Liquid path system and gene sequencer
The introduction of a buffer liquid reservoir and valve system in the liquid route system isolates the injection pump from reagents, addressing clogging and wear issues, thereby reducing maintenance costs and enhancing sequencing accuracy.
Patent Information
- Application Number
- CN202421542777.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-06-28
- Publication Date
- 2025-07-15
- Estimated Expiration
- 2034-06-28
AI Technical Summary
In the existing gene sequencing fluid system, the syringe pump causes stagnation and abnormal wear due to reagent reactions and crystallization, which increases maintenance costs and reduces sequencing accuracy.
The buffer pool and selection valve group are introduced into the liquid system, and the storage chamber is filled with buffer solution, and the syringe pump isolates the syringe pump from reagents and waste liquid to prevent reagents and waste liquid from entering the syringe pump. Multiple selection valves are used to achieve the extraction and removal of reagents and waste liquid.
It reduces the wear and maintenance costs of the syringe pump, improves the accuracy of sequencing, reduces the risk of syringe pump contamination, and improves the reliability of the liquid system.
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Figure CN223102987U_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the field of biological detection technologies, and particularly to a liquid path system and a gene sequencer. Background Art
[0002] In a gene sequencing fluid system, an injection pump serves as a power element for reagent delivery. During detection, the liquid path diagram of the gene sequencing fluid system is as Figure 1 shown. The reagent kit 1 is connected to the flow cell 4 through the first distribution valve 3. The flow cell 4 and the waste liquid tank 2 are connected to the injection pump 6 through the second distribution valve 5. Among them, multiple reagent bottles are provided in the reagent kit 1, and each reagent bottle is used to hold different reagents. When the injection pump 6 extracts reagents, the injection pump 6 is communicated with the flow cell 4 through the second distribution valve 5, and the flow cell 4 selects different reagent bottles to communicate through the first distribution valve, so as to inject different reagents into the flow cell 4. When discharging waste liquid, first, the injection pump 6 extracts the reacted waste liquid in the flow cell 4, then the injection pump 6 is communicated with the waste liquid tank through the second distribution valve 5, and then the waste liquid is discharged to the waste liquid tank.
[0003] Since various reagents will gather in the injection pump and are finally discharged as waste, the injection pump has problems such as jamming and abnormal wear due to reasons such as reagent interaction and crystallization, resulting in increased maintenance costs and reduced sequencing accuracy. Utility Model Content
[0004] The present application provides a liquid path system and a gene sequencer to reduce the wear of the injection pump, reduce the maintenance cost of the entire liquid path system, and improve the sequencing accuracy.
[0005] In a first aspect, a liquid path system is provided. The liquid path system includes: a reagent kit, a flow cell, a waste liquid tank, a buffer tank, a storage cavity, and an injection pump; wherein,
[0006] The reagent kit has at least one reagent bottle;
[0007] The flow cell is selectively communicated with one reagent bottle of the reagent kit through a first selection valve;
[0008] The storage cavity is selectively communicated with the flow cell and the waste liquid tank through a second selection valve;
[0009] A third selection valve is further included. The third selection valve includes a plurality of branch channels and a common channel. The injection pump is connected to the common channel. The storage cavity and the buffer tank are respectively connected to different branch channels. The common channel is selectively communicated with the plurality of branch channels; the injection pump is used to fill at least the buffer liquid in the storage cavity through the cooperation of the second selection valve and the third selection valve before sucking the reagent in the reagent bottle into the flow cell.
[0010] In the above technical solution, by adopting the cooperation of the added buffer solution pool and the selection valve group, before the reagent is extracted, the storage cavity is filled with the buffer agent, so that when the injection pump extracts the reagent, the injection pump is filled with the buffer solution, and the reagent will not enter the injection pump, thereby reducing the wear of the reagent on the injection pump, reducing the maintenance cost of the injection pump, reducing the maintenance cost of the entire liquid path system. At the same time, the injection pump will not be contaminated by the reagent, and the accuracy of sequencing is also improved.
[0011] In a specific feasible implementation, the sum of the total internal volumes of the pipeline between the second selection valve and the storage cavity, the storage cavity, and the pipeline between the storage cavity and the third selection valve is not less than the internal volume of the cavity of the injection pump.
[0012] In a specific feasible implementation, the storage cavity can be any one of a circular cross-section channel, a non-circular cross-section channel, a serpentine channel, an extended pipeline, or a multi-way manifold.
[0013] In a specific feasible implementation, one of the multiple branch channels of the third selection valve is in communication with the air.
[0014] In a specific feasible implementation, the number of flow cells is two, and the two flow cells share one of the first selection valves to be selectively communicated with the reagent bottle in the reagent kit;
[0015] The number of storage cavities is two, and the two storage cavities correspond to the two flow cells one by one. Each storage cavity is selectively communicated with the corresponding flow cell and the waste liquid pool through one of the second selection valves;
[0016] The number of injection pumps is two, and the two injection pumps correspond to the two storage cavities one by one. Each injection pump is selectively communicated with the corresponding storage cavity and the buffer solution pool through one of the third selection valves.
