Centrifugal micro-fluidic chip and detection equipment

By designing a centrifugal microfluidic chip containing sample chamber, reagent module, purification module and amplification module, the sample detection efficiency in the prior art is solved by using structures such as column valves and paraffin valves. The problems of low and low accuracy simplify the detection process and improve the detection accuracy.

CN119216000APending Publication Date: 2024-12-31HUNAN BIOMETA INTELLIGENT MFG TECH CO LTD

Patent Information

Application Number
CN202310781753.X
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2023-06-28
Publication Date
2024-12-31

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Abstract

The invention provides a centrifugal micro-fluidic chip and detection equipment, and the centrifugal micro-fluidic chip comprises a sample cabin used for accommodating a sample liquid; the reagent module is used for accommodating a reagent solution for cracking the sample solution; the purification module comprises a washing cavity containing a washing solution and an elution cavity containing an elution solution; the collection module comprises a uniform mixing cavity, a column passing valve and a storage cavity, the uniform mixing cavity is communicated with the storage cavity through the column passing valve used for adsorbing samples, the sample bin, the reagent module and the washing cavity are all communicated with the liquid inlet end of the uniform mixing cavity, and the elution cavity is communicated with the liquid inlet end of the storage cavity. The column passing valve is matched with the reagent module to extract a sample, amplification reaction can be performed after purification operation of washing and elution is performed, the whole process of splitting decomposition, purification, collection and amplification of the sample can be completed on one chip, the solution transfer process in the prior art can be avoided, the detection process is simplified, and the detection efficiency is improved. The sample detection precision and the detection flow can be simultaneously improved.
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Description

Technical Field

[0001] The invention belongs to the field of microfluidic technology, and in particular relates to a centrifugal microfluidic chip and a detection device. Background Art

[0002] Microfluidic chips can complete the sample detection process of traditional laboratories on a small operating platform. They have the advantages of small size, high integration, fast analysis speed, and low reagent consumption. They are widely used in biomedicine, environmental monitoring, analytical chemistry and other fields. Among them, centrifugal microfluidic chips use centrifugal force as the driving force for liquid flow. Combined with passive valves and active valves, only a small motor is needed to control multiple unit structures at the same time, realizing accurate control of the liquid in the chip. At present, centrifugal microfluidic chips are mostly used for biochemical and immune detection. Due to the small size of microfluidic chips and the limitations of flow channel design, sample extraction and amplification cannot usually be integrated. Generally, sample extraction needs to be performed in other components first, and then the solution is transferred to the microfluidic chip for amplification (such as CN113322172A), resulting in a more complicated detection process and low detection efficiency. In addition, the solution is easily contaminated by the outside world during the external transfer process, resulting in low sample detection accuracy. Summary of the invention

[0003] The main purpose of the present invention is to provide a centrifugal microfluidic chip and a detection device, aiming to solve the technical problems of low efficiency and low precision of microfluidic chip sample detection in the prior art.

[0004] In order to achieve the above-mentioned purpose, the present invention provides a centrifugal microfluidic chip, which includes: a sample chamber for accommodating a sample liquid; a reagent module for accommodating a reagent liquid for lysing the sample liquid; a purification module, including a washing chamber for accommodating a washing liquid and an elution chamber for accommodating an elution liquid; a collection module, including a mixing chamber, a column valve and a storage chamber, the mixing chamber and the storage chamber are connected through the column valve for adsorbing samples, the sample chamber, the reagent module, and the washing chamber are all connected to the liquid inlet end of the mixing chamber, and the elution chamber is connected to the liquid inlet end of the storage chamber; an amplification module, including an amplification chamber and a detection chamber for accommodating a detection reagent, the liquid inlet end of the detection chamber is connected to the liquid outlet end of the mixing chamber, and the liquid outlet end of the detection chamber is connected to the amplification chamber.

[0005] In an embodiment of the present invention, there are multiple amplification modules, and the multiple amplification modules are connected to the mixing chamber through a confluence channel. The confluence channel is connected to a first paraffin valve, and the first paraffin valve is used to conduct the confluence channel at normal temperature and close the confluence channel under heating.

[0006] In an embodiment of the present invention, a connecting flow channel with a first siphon valve and a second paraffin valve is connected between the mixing chamber and the confluence flow channel, the first siphon valve is used to intercept the solution flowing back from the confluence flow channel to the mixing chamber, and the second paraffin valve is used to close the connecting flow channel at room temperature and to conduct the connecting flow channel under heating; and / or, the confluence flow channel is arranged in an arc shape, and the arc radius of the confluence flow channel is gradually expanded from one end close to the mixing chamber to the end away from the mixing chamber.

[0007] In an embodiment of the present invention, there are multiple washing chambers, and the multiple washing chambers are connected to the mixing chamber through a washing flow channel. A second siphon valve is provided on the washing flow channel. The second siphon valve is located between the purification module and the mixing chamber, and is used to intercept the solution flowing back from the mixing chamber to the washing chamber.

