Sequencing chip pretreatment liquid path system

Abstract

The utility model discloses a sequencing chip pretreatment liquid path system which comprises a first rotary valve, a second rotary valve, a chip carrying table, a first electromagnetic valve and a pump. The first rotary valve is used for selectively communicating one reagent; the second rotary valve is communicated with the first rotary valve and is used for conveying one reagent to the plurality of sequencing chips; each group of chip carrying tables is used for carrying at least four sequencing chips; the pump is used for sucking or discharging reagents; the first electromagnetic valve is arranged between the pump and the chip carrying table and is used for selecting the pump to be communicated with the liquid outlet end of the sequencing chip or selecting the pump to be communicated with the waste liquid barrel. According to the sequencing system provided by the invention, liquid adding modification treatment can be simultaneously carried out on a plurality of sequencing chips at one time, so that the pretreatment efficiency of the sequencing chips is improved, and the surface deviation of different sequencing chips caused by manual operation is reduced.

Description

Technical Field

[0001] This application belongs to the technical field of gene sequencing, and specifically relates to a pre-treatment liquid path system for a sequencing chip. Background Art

[0002] When a gene sequencer performs detection, the main carrier part of the sample is the sequencing chip, and the quality of the sequencing chip itself will affect the accuracy and reliability of the sequencing results. Before sequencing, it is necessary to perform pre-treatment on the sequencing chip, that is, chemically modify the chip surface to enhance probe fixation, improve signal intensity and specificity, prevent non-specific adsorption, enhance surface stability, provide a multifunctional surface, optimize reaction conditions, etc. These modifications not only improve the efficiency and accuracy of sequencing, but also expand the application range of the sequencing chip, providing a more powerful tool for genomics and molecular biology research.

[0003] To chemically modify the surface of the sequencing chip, mainly the following various reagents are added during the research and development of samples and the production process in the laboratory: oligo, polymer, cleaning reagent, and chip preservation reagent. This process mainly relies on manual participation in the prior art to sequentially add the above reagents. However, manual operation has low efficiency and cannot meet the demand for improving the production capacity of sequencing chips. Therefore, there is an urgent need for a liquid path system suitable for mass production at present. Summary of the Utility Model

[0004] This application discloses a pre-treatment liquid path system for a sequencing chip to solve the problem of low efficiency in the prior art.

[0005] This application provides a pre-treatment liquid path system for a sequencing chip, including:

[0006] A first rotary valve, including a plurality of first liquid inlet ends and a first liquid outlet end, and the first liquid inlet end is used to selectively communicate with a reagent;

[0007] A second rotary valve, including a second liquid inlet end and a plurality of second liquid outlet ends, and the second liquid inlet end is communicated with the first liquid outlet end;

[0008] Multiple groups of chip carriers, each group of chip carriers is used to carry at least four sequencing chips, the sequencing chip includes a plurality of third liquid inlet ends and a plurality of third liquid outlet ends, and the third liquid inlet end is communicated with the second liquid outlet end;

[0009] A first solenoid valve, including a first common port, a first normally open port, and a first normally closed port;

[0010] A pump is provided below the chip stage. The first common port is in communication with the pump, the first normally open port is in communication with the third liquid outlet end, and the first normally closed port is in communication with the waste liquid bucket. When the first common port is in communication with the first normally open port, the pump is used to extract and temporarily store the reagent. When the first common port is in communication with the first normally closed port, the pump is used to discharge the reagent to the waste liquid bucket.

[0011] Optionally, a 1-to-N joint or a plurality of consecutive three-way joints are provided between the second rotary valve and the chip stage, where N is equal to the total number of sequencing chips on each group of chip stages.

[0012] Optionally, a second solenoid valve and a three-way joint are provided between the second rotary valve and the chip stage. The second solenoid valve includes a second common port, a second normally open port, and a second normally closed port. The second common port is in communication with the second liquid outlet end, and the second normally open port and the second normally closed port are respectively in communication with half of the sequencing chips on the chip stage.

[0013] When the second common port is selected to communicate with the second normally open port or the second normally closed port, the second liquid outlet end is used to supply liquid to half of the sequencing chips on the chip stage.

