Liquid path system and gene sequencer
By designing a liquid system in gene sequencing technology, and using solenoid valves and mixers to achieve automatic mixing and supplementation of reagents, the problem of even mixing polymerases in the prior art requires manual supplementation, simplifying the process and ensuring full mixing of reagents.
Patent Information
- Application Number
- CN202421202429.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-05-30
- Publication Date
- 2025-03-11
- Estimated Expiration
- 2034-05-30
AI Technical Summary
In the existing gene sequencing technology, even mixing of polymerases requires use within half an hour and manual supplementation is required, resulting in complex processes.
A liquid system is designed to use multiple solenoid valves and mixers to realize automatic mixing and replenishment of reagents to ensure that reagents are fully mixed before entering the sequencing chip.
It reduces artificial operations, reduces the risk of reagent mixing and supplementation, ensures that the reagents are fully mixed and evenly, and simplifies the process.
Smart Images
Figure CN222593866U_ABST
Abstract
Description
Technical Field
[0001] The present application belongs to the field of gene sequencing technology, and specifically relates to a liquid circuit system and a gene sequencer. Background Art
[0002] During the sequencing process, different reagents need to be continuously added to the chip and react chemically with the DNC fixed on the chip to ensure the continuous progress of sequencing. The sequencing process is performed by a gene sequencer, which mainly includes: a reagent kit for storing reagents, a carrier for carrying the chip, an optical machine for taking pictures of the clusters generated by the biochemical reaction, and a liquid system for supplying liquid. The liquid system uses a syringe pump and a rotary valve to draw a certain amount of reagent from the corresponding reagent in the reagent kit into the chip.
[0003] In the sequencing process, in order to ensure the high quality and efficiency of high-density chips and improve their specificity, the polymerases prepared in a certain proportion are usually mixed evenly in the reagent kit in advance, and then added to the reaction chip after mixing evenly. In the prior art, the evenly mixed polymerases are usually added to the reagent kit at one time. However, since multiple polymerases will affect each other, such mixed enzymes are required to be used within half an hour of mixing evenly. Such mixed enzymes need to be mixed evenly outside the instrument and then manually added to the reagent kit within half an hour before use, which causes the problem of complicated process. Utility Model Content
[0004] The present application discloses a liquid circuit system and a gene sequencer to solve the problem of complex process in the prior art.
[0005] In a first aspect of the present application, a fluid circuit system is provided, comprising:
[0006] Kit, for storing reagents;
[0007] A rotary valve having a plurality of first liquid inlet ports and a first liquid outlet port, wherein the first liquid inlet port is selectively connected to a reagent in the reagent kit, and the first liquid outlet port is connected to the sequencing chip;
[0008] A syringe pump, connected to the sequencing chip, for aspirating or discharging reagents;
[0009] A selection valve is disposed between the sequencing chip and the injection pump, and has a second common port and a plurality of second liquid inlet ports, wherein the second common port is connected to the injection pump, and one of the second liquid inlet ports is connected to the sequencing chip;
[0010] The bypass is arranged between the reagent box and the selection valve, and includes a first solenoid valve, a second solenoid valve and a mixer. The first solenoid valve is used to select the first liquid inlet port or the second solenoid valve to be connected to the reagent box, and the second solenoid valve is used to select the first solenoid valve or a reagent in the reagent box to be connected to the mixer. The mixer is connected to the injection pump through one of the second liquid inlet ports of the selection valve, and is used to draw two reagents for mixing, and is used to push the mixed reagent back to the reagent box under the action of the injection pump.
[0011] Optionally, a third solenoid valve is further provided between the second solenoid valve and the reagent box, the third solenoid valve is used to select one reagent in the reagent box to be connected to the second solenoid valve, and the mixer is used to absorb at least two of the three reagents for mixing.
[0012] Optionally, a three-way connector is further provided between the third solenoid valve and the reagent box, the three-way connector is used to select two reagents in the reagent box to be connected to the third solenoid valve, and the mixer is used to select and absorb at least two of the four reagents for mixing.
[0013] Optionally, the liquid circuit system further includes a waste liquid barrel, which is connected to the second liquid inlet port and is used to receive the reagent temporarily stored in the injection pump.
[0014] Optionally, a pressure sensor is provided on the pipeline between the sequencing chip and the selection valve, and the pressure sensor is used to detect the fluid pressure in the pipeline.
[0015] Optional,
[0016] The first solenoid valve has a first common port, a first normally open port and a first normally closed port, the first common port is connected to the reagent box, the first normally open port is connected to the second liquid inlet port, and the first normally closed port is connected to the second solenoid valve;
[0017] The second solenoid valve has a second common port, a second normally open port, and a second normally closed port, the second common port is connected to the mixer, the second normally open port is connected to the reagent box, and the second normally closed port is connected to the first normally closed port.
