Microfluidic detection chip

Abstract

The present invention relates to a microfluidic detection chip, which comprises: a storage module, which comprises a plurality of storage bins, each storage bin is used for storing a reagent, and the top and the bottom of each storage bin are configured to be closed before detection; the reaction module is arranged below the storage module, the reaction module comprises a connecting part, the connecting part comprises a plurality of connecting heads, each connecting head is internally provided with a first channel, and the plurality of connecting heads are in one-to-one correspondence with the plurality of storage bins; the connector is used for breaking the sealing of the bottom of the storage bin, so that the reagent in the storage bin flows out through a first channel in the connector; and the reaction bin is arranged below the connecting part and is used for receiving the reagent flowing out through the first channel in the connector. The bottoms of the storage bins on the storage module and the connectors on the reaction module are aligned one by one, then the storage bins and the connectors are tightly pressed with force, the connectors penetrate through seals at the bottoms of the storage bins, chip assembling is completed, operation is easy and convenient, and efficiency is high.

Description

[0001] This application is a divisional application of the invention application with application number CN201910700750.2 and application date of July 31, 2019. Technical Field

[0002] This invention relates to the field of microfluidic detection, and more particularly to a microfluidic detection chip. Background Technology

[0003] Microfluidic chip technology, due to its high integration and strong automation, is increasingly being applied to point-of-care testing (POCT) in clinical testing. However, to port existing reagent systems to a microfluidic platform, challenges need to be overcome, including large reaction systems, complex reaction steps, and high reaction efficiency requirements. Furthermore, the pre-filling, long-term storage, and release of reagents, as well as the directional and sequential flow of released reagents within the chip, place extremely high design and fabrication demands on the connection and matching of the chip reagent storage module and the reaction chip.

[0004] Therefore, how to solve the problems of reagent storage and sealing, how to connect the reagent to the reaction chip after opening, how to guide the flow of reagents in sequence, and how to efficiently complete the reaction between reagents and samples have become the main barriers restricting the clinical application of microfluidic technology. Summary of the Invention

[0005] One objective of this invention is to provide a microfluidic detection chip to alleviate the problems of complex and inefficient reagent-sample reaction operations.

[0006] Some embodiments of the present invention provide a microfluidic detection chip, comprising:

[0007] The storage module includes multiple storage compartments, each used to store reagents. Before testing, the top and bottom of each storage compartment are constructed to be sealed.

[0008] A reaction module, located below the storage module, includes:

[0009] The connecting part includes multiple connectors, each connector having a first channel, and the multiple connectors corresponding one-to-one with the multiple storage chambers; the connectors are used to break the seal at the bottom of the storage chambers, allowing the reagents inside the storage chambers to flow out through the first channels within the connectors; and

[0010] The reaction chamber, located below the connector, is used to receive reagents flowing out through the first channel inside the connector.

[0011] In some embodiments, the top of the storage compartment is larger than the bottom of the storage compartment.

[0012] In some embodiments, the storage module includes a seal, the bottom of the storage compartment is constricted and has a bottom outlet, the seal fills the bottom of the storage compartment and closes the bottom outlet of the storage compartment, and the seal is configured to detach from the bottom of the storage compartment under the force of the connector and move toward the center of the storage compartment to open the bottom outlet of the storage compartment.

[0013] In some embodiments, the storage module includes a stepped hole located below the storage compartment; the stepped hole includes a first hole and a second hole, the diameter of the first hole being smaller than the diameter of the second hole, the top of the first hole connecting to the bottom of the storage compartment, and the bottom of the first hole connecting to the top of the second hole.

[0014] In some embodiments, the connector includes:

[0015] A first connecting segment, in the detection state, is located within the first hole, and the size of the first connecting segment is adapted to the size of the first hole to achieve a seal; and

[0016] The second connecting section is located inside the second hole in the detection state. The size of the second connecting section is adapted to the size of the second hole to achieve a seal.

[0017] In some embodiments, the storage module includes a seal, the bottom of the storage compartment is constricted and has a bottom outlet, the seal fills the bottom of the storage compartment and closes the bottom outlet of the storage compartment;

[0018] The bottom of the second hole of the stepped hole is sealed;

[0019] The first connecting segment of the connector is configured to break the bottom seal of the second hole and push the seal away from the bottom of the storage compartment, moving it toward the center of the storage compartment to open the bottom outlet of the storage compartment.

[0020] In some embodiments, the connecting portion is provided with a groove, and the bottom of the connector is disposed within the groove.

[0021] In some embodiments, the storage module includes a sample compartment and a filter cartridge disposed within the sample compartment, wherein the bottom of the sample compartment extends toward the top of the sample compartment to form a pointed structure, and the pointed structure is inserted into the filter cartridge.