[0014] Optionally, a third solenoid valve is provided between the chip stage and the first solenoid valve. The third solenoid valve includes a third common port, a third normally open port, and a third normally closed port. The third common port is in communication with the second normally open port, and the third normally open port and the third normally closed port are respectively in communication with the third liquid outlet ends of the corresponding half of the sequencing chips on the chip stage.

[0015] Optionally, the number of chip stages is five groups, each group is provided with two chip stages, each chip stage is used to mount two sequencing chips, and each sequencing chip is provided with two flow channels.

[0016] Optionally, the pump is a four-channel pump.

[0017] Optionally, a 1-to-K first liquid path end block is provided at the third liquid inlet end of the chip stage. The first liquid path end block is used to transport the reagent flowing out from the second liquid outlet end to each flow channel of the sequencing chip, and the number of K is the same as the number of flow channels of the sequencing chip.

[0018] Optionally, a second liquid path end block is provided at the third liquid outlet end of the chip stage, and the number of flow channels of the second liquid path end block is the same as the number of flow channels of the sequencing chip.

[0019] As can be seen from the above technical solutions, the sequencing system provided by this application can perform liquid addition and modification processing on multiple sequencing chips simultaneously at one time, thereby improving the pre-processing efficiency of the sequencing chips and reducing the surface deviation of different sequencing chips caused by manual operation. Description of the Drawings

[0020] Figure 1 It is the liquid path schematic diagram of a liquid path system for pre-processing a sequencing chip provided by an embodiment of this application;

[0021] Figure 2 It is the liquid path schematic diagram of another liquid path system for pre-processing a sequencing chip provided by an embodiment of this application;

[0022] Figure 3 It is the liquid path schematic diagram of yet another liquid path system for pre-processing a sequencing chip provided by an embodiment of this application.

[0023] Reference Signs: 1 - First Rotary Valve; 2 - Second Rotary Valve; 3 - Chip Carrier; 4 - First Solenoid Valve; 5 - Pump; 7 - Second Solenoid Valve; 8 - Third Solenoid Valve; 11 - First Liquid Inlet End; 12 - First Liquid Outlet End; 21 - Second Liquid Inlet End; 22 - Second Liquid Outlet End; 30 - Sequencing Chip; 301 - Third Liquid Inlet End; 302 - Third Liquid Outlet End; 31 - Liquid Path End Block; 311 - First Liquid Path End Block; 312 - Second Liquid Path End Block; 41 - First Common Port; 42 - First Normally Open Port; 43 - First Normally Closed Port; 71 - Second Common Port; 72 - Second Normally Open Port; 73 - Second Normally Closed Port; 81 - Third Common Port; 82 - Third Normally Open Port; 83 - Third Normally Closed Port. Detailed Embodiments

[0024] The technical solutions in the embodiments of this application will be described clearly and completely below. Obviously, the described embodiments are only a part of the embodiments of this application, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in this application without creative efforts shall fall within the protection scope of this application.

[0025] The chemical modification of the surface of the sequencing chip mainly involves flowing fluids such as oligo, polymer, and cleaning reagent through the liquid path in sequence through the sequencing chip. These reagents can undergo a series of reactions on the sequencing chip under certain temperature conditions, thereby completing the modification.

[0026] Based on this, an embodiment of this application provides a liquid path system for pre-processing a sequencing chip. Referring to Figure 1 the liquid path schematic diagram of the liquid path system shown, the liquid path system provided in this embodiment includes: a first rotary valve 1, a second rotary valve 2, a chip carrier 3, a first solenoid valve 4, and a pump 5.

[0027] In order to select different reagents to communicate with different chip sets and deliver specific reagents into the chip at the appropriate time, two rotary valves are provided in this application, namely the first rotary valve 1 and the second rotary valve 2. The first rotary valve 1 includes a plurality of first liquid inlet ends 11 and a first liquid outlet end 12. The first liquid inlet ends 11 are used to selectively communicate with one kind of reagent. A reagent needle is connected to the first liquid inlet end 11, and the reagent needle is used to insert into a reagent kit (not shown) to aspirate the reagent. The second rotary valve 2 includes a second liquid inlet end 21 and a plurality of second liquid outlet ends 22. The second liquid inlet end 21 communicates with the first liquid outlet end 12. The first liquid inlet ends 11 are used to selectively communicate with one of the reagents. The reagent flows from the first liquid outlet end 12 into the second liquid inlet end 21 and then into the chip stage 3 from the second liquid outlet ends 22.