[0008] In an embodiment of the present invention, a liquid outlet channel is provided on the washing chamber, and the liquid outlet channel is connected to the washing channel. A third paraffin valve is provided on the washing channel between any two adjacent liquid outlet channels, and the third paraffin valve is used to close the washing channel under normal temperature and to open the washing channel under heating.

[0009] In an embodiment of the present invention, a cut-off cavity for intercepting hot-melt paraffin is also provided on the washing flow channel. The cut-off cavity is located at the front end of the third paraffin valve along the outflow direction of the washing liquid. The number of the cut-off cavity and the third paraffin valve are the same and are arranged one-to-one.

[0010] In an embodiment of the present invention, the purification module, the reagent module and the sample chamber are spaced apart along the first centrifugal direction of the centrifugal microfluidic chip, the storage chamber, the column valve and the mixing chamber are spaced apart along the first centrifugal direction, the sample chamber and the reagent module can transport solution to the mixing chamber along the second centrifugal direction of the centrifugal microfluidic chip, the washing chamber can transport washing solution to the mixing chamber along the first centrifugal direction, and the elution chamber can transport solution to the storage chamber along the first centrifugal direction.

[0011] In an embodiment of the present invention, the inner wall of the sample chamber, the inner wall of the reagent module and the inner wall of the purification module are all located at the same arc radius, and the inner wall of the sample chamber, the outer wall of the reagent module and the outer wall of the purification module are at different arc radii; and / or, the elution chamber is located on the side of the washing chamber away from the reagent chamber, and the elution chamber and multiple washing chambers are located on the same radius arc and are spaced apart along the first centrifugal direction of the centrifugal microfluidic chip.

[0012] In an embodiment of the present invention, the reagent module includes a plurality of reagent chambers, and the plurality of reagent chambers are arranged at intervals along the centrifugal radial direction of the centrifugal microfluidic chip; and / or the centrifugal microfluidic chip also includes a waste liquid chamber, and the waste liquid chamber is located on the outside of the collection module along the centrifugal radial direction of the centrifugal microfluidic chip, and the waste liquid chamber and the storage chamber are connected through a third siphon valve and are used to collect waste liquid, and the third siphon valve is used to intercept waste liquid flowing back from the waste liquid chamber to the storage chamber.

[0013] The present invention also discloses a detection device, which includes the centrifugal microfluidic chip as described above.

[0014] Through the above technical solution, the centrifugal microfluidic chip provided by the embodiment of the present invention has the following beneficial effects:

[0015] When the centrifugal microfluidic chip is used for sample detection, the sample liquid can be injected into the sample chamber, and then the sample liquid in the sample chamber is thrown into the mixing chamber of the collection module through centrifugal action, and then the centrifugal force is adjusted so that the reagent liquid in the reagent module is thrown into the mixing chamber under the centrifugal action, so that the reagent liquid lyses the sample liquid, and the sample pretreatment and sample extraction can be realized. Then the centrifugal force is adjusted, and the solution in the mixing chamber enters the storage chamber through the column valve, and the sample is adsorbed through the column valve for sample collection, and then the washing liquid in the washing chamber can be thrown into the mixing chamber through the centrifugal action, and the centrifugal force is adjusted, and the washing liquid in the mixing chamber is thrown into the storage chamber through the column valve, so as to achieve the washing effect, and then the elution liquid in the elution chamber is thrown into the mixing chamber through the storage chamber, and the sample adsorbed by the column valve can be eluted, so as to achieve sample purification and obtain the liquid to be tested, and the liquid to be tested in the mixing chamber can enter the amplification chamber through the detection chamber through centrifugal adjustment, and the liquid to be tested and the detection reagent can be mixed in the amplification reaction in the amplification chamber. The centrifugal microfluidic chip of the present invention extracts samples through a column valve in conjunction with a reagent module, and can perform an amplification reaction after purification operations such as washing and elution. The entire process of sample lysis, purification, collection and amplification can be completed on one chip, avoiding the solution transfer process in the prior art, simplifying the detection process, and can simultaneously improve the sample detection accuracy and the detection process.

