Packaging cover and sequencing chip packaging structure

Abstract

A packaging cover for packaging a sequencing chip comprises a top surface, a bottom surface, an elastic sealing ring, a first runner and a second runner, wherein the top surface and the bottom surface are opposite to each other; the sealing ring is convexly arranged on the bottom surface and has elasticity; the first flow channel and the second flow channel are arranged in the packaging cover. The first flow channel is used for being connected with the liquid inlet module so as to input fluid into the packaging cover. The first flow channel comprises a first port located on the side where the top face is located and a second port located on the side where the bottom face is located. The second flow channel is used for being connected with the liquid discharging module so as to discharge the fluid from the packaging cover. The second flow channel comprises a third port located on the side where the top face is located and a fourth port located on the side where the bottom face is located. The second port and the fourth port are both located in an area surrounded by the sealing ring. The utility model further provides a sequencing chip packaging structure comprising the packaging cover. According to the sequencing chip packaging structure, the whole packaging process of the sequencing chip is simple, the rejection rate of the sequencing chip during packaging is low, at least the packaging cover of the sequencing chip packaging structure can be recycled after being cleaned, and the cost is low.

Description

TECHNICAL FIELD

[0001] The present application relates to a packaging cover for a sequencing chip and a sequencing chip packaging structure comprising the same. BACKGROUND

[0002] High-throughput gene sequencing requires loading multiple reagents onto the surface of a sequencing chip for biological reactions, and requires that specific modified sites of the sequencing chip be fixed or carry genetic molecules or nucleic acid molecules to ensure the stability and accuracy of biochemical reactions. Sequencing chips are usually made by semiconductor manufacturing processes and use specific materials that are biocompatible, such as silicon wafers, quartz wafers, and CMOS wafers. The reagent loading process needs to strictly control the liquid exchange speed, liquid exchange volume, liquid exchange time, liquid exchange temperature, and liquid exchange stability, and the chip cannot be exposed to air for a long time during the whole process, so the reagent loading process of the sequencing chip needs to be carried out in a specific sealed device. The current mainstream gene sequencing chip mainly uses a fully sealed traditional fluid replacement chip or a microfluidic chip, so that different fluids enter the flow channel type chip through the closed flow path, thereby realizing various functions such as conventional chemistry, biology, and optics. The existing reagent loading scheme for sequencing chips has many drawbacks, such as relatively complex packaging process of the sequencing chip, high precision and sealing requirements of the flow channel, and high scrap rate of the chip during packaging. The microfluidic chip is a consumable and has a high cost. SUMMARY

[0003] The present application provides a packaging cover for packaging a sequencing chip, the packaging cover comprising:

[0004] opposite top and bottom surfaces,

[0005] a sealing ring with elasticity, protruding from the bottom surface;

[0006] a first flow channel arranged in the packaging cover, the first flow channel being used to connect a liquid inlet module to input fluid into the packaging cover, the first flow channel comprising a first port on the side of the top surface and a second port on the side of the bottom surface;

[0007] a second flow channel arranged in the packaging cover, the second flow channel being used to connect a liquid outlet module to discharge fluid from the packaging cover, the second flow channel comprising a third port on the side of the top surface and a fourth port on the side of the bottom surface, the second port and the fourth port being located in an area surrounded by the sealing ring.

[0008] In at least one embodiment, the bottom surface is provided with a sealing groove, and the sealing ring is embedded in the sealing groove.

[0009] In at least one embodiment, the bottom surface is provided with a flow channel groove, and the sealing ring surrounds the flow channel groove.

[0010] In at least one embodiment, the second port and the fourth port are located on opposite sides of the flow channel groove.

[0011] In at least one embodiment, the packaging cover is further provided with a first opening groove and a second opening groove on the side where the top surface is located, the first opening groove is connected to the first port of the first flow channel, and the first opening groove is used to connect the liquid inlet module, the second opening groove is connected to the third port of the second flow channel, and the second opening groove is used to connect the liquid outlet module.