[0017] In a specific feasible implementation, the number of flow cells is two, and each flow cell is selectively communicated with the reagent bottle in the reagent kit through one of the first selection valves;
[0018] The number of storage cavities is two, and the two storage cavities correspond to the two flow cells one by one; each storage cavity is selectively communicated with the corresponding flow cell and the waste liquid pool through one of the second selection valves;
[0019] The injection pump is selectively communicated with one of the two storage cavities and the buffer solution pool through one of the third selection valves.
[0020] In a specific feasible implementation, the number of the flow cells is four, and the four flow cells are divided into two flow cell groups, each flow cell group containing two of the flow cells; the two flow cells in each flow cell group are alternatively communicated with the reagent bottle in the reagent kit through a shared first selection valve;
[0021] The number of the storage cavities is four, the storage cavities correspond to the flow cells one by one, and each storage cavity is alternatively communicated with the corresponding flow cell and the waste liquid pool through a second selection valve;
[0022] The number of the injection pumps is two, and each injection pump is communicated with two of the storage cavities and the buffer solution pool through a third selection valve; wherein, the flow cells corresponding to the two storage cavities connected by each injection pump through the third selection valve belong to two different flow cell groups.
[0023] In a second aspect, a gene sequencer is provided, which includes the liquid path system described in any one of the above.
[0024] In the above technical solution, by adopting the cooperation of the added buffer solution pool and the selection valve group, before extracting the reagent, the storage cavity is filled with the buffer agent, so that when the injection pump extracts the reagent, the injection pump is filled with the buffer solution, and the reagent will not enter the injection pump, thereby reducing the wear of the reagent on the injection pump, reducing the maintenance cost of the injection pump, reducing the maintenance cost of the entire liquid path system, and at the same time, the injection pump will not be contaminated by the reagent, and the sequencing accuracy is also improved. Description of the Drawings
[0025] Figure 1 It is a structural block diagram of the liquid path system in the prior art;
[0026] Figure 2 It is a structural block diagram of the liquid path system provided by the embodiment of the present application;
[0027] Figures 3a to 3e It is a schematic diagram of the flow path of the liquid path system provided by the embodiment of the present application;
[0028] Figure 4 It is a structural block diagram of another liquid path system provided by the embodiment of the present application;
[0029] Figure 5 It is a structural block diagram of another liquid path system provided by the embodiment of the present application;
[0030] Figure 6 It is a structural block diagram of another liquid path system provided by the embodiment of the present application. Detailed Embodiments
[0031] To make the objectives, technical solutions, and advantages of this application clearer, the following will further describe this application in detail with reference to the accompanying drawings.
[0032] It should be noted that unless otherwise defined, the technical terms or scientific terms used in one or more embodiments of this specification should have the ordinary meanings understood by those of ordinary skill in the art to which this disclosure belongs. The "first", "second", and similar terms used in one or more embodiments of this specification do not indicate any order, quantity, or importance, but are only used to distinguish different components. Words such as "including" or "comprising" mean that the elements or objects appearing before this word cover the elements or objects listed after this word and their equivalents, without excluding other elements or objects. Words such as "connected" or "coupled" are not limited to physical or mechanical connections, but may include electrical connections, whether direct or indirect. "Upper", "lower", "left", "right", etc. are only used to represent relative position relationships, and when the absolute position of the object being described changes, the relative position relationship may also change accordingly.
[0033] To facilitate understanding of the liquid path system provided by the embodiments of this application, its application scenario will be described first. The liquid path system provided by the embodiments of this application is applied to a gene sequencer for calibration or detection. In existing liquid path systems, an injection pump is used as the power source to extract reagents and drain waste liquid. During the use of the reagent pump, various reagents will accumulate in the injection pump and are finally discharged as waste. The injection pump has problems such as jamming and abnormal wear due to reasons such as reagent reactions and crystallization. For this reason, the embodiments of this application provide a liquid path system to reduce the wear of the injection pump, reduce the maintenance cost of the entire liquid path system, and improve the accuracy of sequencing. The following will describe it in detail with specific drawings and embodiments.
[0034] Refer to Figure 2 , Figure 2The structural block diagram of the liquid path system provided by the embodiments of the present application is shown. The liquid path system provided by the embodiments of the present application may include different devices such as a reagent kit 100, a flow cell 500, a waste liquid tank 200, a buffer solution tank 300, a storage cavity 600, and an injection pump 400. Among them, the reagent kit 100 is used to carry reagents, and there is at least one reagent bottle in the reagent kit 100, and each reagent bottle is used to carry different reagents. The flow cell 500 is an element with main biochemical reaction and optical acquisition functions, and the reagent can react with the analyte in the reaction cell. The waste liquid tank 200 is used to carry waste liquid, and the waste liquid generated after the reaction of the reagent and the analyte in the flow cell 500 can be discharged into the waste liquid tank 200. The buffer solution tank 300 is used to carry buffer solution, and the buffer solution is used to isolate the waste liquid or reagent from the injection pump 400. When isolating, it is specifically isolated through the storage compartment. The storage cavity 600 will isolate the chamber of the injection pump 400 and the flow cell 500, and is used to carry reagents, buffer solutions or waste liquid. It should be understood that the buffer solution provided by the embodiments of the present application can be purified water (deionized water) or a reagent that is not easy to crystallize (such as 0.05% Tween solution), etc., a liquid that is not easy to react.
