Microfluidic detection chip, detection method and detection equipment

Abstract

The embodiment of the invention provides a micro-fluidic detection chip, a detection method and detection equipment, and relates to the technical field of micro-fluidic chips, the micro-fluidic detection chip comprises a micro-fluidic layer which comprises a substrate, a top sealing layer and a bottom sealing layer, the top sealing layer and the bottom sealing layer are located on the two sides of the substrate, the substrate is provided with a sample cavity, a solid reagent cavity, a plurality of liquid bag buffer cavities, a plurality of liquid reagent cavities, a reagent buffer cavity and a reaction cavity, the sample cavity is communicated with the solid reagent cavity, the plurality of liquid bag buffer cavities are independently arranged, and the plurality of liquid reagent cavities are sequentially arranged at intervals; each liquid bag buffering cavity is internally provided with the corresponding puncturing structure; the liquid bag layer is arranged on one side of the base plate, the liquid bag layer comprises a plurality of liquid bag units which are arranged at intervals and are mutually independent, each liquid bag unit is provided with a liquid bag cavity, and the liquid bag cavities of the liquid bag units are arranged opposite to the at least one puncturing structure. According to the embodiment of the invention, the detection steps can be effectively simplified, and pollution caused by mutual mixing of different reagents is prevented.

Description

Technical Field

[0001] The present application relates to the field of microfluidic chip technology, and in particular to a microfluidic detection chip, a detection method, and a detection device. Background Art

[0002] In related technologies, microfluidic chips can also be called chip labs ( Microfluidic chip technology offers advantages such as low sample volume, rapid analysis speed, ease of fabrication into portable instruments, and suitability for immediate, on-site analysis. It has been widely used in fields such as biology, chemistry, and medicine. Microfluidic chips, combined with in vitro diagnostic reagents and technologies, have led to the development of numerous rapid detection technologies, including microfluidic-based immunocolloidal gold detection, immunofluorescence, chemiluminescence, and microfluidic-based nucleic acid detection.

[0003] Problems faced by existing nucleic acid detection technologies based on strict zoning of molecular laboratories:

[0004] 1. Complex procedures and time-consuming operations. Existing nucleic acid amplification technologies (such as PCR (polymerase chain reaction), fluorescent PCR, isothermal amplification, etc.) have complex procedures involving sample processing, nucleic acid extraction, solution preparation, amplification, and detection. These numerous steps make the test highly dependent on manual intervention, and the test process often takes 4-6 hours or even longer to complete the sample test.

[0005] 2. The degree of automation of the test is low and the requirements for personnel are high. The general process of nucleic acid testing mainly involves sample collection, sample processing, nucleic acid extraction, reaction reagent preparation and PCR amplification detection, etc. Each step is based on the operation of the tester. Some laboratories use automated nucleic acid extraction equipment to replace manual labor, but it can often only realize the automation of part of the test process, and cannot realize the full automation of the process. Therefore, it places high requirements on the operator's operating level;

[0006] 3. High requirements for the operating environment, and a professional molecular diagnostic laboratory is needed. Currently, most nucleic acid detection experiments need to be carried out in a laboratory, and more than one laboratory is required. The nucleic acid detection method is highly sensitive, and thus it is prone to aerosol contamination, resulting in false positive results. Therefore, most laboratories adopt a partitioned design, such as reagent preparation rooms, sample processing rooms, amplification rooms, product analysis rooms, etc. The air pressure in different areas is different, and operators complete the corresponding operation process in different functional areas, and need to strictly abide by the flow of people and logistics in the molecular diagnostic laboratory to prevent aerosol contamination;

[0007] 4. Existing molecular laboratories occupy a large area and require expensive testing equipment. They usually require specialized equipment such as nucleic acid extraction equipment, PCR amplification testing equipment, and biosafety cabinets. Personnel must undergo training before they can take up their posts. The high demand for personnel, space, and funds limits their promotion and use in primary medical institutions.

[0008] 5. Existing nucleic acid detection reagents are mostly stored in liquid form and need to be stored at low temperatures in cold chain transport machines. The storage conditions are strict and the cost is high. When using, the frozen reagents need to be thawed, and then packaged, prepared, and tested on the machine. This operation process is cumbersome, and repeated freezing and thawing of the reagents can easily have an adverse effect on the stability of the reagents. In addition, the reagent packaging process is carried out in an open environment and is easily contaminated by potential external pollutants, thereby affecting the accuracy of the experimental results.

[0009] 6. Prone to aerosol contamination and low biosafety. Although the nucleic acid testing process is carried out in a professional molecular diagnostic laboratory, since the interior of a single laboratory is still an open space, when multiple samples are processed simultaneously, aerosols are still inevitable. With the accumulation of aerosols in different rooms and the flow of people, contamination risks are inevitable over time.

[0010] Furthermore, traditional laboratory testing requires accumulating samples and processing them together before testing. Consequently, immediate testing is impossible, the process is time-consuming, and sample turnaround times are long. Patients must wait for test results, resulting in a poor patient experience. Furthermore, test results cannot be quickly provided to medical staff, hindering rapid diagnosis and treatment. Summary of the Invention

[0011] This application aims to solve at least one of the technical problems existing in the prior art. To this end, this application proposes a microfluidic detection chip, detection method, and detection equipment that can effectively simplify the detection steps, reduce the probability of contamination during the detection process, and help improve biosafety.

[0012] The embodiment of the first aspect of the present application provides a microfluidic detection chip, comprising:

[0013] The microfluidic layer includes a substrate and top and bottom sealing layers located on both sides of the substrate. The substrate is provided with a sample chamber, a solid reagent chamber, a liquid capsule buffer chamber, a liquid reagent chamber, a reagent buffer chamber, and a reaction chamber. The sample chamber is connected to the solid reagent chamber through a flow channel. There are multiple liquid capsule buffer chambers, each of which is independently arranged. There are multiple liquid reagent chambers, each of which is sequentially spaced apart, and at least one reagent buffer chamber is provided between two adjacent liquid reagent chambers.

[0014] The first liquid reagent chamber at the front end is connected to the solid reagent chamber via a flow channel, and the liquid reagent chamber at the rear end is connected to the reaction chamber via a flow channel; one of the liquid capsule buffer chambers is fluidically connected to one of the sample chamber and the first liquid reagent chamber, and except for the first liquid reagent chamber at the front end, each of the remaining liquid reagent chambers is connected to a different liquid capsule buffer chamber via a flow channel;

[0015] A puncture structure is provided in each of the liquid sac buffer cavities;

[0016] The liquid capsule layer is arranged on one side of the substrate, and the liquid capsule layer includes a plurality of liquid capsule units that are arranged at intervals and are independent of each other. The liquid capsule unit has a liquid capsule cavity, and the liquid capsule cavity of the liquid capsule unit is arranged opposite to at least one of the puncture structures.

[0017] Furthermore, the substrate is provided with a first gas docking hole and a first shut-off valve, the first gas docking hole is in fluid communication with the second liquid reagent chamber located at the front end, and the first shut-off valve is used to control the on-off of the flow channel connected to the liquid inlet end of the reaction chamber.

[0018] Furthermore, the substrate is provided with a mixing channel and a mixing chamber, one end of the mixing channel is liquid-connected to the liquid reagent chamber located at the end, the other end of the mixing channel is liquid-connected to the liquid inlet end of the mixing chamber, and the liquid outlet end of the mixing chamber is liquid-connected to the liquid inlet end of the first shut-off valve.

[0019] Furthermore, the substrate is provided with a test paper holding chamber, an air hole, a second stop valve and a third stop valve, the test paper holding chamber is liquid-connected with the liquid outlet end of the reaction chamber through a flow channel, and the air hole is fluid-connected with the liquid outlet end of the reaction chamber through a flow channel, wherein the second stop valve is used to control the on-off of the flow channel between the liquid outlet end of the reaction chamber and the air hole, and the third stop valve is used to control the on-off of the flow channel between the test paper holding chamber and the liquid outlet end of the reaction chamber.

[0020] Furthermore, the substrate is provided with a fourth stop valve, a quantitative mixing chamber and a second gas docking hole. The fourth stop valve is arranged on a flow channel connected to the liquid inlet end of the first stop valve. The quantitative mixing chamber hole of the quantitative mixing chamber is fluidically connected to the liquid outlet end of the fourth stop valve. The top of the quantitative mixing chamber is connected to the second gas docking hole through the flow channel.

[0021] Furthermore, the reaction chamber is flat, and at least one cavity is provided on the periphery of the reaction chamber.

[0022] Furthermore, the number of the reaction chamber is at least one.

[0023] Furthermore, the substrate includes a first part and a second part connected to each other, the thickness of the second part is smaller than the thickness of the first part, the reaction chamber is arranged in the second part, and the reaction chamber is arranged through the upper end surface and the lower end surface of the second part.

[0024] Furthermore, the liquid capsule unit includes a liquid capsule shell and a liquid capsule sealing membrane. The liquid capsule shell forms a liquid capsule cavity with an opening, and the liquid capsule sealing membrane is arranged on a side of the liquid capsule cavity having the opening.

[0025] An embodiment of the second aspect of the present application provides a detection method, which is applied to the microfluidic detection chip as described above, and the detection method comprises the following steps:

[0026] placing a biological sample in the sample chamber and closing the sample chamber;

[0027] squeezing the liquid capsule unit connected to the sample chamber so that the reagent in the liquid capsule unit flows into the sample chamber and mixes with the biological sample;

[0028] driving the mixed solution in the sample chamber to flow into the solid reagent chamber to redissolve the solid reagent preset in the solid reagent chamber to obtain a mixture, wherein magnetic particles are also preset in the solid reagent chamber;

[0029] Driving the mixture in the solid reagent chamber into the first liquid reagent chamber and allowing it to stand;

[0030] Controlling the first magnetic member and the second magnetic member to approach the top and / or bottom of the liquid reagent chamber, and using the first magnetic member and the second magnetic member to drive the magnetic particles in the liquid reagent chamber to pass through each of the liquid reagent chambers and the reagent buffer chamber in sequence, and finally driving the magnetic particles to move to the liquid reagent chamber at the end;

[0031] The first magnetic member maintains an adsorption state of the magnetic particles, and drives the eluted product in the liquid reagent chamber at the end into the reaction chamber to perform an amplification reaction.

[0032] An embodiment of the third aspect of the present application provides a detection device, including:

[0033] at least one pressing structure for squeezing each liquid capsule unit of the liquid capsule layer;

[0034] The magnetic assembly includes a first magnetic member and a second magnetic member that are spaced apart;

[0035] A driving device is used to drive the first magnetic member to move so that the first magnetic member moves in a direction perpendicular to the microfluidic detection chip, and the driving device is also used to drive the first magnetic member to move laterally parallel to the end face of the microfluidic detection chip; the driving device is used to drive the second magnetic member to move so that the second magnetic member moves in a direction perpendicular to the microfluidic detection chip, and the driving device is also used to drive the second magnetic member to move laterally parallel to the end face of the microfluidic detection chip.

[0036] Furthermore, the detection device includes a gas drive control structure, which is used to suck or blow air into the docking hole in the microfluidic detection chip, and the gas drive control structure is also used to control the opening and closing of the docking hole.

[0037] It can be seen from the above technical solutions that the embodiments of the present application have at least the following beneficial effects:

[0038] In the microfluidic detection chip, detection method, and detection device provided in the embodiments of the present application, when the microfluidic detection chip is in operation, different reagents are injected into each liquid reagent chamber, and the different liquid reagent chambers are separated by a reagent buffer chamber, thereby preventing contamination caused by mixing of different reagents. Magnetic particles are pre-installed in the solid reagent chamber. After the magnetic particles flow into the liquid reagent chamber, they are dragged by an external magnetic field, causing the magnetic particles to pass through the different liquid reagent chambers in sequence. This eliminates the need for complex mechanical perturbation structures and simplifies the structure of the entire microfluidic detection chip. During the nucleic acid extraction process, no other consumables (such as magnetic rod sleeves, etc.) are required, and substances already transferred to the liquid reagent chambers, such as lysis and binding solutions and cleaning solutions, do not need to be transferred across chambers. Therefore, no waste liquid is generated, and there is no need to provide a waste liquid chamber on the microfluidic chip. The dead volume during the nucleic acid extraction process is reduced, and the purity of the nucleic acid elution product is high. In addition, the detection chip is pre-loaded with the required reaction reagents in the form of a liquid capsule layer, eliminating the need for manual liquid preparation, simplifying the detection operation, and further reducing the probability of reagent contamination. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative labor.