[0012] In at least one embodiment, the groove walls of the first opening groove and the second opening groove are provided with threads.

[0013] The application also provides a sequencing chip packaging structure, comprising:

[0014] a sequencing chip and a circuit board, the sequencing chip being arranged on the circuit board, the sequencing chip comprising a test surface facing away from the circuit board;

[0015] a chip cover, the cover being arranged on the circuit board, the chip cover being provided with an opening, and the test surface of the sequencing chip being exposed through the opening; and

[0016] The packaging cover described above is detachably arranged on the side of the chip cover facing away from the circuit board, the sealing ring is abutted against the chip cover to make the packaging cover, the chip cover and the sequencing chip cooperate to form a sealed reaction cavity, and the test surface of the sequencing chip is located in the reaction cavity.

[0017] The sequencing chip packaging structure of the application is packaged on the chip cover by the packaging cover provided with flow channels, so that the packaging cover, the chip cover and the sequencing chip cooperate to form a sealed reaction cavity, the first flow channel is connected to the liquid inlet module to input fluid into the reaction cavity, and the second flow channel is used to connect the liquid outlet module to output waste liquid or waste gas from the reaction cavity. In this way, the overall packaging process of the sequencing chip is simple, the scrap rate of the sequencing chip during packaging is low, and at least the packaging cover of the sequencing chip packaging structure can be recycled after cleaning, thereby reducing the cost.

[0018] In at least one embodiment, the packaging cover is provided with a positioning through hole, and a screw is locked in the positioning through hole to fix the packaging cover and the chip cover on the operation platform of the sequencing chip packaging structure.

[0019] In at least one embodiment, the chip cover comprises a bonding surface facing the package cover, and further comprises a slope surface connecting the bonding surface and inclined towards the circuit board, the slope surface being located on opposite sides of the opening.

[0020] In at least one embodiment, the second port and the fourth port are located on opposite sides of the opening. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 It is a perspective view of a sequencing chip package structure according to an embodiment of the present application.

[0022] Figure 2 It is an exploded view of a sequencing chip package structure according to an embodiment of the present application. Figure 1

[0023] Figure 3 It is a schematic view of a package cover of a sequencing chip package structure according to an embodiment of the present application. Figure 1

[0024] Figure 4 It is a schematic view of a chip cover, a sequencing chip and a circuit board of a sequencing chip package structure according to an embodiment of the present application. Figure 1

[0025] Figure 5 It is a sectional view along line V-V. Figure 1

[0026] Figure 6 It is a top view of a sequencing chip package structure according to an embodiment of the present application. Figure 1 MAIN ELEMENT SYMBOL EXPLANATION

[0027]

[0028] Sequencing chip package structure 100, package cover 10, top surface 11, bottom surface 12,

[0029] Sealing ring 13, chip cover 40, opening 401, bonding surface 41, slope surface 42,

[0030] Sequencing chip 50, test surface 51, circuit board 60, sealing groove 101, flow channel groove 102,

[0031] Reaction cavity 103, positioning through hole 104, first flow channel 105, second flow channel 106,

[0032] First port 105a, second port 105b, third port 106a,

[0033] Fourth port 106b, first opening groove 107, second opening groove 108. DETAILED DESCRIPTION ​​​​​

[0034] The sequencing chip packaging structure (also referred to as a "sample loading structure") provided by the embodiments of the present application has a simple packaging process, can reduce the packaging precision requirement of each chip, and does not require expensive packaging processing of the sequencing chip.