[0035] When specifically connecting the above components, the reagent kit 100, the flow cell 500, the waste liquid tank 200, the buffer solution tank 300, the storage cavity 600, and the injection pump 400 are combined into a liquid path through multiple selection valves, and the connected components are selected through the selection valves to realize the extraction of reagents and the discharge of waste liquid. The liquid path of the entire liquid path system will be described in detail below with reference to specific drawings.
[0036] Continue to refer to Figure 2 As shown in
[0037] When specifically forming the liquid path, the reagent kit 100 is connected to the flow cell 500 through the first selection valve 10. The reagent kit 100 may include at least one reagent bottle, such as different numbers of reagent bottles, such as one reagent bottle, two reagent bottles, three reagent bottles, etc. It can be specifically set according to needs. When there are multiple reagent bottles, each reagent bottle can contain different types of reagents. When different reactions are carried out in the flow cell 500, the reagents in different reagent bottles can be selected and added to the flow cell 500.
[0038] The storage chamber 600 is selectively connected to the flow cell 500 and the waste liquid tank 200 through the second selection valve 20, so that the storage chamber 600 can be selectively connected to the flow cell 500 or the waste liquid tank 200 alone. The injection pump 400 is selectively connected to the storage chamber 600 and the buffer tank 300 through the third selection valve 30, so that the injection pump 400 can be selectively connected to the storage chamber 600 or the buffer tank 300 alone. When specifically connected, the third selection valve 30 includes a plurality of branch channels and a common channel. The injection pump 400 is connected to the common channel, and the storage chamber 600 and the buffer tank 300 are respectively connected to different branch channels. The common channel is selectively connected to the plurality of branch channels;
[0039] In the embodiment of the present application, the storage chamber 600 can be implemented through different types of structures. Exemplarily, the storage chamber 600 can be any one of a circular cross-section channel, a non-circular cross-section channel, a serpentine channel, an extended pipeline, or a multi-way manifold. It should be understood that the extended pipeline in the embodiment of the present application refers to a pipeline with a sufficient length so that the pipeline can accommodate a certain amount of buffer solution. The specific length of the extended pipeline is not specifically limited in the embodiment of the present application. It can be set as needed.
[0040] In addition, for the capacity of the storage chamber 600, it should satisfy that the total internal volume of the pipeline between the second selection valve 20 and the storage chamber 600, the storage chamber 600, and the pipeline between the storage chamber 600 and the third selection valve 30 is not less than the internal volume of the cavity of the injection pump 400. So that when the injection pump 400 extracts the reagent or waste liquid, it can be ensured that it is not sucked into the injection pump 400, that is, it can be ensured that the injection pump 400 can be isolated from the reagent or waste liquid by the buffer solution. As an optional solution, in the embodiment of the present application, the internal volume of the storage chamber 600 is not less than the internal volume of the cavity of the injection pump 400.
[0041] In the embodiment of the present application, the first selection valve 10, the second selection valve 20, and the third selection valve 30 can be different types of selection valves, as long as they meet the function of selective selection.
[0042] Exemplarily, the first selection valve 10 can be a 24-way valve. As a distribution valve, the 24-way valve functions to connect any one of the 24 branches to the common passage through the rotation of the valve core, and the 24 branches are not connected to each other. When connecting the reagent kit 100 to the flow cell 500, the common passage is connected to the flow cell 500, and the 24 branches can be respectively connected to the reagent bottles of the reagent kit 100. It should be understood that when using a 24-way valve, it is not necessary to connect each of the 24 branches to a reagent bottle, and the connection can be made according to the actual number of reagent bottles.
[0043] The second selection valve 20 can be a solenoid valve. A solenoid valve is a type of switching valve whose function is to connect either one of two branches to a common passage through the switching of a valve core, and the two branches are not connected to each other. Exemplarily, the solenoid valve has a port A, a port B, and a port C. Among them, when the solenoid valve switches, it can connect the port C to either the port A or the port B to achieve the switching of the liquid path. When specifically connected, the other end of the flow cell 500 is connected to the port A, the waste liquid tank 200 is connected to the port B, and the storage chamber 600 is connected to the port C.
[0044] The third selection valve 30 can be a 6-way valve. Its function is to connect any one of six branches to a common passage through the rotation of a valve core, and the six branches are not connected to each other. Among them, the common passage of the 6-way valve is connected to the syringe pump 400, and one of the six branches is connected to the storage chamber 600, and another branch is connected to the buffer solution tank 300. In one possible implementation, one of the multiple branch channels of the third selection valve 30 is connected to the air. So that the entire device can be connected to the air through this branch channel during a pressure test or other working conditions.
[0045] The following will be described in detail with reference to the drawings on how to isolate the syringe pump 400 from the reagent or waste liquid through the buffer solution.