[0016] Other features and advantages of the present invention will be described in detail in the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The accompanying drawings are used to provide an understanding of the present invention and constitute a part of the specification. Together with the following specific embodiments, they are used to explain the present invention, but do not constitute a limitation of the present invention. In the accompanying drawings:

[0018] Figure 1 is a schematic structural diagram of a centrifugal microfluidic chip according to an embodiment of the present invention;

[0019] Figure 2 is a schematic diagram of the cross-sectional structure of a centrifugal microfluidic chip according to an embodiment of the present invention;

[0020] Figure 3 is a schematic structural diagram of a centrifugal microfluidic chip at one viewing angle according to an embodiment of the present invention;

[0021] Figure 4 is a schematic structural diagram of a centrifugal microfluidic chip according to an embodiment of the present invention at another viewing angle;

[0022] Figure 5 is a schematic structural diagram of a centrifugal microfluidic chip according to another embodiment of the present invention;

[0023] Figure 6 is a schematic structural diagram of a chip bottom plate of a centrifugal microfluidic chip according to an embodiment of the present invention at a viewing angle;

[0024] Figure 7 is a schematic structural diagram of a chip bottom plate of a centrifugal microfluidic chip according to an embodiment of the present invention at another viewing angle;

[0025] Figure 8 2 is a schematic diagram of the column valve structure of a centrifugal microfluidic chip according to an embodiment of the present invention;

[0026] Fig. 9 2 is a schematic diagram of the structure of a first valve body of a centrifugal microfluidic chip according to an embodiment of the present invention;

[0027] Fig.10 Schematic diagram of the second valve body structure of a centrifugal microfluidic chip according to an embodiment of the present invention.

[0028] Description of Reference Numerals

[0029] Label Name Label Name

[0030] 100 Centrifugal Microfluidic Chip 5 Amplification Module

[0031] 1 Sample compartment 51 Amplification chamber

[0032] 2 Reagent module 52 Detection chamber

[0033] 21 Reagent chamber 6 Converging flow channel

[0034] 3 Purification module 61 first paraffin valve

[0035] 31 Washing chamber 62 Pressure stabilizing chamber

[0036] 311 Outlet channel 7 Connecting channel

[0037] 32 Elution chamber 71 First siphon valve

[0038] 4 Collection module 72 Second paraffin valve

[0039] 41 Mixing chamber 8 Washing channel

[0040] 42 Column valve 81 Second siphon valve

[0041] 421 First valve body 82 Third paraffin valve

[0042] 4211 Clamp 83 Cut-off chamber

[0043] 4212 Positioning column 9 Waste chamber

[0044] 422 second valve body 10 chip substrate

[0045] 4221 Card slot 20 Chip base plate

[0046] 4222 Positioning hole 201 Sealing positioning block

[0047] 423 flow channel 202 flow channel hole

[0048] 424 Pressing protrusion 203 Exhaust hole

[0049] 43 Storage chamber 30 Centrifugal hole DETAILED DESCRIPTION

[0050] The specific embodiments of the present invention are described in detail below in conjunction with the accompanying drawings. It should be understood that the specific embodiments described herein are only used to illustrate and explain the present invention, and are not used to limit the present invention.

[0051] The centrifugal microfluidic chip according to the present invention will be described below with reference to the accompanying drawings.

[0052] like Figures 1 to 4As shown, in an embodiment of the present invention, the centrifugal microfluidic chip 100 includes a sample chamber 1, a reagent module 2, a purification module 3, a collection module 4 and an amplification module 5; the sample chamber 1 is used to contain a sample liquid; the reagent module 2 contains a reagent liquid for lysing the sample liquid; the purification module 3 includes a washing chamber 31 containing a washing liquid and an elution chamber 32 containing an elution liquid; the collection module 4 includes a mixing chamber 41, a column valve 42 and a storage chamber 43, the mixing chamber 41 and the storage chamber 43 are connected through the column valve 42 for adsorbing the sample, the sample chamber 1, the reagent module 2, the washing chamber 31 are all connected to the liquid inlet end of the mixing chamber 41, and the elution chamber 32 is connected to the liquid inlet end of the storage chamber 43; the amplification module 5 includes an amplification chamber 51 and a detection chamber 52 containing a detection reagent, the liquid inlet end of the detection chamber 52 is connected to the liquid outlet end of the mixing chamber 41, and the liquid outlet end of the detection chamber 52 is connected to the amplification chamber 51.

[0053] It can be understood that the centrifugal microfluidic chip 100 in this embodiment is mainly used for nucleic acid detection. The centrifugal microfluidic chip 100 is disc-shaped as a whole. The centrifugal microfluidic chip 100 includes a chip base and a chip bottom plate 20, and two groups of sample chambers 1, reagent modules 2, purification modules 3, collection modules 4 and amplification modules 5 are symmetrically and evenly distributed.