[0040] Figure 1 A schematic diagram of the structure of a microfluidic detection chip provided in one embodiment of the present application;

[0041] Figure 2 A schematic diagram of the exploded structure of a microfluidic detection chip provided in one embodiment of the present application;

[0042] Figure 3 This is a schematic structural diagram of a substrate in one embodiment of the present application;

[0043] Figure 4 This is a structural schematic diagram of the front side of a substrate in one embodiment of the present application;

[0044] Figure 5 This is a structural schematic diagram of the back side of a substrate in one embodiment of the present application;

[0045] Figure 6 This is a structural schematic diagram of the front side of a substrate in another embodiment of the present application;

[0046] Figure 7 This is a structural schematic diagram of the back side of a substrate in another embodiment of the present application;

[0047] Figure 8 This is a schematic diagram of the actions of the first magnetic member and the second magnetic member in one step of an embodiment of the present application;

[0048] Figure 9 This is a schematic diagram of the actions of the first magnetic member and the second magnetic member in one step of an embodiment of the present application;

[0049] Figure 10 This is a schematic diagram of the actions of the first magnetic member and the second magnetic member in one step of an embodiment of the present application.

[0050] Reference numerals:

[0051] 1. Magnetic particles; 2. First magnetic member; 3. Second magnetic member;

[0052] 1100, substrate; 1101, sample chamber; 11011, first sample chamber hole; 11012, second sample chamber hole; 11013, third sample chamber hole; 1102, solid reagent chamber;

[0053] 1103, liquid sac buffer cavity; 11031, first liquid sac buffer cavity; 11032, second liquid sac buffer cavity; 11033, third liquid sac buffer cavity; 11034, fourth liquid sac buffer cavity; 11035, fifth liquid sac buffer cavity;

[0054] 1104, liquid reagent chamber; 11041, first reagent chamber; 11042, second reagent chamber; 11043, third reagent chamber; 11044, fourth reagent chamber; 11045, fifth reagent chamber;

[0055] 1105, reagent buffer chamber; 11051, first reagent buffer chamber; 11052, second reagent buffer chamber; 11053, third reagent buffer chamber; 11054, fourth reagent buffer chamber;

[0056] 1106, reaction chamber; 1107, filtration chamber; 1108, mixing chamber; 1109, gas buffer chamber; 1110, cavity; 1111, mixing channel; 1112, first hydrophobic breathable membrane chamber; 1113, test paper receiving chamber; 1114, second hydrophobic breathable membrane chamber; 1115, quantitative mixing chamber; 11151, quantitative mixing cavity hole; 1116, third hydrophobic breathable membrane chamber; 1200, top sealing layer a; 1300, bottom sealing layer; 1400, top sealing layer b;

[0057] 200, puncture structure;

[0058] 310, liquid capsule unit; 320, liquid capsule cover; 321, through hole; 330, adhesive layer;

[0059] 410, first gas connection hole; 420, air hole; 430, second gas connection hole;

[0060] 510, first stop valve; 520, second stop valve; 530, third stop valve; 540, fourth stop valve. DETAILED DESCRIPTION

[0061] The following will be combined with the drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0062] See also Figures 1 to 5 As shown, an embodiment of the first aspect of the present application discloses a microfluidic detection chip, including a microfluidic layer, a puncture structure 200 and a liquid capsule layer.

[0063] Specifically, the microfluidic layer includes a substrate 1100 and a top sealing layer and a bottom sealing layer 1300 located on both sides of the substrate 1100. The substrate 1100 is provided with a sample chamber 1101, a solid reagent chamber 1102, a liquid capsule buffer chamber 1103, a liquid reagent chamber 1104, a reagent buffer chamber 1105 and a reaction chamber 1106. The sample chamber 1101 is fluidically connected to the solid reagent chamber 1102 through a flow channel. The liquid capsule buffer chamber 1103 has multiple, and the multiple liquid capsule buffer chambers 1103 are independently provided. There are multiple reagent chambers 1104, and the multiple liquid reagent chambers 1104 are arranged in sequence at intervals. At least one reagent buffer chamber 1105 is provided between two adjacent liquid reagent chambers 1104; a puncture structure 200 is provided in each liquid capsule buffer chamber 1103; the liquid capsule layer is provided on one side of the substrate 1100, and the liquid capsule layer includes multiple liquid capsule units 310 arranged at intervals and independent of each other. The liquid capsule unit 310 has a liquid capsule cavity, and each puncture structure 200 is opposite to the liquid capsule cavity of one of the liquid capsule units 310.

[0064] Among them, the first liquid reagent chamber 1104 located at the front end is fluidically connected to the solid reagent chamber 1102, and the liquid reagent chamber 1104 located at the end is fluidically connected to the reaction chamber 1106; one of the liquid sac buffer chambers 1103 is fluidically connected to one of the sample chamber 1101 and the first liquid reagent chamber 1104. Except for the first liquid reagent chamber 1104 located at the front end, each of the remaining liquid reagent chambers 1104 is fluidically connected to a different liquid sac buffer chamber 1103 through a flow channel.

[0065] It is worth understanding that the multiple liquid reagent chambers 1104 are connected in sequence, and one end of the multiple liquid reagent chambers 1104 that is directly fluidically connected to the solid reagent chamber 1102 is the front end, and the other end is the end end.

[0066] In the microfluidic detection chip of the embodiment of the present application, the number of the liquid reagent chambers 1104 is set to be no less than 3.

[0067] In this embodiment, see Figure 4 The liquid reagent chambers 1104 have five components, namely the first reagent chamber 11041, the second reagent chamber 11042, the third reagent chamber 11043, the fourth reagent chamber 11044, and the fifth reagent chamber 11045. The first reagent chamber 11041 is in fluid communication with the solid reagent chamber 1102 via a flow channel and is the first liquid reagent chamber 1104 at the front end. The fifth reagent chamber 11045 is in fluid communication with the reaction chamber 1106 and is the liquid reagent chamber 1104 at the rear end.

[0068] In one embodiment of the present application, the sample chamber 1101 is used to place biological samples; the solid sample chamber 1101 is used to place magnetic particles 1, digestive enzymes (including but not limited to proteinase K, lysozyme, wall-breaking enzymes, etc.), internal controls, etc.; the various liquid sac cavities of the liquid sac layer are used to pre-store various reagents required for detection, such as lysis binding solution, cleaning solution, eluent, etc.; the reaction chamber 1106 is pre-stored with amplification reagents, etc.

[0069] During operation, a biological sample is placed in the sample chamber 1101, and the cover of the sample chamber 1101 is closed; the liquid capsule unit 310 connected to the sample chamber 1101 is squeezed so that the reagent in the liquid capsule cavity of the liquid capsule unit 310 flows into the sample chamber 1101 and mixes with the biological sample; the mixed solution in the sample chamber 1101 is driven to flow into the solid reagent chamber 1102 to redissolve the substance preset in the solid reagent chamber 1102 to obtain a mixture; the mixture in the solid reagent chamber 1102 is driven to enter the first liquid reagent chamber 1104 and stand for a certain period of time; the first magnetic member 2 is controlled to be close to the liquid reagent chamber 1104. Near the top of the liquid reagent chamber 1104, control the second magnetic component 3 to be close to the bottom of the liquid reagent chamber 1104, and through the coordinated action of the first magnetic component 2 and the second magnetic component 3, drive the magnetic particles 1 in the reagent chamber to pass through each liquid reagent chamber 1104 and the reagent buffer chamber 1105 in turn, and drive the magnetic particles 1 to finally move to the liquid reagent chamber 1104 at the end; maintain the adsorption state of the first magnetic component 2 and / or the second magnetic component 3 on the magnetic particles 1, and drive the elution product in the liquid reagent chamber 1104 at the end into the reaction chamber 1106 to perform an amplification reaction.

[0070] When the microfluidic detection chip is working, different reagents are injected into each liquid reagent chamber 1104, and different liquid reagent chambers 1104 are separated by reagent buffer chambers 1105 to prevent contamination caused by mixing of different reagents; magnetic particles 1 are preset in the solid reagent chamber 1102. After the magnetic particles 1 flow into the liquid reagent chamber 1104, the magnetic particles 1 are dragged by an external magnetic field so that the magnetic particles 1 pass through different liquid reagent chambers 1104 in sequence. After passing through the reagent solutions of different liquid reagent chambers 1104 in sequence, the magnetic particles 1 can Complete nucleic acid extraction; during the nucleic acid extraction process, no other consumables (such as magnetic rod sleeves, etc.) are required, and the lysis binding solution, cleaning solution, etc. that have been transferred to the liquid reagent chamber 1104 do not need to be transferred across chambers, so no waste liquid is generated, and there is no need to set up a waste liquid chamber on the microfluidic chip. The dead volume in the nucleic acid extraction process is small, the purity of the nucleic acid elution product is high, and the structure of the entire microfluidic detection chip is simple; in addition, the reagents required for the reaction are pre-installed on the detection chip in the form of a liquid capsule layer and a dry reagent, and there is no need for manual liquid preparation, which can simplify the detection operation and further reduce the probability of reagent contamination.

[0071] In some embodiments of this application, see Figure 4The substrate 1100 is provided with a first gas docking hole 410 and a first stop valve 510. The first gas docking hole 410 is fluidically connected to the second liquid reagent chamber 1104 located at the front end. The first stop valve 510 is used to control the on-off of the flow channel connected to the liquid inlet end of the reaction chamber 1106.

[0072] It is worth mentioning that in the scheme where the first gas docking hole 410 is fluidically connected to the second liquid reagent chamber 1104 located at the front end, the first gas docking hole 410 and the second liquid reagent chamber 1104 can be directly fluidically connected, or can be indirectly connected through other flow channels or reagent buffer chambers.

[0073] In a possible implementation, the first gas docking hole 410 is connected to the first reagent buffer chamber 11051 through an air channel, and then connected to other liquid reagent chambers 1104 through a drag channel. The other liquid reagent chambers 1104 include the first reagent chamber 11041 to the fifth reagent chamber 11045.

[0074] Of course, in some other embodiments, the first gas docking hole 410 can also be directly connected to any one of the liquid reagent chamber 1104 and the reagent buffer chamber 1105 through a gas channel, and connected to each other liquid reagent chamber 1104 and reagent buffer chamber 1105 through a drag channel, which is not limited here.

[0075] In practical applications, the gas pressure in each liquid reagent chamber 1104 can be controlled by the first gas docking hole 410 and the first stop valve 510 .

[0076] For example, in one possible application scenario, a gas drive structure within a detection device corresponding to the microfluidic detection chip is docked with the first gas docking port 410, and a valve control structure within the detection device simultaneously controls the first shut-off valve 510 to close the first shut-off valve 510. Subsequently, the gas control structure within the detection device extracts a certain volume of gas from the first gas docking port 410, causing a negative pressure state within the liquid reagent chamber 1104. Under this negative pressure, the mixture within the sample chamber 1101 can be transferred to the first liquid reagent chamber 1104, i.e., the first reagent chamber 11041. At this point, a portion of the space within the chip, such as the liquid reagent chamber 1104, is under negative pressure.

[0077] In some embodiments of this application, see Figure 3 and Figure 4The substrate 1100 is provided with a mixing channel 1111 and a mixing chamber 1108. One end of the mixing channel 1111 is in liquid communication with the liquid reagent chamber 1104 at the end, and the other end of the mixing channel 1111 is in liquid communication with the liquid inlet of the mixing chamber 1108. The liquid outlet of the mixing chamber 1108 is in liquid communication with the liquid inlet of the first shut-off valve 510. After the eluted product in the liquid reagent chamber 1104 at the end leaves the liquid reagent chamber 1104, it passes through the mixing channel 1111 and the mixing chamber 1108 in sequence, and then enters the reaction chamber 1106. The eluted product is mixed while passing through the mixing channel 1111 and then remixed in the mixing chamber 1108.

[0078] In one possible implementation, see Figure 3 and Figure 4 As shown, the direction of the mixing channel 1111 is tortuous, which is conducive to further mixing the elution product.

[0079] In some embodiments of this application, see Figure 4 and Figure 5 The substrate 1100 is provided with a test paper holding chamber 1113, an air hole 420, a second stop valve 520 and a third stop valve 530. The test paper holding chamber 1113 is liquid-connected to the liquid outlet end of the reaction chamber 1106 through a flow channel, and the air hole 420 is fluid-connected to the liquid outlet end of the reaction chamber 1106 through a flow channel. The second stop valve 520 is used to control the flow channel between the liquid outlet end of the reaction chamber 1106 and the air hole 420. The third stop valve 530 is used to control the flow channel between the test paper holding chamber 1113 and the liquid outlet end of the reaction chamber 1106.