[0046] In the embodiment of the present application, the syringe pump 400 is used to fill at least the storage chamber 600 with buffer solution through the cooperation of the second selection valve 20 and the third selection valve 30 before sucking the reagent in the reagent bottle into the flow cell 500. The specific filling process is as follows:
[0047] Refer to Figure 3a shown in Figure 3a which shows a schematic diagram of injecting the buffer solution into the storage chamber 600. In the embodiment of the present application, to prevent the reagent from entering the syringe pump 400 when the syringe pump 400 sucks the reagent, the buffer agent is first filled in the storage chamber 600 through the switching of the second selection valve 20 and the third selection valve 30, so that when the syringe pump 400 sucks the reagent, the syringe pump 400 can be isolated from the reagent by the buffer agent.
[0048] First, connect the third selection valve 30 to the buffer solution tank 300, that is, rotate the valve core of the 6-way valve, and connect the buffer solution tank 300 to the syringe pump 400 connected to the common passage through the rotation of the valve core. The piston of the syringe pump 400 moves in the direction away from the pipeline connection to generate negative pressure, and the entire passage sucks the buffer solution from the buffer solution tank 300 through the 6-way valve into the cavity of the syringe pump 400 under the action of the negative pressure. The flow path of the buffer solution is as Figure 3a the flow path exemplified by the dotted line with arrows in
[0049] After the buffer solution is extracted, the third selection valve 30 is switched to connect the syringe pump 400 to the storage chamber 600. At the same time, the storage chamber 600 is connected to the waste liquid tank 200 through the second selection valve 20. Specifically, the 6-way valve connects the storage chamber 600 to the syringe pump 400 connected to the common path by rotating the valve core, and the solenoid valve connects the storage chamber 600 to the waste liquid tank 200 by switching the valve core. The piston of the syringe pump 400 moves in the direction close to the pipeline connection to generate positive pressure. Under the action of the positive pressure, the reagent in the syringe pump 400 cavity is pushed back to the waste liquid tank 200 in sequence through the 6-way valve, the storage chamber 600, the solenoid valve and the corresponding pipeline. The flow path of the buffer solution is as Figure 3a the flow path exemplified by the solid line with arrows in
[0050] It should be understood that when the total internal volume of the pipeline between the second selection valve 20 and the storage chamber 600, the storage chamber 600, and the pipeline between the storage chamber 600 and the third selection valve 30 is not less than the internal volume of the cavity of the syringe pump 400, the third selection valve 30 can be switched multiple times, and the buffer solution can be extracted again by the syringe pump 400 and injected into the storage chamber 600 until the storage chamber 600 is filled with the buffer solution. The specific path is as Figure 3a the paths shown by the dotted line with arrows and the solid line with arrows in
[0051] After the above switching of the second selection valve 20 and the third selection valve 30, the pipeline and the cavity between the second selection valve 20 and the syringe pump 400 are filled with the buffer solution.
[0052] After the buffer solution is filled, the reagent is extracted by the syringe pump 400. When extracting the reagent, the connection between the syringe pump 400 and the storage chamber 600 is maintained, and the second selection valve 20 is switched to connect the storage chamber 600 to the flow cell 500. Then the first selection valve 10 is switched to connect the flow cell 500 to the reagent bottle containing the reagent required for the reaction. At this time, the reagent bottle, the flow cell 500, the storage chamber 600 (storing the buffer solution), and the syringe pump 400 are connected. The piston of the syringe pump 400 is driven to move outwards to generate negative pressure. The buffer solution in the storage chamber 600 is drawn into the piston pump, and at the same time, the reagent in the reagent bottle is also drawn into the flow cell 500 by the generated negative pressure for reaction.
[0053] Specifically, the 24-way valve connects the reagent bottle to the flow cell 500 connected to the common path by rotating the valve core. The solenoid valve connects the flow cell 500 to the storage cavity 600 by switching the valve core, and the 6-way valve connects the storage cavity 600 to the syringe pump 400 connected to the common path by rotating the valve core. Then, the piston of the syringe pump 400 moves in the direction away from the pipeline connection to generate negative pressure. Under the action of the negative pressure, the reagent is suctioned from the reagent kit 100 through the 24-way valve, the flow cell 500, the solenoid valve and the corresponding pipeline to the storage cavity 600 in sequence, or only the reagent is suctioned to fill the flow cell 500. During the suction process of the syringe pump 400, the buffer solution filled in the storage cavity 600 flows into the syringe pump 400.
[0054] It can be seen from the above description that during the process of sucking the reagent, the buffer solution can be used as an isolation liquid to isolate the reagent outside the syringe pump 400. Thus, during the suction process, the reagent is prevented from entering the syringe pump 400, and the syringe pump 400 will not be contaminated by the reagent. When different reagent reactions are carried out, the doping between reagents is also reduced, improving the accuracy of sequencing. At the same time, the wear of the syringe pump 400 by the reagent can also be reduced, and the maintenance cost of the entire liquid path system can be reduced.
[0055] After the reagent reacts in the flow cell 500, the generated waste liquid needs to be discharged out of the system. When discharging, the waste liquid is also discharged by switching the first selection valve 10 and the second selection valve 20, which will be introduced in detail below.