[0022] In some embodiments, the storage compartment includes a lyophilized reagent compartment for storing lyophilized reagents, the top of which is lower than the top of the other storage compartments.

[0023] In some embodiments, the microfluidic detection chip includes a desiccant module, the desiccant module including a desiccant chamber for holding desiccant, the desiccant module being inserted into the top of the lyophilized reagent chamber; and in the state where the desiccant module is inserted into the top of the lyophilized reagent chamber, the top of the desiccant chamber and the top of the storage chamber are at the same height.

[0024] In some embodiments, the storage compartment includes a lyophilized reagent compartment for storing lyophilized reagents, and the upper part of the lyophilized reagent compartment is provided with a limiting structure to restrict the falling of the desiccant so as to isolate the desiccant from the lyophilized reagents in the lyophilized reagent compartment.

[0025] In some embodiments, the reaction module includes multiple second channels and a valve zone. The second channels are connected one-to-one with the multiple connectors. The second channels are used to direct reagents flowing in through the first channels of the connectors to the valve zones, so that the reagents can be selectively directed to the reaction chamber by valves provided in the valve zones.

[0026] Based on the above technical solution, the present invention has at least the following beneficial effects:

[0027] In some embodiments, the storage module and the reaction module are independent modules. During the detection reaction, the storage module is placed on top of the reaction module, and the bottom of each storage compartment on the storage module is aligned with each connector on the reaction module. Then, the two are pressed together so that the connector penetrates the seal at the bottom of the storage compartment. The first channel inside the connector communicates with the inside of the storage compartment, thus completing the assembly of the detection chip. The operation is simple, convenient, and efficient. Attached Figure Description

[0028] The accompanying drawings, which are included to provide a further understanding of the invention and form part of this application, illustrate exemplary embodiments of the invention and, together with their description, serve to explain the invention and do not constitute an undue limitation thereof. In the drawings:

[0029] Figure 1 A schematic diagram of the assembly direction of a microfluidic detection chip provided in some embodiments of the present invention during preparation for detection;

[0030] Figure 2 This is a schematic diagram of the assembled microfluidic detection chip provided in some embodiments of the present invention;

[0031] Figure 3 This is a schematic diagram of the liquid flow direction inside the microfluidic detection chip after assembly, provided in some embodiments of the present invention.

[0032] Figure 4 This is a schematic diagram showing the arrangement of the connection part, reaction chamber and channel of the reaction module provided in some embodiments of the present invention;

[0033] Figure 5 A schematic diagram of a storage module provided in some embodiments of the present invention;

[0034] Figure 6 A cross-sectional schematic diagram of a storage module provided in some embodiments of the present invention;

[0035] Figure 7 This is a schematic diagram illustrating the assembly orientation of the storage module and the desiccant module according to some embodiments of the present invention;

[0036] Figure 8 for Figure 7 A schematic diagram of the cross-section of the local structure A shown;

[0037] Figure 9 A schematic diagram showing a sealing element provided in the storage compartment of a storage module according to some embodiments of the present invention.

[0038] Explanation of the labels in the attached drawings:

[0039] 1-Storage module; 11-Storage compartment; 111-Lyophilized reagent compartment; 12-Sample compartment; 13-Sealing element;

[0040] 2-Reaction module; 21-Connector; 211-Connector head; 2111-First connecting section; 2112-Second connecting section; 212-Process hole; 22-Reaction chamber; 23-Second channel; 24-Valve area; 25-Waste liquid chamber; 26-Amplification reaction chamber; 27-Sample quantification chamber;

[0041] 3-Desiccant module; 31-Desiccant compartment;

[0042] 4-Valve. Detailed Implementation

[0043] The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0044] In the description of this invention, it should be understood that the terms "center", "longitudinal", "lateral", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limiting the scope of protection of this invention.

[0045] like Figure 1 , Figure 2 The diagram shown is a schematic of a microfluidic detection chip provided in some embodiments.

[0046] In some embodiments, the microfluidic detection chip includes a storage module 1 and a reaction module 2. The storage module 1 enables the sealed storage and release of reagents. The reaction module 2 enables the directional flow of liquids and the execution of the reaction.

[0047] The storage module 1 includes multiple storage compartments 11, each used to store reagents. Before testing, the top and bottom of each storage compartment 11 are sealed. During testing, the seals on the top and bottom of the storage compartment 11 are broken, allowing the reagent to flow out from the bottom of the storage compartment 11. The seal on the top of the storage compartment 11 is also broken to maintain atmospheric pressure balance within the storage compartment 11.

[0048] Optionally, the bottom of the storage compartment 11 is sealed with a sealing film.

[0049] Optionally, the bottom of the storage compartment 11 is sealed by a filling seal 13.

[0050] The reaction module 2 is located below the storage module 1. The reaction module 2 includes a connecting part 21 and a reaction chamber 22. The connecting part 21 of the reaction module 2 can be integrally formed with the part where the reaction chamber 22 is located, or the connecting part 21 and the part where the reaction chamber 22 is located are separate structures.