[0035] Referring to Figure 1 and Figure 2 , the sequencing chip packaging structure 100 provided by the embodiments of the present application comprises, from top to bottom, a packaging cover (also referred to as an "inlet and outlet device") 10, a chip cover 40, and a sequencing chip 50. The sequencing chip 50 is arranged on a circuit board 60 adapted thereto. The sequencing chip 50 has a test surface 51, which is a surface directly contacting a sample (such as DNB) and a reaction reagent. The test surface 51 of the sequencing chip 50 faces away from the circuit board 60. The chip cover 40 is fixedly arranged on the circuit board 60 and is provided with an opening 401 through which the sequencing chip 50 is exposed. The opening 401 is shaped and sized to match the sequencing chip 50. The chip cover 40 is tightly pressed against the sequencing chip 50 so that only the test surface 51 of the sequencing chip 50 is exposed. The chip cover 40 comprises a bonding surface 41 facing the packaging cover 10. The chip cover 40 can be fixed to the circuit board 60 by an adhesive. In the embodiments of the present application, the sequencing chip 50 is a CMOS semiconductor chip, and a conventional semiconductor packaging process is applied to form an open or detachable sequencing chip 50 on the circuit board 60. The sequencing chip 50 is located at a lower position of the sequencing chip packaging structure 100.

[0036] Some circuit structures such as wires and electronic components arranged on the circuit board 60 are packaged between the chip cover 40 and the circuit board 60 and are protected, so that the electrical properties of the circuit structures are effectively prevented from being damaged in the flowing reaction reagent environment.

[0037] Referring to Figure 1 , Figure 2 and Figure 5 , the packaging cover 10 is detachably arranged on a side of the chip cover 40 facing away from the circuit board 60, and the packaging cover 10, the chip cover 40, and the sequencing chip 50 cooperate to form a sealed reaction cavity 103. Referring to Figure 3 , the packaging cover 10 comprises opposite top and bottom surfaces 11 and 12, wherein the bottom surface 12 faces the sequencing chip 50. In the embodiments of the present application, the bottom surface 12 is provided with a sealing ring 13 protruding from the bottom surface 12. The sealing ring 13 can be made of a material such as rubber that has elasticity. The sealing ring 13 is used to abut against the bonding surface 41 of the chip cover 40, so that the packaging cover 10 cooperates with the chip cover 40 and the sequencing chip 50 to form the sealed reaction cavity 103. The sealing ring 13 completely surrounds the opening 401 of the chip cover 40. In the embodiments of the present application, the sealing ring 13 is a rectangular ring, but is not limited thereto.

[0038] In the embodiments of the present application, the packaging cover 10 is provided with a positioning through hole 104. The positioning through hole 104 is arranged at a position close to the edge of the packaging cover 10. An operation platform (not shown in the figure) on which the sequencing chip packaging structure 100 is placed is correspondingly provided with a screw hole corresponding to the positioning through hole 104. The packaging cover 10 can be locked in the screw hole of the operation platform through the screw passing through the positioning through hole 104, so as to realize the fixed combination of the packaging cover 10 with the chip cover 40 and the sequencing chip 50 and the like, and the adjustment of the depth of the sealed reaction cavity 103 by adjusting the fastening degree of the screw in the screw hole.

[0039] As shown in Figure 3 , in some embodiments, a sealing groove 101 is formed on the bottom surface 12, and the shape and size of the sealing groove 101 are matched with the shape and size of the sealing ring 13. The sealing ring 13 can be closely embedded in the sealing groove 101. It can be understood that some sealing grooves 101 can also not be provided, and the sealing ring 13 is fixed on the bottom surface 12 by an adhesive.

[0040] As shown in Figure 3 , in some embodiments, a flow channel groove 102 is also formed on the bottom surface 12. The sealing ring 13 surrounds the flow channel groove 102. The flow channel groove 102 is opposite to the opening 401 of the chip cover 40 and completely covers the opening 401. In the embodiments of the present application, the flow channel groove 102 is a rectangular groove.

[0041] In combination with Figure 5 , the first flow channel 105 and the second flow channel 106 are arranged inside the packaging cover 10 and are independent of each other. The first flow channel 105 includes opposite first and second ports 105a and 105b. The first port 105a is located on the side where the top surface 11 is located, the second port 105b is located on the side where the bottom surface 12 is located, and the first flow channel 105 extends from the first port 105a to the second port 105b. The second flow channel 106 includes opposite third and fourth ports 106a and 106b. The third port 106a is located on the side where the top surface 11 is located, the fourth port 106b is located on the side where the bottom surface 12 is located, and the second flow channel 106 extends from the third port 106a to the fourth port 106b. The shapes of the first flow channel 105 and the second flow channel 106 are not limited to Figure 5 .