[0056] Refer to Figure 3c As shown, by switching the second selection valve 20, the C port of the solenoid valve is connected to the B port, that is, the waste liquid pool 200 is connected to the storage cavity 600. The third selection valve 30 remains in place, and the syringe pump 400 is connected to the storage cavity 600. Push the syringe pump 400 so that the buffer solution in the syringe pump 400 fills the storage cavity 600, and the medium remaining in the storage cavity 600 (this medium can be Figure 3b the gas, reagent or buffer solution in the flow cell 500) is pushed into the waste liquid pool 200. The flow path is as shown by the solid line with arrows in Figure 3c .
[0057] Refer to Figure 3d , by switching the second selection valve 20, the A port of the solenoid valve is connected to the C port, that is, the flow cell 500 is connected to the storage cavity 600. The third selection valve 30 remains in place, and the syringe pump 400 is connected to the storage cavity 600. Pull the piston of the syringe pump 400 in the direction away from the pipeline, and the buffer solution in the storage cavity 600 is sucked into the syringe pump 400 again, and the waste liquid in the flow cell 500 is also sucked into the storage cavity 600. The flow path is as shown by the solid line with arrows in Figure 3d .
[0058] Refer toFigure 3e , switch the second selection valve 20, so that the C port of the solenoid valve is communicated with the B port, that is, the waste liquid pool 200 is communicated with the storage cavity 600. The third selection valve 30 remains in place, and the injection pump 400 is communicated with the storage cavity 600. Push the injection pump 400 so that the buffer solution in the injection pump 400 is filled into the storage cavity 600, and the waste liquid remaining in the storage cavity 600 is pushed into the waste liquid pool 200. The flow path is as Figure 3c shown by the solid line with arrows in
[0059] It can be seen from Figures 3c to 3e that when discharging waste liquid, according to the operation of the injection pump 400, the buffer solution is repeatedly filled into the injection pump 400, ensuring that during the entire waste liquid discharge process, the waste liquid only flows into the storage cavity 600 and does not enter the injection pump 400, thus ensuring the safety of the injection pump 400. The buffer solution can be used as an isolation liquid to isolate the waste liquid outside the injection pump 400. Thus, during the extraction process, the waste liquid is prevented from entering the injection pump 400, and the injection pump 400 will not be contaminated by the waste liquid. When performing different reagent reactions, the contamination of the injection pump 400 can be reduced. At the same time, the wear of the injection pump 400 by the waste liquid can also be reduced, and the maintenance cost of the entire liquid path system can be reduced.
[0060] Combined with Figures 3a to 3c it can be seen that during the sequencing process, by setting the buffer solution pool 300 and the storage cavity 600, it can be ensured that most reagent components do not enter the injection pump 400, reducing the possibility of unnecessary impurities entering the injection pump 400, improving the reliability of the injection pump 400, and reducing its maintenance cost.
[0061] To facilitate understanding of the liquid path system provided by the embodiments of the present application, the embodiments of the present application also provide its usage method, and this method is the usage method corresponding to the above liquid path system. This usage method includes the following steps:
[0062] Step 001: Through the switching of the third selection valve 30, the injection pump 400 fills the buffer solution in the buffer solution pool 300 into at least the storage cavity 600;
[0063] Specifically, this step specifically includes:
[0064] Step a: Connect the injection pump 400 with the buffer solution pool 300 through the third selection valve 30;
[0065] Step b: Extract the buffer solution from the buffer solution pool 300 through the injection pump 400;
[0066] Step c: Connect the injection pump 400 with the storage cavity 600 through the third selection valve 30; and connect the storage cavity 600 with the waste liquid pool 200 through the second selection valve 20;
[0067] Step d: Inject the extracted buffer solution into the storage cavity 600 through the injection pump 400; and repeatedly switch the third selection valve 30 until the storage cavity 600 is filled with buffer solution by at least the injection pump 400.
[0068] Specifically, it can be seen from Figure 3a the relevant description in, which will not be elaborated here in detail.
[0069] Step 002: Connect the reagent kit 100, the flow cell 500, the storage cavity 600, and the injection pump 400 through the first selection valve 10, the second selection valve 20, and the third selection valve 30 to form a passage, and use the negative pressure of the injection pump 400 to suck the reagent in the reagent kit 100 into the flow cell 500.
[0070] Specifically, this step specifically includes:
[0071] Step 1: Connect the flow cell 500 to the reagent kit 100 through the first selection valve 10, and connect the storage cavity 600 to the flow cell 500 through the second selection valve 20; connect the injection pump 400 to the storage cavity 600 through the third selection valve 30;
[0072] Step 2: Extract the reagent in the reagent kit 100 into the flow cell 500 through the negative pressure formed by the injection pump 400.
[0073] Specifically, refer to Figure 3b the relevant description in, which will not be elaborated here.