[0051] The connecting part 21 includes multiple connectors 211. Each connector 211 can be arranged side by side in sequence. Each connector 211 is provided with a first channel. The first channel is used to connect to the storage chamber 11 and to lead the reagent in the storage chamber 11 to the reaction chamber 22.

[0052] Multiple connectors 211 correspond one-to-one with multiple storage chambers 11; each connector 211 is used to break the seal at the bottom of a storage chamber 11, that is, each connector 211 breaks the seal at the bottom of one storage chamber 11, so that the reagent inside the storage chamber 11 flows out through the first channel inside the connector 211, such as... Figure 3 As shown.

[0053] The reaction chamber 22 is located below the connecting part 21 and is used to receive the reagent flowing out through the first channel in the connector 211.

[0054] In some embodiments, the assembly method of the microfluidic detection chip is as follows: the storage module 1 is placed above the reaction module 2, and the bottom of each storage chamber 11 on the storage module 1 is aligned with each connector 211 on the reaction module 2. Then, the two are pressed together so that the connector 211 penetrates the seal at the bottom of the storage chamber 11, and the first channel inside the connector 211 communicates with the inside of the storage chamber 11, thus completing the assembly of the detection chip. The operation is simple, convenient, and efficient. Furthermore, since the connector 211 is located below the storage chamber 11, it is beneficial for the reagent to flow to the connector 211 by gravity.

[0055] The seal on the top of storage chamber 11 can be broken by a component on a detection instrument to equalize the air pressure inside storage chamber 11.

[0056] like Figure 5 As shown, the storage module 1 includes two or more storage compartments 11 arranged side by side. Each storage compartment 11 has a top outlet at the top and a bottom outlet at the bottom, which are respectively the air pressure balance channel and the liquid flow channel of the storage compartment 11.

[0057] In some embodiments, in the initial state, the top outlet and the bottom outlet are sealed by sealing membranes, respectively.

[0058] The microfluidic detection chip provided in this embodiment is simple and convenient to operate. Assembly and operation of the chip can be achieved manually or with simple external instruments, facilitating adjustment. Furthermore, it can be easily adapted to different detection systems by simply increasing the number of storage compartments 11 in the storage module 1, without requiring chip redesign.

[0059] In some embodiments, the top and bottom of the storage compartment 11 can be sealed using a polymer film.

[0060] The polymer membrane can be made of organic polymer materials, and its thickness can be adjusted as needed. The polymer membrane can be tightly bonded to the top and bottom of the storage compartment 11 by hot pressing, ultrasonication, or adhesive bonding.

[0061] Before the test begins, storage module 1 and reaction module 2 are stored separately, and the storage compartment 11 of storage module 1 is sealed with the reagents required for the test experiment.

[0062] When it is necessary to open the seal of the storage chamber 11, the sealing membrane at the bottom of the storage chamber 11 is pierced and fixed through the connector 211 of the connector 21 at the top of the reaction module 2, thereby realizing the directional release of liquid. At the same time, the pierced sealing membrane seals the connection, ensuring a seal during the liquid flow process.

[0063] The sealing is achieved through the interaction between the connector 211, the sealing membrane, and the channel. This results in good sealing performance, a reliable reaction process, a simple principle, and convenient processing. It can be implemented without complex design, which greatly reduces the design and manufacturing costs of the chip.

[0064] In other embodiments, such as Figure 9 As shown, the storage module 1 includes a seal 13. The bottom of the storage compartment 11 is constricted and has a bottom outlet. The seal 13 fills the bottom of the storage compartment 11 and closes the bottom outlet of the storage compartment 11. The seal 13 is configured to detach from the bottom of the storage compartment 11 under the force of the connector 211 and move toward the center of the storage compartment 11 to open the bottom outlet of the storage compartment 11.

[0065] In some embodiments, such as Figure 6 As shown, the top of the storage chamber 11 is larger than the bottom. The larger top of the storage chamber 11 facilitates the injection of reagents through the top, while the smaller bottom facilitates a sealed connection with the connector 211.

[0066] In some embodiments, the cross-section of the portion between the top and bottom of the storage compartment 11 is circular, and the bottom of the storage compartment 11 is constricted.

[0067] like Figure 6 As shown, in some embodiments, the storage module 1 includes a stepped hole located below the storage compartment 11; the stepped hole includes a first hole and a second hole, the diameter of the first hole is smaller than the diameter of the second hole, the top of the first hole is connected to the bottom of the storage compartment 11, and the bottom of the first hole is connected to the top of the second hole.

[0068] Optionally, the bottom of the second hole is sealed with a sealing membrane.