[0080] Specifically, when it is necessary to discharge the gas in the reaction chamber 1106, the second stop valve 520 is controlled to open, and the third stop valve 530 is controlled to close at the same time, so that the gas in the reaction chamber 1106 can be discharged from the air hole 420; when it is necessary to make the amplification product in the reaction chamber 1106 flow to the test paper holding chamber 1113, the second stop valve 520 is controlled to close, and the third stop valve 530 is controlled to open at the same time, so that the amplification product in the reaction chamber 1106 can flow to the test paper holding chamber 1113 and contact with the chromatography membrane strip arranged in the test paper holding chamber 1113, so that the amplification product can be detected using the chromatography membrane strip.

[0081] In some embodiments of this application, see Figure 6 and Figure 7As shown, the substrate 1100 is provided with a fourth stop valve 540, a quantitative mixing chamber 1115 and a second gas docking hole 430. The fourth stop valve 540 is arranged on a flow channel connected to the liquid inlet end of the first stop valve 510. The quantitative mixing chamber hole 11151 of the quantitative mixing chamber 1115 is fluidically connected to the liquid outlet end of the fourth stop valve 540. The top of the quantitative mixing chamber 1115 is connected to the second gas docking hole 430 through the flow channel.

[0082] In one possible implementation, see Figure 6 and Figure 7 The liquid inlet end of the fourth stop valve 540 is fluidically connected to the liquid outlet end of the mixing chamber 1108 through a flow channel, and the liquid outlet end of the fourth stop valve 540 is fluidically connected to the liquid inlet end of the first stop valve 510 through another flow channel, wherein the quantitative mixing cavity hole 11151 is connected to the flow channel between the liquid outlet end of the fourth stop valve 540 and the liquid inlet end of the first stop valve 510; a third hydrophobic breathable membrane cavity 1116 is provided on the flow channel connecting the quantitative mixing cavity 1115 and the second gas docking hole 430.

[0083] In actual application, the fourth stop valve 540 is opened and the first stop valve 510 is closed; the gas drive control structure in the detection equipment is used to dock with the second gas docking hole 430, and a certain amount of air is sucked / aspirated into the detection chip, which can push the nucleic acid elution product in the liquid reagent chamber 1104 at the end through the mixing channel 1111, the mixing chamber 1108, the fourth stop valve 540 in sequence, and enter the quantitative mixing chamber 1115 through the quantitative mixing chamber hole 11151 to redissolve the dry amplification reagent placed inside the quantitative mixing chamber 1115. At the same time, the gas in the quantitative mixing chamber 1115 can be discharged from the second gas docking hole 430 through the flow channel and the hydrophobic breathable membrane in the third hydrophobic breathable membrane chamber 1116. Subsequently, the fourth stop valve 540 is closed, the first stop valve 510 and the second stop valve 520 are opened, and the third stop valve 530 is closed; the gas drive control structure in the detection device is docked with the second gas docking hole 430, and a certain amount of air is injected into the second gas docking hole 430 to push the redissolved amplification reagent in the quantitative mixing chamber 1115 through the quantitative mixing chamber hole 11151, the first stop valve 510 and the reaction chamber 1106 in sequence, and the amplification reagent fills the reaction chamber 1106.

[0084] It is worth mentioning that in addition to placing dry amplification reagents in the quantitative mixing chamber 1115, a small ball that can be adsorbed by a magnetic part (such as a magnet) can also be placed. Under the influence of the external magnetic part, the small ball can move up and down inside the quantitative mixing chamber 1115, and can fully mix the redissolved amplification reagents.

[0085] In some embodiments of the present application, reaction chamber 1106 is flat, and at least one cavity 1110 is disposed on the periphery of reaction chamber 1106. When the amplification reagents undergo an amplification reaction within reaction chamber 1106, the flat shape of reaction chamber 1106 can improve heat conduction efficiency, thereby improving the efficiency of the amplification reaction. Furthermore, cavity 1110 is disposed on the periphery of reaction chamber 1106, and cavity 1110 can block the heat within reaction chamber 1106 from being transferred to the outside, thereby further improving the efficiency of the amplification reaction within reaction chamber 1106.

[0086] It is worth noting that the number of cavities 1110 can be set to multiple as needed, and the shape of the cavity 1110 can be adaptively set according to the shape of the reaction chamber 1106. For example, the shape of the cavity 1110 is arc-shaped, and the arc-shaped cavity 1110 is arranged around the reaction chamber 1106.

[0087] In some embodiments of the present application, there is at least one reaction chamber 1106. In practical applications, the number of reaction chambers 1106 can be set to multiple as needed, and multiple reaction chambers 1106 can be set in series or in parallel.

[0088] In some embodiments of this application, see Figure 1 and Figure 3 Substrate 1100 includes a first portion and a second portion that are interconnected. The second portion is thinner than the first portion. Reaction chamber 1106 is disposed in the second portion and extends through both the upper and lower ends of the second portion. The upper end of the second portion is sealed by a top sealing layer, while the lower end is sealed by a bottom sealing layer 1300. Reaction chamber 1106 is defined by the top sealing layer, the walls of reaction chamber 1106, and the bottom sealing layer 1300. The reduced thickness of the top and bottom sealing layers 1300 further improves heat conduction efficiency, thereby increasing the amplification reaction rate.

[0089] It is worth mentioning that in the above embodiment, the top sealing layer includes a top sealing layer a1200 and a top sealing layer b1400, the top sealing layer a1200 cooperates with the first part, and the top sealing layer b1400 cooperates with the second part.

[0090] In some embodiments of this application, see Figure 2 The liquid capsule unit 310 includes a liquid capsule shell and a liquid capsule sealing membrane. The liquid capsule shell forms a liquid capsule cavity with an opening, and the liquid capsule sealing membrane is arranged on a side of the liquid capsule cavity with the opening.

[0091] It is worth understanding that the liquid capsule shell is made of a soft material. Thus, the puncture structure 200 can puncture the liquid capsule sealing membrane by squeezing the liquid capsule shell, and allow the reagent preset in the liquid capsule cavity to flow from the liquid capsule cavity through the liquid capsule buffer cavity 1103 and the flow channel to the sample cavity 1101 or the liquid reagent cavity 1104.

[0092] In this embodiment, please continue to refer to Figure 2 The microfluidic detection chip includes an adhesive layer 330 , which is disposed between the liquid capsule layer and the end surface of the substrate 1100 provided with the puncture structure 200 . The liquid capsule layer is fixedly connected to the substrate 1100 through the adhesive layer 330 .

[0093] Furthermore, the microfluidic detection chip also includes a sac cover 320, which is arranged around the periphery of the sac layer to prevent the sac layer from being accidentally squeezed. The sac cover 320 is connected to the substrate 1100 via a snap-fit structure. The sac cover 320 has a through hole 321 provided at the position corresponding to the sac unit 310, so that the downward pressure structure of the detection device can pass through the through hole 321 and squeeze the sac unit 310.

[0094] The embodiment of the third aspect of the present application discloses a detection device, comprising:

[0095] At least one pressing structure for respectively squeezing each sac unit 310 of the sac layer;

[0096] The magnetic assembly includes a first magnetic member 2 and a second magnetic member 3 that are spaced apart;

[0097] The driving device is used to drive the first magnetic member 2 to move so that the first magnetic member 2 moves in a direction perpendicular to the microfluidic detection chip. The driving device is also used to drive the first magnetic member 2 to move laterally parallel to the end face of the microfluidic detection chip; the driving device is used to drive the second magnetic member 3 to move so that the second magnetic member 3 moves in a direction perpendicular to the microfluidic detection chip. The driving device is also used to drive the second magnetic member 3 to move laterally parallel to the end face of the microfluidic detection chip.

[0098] In some embodiments of the present application, the detection device drives the first magnetic member 2 and the second magnetic member 3 to move synchronously through a driving device to drag the magnetic particles 1 to move between different positions of the liquid reagent chamber 1104, or to drag the magnetic particles 1 to transfer between different liquid reagent chambers 1104.

[0099] In one possible embodiment, the driving device includes a U-shaped bracket, a first magnetic part 2 is connected to one end of the U-shaped bracket, and a second magnetic part 3 is connected to the other end of the U-shaped bracket, wherein the microfluidic detection chip is located between the first magnetic part 2 and the second magnetic part 3. The driving device can drive the first magnetic part 2 and the second magnetic part 3 to move laterally synchronously by driving the U-shaped bracket to move laterally. By driving the U-shaped bracket to move along the direction of the connection between the first magnetic part 2 and the second magnetic part 3, the first magnetic part 2 can be moved away from the microfluidic detection chip while the second magnetic part 3 is brought close to the microfluidic detection chip, or the first magnetic part 2 can be brought close to the microfluidic detection chip while the second magnetic part 3 is moved away from the microfluidic detection chip. Wherein, the direction of the connection between the first magnetic part 2 and the second magnetic part 3 is perpendicular to the microfluidic detection chip.

[0100] In some other embodiments, there may be two driving devices, namely a first driving device and a second driving device, wherein the first driving device is used to drive the first magnetic member 2 to move independently, and the second driving device is used to drive the second magnetic member 3 to move independently. For example, the first driving device is used to drive the first magnetic member 2 to move so that the first magnetic member 2 moves in a direction perpendicular to the microfluidic detection chip, and the driving device is also used to drive the first magnetic member 2 to move laterally in a direction parallel to the end surface of the microfluidic detection chip, so as to drive the magnetic particles 1 to move laterally.

[0101] In one embodiment, the supporting detection equipment includes a gas drive control mechanism, which is used to suck or blow air into the gas docking hole. The gas drive control structure is also used to control the on and off of the gas docking hole so that the gas docking hole can be connected to the external atmospheric environment, thereby balancing the air pressure inside and outside the chip.

[0102] The gas docking hole may be the first gas docking hole 410 or the second gas docking hole 420 .

[0103] The following specific examples are used to describe in detail the microfluidic detection chip, detection method and detection device of the present application. It is worth noting that the following examples are merely illustrative and should not be construed as limiting the present application.

[0104] In this embodiment, see Figures 1 to 5The liquid capsule buffer chamber 1103 includes a first liquid capsule buffer chamber 11031, a second liquid capsule buffer chamber 11032, a third liquid capsule buffer chamber 11033, a fourth liquid capsule buffer chamber 11034, and a fifth liquid capsule buffer chamber 11035. The liquid reagent chamber 1104 includes a first reagent chamber 11041, a second reagent chamber 11042, a third reagent chamber 11043, a fourth reagent chamber 11044, and a fifth reagent chamber 11045. The fifth reagent chamber 11045 and the reaction chamber 1106 are sequentially connected to a mixing channel 1111 and a mixing chamber 1108. A first shut-off valve 510 is disposed between the liquid outlet of the mixing chamber 1108 and the liquid inlet of the reaction chamber 1106.

[0105] When the detection chip works in the detection equipment, its working principle is as follows:

[0106] The downward pressure structure inside the detection device squeezes the top of the liquid capsule unit 310 corresponding to the first liquid capsule buffer cavity 11031 downward through the through hole 321 on the liquid capsule cover 320, and the liquid capsule sealing membrane below the liquid capsule unit 310 is pierced by the puncture structure 200. The liquid reagent in the liquid capsule cavity can flow out of the liquid capsule cavity into the first liquid capsule buffer cavity 11031, and then flow out through the liquid outlet hole of the first liquid capsule buffer cavity 11031, and enter the sample cavity 1101 through the flow channel and the first sample cavity hole 11011; similarly, other downward pressure structures inside the detection device squeeze other liquid capsule units 310 respectively, so that the liquid reagent in the liquid capsule cavity of each liquid capsule unit 310 flows into the second reagent cavity 11042, the third reagent cavity 11043, the fourth reagent cavity 11044 and the fifth reagent cavity 11045.

[0107] The sample chamber 1101 is connected to the filter chamber 1107 through the second sample chamber hole 11012 and the flow channel. A filter membrane is provided in the filter chamber 1107. The filter membrane can be tightly attached to the bottom wall of the filter chamber 1107 through the filter membrane bonding surface. The top sealing layer a1200 is covered above the filter membrane, and there is a certain distance between the filter membrane and the top sealing layer a1200, thereby forming a cavity 1110. The filter chamber 1107 is fluidically connected to the solid reagent chamber 1102 through the filter chamber outlet flow channel.