[0074] It can be seen from the above description that in the method for using the liquid path system provided in the embodiment of the present application, by using the additional buffer solution pool 300 and the cooperation of the selection valve group, before extracting the reagent, the storage cavity 600 is filled with the buffer agent, so that when the injection pump 400 extracts the reagent, the injection pump 400 is filled with the buffer solution, and the reagent will not enter the injection pump 400, thereby reducing the wear of the reagent on the injection pump 400, reducing the maintenance cost of the injection pump 400, reducing the maintenance cost of the entire liquid path system. At the same time, the injection pump 400 will not be contaminated by the reagent, and the sequencing accuracy is also improved.
[0075] The method for use provided in the embodiment of the present application further includes the following steps:
[0076] Step 003: When discharging the waste liquid, through the switching of the second selection valve 20, first discharge the medium in the storage cavity 600 into the waste liquid pool 200 through the injection pump 400; then extract the waste liquid in the flow cell 500 into the storage cavity 600 through the injection pump 400 and discharge it into the waste liquid pool 200.
[0077] Specifically, this step specifically includes the following steps:
[0078] Step I: First, connect the storage chamber 600 to the waste liquid tank 200 through the second selection valve 20; and drain the medium in the storage chamber 600 into the waste liquid tank 200 through the injection pump 400;
[0079] Step II: Then, connect the storage chamber 600 to the flow cell 500 through the second selection valve 20; and pump the waste liquid in the flow cell 500 into the storage chamber 600 through the injection pump 400;
[0080] Step III: Next, connect the storage chamber 600 to the waste liquid tank 200 through the second selection valve 20, and drain the waste liquid in the storage chamber 600 into the waste liquid tank 200 through the injection pump 400.
[0081] Specifically, refer to the relevant description in Figures 3c to 3e and details will not be repeated here.
[0082] In this step, by using the additional buffer tank 300 and the selection valve group in cooperation, before pumping the waste liquid, the storage chamber 600 is filled with the buffer agent, and the injection pump 400 is filled with the buffer liquid, so that the waste liquid does not enter the injection pump 400, thereby reducing the wear of the injection pump 400 caused by the waste liquid, reducing the maintenance cost of the injection pump 400, and reducing the maintenance cost of the entire liquid path system. At the same time, the injection pump 400 is not contaminated by the waste liquid, and the sequencing accuracy is also improved.
[0083] In order to reduce the experimental time, speed up the experiment, and increase the sequencing data throughput, in the liquid path system provided in the embodiment of the present application, multiple groups of flow cells 500, storage chambers 600, and injection pumps 400 can also be set to work simultaneously or alternately, which can increase the throughput of the flow cell 500, improve the efficiency of the reagent delivery fluid system, and improve the experimental efficiency. The following are examples for illustration.
[0084] Refer to Figure 4 , Figure 4 which is a variant structure of the liquid path system based on Figure 2 . In the liquid path system shown in Figure 4 , the number of flow cells 500 is two, the number of storage chambers 600 is two, and the number of injection pumps 400 is also two. The number of reagent kits 100, waste liquid tanks 200, and buffer tanks 300 is one each.
[0085] Among them, the two flow cells 500 share a first selection valve 10 to selectively communicate with the reagent bottles in the reagent kit 100. The first selection valve 10 can also be a 24-way valve. The common channel of the first selection valve 10 branches out two branches, and the two branches are respectively connected to the two flow cells 500 in one-to-one correspondence. The branches of the first selection valve 10 are respectively connected to the reagent bottles in the reagent kit 100 in one-to-one correspondence.
[0086] The two storage chambers 600 correspond to the two flow cells 500 one by one. Each storage chamber 600 is selectively connected to the corresponding flow cell 500 and the waste liquid tank 200 through a second selection valve 20. The connection mode of the second selection valve 20 with the storage chamber 600, the flow cell 500 and the waste liquid tank 200 can be referred to Figure 2 for the connection mode of the second selection valve 20 in it, which will not be elaborated here.
[0087] The number of injection pumps 400 is two. The two injection pumps 400 correspond to the two storage chambers 600 one by one. Each injection pump 400 is selectively connected to the corresponding storage chamber 600 and the buffer tank 300 through a third selection valve 30. The connection mode of the third selection valve 30 with the storage chamber 600, the injection pump 400 and the buffer tank 300 can be referred to Figure 2 for the connection mode of the third selection valve 30 in it, which will not be elaborated here.
[0088] In Figure 4 when the shown liquid path system is in use, the switching modes of the first selection valve 10, the second selection valve 20 and the third selection valve 30 can be referred to Figures 3a to 3e for the switching mode of the selection valve in it. This will not be elaborated here.
[0089] In Figure 4 in the shown liquid path system, the extraction of reagents and the exclusion of waste liquid can be realized by the cooperation of two injection pumps 400, two storage chambers 600 and two flow cells 500. Similarly, the reliability of the two injection pumps 400 can be ensured, the risk of their being contaminated can be reduced, and the detection efficiency can be improved, etc.
[0090] Refer to Figure 5 , Figure 5 is a deformed structure based on Figure 2 the shown liquid path system. In Figure 4 the shown liquid path system, the number of flow cells 500 is two, the number of storage chambers 600 is two, and the number of injection pumps 400 is one. While the number of reagent kits 100, waste liquid tanks 200 and buffer tanks 300 is all one.
