Flow path control system of flexible film card box

Abstract

The utility model discloses a flexible film card box flow path control system which comprises a supporting layer, a flexible film reagent bag layer and a flow path control layer, the supporting layer is provided with blade holes and magnet telescopic holes, and a heating plate and the magnet telescopic holes are embedded in the supporting layer; a circulating hole is formed in the edge of the flexible membrane reagent bag layer, the circulating hole is communicated with a plurality of groups of reaction chambers through a liquid channel, and the flexible membrane reagent bag layer is used for experimental operation; the flow path control layer is provided with a pneumatic bag, and a flow channel control valve is annularly arranged around the pneumatic bag. According to the utility model, the support layer, the flexible membrane reagent bag layer and the flow path control layer form the interlayer type flexible membrane card box, so that parameters such as flowing direction, dosage, time, sequence and the like of liquid can be accurately controlled in an experiment process, and accurate control of flowing of the liquid in the reagent card box is realized; the processes of reagent and sample loading, sample crushing, nucleic acid extraction and purification, PCR amplification, signal acquisition and analysis and the like in full-automatic PCR detection can be accurately and orderly carried out.

Description

Technical Field

[0001] The utility model relates to the technical field of molecular diagnosis, and particularly relates to a flexible film cartridge flow path control system. Background Art

[0002] Point-of-care testing (POCT) technology refers to a class of methods that perform analysis immediately at the sampling site, eliminating the complex processing procedures of specimens during laboratory testing and quickly obtaining test results. It can be applied to processes such as reagent and sample loading, fragmentation, nucleic acid extraction and purification, PCR amplification, signal acquisition and analysis in fully automated polymerase chain reaction (PCR) technology.

[0003] In point-of-care testing instruments, the reagent kits usually adopt a cartridge design. The reagents required in the experiment are stored in a lyophilized form and are obtained as the reaction solution by adding buffer during use, which facilitates the transportation and storage of reagent consumables at room temperature. During the testing process, the reagents need to flow, mix, and react in reagent bags (channels and cavities) formed by bonding flexible film materials. The flow path of the existing cartridge structure is relatively simple, unable to achieve precise control of the flow, and only one condition can be tested at a time, resulting in a long testing process and high test costs. Summary of the Utility Model

[0004] The purpose of the utility model is: to solve the above problems, the utility model provides a flexible film cartridge flow path control system.

[0005] The utility model specifically adopts the following technical solutions to achieve the above purpose, including:

[0006] A support layer, a flexible film reagent bag layer, and a flow path control layer, wherein the flexible film reagent bag layer is disposed between the support layer and the flow path control layer;

[0007] The support layer is provided with blade holes and magnet expansion and contraction holes, and a heating plate and magnet expansion and contraction holes are embedded in the support layer. The support layer is used to support the flexible film reagent bag layer;

[0008] The edge of the flexible film reagent bag layer is provided with flow holes, and the flow holes are connected to multiple reaction chambers through liquid channels. The flexible film reagent bag layer is used for experimental operations;

[0009] The flow path control layer is provided with a pneumatic bladder, and flow path control valves are arranged around the pneumatic bladder. The flow path control layer is used to control the flow path of the liquid in the flexible film reagent bag layer.

[0010] As a further description of the above technical solution, the blade holes are arranged on one side of the support layer, and the blade holes are groove-shaped holes.

[0011] As a further description of the above technical solution, the magnet expansion and contraction holes are arranged in the middle of the support layer, and the magnet expansion and contraction holes are circular or square holes.

[0012] As a further description of the above technical solution, the heating plates are arranged on the other side of the support layer, and 2-5 groups of heating plates are provided.

[0013] As a further description of the above technical solution, the flexible membrane reagent bag is formed by bonding a double-layer membrane to form a liquid channel and a reaction chamber, and magnetic beads can be selectively arranged at the bottom of the reaction chamber.

[0014] As a further description of the above technical solution, the reaction chamber includes a first chamber, a second chamber and a third chamber, and 2-5 groups of the second chambers are provided.

[0015] As a further description of the above technical solution, the second chamber includes an upper chamber and a lower chamber, and the upper chamber and the lower chamber are equally spaced.

[0016] As a further description of the above technical solution, no magnetic beads are arranged in the upper chamber, and magnetic beads are arranged in the lower chamber.

[0017] As a further description of the above technical solution, the pneumatic bladder includes a first bladder, a second bladder and a third bladder, and the third bladder is made of a light-transmitting material.

[0018] As a further description of the above technical solution, the inner contour of the pneumatic bladder fits the outer contour of the reaction chamber, and the pneumatic bladder is connected to an external air source.