[0028] The number of the first liquid inlet ends 21 is at least equal to the number of reagent types. For example, if 5 kinds of reagents are required in this embodiment, the number of the first liquid inlet ends 21 is 5. Each second liquid inlet end 21 communicates with one of the reagents. When a certain reagent is needed, it is only necessary to control the connection of the first liquid inlet end 21 connected to the reagent.

[0029] The number of the second liquid outlet ends 22 is at least equal to the number of groups of the chip stage 3. For example, if 5 groups of chip stages 3 are provided in this embodiment, the number of the second liquid outlet ends 22 is 5. Each second liquid outlet end 22 communicates with one of the groups of chip stages 3. Since the reagent flows out from the second liquid outlet ends 22 simultaneously, if the pipeline paths between each chip stage 3 and the second liquid outlet ends 22 are controlled to be equal, it can ensure that the reagent is injected into the chip stage 3 simultaneously, thereby ensuring that the chemical reagent amounts required for each stage are the same.

[0030] In this embodiment, multiple groups of chip stages 3 are provided. Each group of the chip stage 3 includes two stages, and each stage is used to carry two sequencing chips 30. The sequencing chip includes a plurality of third liquid inlet ends 301 and a plurality of third liquid outlet ends 302. In this embodiment, a single sequencing chip 30 is provided with two flow channels, and each flow channel corresponds to a third liquid inlet end 301 and a third liquid outlet end 302 respectively. Then each sequencing chip 30 has two third liquid inlet ends 301 and two third liquid outlet ends 302. Relying on reasonable design and layout, five groups of chip stages 3 can be jointly arranged on a rotating disc in this application. Therefore, a maximum of 20 chips can be simultaneously subjected to liquid addition and modification treatment at one time, thereby improving the pre-treatment efficiency of the sequencing chip and reducing the surface deviation of different sequencing chips caused by manual operation.

[0031] To provide the driving force for sucking reagents and suck the reagents into the chip, the embodiment of the present application is provided with a pump 5. The pump structure is located below the chip stage and is composed of 5 components. There is a pump structure below each chip stage. On the one hand, it is to reduce the length of the liquid path pipeline and reduce the amount of reagents; on the other hand, it is to make reasonable use of space and reduce the floor space of the device.

[0032] During the chip preparation process, the reagents flow through the sequencing chip at a certain flow rate. A part of the reagents participate in the reaction and stay on the chip, and the other part is sucked by the pump 5 and temporarily stored inside the pump. This part of the reagents is waste liquid. To discharge the waste liquid, the embodiment of the present application is provided with a first solenoid valve 4. The first solenoid valve 4 can be a two-position three-way solenoid valve. The first solenoid valve 4 is arranged between the pump 5 and the chip stage 3 and is used to select to connect the pump 5 with the liquid outlet end of the sequencing chip. At this time, the pump 5 is used to suck the reagents; or, select to connect the pump 5 with the waste liquid bucket. At this time, the pump 5 is used to discharge the reagents into the waste liquid bucket (waste).

[0033] The first solenoid valve 4 includes a first common port 41, a first normally open port 42 and a first normally closed port 43; the first common port 41 is connected to the pump 5, the first normally open port 42 is connected to the third liquid outlet end 301, and the first normally closed port 43 is connected to the waste liquid bucket (waste); when the first common port 41 is connected to the first normally open port 42, the pump 5 is used to extract and temporarily store the reagents; when the first common port 41 is connected to the first normally closed port 43, the pump 5 is used to discharge the reagents into the waste liquid bucket.

[0034] As can be seen from the above technical solutions, the chip surface chemical modification device provided in this embodiment mainly improves the chip processing efficiency and saves the labor operation cost and time.