[0108] Solid reagents can be placed in the solid reagent chamber 1102, and the solid reagents are preferably prepared by freeze-drying. The bottom of the solid reagent chamber 1102 preferably adopts a downwardly concave structure to facilitate the discharge of the reagents or magnetic particles 1 in the solid reagent chamber 1102. A solid reagent cavity hole is set in the middle of the bottom of the solid reagent chamber 1102, and the solid reagent cavity hole is at the lowest position of the bottom of the solid reagent chamber 1102;

[0109] The solid reagent cavity hole is connected to the liquid inlet hole of the first reagent cavity 11041 through a flow channel. The position of the liquid inlet hole inside the first reagent cavity 11041 can be set at the bottom position of the first reagent cavity 11041, or the liquid inlet hole can be set above the bottom position of the first reagent cavity 11041 through a columnar flow channel;

[0110] Among them, a first reagent buffer chamber 11051 is arranged between the first reagent chamber 11041 and the second reagent chamber 11042, a second reagent buffer chamber 11052 is arranged between the second reagent chamber 11042 and the third reagent chamber 11043, a third reagent buffer chamber 11053 is arranged between the third reagent chamber 11043 and the fourth reagent chamber 11044, and a fourth reagent buffer chamber 11054 is arranged between the fourth reagent chamber 11044 and the fifth reagent chamber 11045.

[0111] In the microfluidic detection chip of this embodiment, one or more reagent buffer chambers 1105 may be provided between two adjacent liquid reagent chambers 1104. Liquid overflowing from each liquid reagent chamber 1104 can enter the reagent buffer chamber 1105, thereby preventing mixing of liquid reagents in different liquid reagent chambers 1104.

[0112] Different liquid reagent chambers 1104 and reagent buffer chambers 1105 are connected through a drag channel, and the drag channel is configured as a channel structure for the magnetic particles 1 close to the top sealing layer a1200 to pass through.

[0113] The external magnetic field adsorbs the magnetic particles 1 in the liquid reagent chamber 1104 up and down, so that the magnetic particles 1 are fully mixed with the liquid reagent chamber 1104. By dragging the magnetic particles 1 laterally by the external magnetic field, the magnetic particles 1 can be transferred between different liquid reagent chambers 1104 and reagent buffer chambers 1105.

[0114] After the magnetic particles 1 are transferred to the fifth reagent chamber 11045, the eluted product in the fifth reagent chamber 11045 is fluidically connected to the mixing channel 1111 through the liquid outlet and the flow channel, the mixing channel 1111 is fluidically connected to the mixing chamber 1108, the mixing chamber 1108 is fluidically connected to the liquid inlet end of the first stop valve 510 through the flow channel, and the liquid outlet end of the first stop valve 510 is fluidically connected to the liquid inlet end of the reaction chamber 1106 through the flow channel.

[0115] Among them, the reaction chamber 1106 has a flat structure, and a number of cavities 1110 are set around it, and the cavity 1110 runs through the microfluidic layer; the upper part of the reaction chamber 1106 is covered with a top sealing layer b1400, and the lower part is covered with a bottom sealing layer 1300; the plane where the top sealing layer b1400 is located is located between the top sealing layer a1200 and the bottom sealing layer 1300.

[0116] The liquid outlet of the reaction chamber 1106 is connected to one end of another flow channel, the other end of which is provided with branch channels a and b. A second shut-off valve 520 is provided between the branch channel a and the second gas docking hole 430 .

[0117] Furthermore, a second hydrophobic breathable membrane cavity 1114 is provided between the second stop valve 520 and the air hole 420, and the second hydrophobic breathable membrane is provided in the second hydrophobic breathable membrane cavity 1114 and is tightly fitted with the surface of the bottom microfluidic layer of the second hydrophobic breathable membrane cavity 1114. In this embodiment, the hydrophobic breathable membrane used in the microfluidic detection chip allows gas to pass through, but can block the passage of liquid. A third stop valve 530 is provided between the branch channel b and the test paper holding cavity 1113. Among them, the opening side of the test paper membrane strip cavity is covered with a bottom sealing layer 1300; a number of supporting and positioning structures are provided in the test paper membrane strip cavity for placing and fixing the chromatographic membrane strip, such as 5 and Figure 7 shown.

[0118] The flow of some liquid within the microfluidic detection chip of this embodiment is driven by gas. Specifically, the first hole in the top sealing layer a1200 of the detection chip corresponds to the first gas docking hole 410. The first hole is used to dock with the gas drive structure within the detection device. External gas can pass through the first gas docking hole 410, through the first hydrophobic breathable membrane within the first hydrophobic breathable membrane cavity 1112, into the first reagent buffer chamber 1105 and the second reagent chamber 11042, and then connect to other liquid reagent chambers 1104 and reagent buffer chambers 1105 (such as the first reagent chamber 11041, the third reagent chamber 11043, the second reagent buffer chamber 11052, and the third reagent buffer chamber 11053) via the drag channel.

[0119] In addition, to buffer the internal gas pressure of the microfluidic detection chip during operation, a plurality of gas buffer chambers 1109 are provided inside the detection chip, and the gas buffer chambers 1109 are connected to each other through gas channels. Specifically, the sample chamber 1101 has a third sample cavity hole 11013, one end of which is connected to a columnar flow channel, and the end of the columnar flow channel is higher than the liquid level of the sample solution in the sample chamber 1101. In this way, the sample chamber 1101 can be fluidically connected to the gas buffer chamber 1109 through the columnar flow channel, the third sample cavity hole 11013, and the gas channel. Figure 4 shown.

[0120] The second embodiment of the present application discloses a detection method, which is applied to the microfluidic detection chip as described above, and the method comprises the following steps:

[0121] Place the biological sample in the sample chamber 1101 and close the sample chamber 1101;

[0122] Squeeze the liquid capsule unit 310 connected to the sample chamber 1101 so that the reagent in the liquid capsule unit 310 flows into the sample chamber 1101 and mixes with the biological sample to obtain a mixed solution;

[0123] Driving the mixed solution to flow toward the solid reagent chamber 1102 to redissolve the substance in the solid reagent chamber 1102 to obtain a mixture, wherein the solid reagent chamber 1102 is pre-set with magnetic particles 1;

[0124] The mixture in the solid reagent chamber 1102 is driven into the first liquid reagent chamber 1104 and allowed to stand;

[0125] The magnetic member is controlled to be close to the top and / or bottom of the liquid reagent chamber 1104, and the magnetic member is used to drive the magnetic particles 1 in the liquid reagent chamber 1104 to pass through each liquid reagent chamber 1104 and the reagent buffer chamber 1105 in sequence, and finally drive the magnetic particles 1 to move to the liquid reagent chamber 1104 at the end;

[0126] The magnetic element maintains the adsorption state of the magnetic particles 1, and drives the eluted product in the liquid reagent chamber 1104 at the end into the reaction chamber 1106 to perform an amplification reaction.

[0127] In some embodiments of the present application, gas can be repeatedly pumped into the microfluidic detection chip through the first gas docking hole 410, so that the liquid inside the first liquid reagent chamber 1104 flows back and forth between the sample chamber 1101 and the solid reagent chamber 1102 to achieve mixing; then, the microfluidic detection chip is aspirated through the first gas docking hole 410 to allow all the liquid to enter the first liquid reagent chamber 1104, and then allowed to stand.

[0128] The microfluidic chip of the embodiment of the present application can be combined with in vitro diagnostic reagents and technologies to develop a variety of rapid detection technologies, including but not limited to microfluidics-based immunocolloidal gold detection technology, immunofluorescence detection technology, chemiluminescence technology, and microfluidics-based nucleic acid detection technology.

[0129] The following describes in detail the microfluidic detection chip, detection method and detection device of the present invention with specific examples. It should be noted that the following examples are merely illustrative descriptions and should not be construed as limiting the present invention.

[0130] Example 1:

[0131] In Example 1, a chromatographic membrane strip is used to detect nucleic acid amplification products. The solid reagent chamber 1102 of the microfluidic detection chip is preloaded with freeze-dried magnetic particles 1, digestive enzymes (including but not limited to proteinase K, lysozyme, and cell wall-breaking enzymes), and internal controls. The capsule units 310 include a first capsule unit, a second capsule unit, a third capsule unit, a fourth capsule unit, and a fifth capsule unit. The first capsule unit's cysteine chamber is preloaded with a lysis and binding solution, the second capsule unit's cysteine chamber is preloaded with a wash solution 1, the third capsule unit's cysteine chamber is preloaded with a wash solution 2, the fourth capsule unit's cysteine chamber is preloaded with a wash solution 3, and the fifth capsule unit's cysteine chamber is preloaded with an eluent. Amplification reagents (PCR reagents, isothermal amplification reagents, etc.) are preloaded in a dry form (including but not limited to freeze-dried or air-dried forms) in the reaction chamber 1106. A chromatographic membrane strip for nucleic acid detection is preloaded in the test paper holding chamber 1113.

[0132] Step 1: Add a certain volume of biological sample (including but not limited to blood sample, respiratory sample, urine sample, stool sample, cell culture sample, etc.) to the sample chamber 1101 of the microfluidic detection chip. Close the cover of the sample chamber 1101 and insert the entire microfluidic detection chip into the detection device. The detection device begins to operate according to the set program.

[0133] Step 2: The downward pressure structure inside the detection device presses the first liquid capsule unit downward, and the liquid capsule sealing membrane at the bottom of the first liquid capsule unit is broken by the puncture structure 200. Under the continuous downward pressure of the downward pressure structure, the lysis and binding liquid inside is released. After the downward pressure structure is completed, the final position of the downward pressure structure is maintained. At the same time, the lysis and binding liquid passes through the liquid outlet at the bottom of the liquid capsule buffer chamber 1103 and enters the sample chamber 1101 through the flow channel. Then, the lysis and binding liquid forms a mixture with the biological sample in the sample chamber 1101. The mixture in the sample chamber 1101 flows out from the second sample chamber hole 11012 due to the positive pressure in the sample chamber 1101, and then enters the solid reagent chamber 1102 after being filtered through the filter membrane of the filter chamber 1107. The magnetic particles 1, digestive enzymes and other substances pre-loaded in the solid reagent chamber 1102 are redissolved. Then, the mixture in the solid reagent chamber 1102 flows into the first reagent chamber 11041 through the flow channel.

[0134] Step 3: At this point, the gas driving structure inside the detection device is docked with the first gas docking hole 410 on the detection chip, and the valve control structure inside the detection device controls the first stop valve 510 to be closed. At this time, the flow path between the liquid inlet end of the reaction chamber 1106 and the mixing chamber 1108 is cut off by the first stop valve 510;

[0135] Step 4: The gas control structure in the detection device draws a certain amount of gas from the first gas docking port 410, causing each liquid reagent chamber 1104 to be in a negative pressure state. Due to the pressure difference, the mixture in the sample chamber 1101 is completely transferred to the first reagent chamber 11041. At this time, some spaces inside the chip, such as the liquid reagent chamber 1104, will be in a negative pressure state.

[0136] Step 5: Maintaining negative pressure, the mixture of the biological sample, lysis and binding solution, magnetic particles 1, and digestive enzyme is allowed to incubate in the first reagent chamber 11041 for a certain period of time. The incubation process may be performed by heat incubation with the aid of equipment.

[0137] Step 6: The detection device applies an external magnetic field above the top sealing layer a1200 above the first reagent chamber 11041 and below the bottom sealing layer 1300 below the first reagent chamber 11041. The external magnetic field can be an electromagnet or a permanent magnet. In this embodiment, a permanent magnet is preferably used. The detection device moves the top magnet and the bottom magnet to positions above and below the first reagent chamber 11041.