[0019] The beneficial effects of the present utility model are as follows:

[0020] In the present utility model, a sandwich-type flexible membrane cartridge is formed by a support layer, a flexible membrane reagent bag layer and a flow path control layer. During the experiment, parameters such as the flow direction, dosage, time and sequence of the liquid can be accurately controlled through magnetic beads, pneumatic bladders and flow channel control valves, realizing precise control of the liquid flow in the reagent cartridge, so that the processes of loading reagents and samples, crushing samples, nucleic acid extraction and purification, PCR amplification, signal collection and analysis, etc. in the fully automated PCR detection can be carried out precisely and orderly.

[0021] To more clearly illustrate the structural features and functions of the present utility model, the present utility model will be described in detail below with reference to the drawings and specific embodiments. Description of the Drawings

[0022] Figure 1It is a schematic structural diagram of the flow path control system of the flexible film cartridge of the present utility model;

[0023] Figure 2 It is a schematic structural diagram of the support layer of the present utility model;

[0024] Figure 3 It is a schematic structural diagram of the flexible film reagent bag layer of the present utility model;

[0025] Figure 4 It is a schematic structural diagram of the flow path control layer of the present utility model.

[0026] Reference numerals:

[0027] 1. Support layer; 11. Blade hole; 12. Magnet telescopic hole; 13. Heating plate; 2. Flexible film reagent bag layer; 21. Circulation hole; 22. Liquid channel; 23. Reaction chamber; 231. First chamber; 232. Second chamber; 2321. Upper chamber; 2322. Lower chamber; 233. Third chamber; 24. Magnetic bead; 3. Flow path control layer; 31. Pneumatic bladder; 311. First bladder; 312. Second bladder; 313. Third bladder; 32. Flow path control valve. Detailed implementation manners

[0028] To make the objectives, technical solutions, and advantages of the embodiments of the present utility model clearer, the technical solutions in the embodiments of the present utility model will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present utility model.

[0029] As Figures 1-4 shown, in one embodiment, a flexible film cartridge flow path control system includes: a support layer 1, a flexible film reagent bag layer 2, and a flow path control layer 3. The flexible film reagent bag layer 2 is disposed between the support layer 1 and the flow path control layer 3, and the support layer 1 and the flow path control layer 3 assist the flexible film reagent bag layer 2 to complete the experimental process. Among them, the support layer 1 is used to support the flexible film reagent bag layer 2, the flexible film reagent bag layer 2 is used to perform experimental processes such as sample injection, cell lysis, nucleic acid extraction and purification, PCR amplification, and signal acquisition, and the flow path control layer 3 is used to control the flow path of the liquid in the membrane reagent bag layer.

[0030] Please continue to refer to Figure 2 , in this embodiment, the support layer 1 is provided with a blade hole 11 and a magnet telescopic hole 12, and the support layer 1 is embedded with a heating plate 13 and a magnet telescopic hole 12.

[0031] Among them, the blade holes 11 are provided on one side of the support layer 1. The blade holes 11 are long and narrow groove-shaped holes. In the operation of cell mechanical disruption, the blades linked to the external motor can knock on the sample disruption sac of the flexible membrane reagent bag layer 2 through the blade holes 11 at a high frequency, thereby driving the high-speed movement of the zirconia beads and squeezing the cells to achieve cell mechanical disruption.

[0032] Furthermore, the magnet telescopic holes 12 are provided in the middle of the support layer 1. The magnet telescopic holes 12 are circular or square holes. The adsorption force can be generated by the extension or retraction of the external magnet, and then the magnetic beads 24 in the flexible membrane reagent bag layer 2 can be adsorbed or released to carry out the washing and elution processes of nucleic acids, thus completing the nucleic acid purification process.

[0033] In addition, the heating plates 13 are provided on the other side of the support layer 1. There are 2 - 5 groups of heating plates 13, which are used to realize the temperature increase and decrease operations during the polymerase chain reaction (PCR) amplification process of the flexible membrane reagent bag layer 2. And multiple heating plates 13 can achieve zone heating, so as to adapt to various types of experiments such as multi-well PCR experiments, nested PCR experiments, and array PCR experiments.

[0034] Please continue to refer to Figure 3 , in this embodiment, the flexible membrane reagent bag is formed by bonding a double-layer membrane to form a liquid channel 22 and a reaction chamber 23.

[0035] Among them, a circulation hole 21 is opened at the edge of the flexible membrane reagent bag layer 2. The circulation hole 21 is connected to multiple groups of reaction chambers 23 through the liquid channel 22, and magnetic beads 24 can be optionally arranged at the bottom of the reaction chamber 23.

