Micro-fluidic chip reagent injection device and injection method

Abstract

The application discloses a micro-fluidic chip reagent injection device, which comprises a liquid storage part with at least one quantitative sealed container, a flexible pressure-bearing membrane arranged on the top of the container body of the quantitative sealed container, a hard flow guide column arranged on the bottom of the container body, and a sealing membrane arranged on the liquid outlet; a liquid inlet part comprising a flow column and a liquid storage pool arranged on the micro-fluidic chip, the inner cavity of the flow column is matched with the outer diameter of the hard flow guide column, a gas guide channel is arranged on the contact surface of the flow column and the hard flow guide column for connecting the inner cavity of the flow column with the external environment, and a puncture part opposite to the sealing membrane is arranged on the flow column; wherein the hard flow guide column has a first plug-in position for making the puncture part puncture the sealing membrane when the hard flow guide column is pressed down. The device has the advantages of simple structure, low cost, convenient use, accurate quantitative injection and biological hazard prevention. The application also discloses a micro-fluidic chip reagent injection method.

Description

Technical Field

[0001] This invention relates to the field of microfluidic chip sample introduction technology, and in particular to a microfluidic chip reagent injection device and injection method. Background Technology

[0002] Microfluidic chips are a technology that integrates basic operational units such as sample preparation, reaction, separation, and detection in biological, chemical, and medical analysis processes onto a chip of only a few square centimeters. First, liquid is injected into the microfluidic chip. Then, through pressure-driven, electrowetting, centrifugal-driven, or capillary-driven methods, the movement of the liquid within the microfluidic chip is driven and precisely controlled, thereby enabling routine operations such as sample introduction, separation, reaction, and detection. This technology has advantages such as low reagent consumption, high sensitivity, high integration, and high detection accuracy, and has gained increasingly widespread application. Currently, liquid injection in microfluidic chips is mostly performed using pipettes, pumps and tubing, or vesicles. Pipette injection poses biological hazards, requires high operator precision and a suitable operating environment, and is also costly due to the price of pipettes. Using pumps and tubing requires additional pump and valve lines, which are complex and costly. Furthermore, a significant amount of reagent often remains in the tubing after the reaction, resulting in waste. Vesicle injection requires pressing the vesicles, but the uncontrollable deformation of the vesicles and the potential for air bubbles to be introduced lead to lower injection accuracy. Summary of the Invention

[0003] To address the problems of high cost, low accuracy, easy bubble generation, and biohazard associated with existing microfluidic chip sample injection methods, this invention provides a simple and easy-to-use microfluidic chip reagent injection device, and also provides an injection method based on the above-mentioned injection device. Specifically, the following technical solutions can be adopted:

[0004] The microfluidic chip reagent dispensing device of the present invention includes:

[0005] The liquid storage unit includes at least one quantitative sealed chamber. The top of the quantitative sealed chamber is provided with a flexible pressure-bearing membrane, and the bottom is provided with a rigid guide column. The bottom of the rigid guide column is provided with a liquid outlet, and the liquid outlet is provided with a sealing membrane.

[0006] The liquid inlet section includes a flow column and a liquid reservoir disposed on the microfluidic chip. The inner cavity of the flow column is adapted to the outer diameter of the rigid guide column. A gas guiding channel for connecting the inner cavity of the flow column with the external environment is provided on the contact surface of the flow column and the rigid guide column. A puncture element opposite to the sealing membrane is also provided on the flow column.

[0007] The rigid guide column, when pressed down, has a first insertion position that allows the piercing element to pierce the sealing film.

[0008] To form a seal and prevent biological hazards, the rigid flow guide column has a second insertion position that isolates the gas guide channel from the external environment when it is pressed down, or the liquid storage section and the liquid inlet section are connected together, that is, a sealing cover connected to the micro-flow chip is set on the outside of the quantitative sealing chamber.

[0009] The above-mentioned liquid inlet section can be configured in the following two forms:

[0010] The quantitative sealing chamber and the rigid guide column are integrated and mounted on the first main board. The flexible pressure-bearing membrane is a flat membrane that is sealed at the top opening of the quantitative sealing chamber body through the first cover plate. The pressure inside the quantitative sealing chamber can be changed by pressing the flat membrane, making operation convenient.