[0054] When the centrifugal microfluidic chip 100 in this embodiment is used for sample detection, the sample liquid can be injected into the sample chamber 1, and then the sample liquid in the sample chamber 1 is thrown into the mixing chamber 41 of the collection module 4 by centrifugal action, and then the centrifugal force is adjusted to make the reagent liquid in the reagent module 2 be thrown into the mixing chamber 41 under the centrifugal action, so that the reagent liquid lyses the sample liquid, which can realize sample pretreatment and sample extraction, and then the centrifugal force is adjusted to make the solution in the mixing chamber 41 pass through the column valve 42 into the receiving chamber 43, and the sample is adsorbed by the column valve 42 to collect the sample. Then, the washing liquid in the washing chamber 31 can be thrown into the mixing chamber 41 by centrifugal action, and the centrifugal force is adjusted to throw the washing liquid in the mixing chamber 41 into the storage chamber 43 through the column valve 42, so as to achieve the washing effect. Then, the elution liquid in the elution chamber 32 is thrown into the mixing chamber 41 through the storage chamber 43, and the sample adsorbed by the column valve 42 can be eluted to purify the sample and obtain the liquid to be tested. Through centrifugal adjustment, the liquid to be tested in the mixing chamber 41 can enter the amplification chamber 51 through the detection chamber 52, and the liquid to be tested and the detection reagent can be mixed and then an amplification reaction can be carried out in the amplification chamber 51. The centrifugal microfluidic chip 100 in this embodiment extracts the sample through the column valve 42 in cooperation with the reagent module 2, and can carry out an amplification reaction after washing and eluting purification operations. The entire process of sample lysis, purification, collection and amplification can be completed on one chip, which can avoid the solution transfer process in the prior art, simplify the detection process, and improve the sample detection accuracy and detection process at the same time.

[0055] like Figures 1 to 5 As shown, there are multiple amplification modules 5, and the multiple amplification modules 5 are connected to the mixing chamber 41 through the confluence channel 6. The confluence channel 6 is connected to a first paraffin valve 61, and the first paraffin valve 61 is used to conduct the confluence channel 6 under normal temperature and close the confluence channel 6 under heating. A centrifugal hole 30 is provided at the center of the centrifugal microfluidic chip 100. The centrifugal hole 30 can cooperate with a centrifugal drive. Under the drive of the centrifugal drive, the centrifugal microfluidic chip 100 can rotate around the rotation center of the centrifugal hole 30. Multiple amplification modules 5 can be arranged at intervals along the circumference of the centrifugal hole 30, and the detection reagents contained in the detection chamber 52 of each amplification module 5 are different from each other. Under the action of centrifugation, the liquid to be tested in the mixing chamber 41 can enter the multiple amplification modules 5 through the confluence flow channel 6. After the centrifugation is completed, the first paraffin valve 61 can be heated to make the hot-melt paraffin valve close the confluence flow channel 6, thereby ensuring that the amplification module 5 is always in a closed environment during the amplification process. The first paraffin valve 61 is located on the side of the confluence flow channel 6 close to the centrifugal hole 30. After the paraffin in the first paraffin valve 61 is hot-melted, it can enter the confluence flow channel 6 under the action of centrifugation. Multiple amplification modules 5 can simultaneously perform multiple groups of tests on samples in a closed environment, further improving the sample detection efficiency.

[0056] In the prior art, when multiple tests are required, considering the cross-mixing problem of the reagent chamber, in order to ensure the accuracy of the test, it is necessary to distinguish between independent tests and ensure that the properties of the samples and reagents entering each test reagent chamber are consistent. As a result, the liquid circuit and control structure of the existing multi-flux detection consumables are relatively complex and the manufacturing cost is high. In this embodiment, through the layout and coordination between the sample chamber 1, the reagent module 2, the purification module 3, the collection module 4 and the multiple amplification modules 5, independent tests can be performed while ensuring that the amount of solution entering each amplification module 5 is consistent, and the liquid circuit and control structure are simplified, reducing the manufacturing cost.

[0057] In the embodiment of the present invention, Figure 4 and Figure 5As shown, a connecting flow channel 7 with a first siphon valve 71 and a second paraffin valve 72 is connected between the mixing chamber 41 and the confluence flow channel 6. The first siphon valve 71 is used to intercept the solution flowing back from the confluence flow channel 6 to the mixing chamber 41, and the second paraffin valve 72 is used to close the connecting flow channel 7 at room temperature and to conduct the connecting flow channel 7 under heating. In addition, the confluence flow channel 6 is arranged in an arc shape, and the arc radius of the confluence flow channel 6 is gradually expanded from one end close to the mixing chamber 41 to the end away from the mixing chamber 41. The connecting flow channel 7 in the present embodiment is located between the converging flow channel 6 and the mixing chamber 41. The first siphon valve 71 may be provided with a cut-off bend, which can cut off the solution flowing back from the converging flow channel 6 to the mixing chamber 41. When it is necessary to throw the test liquid in the mixing chamber 41 into the detection chamber 52, the first siphon valve 71 is located at the front end of the second paraffin valve 72 along the outflow direction of the test liquid. The centrifugal force can be adjusted first so that the test liquid can break through the adsorption force of the first siphon valve 71 on the test liquid under the action of the centrifugal force, and the second paraffin valve 72 is heated to make the second paraffin valve 72 conduct to the converging flow channel 6. In the present embodiment, the first siphon valve 71 and the second paraffin valve 72 cooperate to ensure that the test liquid in the mixing chamber 41 is accurately thrown to the converging flow channel 6, and can avoid accidental throwing and the situation where the solution cannot be thrown out smoothly.