[0036] Furthermore, the reaction chamber 23 includes a first chamber 231, a second chamber 232, and a third chamber 233. The first chamber 231 is used for sample lysis, the second chamber 232 is used for operations such as reaction, dilution, mixing, and pre-amplification, and the third chamber 233 is used for operations such as nucleic acid target detection.

[0037] There are 2 - 5 groups of the second chambers 232. The second chamber 232 includes an upper chamber 2321 and a lower chamber 2322. The upper chamber 2321 is not provided with magnetic beads 24, and the lower chamber 2322 is provided with magnetic beads 24. The upper chamber 2321 and the lower chamber 2322 are equally spaced. Multiple groups of liquids are led out through multiple second chambers 232 to realize various sampling and analysis operations.

[0038] Please continue to refer to Figure 4, in this embodiment, the flow path control layer 3 is provided with a pneumatic bladder 31, and a flow path control valve 32 is arranged around the pneumatic bladder 31. During use, the flow path control valve 32 closes or opens the flow path by stretching and squeezing the liquid channel 22, thereby controlling the flow direction of the liquid or controlling the liquid in one or more reaction chambers 23.

[0039] Further, the pneumatic bladder 31 includes a first bladder 311, a second bladder 312, and a third bladder 313. The inner contour of the pneumatic bladder 31 is adapted to the outer contour of the reaction chamber 23, and the pneumatic bladder 31 is connected to an external air source. When the pneumatic bladder 31 is inflated, it applies pressure to the reaction chamber 23, and when the pneumatic bladder 31 is deflated, it withdraws the pressure from the reaction chamber 23, thereby realizing operations such as mixing and flowing of the liquid in the reagent bag.

[0040] In addition, the third bladder 313 is made of a light-transmitting material and can be used in conjunction with fluorescence signal collection and detection, meeting the requirements of the optical system.

[0041] This application also provides a method for controlling the flow path of a flexible membrane cartridge, and the steps include:

[0042] Liquid addition: Close the flow path control valve 32 that controls the on-off of the liquid channel 22 between the corresponding chambers, and perform the liquid injection operation through the through-hole 21, and the pneumatic bladder 31 of the corresponding reaction chamber 23 is not inflated;

[0043] Liquid transfer: When performing liquid transfer operations between the reaction chambers 23, close all the liquid channels 22 connected to the two reaction chambers 23 (except for the liquid channel 22 directly connected between the two reaction chambers 23), inflate the pneumatic bladder 31 corresponding to the outflow-side reaction chamber 23, and after the liquid is transferred to another reaction chamber 23, close the flow path control valve 32 between the two reactions;

[0044] Mixing: When performing mixing operations between the reaction chambers 23, close all the liquid channels 22 connected to the two reaction chambers 23 (except for the liquid channel 22 directly connected between the two reactions), and by alternately inflating the pneumatic bladders 31 corresponding to the two reactions, make the liquid flow back and forth between the two reaction chambers 23 to achieve liquid mixing; and when mixing the liquid, the amount of liquid to be mixed should not be too much. If the two reaction chambers 23 are filled with liquid, the liquid will not be able to continue to flow and mix or cannot be fully mixed;

[0045] Reaction: When the liquid needs to undergo a certain experiment or reaction in one or more reaction chambers 23, close the liquid channels 22 between these reaction chambers 23 and the outside, give reaction conditions (such as temperature, etc.), and maintain the corresponding reaction time; specifically, during the reaction, the reagents in different reaction chambers 23 can be mixed and then reacted, or the flowing-in liquid can react with the freeze-dried reagents pre-embedded in the reaction chamber 23 after reconstitution;

[0046] Fragmentation: Sample fragmentation includes physical fragmentation and chemical fragmentation; for physical fragmentation, the reagent bag contains pre-placed zirconia beads in the bag. The blades driven by the motor strike the sample fragmentation bag layer through the blade holes 11 of the support layer 1 at high frequency, causing the zirconia beads to move at high speed and crushing cells by extrusion; while for chemical fragmentation, chemical components such as detergents are used to destroy the cell protein structure to release nucleic acids.

[0047] Heating: The heating plate 13 embedded in the support layer 1 is controlled by a temperature control module for heating and is in close contact with the reagent bag. By raising and lowering the temperature, biological processes such as denaturation, annealing, and extension in the PCR reaction are achieved; since the liquid in the membranous reagent bag is in large-area and close contact with the heating plate 13, the heat conduction efficiency is high, the speed is fast, and the temperature control is precise, which can meet the conditions of rapid and ultra-rapid PCR reactions.