[0138] Step 7: The top magnet moves downwardly close to the top sealing layer a1200 of the first reagent chamber 11041 to adsorb the magnetic particles 1 in the first reagent chamber 11041 until the magnetic particles 1 are adsorbed and gathered on one side of the top sealing layer located inside the first reagent chamber 11041;

[0139] Step 8: At this time, the top magnet moves upward away from the top sealing layer a1200 of the first reagent chamber 11041, and the bottom magnet moves upward toward the bottom sealing layer 1300 of the reagent chamber 1, so as to attract the magnetic particles 1 from the top sealing layer downward to the bottom of the reagent chamber 1;

[0140] Step 9: Repeat steps 7 and 8 several times;

[0141] Step 10: The bottom magnet is away from the bottom of the first reagent chamber 11041, and the top magnet is close to the top of the first reagent chamber 11041, so as to adsorb the magnetic particles 1 in the first reagent chamber 11041 to one side of the top sealing layer a located inside the first reagent chamber 11041;

[0142] Step 11: The gas control structure inside the detection device that is connected to the first gas connection hole 410 releases the negative pressure inside the chip, so that the gas pressure inside the microfluidic detection chip is consistent with the external ambient pressure and maintains a pressure balance;

[0143] Step 12: The detection device sequentially squeezes the fifth liquid capsule unit, the fourth liquid capsule unit, the third liquid capsule unit, and the second liquid capsule unit to transfer the pre-loaded eluent, cleaning solution 3, cleaning solution 2, and cleaning solution 1 therein to the fifth reagent chamber 11045, the fourth reagent chamber 11044, the third reagent chamber 11043, and the second reagent chamber 11042 through the corresponding flow channels, while maintaining the final position of each pressing structure;

[0144] Step 13: Move the top magnet laterally and the bottom magnet synchronously to transfer the magnetic particles 1 to the first reagent buffer chamber 11051 through the drag channel. Continue dragging and transfer the magnetic particles 1 to the top sealing layer a1200 above the second reagent chamber 11042 through the push-pull channel, located on one side of the second reagent chamber 11042.

[0145] Step 14: Move the bottom magnet upwards towards the bottom sealing layer 1300 below the second reagent chamber 11042 , and move the top magnet upwards away from the top sealing layer a1200 , so that the magnetic particles 1 are adsorbed to the bottom of the second reagent chamber 11042 ;

[0146] Step 15: At this time, the top magnet moves downward toward the top sealing layer a1200 of the second reagent chamber 11042, while the bottom magnet moves away from the bottom sealing layer 1300 below the second reagent chamber 11042, and the magnetic particles 1 are again adsorbed to one side of the top sealing layer a1200 above the second reagent chamber 11042, which is located inside the second reagent chamber 11042;

[0147] Step 16: Repeat steps 14 and 15 several times; the top magnet may also be moved laterally to multiple other locations of the top sealing layer a1200 above the second reagent chamber 11042, and steps 14 and 15 may be repeated several times to allow the magnetic particles 1 to be fully cleaned in different areas of the cleaning solution 2 in the second reagent chamber 11042 to remove impurities;

[0148] Step 17: Following the above method, magnetic particles 1 are sequentially dragged into the third reagent chamber 11043 (infused with cleaning solution 2) and the fourth reagent chamber 11044 (infused with cleaning solution 3) for cleaning. During this process, magnetic particles 1 pass through the third drag channel, the second reagent buffer chamber 11052, the fourth drag channel, the third reagent chamber 11043, the fifth drag channel, the third reagent buffer chamber 11053, the sixth drag channel, and the fourth reagent chamber 11044.

[0149] Step 18: Finally, magnetic particles 1 are dragged into the fifth reagent chamber 11045. The magnet is then moved up and down and laterally as described in steps 14, 15, and 16 to release the nucleic acids adsorbed on the surface of magnetic particles 1 into the elution solution, thereby obtaining a nucleic acid elution product. During the elution process, auxiliary equipment may be used to perform thermal incubation.

[0150] It is worth mentioning that the process of magnet adsorption and dragging from step 6 to step 18 is as follows: Figures 8 to 10 shown.

[0151] Step 19: Keep the magnet at the top of the fifth reagent chamber 11045 adsorbing the magnetic particles 1 in the reagent chamber, open the first stop valve 510, and close the third stop valve 530;

[0152] Step 20: The gas drive control structure in the detection device docks with the first gas docking port 410 and injects a certain amount of air into the chip, pushing the liquid nucleic acid elution product in the fifth reagent chamber 11045 through the mixing channel 1111, the mixing chamber 1108, the first shut-off valve 510, and the reaction chamber 1106, filling the reaction chamber 1106. Dry amplification reagent is pre-placed in the reaction chamber 1106.

[0153] Step 21: Close the first stop valve 510 and the second stop valve 520. With the support of the detection equipment, an amplification reaction is performed inside the reaction chamber 1106;

[0154] Step 22: After the amplification reaction is completed, the first shut-off valve 510 and the third shut-off valve 530 are opened, the gas drive control structure in the detection device is connected to the first gas docking port 410, and a certain amount of air is injected into the microfluidic detection chip, so that the amplification product in the reaction chamber 1106 enters the test paper receiving chamber 1113 through the flow channel and the third shut-off valve 530 for chromatographic detection;

[0155] Step 23: During the chromatography detection process, the third shut-off valve 530 may be closed, or a positive pressure state may be maintained in each flow channel inside the detection chip connected to the first gas docking hole 410. In the chromatography process, a corresponding heating device may be provided in the detection equipment according to the detection needs, and the test paper receiving cavity 1113 may be thermally incubated by the heating device so as to maintain a certain range of chromatography temperature in the cavity, thereby making the chromatography detection more accurate.

[0156] Step 24: After the chromatography test is completed, the internal structure of the test equipment is reset and the microfluidic test chip is removed.

[0157] Example 2:

[0158] In Example 2, amplification results were detected using real-time fluorescence. The solid reagent chamber 1102 of the microfluidic detection chip was preloaded with freeze-dried magnetic particles 1, digestive enzymes (including but not limited to proteinase K, lysozyme, and cell wall-breaking enzymes), and internal controls. The capsule units 310 included a first capsule unit, a second capsule unit, a third capsule unit, a fourth capsule unit, and a fifth capsule unit. The first capsule unit's capsule chamber was preloaded with a lysis and binding solution, the second capsule unit's capsule chamber was preloaded with a wash solution 1, the third capsule unit's capsule chamber was preloaded with a wash solution 2, the fourth capsule unit's capsule chamber was preloaded with a wash solution 3, and the fifth capsule unit's capsule chamber was preloaded with an eluent. Amplification reagents (fluorescent PCR reagents, fluorescent isothermal amplification reagents, etc.) were pre-placed in a dry form (including but not limited to freeze-dried or air-dried forms) in the reaction chamber 1106. No chromatographic membrane strips were placed in the test paper holding chamber 1113.

[0159] The specific steps of the test are as follows:

[0160] Step 1: Add a certain volume of biological sample (including but not limited to blood sample, respiratory sample, urine sample, stool sample, cell culture sample, etc.) to the sample chamber 1101 of the microfluidic detection chip. Close the cover of the sample chamber 1101, insert the microfluidic detection chip into the detection device, and the device starts to operate according to the set program.

[0161] Step 2: The downward pressure structure inside the device squeezes the first liquid capsule unit downward, and the liquid capsule sealing membrane at the bottom of the first liquid capsule unit is broken by the puncture structure 200. Under the continuous downward pressure of the downward pressure structure, the internal lysis and binding liquid is released, and the final position of the downward pressure structure is maintained. At the same time, the lysis and binding liquid passes through the liquid outlet at the bottom of the first liquid capsule buffer chamber 11031 and enters the sample chamber 1101 through the flow channel, forming a mixture with the biological sample in the sample chamber 1101. The mixture in the sample chamber 1101 flows out of the second sample chamber hole 11012 due to the positive pressure in the sample chamber 1101, and enters the solid reagent chamber 1102 after being filtered through the filter membrane of the filter chamber 1107, and redissolves the magnetic particles 1, digestive enzymes and other substances pre-loaded in the solid reagent chamber 1102. Then, the mixture in the solid reagent chamber 1102 flows into the first reagent chamber 11041.

[0162] Step 3: At this time, the gas driving structure inside the detection device is docked with the first gas docking hole 410 on the detection chip, and at the same time, the valve control structure inside the device controls the first stop valve 510 to be in a closed state;

[0163] Step 4: The gas control structure in the detection device extracts a certain amount of gas from the first gas docking port 410 of the microfluidic chip, so that the mixture in the sample chamber 1101 is completely transferred to the first reagent chamber 11041. At this time, part of the space inside the detection chip, such as the liquid reagent chamber 1104, will be in a negative pressure state.

[0164] Step 5: Maintaining negative pressure, the mixture of the biological sample, lysis and binding solution, magnetic particles 1, and digestive enzyme is allowed to incubate in the first reagent chamber 11041 for a certain period of time. The incubation process may be performed by heat incubation with the aid of equipment.

[0165] Step 6: The detection device then applies an external magnetic field above the top sealing layer a1200 above the first reagent chamber 11041 and below the bottom sealing layer 1300 below the first reagent chamber 11041. The external magnetic field can be an electromagnet or a permanent magnet, and in this embodiment, a permanent magnet is preferably used. The detection device then moves the top magnet and the bottom magnet to positions above and below the first reagent chamber 11041.

[0166] Step 7: The top magnet moves downwardly close to the top sealing layer a1200 of the first reagent chamber 11041 to adsorb the magnetic particles 1 until the magnetic particles 1 are adsorbed and gathered on one side of the top sealing layer a1200 located inside the first reagent chamber 11041;

[0167] Step 8: At this time, the top magnet moves upward away from the top sealing layer a1200 of the first reagent chamber 11041, while the bottom magnet moves upward toward the bottom sealing layer 1300 of the first reagent chamber 11041, adsorbing the magnetic particles 1 from the top sealing layer a1200 downward to the bottom of the first reagent chamber 11041;

[0168] Step 9: Repeat steps 7 and 8 several times;

[0169] Step 10: The bottom magnet is away from the bottom of the first reagent chamber 11041, and the top magnet is close to the top of the first reagent chamber 11041, so as to adsorb the magnetic particles 1 in the first reagent chamber 11041 to one side of the top sealing layer a1200 located inside the first reagent chamber 11041;

[0170] Step 11: The gas control structure inside the detection device that is connected to the first gas connection hole 410 releases the negative pressure inside the chip, so that the gas pressure inside the microfluidic detection chip is consistent with the external ambient pressure and maintains a pressure balance;

[0171] Step 12: The detection device sequentially squeezes the fifth liquid capsule unit, the fourth liquid capsule unit, the third liquid capsule unit, and the second liquid capsule unit to transfer the pre-loaded eluent, cleaning solution 3, cleaning solution 2, and cleaning solution 1 to the fifth reagent chamber 11045, the fourth reagent chamber 11044, the third reagent chamber 11043, and the second reagent chamber 11042 through the corresponding flow channels, while maintaining the final position of the downward pressure structure;

[0172] Step 13: Move the top magnet laterally and the bottom magnet synchronously to transfer the magnetic particles 1 to the first reagent buffer chamber 11051 through the drag channel 1. Continue dragging and transfer the magnetic particles 1 to the second reagent chamber 11042 through the second push-pull channel. The top sealing layer is located on one side of the second reagent chamber 11042.

[0173] Step 14: Move the bottom magnet upwards towards the bottom sealing layer 1300 below the second reagent chamber 11042 , and move the top magnet upwards away from the top sealing layer a1200 , so that the magnetic particles 1 are adsorbed to the bottom of the second reagent chamber 11042 ;

[0174] Step 15: At this time, the top magnet moves downward toward the top sealing layer a1200 of the second reagent chamber 11042, while the bottom magnet moves away from the bottom sealing layer 1300 below the second reagent chamber 11042, and the magnetic particles 1 are again adsorbed to one side of the top sealing layer a1200 above the second reagent chamber 11042, which is located inside the second reagent chamber 11042;

[0175] Step 16: Repeat steps 14 and 15 several times; the top magnet may also be moved laterally to multiple other locations of the top sealing layer a1200 above the second reagent chamber 11042, and steps 14 and 15 may be repeated several times to allow the magnetic particles 1 to be fully cleaned in different areas of the cleaning solution 2 to remove impurities;

[0176] Step 17: Following the above method, magnetic particles 1 are sequentially dragged into the third reagent chamber 11043 (infused with cleaning solution 2) and the fourth reagent chamber 11044 (infused with cleaning solution 3) for cleaning. During this process, magnetic particles 1 pass through the third drag channel, the second reagent buffer chamber 11052, the fourth drag channel, the third reagent chamber 11043, the fifth drag channel, the third reagent buffer chamber 11053, the sixth drag channel, and the fourth reagent chamber 11044.

[0177] Step 18: Finally, the magnetic particles 1 are dragged into the fifth reagent chamber 11045. Following the vertical and lateral movement of the magnet as described in steps 14, 15, and 16, the nucleic acids adsorbed on the surface of the magnetic particles 1 are released into the elution solution to obtain a nucleic acid elution product. During the elution process, auxiliary equipment may be used to perform thermal incubation. During this period, the magnetic particles 1 will successively pass through the seventh drag channel, the fourth reagent buffer chamber 11054, and then enter the fifth reagent chamber 11045.