[0042] As shown in Figure 3 , the second port 105b and the fourth port 106b are both located in the area surrounded by the sealing ring 13, and at least part of them is located in the flow channel groove 102. The second port 105b and the fourth port 106b are located on opposite sides of the flow channel groove 102.

[0043] The first flow channel 105 is used to connect a liquid inlet module (not shown in the figure) to input fluid into the packaging cover 10. In some embodiments, the liquid inlet module includes a reagent storage module, a liquid inlet pipeline, a pump, a liquid inlet valve, an air source, and the like. The reagent storage module is used to store reaction reagents. The injection pump serves as a power source to pump the reaction reagents in the reagent storage module into the liquid inlet pipeline and the first flow channel 105. The number of liquid inlet valves can be one or more, and the liquid inlet valve can be a solenoid valve. The liquid inlet valve is used to switch the reagents entering the first flow channel 105 and control the liquid addition. The air source is also provided with an air inlet valve to control whether the gas enters the liquid inlet pipeline and the first flow channel 105, and finally enters the reaction cavity 103.

[0044] As shown in Figure 5 The packaging cover 10 is also provided with a first opening groove 107 on the side where the top surface 11 is located, and the first opening groove 107 is connected to the first port 105a of the first flow channel 105. In the embodiments of the present application, the first port 105a penetrates the bottom wall of the first opening groove 107. The inner diameter of the first opening groove 107 is greater than the opening inner diameter of the first port 105a. In the embodiments of the present application, threads are arranged on the groove wall (at least the groove side wall) of the first opening groove 107, and an external thread is arranged at the port of the liquid inlet pipeline. In this way, the liquid inlet pipeline can be screwed into the first opening groove 107 to realize the sealed insertion of the liquid inlet pipeline and the packaging cover 10. It can be understood that the connection mode of the liquid inlet pipeline and the packaging cover 10 is not limited to the screwing mode of the internal and external threads, and can also be other various sealed connection modes.

[0045] The second flow channel 106 is used to connect a liquid outlet module (not shown in the figure) to output fluid from the packaging cover 10. The liquid outlet module includes a waste liquid storage module, a liquid outlet pipeline, a pump, and a liquid outlet valve. The liquid outlet pipeline is connected to the waste liquid storage module to transfer the waste liquid of the packaging cover 10 to the waste liquid storage module. The waste liquid storage module is used to collect the waste liquid generated by the reaction. The pump serves as a power source to pump the waste liquid of the reaction reagents into the second flow channel 106 and the liquid outlet pipeline. The liquid outlet valve can be used as a switch to control the liquid outlet.

[0046] As shown in Figure 5As shown, the packaging cover 10 is also provided with a second opening groove 108 on the side where the top surface 11 is located, and the second opening groove 108 is connected with the third port 106a of the second flow channel 106. In the embodiment of the present application, the third port 106a penetrates through the bottom wall of the second opening groove 108. The inner diameter of the second opening groove 108 is larger than the opening inner diameter of the third port 106a. The second opening groove 108 is used to connect the liquid discharge pipeline. In the embodiment of the present application, the groove wall (at least the side wall) of the second opening groove 108 is provided with a thread, and the port of the liquid discharge pipeline is provided with an external thread. The liquid discharge pipeline is screwed in the second opening groove 108 to realize the sealed insertion of the liquid discharge pipeline and the packaging cover 10. It can be understood that the connection mode of the liquid discharge pipeline and the packaging cover 10 is not limited to the screwing mode of the internal and external threads, and can also be other various sealed connection modes.

[0047] The packaging cover 10 of the present application is detachably arranged, which can be recycled and used multiple times, and is suitable for multiple different sequencing chips 50.