[0069] In some embodiments, the connector 211 includes a first connecting segment 2111 and a second connecting segment 2112. The width of the first connecting segment 2111 is smaller than the width of the second connecting segment 2112.

[0070] In the detection state, the first connecting segment 2111 is located inside the first hole, and the size of the first connecting segment 2111 is adapted to the size of the first hole. For example, the size of the first connecting segment 2111 is the same as the size of the first hole, or the first connecting segment 2111 is interference-fitted with the first hole to achieve a seal.

[0071] The second connecting section 2112 is located inside the second hole in the detection state, and the size of the second connecting section 2112 is adapted to the size of the second hole. For example, the size of the second connecting section 2112 is the same as the size of the second hole, or the second connecting section 2112 is interference-fitted with the second hole to achieve a seal.

[0072] like Figure 6 As shown, the stepped hole at the bottom of the storage chamber 11 cooperates with the first connecting section 2111 and the second connecting section 2112 of the connector 211 to achieve a seal at the connection point between the connector 211 and the storage chamber 11 after the seal at the bottom of the storage chamber 11 is broken, preventing the leakage of reagents led out of the storage chamber 11 through the first channel of the connector 211, and ensuring that the reagents are completely led to the reaction chamber 22.

[0073] In other embodiments, such as Figure 9 As shown, the storage module 1 includes a seal 13. The bottom of the storage compartment 11 is constricted and has a bottom outlet. The seal 13 fills the bottom of the storage compartment 11 and seals the bottom outlet of the storage compartment 11. The bottom of the second hole of the stepped hole is sealed.

[0074] The first connecting segment 2111 of the connector 211 is configured to break the bottom seal of the second hole and push the seal 13 away from the bottom of the storage chamber 11 and move towards the center of the storage chamber 11 to open the bottom outlet of the storage chamber 11.

[0075] In some embodiments, the second hole of the stepped hole is sealed. If the bottom opening connecting the storage chamber 11 to the first hole of the stepped hole is not sealed, the reagent stored in the storage chamber 11 will flow into the stepped hole at the bottom of the storage chamber 11 under the influence of physical factors such as bumps and vibrations. This will cause the reagent liquid to leak during the process of the reaction module 2 piercing and connecting the storage module 1.

[0076] Therefore, in another embodiment, to prevent the leakage, the seal 13 is filled into the bottom of the storage chamber 11 to seal the bottom outlet of the storage chamber 11.

[0077] Optionally, the seal 13 includes a sealing ball or a sealing block.

[0078] Optionally, the material of the seal 13 may include high polymer materials such as paraformaldehyde, polycarbonate, and polytetrafluoroethylene.

[0079] The diameter of the seal 13 should be slightly larger than the diameter of the bottom of the storage chamber 11 to form an interference fit and achieve a seal at the bottom outlet of the storage chamber 11.

[0080] During operation, the first connecting segment 2111 of connector 211 first punctures the sealing membrane at the bottom of the second hole of the stepped orifice. At this time, due to the presence of seal 13, the reagent is prevented from flowing downward, and therefore, no reagent leakage occurs.

[0081] As the first connecting section 2111 is advanced further, and the connector 211 is about to fully engage with the stepped orifice, the first connecting section 2111 contacts the liquid-resistant seal 13. At this point, as the first connecting section 2111 continues to advance, it pushes open the seal 13, achieving a complete engagement and seal between the connector 211 and the stepped orifice. The reagent then begins to flow along the pipeline, effectively preventing reagent leakage during module connection and avoiding reagent loss and contamination of the testing instrument.

[0082] In some embodiments, the storage module 1 is provided with a plurality of storage chambers 11 for storing reaction reagents. The bottom of each storage chamber 11 is equipped with a channel that connects downward to the reaction module 2 and is used to guide the flow of reagents. The top of the storage chamber 11 is open upward to connect to the external atmosphere and balance the air pressure inside the storage chamber 11.

[0083] In some embodiments, the first connecting segment 2111 and the second connecting segment 2112 of the connector 211 can be integrally molded from plastic. Alternatively, the first connecting segment 2111 can be a metal pin assembled with the second connecting segment 2112.

[0084] In some embodiments, such as Figure 6 As shown, a process hole 212 is also provided between two adjacent stepped holes on the storage module 1 to reduce the weight of the chip and save materials. Figure 3 As shown, in some embodiments, the connecting part 21 is provided with a groove, and the bottom of the connector 211 is disposed in the groove.

[0085] Optionally, the connector 211 further includes a third connecting segment disposed within the groove. The width of the third connecting segment is less than the width of the second connecting segment, the width of the third connecting segment is the same as the width of the groove, or the third connecting segment is interference-fitted with the groove.

[0086] A third channel is provided on the connecting part 21. The third channel connects the first channel in the connector 211 and the second channel 23 on the reaction module 2, and the opening of the third channel is located in the groove.