[0178] It is worth mentioning that the process of magnet adsorption and dragging from step 6 to step 18 is referenced Figures 8 to 10 As shown;

[0179] Step 19: Keep the magnet at the top of the fifth reagent chamber 11045 adsorbing the magnetic particles 1 in the reagent chamber, open the first stop valve 510, and close the third stop valve 530;

[0180] Step 20: The gas drive control structure in the detection device docks with the first gas docking port 410 and injects a certain amount of air into the chip, pushing the liquid nucleic acid elution product in the fifth reagent chamber 11045 through the mixing channel 1111, the mixing chamber 1108, the first stop valve 510, and then into the reaction chamber 1106, filling the reaction chamber 1106. The reaction chamber 1106 is pre-filled with dry amplification reagents.

[0181] Step 21: Close the first stop valve 510 and the second stop valve 520. With the support of the detection equipment, an amplification reaction is carried out inside the reaction chamber 1106, and the detection equipment performs real-time fluorescence detection;

[0182] Step 22: After the test is completed, the internal structure of the test equipment is reset and the microfluidic test chip is removed.

[0183] Example 3:

[0184] In Example 3, see Figure 6 and Figure 7 In order to fully re-dissolve and mix the dried amplification reagent, a quantitative mixing chamber 1115 and its auxiliary structure are added to the microfluidic detection chip, which can better ensure the quantitative re-dissolution and sufficient mixing of the amplification reagent, improve the re-dissolution accuracy and reaction efficiency of the detection reagent, and the amplification reagent is re-dissolved and mixed in the quantitative mixing chamber 1115 before being injected into the reaction chamber 1106 for amplification reaction.

[0185] Please continue to see Figure 6 and Figure 7As shown, a quantitative mixing chamber 1115 and its auxiliary structures are provided on the substrate 1100. Specifically, the fifth reagent chamber 11045 is connected to the mixing flow channel 1111 through the liquid outlet and the flow channel, and the mixing flow channel 1111 is connected to the mixing chamber 1108. The liquid outlet of the mixing chamber 1108 is fluidically connected to the input end of the fourth stop valve 540 through the flow channel, and the output end of the fourth stop valve 540 is fluidically connected to the input end of the first stop valve 510 through the flow channel. At the same time, the mixing cavity hole of the quantitative mixing chamber 1115 is fluidically connected to the flow channel between the fourth stop valve 540 and the first stop valve 510. The bottom of the quantitative mixing chamber 1115 is preferably designed as a downwardly concave structure, and the quantitative mixing cavity hole 11151 is located at the lowest position of the bottom of the quantitative mixing chamber 1115. The top of the quantitative mixing chamber 1115 communicates with the third hydrophobic, breathable membrane chamber 1116 via a flow channel. This chamber is equipped with a third hydrophobic, breathable membrane that fits snugly within it. Gas within the third hydrophobic, breathable membrane chamber 1116 passes through the membrane and then connects to the second gas connection port 430 via a gas channel. Furthermore, the bottom sealing layer 1300 is provided with a hole 3 corresponding to the second gas connection port 430.

[0186] In Example 3, a chromatographic membrane strip is used to detect nucleic acid amplification products. The solid reagent chamber 1102 of the microfluidic detection chip is preloaded with freeze-dried magnetic particles 1, digestive enzymes (including but not limited to proteinase K, lysozyme, and cell-breaking enzymes), internal controls, etc. The first liquid capsule unit is preloaded with a lysis and binding solution, the second liquid capsule unit is preloaded with a cleaning solution 1, the third liquid capsule unit is preloaded with a cleaning solution 2, the fourth liquid capsule unit is preloaded with a cleaning solution 3, and the fifth liquid capsule unit is preloaded with an eluent. Amplification reagents (PCR reagents, isothermal amplification reagents, etc.) are preloaded in a dry form (including but not limited to freeze-dried, air-dried, or other dry forms) in the reaction chamber 1106. A chromatographic membrane strip for nucleic acid detection is preloaded in the test paper holding chamber 1113. After the microfluidic detection chip is added with a quantitative mixing chamber 1115 and its auxiliary structures, the detection steps are as follows:

[0187] Step 1: Add a certain volume of biological sample (including but not limited to blood sample, respiratory sample, urine sample, stool sample, cell culture sample, etc.) to the sample chamber 1101 of the microfluidic detection chip. Close the cover of the sample chamber 1101, insert the detection chip into the detection device, and the device starts to operate according to the set program.

[0188] Step 2: The downward pressure structure inside the device squeezes the first liquid capsule unit downward, and the liquid capsule sealing membrane under the first liquid capsule unit is broken by the puncture structure 200. Under the continuous downward pressure of the downward pressure structure, the internal lysis and binding liquid is released, and the final position of the downward pressure structure is maintained; at the same time, the lysis and binding liquid flows out through the liquid outlet at the bottom of the liquid capsule buffer chamber 1103 and enters the sample chamber 1101 through the flow channel, and then forms a mixture with the biological sample in the sample chamber 1101; the mixture in the sample chamber 1101 flows out from the second sample chamber hole 11012 due to the positive pressure in the sample chamber 1101, and enters the solid reagent chamber 1102 after being filtered through the filter membrane of the filter chamber 1107, and then dissolves the magnetic particles 1, digestive enzymes and other substances pre-loaded in the solid reagent chamber 1102, and then the mixture in the solid reagent chamber 1102 flows into the first reagent chamber 11041;

[0189] Step 3: At this time, the gas driving structure inside the detection device is docked with the first gas docking hole 410 on the detection chip, and at the same time, the valve control structure inside the device controls the fourth shut-off valve 540 to be in a closed state;

[0190] Step 4: The gas control structure in the detection device extracts a certain amount of gas from the first gas docking port 410 of the microfluidic chip, so that the mixture in the sample chamber 1101 is completely transferred to the first reagent chamber 11041. At this time, some spaces inside the chip, such as the liquid reagent chamber 1104, will be in a negative pressure state.

[0191] Step 5: Maintaining negative pressure, the mixture of the biological sample, lysis and binding solution, magnetic particles 1, and digestive enzyme is allowed to incubate in the first reagent chamber 11041 for a certain period of time. The incubation process may be performed by heat incubation with the aid of equipment.

[0192] Step 6: The detection device then applies an external magnetic field above the top sealing layer a1200 above the first reagent chamber 11041 and below the bottom sealing layer 1300 below the first reagent chamber 11041. The external magnetic field can be an electromagnet or a permanent magnet, and in this embodiment, a permanent magnet is preferably used. The detection device then moves the top magnet and the bottom magnet to positions above and below the first reagent chamber 11041.

[0193] Step 7: The top magnet moves downwardly close to the top sealing layer a1200 of the first reagent chamber 11041 to adsorb the magnetic particles 1 until the magnetic particles 1 are adsorbed and gathered on one side of the top sealing layer a1200 located inside the first reagent chamber 11041;

[0194] Step 8: At this time, the top magnet moves upward away from the top sealing layer a1200 of the first reagent chamber 11041, while the bottom magnet moves upward toward the bottom sealing layer 1300 of the first reagent chamber 11041, adsorbing the magnetic particles 1 from the top sealing layer downward to the bottom of the first reagent chamber 11041;

[0195] Step 9: Repeat steps 9 and 10 several times;

[0196] Step 10: The bottom magnet is away from the bottom of the first reagent chamber 11041, and the top magnet is close to the top of the first reagent chamber 11041, so as to adsorb the magnetic particles 1 in the first reagent chamber 11041 to one side of the top sealing layer a1200 located inside the first reagent chamber 11041;

[0197] Step 11: The gas control structure inside the detection device that is connected to the first gas connection hole 410 releases the negative pressure inside the chip, so that the gas pressure inside the microfluidic detection chip is consistent with the external ambient pressure and maintains a pressure balance;

[0198] Step 12: The detection device sequentially squeezes the fifth liquid capsule unit, the fourth liquid capsule unit, the third liquid capsule unit, and the second liquid capsule unit to transfer the pre-loaded eluent, cleaning solution 3, cleaning solution 2, and cleaning solution 1 therein to the fifth reagent chamber 11045, the fourth reagent chamber 11044, the third reagent chamber 11043, and the second reagent chamber 11042 through the corresponding flow channels, while maintaining the final position of the downward pressure structure;

[0199] Step 13: Move the top magnet laterally and the bottom magnet synchronously to transfer the magnetic particles 1 to the first reagent buffer chamber 11051 through the drag channel. Continue dragging and transfer the magnetic particles 1 to the top sealing layer a1200 above the second reagent chamber 11042 through the push-pull channel, located on one side of the second reagent chamber 11042.

[0200] Step 14: Move the bottom magnet upwards towards the bottom sealing layer 1300 below the second reagent chamber 11042 , and move the top magnet upwards away from the top sealing layer a1200 , so that the magnetic particles 1 are adsorbed to the bottom of the second reagent chamber 11042 ;

[0201] Step 15: At this time, the top magnet moves downward toward the top sealing layer a1200 of the second reagent chamber 11042, while the bottom magnet moves away from the bottom sealing layer 1300 below the second reagent chamber 11042, and the magnetic particles 1 are again adsorbed to one side of the top sealing layer a1200 above the second reagent chamber 11042, which is located inside the second reagent chamber 11042;

[0202] Step 16: Repeat steps 14 and 15 several times. Of course, the top magnet can also be moved laterally to multiple other locations of the top sealing layer a1200 above the second reagent chamber 11042, and steps 14 and 15 can be repeated several times to allow the magnetic particles 1 to be fully cleaned in different areas of the cleaning solution 2 to remove impurities.

[0203] Step 17: Following the above method, magnetic particles 1 are sequentially dragged into the third reagent chamber 11043 (infused with cleaning solution 2) and the fourth reagent chamber 11044 (infused with cleaning solution 3) for cleaning. During this process, magnetic particles 1 pass through the second reagent buffer chamber 11052, the third reagent chamber 11043, the third reagent buffer chamber 11053, and the fourth reagent chamber 11044.

[0204] Step 18: Finally, the magnetic particles 1 are dragged into the fifth reagent chamber 11045. Following the vertical and lateral movement of the magnet as described in steps 14, 15, and 16, the nucleic acids adsorbed on the surface of the magnetic particles 1 are released into the elution solution to obtain a nucleic acid elution product. Auxiliary equipment may also be used to perform thermal incubation during the elution process. During this time, the magnetic particles 1 will gradually pass through the fourth reagent buffer chamber 11054 and then enter the fifth reagent chamber 11045.

[0205] It is worth mentioning that the process of magnet adsorption and dragging from step 6 to step 18 is referenced Figures 8 to 10 shown.

[0206] Step 19: Keep the magnet at the top of the fifth reagent chamber 11045 adsorbing the magnetic particles 1 in the reagent chamber, open the fourth stop valve 540, and close the first stop valve 510;

[0207] Step 20: The gas drive control structure in the detection device is docked with the first gas docking hole 410 and a certain amount of air is injected into the chip, pushing the nucleic acid elution product in the fifth reagent chamber 11045 through the mixing channel 1111, the mixing chamber 1108, the fourth stop valve 540, and the quantitative mixing hole 11151 into the quantitative mixing chamber 1115 to redissolve the dried amplification reagent placed therein. The gas in the quantitative mixing chamber passes through the flow channel and the third hydrophobic breathable membrane cavity 1116, and is discharged from the second gas docking hole 430 through the gas channel. The fourth stop valve 540 is then closed.

[0208] Step 21: In addition to the amplification reagents, a small ball that can be attracted by a magnet can also be placed in the quantitative mixing chamber 1115. Under the influence of the external magnet, the ball can move up and down in the quantitative mixing chamber 1115 to fully mix the reconstituted amplification reagents.

[0209] Step 22: Keep the fourth stop valve 540 closed, open the first stop valve 510 and the second stop valve 520, and close the third stop valve 530;

[0210] Step 23: The gas drive control structure in the detection device is docked with the second gas docking hole 430 and a certain amount of air is injected therein, pushing the reconstituted amplification reagent in the quantitative mixing chamber 1115 to pass through the quantitative mixing chamber hole 11151, the flow channel, the first shut-off valve 510, and the reaction chamber 1106 in sequence, filling the reaction chamber 1106.