[0048] As shown in Figure 2 and Figure 4 As shown, the chip cover 40 further includes a slope surface 42, which is connected with the joint surface 41 and inclined towards the sequencing chip 50 and the circuit board 60. The slope surface 42 is located on the opposite sides of the opening hole 401, thereby defining the opposite sides of the opening hole 401. In combination with Figure 6 One of the slope surfaces 42 is relatively close to the second port 105b of the first flow channel 105, and the other slope surface 42 is relatively close to the fourth port 106b of the second flow channel 106. Thus, the reaction reagent fluid from the packaging cover 10 can flow along the slope surface 42 to the sequencing chip 50, and the waste liquid from the surface of the sequencing chip 50 can flow along the slope surface 42 to the second flow channel 106.

[0049] In an embodiment, the method for using the sequencing chip packaging structure 100 includes the following steps:

[0050] (1) storing the reaction reagent and the cleaning liquid by using the reagent storage module;

[0051] (2) connecting the reagent storage module and the packaging cover 10 by using the liquid inlet pipeline;

[0052] (3) opening the liquid inlet valve of the corresponding reagent, and passing the reaction reagent until the liquid reaches the second port 105b of the bottom surface 12 of the packaging cover 10;

[0053] (4) installing the packaging cover 10 on the chip cover 40 of the sequencing chip 50 to form a sealed reaction cavity 103;

[0054] (5) loading the corresponding reaction reagent to the surface of the sequencing chip 50 according to the set volume and flow rate for reaction;

[0055] (6) Close the reagent inlet valve, open the cleaning liquid inlet valve and the outlet valve, and pass the cleaning liquid according to the set volume and flow rate until the reaction reagent is completely replaced;

[0056] (7) Close the cleaning liquid inlet valve and the outlet valve, and open the air inlet valve until no liquid is discharged from the outlet of the outlet pipeline;

[0057] (8) Close the air inlet valve and open the next reagent inlet valve, and continue to load the reagent to the surface of the sequencing chip 50 for reaction;

[0058] (9) After all the reagents are reacted, close the injection pump and all the valves.

[0059] In another embodiment, the liquid loading and replacement process of the sequencing chip packaging structure is as follows: after adding the reaction reagent to the surface of the open sequencing chip 50 by a pipette or liquid printing, etc., the packaging cover 10 is installed on the chip cover 40 to form a closed reaction cavity, and the reagent A incubation reaction is carried out, after which the buffer is passed to flush the last round of reagent A, and the liquid on the surface of the sequencing chip 50 is discharged by gas, then the packaging cover 10 is opened, and the reagent B is distributed to the surface of the sequencing chip 50, and so on.

[0060] The sequencing chip packaging structure 100 of the embodiment has the following beneficial effects:

[0061] (1) The operation method is simple and efficient, the reagent loading process is stable, which is beneficial to rapid biochemical reaction; it can adapt to various reagent loading systems, including traditional flow channels and open liquid loading systems.

[0062] (2) The packaging cover 10 is very simple to be pressed and installed on the chip cover 40, which simplifies the packaging process of the sequencing chip and improves the chip yield.

[0063] (3) The liquid flow channel is designed on the packaging cover 10, so that the system error of loading between different chips is small, and the test result is more reliable.

[0064] (4) The packaging cover 10 can be cleaned and recycled, which reduces the consumption of consumables-reagents, reduces the sequencing cost, saves resources, and protects the environment.

[0065] (5) The sinking chip packaging structure design can reduce the amount and consumption of reagents on small chips, which is beneficial to the concentration of liquid; at the same time, in the open liquid loading system, it is beneficial to form a thin liquid film, compared with the flow channel type fluid which needs reagent replacement, the amount of reagent is greatly reduced

[0066] (6) The liquid adding mode and the liquid changing mode can be separated. When the sequencing chip packaging structure is used, the liquid inlet port area of the packaging only contains the buffer solution, and no other pollution is caused to the flow channel and the sequencing chip 50. At the same time, the flow channel structure contained in the sequencing chip 50 is avoided, and the pollution or impurities in the front flow path are further reduced to the sequencing chip 50.