[0011] Alternatively, the rigid guide column is mounted on the second main board, and the flexible pressure-bearing membrane is a spherical membrane sealed at the top opening of the rigid guide column by the second cover plate. The inner cavity of the spherical membrane constitutes the chamber of the quantitative sealing chamber, and a negative pressure sealing cover connected to the second cover plate is provided on the outside of the spherical membrane. Adjustment components for changing the pressure inside the negative pressure sealing cover are provided on the second main board and the second cover plate.

[0012] The aforementioned adjusting component can be an air hole 8 opened on the second main plate and the second cover plate. A sealing membrane is provided at the bottom of the air hole 8. Correspondingly, a puncture component is provided on the second main plate. When changing the pressure inside the quantitative sealing chamber, simply press down on the second cover plate to allow the puncture component to puncture the sealing membrane, thereby connecting the negative pressure sealing cover with the atmospheric environment and thus realizing the change of pressure inside the quantitative sealing chamber.

[0013] Preferably, the air guide channel is a vertical groove formed on the flow column or rigid flow guide column.

[0014] Preferably, the puncturing element is disposed in the inner cavity of the flow column.

[0015] Preferably, a sleeve is provided on the outer side of the rigid guide column, and the inner diameter of the sleeve is adapted to the outer diameter of the flow column. This makes the assembly of the flow column and the rigid guide column more stable.

[0016] Preferably, the edge of the sealing film extends outward and connects to the sleeve.

[0017] Preferably, the puncture element is disposed on the top or outside of the flow column.

[0018] At this time, the air guide channel is a U-shaped groove that extends from the outer wall of the rigid guide column to the inner wall of the sleeve, and the end of the U-shaped groove is flush with the bottom of the sleeve.

[0019] The microfluidic chip reagent dispensing method of the present invention includes the following steps:

[0020] The first step is to place the liquid storage unit above the liquid inlet unit, aligning the rigid guide column with the flow column one by one, inserting the rigid guide column into the inner cavity of the flow column, and pressing down on the liquid storage unit. When the rigid guide column reaches the first insertion position, the piercing component will pierce the sealing film, thus achieving communication between the quantitative sealing chamber and the inner cavity of the flow column.

[0021] The second step is to apply pressure to the flexible pressure-bearing membrane. During this process, the liquid in the quantitative sealing chamber is squeezed and enters the storage tank through the flow column. Excess air in the flow column is discharged to the external environment through the air guide channel to avoid the generation of bubbles in the storage tank.

[0022] The third step is to continue pressing down on the liquid storage section until the rigid guide column reaches the second insertion position, completing the sealing operation of the quantitative sealing chamber and the microfluidic chip.

[0023] The microfluidic chip reagent injection device provided by this invention has a simple structure, low cost, and is easy to use. It adopts a quantitative sealed chamber that can accurately store liquid and is pre-encapsulated by a flexible pressure-bearing membrane to avoid biological hazards caused by reagent exposure. During the injection process, applying micro-pressure to the flexible pressure-bearing membrane seal can reduce the injection pressure and control the injection speed to achieve precise injection. Furthermore, a gas guiding channel that connects the inner cavity of the flow column to the external environment is set on the contact surface of the flow column and the rigid guide column, which can avoid the adverse phenomenon of air bubbles being generated in the microfluidic chip during injection, thereby ensuring the accuracy of microfluidic chip detection. Attached Figure Description

[0024] Figure 1 This is a schematic diagram of the structure of Example 1.

[0025] Figure 2 yes Figure 1 A schematic diagram of the assembly structure of a single quantitative sealed chamber.

[0026] Figure 3 This is a schematic diagram of the assembly structure of a single quantitative sealing chamber in Example 2.

[0027] Figure 4 This is a structural schematic diagram of Example 4.

[0028] Figure 5 yes Figure 4 A schematic diagram of the assembly structure of a single quantitative sealed chamber. Detailed Implementation

[0029] The embodiments of the present invention will be described in detail below with reference to the accompanying drawings. These embodiments are implemented based on the technical solution of the present invention, and detailed implementation methods and specific working processes are given. However, the scope of protection of the present invention is not limited to the following embodiments.