[0087] Of course, the third channel and the second channel 23 can be a single channel. The second channel 23 is connected to the first channel of the connector 211, and the opening of the second channel 23 is located in the groove.

[0088] like Figure 6 As shown, in some embodiments, the storage module 1 includes a sample compartment 12 and a filter element disposed within the sample compartment 12.

[0089] The bottom of sample chamber 12 extends towards the top of sample chamber 12 to form a pointed structure, which is inserted into the filter element.

[0090] Sample compartment 12 typically contains whole blood samples. The filter cartridge is used to adsorb most of the red blood cells in the whole blood sample. The pointed structure that pierces into the filter cartridge allows for efficient and rapid direct extraction of plasma, which has been initially separated from the whole blood sample, from inside the cartridge. The initially separated plasma contains white blood cells, platelets, and a small number of red blood cells.

[0091] In some embodiments, the storage chamber 11 includes a lyophilized reagent chamber 111 for storing lyophilized reagents, wherein one of the storage chambers 11 contains a reconstitution reagent. When reconstituted lyophilized reagents, the corresponding reconstitution reagent is first pumped into the reaction chamber 22 by means of a liquid flow driven pump and valve 4, and then the reagent is pushed from the reaction chamber 22 to the lyophilized reagent chamber 111 by a reverse pump. The reconstituted lyophilized reagent can then enter the reaction chamber 22 again by means of a liquid flow driven pump and valve 4.

[0092] like Figure 7 , Figure 8 As shown, in some embodiments, the top of the freeze-dried reagent compartment 111 is lower than the top of the other storage compartments 11.

[0093] The microfluidic detection chip also includes a desiccant module 3, which includes a desiccant chamber 31 for placing desiccant. The desiccant module 3 is used to insert into the top of the freeze-drying reagent chamber 111. When the desiccant module 3 is inserted into the top of the freeze-drying reagent chamber 111, the top of the desiccant chamber 31 and the top of the storage chamber 11 are at the same height.

[0094] The seal at the bottom of the desiccant compartment 31 is broken, and the size of the bottom of the desiccant compartment 31 is smaller than the size of the desiccant to prevent the desiccant from falling out of the desiccant compartment 31 into the lyophilized reagent compartment 111. The presence of desiccant helps maintain the dryness of the lyophilized reagent, facilitating its long-term preservation.

[0095] In some embodiments, the upper part of the lyophilized reagent compartment 111 is provided with a limiting structure to restrict the falling of the desiccant, so as to isolate the desiccant from the lyophilized reagent in the lyophilized reagent compartment 111.

[0096] In some embodiments, the limiting structure may include a limiting platform disposed on the upper part inside the lyophilized reagent chamber 111. The desiccant is placed on the limiting platform on the upper part of the lyophilized reagent chamber 111, and the limiting platform limits the desiccant to prevent it from contacting the lyophilized reagent.

[0097] In some embodiments, the upper part of the lyophilized reagent compartment 111 is configured as a constricted section, and the upper part of the constricted section is a flared section. The flared section holds the desiccant, and the size of the desiccant is larger than the size of the constricted section. The constricted section limits the desiccant from contacting the lyophilized reagent.

[0098] like Figure 4As shown, in some embodiments, the reaction module 2 includes multiple second channels 23 and a valve region 24. Each second channel 23 is connected to a corresponding connector 211. That is, each connector 211 is connected to one second channel 23.

[0099] The second channel 23 is used to guide the reagent led out through the first channel via the connector 211 to the valve area 24, so that the reagent can be selectively led to the reaction chamber 22 through the valve 4 provided in the valve area 24.

[0100] The reaction module 2 includes a plane that mates with the valve 4, which is called valve zone 24.

[0101] The reaction chamber 22 of the reaction module 2 can be any shape suitable for accommodating the reaction. The reaction chamber 22 has at least two channels connected to it, which serve as channels for liquid flow and gas pressure balance.

[0102] The reaction module 2 includes a waste liquid tank 25. The waste liquid tank 25 is connected to the reaction chamber 22 through a channel. A hole is drilled on the side of the liquid inlet channel away from the waste liquid tank 25, or a separate channel is opened to balance the gas pressure in the waste liquid tank 25.

[0103] Furthermore, the waste liquid tank 25 can be of any shape, and its capacity can be whatever size meets the application requirements.

[0104] Furthermore, the reaction module 2 includes any number of waste liquid tanks 25 for holding waste liquid generated in different reaction steps, so as to achieve a better effect of preventing biological contamination.

[0105] Optionally, sufficient filter paper, absorbent paper, or other absorbent materials with liquid-fixing capabilities can be placed in the waste liquid tank 25 to fix the waste liquid and prevent it from overflowing.

[0106] The reaction module 2 also includes an amplification reaction chamber 26 and a sample quantification chamber 27.