[0048] Dilution: In the nested PCR mode, the sample is pre-amplified, and the reaction solution after pre-amplification needs to be diluted 100 - 10,000 times before it can be used for the second-stage internal amplification. Liquid dilution can be achieved by squeezing most of the reaction solution into the waste liquid chamber and adding buffer for dilution; one method is to control the size and inflation volume of the pneumatic bag 31 to change the amount of liquid squeezed into the waste liquid chamber and the amount of liquid retained for the next-stage amplification; another method is to quantify the pre-amplified reaction solution through a small-volume flow hole 21 and add a large amount of buffer to complete the dilution.

[0049] Through the above technical solutions, this application forms a sandwich-type flexible membrane cartridge through the support layer 1, the flexible membrane reagent bag layer 2, and the flow path control layer 3. During the experiment, parameters such as the flow direction, dosage, time, and sequence of the liquid can be precisely controlled through the magnetic beads 24, the pneumatic bag 31, and the flow path control valve 32, realizing precise control of the liquid flow in the reagent cartridge, enabling the processes of reagent and sample loading, sample fragmentation, nucleic acid extraction and purification, PCR amplification, signal acquisition and analysis, etc. in fully automated PCR detection to proceed precisely and orderly.

[0050] The above description of the disclosed embodiments enables those skilled in the art to implement or use the present utility model. Various modifications to these embodiments will be obvious to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present utility model. Therefore, the present utility model will not be limited to these embodiments shown herein, but will conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A flexible membrane cartridge flow control system, characterized in that: include: A support layer (1), a flexible membrane reagent bag layer (2) and a flow path control layer (3), wherein the flexible membrane reagent bag layer (2) is arranged between the support layer (1) and the flow path control layer (3); The support layer (1) is provided with a blade hole (11) and a magnet telescopic hole (12), a heating plate (13) and a magnet telescopic hole (12) are embedded in the support layer (1), and the support layer (1) is used to support the flexible membrane reagent bag layer (2); The flexible membrane reagent bag layer (2) is provided with a flow hole (21) at the edge thereof, and the flow hole (21) is connected to a plurality of reaction chambers (23) through a liquid channel (22). The flexible membrane reagent bag layer (2) is used for conducting experimental operations; The flow path control layer (3) is provided with a pneumatic bag (31), and a flow path control valve (32) is arranged around the pneumatic bag (31). The flow path control layer (3) is used to control the flow path of the liquid in the membrane reagent bag layer.

2. The flexible membrane cartridge flow control system according to claim 1, characterized in that: The blade hole (11) is arranged on one side of the support layer (1), and the blade hole (11) is a slot-shaped hole.

3. The flexible membrane cartridge flow control system according to claim 1, characterized in that: The magnet telescopic hole (12) is arranged in the middle of the support layer (1), and the magnet telescopic hole (12) is a circular or square hole.

4. The flexible membrane cartridge flow control system according to claim 1, characterized in that: The heating plates (13) are arranged on the other side of the support layer (1), and 2 to 5 groups of the heating plates (13) are arranged.

5. The flexible membrane cartridge flow control system according to claim 1, characterized in that: The flexible membrane reagent bag is formed of a double-layer membrane through a bonding process to form a liquid channel (22) and a reaction chamber (23), and magnetic beads (24) are optionally arranged at the bottom of the reaction chamber (23).

6. The flexible membrane cartridge flow control system according to claim 1, characterized in that: The reaction chamber (23) comprises a first chamber (231), a second chamber (232) and a third chamber (233), and the second chamber (232) is provided with 2-5 groups.

7. The flexible membrane cartridge flow control system according to claim 6, characterized in that: The second chamber (232) includes an upper chamber (2321) and a lower chamber (2322), and the upper chamber (2321) and the lower chamber (2322) are equidistantly spaced apart.

8. The flexible membrane cartridge flow control system according to claim 7, characterized in that: The upper chamber (2321) is not provided with magnetic beads (24), and the lower chamber (2322) is provided with magnetic beads (24).

9. The flexible membrane cartridge flow control system according to claim 1, characterized in that: The pneumatic bag (31) comprises a first bag (311), a second bag (312) and a third bag (313), and the third bag (313) is made of a light-transmitting material.

10. The flexible membrane cartridge flow control system according to claim 1, characterized in that: The inner contour of the pneumatic bag (31) is adapted to the outer contour of the reaction chamber (23), and the pneumatic bag (31) is connected to an external air source.

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