[0030] Example 1:

[0031] The microfluidic chip reagent dispensing device of the present invention comprises a liquid storage section and a liquid inlet section. For example... Figure 1 , 2 As shown, the liquid storage section includes multiple quantitative sealing chambers. Each quantitative sealing chamber consists of a chamber body 11, a flexible pressure-bearing membrane 12, and a rigid guide column 13. The chamber body 11 and the rigid guide column 13 are integrated on the first main board 2, forming a long-necked funnel shape. Depending on the required liquid volume, the chamber body 11 can be large or small, and can be designed in various shapes such as hemispherical or inverted conical. Its top opening is sealed by the flexible pressure-bearing membrane 12, and its bottom is sealed by a sealing membrane at the outlet of the rigid guide column 13. The flexible pressure-bearing membrane 12 is a planar membrane, which is bonded to the first cover plate 3 by two-color plastic bonding, mechanical force, or other bonding methods. During installation, the first cover plate 3 is simply bonded to the first main board 2. When it is necessary to change the pressure inside the quantitative sealing chamber, this can be achieved by pressing the planar membrane, which is convenient to operate.

[0032] The liquid inlet section includes a flow column 5 and a reservoir 6 disposed on the microfluidic chip 4. The inner cavity of the flow column 5 is adapted to the outer diameter of the rigid guide column 13, and the inner cavity of the flow column 5 is provided with a piercing element for breaking the seal at the bottom of the rigid guide column 13. When the flow column 5 and the rigid guide column 13 are assembled, when the rigid guide column 13 is pressed down to the first insertion position, the piercing element punctures the seal, opening the quantitative sealing chamber and the inner cavity of the flow column 5. To promptly exhaust the gas in the flow column 5, balance the gas pressure in the quantitative sealing chamber and the microfluidic chip 4, and prevent gas generation in the microfluidic chip 4 during sample injection, a gas guiding channel 7 is provided on the contact surface between the flow column 5 and the rigid guide column 13 to connect the inner cavity of the flow column 5 to the external environment. The gas guiding channel 7 is typically a vertical groove, which can be formed on the inner surface of the flow column 5 or the outer surface of the rigid guide column 13.

[0033] Based on the above-mentioned microfluidic chip reagent dispensing device, the microfluidic chip reagent dispensing method of the present invention includes the following steps:

[0034] The first step is to place the first motherboard 2 on top of the microfluidic chip 4, so that each quantitative sealing chamber corresponds to the flow column 5 on the microfluidic chip 4 one by one. The rigid guide column 13 at the bottom of the quantitative sealing chamber is inserted into the inner cavity of the corresponding flow column 5. The first motherboard 2 is pressed down. When the rigid guide column 13 reaches the first insertion position, the piercing component pierces the sealing film at the bottom of the quantitative sealing chamber, realizing the connection between the quantitative sealing chamber and the inner cavity of the flow column 5.

[0035] The second step involves gently pressing the flexible pressure-bearing membrane 12. The flexible pressure-bearing membrane 12 overcomes its elasticity, causing the liquid in the quantitative sealing chamber to be squeezed and enter the storage tank 6 through the flow column 5. Under the action of the oil phase in the microfluidic chip 4, the liquid quickly flows to the bottom surface of the microfluidic chip 4, waiting for the next operation of the microfluidic chip 4. During this process, excess air in the flow column 5 is discharged to the external environment through the air guide channel 7 to prevent the formation of bubbles in the storage tank 6.

[0036] The third step is to continue pressing down on the first main board 2 until the rigid guide column 13 reaches the second insertion position, so that the chamber of the quantitative sealing chamber is tightly pressed onto the flow column 5, the gas guide channel 7 is blocked, and the microfluidic chip 4 is sealed to avoid the influence of the external environment on the detection and to avoid the generation of biological hazards.

[0037] Example 2:

[0038] like Figure 3 As shown, the microfluidic chip reagent dispensing device of the present invention is an optimization based on Example 1. An integrated sleeve 14 is also provided on the outside of the rigid guide column 13, the inner diameter of which is adapted to the outer diameter of the flow column 5. This makes the assembly of the flow column 5 and the rigid guide column 14 more stable. At this time, the gas guiding channel 7 adopts a U-shaped groove, and each gas guiding channel 7 extends from the outer wall of the rigid guide column 13 to the inner wall of the sleeve 14, with its end flush with the bottom of the sleeve 14. The bottom sealing film of the quantitative sealing chamber not only seals the outlet of the rigid guide column 13, but its edge can also extend outward to the sleeve 14. Correspondingly, the puncture element is provided on the top or outside of the flow column 5.