[0107] The reaction module 2 has multiple channels, such as multiple second channels, to guide the flow of liquid. The connections between the channels of the reaction module 2 are achieved through valves 4 installed in the valve section 24.

[0108] In some embodiments, the microfluidic chip includes a valve 4 to enable directional flow of liquid. The storage module 1 and the reaction module 2 are connected by a connector 21. After the reagent flows out of the storage module 1, it enters the reaction module 2 through the connector 211, and is then guided by the valve 4 on the reaction module 2 to achieve sequential release and reaction of the reagent.

[0109] The reaction module 2 integrates the reaction chamber 22, the waste liquid chamber 25, and several channels. The reaction chamber 22 is connected to the valve 4 through a separate inlet and outlet channel, and can be connected to the other channels of the valve area 24 by rotating the valve 4.

[0110] The microfluidic chip provided in this embodiment is made of common and inexpensive materials, and its pipeline design is at the millimeter level, enabling large-scale mold injection molding and easy mass production.

[0111] The microfluidic chip provided in this disclosure integrates reagent storage, release, sequential and directional flow, mixing reaction, and final signal detection.

[0112] The microfluidic chip provided in this embodiment can easily adjust the size and number of storage chambers 11 as needed to meet the requirements of different testing items. It can seamlessly connect with existing testing reagents, significantly reduce the production and R&D processing costs of microfluidic chips, and enhance the clinical application value of microfluidic chips.

[0113] The following are some specific examples of microfluidic chips.

[0114] The main body of storage module 1 is made of PC material and its dimensions are 78 mm × 23 mm × 8 mm. It contains 11 cup-shaped storage compartments 11 with a diameter of 6 mm and a depth of 20 mm.

[0115] The material for storage module 1 can also be selected from polymer materials such as PP and PET. There are no special requirements for the material thickness, but it needs to be optimized according to the material properties and bonding technology. Bonding technology can be completed using adhesive bonding, thermal bonding, ultrasonic bonding, ion bonding, etc.

[0116] The specific implementation of the storage module 1 is as follows: First, the stepped hole at the bottom of the storage compartment 11 is sealed with a thin film, and then the reagent is poured into the storage compartment 11 through the opening at the top. At the same time, the two lyophilized reagents are placed into the storage compartment 11 corresponding to the chip.

[0117] In this embodiment, 100 μL of extraction buffer, 2 x 200 μL of washing buffer one, 2 x 200 μL of washing buffer two, 200 μL of washing buffer three, 100 μL of elution buffer, 100 μL of paraffin oil, one lyophilized bead each of extraction reagent A and B, and one lyophilized bead of amplification reagent are perfused. Simultaneously, whole blood separation filler is placed in sample chamber 12. The chip is then sealed with another membrane.

[0118] The reaction module 2 is made of PC material. Its appearance is an irregular three-dimensional plastic structure. The reaction module 2 includes five parts: waste liquid tank 25, connecting part 21, reaction chamber 22, valve area 24 and amplification reaction chamber 26, which are located directly below, directly above, one side of the middle, the other side of the middle and external attachment area of ​​the reaction module 2, respectively.

[0119] The waste liquid tank 25 is located at the bottom of the reaction module 2. Its internal dimensions are 51 mm × 15 mm × 2 mm, with a chamfer radius of 1.5 mm on all four sides, a total volume of 1530 μL, and a wall thickness of 1 mm. Both the liquid and gas channels are connected to the through holes of the valve area 24 through pipelines.

[0120] The connecting part 21 is located at the top of the reaction module 2 and consists of a row of needle-like structures with frustums. The needle tip (first connecting section 2111) has an outer diameter of 1.5 mm, an inner diameter of 0.8 mm, and a length of 2.0 mm. The frustum base (second connecting section 2112) has a diameter of 3.0 mm and a height of 1.5 mm. Its dimensions match the stepped holes below the storage compartment 11 to achieve a seal.

[0121] The reaction chamber 22 is located on one side of the chip. It is circular in shape, with a diameter of 38 mm. The front of the chamber rises approximately 2 mm from the center and gradually slopes downwards towards the circumference. The internal depth of the chamber is 2 mm. A liquid flow channel extends tangentially from directly below the reaction chamber 22 and connects to the central hole of the valve area 24. A gas pressure channel extends linearly from directly above the reaction chamber 22, serving as a channel for regulating the gas pressure within the chamber. This channel works in conjunction with the instrument to power the flow of reagents within the chip.

[0122] The amplification reaction chamber 26, also known as the secondary reaction chamber, is located on the other side of the chip and is connected to the valve region 24 via a channel. Its internal volume is 100 μL and its depth is 0.5 mm. Its main shape consists of an 8 mm × 8 mm square and a semicircle with a radius of 4 mm.