[0058] Moreover, in the present embodiment, the arc radius of the converging flow channel 6 from the rotation center is smaller at the end close to the mixing chamber 41 and larger at the end away from the mixing chamber 41, which can balance the amount of the liquid to be detected transported by the converging flow channel 6 to multiple amplification modules 5, overcome the problem of uneven liquid to be detected in multiple amplification modules 5 caused by the distribution of the flow channel and the amplification modules 5, avoid the situation where the uneven liquid to be detected in each amplification module 5 affects the detection sensitivity, improve the detection sensitivity of each amplification module 5, and ensure the overall detection sensitivity and stability of the centrifugal microfluidic chip 100.

[0059] In one embodiment, both ends of the converging flow channel 6 are provided with a pressure-stabilizing chamber 62 for accommodating excess test liquid. The two pressure-stabilizing chambers 62 are both connected to the outside of the converging flow channel 6. One of the pressure-stabilizing chambers 62 is arranged close to the connecting flow channel 7 and is located on the outside of the second paraffin valve 72, and can intercept the hot-melt paraffin in the second paraffin valve 72 and excess test liquid. The other pressure-stabilizing chamber 62 is arranged far away from the connecting flow channel 7, and the multiple amplification modules 5 are evenly spaced. The distance between any two adjacent amplification modules 5 is d1, and the distance between the pressure-stabilizing chamber 62 and the amplification module 5 is d2, d2>d1, which can facilitate balancing the test liquid entering the multiple amplification modules 5.

[0060] In one embodiment, there are multiple washing chambers 31, and the multiple washing chambers 31 are connected to the mixing chamber 41 through the washing channel 8. The washing channel 8 is provided with a second siphon valve 81, which is located between the purification module 3 and the mixing chamber 41 and is used to intercept the solution flowing back from the mixing chamber 41 to the washing chamber 31. The purification module 3 is arranged close to the centrifugal hole 30, and the collection module 4 is located outside the purification module 3. When it is necessary to throw the washing liquid in the washing chamber 31 into the collection module 4, the centrifugal force can be adjusted so that the washing liquid can break through the adsorption force of the second siphon valve 81 on the solution under the centrifugal action, and the second siphon valve 81 can also intercept the solution flowing back from the mixing chamber 41 to the washing chamber 31. In this embodiment, the cross-sections of the multiple washing chambers 31 can all be fan-shaped, and the multiple washing chambers 31 are arranged at intervals around the circumference of the centrifugal hole 30, and are all connected to the mixing chamber 41 through the washing channel 8, which can improve the structural compactness of the centrifugal microfluidic chip 100.

[0061] Specifically, a liquid outlet channel 311 is provided on the washing chamber 31, and the liquid outlet channel 311 is connected to the washing channel 8. A third paraffin valve 82 is provided on the washing channel 8 between any two adjacent liquid outlet channels 311. The third paraffin valve 82 is used to close the washing channel 8 at room temperature and to conduct the washing channel 8 under heating. The liquid outlet channel 311 in this embodiment extends outward from the bottom of the washing chamber 31. The third paraffin valve 82 in this embodiment is located between the two liquid outlet channels 311, and can isolate two independent washing chambers 31 at room temperature. In one embodiment, the number of washing chambers 31 is four, and the number of third paraffin valves 82 is three. One of the four washing chambers 31 close to the mixing chamber 41 is connected to the mixing chamber 41 through the second siphon valve 81. Through the second siphon valve 81 and the three third paraffin valves 82 that are heated and melted, the liquid outlet control accuracy of the washing liquid in the washing chamber 31 can be improved. In this embodiment, there is only one elution chamber 32, and the elution chamber 32 and the storage chamber 43 can be connected through an elution channel. The elution channel is located on the outside of the washing channel 8, and a paraffin valve can be provided on the elution channel to close or conduct the elution channel.

[0062] like Figure 4 and Figure 5 As shown, the washing flow channel 8 and the elution flow channel are also provided with an interception cavity 83 for intercepting hot-melt paraffin. The interception cavity 83 on the elution flow channel is located at the front end of the paraffin valve along the outflow direction of the elution liquid, and the interception cavity 83 is located at the front end of the third paraffin valve 82 along the outflow direction of the washing liquid. The number of the interception cavities 83 and the third paraffin valve 82 is consistent and arranged in a one-to-one correspondence. The interception cavity 83 in this embodiment can be arranged obliquely along the outflow direction of the washing liquid, so as to facilitate the hot-melt paraffin to flow into the interception cavity 83 under the centrifugal action, and the bottom of the interception cavity 83 is provided with an interception arc surface protruding toward the mixing cavity 41, which can prevent the solution from flowing out of the interception cavity 83.