[0039] The injection method of the microfluidic chip reagent injection device is the same as in Example 1.

[0040] Example 3:

[0041] The microfluidic chip reagent dispensing device of the present invention is an optimization based on Example 1. A sealing cover, connected to the microfluidic chip 4, extends downwards from the periphery of the first main board 2 to isolate the dispensing component from the external environment, preventing biological hazards. This sealing cover can replace the sealed environment created when the rigid flow guide column 13 is inserted into the flow column 5 and pressed down to the second insertion position.

[0042] Example 4:

[0043] like Figure 4 , 5As shown, the microfluidic chip reagent dispensing device of the present invention comprises a liquid storage section and a liquid inlet section. The liquid storage section includes multiple quantitative sealing chambers composed of flexible pressure-bearing membranes 12 and rigid flow guide columns 13. The rigid flow guide columns 13 are mounted on the second main board 15, and a sealing membrane is provided at the liquid outlet at the bottom of the rigid flow guide column 13. The flexible pressure-bearing membrane is a spherical membrane bonded to the second cover plate 16 by two-color plastic bonding, mechanical force, or other bonding methods. The second cover plate 16 and the second main board 15 are sealed together. Each spherical membrane is fitted over the top opening of a rigid flow guide column 13, so that the inner cavity of the spherical membrane constitutes the chamber body 11 of the quantitative sealing chamber. In addition, a negative pressure sealing cover 17 is provided on the outside of the second cover plate 16, which is in a negative pressure state when the quantitative sealing chamber is filled with liquid. In order to realize liquid dispensing, an adjustment component for changing the pressure inside the negative pressure sealing cover 17 is also provided on the second main board 15 and the second cover plate 16. Normally, the adjusting component uses air holes 8 formed on the second main plate 15 and the second cover plate 16. A sealing membrane is provided at the bottom of the air holes 8. Correspondingly, a puncture element 9 is provided on the second main plate 16. When it is necessary to change the pressure inside the quantitative sealing chamber, simply press down on the second cover plate 16 to puncture the sealing membrane with the puncture element 9. At this time, the negative pressure sealing cover 17 is connected to the atmospheric environment, thereby changing the pressure inside the quantitative sealing chamber and realizing automatic liquid injection. The structure of the remaining parts in this embodiment is the same as in embodiment 2.

[0044] Based on the above-mentioned microfluidic chip reagent dispensing device, the microfluidic chip reagent dispensing method of the present invention includes the following steps:

[0045] The first step is to place the second main board 15 above the microfluidic chip 4, so that each quantitative sealing chamber corresponds to the flow column 5 on the microfluidic chip 4 one by one. The rigid guide column 13 at the bottom of the quantitative sealing chamber is inserted into the inner cavity of the corresponding flow column 5. The second main board 15 is pressed down. When the rigid guide column 13 reaches the first insertion position, the piercing component pierces the sealing film at the bottom of the quantitative sealing chamber, realizing the connection between the quantitative sealing chamber and the inner cavity of the flow column 5. At this time, the negative pressure sealing cover 17 is still in a negative pressure state.

[0046] The second step involves pressing down on the second mainboard 15. The piercing element 9 punctures the sealing membrane at the bottom of the air hole 8 on the second mainboard. At this point, the negative pressure sealing cover 17 is connected to the atmospheric environment, and the pressure inside the quantitative sealing chamber changes from negative to positive. The flexible pressure-bearing membrane 12 overcomes its elasticity, causing the liquid inside the quantitative sealing chamber to be squeezed and enter the storage tank 6 through the flow column 5. Under the action of the oil phase inside the microfluidic chip 4, the liquid quickly flows to the bottom surface of the microfluidic chip 4, waiting for the next operation of the microfluidic chip 4. During this process, excess air in the flow column 5 is discharged to the outside environment through the air guide channel 7 to prevent the generation of bubbles in the storage tank 6.