[0018] Optionally, the third solenoid valve has a third common port, a third normally open port and a third normally closed port, the third common port is connected to the second solenoid valve, and the third normally open port and the third normally closed port are respectively connected to a reagent in the reagent kit.
[0019] A second aspect of the present application provides a gene sequencer, comprising a liquid path system provided by any one of the implementations of the first aspect.
[0020] It can be seen from the above technical solutions that the liquid circuit system provided in the present application utilizes multiple solenoid valves and mixers to achieve mixing of multiple reagents, reduce manual operations, and reduce the risk of reagent mixing and replenishment; it can ensure that multiple reagents to be mixed are stored inside the instrument, and the mixing is completed before entering the sequencing chip, and it can ensure that they can be fully mixed evenly, thereby solving the problem of complex processes existing in the prior art. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] Figure 1 A schematic diagram of the structure of a fluid circuit system provided in an embodiment of the present application;
[0022] Figure 2 A schematic diagram of the structure of another fluid circuit system provided in an embodiment of the present application;
[0023] Figure 3 A schematic diagram of the structure of another fluid circuit system provided in an embodiment of the present application;
[0024] Figure markings: 1-reagent box; 2-rotary valve; 21-first liquid inlet port; 22-first liquid outlet port; 3-syringe pump; 4-selection valve; 41-second common port; 42-second liquid inlet port; 5-first solenoid valve; 6-second solenoid valve; 7-mixer; 8-waste liquid bucket; 9-third solenoid valve; 10-three-way connector; 51-first common port; 52-first normally open port; 53-first normally closed port; 61-second common port; 62-second normally open port; 63-second normally closed port; 91-third common port; 92-third normally open port; 93-third normally closed port. DETAILED DESCRIPTION
[0025] The technical solutions in the embodiments of the present application are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present application.
[0026] Reference Figure 1As shown in the structural schematic diagram, the embodiment of the present application provides a liquid circuit system, including: a reagent kit 1 for storing reagents; a rotary valve 2, having a plurality of first liquid inlet ports 21 and a first liquid outlet port 22, wherein the first liquid inlet port 21 is selectively connected to a reagent in the reagent kit 1, and the first liquid outlet port 22 is connected to the sequencing chip; a syringe pump 3 is connected to the sequencing chip and is used to absorb or discharge the reagent; a selection valve 4 is arranged between the sequencing chip and the syringe pump 3, having a second common port 41 and a plurality of second liquid inlet ports 42, wherein the second common port 41 is connected to the syringe pump 3, and one of the second liquid inlet ports 42 is connected to the sequencing chip. The bypass is arranged between the reagent box 1 and the selection valve 4, and includes a first solenoid valve 5, a second solenoid valve 6 and a mixer 7. The first solenoid valve 5 is used to select the first liquid inlet port 21 or the second solenoid valve 6 to be connected to the reagent box 1, and the second solenoid valve 6 is used to select the first solenoid valve 5 or a reagent in the reagent box 1 to be connected to the mixer 7. The mixer 7 is connected to the injection pump 3 through one of the second liquid inlet ports 42 of the selection valve 4. The mixer 7 is used to absorb two reagents for mixing, and is used to push the mixed reagent back to the reagent box under the action of the injection pump 3.
[0027] In this embodiment, any reagent in the reagent kit is selected by rotating the valve 2, and a negative pressure is formed in the pipeline when the syringe pump 8 draws liquid. Under the action of the negative pressure, the reagent enters the sequencing chip from the first liquid outlet port 22 of the rotary valve 2, and then flows into the syringe pump. According to the progress of the experiment, the first liquid inlet port 21 of the rotary valve 2 is connected with the corresponding target reagent in turn, so that the target reagent can be introduced into the sequencing chip.
[0028] Based on the requirements of mixing and preparation, this embodiment adds a bypass, and selects to absorb one reagent in the reagent kit 1, such as a library, through the first solenoid valve 5; selects to absorb another reagent in the reagent kit 1, such as an enzyme, through the second solenoid valve 6; by controlling the amount of the absorbed reagent, a certain amount of library and enzyme are temporarily stored in the mixer 7, and the mixer has the function of mixing fluids. When at least two reagents are absorbed, the injection pump 3 is controlled to push the fluid in the bypass backward, and the fluid mixed with at least two reagents is pushed backward from the mixer 7 to a hole in the reagent kit. During the backward pushing process, the fluid passes through components such as solenoid valves, which form disturbances on the fluid, so that the mixed fluid achieves turbulent mixing. At this time, the reagent kit 1 stores mixed reagents, and the first liquid inlet port 21 of the rotary valve 2 is connected to the mixed reagent in the reagent kit 1, so that the mixed reagent can be passed into the sequencing chip. It can be seen from the above technical solutions that the liquid path system provided in this embodiment uses multiple solenoid valves and mixers to increase fluid disturbance to achieve turbulent mixing, thereby fully mixing different reagents, reducing manual operations, and reducing the risk of reagent mixing and replenishment; it can ensure that a variety of reagents to be mixed are stored inside the instrument, and the mixing is completed before entering the sequencing chip, and it can ensure that they are fully mixed and evenly mixed.