[0035] To send the reagents flowing out from the second liquid outlet end 22 of the second rotary valve 2 to each chip on the chip stage 3, a 1-to-N joint or a plurality of consecutive three-way joints (not labeled) are arranged between the second rotary valve 2 and the chip stage 3, where N is equal to the total number of sequencing chips on each group of chip stages. In this embodiment, two sequencing chips are in a group, and two sequencing chips are arranged on the same chip stage 3. Two chip stages 3 are used as a group, and there are a total of five groups of chip stages. Therefore, one group of chip stages 3 corresponds to 4 sequencing chips. In this case, if a 1-to-4 joint is set, the reagents flowing out from the second liquid outlet end 22 can be divided into 4 paths; or, a three-way joint is connected to the second liquid outlet end 22. At this time, the reagents flowing out from the second liquid outlet end 22 can be divided into 2 paths, and then a three-way joint is respectively connected to the liquid outlet ends of the three-way joint, and the reagents flowing out from the second liquid outlet end 22 can be divided into 4 paths.

[0036] In this application, liquid path end blocks 31 are provided at both ends of the sequencing chip on the chip stage. There are two types of liquid path end blocks 31, namely the first liquid path end block 311 and the second liquid path end block 312. The first liquid path end block 311 is a Y-shaped flow channel provided at the third liquid inlet end 301, and the second liquid path end block 312 is an I-shaped flow channel provided at the third liquid outlet end 302. The first liquid path end block is used to transport the reagent flowing out from the second liquid outlet end 22 to each flow channel of the sequencing chip. It is a liquid path end block with a 1-to-K split, and the number of K is the same as the number of flow channels on a single sequencing chip. The number of flow channels of the second liquid path end block is the same as the number of flow channels on a single sequencing chip.

[0037] The reagent flowing out from the 1-to-N joint or three-way joint is split into two by the first liquid path end block 311 and then flows into the flow channels of the chip respectively. At the liquid outlet end of the sequencing chip, a second liquid path end block 322 is provided. This liquid path end block sends the reagent flowing out from each flow channel into the first solenoid valve 4. In Figure 1 In the shown liquid path schematic diagram, each chip stage 3 has 4 sequencing chips. Each flow channel needs to correspond to a pump. Then, an eight-connected pump is required for each chip stage 3 to form a complete liquid path system.

[0038] The embodiment of this application further provides an improved liquid path system. Referring to Figure 2 In the shown liquid path schematic diagram, in this system, a second solenoid valve 7 and a three-way joint are provided between the second rotary valve 2 and the chip stage 3. The second solenoid valve 7 includes a second common port 71, a second normally open port 72, and a second normally closed port 73. The second common port 71 is communicated with the second liquid outlet end 22. The second normally open port 72 and the second normally closed port 73 are respectively communicated with a three-way joint, and this three-way joint is used to connect half of the sequencing chips on each chip stage; when the second common port 71 selects to communicate with the second normally open port 72 or the second normally closed port 73, the second liquid outlet end 22 is used to supply liquid to half of the sequencing chips on the chip stage.

[0039] Since the second solenoid valve 7 divides 8 sequencing chips into two groups, and the second solenoid valve 7 only selects 4 of the sequencing chips for liquid supply. When 4 of the sequencing chips are selected for liquid supply, the other 4 sequencing chips can suspend liquid supply. In this case, taking 4 chips as a group, two four-connected pumps are required to achieve a complete liquid path system.

[0040] Since when one group of four-connected pumps is working, the other group of four-connected pumps is in a non-working state. Further, in order to save one group of four-connected pumps, the embodiment of this application provides another improved liquid path system. Referring to Figure 3The liquid path schematic diagram shown. Based on the aforementioned sequencing system, a third solenoid valve 8 is provided between the chip stage 3 and the first solenoid valve 4. The third solenoid valve 8 includes a third common port 81, a third normally open port 82, and a third normally closed port 83. The third common port 81 is communicated with the second normally open port 82, and the third normally open port 82 and the third normally closed port 83 are respectively communicated with the third liquid outlet end 302 of half of the sequencing chips corresponding to the chip stage.