[0063] like Figures 1 to 3 As shown, the purification module 3, the reagent module 2 and the sample chamber 1 are arranged at intervals along the first centrifugal direction of the centrifugal microfluidic chip 100, the storage chamber 43, the column valve 42 and the mixing chamber 41 are arranged at intervals along the first centrifugal direction, the sample chamber 1 and the reagent module 2 can transport the solution to the mixing chamber 41 along the second centrifugal direction of the centrifugal microfluidic chip 100, the washing chamber 31 can transport the washing solution to the mixing chamber 41 along the first centrifugal direction, and the elution chamber 32 can transport the solution to the storage chamber 43 along the first centrifugal direction. The first centrifugal direction is the rotation direction of the centrifugal microfluidic chip 100 rotating forward around the centrifugal hole 30, and the second centrifugal direction is the rotation direction of the centrifugal microfluidic chip 100 rotating reversely around the centrifugal hole 30. In this embodiment, the purification module 3, the reagent module 2 and the sample chamber 1 are arranged at intervals along the first centrifugal direction of the centrifugal microfluidic chip 100, and the storage chamber 43, the column valve 42 and the mixing chamber 41 are arranged at intervals along the first centrifugal direction. The overall weight distribution of the centrifugal microfluidic chip 100 can be balanced to facilitate centrifugal operation. At the same time, the sample chamber 1 and the reagent module 2 can transport the solution to the mixing chamber 41 along the second centrifugal direction of the centrifugal microfluidic chip 100, the washing chamber 31 can transport the washing solution to the mixing chamber 41 along the first centrifugal direction, and the elution chamber 32 can transport the solution to the storage chamber 43 along the first centrifugal direction, so as to realize the solution transportation in different directions, avoid the situation where the solution is accidentally thrown away, and at the same time improve the compactness of the structure and the weight balance.

[0064] In one embodiment, the inner wall of the sample chamber 1, the inner wall of the reagent module 2 and the inner wall of the purification module 3 are all located at the same arc radius, and the inner wall of the sample chamber 1, the outer wall of the reagent module 2 and the outer wall of the purification module 3 are at different arc radii; and, the elution chamber 32 is located on the side of the washing chamber 31 away from the reagent chamber 21, and the elution chamber 32 and the multiple washing chambers 31 are located on the same radius arc and are spaced apart along the first centrifugal direction of the centrifugal microfluidic chip 100.

[0065] The distances between the inner wall of the sample chamber 1, the inner wall of the reagent module 2, the inner wall of the purification module 3 and the rotation center are the same, and the distances between the inner wall of the sample chamber 1, the outer wall of the reagent module 2, the outer wall of the purification module 3 and the rotation center are different, so that the critical centrifugal speeds of the liquid out of the sample chamber 1, the reagent module 2 and the purification module 3 are different, which can facilitate the centrifugal control of the sample chamber 1, the reagent module 2 and the purification module 3, and the elution chamber 32 is located on the side of the washing chamber 31 away from the reagent chamber 21, which can facilitate the centrifugal discharge of the eluent.

[0066] like Figures 1 to 5As shown, the reagent module 2 includes a plurality of reagent chambers 21, and the plurality of reagent chambers 21 are arranged at intervals along the centrifugal radial direction of the centrifugal microfluidic chip 100; and the centrifugal microfluidic chip 100 also includes a waste liquid chamber 9, which is located on the outside of the collection module 4 along the centrifugal radial direction of the centrifugal microfluidic chip 100, and the waste liquid chamber 9 and the storage chamber 43 are connected through a third siphon valve and are used to collect waste liquid, and the third siphon valve is used to intercept waste liquid flowing back from the waste liquid chamber 9 to the storage chamber 43. The centrifugal radial direction in this embodiment can be the radial direction of the centrifugal hole 30, and the multiple reagent chambers 21 are all fan-shaped. The multiple reagent chambers 21 are spaced apart along the centrifugal radial direction. In one embodiment, the distance between the outer wall of the sample chamber 1 and the rotation center is r1, the distance between the outer wall of the reagent chamber 21 located at the outermost side and the rotation center is r2, and the distance between the outer wall of the washing chamber 31 and the rotation center is r3. r1>r3>r2 can facilitate the liquid discharge sequence control of the sample chamber 1, the reagent module 2 and the purification module 3. The waste liquid chamber 9 can be located outside the collection module 4 along the centrifugal radial direction. After the solution in the mixing chamber 41 enters the storage chamber 43 through the column valve 42, centrifugal adjustment can be performed to throw the waste liquid in the storage chamber 43 into the waste liquid chamber 9 through the third siphon valve. The third siphon valve can prevent the waste liquid from the waste liquid chamber 9 from flowing back into the storage chamber 43.

