking film is provided at the gas outlet of the exhaust hole 16 and at the connection of the exhaust channel 15 and the reaction cavity 14, and the material of the exhaust liquid-blocking film is polytetrafluoroethylene.

[0042] The reaction cavity 14 is pre-loaded with reagents, or external reagents are added to the reaction cavity 14 during use.

[0043] Press the pressure cover 3. The pressure cover 3 is detachably threadedly connected to the sample part 2. An airbag is provided on the pressure cover 3, and the airbag is arranged on one side of the pressure cover 3 in the axial direction. When the airbag is pressed to deform, the solution finally flows into the reaction chamber 14 through the sample addition channel 11.

[0044] As Figure 7 shown, the liquid distribution channel 13 includes a first branch channel 131 and a second branch channel 132; one end of the first branch channel 131 is communicated with the diversion chamber 12, and the other end is closed; one end of the second branch channel 132 is connected to the reaction chamber 14, and the other end is closed; a number of thermal valves 133 are equidistantly installed on the second branch channel 132 along its track direction. Adjacent two thermal valves 133 form a quantitative section of the second branch channel 132. As Figure 9 shown, the thermal valve 133 adopts a three-way valve structure and has a first, a second, and a third end. The first and second ends of the thermal valve 133 are connected to the second branch channel 132, and the third end of the thermal valve 133 is communicated with the first branch channel 131. The second end of the thermal valve 133 is closer to the reaction chamber 14 than the first end;

[0045] The thermal valve 133 is internally provided with a bimetallic sheet 1331. The bimetallic sheet 1331 is composed of two metal sheets with different thermal expansion coefficients. When the bimetallic sheet 1331 is not heated under normal conditions, as Figure 8 shown, at this time, the bimetallic sheet 1331 closes the second end of the thermal valve 133, and the first and third ends of the thermal valve 133 communicate with each other; when the bimetallic sheet 1331 is heated, as Figure 9 shown, the bimetallic sheet 1331 deforms to close the third end of the thermal valve 133, and the second and third ends of the thermal valve 133 communicate with each other.

[0046] As Figure 3 shown, the heat transfer layer 4 includes a reaction chamber heat conduction area 41 and a plurality of independent thermal valve heat conduction areas 42. The area of the heat transfer layer 4 other than the reaction chamber heat conduction area 41 and the thermal valve heat conduction area 42 has poor heat conduction performance. The reaction chamber heat conduction areas 41 correspond to their respective reaction chambers 14 one by one. A number of thermal valve heat conduction areas 42 are independently combined and arranged along the track direction of the liquid distribution channel 13, so that one thermal valve heat conduction area 42 just aligns with one thermal valve 133.

[0047] As Figure 4 、 5 shown, the self-heating layer 5 includes a liquid area 51, a plurality of reaction chamber solid areas 52, thermal valve solid areas 53, a liquid discharge channel 54, and a partition valve 55. The reaction chamber solid areas 52 correspond to their respective reaction chambers 14 one by one. A number of thermal valve solid areas 53 are independently combined and arranged along the track direction of the liquid distribution channel 13, so that one thermal valve solid area 53 just aligns with one thermal valve 133;

[0048] Water is stored inside the liquid area 51, and calcium oxide particles with a particle size of 0.1 to 100 microns are built into the reaction chamber solid area 52 and the thermosensitive valve solid area 53 respectively.

[0049] As Figure 4 The drainage channel 54 shown by the red line and the space of the thermosensitive valve solid area 53 shown by the black line are arranged with spatial dislocation.

[0050] One end of the drainage channel 54 is connected to the liquid area 51 through a screw-type isolation valve 55, and the other end is closed; the trajectory of the liquid separation flow channel 13 is the same as that of the local drainage channel 54. A number of drainage ports 56 are arranged at equal intervals along the trajectory direction of the drainage channel 54. A set of more than one water-soluble membrane 561 is built into the drainage port 56, and a certain distance is left between two adjacent sets of water-soluble membranes 561. The water-soluble membrane 561 dissolves in water within a set time, and the dissolution speed of the water-soluble membrane 561 can be adjusted by controlling the number and thickness of the water-soluble membranes 561. The drainage ports 56 correspond to and are connected to the reaction chamber solid area 52 and the thermosensitive valve solid area 53 one by one. One drainage channel 54 corresponds to one reaction chamber solid area 52 and is matched with a number of thermosensitive valve solid areas 53. This reaction chamber solid area 52 and a number of thermosensitive valve solid areas 53 correspond to one reaction chamber 14 and its liquid separation flow channel 13.