[0041] To ensure the liquid inlet efficiency and reduce the complexity of the liquid path, the device divides 20 chips into 5 groups, with 4 chips in each group. The liquid path reagents are also divided into 5 groups during liquid inlet to reduce the number and cost of the liquid path pumps and valves. When the number of chips for surface chemical modification at one time is less than 5 groups or it is necessary to control the chemical modification progress of different groups of chips, the second rotary valve can be used to select to supply liquid to one of the groups or delay the liquid supply, so as to achieve the process differentiation of different groups of chips.

[0042] As can be seen from the above, two chip stages are provided in each group, each chip stage is used to carry two sequencing chips, and two flow channels are provided on each sequencing chip. In this embodiment, a total of 20 chips are provided, so at most 20 chips can be simultaneously subjected to liquid addition and modification treatment at one time, thereby improving the pre-processing efficiency of the sequencing chips and reducing the surface deviation of different sequencing chips caused by manual operation.

[0043] The above are only embodiments of the present application and are not used to limit the present application. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present application are included in the scope of the claims of the present application pending approval.

Claims

1. A sequencing chip pre-treatment liquid path system, characterized in that: include: A first rotary valve comprises a plurality of first liquid inlet ends and a first liquid outlet end, wherein the first liquid inlet end is used for selectively connecting a reagent; A second rotary valve, comprising a second liquid inlet end and a plurality of second liquid outlet ends, wherein the second liquid inlet end is in communication with the first liquid outlet end; A plurality of groups of chip carriers, each group of the chip carriers is used to carry at least four sequencing chips, the sequencing chips include a plurality of third liquid inlet ends and a plurality of third liquid outlet ends, the third liquid inlet ends are connected to the second liquid outlet ends; A first solenoid valve comprising a first common port, a first normally open port and a first normally closed port; A pump is arranged below the chip carrier, the first common port is connected to the pump, the first normally open port is connected to the third liquid outlet, and the first normally closed port is connected to the waste liquid barrel; when the first common port is connected to the first normally open port, the pump is used to extract the reagent and store it temporarily; when the first common port is connected to the first normally closed port, the pump is used to discharge the reagent into the waste liquid barrel.

2. A sequencing chip pre-treatment liquid path system according to claim 1, characterized in that: A 1-way N connector or a plurality of continuous three-way connectors are provided between the second rotary valve and the chip carrier, wherein N is equal to the total number of sequencing chips on each group of chip carriers.

3. A sequencing chip pre-treatment liquid path system according to claim 1, characterized in that: A second solenoid valve and a three-way connector are provided between the second rotary valve and the chip carrier, the second solenoid valve comprises a second common port, a second normally open port and a second normally closed port, the second common port is connected to the second liquid outlet, and the second normally open port and the second normally closed port are respectively connected to one half of the sequencing chips on the chip carrier; When the second common port is connected to the second normally open port or the second normally closed port, the second liquid outlet is used to supply liquid to half of the sequencing chips on the chip carrier.

4. A sequencing chip pre-treatment liquid path system according to claim 3, characterized in that: A third solenoid valve is arranged between the chip carrier and the first solenoid valve, and the third solenoid valve includes a third common port, a third normally open port and a third normally closed port. The third common port is connected with the second normally open port, and the third normally open port and the third normally closed port are respectively connected with the third liquid outlet ends of half of the sequencing chips corresponding to the chip carrier.

5. A sequencing chip pre-treatment liquid path system according to claim 4, characterized in that: The number of the chip carriers is five groups, each group is provided with two chip carriers, each chip carrier is used to install two sequencing chips, and each sequencing chip is provided with two flow channels.

6. A sequencing chip pre-treatment liquid path system according to claim 5, characterized in that: The pump is a quadruple pump.

7. A sequencing chip pre-treatment liquid path system according to any one of claims 1 to 6, characterized in that: The third liquid inlet end of the chip carrier is provided with a first liquid path end block divided into K, and the first liquid path end block is used to transport the reagent flowing out from the second liquid outlet end to each flow channel of the sequencing chip, and the number of K is consistent with the number of flow channels of the sequencing chip.

8. A sequencing chip pre-treatment liquid path system according to any one of claims 1 to 6, characterized in that: The third liquid outlet end of the chip carrier is provided with a second liquid path end block, and the number of flow channels of the second liquid path end block is consistent with the number of flow channels of the sequencing chip.

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