[0067] The present invention also discloses a detection device, which includes the centrifugal microfluidic chip 100 as described above. The specific structure of the centrifugal microfluidic chip 100 refers to the above embodiment. Since the detection device adopts all the technical solutions of all the above embodiments, it at least has all the beneficial effects brought by the technical solutions of the above embodiments, which will not be repeated here one by one.

[0068] In one embodiment, if Figures 8 to 10 As shown, the column valve 42 may include a first valve body 421 with a plurality of positioning posts 4212, and a second valve body 422 with a plurality of positioning holes 4222. The positioning posts 4212 and the positioning holes 4222 can be positioned and matched one by one, so that a flow channel 423 for the solution to pass through is formed on the column valve 42. The first valve body 421 and the second valve body 422 may be both provided with a clamping protrusion 424, which can clamp a silicone membrane located at the flow channel 423, and the silicone membrane is used to adsorb nucleic acids. In addition, the outer ring of the plurality of clamping protrusions 424 of the first valve body 421 is provided with a clamping ring 4211 protruding outward, and the second valve body 422 is provided with a clamping groove 4221 that is clamped and matched with the clamping ring 4211. After the positioning posts 4212 and the positioning holes 4222 are positioned and matched, the clamping ring 4211 can extend into the clamping groove 4221 to connect the first valve body 421 and the second valve body 422, and the installation of the silicone membrane can be facilitated.

[0069] Specifically, Figure 6 and Figure 7As shown, a sealing positioning block 201 is provided on the chip bottom plate 20 for positioning with the chip substrate 10. After the sealing positioning block 201 is extended into the open groove provided in the chip substrate 10, the shape of the open groove and the sealing positioning block 201 are consistent, and the positioning is more accurate, so that the chip substrate 10 and the chip bottom plate 20 can be sealed and connected, and each complete closed cavity can be formed. The sealing positioning block 201 is provided with a flow channel hole 202 for solution to pass through corresponding to the flow channel of each cavity. To facilitate the solution flow channel, each flow channel hole 202 is an arc hole. An exhaust hole 203 is provided on the chip bottom plate 20 corresponding to each paraffin valve. Paraffin is injected into the paraffin valve through the exhaust hole 203. After the paraffin is pre-set, the exhaust hole 203 is completely blocked, and a waterproof and breathable film can be covered at the exhaust hole 203. After the paraffin in the paraffin valve is hot-melted, it can be exhausted to the outside of the centrifugal microfluidic chip 100 through the exhaust hole 203, thereby balancing the centrifugal microfluidic chip 100 and the external atmospheric pressure.

[0070] In addition, in order to facilitate the smooth flow of the sample liquid in the sample chamber 1, the sample chamber 1 is provided with a guide arc side wall and a confluence sharp corner in sequence along the second centrifugal direction. The confluence sharp corner is connected to the mixing chamber 41 through a capillary valve. The guide arc side wall can facilitate the sample liquid to be thrown out, and avoid the situation where the sample liquid is adsorbed to the side wall and cannot be thrown out. The confluence sharp corner arranged near the mixing chamber 41 can facilitate the liquid confluence and fully throw the sample liquid into the mixing chamber 41. The upper end of the sample chamber 1 is open, and a cover body can be used to cover the opening. The outer side of the cover body can be provided with an anti-slip layer for easy holding, and the outer side can be convenient for opening or closing the opening. The cover body can be threadedly connected to the outer wall of the sample chamber 1.

[0071] In the description of the present invention, it should be understood that the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one of the features. In the description of the present invention, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0072] In the present invention, unless otherwise clearly specified and limited, the terms "installed", "connected", "connected", "fixed" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral one; it can be a mechanical connection, an electrical connection, or communication with each other; it can be a direct connection, or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements, unless otherwise clearly defined. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0073] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine the different embodiments or examples described in this specification and the features of the different embodiments or examples, without contradiction.

[0074] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations of the present invention. A person skilled in the art may change, modify, replace and vary the above embodiments within the scope of the present invention.

Claims

1. A centrifugal microfluidic chip, characterized in that: The centrifugal microfluidic chip (100) comprises: A sample chamber (1), used for containing a sample liquid; A reagent module (2) containing a reagent solution for lysing a sample solution; A purification module (3) comprising a washing chamber (31) containing a washing liquid and an elution chamber (32) containing an elution liquid; The collecting module (4) comprises a mixing chamber (41), a column valve (42) and a storage chamber (43); the mixing chamber (41) and the storage chamber (43) are connected via the column valve (42) for adsorbing samples; the sample chamber (1), the reagent module (2) and the washing chamber (31) are all connected to the liquid inlet end of the mixing chamber (41); and the elution chamber (32) and the liquid inlet end of the storage chamber (43) are connected; The amplification module (5) comprises an amplification chamber (51) and a detection chamber (52) containing a detection reagent, wherein the liquid inlet end of the detection chamber (52) is connected to the liquid outlet end of the mixing chamber (41), and the liquid outlet end of the detection chamber (52) is connected to the amplification chamber (51).