[0029] Reference Figure 1 As shown in the structural schematic diagram, the liquid circuit system further includes a waste liquid barrel 8 , which is connected to the second liquid inlet port 42 and is used to receive the reagent temporarily stored in the injection pump 3 .
[0030] In this embodiment, three second liquid inlet ports 42 are provided, which are respectively connected to the mixer 7, the sequencing chip and the waste liquid bucket 8. In practical applications, any one of the second liquid inlet ports 42 is selected to be connected to the second common port 41 to achieve the absorption or discharge of the reagent.
[0031] During the sequencing process, the test is interrupted due to the sequencing quality itself or external abnormalities, and the cleaning procedure cannot be performed immediately. The reagents produce gel-like substances or grow fungi in the pipeline for a long time, which leads to blockage of the liquid path and requires cleaning and maintenance. If the common liquid path system is blocked in the public pipeline, since the liquid inlet end is blocked, the liquid can only be pushed back from the second liquid inlet port 42 (i.e., the waste liquid port) used to connect to the waste liquid barrel 8. Since the waste liquid port has been placed in the waste liquid for a long time, it is uncertain whether there are pollutants in the waste liquid pipe. It is necessary to connect the waste liquid port of the injection pump to a new pipeline, insert it into the clean cleaning liquid, and then extract the clean cleaning liquid from the waste liquid port and push it back from the chip to the public pipeline. In the process of performing this maintenance operation, it is necessary to disassemble the outer frame of the instrument, and the difficulty of maintenance must be operated on site by maintenance personnel, which is too complicated.
[0032] In order to solve the above technical problems, based on the liquid path system provided in the embodiment of the present application, when the pipeline between the rotary valve 2 and the sequencing chip is blocked, the injection pump 3 is also used to absorb the cleaning reagent from the bypass and push the cleaning reagent back to the pipeline between the rotary valve 2 and the sequencing chip, thereby achieving simple maintenance without disassembling the pipeline.
[0033] Reference Figure 2 As shown in the structural schematic diagram, a third solenoid valve 9 is also arranged between the second solenoid valve 6 and the reagent box 1, and the third solenoid valve 9 is used to select a reagent in the reagent box 1 to be connected to the second solenoid valve 6, and the mixer 7 is used to absorb at least two of the three reagents for mixing.
[0034] Reference Figure 3 In the structural schematic diagram shown, a three-way connector 10 is further provided between the third solenoid valve 9 and the reagent box 1, and the three-way connector 10 is used to select two reagents in the reagent box to be connected to the third solenoid valve 9, and the mixer 7 is used to select at least two of the four reagents to be drawn for mixing. In practical applications, due to the difference in viscosity between the reagents, the actual amount of absorption will be different. When two reagents are simultaneously absorbed using the three-way connector 10, the viscosity of the two reagents is required to be consistent to ensure that there is no difference in the amount of liquid inlet.
[0035] In one feasible manner, the mixer 7 respectively absorbs the four reagents of library, enzyme 1, enzyme 2 and enzyme 3 for mixing, and after mixing, the syringe pump 3 is used to push the four reagents back to the location of the library, so that the mixed reagents are placed in the reagent box for standby use.
[0036] In this embodiment, a single liquid circuit is completely independent and can be used for simultaneous independent sequencing of multiple chips; in addition, this embodiment can achieve sufficient mixing of more or fewer types of reagents by adding a solenoid valve and replacing the three-way connector with a 1-way N connector.
[0037] Reference Figure 1 As shown in the structural schematic diagram, a pressure sensor (not numbered in the figure) is provided on the pipeline between the sequencing chip and the selection valve 4, and the pressure sensor is used to detect the fluid pressure in the pipeline. According to the pressure measurement value of the pressure sensor, it is possible to monitor whether the fluid system flowing through the sequencing chip is working normally. For example, a threshold interval of the pressure measurement value is pre-set, and if it exceeds the threshold interval, it is determined that the fluid system is abnormal. The abnormal types mainly include blockage and leakage. Further, the abnormal type can be determined according to the pressure measurement value. In an achievable manner, the current pressure measurement value is obtained to determine whether the current pressure measurement value is within the preset threshold interval; if the current pressure measurement value is greater than the upper limit value of the threshold interval, it is determined that the current pipeline has a leakage abnormality; if the current pressure measurement value is less than the lower limit value of the threshold interval, it is determined that the current pipeline has a blockage abnormality. Among them, the threshold interval is determined according to experimental determination and is not specifically limited here.