[0067] (7) The loading structure can be adapted to the open liquid adding mode, and the application can be directly extended from the DNB loading to other processes required for sequencing.

[0068] Compared with the completely closed integrated packaging chip with the directly connected flow channel, the sequencing chip packaging structure of the application will be in contact with the air for a short time during the waste liquid discharge process, but the DNB loading quality does not decrease significantly.

[0069] The sequencing chip packaging structure 100 of the application is packaged on the chip cover 40 by the packaging cover 10 provided with the flow channel, so that a closed reaction cavity is formed between the packaging cover 10 and the chip cover 40. The first flow channel 105 is connected to the liquid inlet module to input the fluid to the reaction cavity. The second flow channel 106 is used to connect the liquid outlet module to output the waste liquid or waste gas from the reaction cavity. In this way, the overall packaging process of the sequencing chip 50 is simple, the scrap rate of the sequencing chip 50 during packaging is low, and at least the packaging cover 10 of the sequencing chip packaging structure 100 can be recycled after cleaning, and the cost is low.

[0070] Those skilled in the art should appreciate that the above embodiments are only used to illustrate the application, and are not used as a limitation to the application. Any appropriate changes and modifications made to the above embodiments within the spirit and principle of the application fall within the scope of the application.

Claims

1. A package lid for packaging a sequencing chip, the package lid comprising: The packaging cover comprises: opposite top and bottom surfaces, a sealing ring with elasticity, protruding on the bottom surface; a first flow channel provided in the packaging cover, the first flow channel being used for connecting a liquid inlet module to input fluid into the packaging cover, the first flow channel comprising a first port located on the side of the top surface and a second port located on the side of the bottom surface; a second flow channel provided in the packaging cover, the second flow channel being used for connecting a liquid outlet module to output fluid from the packaging cover, the second flow channel comprising a third port located on the side of the top surface and a fourth port located on the side of the bottom surface, the second port and the fourth port being located in the area surrounded by the sealing ring.

2. The package lid of claim 1, wherein, The bottom surface is provided with a sealing groove, and the sealing ring is embedded in the sealing groove.

3. The package lid of claim 1, wherein, The bottom surface is provided with a flow channel groove, and the sealing ring surrounds the flow channel groove.

4. The package lid of claim 3, wherein, The second port and the fourth port are located on opposite sides of the flow channel groove.

5. The package lid of claim 1, wherein, The packaging cover is also provided with a first opening groove and a second opening groove on the side of the top surface, the first opening groove connects the first port of the first flow channel, and the first opening groove is used for connecting the liquid inlet module, the second opening groove connects the third port of the second flow channel, and the second opening groove is used for connecting the liquid outlet module.

6. The package lid of claim 5, wherein, The groove walls of the first opening groove and the second opening groove are provided with threads.

7. A sequencing chip package structure, characterized by, It comprises: a sequencing chip and a circuit board, the sequencing chip being provided on the circuit board, the sequencing chip comprising a test surface facing away from the circuit board; a chip cover fixedly provided on the circuit board, the chip cover being provided with an opening, and the test surface of the sequencing chip being exposed through the opening; and The packaging cover according to any one of claims 1 to 6 is detachably located on the side of the chip cover facing away from the circuit board, and the sealing ring abuts against the chip cover to make the packaging cover, the chip cover and the sequencing chip cooperate to form a sealed reaction cavity, and the test surface of the sequencing chip is located in the reaction cavity.

8. The sequencing chip package structure of claim 7, wherein, The packaging cover is provided with a positioning through hole, and a screw is locked in the sequencing chip packaging structure through the positioning through hole to fix the packaging cover and the chip cover.

9. The sequencing chip package structure of claim 7, wherein, The chip cover comprises a bonding surface facing the packaging cover, and the chip cover further comprises a slope surface connected to the bonding surface and inclined towards the circuit board, the slope surface being located on opposite sides of the opening.

10. The sequencing chip package structure of claim 9, wherein, The second port and the fourth port are located on opposite sides of the opening. The second port and the fourth port are located on opposite sides of the opening.

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