2. The centrifugal microfluidic chip according to claim 1, characterized in that: There are multiple amplification modules (5), and the multiple amplification modules (5) are connected to the mixing chamber (41) through a confluence channel (6). The confluence channel (6) is connected to a first paraffin valve (61), and the first paraffin valve (61) is used to conduct the confluence channel (6) under normal temperature and close the confluence channel (6) under heating.

3. The centrifugal microfluidic chip according to claim 2, characterized in that: A connecting flow channel (7) having a first siphon valve (71) and a second paraffin valve (72) is connected between the mixing chamber (41) and the converging flow channel (6); the first siphon valve (71) is used to intercept the solution flowing back from the converging flow channel (6) to the mixing chamber (41); the second paraffin valve (72) is used to close the connecting flow channel (7) under normal temperature and to open the connecting flow channel (7) under heating; and / or, The converging flow channel (6) is arranged in an arc shape, and the arc radius of the converging flow channel (6) is arranged to gradually expand from an end close to the mixing chamber (41) to an end away from the mixing chamber (41).

4. The centrifugal microfluidic chip according to claim 1, characterized in that: There are a plurality of washing chambers (31), and the plurality of washing chambers (31) are connected to the mixing chamber (41) through a washing channel (8). A second siphon valve (81) is provided on the washing channel (8). The second siphon valve (81) is located between the purification module (3) and the mixing chamber (41), and is used to intercept the solution flowing back from the mixing chamber (41) to the washing chamber (31).

5. The centrifugal microfluidic chip according to claim 4, characterized in that: The washing chamber (31) is provided with a liquid outlet channel (311), the liquid outlet channel (311) is connected to the washing channel (8), and a third paraffin valve (82) is provided on the washing channel (8) between any two adjacent liquid outlet channels (311), the third paraffin valve (82) is used to close the washing channel (8) under normal temperature and to open the washing channel (8) under heating.

6. The centrifugal microfluidic chip according to claim 5, characterized in that: The washing flow channel (8) is also provided with an intercepting cavity (83) for intercepting hot-melt paraffin. The intercepting cavity (83) is located at the front end of the third paraffin valve (82) along the outflow direction of the washing liquid. The number of the intercepting cavities (83) and the third paraffin valve (82) is the same and they are arranged in a one-to-one correspondence.

7. The centrifugal microfluidic chip according to any one of claims 1 to 6, characterized in that: The purification module (3), the reagent module (2) and the sample chamber (1) are arranged at intervals along the first centrifugal direction of the centrifugal microfluidic chip (100); the storage chamber (43), the column valve (42) and the mixing chamber (41) are arranged at intervals along the first centrifugal direction; the sample chamber (1) and the reagent module (2) can transport a solution to the mixing chamber (41) along the second centrifugal direction of the centrifugal microfluidic chip (100); the washing chamber (31) can transport a washing solution to the mixing chamber (41) along the first centrifugal direction; and the elution chamber (32) can transport a solution to the storage chamber (43) along the first centrifugal direction.

8. The centrifugal microfluidic chip according to claim 7, characterized in that: The inner wall of the sample chamber (1), the inner wall of the reagent module (2) and the inner wall of the purification module (3) are all located at the same arc radius, and the inner wall of the sample chamber (1), the outer wall of the reagent module (2) and the outer wall of the purification module (3) are located at different arc radii; and / or, The elution chamber (32) is located on a side of the washing chamber (31) away from the reagent chamber (21); the elution chamber (32) and the plurality of washing chambers (31) are located on the same radius arc and are spaced apart along the first centrifugal direction of the centrifugal microfluidic chip (100).

9. The centrifugal microfluidic chip according to any one of claims 1 to 6, characterized in that: The reagent module (2) comprises a plurality of reagent chambers (21), and the plurality of reagent chambers (21) are arranged at intervals along the centrifugal radial direction of the centrifugal microfluidic chip (100); and / or, The centrifugal microfluidic chip (100) further comprises a waste liquid chamber (9), wherein the waste liquid chamber (9) is located outside the collection module (4) along the centrifugal radial direction of the centrifugal microfluidic chip (100), the waste liquid chamber (9) and the storage chamber (43) are connected via a third siphon valve and are used to collect waste liquid, and the third siphon valve is used to intercept waste liquid flowing back from the waste liquid chamber (9) to the storage chamber (43).

10. A detection device, characterized in that: The detection device comprises the centrifugal microfluidic chip (100) according to any one of claims 1 to 9.

Citation Information

Patent Citations

  • Micro-fluidic chip for nucleic acid detection and nucleic acid detection device

    CN113322172A

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