[0123] The experimental preparation for the detection chip is as follows: Remove reaction module 2 and storage module 1, align the liquid flow interface of storage module 1 with the liquid flow interface of reaction module 2, and place them vertically on the shelf. Simultaneously, ensure valve 4 is in the closed state. Add the sample through sample quantification chamber 27.

[0124] The detection chip starts working. Align the connector 211 of the reaction module 2 with the bottom of the storage chamber 11 and press down firmly to make the connector 211 of the reaction module 2 pierce the sealing film at the bottom of the storage chamber 11, thus completing the connection between the reaction module 2 and the storage module 1. Then, place it into the matching instrument.

[0125] The workflow for nucleic acid extraction and amplification detection using the microfluidic chip provided in the above embodiments is listed below:

[0126] The valve 4 is rotated to the channel of the sample quantification chamber 27, and air is drawn from the air pressure port of the reaction chamber 22 to create negative pressure, so that the sample is drawn into the reaction chamber 22 after being filtered by the filling material.

[0127] Rotate valve 4 to the storage chamber 11 containing the pyrolysis reagent, draw air from the gas pressure port of reaction chamber 22 to create negative pressure, and draw the pyrolysis reagent into reaction chamber 22.

[0128] Rotate valve 4 to the lyophilized reagent chamber 111, pressurize the air pressure port of reaction chamber 22, push the lysis reagent and sample mixture through the lyophilized reagent chamber 111, and then pump the lyophilized reagent into reaction chamber 22 under negative pressure after reconstitution.

[0129] Close valve 4 and use ultrasound to react the liquid in reaction chamber 22.

[0130] The magnet adsorbs magnetic particles in the reaction system. Valve 4 is rotated to the opening of waste liquid tank 25, and pressure is applied from the gas pressure port of reaction tank 22 to discharge waste liquid into waste liquid tank 25.

[0131] Rotate valve 4 to the storage chamber 11 of washing liquid 1, and draw air from the air pressure port of reaction chamber 22 to create negative pressure to draw in washing liquid 1.

[0132] Close valve 4 and use ultrasound to react the liquid in reaction chamber 22.

[0133] The magnet adsorbs magnetic particles in the reaction system. Valve 4 is rotated to the opening of waste liquid tank 25, and pressure is applied from the gas pressure port of reaction tank 22 to discharge waste liquid into waste liquid tank 25.

[0134] Repeat 5 to 7 times.

[0135] Valve 4 is rotated to the storage chamber 11 of washing liquid II, and air is drawn from the air pressure port of reaction chamber 22 to create negative pressure to draw in washing liquid II.

[0136] Close valve 4 and use ultrasound to react the liquid in reaction chamber 22.

[0137] The magnet adsorbs magnetic particles in the reaction system. Valve 4 is rotated to the opening of waste liquid tank 25, and pressure is applied from the gas pressure port of reaction tank 22 to discharge waste liquid into waste liquid tank 25.

[0138] Repeat 9 to 11 times.

[0139] Rotate valve 4 to the storage chamber 11 of washing liquid 3, and draw air from the air pressure port of reaction chamber 22 to create negative pressure to draw in washing liquid 3.

[0140] Close valve 4, the magnet remains in an attracted state, and soak for washing.

[0141] Rotate valve 4 to the opening of waste liquid chamber 25, pressurize from the gas pressure port of reaction chamber 22, and discharge waste liquid into waste liquid chamber 25.

[0142] Rotate valve 4 to the eluent storage chamber 11, and draw air from the air pressure port of reaction chamber 22 to create negative pressure to draw in the eluent.

[0143] Close valve 4 and use ultrasound to react the liquid in reaction chamber 22.

[0144] The magnet adsorbs the magnetic particles in the reaction system. Valve 4 is rotated to the lyophilized reagent chamber 111, and pressure is applied from the gas pressure port of reaction chamber 22 to push the elution product into the lyophilized reagent chamber 111 to reconstitute the reagent.

[0145] The magnet maintains the adsorption, and air is drawn out from the gas pressure port of reaction chamber 22 to return the reconstituted reaction system to reaction chamber 22.

[0146] Rotate valve 4 to amplification reaction chamber 26, pressurize from the gas pressure port of reaction chamber 22, and slowly push the reaction system into amplification reaction chamber 26.

[0147] Rotate valve 4 to the paraffin oil storage chamber 11 to pump paraffin oil into the reaction chamber 22. Then rotate it to the opening of the amplification reaction chamber 26 to push paraffin oil into the sealing chamber 26.

[0148] Close valve 4 and perform amplification detection.

[0149] After the reaction is complete, remove the chip from the instrument and discard it as a whole.

[0150] Some embodiments of this disclosure simply utilize valve 4 in conjunction with a variable pressure source to achieve reagent flow control, significantly reducing the technical requirements of the testing instrument. Furthermore, this technical solution only requires replacing the storage module 1 containing different reagents to meet the needs of various testing items, greatly improving the clinical applicability of this design. Simultaneously, its versatility reduces the complexity and difficulty of mass production, facilitating the large-scale production and promotion of this product.