[0047] Third, continue to press down on the second main board 15 until the rigid guide column 13 reaches the second insertion position, so that the chamber of the quantitative sealing chamber is tightly pressed onto the flow column 5, the gas guide channel 7 is blocked, and the microfluidic chip 4 is sealed to avoid the influence of the external environment on the detection and to avoid the generation of biological hazards.

[0048] It should be noted that in the description of this invention, terms such as "front," "rear," "left," "right," "vertical," "horizontal," "inner," and "outer" indicating orientation or positional relationships are based on the orientation or positional relationships shown in the accompanying drawings. They are used only for the convenience of describing this invention and simplifying the description, and are not intended to indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this invention.

Claims

1. A microfluidic chip reagent dispensing device, characterized in that: include The liquid storage unit includes at least one quantitative sealed chamber. The top of the quantitative sealed chamber is provided with a flexible pressure-bearing membrane, and the bottom is provided with a rigid guide column. The bottom of the rigid guide column is provided with a liquid outlet, and the liquid outlet is provided with a sealing membrane. The liquid inlet section includes a flow column and a liquid reservoir disposed on the microfluidic chip. The inner cavity of the flow column is adapted to the outer diameter of the rigid guide column. A gas guiding channel for connecting the inner cavity of the flow column with the external environment is provided on the contact surface of the flow column and the rigid guide column. A puncture element opposite to the sealing membrane is also provided on the flow column. Among them, when the rigid guide column is pressed down, it has a first insertion position that allows the piercing element to pierce the sealing film; When the rigid guide column is pressed down, it also has a second insertion position that isolates the air guide channel from the external environment.

2. The microfluidic chip reagent dispensing device according to claim 1, characterized in that: The quantitative sealing chamber body and rigid guide column are integrated on the first main board, and the flexible pressure-bearing membrane is a planar membrane that is sealed at the top opening of the quantitative sealing chamber body through the first cover plate.

3. The microfluidic chip reagent dispensing device according to claim 1, characterized in that: The rigid guide column is mounted on the second main board. The flexible pressure-bearing membrane is a spherical membrane that is sealed at the top opening of the rigid guide column by the second cover plate. The inner cavity of the spherical membrane constitutes the chamber of the quantitative sealing chamber. A negative pressure sealing cover connected to the second cover plate is provided on the outside of the spherical membrane. Adjustment components for changing the pressure inside the negative pressure sealing cover are provided on the second main board and the second cover plate.

4. The microfluidic chip reagent dispensing device according to claim 1, characterized in that: The air guide channel is a vertical groove formed on the flow column or rigid flow guide column, and the puncturing element is set in the inner cavity of the flow column.

5. The microfluidic chip reagent dispensing device according to claim 1, characterized in that: The rigid guide column is provided with a sleeve on its outer side, and the inner diameter of the sleeve is adapted to the outer diameter of the flow column.

6. The microfluidic chip reagent dispensing device according to claim 5, characterized in that: The edge of the sealing film extends outward and connects to the sleeve.

7. The microfluidic chip reagent dispensing device according to claim 6, characterized in that: The puncturing element is located on the top or outside of the flow column.

8. The microfluidic chip reagent dispensing device according to claim 5, characterized in that: The air guide channel is a U-shaped groove that extends from the outer wall of the rigid guide column to the inner wall of the sleeve, and the end of the U-shaped groove is flush with the bottom of the sleeve.

9. The liquid injection method of the microfluidic chip reagent injection device according to any one of claims 1-8, characterized in that, Includes the following steps: The first step is to place the liquid storage unit above the liquid inlet unit, aligning the rigid guide column with the flow column one by one, inserting the rigid guide column into the inner cavity of the flow column, and pressing down on the liquid storage unit. When the rigid guide column reaches the first insertion position, the piercing component will pierce the sealing film, thus achieving communication between the quantitative sealing chamber and the inner cavity of the flow column. The second step is to apply pressure to the flexible pressure-bearing membrane. During this process, the liquid in the quantitative sealing chamber is squeezed and enters the storage tank through the flow column. Excess air in the flow column is discharged to the outside environment through the air guide channel to avoid the generation of bubbles in the storage tank. The third step is to continue pressing down on the liquid storage section until the rigid guide column reaches the second insertion position, completing the sealing operation of the quantitative sealing chamber and the microfluidic chip.

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