[0051] The drainage port 56 corresponding to the reaction chamber solid area 52 is the closest to the isolation valve 55, and the number of water-soluble membranes 561 in this drainage port 56 is the least or there is no water-soluble membrane 561; the number of water-soluble membranes 561 in the drainage port 56 corresponding to the thermosensitive valve solid area 53 is more as the distance from the isolation valve 55 is farther.

[0052] Working principle:

[0053] The solution to be detected is added into the inner cavity of the sample part 2, and the pressure application cover body 3 is threadedly connected to the opening of the sample part 2. Press the airbag of the pressure application cover body 3 to push the solution through the sampling channel 11 into the shunt cavity 12, and then through the liquid separation flow channel 13 into the corresponding reaction chamber 14 and react with the reagent in the reaction chamber 14. During this process, the air flow generated by the deformation of the airbag under pressure will be discharged through the exhaust flow channel 15 and the exhaust hole 16. After sampling, the microfluidic chip is placed into the corresponding detection instrument for detection.

[0054] During this process, the solution in the shunt cavity 12 first enters the first branch flow channel 131, and then enters the quantitative sections of the second branch flow channels 132 through the third end and the first end of the thermosensitive valve 133, as Figure 7 、 8 shown by the red arrows in

[0055] During this process, the partition valve 55 is opened, and the water in the liquid area 51 flows into the liquid discharge channel 54. The water in the liquid discharge channel 54 is discharged through the liquid discharge port 56. Since the number of melting water membranes 561 of the liquid discharge port 56 corresponding to the solid area 52 of the reaction chamber is the least or there is none, the calcium oxide particles in the solid area 52 of the reaction chamber first come into contact with water and undergo an exothermic reaction, and the reaction chamber 14 is heated through the heat conduction area 41 of the reaction chamber. The heating of the reaction chamber 14 provides a specific temperature condition for the reaction.

[0056] After that, the melting water membranes 561 of the liquid discharge ports 56 closest to the solid area 52 of the reaction chamber or the reaction chamber 14 are all dissolved by water to achieve communication. The calcium oxide particles in the corresponding thermosensitive valve solid area 53 first come into contact with water and undergo an exothermic reaction, and the heat is conducted to the corresponding thermosensitive valve 133 through the corresponding thermosensitive valve heat conduction area 42. The bimetallic strip 1331 in this thermosensitive valve 133 is heated and deformed to be as Figure 9 shown, so that the solution in the subsequent corresponding quantitative section can be as Figure 9 the red arrow direction in, attached Figure 7 the green arrow in flows into the reaction chamber 14; at this time, the solution in the subsequent quantitative section is blocked by the bimetallic strip 1331 in the normal state as Figure 8 described;

[0057] After that, the melting water membranes 561 of another adjacent group of liquid discharge ports 56 are all dissolved by water to achieve communication, so that the adjacent other group of thermosensitive valves 133 change their states after a certain time interval, so as to achieve the communication between the adjacent subsequent other group of quantitative sections and the previous group of quantitative sections;

[0058] By the speed at which the melting water membranes 561 with different numbers or thicknesses in the respective liquid discharge ports 56 are dissolved in water, the times when different thermosensitive valves 133 change their states are different. Thus, the second branch channel 132 conveys a quantitative solution to the reaction chamber 14 at equal time intervals.

[0059] Embodiment 2:

[0060] It includes all the contents of Embodiment 1, the difference being that one end of the second branch channel 132 is connected to the reaction chamber 14, and the other end is connected to the shunt chamber 12 through a thermosensitive valve 133. After the thermosensitive valve 133 is heated and deformed, the communication between the shunt chamber 12 and the second branch channel 132 is achieved, and the communication between the shunt chamber 12 and the reaction chamber 14 is achieved through the second branch channel 132. The airflow generated by pressing the airbag of the pressing cover body 3 can push the solution in the second branch channel 132 into the reaction chamber 14.

[0061] Embodiment 3:

[0062] It includes all the content of Embodiment 1 or 2, with the difference that a partition valve 55 can be arranged between two adjacent liquid discharge ports 56 of the liquid discharge channel 54. Since the volume of the solution stored in the quantitative section of the second branch channel 132 is certain, the total volume of the solution entering the reaction chamber 14 can be controlled according to the number of continuously opened partition valves 55.

[0063] Embodiment 4:

[0064] It includes all the content of Embodiment 3, with the difference that first positioning holes are provided around the heat transfer layer 4, and second positioning holes are provided at the positions corresponding to the first positioning holes on the self-heating layer 5. There are multiple groups of heat transfer layers 4, and the corresponding number of heat transfer layers 4 can be selected according to requirements to form a set thickness. The clamping screw is threadedly connected to the chip body 1 through the second positioning hole and the first positioning hole.

[0065] The conduction efficiency of temperature is adjusted by controlling the thickness formed by different numbers of heat transfer layers 4.