[0211] Step 24: Close the first stop valve 510 and the second stop valve 520. With the support of the detection equipment, an amplification reaction is performed inside the reaction chamber 1106;

[0212] Step 25: After the amplification reaction is completed, the first shut-off valve 510 and the third shut-off valve 530 are opened. The gas drive control structure in the detection device is connected to the second gas docking hole 430, and a certain amount of air is injected into the chip. The amplification product in the reaction chamber 1106 enters the test paper receiving chamber 1113 after passing through the third shut-off valve 530 for chromatographic detection.

[0213] Step 26: During the chromatography detection process, the third shut-off valve 530 may be closed, or a positive pressure state may be maintained in each flow channel inside the detection chip connected to the second gas docking hole 430. In the chromatography process, a corresponding heating device may be provided in the detection equipment according to the detection needs, and the test paper receiving cavity 1113 may be thermally incubated by the heating device so as to maintain a certain range of chromatography temperature in the cavity, thereby making the chromatography detection more accurate.

[0214] Step 27: After the chromatography test is completed, the internal structure of the detection device is reset and the microfluidic detection chip is removed.

[0215] Example 4:

[0216] In Example 4, see Figure 6 and Figure 7 , using a microfluidic detection chip with an additional quantitative mixing chamber 1115 and its auxiliary structures, and detecting amplification results using real-time fluorescence. Specifically, the solid reagent chamber 1102 of the microfluidic detection chip is preloaded with freeze-dried magnetic particles 1, digestive enzymes (including but not limited to proteinase K, lysozyme, and cell wall-breaking enzymes), internal controls, etc.; lysis and binding solution is preloaded in liquid capsule 1; cleaning solution 1 is preloaded in liquid capsule 2; cleaning solution 2 is preloaded in liquid capsule 3; cleaning solution 3 is preloaded in liquid capsule 4; and eluent is preloaded in liquid capsule 5. Amplification reagents (fluorescent PCR reagents, fluorescent isothermal amplification reagents, etc.) are pre-placed in reaction chamber 1106 in a dry form (including but not limited to freeze-dried, air-dried, or other dry forms); and no chromatography membrane strip is placed in the test paper holding chamber 1113.

[0217] Step 1: Add a certain volume of biological sample (including but not limited to blood sample, respiratory sample, urine sample, stool sample, cell culture sample, etc.) to the sample chamber 1101 of the microfluidic detection chip. Close the cover of the sample chamber 1101, insert the microfluidic detection chip into the detection device, and the device begins to operate according to the set program.

[0218] Step 2: The downward pressure structure inside the device squeezes the first liquid capsule unit downward, and the liquid capsule sealing membrane of the first liquid capsule unit is broken by the puncture structure 200. Under the continuous downward pressure of the downward pressure structure, the internal lysis and binding liquid is released, and the final position of the downward pressure structure is maintained; at the same time, the lysis and binding liquid passes through the liquid outlet at the bottom of the liquid capsule buffer chamber 1103 and enters the sample chamber 1101 through the flow channel, and then forms a mixture with the biological sample in the sample chamber 1101; the mixture in the sample chamber 1101 flows out of the sample hole due to the positive pressure in the sample chamber 1101, and then enters the solid reagent chamber 1102 after being filtered through the filter membrane, and redissolves the magnetic particles 1, digestive enzymes and other substances pre-loaded in the solid reagent chamber 1102, and then the mixture in the solid reagent chamber 1102 flows into the first reagent chamber 11041 through the flow channel;

[0219] Step 3: At this time, the gas driving structure inside the detection device is docked with the first gas docking hole 410 on the detection chip, and at the same time, the valve control structure inside the detection device controls the fourth stop valve 540 to be in a closed state;

[0220] Step 4: The gas control structure in the detection device extracts a certain amount of gas from the first gas docking port 410 to transfer the mixture inside the sample chamber 1101 to the first reagent chamber 11041. At this time, some spaces inside the chip, such as the liquid reagent chamber 1104, will be in a negative pressure state.

[0221] Step 5: Maintaining negative pressure, the mixture of the biological sample, lysis and binding solution, magnetic particles 1, and digestive enzyme is allowed to incubate in the first reagent chamber 11041 for a certain period of time. The incubation process may be performed by heat incubation with the aid of equipment.

[0222] Step 6: The detection device then applies an external magnetic field above the top sealing layer a1200 above the first reagent chamber 11041 and below the bottom sealing layer 1300 below the first reagent chamber 11041. The external magnetic field can be an electromagnet or a permanent magnet, with permanent magnets being preferred in this embodiment. The detection device then moves the top magnet and the bottom magnet to positions above and below the first reagent chamber 11041.

[0223] Step 7: The top magnet moves downwardly close to the top sealing layer a1200 of the first reagent chamber 11041 to adsorb the magnetic particles 1 until the magnetic particles 1 are adsorbed and gathered on one side of the top sealing layer a1200 located inside the first reagent chamber 11041;

[0224] Step 8: At this time, the top magnet moves upward away from the top sealing layer a1200 of the first reagent chamber 11041, and the bottom magnet moves upward toward the bottom sealing layer 1300 of the first reagent chamber 11041, so as to adsorb the magnetic particles 1 downward from the top sealing layer a1200 to the bottom of the first reagent chamber 11041;

[0225] Step 9: Repeat steps 7 and 8 several times;

[0226] Step 10: The bottom magnet is away from the bottom of the first reagent chamber 11041, and the top magnet is close to the top of the first reagent chamber 11041, so as to adsorb the magnetic particles 1 in the first reagent chamber 11041 to one side of the top sealing layer a1200 located inside the first reagent chamber 11041;

[0227] Step 11: The gas control structure inside the detection device that is connected to the first gas connection hole 410 releases the negative pressure inside the chip, so that the gas pressure inside the microfluidic detection chip is consistent with the external ambient pressure and maintains a pressure balance;

[0228] Step 12: The detection device sequentially squeezes the fifth liquid capsule unit, the fourth liquid capsule unit, the third liquid capsule unit, and the second liquid capsule unit to transfer the pre-loaded eluent, cleaning solution 3, cleaning solution 2, and cleaning solution 1 therein to the fifth reagent chamber 11045, the fourth reagent chamber 11044, the third reagent chamber 11043, and the reagent chamber 2 through the corresponding flow channels, while maintaining the final position of the downward pressure structure;

[0229] Step 13: Move the top magnet laterally and the bottom magnet synchronously to transfer the magnetic particles 1 to the first reagent buffer chamber 11051 through the drag channel 1. Continue dragging and transfer the magnetic particles 1 to the top sealing layer a1200 above the second reagent chamber 11042 through the push-pull channel, located on one side of the second reagent chamber 11042.

[0230] Step 14: Move the bottom magnet upwards towards the bottom sealing layer 1300 below the second reagent chamber 11042 , and move the top magnet upwards away from the top sealing layer a1200 , so that the magnetic particles 1 are adsorbed to the bottom of the second reagent chamber 11042 ;

[0231] Step 15: At this time, the top magnet moves downward toward the top sealing layer a1200 of the second reagent chamber 11042, while the bottom magnet moves away from the bottom sealing layer 1300 below the second reagent chamber 11042, and the magnetic particles 1 are again adsorbed to one side of the top sealing layer a1200 above the second reagent chamber 11042, which is located inside the second reagent chamber 11042;

[0232] Step 16: Repeat steps 14 and 15 several times; the top magnet may also be moved laterally to multiple other locations of the top sealing layer a1200 above the second reagent chamber 11042, and steps 14 and 15 may be repeated several times to allow the magnetic particles 1 to be fully cleaned in different areas of the cleaning solution 2 in the second reagent chamber 11042 to remove impurities;

[0233] Step 17: Following the above method, magnetic particles 1 are sequentially dragged into the third reagent chamber 11043 (infused with cleaning solution 2) and the fourth reagent chamber 11044 (infused with cleaning solution 3) for cleaning. During this process, magnetic particles 1 pass through the dragging channel, the second reagent buffer chamber 11052, the dragging channel, the third reagent chamber 11043, the dragging channel, the third reagent buffer chamber 11053, the dragging channel, and the fourth reagent chamber 11044.

[0234] Step 18: Finally, the magnetic particles 1 are dragged to the fifth reagent chamber 11045, and then the nucleic acids adsorbed on the surface of the magnetic particles 1 are released in the eluent by moving the magnet up and down and laterally as described in steps 14, 15, and 16 to obtain nucleic acid elution products.

[0235] During the elution process, auxiliary equipment can also be used for thermal incubation of the elution process. During this period, the magnetic particles 1 will successively pass through the drag channel 7, the fourth reagent buffer chamber 11054, and then enter the fifth reagent chamber 11045; the process of magnet adsorption and dragging from step 6 to step 18 is shown in FIG. Figures 8 to 10 As shown;

[0236] Step 19: Keep the magnet at the top of the fifth reagent chamber adsorbing the magnetic particles 1 in the reagent chamber, open the fourth stop valve 540, and close the first stop valve 510;

[0237] Step 20: The gas drive control structure in the detection device is docked with the first gas docking port 410 and a certain amount of air is injected into the chip, pushing the nucleic acid elution product in the fifth reagent chamber 11045 through the mixing channel 1111, the mixing chamber 1108, the fourth shut-off valve 540, and into the quantitative mixing chamber 1115 through the quantitative mixing cavity 11151, thereby redissolving the dried amplification reagent placed therein. The gas in the mixture passes through the flow channel, the hydrophobic breathable membrane, and the gas channel, and is finally discharged from the second gas docking port 430.

[0238] Step 21: In addition to the amplification reagents, a small ball that can be attracted by a magnet can also be placed in the quantitative mixing chamber 1115. Under the influence of the external magnet, the ball can move up and down in the quantitative mixing chamber 1115 to fully mix the reconstituted amplification reagents.

[0239] Step 22: Keep the fourth stop valve 540 closed, open the first stop valve 510 and the second stop valve 520, and close the third stop valve 530;

[0240] Step 23: The gas drive control structure in the detection device is docked with the second gas docking port 430 and a certain amount of air is injected therein to push the reconstituted liquid amplification reagent in the quantitative mixing chamber 1115 through the quantitative mixing chamber 11151, the first shut-off valve 510, and the reaction chamber 1106, filling the reaction chamber 1106.

[0241] Step 24: Close the first stop valve 510 and the second stop valve 520. With the support of the detection equipment, an amplification reaction is carried out inside the reaction chamber 1106; and the detection equipment performs real-time fluorescence detection;

[0242] Step 25: After the test is completed, the internal structure of the test equipment is reset and the microfluidic test chip is removed.

[0243] Microfluidic detection chip embodiment 5:

[0244] In Example 5, other dry reagents except the magnetic particles 1 can be selectively placed in the sample chamber 1101, including digestive enzymes, internal controls, and some lysis binding liquid components that can be stored in dry form. The rest of the process is basically the same as in Example 1, Example 2, Example 3, and Example 4.

[0245] Example 6:

[0246] In Example 6, a microfluidic detection chip with a quantitative mixing chamber 1115 and its auxiliary structures is used, such as Figure 6 and Figure 7 The nucleic acid elution product in the fifth reagent chamber 11045 can be transferred to the quantitative mixing chamber 1115 through the following process, and then further transferred to the reaction chamber 1106 after redissolution and mixing. The specific steps are as follows:

[0247] Step 1: Open the fourth stop valve 540 and close the first stop valve 510;

[0248] Step 2: The gas driving control structure in the detection device is used to open the first gas connection hole 410 (i.e., the first gas connection hole 410 is connected to the external atmospheric environment of the chip);

[0249] Step 3: The gas-driven control structure in the detection device docks with the second gas docking port 430 and draws a certain amount of gas from the chip, causing the nucleic acid elution product in the fifth reagent chamber 11045 to pass through the liquid outlet, the flow channel, the mixing flow channel 1111, the mixing chamber, the fourth shut-off valve 540, and the quantitative mixing chamber hole 11151 into the quantitative mixing chamber 1115, thereby redissolving and mixing the dried amplification reagent placed therein;

[0250] Step 4: Close the fourth stop valve 540 and the third stop valve 530, and open the first stop valve 510 and the second stop valve 520;

[0251] Step 5: Through the gas-driven control structure in the detection device, dock with the gas docking hole 2 and inject a certain amount of air into it to push the re-dissolved liquid amplification reagent in the quantitative mixing chamber 1115, which passes through the quantitative mixing chamber hole 11151, the flow channel, the first stop valve 510, and then enters the reaction chamber 1106.