[0091] Among them, each flow cell 500 is selectively connected to the reagent bottle in the reagent kit 100 through a first selection valve 10. That is, the number of first selection valves 10 is also two, and the two flow cells 500 correspond to the two first selection valves 10 one by one. The connection mode of each first selection valve 10 connecting the flow cell 500 and the reagent kit 100 is the same as that of Figure 2 the first selection valve 10 in it, which will not be elaborated here.
[0092] Two storage chambers 600 correspond to two flow cells 500 one by one; each storage chamber 600 is selectively communicated with the corresponding flow cell 500 and waste liquid tank 200 through a second selection valve 20. The connection mode of the second selection valve 20 with the storage chamber 600, the flow cell 500 and the waste liquid tank 200 can refer to Figure 2 the connection mode of the second selection valve 20 in
[0093] The injection pump 400 is selectively communicated with one of two storage chambers 600 and the buffer tank 300 through a third selection valve 30. The third selection valve 30 can also be a 6-way valve. Two branches of the third selection valve 30 are respectively communicated with two storage chambers 600 one by one, and the third branch is communicated with the buffer tank 300. And the common passage of the third selection valve 30 is communicated with the injection pump 400.
[0094] In Figure 5 when the shown liquid path system is in use, the switching modes of the first selection valve 10, the second selection valve 20 and the third selection valve 30 can refer to Figures 3a to 3e the switching mode of the selection valve in
[0095] In Figure 5 the shown liquid path system, the extraction of reagents and the exclusion of waste liquid can be realized by an injection pump 400 cooperating with two storage chambers 600 and two flow cells 500. Similarly, the reliability of two injection pumps 400 can be ensured, the risk of their being contaminated can be reduced, and the detection efficiency can be improved, etc.
[0096] Refer to Figure 6 , Figure 6 is a deformed structure based on Figure 2 the shown liquid path system. Comparing Figure 4 , Figure 5 and Figure 6 , it can be seen that Figure 6 can also be regarded as Figure 4 and Figure 5 a combination of two different liquid path systems shown.
[0097] In Figure 6 the shown liquid path system, the number of flow cells 500 is four, the number of storage chambers 600 is four, the number of injection pumps 400 is two, the number of the first selection valve 10 and the third selection valve 30 is two each, and the number of the second selection valve 20 is two. Among them, two flow cells 500 in each flow cell group are selectively communicated with the reagent bottles in the reagent kit through a shared first selection valve 10; the storage chambers 600 correspond to the flow cells 500 one by one, and each storage chamber 600 is selectively communicated with the corresponding flow cell and waste liquid tank through a second selection valve 20.
[0098] Among them, the four flow cells 500 are divided into two flow cell groups, and each flow cell group contains two flow cells 500. The four storage cavities 600 are divided into two storage cavity groups, and each storage cavity group contains two storage cavities 600. Among them, the two storage cavity groups correspond to the two flow cell groups one by one, and the storage cavities 600 in each storage cavity group correspond to the flow cells 500 in the corresponding flow cell group one by one.
[0099] Exemplarily, among Figure 6 the four flow cells exemplified in are flow cell A, flow cell B, flow cell C, and flow cell D respectively. Among them, flow cell A and flow cell C form a flow cell group, and flow cell B and flow cell D also form a flow cell group. The four storage cavities are storage cavity A, storage cavity B, storage cavity C, and storage cavity D respectively. Among them, storage cavity A and storage cavity C form a storage cavity group, and storage cavity B and storage cavity D also form a storage cavity group. When corresponding, flow cell A corresponds to storage cavity A, flow cell B corresponds to storage cavity B, flow cell C corresponds to storage cavity C, and flow cell D corresponds to storage cavity D.
[0100] When specifically connecting, the two flow cells in each flow cell group are selectively communicated with the reagent bottles in the reagent kit 100 through a shared first selection valve 10. The connection mode between the flow cells in each flow cell group and the first selection valve 10 can refer to Figure 4 the connection mode between the flow cell and the first selection valve 10 in. This will not be elaborated here.
[0101] Each storage cavity is selectively communicated with the corresponding flow cell and the waste liquid pool 200 through a second selection valve 20. The connection mode of the second selection valve 20 with the storage cavity, the flow cell, and the waste liquid pool 200 can refer to Figure 2 the connection mode of the second selection valve 20 in, which will not be elaborated here.
[0102] Specifically, the number of injection pumps 400 is set to two. Each injection pump 400 is communicated with two storage cavities and a buffer solution pool through a third selection valve 30; among them, the two storage cavities connected by the injection pump 400 through the third selection valve 30 belong to two different storage cavity groups, and the flow cells corresponding to the two storage cavities connected by each injection pump 400 through the third selection valve 30 belong to two different flow cell groups. Exemplarily, the two injection pumps 400 are injection pump 400A and injection pump 400B respectively. Among them, injection pump 400A is connected with a third selection valve 30A, and the third selection valve 30A is respectively connected with storage cavity A, storage cavity B, and the buffer solution pool. Among them, storage cavity A and storage cavity B belong to different storage cavity groups. Injection pump 400B is connected with a third selection valve 30B, and the third selection valve 30B is respectively connected with storage cavity C, storage cavity D, and the buffer solution pool. Among them, storage cavity C and storage cavity D belong to different storage cavity groups.