[0038] In this embodiment, the solenoid valve can be a two-position three-way solenoid valve. Figure 1 As shown in the structural schematic diagram, the first solenoid valve 5 has a first common port 51, a first normally open port 52 and a first normally closed port 53, the first common port 51 is connected to the reagent box 1, the first normally open port 52 is connected to the second liquid inlet port 42, and the first normally closed port 53 is connected to the second solenoid valve 6; the second solenoid valve 6 has a second common port 61, a second normally open port 62 and a second normally closed port 63, the second common port 61 is connected to the mixer 7, the second normally open port 62 is connected to the reagent box 1, and the second normally closed port 63 is connected to the first normally closed port 53.
[0039] Optionally, the third solenoid valve 9 has a third common port 91 , a third normally open port 92 and a third normally closed port 93 , the third common port 91 is connected to the second solenoid valve 6 , and the third normally open port 92 and the third normally closed port 93 are respectively connected to a reagent in the reagent kit 1 .
[0040] In one achievable manner, a three-way connector 10 is provided between the third normally closed port 93 and the reagent kit, and the three-way connector 10 is selectively connected to two reagents in the reagent kit, thereby realizing the selection of multiple reagents.
[0041] The present application also provides a gene sequencer, comprising Figure 1 The liquid circuit system provided by any one of the implementation modes. The gene sequencer has all the technical effects of the above-mentioned liquid circuit system, which will not be described in detail here.
[0042] The above are merely embodiments of the present application and are not intended to limit the present application. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present application are included in the scope of the claims of the present application to be approved.
Claims
1. A liquid circuit system, characterized in that: include: Kit, for storing reagents; A rotary valve having a plurality of first liquid inlet ports and a first liquid outlet port, wherein the first liquid inlet port is selectively connected to a reagent in the reagent kit, and the first liquid outlet port is connected to the sequencing chip; A syringe pump, connected to the sequencing chip, for aspirating or discharging reagents; A selection valve is disposed between the sequencing chip and the injection pump, and has a second common port and a plurality of second liquid inlet ports, wherein the second common port is communicated with the injection pump, and one of the second liquid inlet ports is communicated with the sequencing chip; The bypass is arranged between the reagent box and the selection valve, and includes a first solenoid valve, a second solenoid valve and a mixer. The first solenoid valve is used to select the first liquid inlet port or the second solenoid valve to be connected to the reagent box, and the second solenoid valve is used to select the first solenoid valve or a reagent in the reagent box to be connected to the mixer. The mixer is connected to the injection pump through one of the second liquid inlet ports of the selection valve, and is used to draw two reagents for mixing, and is used to push the mixed reagent back to the reagent box under the action of the injection pump.
2. A fluid path system according to claim 1, characterized in that: A third solenoid valve is further provided between the second solenoid valve and the reagent box, and the third solenoid valve is used to select one reagent in the reagent box to be connected to the second solenoid valve, and the mixer is used to absorb at least two of the three reagents for mixing.
3. A fluid path system according to claim 2, characterized in that: A three-way connector is also provided between the third solenoid valve and the reagent box, and the three-way connector is used to select two reagents in the reagent box to be connected to the third solenoid valve, and the mixer is used to select and absorb at least two of the four reagents for mixing.
4. A fluid path system according to claim 1, characterized in that: The liquid circuit system further comprises a waste liquid barrel, which is communicated with the second liquid inlet port and is used for receiving the reagent temporarily stored in the injection pump.
5. A fluid path system according to claim 1, characterized in that: A pressure sensor is provided on the pipeline between the sequencing chip and the selection valve, and the pressure sensor is used to detect the fluid pressure in the pipeline.
6. A fluid path system according to claim 1, characterized in that: The first solenoid valve has a first common port, a first normally open port and a first normally closed port, the first common port is connected to the reagent box, the first normally open port is connected to the second liquid inlet port, and the first normally closed port is connected to the second solenoid valve; The second solenoid valve has a second common port, a second normally open port, and a second normally closed port, the second common port is connected to the mixer, the second normally open port is connected to the reagent box, and the second normally closed port is connected to the first normally closed port.
7. A fluid path system according to claim 2, characterized in that: The third solenoid valve has a third common port, a third normally open port and a third normally closed port. The third common port is connected to the second solenoid valve. The third normally open port and the third normally closed port are respectively connected to a reagent in the reagent box.
8. A gene sequencer, characterized in that: A fluid path system comprising any one of claims 1 to 7.