[0252] Example 7:

[0253] In Example 7, a microfluidic detection chip with a quantitative mixing chamber 1115 and its auxiliary structures is used, such as Figure 6 and Figure 7 The nucleic acid elution product in the fifth reagent chamber 11045 can be transferred to the quantitative mixing chamber 1115 through the following process, and then further transferred to the reaction chamber 1106 after redissolution and mixing. The specific steps are as follows:

[0254] Step 1: Open the fourth stop valve 540 and close the first stop valve 510;

[0255] Step 2: The gas-driven control structure in the detection device is used to open the first gas connection hole 410 (i.e., the first gas connection hole is in communication with the external atmosphere of the chip 410);

[0256] Step 3: The gas drive control structure in the detection device is connected to the second gas docking port 430, and a certain amount of gas is drawn from the chip. This allows the nucleic acid elution product in the fifth reagent chamber 11045 to pass through the liquid outlet, the flow channel, the mixing flow channel 1111, the mixing chamber, the fourth shut-off valve 540, and the quantitative mixing chamber hole 11151 into the quantitative mixing chamber 1115, thereby redissolving and mixing the dried amplification reagent placed therein.

[0257] Step 4: Close the fourth stop valve 540 and the third stop valve 530, and open the first stop valve 510 and the second stop valve 520;

[0258] Step 5: The gas driving control structure in the detection device is used to open the second gas connection hole 430 (i.e., the second gas connection hole 430 is in communication with the atmosphere outside the chip);

[0259] Step 6: The gas-driven control structure in the detection device docks with the air hole 420 and absorbs a certain amount of gas from the chip, so that the liquid in the quantitative mixing chamber 1115 passes through the flow channel, the first stop valve 510, and then enters the reaction chamber 1106.

[0260] Example 8:

[0261] In Example 8, a microfluidic detection chip without the addition of the quantitative mixing chamber 1115 and its auxiliary structures is used. The nucleic acid elution product in the fifth reagent chamber 11045 can be transferred to the reaction chamber 1106 by the following process. The steps of this example are as follows:

[0262] Step 1: Open the first stop valve 510 and the second stop valve 520, and close the third stop valve 530;

[0263] Step 2: The gas driving control structure in the detection device is used to open the first gas connection hole 410 (i.e., the first gas connection hole 410 is connected to the external atmospheric environment of the chip);

[0264] Step 3: The gas-driven control structure in the detection device docks with the air hole 420 and draws a certain amount of gas from the chip, so that the nucleic acid elution product in the fifth reagent chamber 11045 enters the reaction chamber 1106 through the flow channel, the mixing flow channel 1111, the mixing chamber, the first shut-off valve 510, and the flow channel, filling the reaction chamber 1106.

[0265] Example 9:

[0266] In Example 9, a microfluidic detection chip with a quantitative mixing chamber 1115 and its auxiliary structures is used, such as Figure 6 and Figure 7 After the amplification reaction is completed, the amplification product in the reaction chamber 1106 can be transferred to the test paper receiving chamber 1113 through the following process. The steps of this embodiment are as follows:

[0267] Step 1) After the amplification reaction is completed, the fourth stop valve 540, the first stop valve 510, and the third stop valve 530 are opened, and the second stop valve 520 is kept closed;

[0268] Step 2) The gas driving control structure in the detection device is used to close the second gas connection hole 430 (i.e., the second gas connection hole 430 is not connected to the external atmospheric environment of the chip);

[0269] Step 3) The gas driving control structure in the detection device docks with the first gas docking hole 410 and injects a certain amount of air into the chip to transfer the amplification product in the reaction chamber 1106 to the test paper receiving chamber 1113 .

[0270] Example 10:

[0271] When liquid is transferred using the methods described in Examples 6, 7, and 8, it is not necessary to maintain the final position of the liquid capsule's downward pressure structure; and the number of downward pressure structures can be reduced, such as using only one downward pressure structure and achieving reuse of the same downward pressure structure through relative movement between the chip and the downward pressure structure.

[0272] Example 11:

[0273] In Example 11, the magnetic particles 1 can be placed in the sample chamber 1101 in a dry solid form or in a liquid capsule unit (e.g., the first liquid capsule unit) in a liquid capsule unit. If placed in a liquid capsule unit, the magnetic particles 1 can be manually shaken to resuspend and mix the settled magnetic particles in the capsule before use. Alternatively, the particles can be resuspended and mixed by shaking the instrument after the microfluidic detection chip is inserted into the instrument.

[0274] Example 12:

[0275] The detection device paired with the microfluidic chip in this application has multiple functional modules, including but not limited to a nucleic acid extraction module (liquid sac pressure module, magnet module), a thermal incubation module (to assist nucleic acid extraction and membrane strip chromatography process), a valve control module, a mechanical transmission module, a gas drive control module (wherein the gas drive control structure of the detection device and the microfluidic detection chip can have multiple docking structures to meet the transfer and control of the fluid in the detection chip), a temperature control module (for supporting amplification reactions), a fluorescence acquisition and analysis module (for fluorescence detection schemes), an image acquisition and analysis module (for chromatography detection schemes), a software system, a hardware system, a user interface, etc.

[0276] In the description of this application, it should be understood that the terms "center", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", etc., indicating the orientation or position relationship, are based on the orientation or position relationship shown in the accompanying drawings, and are only for the convenience of describing this application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as a limitation on this application.

[0277] The terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of the technical features being referred to. Thus, a feature specified as "first" or "second" may explicitly or implicitly include one or more of such features. Throughout this application, unless otherwise specified, "plurality" means two or more.

[0278] In the description of this application, it should be noted that, unless otherwise expressly specified or limited, the terms "mounted," "connected," and "connected" should be understood broadly. For example, they can refer to fixed connections, detachable connections, or integral connections; they can refer to direct connections, indirect connections through an intermediate medium, or internal communication between two components. Those skilled in the art will understand the specific meanings of these terms in this application based on specific circumstances.

[0279] In the description of this specification, specific features, structures, materials or characteristics may be combined in an appropriate manner in any one or more embodiments or examples.

[0280] It should be understood that although the steps in the flowcharts of the accompanying drawings are shown in sequence as indicated by the arrows, these steps are not necessarily executed in the order indicated by the arrows. Unless otherwise specified herein, there is no strict order restriction on the execution of these steps, and they can be executed in other orders. Moreover, at least some of the steps in the flowcharts of the accompanying drawings may include multiple sub-steps or multiple stages, and these sub-steps or stages are not necessarily executed at the same time, but can be executed at different times, and their execution order is not necessarily sequential, but can be executed in turn or alternately with other steps or at least a portion of the sub-steps or stages of other steps.

Claims

1. A microfluidic detection chip, characterized in that: include: The microfluidic layer includes a substrate and top and bottom sealing layers located on both sides of the substrate. The substrate is provided with a sample chamber, a solid reagent chamber, a liquid capsule buffer chamber, a liquid reagent chamber, a reagent buffer chamber, and a reaction chamber. The sample chamber is connected to the solid reagent chamber through a flow channel. There are multiple liquid capsule buffer chambers, each of which is independently arranged. There are multiple liquid reagent chambers, each of which is sequentially spaced apart, and at least one reagent buffer chamber is provided between two adjacent liquid reagent chambers. The first liquid reagent chamber at the front end is connected to the solid reagent chamber via a flow channel, and the liquid reagent chamber at the rear end is connected to the reaction chamber via a flow channel; one of the liquid capsule buffer chambers is fluidically connected to one of the sample chamber and the first liquid reagent chamber, and except for the first liquid reagent chamber at the front end, each of the remaining liquid reagent chambers is connected to a different liquid capsule buffer chamber via a flow channel; A puncture structure is provided in each of the liquid sac buffer cavities; The liquid capsule layer is arranged on one side of the substrate, and the liquid capsule layer includes a plurality of liquid capsule units that are arranged at intervals and are independent of each other. The liquid capsule unit has a liquid capsule cavity, and the liquid capsule cavity of the liquid capsule unit is arranged opposite to at least one of the puncture structures.

2. The microfluidic detection chip according to claim 1, characterized in that: The substrate is provided with a first gas docking hole and a first shut-off valve. The first gas docking hole is in fluid communication with the second liquid reagent chamber located at the front end. The first shut-off valve is used to control the on-off of the flow channel connected to the liquid inlet end of the reaction chamber.

3. The microfluidic detection chip according to claim 2, characterized in that: The substrate is provided with a mixing flow channel and a mixing chamber, one end of the mixing flow channel is in liquid communication with the liquid reagent chamber located at the end, the other end of the mixing flow channel is in liquid communication with the liquid inlet end of the mixing chamber, and the liquid outlet end of the mixing chamber is in liquid communication with the liquid inlet end of the first shut-off valve.

4. The microfluidic detection chip according to claim 2 or 3, characterized in that: The substrate is provided with a test paper holding chamber, an air hole, a second stop valve and a third stop valve. The test paper holding chamber is in liquid communication with the liquid outlet of the reaction chamber through a flow channel, and the air hole is in fluid communication with the liquid outlet of the reaction chamber through a flow channel. The second stop valve is used to control the on-off of the flow channel between the liquid outlet of the reaction chamber and the air hole, and the third stop valve is used to control the on-off of the flow channel between the test paper holding chamber and the liquid outlet of the reaction chamber.

5. The microfluidic detection chip according to claim 4, characterized in that: The substrate is provided with a fourth stop valve, a quantitative mixing chamber and a second gas docking hole. The fourth stop valve is arranged on a flow channel connected to the liquid inlet end of the first stop valve. The quantitative mixing chamber hole of the quantitative mixing chamber is fluidically connected to the liquid outlet end of the fourth stop valve. The top of the quantitative mixing chamber is connected to the second gas docking hole through a flow channel.

6. The microfluidic detection chip according to claim 1, characterized in that: The reaction chamber is flat, and at least one cavity is provided on the periphery of the reaction chamber.

7. The microfluidic detection chip according to claim 1 or 6, characterized in that: The number of the reaction chamber is at least one.

8. The microfluidic detection chip according to claim 7, characterized in that: The substrate includes a first part and a second part connected to each other, the thickness of the second part is smaller than that of the first part, the reaction chamber is set in the second part, and the reaction chamber is set through the upper end surface and the lower end surface of the second part.

9. The microfluidic detection chip according to claim 1, characterized in that: The liquid capsule unit includes a liquid capsule shell and a liquid capsule sealing membrane. The liquid capsule shell forms a liquid capsule cavity with an opening. The liquid capsule sealing membrane is arranged on a side of the liquid capsule cavity with the opening.

10. A detection method, characterized in that: Applied to the microfluidic detection chip according to any one of claims 1 to 9, the detection method comprises the following steps: placing a biological sample in the sample chamber and closing the sample chamber; squeezing the liquid capsule unit connected to the sample chamber so that the reagent in the liquid capsule unit flows into the sample chamber and mixes with the biological sample; driving the mixed solution in the sample chamber to flow into the solid reagent chamber to redissolve the solid reagent preset in the solid reagent chamber to obtain a mixture, wherein magnetic particles are also preset in the solid reagent chamber; Driving the mixture in the solid reagent chamber into the first liquid reagent chamber and allowing it to stand; Controlling the first magnetic member and the second magnetic member to approach the top and / or bottom of the liquid reagent chamber, and using the first magnetic member and the second magnetic member to drive the magnetic particles in the liquid reagent chamber to pass through each of the liquid reagent chambers and the reagent buffer chamber in sequence, and finally driving the magnetic particles to move to the liquid reagent chamber at the end; The first magnetic member maintains an adsorption state of the magnetic particles, and drives the eluted product in the liquid reagent chamber at the end into the reaction chamber to perform an amplification reaction.

11. A detection device, characterized in that: include: at least one pressing structure for squeezing each liquid capsule unit of the liquid capsule layer; The magnetic assembly includes a first magnetic member and a second magnetic member that are spaced apart; A driving device is used to drive the first magnetic member to move so that the first magnetic member moves in a direction perpendicular to the microfluidic detection chip, and the driving device is also used to drive the first magnetic member to move laterally parallel to the end face of the microfluidic detection chip; the driving device is used to drive the second magnetic member to move so that the second magnetic member moves in a direction perpendicular to the microfluidic detection chip, and the driving device is also used to drive the second magnetic member to move laterally parallel to the end face of the microfluidic detection chip.

12. The detection device according to claim 11, characterized in that The detection device includes a gas drive control structure, which is used to suck or blow air into the docking hole in the microfluidic detection chip. The gas drive control structure is also used to control the opening and closing of the docking hole.

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