[0151] The microfluidic detection chip provided in this embodiment can be applied in the field of clinical testing.

[0152] In the description of this invention, it should be understood that the use of terms such as "first," "second," and "third" to define components is merely for the purpose of distinguishing the aforementioned components. Unless otherwise stated, these terms have no special meaning and therefore should not be construed as limiting the scope of protection of this invention.

[0153] Furthermore, in the absence of explicit denial, the technical features of one embodiment may be advantageously combined with one or more other embodiments.

[0154] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them; although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications can still be made to the specific implementation of the present invention or equivalent substitutions can be made to some technical features without departing from the spirit of the technical solutions of the present invention, and all such modifications and substitutions should be covered within the scope of the technical solutions claimed in the present invention.

Claims

1. A microfluidic detection chip, characterized in that, include: The storage module (1) includes multiple storage compartments (11), each of which is used to store reagents; the bottom of each storage compartment (11) is constricted and has a bottom outlet; the bottom of each storage compartment (11) is filled with a sealing element (13), which seals the bottom outlet of the storage compartment (11); a stepped hole is provided below each storage compartment (11); the stepped hole includes a first hole and a second hole, the diameter of the first hole is smaller than the diameter of the second hole, the top of the first hole is connected to the bottom of the storage compartment (11), the bottom of the first hole is connected to the top of the second hole, and the bottom of the second hole is sealed; and The reaction module (2) includes a connecting part (21) and a reaction chamber (22); The connecting part (21) includes multiple connectors (211), each connector (211) having a first channel, and the multiple connectors (211) corresponding one-to-one with the multiple storage compartments (11); the connector (211) includes a first connecting section (2111) and a second connecting section (2112). The reaction chamber (22) is located below the connecting part (21) and is used to receive the reagent flowing out through the first channel in the connector (211); The storage module (1) and the reaction module (2) are constructed as independent modules; When testing is required, the bottom of each storage chamber (11) on the storage module (1) is aligned with each connector (211) on the reaction module (2), and then the two are pressed together. The first connecting segment (2111) of the connector (211) is configured to break the bottom seal of the second hole and push the seal (13) to disengage from the bottom of the storage chamber (11) and move towards the middle of the storage chamber (11) to open the bottom outlet of the storage chamber (11) so that the reagent in the storage chamber (11) can flow out through the first channel in the connector (211). The first connecting segment (2111) is located in the first hole, and the size of the first connecting segment (2111) is adapted to the size of the first hole to achieve a seal. The second connecting segment (2112) is located in the second hole, and the size of the second connecting segment (2112) is adapted to the size of the second hole to achieve a seal.

2. The microfluidic detection chip as described in claim 1, characterized in that, The top of the storage compartment (11) is larger than the bottom of the storage compartment (11).

3. The microfluidic detection chip as described in claim 1, characterized in that, The connecting part (21) is provided with a groove, and the bottom of the connector (211) is located in the groove.

4. The microfluidic detection chip as described in claim 1, characterized in that, The storage module (1) includes a sample compartment (12) and a filter element disposed in the sample compartment (12). The bottom of the sample compartment (12) extends towards the top of the sample compartment (12) to form a pointed structure, and the pointed structure is inserted into the filter element.

5. The microfluidic detection chip as described in claim 1, characterized in that, The storage compartment (11) includes a lyophilized reagent compartment (111) for storing lyophilized reagents, the top of which is lower than the top of the other storage compartments (11).

6. The microfluidic detection chip as described in claim 5, characterized in that, The desiccant module (3) includes a desiccant chamber (31) for placing the desiccant. The desiccant module (3) is used to insert into the top of the freeze-dried reagent chamber (111). When the desiccant module (3) is inserted into the top of the freeze-dried reagent chamber (111), the top of the desiccant chamber (31) and the top of the storage chamber (11) are at the same height.

7. The microfluidic detection chip as described in claim 1, characterized in that, The storage compartment (11) includes a lyophilized reagent compartment (111) for storing lyophilized reagents. The upper part of the lyophilized reagent compartment (111) is provided with a limiting structure to restrict the falling of the desiccant so as to isolate the desiccant from the lyophilized reagents in the lyophilized reagent compartment (111).

8. The microfluidic detection chip as described in claim 1, characterized in that, The reaction module (2) includes multiple second channels (23) and a valve area (24). The second channels (23) are connected one-to-one with the multiple connectors (211). The second channels (23) are used to guide the reagent flowing in through the first channel of the connector (211) to the valve area (24) so ​​that the reagent can be selectively guided to the reaction chamber (22) through the valve (4) provided in the valve area (24).

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