[0066] The above embodiments only represent the specific implementation manners of the present invention. The description is relatively specific and detailed, but it should not be construed as a limitation to the scope of the patent of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the concept of the present invention, several deformations and improvements can still be made, and these all belong to the protection scope of the present invention.

Claims

1. A microfluidic chip, comprising a chip body (1). A sample addition channel (11), a flow splitting chamber (12) and a reaction chamber (14) are provided inside the chip body (1). One end of the sample addition channel (11) communicates with the flow splitting chamber (12), and the flow splitting chamber (12) communicates with the reaction chamber (14) through a liquid distribution channel (13). A heat transfer layer (4), a self-heating layer (5) and a base layer (6) are sequentially arranged on one side of the chip body (1). It is characterized in that: The liquid distribution channel (13) is divided into a number of independent quantitative segments along its track direction, and adjacent two groups of quantitative segments are connected by a thermal valve (133); The self-heating layer (5) includes a liquid area (51), a reaction chamber solid area (52), a plurality of independent thermal valve solid areas (53), a drainage channel (54) and a cut-off valve (55). The reaction chamber solid area (52) is aligned with the position of the reaction chamber (14), the thermal valve solid areas (53) are aligned with the corresponding thermal valves (133) one by one. The drainage channel (54) is connected to the liquid area (51) through the cut-off valve (55). A plurality of drainage ports (56) are provided on the drainage channel (54). The reaction chamber solid area (52) and the plurality of thermal valve solid areas (53) each align with a drainage port (56). A water melting film (561) is arranged inside the drainage port (56). The number of water melting films (561) in the drainage port (56) corresponding to the thermal valve solid area (53) is more as the distance from the cut-off valve (55) is farther; A reaction chamber heat conduction area (41) is provided at the position of the heat transfer layer (4) corresponding to the reaction chamber (14), and a plurality of independent thermal valve heat conduction areas (42) are provided at the position of the heat transfer layer (4) corresponding to the liquid distribution channel (13). The thermal valve heat conduction areas (42) correspond to the positions of the thermal valves (133) one by one; The liquid distribution channel (13) includes a first branch channel (131) and a second branch channel (132); one end of the first branch channel (131) communicates with the flow splitting chamber (12), and the other end is closed; one end of the second branch channel (132) communicates with the reaction chamber (14); the thermal valve (133) is of a three-way valve structure. The first end and the second end of the thermal valve (133) of the three-way valve structure communicate with the second branch channel (132). The part of the second branch channel (132) located between adjacent two groups of the thermal valves (133) forms a quantitative segment. The third end of the thermal valve (133) communicates with the first branch channel (131); The thermal valve (133) of the three-way valve structure is internally provided with a bimetallic sheet (1331), and the thermal valve (133) has two states; In the first state, when the bimetallic sheet (1331) is not heated, the first end and the third end of the thermal valve (133) are connected, and the second end is closed; In the second state, when the bimetallic sheet (1331) is heated, the first end and the second end of the thermal valve (133) are connected, and the third end is closed.

2. A microfluidic chip according to claim 1, characterized in that, The solid regions of the reaction chamber (52) and the thermosensitive valve (53) are filled with calcium oxide particles having a particle size of 0.1 to 100 microns; the liquid region (51) is filled with water.

3. A microfluidic chip according to claim 1, characterized in that, A sample portion (2) is provided on the chip body (1), the sample addition channel (11) communicates with the sample portion (2), and further includes a pressing cover body (3) for opening and closing the opening of the sample portion (2).

4. A microfluidic chip according to claim 3, wherein An airbag is provided on the pressing cover body (3), and an exhaust flow channel (15) is provided in the chip body (1); one end of the exhaust flow channel (15) communicates with the reaction chamber (14), and the other end is provided with an exhaust hole (16), and an exhaust liquid-blocking film is provided in the exhaust hole (16).

5. A microfluidic chip according to claim 4, characterized in that, The pressing cover body (3) is threadedly connected to the sample portion (2).

6. A microfluidic chip according to claim 1, wherein, The other end of the second branch channel (132) away from the reaction chamber (14) communicates with the shunt chamber (12), and the first end of the thermosensitive valve (133) of the three-way valve structure is located on the side close to the shunt chamber (12).

7. A microfluidic chip according to claim 6, characterized in that, The end of the second branch channel (132) is connected to the shunt chamber (12) through a group of thermosensitive valves (133), and a corresponding exhaust liquid-blocking film is provided inside the first end of the thermosensitive valve (133).

Citation Information

Patent Citations

  • Microfluidic chip for analyte detection

    CN117654653A

  • Self-heating microfluidic chip

    CN103301891A

  • Multi-flux micro-fluidic chip based on active control on liquid flowing

    CN107225006A

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