[0103] InFigure 6 When the shown liquid path system is in use, the switching modes of the first selection valve 10, the second selection valve 20, and the third selection valve 30 can refer to Figures 3a to 3e the switching modes of the selection valves in
[0104] In Figure 6 the shown liquid path system, multiple injection pumps 400 can be used in cooperation with multiple storage chambers and multiple flow cells to achieve the extraction of reagents and the exclusion of waste liquid. Similarly, the reliability of multiple injection pumps 400 can be ensured, the risk of their being contaminated can be reduced, and the detection efficiency can be improved, etc.
[0105] It should be understood that in combination with Figure 4 , Figure 5 and Figure 6 it can be seen that in the liquid path system provided by the embodiments of the present application, the number of different flow cells, storage cells, and injection pumps can be selected according to actual needs, and the number of selection valves can also change correspondingly according to the number of flow cells, storage cells, and injection pumps, and all can achieve ensuring the reliability of the injection pumps, reducing the risk of their being contaminated, improving the detection efficiency, etc.
[0106] One or more embodiments of this specification are intended to cover all such substitutions, modifications, and variations that fall within the broad scope of the appended claims. Therefore, any omissions, modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of one or more embodiments of this specification shall be included within the protection scope of this disclosure.
[0107] The above is only the specific implementation manner of this application, but the protection scope of this application is not limited thereto. Any person skilled in the art within the technical scope disclosed by this application can easily think of changes or substitutions, which should all be covered within the protection scope of this application. Therefore, the protection scope of this application shall be subject to the protection scope of the claims.
Claims
1. A liquid path system, characterized in that, Comprising: A kit, a flow cell, a waste liquid pool, a buffer solution pool, a storage cavity, and an injection pump; wherein, The kit has at least one reagent bottle; The flow cell is selectively communicated with one reagent bottle of the kit through a first selection valve; The storage cavity is selectively communicated with the flow cell and the waste liquid pool through a second selection valve; It further includes a third selection valve, the third selection valve includes a plurality of branch channels and a common channel, the injection pump is connected to the common channel, the storage cavity and the buffer solution pool are respectively connected to different branch channels, and the common channel is selectively communicated with the plurality of branch channels; the injection pump is used to fill at least the buffer solution in the storage cavity through the cooperation of the second selection valve and the third selection valve before sucking the reagent in the reagent bottle into the flow cell.
2. The liquid path system according to claim 1, characterized in that, The sum of the total internal volumes of the pipeline between the second selection valve and the storage cavity, the storage cavity, and the pipeline between the storage cavity and the third selection valve is not less than the internal volume of the cavity of the injection pump.
3. The liquid path system according to claim 1, wherein The storage cavity can be any one of a circular cross-section channel, a non-circular cross-section channel, a serpentine channel, an extended pipeline, or a multi-way manifold.
4. The liquid path system according to claim 1, characterized in that, One of the plurality of branch channels of the third selection valve is communicated with the air.
5. The liquid path system according to any one of claims 1 to 4, characterized in that, The number of the flow cells is two, and the two flow cells share one first selection valve to be selectively communicated with the reagent bottle in the kit; The number of the storage cavities is two, and the two storage cavities correspond to the two flow cells one by one. Each storage cavity is selectively communicated with the corresponding flow cell and the waste liquid pool through a second selection valve; The number of the injection pumps is two, and the two injection pumps correspond to the two storage cavities one by one. Each injection pump is communicated with the corresponding storage cavity and the buffer solution pool through a third selection valve.
6. The liquid path system according to any one of claims 1 to 4, characterized in that, The number of the flow cells is two, and each flow cell is selectively communicated with the reagent bottle in the kit through a first selection valve; The number of the storage cavities is two, and the two storage cavities correspond to the two flow cells one by one; each storage cavity is selectively communicated with the corresponding flow cell and the waste liquid pool through a second selection valve; The injection pump is communicated with the two storage cavities and the buffer solution pool through a third selection valve.
7. The liquid path system according to any one of claims 1 to 4, characterized in that, The number of the flow cells is four, and the four flow cells are divided into two flow cell groups, and each flow cell group includes two flow cells; the two flow cells in each flow cell group are selectively communicated with the reagent bottle in the kit through a shared first selection valve; The number of the storage cavities is four, the storage cavities correspond to the flow cells one by one, and each storage cavity is selectively communicated with the corresponding flow cell and the waste liquid pool through a second selection valve; The number of the injection pumps is two, and each injection pump is communicated with the two storage cavities and the buffer solution pool through a third selection valve; wherein, the flow cells corresponding to the two storage cavities connected by each injection pump through the third selection valve belong to two different flow cell groups.
8. A gene sequencer, characterized in that, Comprising the liquid path system according to any one of claims 1-7.